Saturday, July 21, 2018

Those who cannot remember the past are condemned to repeat it. Vietnam and Afghanistan/iraq

Those who cannot remember the past are condemned to repeat it. —GEORGE SANTAYANA, PHILOSOPHER (1863— 1952)

 Recently I saw the Netflix series on Vietnam in a marathon session.

 It is so striking that  it took only 26 years to forget all the lessons learnt 
April 30, 1975
The War in Afghanistan (or the U.S. War in Afghanistan; code named Operation Enduring Freedom – Afghanistan (2001–2014) and Operation Freedom's Sentinel (2015–present))[50][51]followed the United States invasion of Afghanistan[52] of October 7, 2001. The U.S. was supported initially by the United Kingdom and Canada[53] and later by a coalition of over 40 countries, including all NATO members. The war's public aims were to dismantle al-Qaeda and to deny it a safe base of operations in Afghanistan by removing the Taliban from power.[54] The War in Afghanistan is the second longest war in United States history, behind the Vietnam War.[55][56][57][58][59]

 "

NO GOOD MEN AMONG THE LIVING: AMERICA, THE TALIBAN, AND THE WAR THROUGH AFGHAN EYES

Metropolitan Books/ Henry Holt and Company
ISBN: 978-0805091793


CITATION

Vivid, haunting, and courageous, No Good Men Among the Living by Anan"d  Gopal illuminates a war shaped and distorted by powerful convictions of categorical morality, of starkly contrasting rights and wrongs imposed on a complex and alien culture. Learning local languages and immersing himself in Afghani life, Anand Gopal offers a richly particular account of the American entanglement in Afghanistan. Through the lives and tales of three Afghanis, Gopal recovers a rich texture of absurdity and tragedy as distant people become enmeshed with a superpower.
"There are no good men among the living, and no bad ones among the dead."
"three people in particular who've lived this reality. One is an insurgent Taliban commander fighting against the Americans; another, a powerful member of the US-backed Afghan government; and the third, a village housewife—or, in the language of America's categories, our enemy, our ally, and a civilian."

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Planned obsolescence:The trap in to which india is falling

Planned obsolescence :
అడుసు తొక్కనేల కాలు కడుగనేల 
This is  a telugu saying  which  why to put your  feet in the mud  and  then  go and  wash your feet,i.e avoid  stepping in to mud
The trap in to which India is falling along with the major economies of the world
 when I was growing up in India 1956 to 1990
Share, reuse and prolong life of products.
was the philosophy. now having the latest  version of iphone is the goal. Periya kovil

Brihadisvara Temple, Thanjavur

Built by Raja Raja Chola I between 1003 and 1010 AD
At a time when Planned permanence was the ruling  Philosophy and  nobody needed to lecture  people  on sustainability  and  there were no "Save Earth" days (

Annual ‘Earth Day’ Will Not Save Earth

planned ob·so·les·cence
ˌpland ˌäbsəˈlesəns/
noun
  1. A policy of producing consumer goods that rapidly become obsolete and so require replacing, achieved by frequent changes in design, termination of the supply of spare parts, and the use of nondurable materials.

"Planned obsolescence is a common practice in product design; for example, in the computer industry. From a business point of view, it makes sense to deliberately shorten the life cycle of a product — think of your smartphone - to stimulate consumption. From a sustainability perspective, such a business strategy is obscene and should be banned. "
Professor Klaus Bosselmann, The University of Auckland

" unlike automobiles, Steinways don't have annual model changes. Former CEO Peter Perez reportedly said that the most serious competition he faced came from vintage Steinway grands, which sometimes  command four times more than their original retail prices.""

 caring for the Earth shouldn’t be limited to a span of 24 hours. People ought to act as they do on April 22 everyday of the year

"In a time when ecological crisis is about to turn into a catastrophe for Planet Earth and all living creatures, humankind is desperately seeking solutions and the discussion about our way of life and bad habits have become crucial. In such a complex society as the one we live in, mostly based on capital circulation nourished by induced irrational consumption, planned obsolescence, as a main instrument to perpetuate the unsustainable 'status quo', is right in the heart of this urgent discussion towards sustainability. This is what this book is about: questioning these bad habits that sustain consumer society; explaining why they are poisoning the environment and killing the life on the Planet; proposing new standards of human behaviour; pointing to sustainability through an 'Ecological Economics', that Green or even the most recent concept of Circular Economy does not fit yet, because it is still based on 'Environmental Neoclassical Economics'; creating a 'new paradigm' and a 'revolutionary reform'. As the author concludes, this book intends 'to show the possibility of concrete action that works towards socio-environmentally responsible productive behaviour, especially about durability of goods'. 
Branca Martins da Cruz Cathedratic Professor on Environmental Law at Universidade Lusiada de Lisboa Director of ILDA — Lusiada Environmental Law Institute Counsellor of the Foreign Affairs Ministry of Portugal

 "As we saw in the first chapter, the majority of today's societies can be described as consumer societies, the main driver of which is, obviously, consumerism; this is generated by manipulation of the behavioural patterns of individuals to get them to consume increasingly superfluous products in ever greater amounts and at ever greater speed. This type of society, with its values of abundance and wastage, has not come about by chance. As well as being the result of an extremely predatory anthropocentric perspective, which has distanced humans from the natural cycles of recovery and resilience, it was forged to succeed the society of producers and to maintain an economic model based on the idea of infinite growth."
IKEA  one of the worst furniture company in my opinion,when it comes to sustainability.
Read its ironic Sustainability Strategy, People & Planet Positivehttps://www.ikea.com/ms/en_US/pdf/people_planet_positive/IKEA_Sustainability_Strategy_People_Planet_Positive_v3.pdf

ABRELPE 
CCMI 
CDC 
ECHR 
EEA 
EESC 
EMF 
EPA 
EU 
FAO 
FCC 
GDP 
GM 
GNP 
HG 
Associac,io Brasileira de Empresas de Limpeza Pliblica e 
Residuos Especiais (Brazilian Association of Public 
Cleaning and Special Waste Companies) 
Consultative Commission on Industrial Change 
Cödigo de Defesa do Consumidor (Brazilian Consumer 
Protection Code) 
European Convention on Human Rights 
European Environment Agency 
European Economic and Social Committee 
Ellen MacArthur Foundation 
Environmental Protection Agency 
European Union 
Food and Agriculture Organization of the United Nations 
Federal Communications Commission 
Gross Domestic Product 
General Motors 
Gross National Product 
Hunter-gatherers 

IBDI 

IBGE 

IPP 
ISO 
IUCN 
JPOI 
NGO 
PBT 
Ri092 
Ri0+5 
Ri0+10 
Ri0+20 
SCP 
Instituto Brasileiro de Politica e Direito da Informåtica 
(Brazilian Institute Of IT Law and Policy) 
Instituto Brasileiro de Geografia e Estatistica (Brazilian 
Institute of Geography and Statistics) 
Integrated Product Policy 
International Organization for Standardization 
International Union for Conservation of Nature 
Johannesburg Plan of Implementation 
Non-governmental organization 
Persistent Bioaccumulative and Toxic 
United Nations Conference on Environment and 
Development 
19th Special Session of the UN General Assembly 
World Summit on Sustainable Development 
United Nations Conference on Sustainable Development 
Sustainable Consumption and Production 

SDG 

SIP 

STJ 
UNEP 
Unesco 
US 
USA 
WCED 
wcs 
WEEE 
WSSD 
IOYFP 
Sustainable Development Goals 
Sustainable Industrial Policy 
Superior Tribunal de Justi€a (Brazilian Superior Court Of 
Justice) 
United Kingdom 
United Nations 
United Nations Environment Programme 
United Nations Educational, Scientific and Cultural 
Organization 
United States of America 
United States of America 
World Commission on Environment and Development 
World Conservation Strategy 
Waste from electrical and electronic equipment 
World Summit on Sustainability and Development 
World Wildlife Fund 
I O-year Framework Of Programmes 

CIRCULAR ECONOMY 

Concept 

The economy that is restorative and regenerative by 
design and aims to keep products, components, and 
materials at their highest utility and value at all times. 
The concept distinguishes between technical and 
biological cycles 

Foundations 

Cradle to Cradle, Biomimicry, Industrial Ecology, among others 

Characteristics 

design out waste; 
build resilience through diversity; 
work towards energy from renewable sources; 
systemic thinking; and think in cascades 

Principles 

Preserve and enhance natural capital by controlling finite stocks and balancing renewable resource flows; 
-Optimize resource yields by circulating products



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IT fundamentals and related jargon

Compare and contrast common computer connector types.

older legacy connectors 

DIN connector


Video
- VGA
- DVI
- HDMI
- Display port/Thunderbolt
- USB
- S-video
- Component - RGB
• FireWire
• eSATA
• Thunderbolt
• USB
• PS/2
• Parallel
• Serial
• RJ-45
• RJ-11
• Audio
• Power
- AC/DC

Identify the purpose of internal computer components.

• CPU
• RAM

• Expansion cards

- Video card
- Audio card
- Network card
- Modem
• Motherboard/mainboard
• System cooling
- Case fans
- CPU fans
- Liquid cooling
2.0 Hardware

Identify basic wired and wireless peripherals and their purpose.

Identify


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Friday, July 20, 2018

Bloody bastards selling their stupid stuff and fooling the public in India

 How can you expect the Indian Government to stop these quacks who are spreading misinformation about Diabetes and marketing their easy cures?

Let us  realize this
Unfortunately so far there are no scientifically proven easy methods to Cure  Diabetes.
the only known cures are
Pancreatic whole organ or Islet transplantation Mainly for type 1
Bariatric Surgery in Obese type 2 diabetics.
The following Charlatans are peddling their Snake oil.  Do not believe them and waste your money and  make them millionaires.

Rouges Gallery 
rogues' gal·ler·y
noun
informal
noun: rogues' gallery; plural noun: rogues' galleries
  1. a collection of photographs of known criminals, used by police to identify suspects.
    • a collection of people or creatures notable for a certain shared quality or characteristic, typically a disreputable one

BABA RAMDEV
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PUBLIC RELEASE: 

Cell-based therapy for type 1 diabetes?

Scientists reverse diabetes in a mouse model using modified blood stem cells
BOSTON CHILDREN'S HOSPITAL
 
IMAGE: IN TYPE 1 DIABETES, AUTOREACTIVE T-CELLS ATTACK INSULIN-PRODUCING ISLET CELLS IN THE PANCREAS (FRAME 1). FIORINA AND COLLEAGUES SHOWED THAT THE NETWORK OF GENETIC REGULATORY FACTORS CONTROLLING PRODUCTION OF... view more 
CREDIT: ANDREA PANIGADA/NANCY FLIESLER
Researchers at Boston Children's Hospital have successfully reversed type 1 diabetes in a mouse model by infusing blood stem cells pre-treated to produce more of a protein called PD-L1, which is deficient in mice (and people) with type 1 diabetes. The cells curbed the autoimmune reaction in cells from both mice and humans and reversed hyperglycemia in diabetic mice.
Findings were published today in Science Translational Medicine. "There's really a reshaping of the immune system when you inject these cells," says Paolo Fiorina, MD, PhD, of Boston Children's, senior investigator on the study.
The study shows that the treated stem cells, given to mice, home to the pancreas where islet cells are made. Almost all the mice were cured of diabetes in the short term, and one third maintained normal blood sugar levels for the duration of their lives. The treatment was effective whether PD-L1 production was stimulated through gene therapy or pre-treatment with small molecules.
The powers of PD-L1
Previous studies have tried using immunotherapies for type 1 diabetes, aiming to curb the autoimmune attack on the body's islet cells. These attempts have failed, in part because the therapies have not targeted diabetes specifically. Autologous bone-marrow transplant -- infusing patients with their own blood stem cells to reboot their immune system -- has helped some patients, but not all.
"Blood stem cells have immune-regulatory abilities, but it appears that in mice and humans with diabetes, these abilities are impaired," says Fiorina, in Boston Children's Division of Nephrology. "We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease."
A team led by Fiorina and first author Moufida Ben Nasr, PhD, also of Boston Children's, began by profiling the transcriptome of blood stem cells to find out what proteins the cells are making.
Using a gene expression microarray, they found that the network of genetic regulatory factors (microRNAs) controlling production of PD-L1 is altered in blood stem cells from diabetic mice and humans. This prevents production of PD-L1, even early in the disease.
They further showed that PD-L1 has a potent anti-inflammatory effect in the context of type 1 diabetes.
PD-L1 is known as an immune "checkpoint" molecule. It binds to the PD-1 receptor (inhibitory programmed death 1) on the inflammatory T-cells that are activated to cause autoimmune reactions. This causes the T-cells to die or become anergic (or inactive).
When Fiorina, Ben Nasr and colleagues introduced a healthy gene for PD-L1 into the stem cells, using a harmless virus as the carrier, the treated cells reversed diabetes in the mice. Fiorina and colleagues also found they could achieve the same effect by treating the cells with a "cocktail" of three small molecules: interferon beta, interferon gamma and polyinosinic-polycytidylic acid.
"We think resolution of PD-L1 deficiency may provide a novel therapeutic tool for the disease," Ben Nasr says.
Future directions
Further study will be needed to determine how long the effects of the cell therapy last and how often the treatment would need to be given. "The beauty of this approach is the virtual lack of any adverse effects, since it would use the patients' own cells," says Fiorina.
In collaboration with scientists from Fate Therapeutics (San Diego, Calif.), Fiorina and colleagues are working to optimize the small-molecule "cocktail" used to modulate the blood stem cells. The team has completed a pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration to support the conduct of a clinical trial in type 1 diabetes.
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Thursday, July 19, 2018

'Molecular microscope' system safer, more effective in heart and lung transplant biopsies

'Molecular microscope' system safer, more effective in heart and lung transplant biopsies

Research shows system requires less tissue samples and provides more precise readings
UNIVERSITY OF ALBERTA FACULTY OF MEDICINE & DENTISTRY
 
IMAGE
IMAGE: PHILIP HALLORAN, THE FOUNDER OF THE 'MOLECULAR MICROSCOPE' SYSTEM FOR TRANSPLANT BIOPSY, IS PRESENTING EARLY CLINICAL TRIAL FINDINGS ON THE SYSTEM TODAY AT THE 2018 MEETING OF THE INTERNATIONAL SOCIETY... view more 
CREDIT: UNIVERSITY OF ALBERTA
A transplant biopsy system that uses gene chips to read molecules is far safer and more effective than existing approaches used for heart transplant biopsies and is showing promising results for lung transplant biopsies, new University of Alberta-led research shows.
An international team of transplant specialists--including Philip Halloran, the founder of the "molecular microscope" system--presented early clinical trial findings of the system today at the 2018 meeting of the International Society for Heart and Lung Transplantation in Nice, France.
"Our research indicates that the molecular microscope system is more precise and accurate than conventional methods, which often involve extensive disagreement between doctors reading the biopsies, and therefore errors," said Halloran, a U of A transplant physician and globally recognized leader in the field.
The method uses gene chips (similar to computer chips) to read the molecules in heart and lung transplant biopsies. In the molecular microscope system developed by the U of A's Alberta Transplant Applied Genomics Centre (ATAGC) and investigators in North America, Europe and Australia, software converts the chip readings into diagnoses automatically.
Halloran said that the molecular microscope is a game changer in transplant medicine because it not only provides clinicians with insightful information for managing heart transplant rejection and treatment--which occurs in 150,000 patients worldwide every year--but also eliminates the confusion of unrecognized injury with rejection.
"Our findings suggest that, not infrequently, the current standard lacks the refinement to distinguish true rejection from other processes causing injury," said Daniel Kim, U of A transplant cardiologist. "This implies that, at times, patients could be treated for a condition they don't have. The molecular microscope's ability to more accurately diagnose rejection, before structural damage has occurred in a patient's heart, provides us with an essential tool in the evolution towards true precision medicine."
The molecular microscope system is now being developed for lung transplant biopsies, with the goal of changing care for those patients as well.
"Reading small lung transplant biopsies with a microscope is challenging--much more so than other transplantable organs--and that makes diagnosing rejection that much more difficult and prone to error," explained Kieran Halloran, assistant professor of medicine in the U of A's Faculty of Medicine & Dentistry. "This molecular diagnostic system is at an earlier stage in lung compared to heart and certainly to kidney, but is showing promising results that it can see similar information. That potential is very exciting for lung transplant clinicians."
He noted there is a huge unmet need for this type of precision medicine among lung transplant patients, who experience the shortest of all survival rates, often running into transplant trouble within five years.
"You can't hit what you can't see," added Philip Halloran. "Transplant rejection can be going on and we are missing it. And more commonly, rejection is way overdiagnosed, and patients are experiencing treatment complications for a condition they didn't have. Our system will change the approach to care."
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Autoimmune reaction successfully halted in early stage islet autoimmunity

Autoimmune reaction successfully halted in early stage islet autoimmunity

HELMHOLTZ ZENTRUM MÜNCHEN - GERMAN RESEARCH CENTER FOR ENVIRONMENTAL HEALTH
 
Type 1 diabetes is the most common metabolic disease in childhood and adolescence. In this disease, the body's own immune system attacks and destroys the insulin-producing cells of the pancreas. Regulatory T cells (Tregs) play an important role in this process: In healthy people, they suppress excessive immune reactions and thus prevent autoimmune diseases.
Dr. Carolin Daniel's team is investigating why Tregs fail to protect the islet cells in type 1 diabetes. She is a group leader at the Institute for Diabetes Research (IDF) of Helmholtz Zentrum München and a scientist in the DZD. In the current study, she and her team elucidated a mechanism that causes fewer Tregs to be produced during islet autoimmunity onset and that therefore allows the immune system to get out of control and attack.
According to the findings of the study, miRNA181a and NFAT5 molecules play a key role. "We showed that miRNA181a leads to the activation of the transcription factor NFAT5 during islet autoimmunity onset," said Daniel.* "The consequence is an inhibition of Treg induction and thus increased immune activation."
Axis pharmacologically interrupted
In order to test the suitability of this new finding for possible therapeutic approaches, the scientists led by the first author Isabelle Serr investigated a preclinical model with early-stage islet autoimmunity. If the researchers interrupted the miRNA181a/NFAT5-axis, they observed a significantly lower activation of the immune system and an increased formation of Tregs. This was achieved both by the pharmacological inhibition of miRNA181a as well as of NFAT5.
"The targeted inhibition of miRNA181a or NFAT5 could open up new approaches to reduce the activity of the immune system against its own islet cells," said Professor Anette-Gabriele Ziegler, director of the IDF. "The combination with other immune modulating therapeutic approaches would also be conceivable as an intervention."
In the future, the scientists want to further investigate these findings in preclinical tests. To this end, humanized models will be used to test whether the combination of insulin vaccination and inhibition of the miRNA181a/NFAT5 axis leads to a more tolerant immune system towards insulin-producing cells.
###
Further Information
* The researchers suspect indirect mechanisms such as the inhibition of phosphatase PTEN.
Background:
"The cooperation with Benno Weigmann's group at the University Hospital Erlangen-Nuremberg was important for the success of the research," said Carolin Daniel. With her research group "Immunological Tolerance in Diabetes," she is investigating the role of regulatory T cells in type 1 diabetes. She tells more in the research portrait, which includes a video interview, in which she explains how the disease develops and her strategy against it https://www.helmholtz-muenchen.de/en/research/research-excellence/portraits-of-researchers/dr-carolin-daniel/index.html. The video Type 1 Diabetes: Development and Prevention was produced by the Diabetes Information Service Munich https://www.diabetesinformationsdienst-muenchen.de/erkrankungsformen/typ-1-diabetes/forschungsansaetze/index.html (only available in German).
Original Publication:
Serr, I. et al. (2017): A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune Type 1 diabetes. Science Translational Medicine, http://stm.sciencemag.org/
DOI: 10.1126/scitranslmed.aag1782
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.https://www.helmholtz-muenchen.de/en/index.html
The Institute of Diabetes Research (IDF) focuses on the pathogenesis and prevention of type 1 diabetes and type 2 diabetes and the long-term effects of gestational diabetes. A major project is the development of an insulin vaccination against type 1 diabetes. The IDF conducts long-term studies to examine the link between genes, environmental factors and the immune system for the pathogenesis of type 1 diabetes. Findings of the BABYDIAB study, which was established in 1989 as the world's first prospective birth cohort study, identified risk genes and antibody profiles. These permit predictions to be made about the pathogenesis and onset of type 1 diabetes and will lead to changes in the classification and the time of diagnosis. The IDF is part of the Helmholtz Diabetes Center (HDC). https://www.helmholtz-muenchen.de/en/idf/index.html
The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München - German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. https://www.dzd-ev.de/en/index.html
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Biomaterial particles educate immune system to accept transplanted islets

Biomaterial particles educate immune system to accept transplanted islets

GEORGIA INSTITUTE OF TECHNOLOGY
 
IMAGE
IMAGE: JESSICA WEAVER, A POSTDOCTORAL RESEARCHER IN GEORGIA TECH'S WOODRUFF SCHOOL OF MECHANICAL ENGINEERING, HOLDS A MULTIWALL PLATE CONTAINING HYDROGELS WITH PANCREATIC ISLET CELLS. view more 
CREDIT: GEORGIA TECH
By instructing key immune system cells to accept transplanted insulin-producing islets, researchers have opened a potentially new pathway for treating type 1 diabetes. If the approach is ultimately successful in humans, it could allow type 1 diabetes to be treated without the long-term complications of immune system suppression.
The technique, reported June 4 in the journal Nature Materials, uses synthetic hydrogel particles (microgels) to present a protein known as the Fas ligand (FasL) to immune system T-effector cells along with the pancreatic islets being transplanted. The FasL protein "educates" the effector cells - which serve as immune system watchdogs - causing them to accept the graft without rejection for at least 200 days in an animal model.
The FasL-presenting particles are simply mixed with the living islets before being transplanted into the mice, which suffer from chemically-induced diabetes. The researchers believe the FasL-presenting hydrogels would not need to be personalized, potentially allowing an "off-the-shelf" therapy for the transplanted islets.
Researchers from the Georgia Institute of Technology, University of Louisville and University of Michigan collaborated on the work, which was supported by the Juvenile Diabetes Research Foundation and the National Institutes of Health. A follow up study testing the approach in non-human primates has already begun.
"We have been able to demonstrate that we can create a biomaterial that interrupts the body's desire to reject the transplant, while not requiring the recipient to remain on continuous standard immunosuppression," said Haval Shirwan, the Dr. Michael and Joan Hamilton Endowed Chair in Autoimmune Disease at the University of Louisville School of Medicine and director of the Molecular Immunomodulation Program at the Institute for Cellular Therapeutics at the university. "We anticipate that further study will demonstrate potential use for many transplant types, including bone marrow and solid organs."
In the United States, some 1.25 million persons have type 1 diabetes, which is different from the more common type 2 diabetes. Type 1 diabetes is caused by immune system destruction of the pancreatic islet cells that produce insulin in response to glucose levels. Treatment involves frequent injection of insulin to replace what the islets no longer produce. There is no long-term cure for the disease, though persons with type 1 diabetes have been treated experimentally with islet cell transplants - which almost always fail after a few years even with strong suppression of the immune system.
"Drugs that allow the transplantation of the islet cells are toxic to them," said Andrés García, the Rae S. and Frank H. Neely Chair and Regents' Professor in Georgia Tech's George W. Woodruff School of Mechanical Engineering. "Clinical trials with transplantation of islets showed effectiveness, but after a few years, the grafts were rejected. There is a lot of hope for this treatment, but we just can't get consistent improvement."
Among the problems, García said, is toxicity to the islet cells from the immune system suppression, which also makes patients more susceptible to other adverse effects such as infections and tumors. Other researchers are exploring techniques to protect the islets from attack, but have so far not been successful.
The research reported in Nature Materials takes a totally different approach. By presenting the FasL protein - which is a central regulator of immune system cells - the researchers can prevent the immune system from attacking the cells. Once they are educated at the time of transplantation, the cells appear to retain their acceptance of the transplanted islet cells long after the FasL has disappeared.
"At the time of transplantation, we take the islets that are harvested from cadavers and simply mix them with our particles in the operating room and deliver them to the animal," García explained. "We do not have to modify the islets or suppress the immune system. After treatment, the animals can function normally and are cured from the diabetes while retaining their full immune system operation."
The hydrogels can be prepared up to two weeks ahead of the transplant, and can be used with any islet cells. "The key technical advance is the ability to make this material that induces immune acceptance that can simply be mixed with the islets and delivered. We can make the biomaterial in our lab and ship them to where the transplantation will be done, potentially making it an off-the-shelf therapeutic."
In the experimental mice, the islets were implanted into the kidneys and into an abdominal fat pad. If the treatment is ultimately used in humans, the islets and biomaterial would likely be placed laparoscopically into the omentum, a tissue with significant vasculature that is similar to the fat pad in mice. Garcia's lab has previously shown that it can stimulate blood vessel growth into islet cells transplanted into this tissue in mice.
In future work, the researchers want to see if the graft acceptance can be retained in more complex immune systems, and for longer periods of time. By reducing damage to the cadaver islets, the new technique may be able to expand the number of patients that can treated with available donor cells.
García's lab uses polymer hydrogel particles that are about 150 microns in diameter, about the same size as the islet cells. They engineer the particles to capture the FasL - a novel recombinant protein developed by Shirwan and Esma S. Yolcu, associate professor of microbiology and immunology at the University of Louisville - on the particle surface, where it can be seen by the effector cells.
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