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Thursday, December 8, 2011

Objectives and Methods of Analysis and Design, and Properties of Concrete and Steel


Module 1

Objectives and Methods of Analysis and Design, and Properties of Concrete and Steel

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Lesson 1

Objectives and Methods of Analysis and Design

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Instructional Objectives:

At the end of this lesson, the student should be able to:

• state the four objectives of the design of reinforced concrete structures, • name the three methods of design of concrete structure and identify the best

method of design, • state the basis of the analysis of the structure, • express the design loads in terms of characteristic loads in limit state and

working stress methods, • define the characteristic load, • name the different loads, forces and effects to be considered in the design, • state the basis of determining the combination of different loads acting on the

structure

1.1.1 Introduction

Reinforced concrete, as a composite material, has occupied a special place in the modern construction of different types of structures due to its several advantages. Italian architect Ponti once remarked that concrete liberated us from the rectangle. Due to its flexibility in form and superiority in performance, it has replaced, to a large extent, the earlier materials like stone, timber and steel. Further, architect's scope and imaginations have widened to a great extent due to its mouldability and monolithicity. Thus, it has helped the architects and engineers to build several attractive shell forms and other curved structures. However, its role in several straight line structural forms like multistoried frames, bridges, foundations etc. is enormous.

The design of these modern reinforced concrete structures may appear to be highly complex. However, most of these structures are the assembly of several basic structural elements such as beams, columns, slabs, walls and foundations (Anim. 1.1.1). Accordingly, the designer has to learn the design of these basic reinforced concrete elements. The joints and connections are then carefully developed.

Anim. 1.1.1

Design of reinforced concrete structures started in the beginning of last century following purely empirical approach. Thereafter came the so called rigorous elastic theory where the levels of stresses in concrete and steel are limited so that stress-deformations are taken to be linear. However, the limit state method, though semi-empirical approach, has been found to be the best for the design of reinforced concrete structures (see sec. 1.1.3.1 also). The constraints and applicabilities of both the methods will be discussed later.

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1.1.2 Objectives of the Design of Reinforced Concrete Structures

Every structure has got its form, function and aesthetics. Normally, we consider that the architects will take care of them and the structural engineers will be solely responsible for the strength and safety of the structure. However, the roles of architects and structural engineers are very much interactive and a unified approach of both will only result in an "Integrated" structure, where every material of the total structure takes part effectively for form, function, aesthetics, strength as well as safety and durability. This is possible when architects have some basic understanding of structural design and the structural engineers also have the basic knowledge of architectural requirements.

Both the engineer and the architect should realize that the skeletal structure without architecture is barren and mere architecture without the structural strength and safety is disastrous. Safety, here, includes consideration of reserve strength, limited deformation and durability. However, some basic knowledge of architectural and structural requirements would facilitate to appreciate the possibilities and limitations of exploiting the reinforced concrete material for the design of innovative structures.

Before proceeding to the design, one should know the objectives of the design of concrete structures. The objectives of the design are as follows:

1.1.2.1 The structures so designed should have an acceptable probability of performing satisfactorily during their intended life.

This objective does not include a guarantee that every structure must perform satisfactorily during its intended life. There are uncertainties in the design process both in the estimation of the loads likely to be applied on the structure and in the strength of the material. Moreover, full guarantee would only involve more cost. Thus, there is an acceptable probability of performance of structures as given in standard codes of practices of different countries.

1.1.2.2 The designed structure should sustain all loads and deform within limits for construction and use.

Anim. 1.1.2 Anim. 1.1.3 Anim. 1.1.4

Adequate strengths and limited deformations are the two requirements of the designed structure. The structure should have sufficient strength and the deformations must be within prescribed limits due to all loads during construction and use as seen in Anim. 1.1.2. Animation 1.1.3 shows the structure having insufficient strength of concrete which fails in bending compression with the increase of load, though the deformation of the structure is not alarming. On the

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other hand, Anim. 1.1.4 shows another situation where the structure, having sufficient strength, deforms excessively. Both are undesirable during normal construction and use.

However, sometimes structures are heavily loaded beyond control. The structural engineer is not responsible to ensure the strength and deformation within limit under such situation. The staircases in residential buildings during festival like marriage etc., roof of the structures during flood in the adjoining area or for buildings near some stadium during cricket or football matches are some of the examples when structures get overloaded. Though, the structural designer is not responsible for the strength and deformations under these situations, he, however, has to ensure that the failure of the structures should give sufficient time for the occupants to vacate. The structures, thus, should give sufficient warning to the occupants and must not fail suddenly.

1.1.2.3 The designed structures should be durable.

The materials of reinforced concrete structures get affected by the environmental conditions. Thus, structures having sufficient strength and permissible deformations may have lower strength and exhibit excessive deformations in the long run. The designed structures, therefore, must be checked for durability. Separate checks for durability are needed for the steel reinforcement and concrete. This will avoid problems of frequent repairing of the structure.

1.1.2.4 The designed structures should adequately resist to the effects of misuse and fire.

Structures may be misused to prepare fire works, store fire works, gas and other highly inflammable and/or explosive chemicals. Fire may also take place as accidents or as secondary effects during earthquake by overturning kerosene stoves or lantern, electrical short circuiting etc. Properly designed structures should allow sufficient time and safe route for the persons inside to vacate the structures before they actually collapse.

How to fulfill the objectives?

All the above objectives can be fulfilled by understanding the strength and deformation characteristics of the materials used in the design as also their deterioration under hostile exposure. Out of the two basic materials concrete and steel, the steel is produced in industries. Further, it is available in form of standard bars and rods of specific diameters. However, sample testing and checking are important to ensure the quality of these steel bars or rods. The concrete, on the other hand, is prepared from several materials (cement, sand,

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coarse aggregate, water and admixtures, if any). Therefore, it is important to know the characteristic properties of each of the materials used to prepare concrete. These materials and the concrete after its preparation are also to be tested and checked to ensure the quality. The necessary information regarding the properties and characteristic strength of these materials are available in the standard codes of practices of different countries. It is necessary to follow these clearly defined standards for materials, production, workmanship and maintenance, and the performance of structures in service.

1.1.3 Method of Design

Three methods of design are accepted in cl. 18.2 of IS 456:2000 (Indian Standard Plain and Reinforced Concrete - Code of Practice, published by the Bureau of Indian Standards, New Delhi). They are as follows:

1.1.3.1 Limit state method

The term “Limit states” is of continental origin where there are three limit states - serviceability / crack opening / collapse. For reasons not very clear, in English literature limit state of collapse is termed as limit state.

As mentioned in sec. 1.1.1, the semi-empirical limit state method of design has been found to be the best for the design of reinforced concrete members. More details of this method are explained in Module 3 (Lesson 4). However, because of its superiority to other two methods (see sections 2.3.2 and 2.3.3 of Lesson 3), IS 456:2000 has been thoroughly updated in its fourth revision in 2000 taking into consideration the rapid development in the field of concrete technology and incorporating important aspects like durability etc. This standard has put greater emphasis to limit state method of design by presenting it in a full section (section 5), while the working stress method has been given in Annex B of the same standard. Accordingly, structures or structural elements shall normally be designed by limit state method.

1.1.3.2 Working stress method

This method of design, considered as the method of earlier times, has several limitations. However, in situations where limit state method cannot be conveniently applied, working stress method can be employed as an alternative. It is expected that in the near future the working stress method will be completely replaced by the limit state method. Presently, this method is put in Annex B of IS 456:2000.

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1.1.3.3 Method based on experimental approach

The designer may perform experimental investigations on models or full size structures or elements and accordingly design the structures or elements. However, the four objectives of the structural design (sec. 1.1.2) must be satisfied when designed by employing this approach. Moreover, the engineer-in- charge has to approve the experimental details and the analysis connected therewith.

Though the choice of the method of design is still left to the designer as per cl. 18.2 of IS 456:2000, the superiority of the limit state method is evident from the emphasis given to this method by presenting it in a full section (Section 5), while accommodating the working stress method in Annex B of IS 456:2000, from its earlier place of section 6 in IS 456:1978. It is expected that a gradual change over to the limit state method of design will take place in the near future after overcoming the inconveniences of adopting this method in some situations.

1.1.4 Analysis of Structures

Structures when subjected to external loads (actions) have internal reactions in the form of bending moment, shear force, axial thrust and torsion in individual members. As a result, the structures develop internal stresses and undergo deformations. Essentially, we analyse a structure elastically replacing each member by a line (with EI values) and then design the section using concepts of limit state of collapse. Figure 1.1.1 explains the internal and external reactions of a simply supported beam under external loads. The external loads to be applied on the structures are the design loads and the analyses of structures are based on linear elastic theory (vide cl. 22 of IS 456:2000).

1.1.5 Design Loads

The design loads are determined separately for the two methods of design as mentioned below after determining the combination of different loads.

1.1.5.1 In the limit state method, the design load is the characteristic load with appropriate partial safety factor (vide sec. 2.3.2.3 for partial safety factors).

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1.1.5.2 In the working stress method, the design load is the characteristic load only.

What is meant by characteristic load?

Characteristic load (cl. 36.2 of IS 456:2000) is that load which has a ninety-five per cent probability of not being exceeded during the life of the structure.

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The various loads acting on structures consist of dead loads, live loads, wind or earthquake loads etc. These are discussed in sec. 1.1.6. However, the researches made so far fail to estimate the actual loads on the structure. Accordingly, the loads are predicted based on statistical approach, where it is assumed that the variation of the loads acting on structures follows the normal distribution (Fig. 1.1.2). Characteristic load should be more than the average/mean load. Accordingly,

Characteristic load = Average/mean load + K (standard deviation for load)

The value of K is assumed such that the actual load does not exceed the characteristic load during the life of the structure in 95 per cent of the cases.

1.1.6 Loads and Forces

The following are the different types of loads and forces acting on the structure. As mentioned in sec. 1.1.5, their values have been assumed based on earlier data and experiences. It is worth mentioning that their assumed values as stipulated in IS 875 have been used successfully.

1.1.6.1 Dead loads

Anims. 1.1.5 a and

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b

These are the self weight of the structure to be designed (see Anim. 1.1.5a). Needless to mention that the dimensions of the cross section are to be assumed initially which enable to estimate the dead loads from the known unit weights of the materials of the structure. The accuracy of the estimation thus depends on the assumed values of the initial dimensions of the cross section. The values of unit weights of the materials are specified in Part 1 of IS 875.

1.1.6.2 Imposed loads

They are also known as live loads (Anim. 1.1.5a) and consist of all loads other than the dead loads of the structure. The values of the imposed loads depend on the functional requirement of the structure. Residential buildings will have comparatively lower values of the imposed loads than those of school or office buildings. The standard values are stipulated in Part 2 of IS 875.

1.1.6.3 Wind loads

These loads (Anim. 1.1.5a) depend on the velocity of the wind at the location of the structure, permeability of the structure, height of the structure etc. They may be horizontal or inclined forces depending on the angle of inclination of the roof for pitched roof structures. They can even be suction type of forces depending on the angle of inclination of the roof or geometry of the buildings (Anim. 1.1.5b). Wind loads are specified in Part 3 of IS 875.

1.1.6.4 Snow loads

These are important loads for structures located in areas having snow fall, which gets accumulated in different parts of the structure depending on projections, height, slope etc. of the structure (Anim. 1.1.6). The standard values of snow loads are specified in Part 4 of IS 875.

1.1.6.5 Earthquake forces

Anim. 1.1.6

Anim. 1.1.7

Earthquake generates waves which move from the origin of its location (epicenter) with velocities depending on the intensity and magnitude of the earthquake. The impact of earthquake on structures depends on the stiffness of the structure, stiffness of the soil media, height and location of the structure etc. (Anim. 1.1.7). Accordingly, the country has been divided into several zones depending on the magnitude of the earthquake. The earthquake forces are

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prescribed in IS 1893. Designers have adopted equivalent static load approach or spectral method.

1.1.6.6 Shrinkage, creep and temperature effects

Anim. 1.1.8, 9 and 10

Shrinkage, creep and temperature (high or low) may produce stresses and cause deformations like other loads and forces (Anim. 1.1.8, 9 and 10). Hence, these are also considered as loads which are time dependent. The safety and serviceability of structures are to be checked following the stipulations of cls. 6.2.4, 5 and 6 of IS 456:2000 and Part 5 of IS 875.

1.1.6.7 Other forces and effects

It is difficult to prepare an exhaustive list of loads, forces and effects coming onto the structures and affecting the safety and serviceability of them. However, IS 456:2000 stipulates the following forces and effects to be taken into account in case they are liable to affect materially the safety and serviceability of the structures. The relevant codes as mentioned therein are also indicated below:

• Foundation movement (IS 1904) (Fig. 1.1.3) • Elastic axial shortening

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• Soil and fluid pressures (vide IS 875 - Part 5) • Vibration • Fatigue • Impact (vide IS 875 - Part 5) • Erection loads (Please refer to IS 875 - Part 2) (Fig. 1.1.4) • Stress concentration effect due to point of application of load and the

like.

1.1.6.8 Combination of loads

Design of structures would have become highly expensive in order to maintain their serviceability and safety if all types of forces would have acted on all structures at all times. Accordingly, the concept of characteristic loads has been accepted to ensure that in at least 95 per cent of the cases, the characteristic loads considered will be higher than the actual loads on the structure. However, the characteristic loads are to be calculated on the basis of average/mean load of some logical combinations of all the loads mentioned in sec. 1.1.6.1 to 7. These logical combinations are based on (i) the natural phenomena like wind and earthquake do not occur simultaneously, (ii) live loads on roof should not be present when wind loads are considered; to name a few. IS 875 Part 5 stipulates the combination of loads to be considered in the design of structures.

1.1.7 Practice Questions and Problems with Answers

Q.1: Show two reasons why concrete is superior to stone, timber and steel?

A.1:

(i) Stone, timber and steel cannot be fitted to any mould, but concrete during its green stage can fit to any mould.

(ii) Structures made of stone, timber and steel have several joints, but different elements of concrete structures can be cast monolithically.

Q.2: Define integrated structure.

A.2:

Integrated structure is one where each part of the structure satisfies both the structural requirements of strength and serviceability and architectural requirements of aesthetics and functionality.

Q.3: State four objectives of the design of reinforced concrete structure.

A.3: Properly designed reinforced concrete structures should:

(i)

have acceptable probability of performing satisfactorily during their intended life,

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(ii)

(iii)

(iv)

sustain all loads with limited deformations during construction and use,

be durable,

adequately resist the effects of misuse and fire.

Q.4: How to fulfil the four objectives of the design of reinforced concrete structures?

A.4: The four objectives can be fulfilled by:

(i)

(ii)

understanding the strength and deformation characteristics of concrete and steel,

following the clearly defined standards for materials, production, workmanship and maintenance, and use of structures in service,

(iii)

adopting measures needed for durability.

Q.5: What are the three methods of design of reinforced concrete structural elements?

A.5: The three methods are:

(i) limit state method, (ii) working stress method, (iii) method based on experimental approach

Q.6: Which of the three methods is the best?

A.6: Limit state method is the best of the three methods when clearly applicable.

Q.7: What is the basis of the analysis of structures to be designed?

A.7: The basis of the analysis is the employment of linear elastic theory.

Q.8: How to estimate the design loads in (i) limit state method, and (ii) working stress method?

A.8:

(i) In limit state method,

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Design loads = Characteristic loads multiplied by the partial safety factor for loads

(ii) In working stress method,

Design loads = Characteristic loads

Q.9: Define characteristic load.

A.9: Characteristic load is that load which has a ninety-five per cent probability of not being exceeded during the life of the structure.

Q.10: What are the main (i) loads, (ii) forces and (iii) effects to be considered while designing the structures?

A.10: (i) The main loads are:

(a) Dead loads (b) Imposed loads or live loads (c) Wind loads (d) Snow loads (e) Erection loads

(ii) The main force is:

(a) Earthquake force

(iii) The main effects are:

(a) Shrinkage, creep and temperature effects (b) Foundation movements (c) Elastic axial shortening (d) Soil and fluid pressures (e) Vibration (f) Fatigue (g) Impact (h) Stress concentration effects due to application of point loads

Q.11: What are the basis of combining different loads for the design?

A.11: Natural phenomenon and common sense are the basis of selecting the combination different loads acting on the structure while designing.

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1.1.8 References

Reinforced Concrete Limit State Design, 6th Edition, by Ashok K. Jain, Nem Chand & Bros, Roorkee, 2002.
Limit State Design of Reinforced Concrete, 2nd Edition, by P.C.Varghese,
Prentice-Hall of India Pvt. Ltd., New Delhi, 2002. 3. Advanced Reinforced Concrete Design, by P.C.Varghese, Prentice-Hall of

India Pvt. Ltd., New Delhi, 2001. 4. Reinforced Concrete Design, 2nd Edition, by S.Unnikrishna Pillai and

Devdas Menon, Tata McGraw-Hill Publishing Company Limited, New Delhi, 2003. 5. Limit State Design of Reinforced Concrete Structures, by P.Dayaratnam,

Oxford & I.B.H. Publishing Company Pvt. Ltd., New Delhi, 2004. 6. Reinforced Concrete Design, 1st Revised Edition, by S.N.Sinha, Tata

McGraw-Hill Publishing Company. New Delhi, 1990. 7. Reinforced Concrete, 6th Edition, by S.K.Mallick and A.P.Gupta, Oxford &

IBH Publishing Co. Pvt. Ltd. New Delhi, 1996. 8. Behaviour, Analysis & Design of Reinforced Concrete Structural Elements,

by I.C.Syal and R.K.Ummat, A.H.Wheeler & Co. Ltd., Allahabad, 1989. 9. Reinforced Concrete Structures, 3rd Edition, by I.C.Syal and A.K.Goel,

A.H.Wheeler & Co. Ltd., Allahabad, 1992. 10. Textbook of R.C.C, by G.S.Birdie and J.S.Birdie, Wiley Eastern Limited,

New Delhi, 1993. 11. Design of Concrete Structures, 13th Edition, by Arthur H. Nilson, David

Darwin and Charles W. Dolan, Tata McGraw-Hill Publishing Company Limited, New Delhi, 2004. 12. Concrete Technology, by A.M.Neville and J.J.Brooks, ELBS with

Longman, 1994. 13. Properties of Concrete, 4th Edition, 1st Indian reprint, by A.M.Neville,

Longman, 2000. 14. Reinforced Concrete Designer’s Handbook, 10th Edition, by C.E.Reynolds

and J.C.Steedman, E & FN SPON, London, 1997. 15. Indian Standard Plain and Reinforced Concrete – Code of Practice (4th

Revision), IS 456: 2000, BIS, New Delhi. 16. Design Aids for Reinforced Concrete to IS: 456 – 1978, BIS, New Delhi.

1.1.9 Test 1 with Solutions

Maximum Marks = 50, Maximum Time = 30 minutes

Answer all questions.

TQ.1: Tick the correct answer: (4 x 7 = 28 marks)

(i) Properly designed concrete structures should

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(a) sustain all loads likely to come during next 50 years

(b) sustain all loads and deformations without collapse or any damage

(c) sustain all loads with limited deformations during construction and use

(d) sustain characteristic loads and deformations during the next 50 years

A.TQ.1: (i): (c)

(ii) In the limit state method, the design load is

(a) the characteristic load

(b) the ultimate load

(c) the characteristic load divided by the partial safety factor for loads

(d) the characteristic load multiplied by the partial safety for loads

A.TQ.1: (ii): (d)

(iii) In the limit state method, the basis of the analysis of structure is

(a) linear elastic theory

(b) non-linear theory

(c) plastic method of analysis

(d) involving fracture mechanics

A.TQ.1: (iii): (a)

(iv) The characteristic load is

(a) the load at first crack

(b) that load which has a probability of ninety-five per cent of not being exceeded during the life of the structure

(c) the ultimate collapse load

(d) the ultimate collapse load multiplied by the partial safety factor for loads

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A.TQ.1: (iv): (b)

TQ.2: Name the main (i) loads, (ii) forces and (iii) effects to be considered while designing the structures.

(5 + 1 + 8 = 14 marks) (5 marks for five loads, 1 mark for one force and 8 marks for eight effects)

A.TQ.2: See A.10 of sec. 1.1.7.

TQ.3: State the basis of determining the combination of different loads acting on the structure.

(8 marks)

A.TQ.3: See A.11 of sec. 1.1.7.

1.1.10 Summary of this Lesson

This lesson explains the four objectives of the design of reinforced concrete structures. It also mentions the three methods of design and states about the superiority of the limit state method. The basis of the analysis of structure is discussed. The terminologies like design loads, characteristic loads etc. are defined and explained. The different loads, forces and effects to be considered have been listed and discussed. Finally, the basis of the combination of different loads to be considered is also explained.

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Mashing newspaper PDFs for ebooks with PdfMasher

 PdfMasher is a tool to convert PDF articles (newspaper, academic) to MOBI or EPUB documents. Most ebook readers support PDF files natively, but it's often a real pain to read those documents because we don't have font size control over the document like we have with native ebooks. In many cases, we have to use the zooming feature and it's just a pain. Another drawback of PDFs on ebook readers is that annotations are not supported.
There are already tools to convert PDFs to ebooks like Calibre, but what they do is that they try to guess the role of each piece of text in the PDF (and that's if you're lucky). I think that in all but the simplest cases, it's a mistake to think that anything short of an AI can do that kind of guessing.
Enter PdfMasher. PdfMasher asks the user about the role of each piece of text, and does it in an efficient manner. Your PDF has a header on each page and you don't want them to litter your text? Sort text elements by Y-position (thus grouping them all together), shift select the elements and flag them as ignored. They will not appear on your final HTML. Your PDF has footnotes on many pages? Sort your elements by text content (thus grouping all elements with the text starting with a number together) and flag them as footnotes. They will be moved to the end of the document, and PdfMasher will try to create hyperlinks to footnote references.

bangaru babu-4 rare movie. vasantha maligai shooting scene..avi

Materials Tortured in Space



An ongoing experiment tests the mettle of glass and other materials

High-energy radiation and atomic oxygen wreak havoc on satellite parts. To evaluate the durability of materials being developed for future satellites, the U.S. Naval Research Laboratory is running samples through a space-based torture test called MISSE-8. Astronauts bolted a platform full of one-inch samples of mirror coatings, laser-tuning crystals, structural foam and other materials to the outside of the International Space Station, where it will remain for just over two years. The samples, which were sent to the ISS on one of the last space shuttle flights, in May, will return to Earth in July 2013 on the SpaceX Dragon capsule. Scientists from the labs that made each sample will examine them for pitting, cracks and discolouration.

World Biggest Ship - Oasis of Seas






































Researchers Watch Type 1 Diabetes As It Unfolds, in Real Time


Real-time immune attack could pinpoint new interventions, thanks to a new procedure
T Cells Attacking This image, captured from video, shows the T cells (purple dots) attacking the pancreatic islets (green images in center), which contain the insulin‑producing beta cells. Beta cell destruction leads to type 1 diabetes. The attack continues over several hours before a number of beta cells are destroyed. La Jolla Institute for Allergy & Immunology
A new real-time view of immune cells attacking the pancreas sheds light on how type 1 diabetes unfolds, as white blood cells seek out and destroy insulin-producing beta cells. Researchers believe it could help point the way to new intervention methods to halt the destruction before the onset of type 1 diabetes, also known as juvenile diabetes.
Diabetes results from the body’s lack of ability to produce sufficient insulin, which keeps blood glucose levels in check. Type 1 is an autoimmune disorder in which the body’s T lymphocytes attack and kill the pancreas’ insulin-making beta cells; type 2 also involves pancreatic destruction and can result from several factors, though in this country it is often the result of poor diet and obesity. There is no cure, at least not yet. Watching exactly how the destructive process unfolds could be a major step in that direction, however.

Researchers at the La Jolla Institute for Allergy & Immunology used two-photon excitation microscopy and a new imaging technique to access a live, functioning pancreas in a mouse. The pancreas is small, soft and tucked away beneath other organs in the abdominal area, so it’s difficult to see in action. This study marks the first time researchers have used two-photon microscopy to study the pancreas (it’s previously been used to image the liver, lymph nodes and some other organs).
Two-photon microscopes use ultra-fast pulses of infrared light to excite fluorescent dyes that have been attached to specific cells. The IR light minimizes light scattering as well as harmful bleaching of tissues, so it’s useful for penetrating deep into live tissue, around one millimeter.
Led by Ken Coppieters, now at Ghent University in Belgium, La Jolla researchers attached green and blue fluorescent proteins to cytotoxic T cells, a type of white blood cell, and transplanted them into a mouse. The cells migrated randomly throughout the pancreas, making their way to beta cells and eventually killing them. Though they moved in random patterns, the cells were observed to accumulate within and around the β cell population, the authors say. They moved at an average 10 microns per minute and up to 25 microns per minute — not the world’s fastest cells by a long stretch. This comparatively slow process could be one reason why diabetes takes a while to present itself clinically — by the time a patient is diagnosed, up to 90 percent of his or her beta cells have already been destroyed.
This entire cell-hunting process was imaged with the two-photon microscope, and you can see a video of it below. The live imaging of the white blood cells is “remarkable,” according to George Eisenbarth, M.D., a prominent type 1 diabetes researcher and executive director of the Barbara Davis Center for Childhood Diabetes in Denver.
“These images provide critical information about the disease process, in particular showing us the reasons why the beta cell destruction occurs very slowly over time,” he said in a statement. “Such information may enable new approaches to stop the destruction process, with the ultimate goal being prevention.”
Researchers are still not sure what sparks the immune cells into destroying the helpful beta cells. But this study could spark new research into that question, as well as how their destructive abilities might be thwarted, said Matthias von Herrath, M.D., coauthor of the paper.
“These studies suggest that we may need to find a way to prevent the T cells from accessing the pancreas in the first place, since once they do, they have the ability to destroy several beta cells at a time,” he said.
The paper appears in the Journal of Clinical Investigation.

New insights into how the brain reconstructs the third dimension




New insights into how the brain reconstructs the third dimensionThis is a new illusion in which random noise (left) is made to look like a 3-D shape (right). Credit: MPI for Biological Cybernetics
A new visual illusion has shed light on a long-standing mystery about how the brain works out the 3-D shapes of objects.
As dizzying as it may sound, the impression that we are living in a 3D world is actually a continuous fabrication of our brains. When we look at things, the world gets projected onto the retina and information about the third dimension is lost — a bit like when a 3D object casts a shadow onto a flat, 2D wall. Somehow the brain is able to reconstruct the third dimension from the image, allowing us to experience a convincing 3D world. A team of scientists from Giessen University, Yale and the Max Planck Institute for Biological Cybernetics in Tübingen has recently discovered how cells in visual cortex might help solve this mystery. They created special 2D patterns designed to stimulate specific nerve cells when we look at them. They find that the result is a vivid illusion of 3D shape, which suggests these cells play an important role in reconstructing 3D shape.
"We created the images by taking random noise and smearing it out across the image in specific patterns. It's a bit like finger painting, except it's done by computer", explains Roland Fleming, Professor of Psychology at the University of Giessen. "The way the texture gets smeared out is not the way texture behaves in the real 3D world. But it allows us to selectively stimulate so-called 'complex cells' in visual cortex, which measure the local 2D orientation of patterns in the retinal image".
These cells — whose discovery led to a Nobel Prize for David Hubel and Torsten Wiesel – are often described as 'edge detectors' because they respond to boundaries or edges in the image. What was not known was that these cells could play a key role in estimating 3D shape.
"We asked people to adjust small probes to report what they saw. The settings allow us to reconstruct exactly which 3D shapes they perceived," says Heinrich Bülthoff, director of the department of Human Perception, Cognition and Action at the Max Planck Institute for Biological Cybernetics. "What's striking is how close the results are to predictions of a model based on cell responses".
The authors suggest the strongest evidence implicating the cells comes from an experiment in which participants stared at patterns for 30 seconds at a time, to change the way the cells respond. The resulting 'adaptation' causes random noise—which normally looks completely flat—to appear like a specific 3D shape.
"It's a kind of aftereffect, a bit like when you stare at a waterfall for a while, adaptation makes things that are stationary look like they are moving in the opposite direction. Except here, the aftereffect makes the noise look 3D," says Daniel Holtmann-Rice, who is currently doing his PhD at Yale University. "We didn't think it was going to work. It was so exciting to get the first data where we could clearly see the predicted shapes emerging in the participants' settings."
The authors are currently working on generalizing the findings to other kinds of information about 3D shape, such as shading and highlights.
More information: Fleming, RW, Holtmann-Rice D & HH Bülthoff Estimation of 3D shape from image orientations. PNAS, published ahead of print December 6, 2011, doi:10.1073/pnas.1114619109
 


Provided by Max-Planck-Gesellschaft
"New insights into how the brain reconstructs the third dimension." December 7th, 2011. http://medicalxpress.com/news/2011-12-insights-brain-reconstructs-dimension.html
 

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Robert Karl Stonjek

Measuring Living Cells' Mechanical Properties: Technology Could Diagnose Human Disease, Shed Light On Biological Processes


   This artist's conception depicts the use of an atomic force microscope to study the mechanical properties of cells, an innovation that might result in a new way to diagnose disease and study biological processes. Here, three types of cells are studied using the instrument: a rat fibroblast is the long slender cell in the center, an E coli bacterium is at the top right and a human red blood cell is at the lower left. The colored portions show the benefit of the new technique, representing the mechanical properties of the cells, whereas the gray portions represent what was possible using a conventional approach. (Credit: Purdue University image/Alexander Cartagena) 

Science Daily — Researchers are making progress in developing a system that measures the mechanical properties of living cells, a technology that could be used to diagnose human disease and better understand biological processes.

For example, the technique could be used to study how cells adhere to tissues, which is critical for many disease and biological processes; how cells move and change shape; how cancer cells evolve during metastasis; and how cells react to mechanical stimuli needed to stimulate production of vital proteins. The technique could be used to study the mechanical properties of cells under the influence of antibiotics and drugs that suppress cancer to learn more about the mechanisms involved.The team used an instrument called an atomic force microscope to study three distinctly different types of cells to demonstrate the method's potentially broad applications, said Arvind Raman, a Purdue University professor of mechanical engineering.
Findings have been posted online in the journal Nature Nanotechnology and will appear in the December print issue. The work involves researchers from Purdue and the University of Oxford.
"There's been a growing realization of the role of mechanics in cell biology and indeed a lot of effort in building models to explain how cells feel, respond and communicate mechanically both in health and disease," said Sonia Contera, a paper co-author and director of the Oxford Martin Programme on Nanotechnology and an academic fellow at Oxford physics. "With this paper, we provide a tool to start addressing some of these questions quantitatively: This is a big step."
An atomic force microscope uses a tiny vibrating probe to yield information about materials and surfaces on the scale of nanometers, or billionths of a meter. Because the instrument enables scientists to "see" objects far smaller than possible using light microscopes, it could be ideal for "mapping" the mechanical properties of the tiniest cellular structures.
"The maps identify the mechanical properties of different parts of a cell, whether they are soft or rigid or squishy," said Raman, who is working with doctoral student Alexander Cartagena and other researchers. "The key point is that now we can do it at high resolution and higher speed than conventional techniques."
The high-speed capability makes it possible to watch living cells and observe biological processes in real time. Such a technique offers the hope of developing a "mechanobiology-based" assay to complement standard biochemical assays.
"The atomic force microscope is the only tool that allows you to map the mechanical properties -- take a photograph, if you will -- of the mechanical properties of a live cell," Raman said.
However, existing techniques for mapping these properties using the atomic force microscope are either too slow or don't have high enough resolution.
"This innovation overcomes those limitations, mostly through improvements in signal processing," Raman said. "You don't need new equipment, so it's an economical way to bump up pixels per minute and get quantitative information. Most importantly, we applied the technique to three very different kinds of cells: bacteria, human red blood cells and rat fibroblasts. This demonstrates its potential broad utility in medicine and research."
The technique is nearly five times faster than standard atomic force microscope techniques.
The Nature Nanotechnology paper was written by Raman; Cartagena; Sonia Trigueros, a Senior Research Fellow in the Oxford Martin Programme on Nanotechnology; Oxford doctoral student Amadeus Stevenson; Purdue instructor Monica Susilo; Eric Nauman, an associate professor of mechanical engineering; and Contera.
The National Science Foundation and Engineering and Physical Sciences Research Council of the U.K. funded the research.

Oxidative Stress: Less Harmful Than Suspected?


                             Yellow light signals emitted by the biosensor indicate oxidant production in the tissue of a migrating fly larva. (Credit: Tobias Dick, German Cancer Research Center)

Science Daily  — Oxidative stress is considered to be involved in a multitude of pathogenic processes and is also implicated in the proces of aging. For the first time, scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have been able to directly observe oxidative changes in a living organism. Their findings in fruit flies raise doubts about the validity of some widely held hypotheses: The research team has found no evidence that the life span is limited by the production of harmful oxidants.

For the first time, Tobias Dick and his co-workers have been able to observe these processes in a living animal. Jointly with Dr. Aurelio Teleman (also of DKFZ), they introduced genes for biosensors into the genetic material of fruit flies. These biosensors are specific for various oxidants and indicate the oxidative status of each cell by emitting a light signal -- in realtime, in the whole organism and across the entire life span.Arterial calcification and coronary heart disease, neurodegenerative diseases such as Parkinson's and Alzheimer's, cancer and even the aging process itself are suspected to be partially caused or accelerated by oxidative stress. Oxidative stress arises in tissues when there is an excess of what are called reactive oxygen species (ROS). "However, up to now, nobody was able to directly observe oxidative changes in a living organism and certainly not how they are connected with disease processes," said Associate Professor (PD) Dr. Tobias Dick of DKFZ. "There were only fairly unspecific or indirect methods of detecting which oxidative processes are really taking place in an organism."
In the fly larvae, the investigators already discovered that oxidants are produced at very differing levels in different tissue types. Thus, blood cells produce considerably more oxidants in their energy plants, the mitochondria, than, for example, intestinal or muscle cells. In addition, the larvae's behavior is reflected in the production of oxidants in individual tissues: The researchers were able to distinguish whether the larvae were eating or moving by the oxidative status of the fat tissue.
Up to now, many scientists have assumed that the aging process is associated with a general increase in oxidants throughout the body. However, this was not confirmed by the observations made by the investigators across the entire life span of the adult animals. They were surprised that almost the only age-dependent increase in oxidants was found in the fly's intestine. Moreover, when comparing flies with different life spans, they found out that the accumulation of oxidants in intestinal tissue even accelerated with a longer life span. The group thus found no evidence supporting the frequently voiced assumption that an organism's life span is limited by the production of harmful oxidants.
Even though comprehensive studies have failed to provide proof until the present day, antioxidants are often advertised as a protection against oxidative stress and, thus, health-promoting. Dick and colleagues fed their flies with N-acetyl cysteine (NAC), a substance which is attributed an antioxidant effect and which some scientists consider suitable for protecting the body against presumably dangerous oxidants. Interestingly, no evidence of a decrease in oxidants was found in the NAC-fed flies. On the contrary, the researchers were surprised to find that NAC prompted the energy plants of various tissues to significantly increase oxidant production.
"Many things we observed in the flies with the help of the biosensors came as a surprise to us. It seems that many findings obtained in isolated cells cannot simply be transferred to the situation in a living organism," said Tobias Dick, summarizing their findings. "The example of NAC also shows that we are currently not able to predictably influence oxidative processes in a living organism by pharmacology," he adds. "Of course, we cannot simply transfer these findings from fly to man. Our next goal is to use the biosensors to observe oxidative processes in mammals, especially in inflammatory reactions and in the development of tumors."

Why Does the Same Mutation Kill One Person but Not Another?


                           The figure shows how the same mutation can differently affect each individual from C. elegans. The dice represent the stochastic component in the gene expression. (Credit: Image courtesy of Centre for Genomic Regulation)

Science Daily — The vast majority of genetic disorders (schizophrenia or breast cancer, for example) have different effects in different people. Moreover, an individual carrying certain mutations can develop a disease, whereas another one with the same mutations may not. This holds true even when comparing two identical twins who have identical genomes. But why does the same mutation have different effects in different individuals?

Since the early twentieth century researchers have studied the role that genetic variability (mutations) and the environment (consumption habits, lifestyle, etc.) have in the development of diseases. "However, genetic and environmental differences are not enough" said Alejandro Burga, one of the authors of the article. "In the last decade we have learned by studying very simple organisms such as bacteria that gene expression -- the extent to which a gene is turned on or off -- varies greatly among individuals, even in the absence of genetic and environmental variation. Two cells are not completely identical and sometimes these differences have their origin in random or stochastic processes. The results of our study show that this type of variation can be an important influence the phenotype of animals, and that its measurement can help to reliably predict the chance of developing an abnormal phenotype such as a disease ."
The researchers conducted their study using the roundwormCaenorhabditis elegans as a model. Due to its simplicity, this microscopic worm is one of the most widely studied organisms in biology, and was the first animal to have its genome sequenced. Recently three different Nobel Prizes have been awarded for research using C. elegans.
Since the genetic composition and the environment are insufficient to determine whether or not a mutation will affect an individual, they developed a methodology to measure small differences in gene expression in vivo. "The challenge was not only to develop a method to quantify these small differences among individuals, but also to predict which genes are relevant for a particular mutation," adds Ben Lehner, coordinator of the study and ICREA Research Professor in the European Molecular Biology Laboratory-Centre for Genomic Regulation Systems Biology Research Unit. "In both round worms and humans, genes cooperate and help each other to perform functions within the cell. A few genes are very "generous" and help hundreds of others to perform many different processes, whereas others only help a few other genes to perform more specific functions. The key to predict what will happen in each individual is to measure variation in the expression of both types of gene."
The work suggests that, even if we completely understand all of the genes important for a particular human disease, we may never be able to predict what will happen to each person from their genome sequence alone. Rather, to develop personalised and predictive medicine it will also be necessary to consider the varying extent to which genes are turned on or off in each person.
The study was funded by the European Research Council, the Institució Catalana de recerca i Estudis Avanzats (ICREA) and the Ministry of Science and Innovation (MICINN).

Optical illusion reveals reflexes in the brain




New research by psychologists at Queen Mary, University of London has revealed that the way we see the world might depend on reflexes in the brain.
Writing in the Journal of Vision, Dr Michael Proulx from Queen Mary's School of Biological and Chemical Sciences, and former student Monique Green, explain how an optical illusion known as the Müller-Lyer Illusion captures our attention more strongly than other visual tests, suggesting that the brain calculates size as a reflex fast enough to guide where the eyes look.
The Müller-Lyer illusion was first described by F.C. Müller-Lyer in 1889, and is one of the most famous size illusions. He found that two lines of the same length can be seen as longer or shorter by simply adding arrow heads that point in or out at either end.
In this study, Dr Proulx and Green asked participants to search for a vertical line among distracting lines tilted to the left and right. All of the lines had arrow heads at either end that randomly pointed in or out, making some lines appear to be longer or shorter than others due to the illusion. They found that the line that appeared to be the longest captured the participants' attention the most.
Dr Proulx explains: "The surprising difference here is that the perceived longer line not only captured their attention, but was even more distracting than the sudden appearance of something new as shown in prior research.
"This suggests that many visual illusions might be so effective because they tap into how the human brain reflexively processes information."
Reflexes are immediate and involuntary responses that allow a quick reaction, such as pulling your hand away from a hot surface.
Dr Proulx adds: "If an illusion can capture attention in this way, then this suggests that the brain processes these visual clues rapidly and unconsciously. This also suggests that perhaps optical illusions represent what our brains like to see."
The team hope that their findings can be used to help unlock clues about how the brain has evolved to not just represent the world as it is, but in a way that is most effective for survival. "A number of conditions exhibit differences in attention, such as Autism and schizophrenia, and it would be useful to see whether visual illusions are still given priority even when other aspects of attention are affected," adds Proulx.
Provided by Queen Mary, University of London
"Optical illusion reveals reflexes in the brain." December 7th, 2011. http://medicalxpress.com/news/2011-12-optical-illusion-reveals-reflexes-brain.html
 

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Robert Karl Stonjek