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VATIS Update Biotechnology . Jul-Aug 2009
Indian biotech sector impacted in the meltdown
The global meltdown and the foreign exchange rate have impacted Indian biotechnology sector. The industry growth rate slipped to 18 per cent in 2008-09, compared with 30-34 per cent in the previous years. The sectors overall turnover in 2008-09 was Rs 121.37 billion (US$2.5 billion), said Ms. Kiran Mazumdar-Shaw, CMD of Biocon, citing the annual Biospectrum survey of industry.
With 60 per cent of the income coming from exports, the turnover in dollar terms was static year-on-year at US$2.5 billion, as the exchange rate last year was Rs 47/dollar compared with Rs 40/dollar in 2007-08. The Bangalore cluster, with 187 or nearly half of the 370 biotech industries, topped among clusters, with a turnover of Rs 25 billion. The Mumbai-Pune cluster, Ms. Mazumdar-Shaw said, is catching up with the highest growth rate among all clusters. Bio-pharma contributed Rs 78.8 billion, bio-agri nearly Rs 15 billion, bio-industrial segment Rs 4.8 billion and bio-informatics touched Rs 2.2 billion.
Israel sets up biotech fund
Israel is setting up a capital fund of up to 1 billion shekels (US$255 million) to finance biotechnology start-up companies, its industry and trade and finance ministries said recently. The state would contribute about a quarter of the fund, which it hopes to raise to the target amount using loans from private investors. The aim of the initiative is to encourage and advance growth in Israels biotech sector. The government will split profits from activities in the fund between itself and the private investors, the ministries stated.
Tsinghua University gets a cryo-electron microscope
Tsinghua University in Beijing, China, has procured a cryo-transmission electron microscope (cryo-TEM) from the United States-based FEI Company, a leading provider of three-dimensional (3-D) molecular, cellular and atomic-scale imaging systems. The acquisition of this advanced, multi-million dollar microscope, marks the first Titan KriosTM to be installed in Asia. Titan Krios unique capabilities in automation, cryogenic sample handling and low dose imaging are essential for the advanced structural biological research we pursue here, said Prof. Yigong Shi, Senior Vice Dean of the Medical School at Tsinghua University.
Titan Krios provides a high resolution 3-D imaging solution, which is specifically designed to image biological structures down to the molecular level in structural biology applications. Its integrated cryogenic sample handling robotics offer improved automation over existing cryo-TEMs, and the solution permits a full range of high resolution and 3-D techniques including: cryo electron microscopy; single particle analysis; and dual-axis tomography of frozen hydrated samples, such as cells. Cryogenic imaging techniques preserve sample integrity by maintaining it in its native hydrated condition, and proteins in their naturally occurring conformation. Low electron dose methods enable data acquisition with minimal sample damage. Contact: Mr. Fletcher Chamberlin, FEI Company, North America NanoPort, 5350 NE Dawson Creek Drive, Hillsboro, Oregon, 97124, United States of America. Tel: +1 (503) 726-7710; Fax: +1 (503) 726 2570; E-mail: email@example.com.
New national genome centre launched in the United Kingdom
A new national genome centre was opened recently in the United Kingdom by Nobel Laureate and genome pioneer Prof. Sir John Sulston. The new Genome Analysis Centre (TGAC) will further the United Kingdoms capacity in genomics for use in developments that include the production of new antibiotics to fight superbugs, breeding of new crops with increased tolerance of drought, and the breeding of livestock better able to resist emerging exotic disease. TGAC will underpin these advances, as well as make a significant contribution to economic development.
TGAC has been established in Norwich by the Biotechnology and Biological Sciences Research Council (BBSRC) in partnership with regional economic development partners. The centre represents an investment by all the partners in the capital infrastructure of 13.5 million. TGAC will concentrate on understanding the genomes of economically and socially important plants, animals and microbes. The exact projects that TGAC will initially work on will be decided by an independent advisory board but candidates include: helping to replace petrol with eco-friendly bioenergy, protecting livestock from exotic diseases, and producing more nutritious fruit and vegetables.
A key aim for TGAC is to combine world-class genome science with an innovation programme that aims to benefit the regional and national economy. TGAC will utilize its own discoveries to maximize economic and social impact and is also committed to making cutting edge facilities available to the industry in the United Kingdom. The centre is estimated to generate 5 million of revenue annually and create up to 750 highly-skilled local jobs through commercial development in the next three to seven years.
Pakistan in talks to buy Bt cotton seed
Pakistan is in the process of signing a US$1 billion agreement for the purchase of Bt cotton seed from Monsanto of the United States. It has finalized issues in its negotiations with Monsanto about growing Bt cotton, which is expected to increase the yield by 40 per cent. However, the quantity that the country would purchase has not yet been agreed upon.
Last year, around 28 per cent land was cultivated with Bt cotton, but this year our target is 60 per cent, said Textiles Adviser Dr. Mirza Ikhtiar Baig. There are also arrangements to produce Bt seeds locally, and the Economic Coordination Committee has approved growing Bt cotton to increase production, he said. Currently, farmers are using Bt cotton seed on around 2.7 million acres of land against total cultivation of over eight million acres in the country. But the Bt cotton seed being sold in the country was smuggled in and therefore illegal, said the textile adviser.
The package negotiated includes latest Bt cotton seed with weed control feature called Bollguard II with round-up ready flex, which would save up to US$250 million spent on pest control. According to preliminary talks with Monsanto, the company would charge US$21 for sowing BT seeds over one acre. Of that amount, the company would return US$4.2 to the farmer for research purpose.
Chinese scientists create pig stem cells
Scientists have managed to induce cells from pigs to transform into pluripotent stem cells that, like embryonic stem cells, are capable of developing into any type of cell in the body. It is the first time that this has been achieved using somatic cells (cells that are not sperm or egg cells) from any animal with hooves (ungulates). The research could open the way to creating models for human genetic diseases, genetically engineering animals for organ transplants for humans, and for developing pigs that are resistant to diseases such as swine flu.
Dr. Lei Xiao, who heads the stem cell lab at the Shanghai Institute of Biochemistry and Cell Biology, China, and colleagues succeeded in generating induced pluripotent stem (iPS) cells by using transcription factors to reprogramme cells taken from a pigs ear and bone marrow. After the cocktail of reprogramming factors had been introduced into the cells via a virus, the cells changed and developed in the laboratory into colonies of embryonic-like stem cells. Further tests confirmed that they were pluripotent stem cells. The development could make it much easier for researchers to develop embryonic stem cells (ES cells) that originate from pig or other ungulate embryos.
However, Dr Xiao warned that it could take several years before some of the potential medical applications of his research could be used in the clinic. The next stage of his research is to use the pig iPS cells to generate gene-modified pigs that could provide organs for patients, improve the pig species or be used for disease resistance. The modified animals would be either knock in pigs where the iPS or ES cells have been used to transfer an additional bit of genetic material into the pigs genome, or knock out pigs where the technology is used to prevent a particular gene functioning.
NeoStem inks pact with Enhance BioMedical for stem cell collection
NeoStem Inc., the United States, has signed an exclusive ten-year agreement with Enhance BioMedical Holdings Ltd., China, to develop a stem cell collection and treatment network using NeoStems proprietary adult stem cell technologies in Chinese provinces as well as Taiwan. Enhance BioMedical Holdings is a subsidiary of Enhance Holding Corporation, a multinational conglomerate with successful businesses in various market sectors including healthcare.
The agreement expands NeoStems China-related activities, which are focused on regenerative medical therapies and medical tourism for clientele seeking high-quality treatments not available in their own countries. Under the agreement, Enhance BioMedical is given the exclusive rights to utilize NeoStems proprietary adult stem cell technologies identified by NeoStem from time to time to provide adult stem cell services and therapies in the Asian territory. NeoStem will train Enhance BioMedical staff in the proprietary knowledge, technology and operating procedures.
In return, NeoStem is entitled to a six-figure technical assistance fee. NeoStem also will be entitled to a stated royalty on gross revenues generated by Enhance from providing the NeoStem stem cell services for the duration of the renewable agreement and may receive other fees also in connection with assisting in the launching of the network.
Kemwell to set up new biopharma facility
Kemwell Pvt. Ltd., a leading contract manufacturing and development services company based in India, would invest around Rs 2.0-2.5 billion to set up an advanced biopharmaceutical manufacturing plant in the outskirts of Bangalore, India. The facility would be opened in two years, and the financing would come from the companys own funds and through a private equity partner.
Kenwell has also entered into a strategic collaboration with Boehringer Ingelheim (BI), Germany, wherein Kemwell will complement BIs early clinical supply services ranging from full-service process development, manufacture, formulation, and fill-and-finish at the current good manufacturing practices (cGMP) facility. It will have access to BIs cell line development with the HEX technology platform, followed by a preferred access to the large-scale commercial production of its facilities in Europe.
The Greenfield project which spans over an area of 15,000 sq m will be designed for process development, fermentation, purification and formulation of biologics for early-phase preclinical and clinical studies. The facility will consist of a cGMP drug substance manufacturing facility and a sterile fill-and-finish facility for drug product with a floor for process development laboratories to support production of protein therapeutics from mammalian-cell culture or microbial fermentation.
AstraZeneca, Merck collaborate on cancer treatment
AstraZeneca PLC, based in the United Kingdom, and Merck & Co., based in the United States, will jointly develop a pair of drugs meant to hit cancer with a one-two punch, part of a growing trend of combination cancer treatments. The companies, two of the worlds largest multinational drug-makers, said they would combine efforts with Mercks MK-2206 and AstraZenecas AZD6244, both of which are still in very early development. Such a partnership among major pharmaceutical companies on a combination treatment at nascent stage is unusual.
In a statement, the companies said that by working together, they could bring the treatment to patients more quickly. Pre-clinical studies have indicated the combination has potential as an anticancer drug, the statement said. AstraZenecas AZD6244 is currently in mid-stage, or Phase II development, as a potential treatment for several tumour types, while Mercks MK-2206 is in early-stage studies focusing in general on treating solid tumours. Each drug targets a different protein that is abnormally activated in cancer, one called MEK and the other AKT.
Biocon, Mylan tie up for generic biologic drugs
Biocon Ltd., a premier biotechnology firm in India, has signed a definitive agreement with the worlds third largest biopharma company, Mylan Inc., the United States, to develop, manufacture and supply generic biologic drugs globally. As part of this collaboration, the companies will share capital, development, and certain other costs to bring products to market. Mylan will have exclusive commercialization rights in the United States, Canada, Japan, Australia, New Zealand, as well as in the European Union and European Free Trade Association nations under a profit sharing arrangement with Biocon. Mylan will also have co-exclusive commercialization rights with Biocon in all other markets around the world.
Luminex launches two new cystic fibrosis test
Luminex Corporation, the United States-based worldwide leader in multiplexed solutions, has announced the launch two new cystic fibrosis (CF) tests in Europe the xTAG Cystic Fibrosis 39 Kit v2 and xTAG Cystic Fibrosis 71 Kit v2 as CE IVD Marked products under the European Directive on In Vitro Diagnostic Medical Devices.
As the most comprehensive CF tests available, the new xTAG tests will be used to provide assistance in CF screening for newborns and confirmatory diagnostic testing in infants and children. The tests can be used also for carrier testing in adults of reproductive age, for mutation in the CF transmembrane conductance regulator (CFTR) gene, which leads to the disease.
The xTAG Cystic Fibrosis 39 Kit v2 can quickly and accurately detect up to 39 of the most common CFTR mutations from a child or parents blood sample or bloodspot in a matter of hours. The xTAG Cystic Fibrosis 71 Kit v2 can screen for all of the genetic mutations in the xTAG Cystic Fibrosis 39 Kit v2 plus an additional 32 mutations including those that are typically found in specific ethnic populations. The xTAG tests are uniquely designed to be fast and easy for use, requiring only about one hour of hands-on time to process 48 purified samples. They also offer physicians the ability to select the CFTR gene mutations for which they want to test.
Juvaris BioTherapeutics joins hands with Antigen Discovery
In the United States, Juvaris BioTherapeutics Inc. has signed a definitive agreement with Antigen Discovery Inc. (ADi) to access ADs proprietary high-throughput protein microarray screening system to discover novel disease-specific antigens to fuel Juvaris vaccine pipeline. Juvaris will sponsor research for multiple disease targets and pay ADi upfront payments, development milestones and royalties on licensed products in exchange for full product development rights to all fields except diagnostics, which will belong to ADi.
ADis antigen discovery platform involves assaying the entire proteome of a disease target to identify every possible protein antigen. The selected antigens are derived from reactive antibodies generated by infected individuals. They mimic the presence, accessibility and antigenicity of relevant proteins from the particular pathogens in humans. This process identifies antigens that best stimulate the immune system and are thus ideal targets for vaccine and diagnostic development. Through the collaboration, Juvaris will select the optimal antigens from the discovery efforts of ADi to combine with its proprietary adjuvant technology to create highly immunogenic prophylactic and therapeutic vaccines against major unmet medical needs.
Glaxosmithkline opens largest vaccine plant in Asia
Glaxo SmithKline (GSK), the global pharmaceutical company, has officially opened its largest vaccine plant in Asia and the first of its kind in Singapore. The new plant was inaugurated by the Prime Minister of Singapore, Mr. Lee Hsien Loong. GSK has so far invested more than US$1 billion and expanded its activities in Singapore into drug discovery, clinical research and manufacturing, making the city-state one of the companys two global strategic manufacturing hubs as well as its regional headquarters for Asia-Pacific.
Japanese scientists create transgenic monkeys
Japanese scientists announced recently that they had created the worlds first transgenic primates, breeding monkeys with a gene that made the animals skin glow a fluorescent green. The exploit opens up exciting prospects for medical research, and could eventually lead to lab monkeys that could provide a new model for investigating the cause of and cure for human disorders.
In a study published in the journal Nature, a team led by Dr. Erika Sasaki of the Central Institute for Experimental Animals at Keio University reported on experiments on common marmosets (Callithrix jacchus), a small monkey native to Brazil. The team introduced a foreign gene, tucked inside a virus, into marmoset embryos that were then nurtured in a bath of sucrose. The gene codes for green fluorescent protein (GFP), a substance that was originally isolated from a jellyfish and is now commonly used as a biotech marker.
The transgenic embryos were then implanted in the uterus of seven surrogate mother marmosets. Three of the recipients miscarried. The other four gave birth to five offspring, all of which carried the GFP gene. In two of these five, the GFP gene had been incorporated into the reproductive cells. A second generation of marmosets was then derived from one of the two.
The work is important, because medical researchers have hankered for an animal model that is closer to the human anatomy than rodents. Mice and rats, genetically engineered to have the symptoms of certain human diseases, are the mainstay of pre-clinical lab work, in which scientists test their theories before trying out any outcome on human volunteers. But many disorders, especially neurological diseases such as Alzheimers and Parkinsons, are so complex that they cannot be reproduced meaningfully in rodents because their biology is different. Hopes for a non-human primate model have until now been dashed by the failure to insert a gene into monkey sperm and eggs, to ensure the passing of the inserted DNA on to future generations.
A gene that regulates tumours in neuroblastoma
In the United States, Virginia Commonwealth University (VCU) researchers have identified a gene that may play a key role in regulating tumour progression in neuroblastoma, a form of cancer usually found in young children. According to co-lead investigators of the study Dr. Paul B. Fisher from VCU Massey Cancer Centre, and Dr. Seok-Geun Lee from the VCU Department of Human and Molecular Genetics their work has demonstrated that astrocyte elevated gene-1, AEG-1, a cancer promoting gene, is frequently activated in neuroblastoma.
In the study, the VCU team found that the elevated expression of AEG-1 makes cancer cells highly aggressive and resistant to factors that may influence cell suicide, and that loss of AEG-1 reduces the tumour-causing properties of highly aggressive neuroblastoma cells. Additionally, the expression of AEG-1 was significantly elevated in six of 10 neuroblastoma patient-derived samples compared with normal peripheral nerve tissues. The team also established the potential correlation between AEG-1 and MYCN in neuroblastoma. MYCN is a known genetic determinant of neuroblastoma and elevated levels have been observed in one-third of neuroblastoma patients.
The team has already begun analysing the expression of AEG-1 and its relationship with MYCN status in neuroblastoma patient samples. They will also test if inactivation of AEG-1 using small interfering RNA could be a therapeutic intervention for neuroblastoma through second collaborative effort.
New genetic immune disorder in children
At the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the United States, researchers have discovered a new auto-inflammatory syndrome, a rare genetic condition that affects children around the time of birth. The new auto-inflammatory syndrome has been named deficiency of the interleukin-1 receptor antagonist (DIRA). The research was supported by several other institutes under the National Institutes of Health, as well as institutes and universities from Canada, the Netherlands and Sweden.
Children with the disorder display several serious and potentially fatal symptoms such as: swelling of bone tissue; bone pain and deformity; inflammation of the periosteum; and a rash that can span from small individual pustules to extensive pustulosis. Most of the children begin to have symptoms from birth to two weeks of age. All these children have inherited mutations in IL1RN, a gene that encodes a protein known as interleukin-1 receptor antagonist (IL-1Ra). IL-1Ra binds to the same cell receptors as the inflammatory protein interleukin-1 (IL-1) and acts as a brake on it. Without IL-1Ra, the childrens bodies cannot control systemic inflammation caused by IL-1.
The scientists identified nine patients from six families with DIRA in Canada, the Netherlands, Lebanon and Puerto Rico. The six patients who were alive at the time of diagnosis were treated with anakinra, a drug that is normally used for rheumatoid arthritis and is a synthetic form of human IL-1Ra. Most patients responded successfully and immediately to anakinra, although they were resistant to other medications such as steroids.
Discovery of facial malformation gene
The first specific genetic mutation, which can cause a potentially serious facial disfigurement, has been identified jointly by researchers in the United Kingdom and the Netherlands. The finding offers the promise of improved genetic counselling for parents at risk. The researchers led by Prof. Andrew Wilkie from the Weatherall Institute for Molecular Medicine at the University of Oxford and Dr. Irene Mathijssen from the Erasmus Medical Centre in the Netherlands identified individuals from seven families who had frontorhiny, a distinctive facial appearance that include a wide, malformed nose and an abnormally large distance between the eyes.
Genetic analysis showed that each of the individuals carried two copies of a mutation in the gene ALX3. Mouse models have previously highlighted the involvement of the equivalent gene in the production of a protein that regulates other genes involved in facial development. However, while the absence of the protein produced by this gene does not disrupt facial development in mice, Prof. Wilkie and colleagues found that it leads to frontorhiny in humans.
The researchers believe that by identifying and naming the condition, they will be able to diagnose more cases and provide improved genetic counselling. Because this is a recessive genetic disorder, a parent with the condition is very unlikely to have a similarly affected child. However, where unaffected parents have a child with the condition, they have a one in four chance of each future child being affected.
Cholesterol-regulating genes
In Germany, scientists at the European Molecular Biology Laboratory (EMBL) and the University of Heidelberg (UH) have come one step closer to understanding how cholesterol levels are regulated. In a study published in Cell Metabolism, the researchers identified 20 genes that are involved in this process. Besides giving scientists a better idea of where to look to uncover the mechanisms that ensure cholesterol balance is maintained, the discovery could lead to new treatments for cholesterol-related diseases. This finding may open new avenues for designing targeted therapies, for example by looking for small molecules that could impact these genes, says Dr. Heiko Runz, whose group at the UoH Clinic carried out the research together with Dr. Rainer Pepperkoks laboratory at EMBL.
The researchers deprived isolated human cells of cholesterol and then looked at the whole genome to find the genes that react to changes in cholesterol levels by altering their expression. This large-scale approach pointed to hundreds of genes that might be involved in cholesterol regulation. To identify the genes were involved, the scientists used RNA interference to systematically turn each of the candidate genes off. With a microscope they then observed what effect the switching off of different genes had, both on cholesterol uptake and on the amount of cholesterol inside cells.
Of the 20 genes the scientists identified as involved in regulating cholesterol levels and uptake, 12 were previously unknown. The remainder were known to have some link to lipid metabolism how the body breaks down fat including two genes that when mutated may cause heart disease, but which were only now shown to also play a part in bringing cholesterol into cells in the first place. The scientists are now trying to discover how the novel genes regulate cholesterol levels inside cells, whether these genes (or alterations in them) constitute risk factors, and how they could be useful drug targets.
One-step test for abnormalities in embryos
One-step screening for both genetic and chromosomal abnormalities has come a stage closer, as scientists announced that an embryo test they have been developing has successfully screened cells taken from spare embryos that were known to have cystic fibrosis. The researchers based in the United States and the United Kingdom have been able to prove that the technique, known as genome-wide karyomapping, was capable of detecting not only diseases caused by a specific gene mutation but also aneuploidy (an abnormal number of any of the 23 pairs of chromosome).
Dr. Gary Harton, a scientific director of the Genetics & IVF Institute in Virginia, the United States, said: Karyomapping is a universal method for analysing the inheritance of genetic defects in the pre-implantation embryo without any prior patient or disease specific test development, which often delays patient treatment. For the first time, the inheritance of both single gene defects and chromosomal abnormalities can be detected simultaneously at the single cell level. As karyomapping involves analysing chromosomes, it also detects the existence of aneuploidy at the same time. The DNA sequence is analysed at over 300,000 locations genome-wide in parents and appropriate family members, and their sequence is compared with that inherited by the embryo.
Karyomapping was developed by Prof. Alan Handyside of the London Bridge Fertility Gynaecology and Genetics Centre in London, the United Kingdom. The hope is that clinicians will be able to test embryos for specific genetic diseases and know that, with one test, they are transferring chromosomally normal embryos. This will be a step forward from current technology that is mostly limited to choosing one test or the other, explained Prof. Handyside. Karyomapping would also be quicker and hence, cheaper. Currently, developing a pre-implantation genetic diagnosis test for a single gene defect can take weeks or months. By contrast, karyomapping can be carried out without such extended pre-test development; at present, it takes about three days, but the researchers believe this could be reduced to 18-24 hours.
Gene mutation responsible for catastrophic epilepsy
Catastrophic epilepsy characterized by severe muscle spasms, persistent seizures, mental retardation and sometimes autism results from a mutation in a single gene, write researchers from Baylor College of Medicine (BCM) in the United States. The BCM team replicated the defect in mice, developing a mouse model of the disease that could help researchers figure out effective treatments for and new approaches to curing the disease, said Dr. Jeffrey Noebels, professor of neurology, neuroscience and molecular & human genetics, and director of the Blue Bird Circle Developmental Neurogenetics Laboratory.
Why some children have a more complicated set of disorders was a mystery. A gene known as Aristaless-related homeobox (ARX) has a specific mutation called a triplet repeat, which means that a particular nucleotide triplet (in this case, Guanidine-Cytosine-Guanidine) is repeated in the gene. When this particular mutation was duplicated in specially bred mice, the animals had motor spasm similar to those seen in human infants.
Brain waves of the animals showed that they had several kinds of seizures, including absence epilepsy and general convulsion. They also had learning disabilities and were four times more likely to avoid contact with other mice than their normal counterparts a behaviour similar to that seen in children with autism or other such disorders. Mutation of the ARX gene was previously known to affect interneurons, a class of cells that inhibit electrical activity in the brain. When the scientists evaluated the brains of the adult mice with the mutated gene, they found that a special class of interneurons had never developed in specific brain regions.
Stem cell protein as a new cancer target
RA protein abundant in embryonic stem cells is now shown to be important in cancer, and offers a possible new target for drug development, say researchers from the Stem Cell Programme at Childrens Hospital Boston, the United States. Dr. George Daley, graduate student Mr. Srinivas Viswanathan and colleagues have shown that the protein LIN28 can transform cells to a cancerous state, and that it is abundant in a variety of advanced human cancers.
Last year, Dr. Daley and Mr. Viswanathan, in collaboration with Dr. Richard Gregory, had shown that LIN28 regulates an important group of tumour-suppressing microRNAs known as let-7. Rising LIN28 production in a cell prevents let-7 from maturing, making the cell more immature and stem-like. Since these qualities also make a cell more cancerous, and because low levels of mature let-7 have been associated with breast and lung cancer, the discovery had suggested that LIN28 might be oncogenic.
The scientists believe that overall, LIN28 and a related protein, LIN28B, may be involved in some 15 per cent of human cancers, particularly liver cancer, ovarian cancer, chronic myeloid leukaemia, germ cell tumours and Wilms tumour (a childhood kidney cancer). By blocking or suppressing LIN28, it might be possible to revive the let-7 familys natural tumour-suppressing action. It gives us a new target to attack, especially in the most resistant and hard-to-treat cases, said Dr. Daley.
Key regulator of fat cell development discovered
Scientists at the Cornell University, the United States, have discovered how two related proteins and their roles in a key molecular pathway are critical to creating obesity-causing fat cells. Targeting the proteins, IRE1alpha and XBP1, could hopefully lead to drug therapies to fight obesity, which affects one in three adults and contributes to heart disease, diabetes, some cancers and high blood pressure. The study is the first to show that endoplasmic reticulum and the IRE1alpha-XBP1 pathway are involved in the genesis of fat cells.
The creation of fat cells involves a two-step process: stem cells first develop into precursors of fat cells called pre-adipocytes, and then these develop into adipocytes, the mature fat cells. The new study focuses on this second phase in which the pre-adipocytes experience a low level of stress in the endoplasmic reticulum, the organelle where new proteins are made, folded and then transported out for use by the cell. The stress caused by an accumulation of mis- or un-folded proteins is critical for the transition from pre-adipocytes to mature fat cells, the researchers found.
To counter the stress, cells activate IRE1alpha, a protein that resides in the endoplasmic reticulum and that senses unfolded proteins as a part of a cellular defence mechanism, called the unfolded protein response. Dr. Ling Qi, Assistant Professor of nutritional sciences and senior author of the paper, and his colleagues created cells lacking IRE1alpha and demonstrated that these cells were unable to develop from pre-adipocytes into adipocytes. This evidence indicates that IRE1alpha is a key component of the pathway that leads to fat cell development. Activated IRE1alpha then converts the protein XBP1 into a new form. In its new configuration, XBP1 moves into the cells nucleus, where it turns on genes that work to resume normal protein folding and balance to the endoplasmic reticulum. The researchers also found that loss of XBP1 interferes with the conversion of pre-adipocytes into mature fat cells.
Fish protein link to controlling high blood pressure
Medical scientists at the University of Leicester, the United Kingdom, are investigating how a fish species from the Pacific Ocean could help provide answers to tackling chronic conditions such as hereditary high blood pressure and kidney disease. They are examining whether the Goby fish can help researchers locate genes linked to high blood pressure. This is because a protein called Urotensin II, first identified in the fish, is important for regulating blood pressure in all vertebrates, from fish to humans, said researcher Dr. Radoslaw Debiec from the Universitys Department of Cardiovascular Sciences.
The protein found in the fish has remained almost unaltered during evolution. This indicates that the protein might be of critical importance in the regulation of blood pressure and understanding the genetic background of high blood pressure, Dr. Debiec said. Drugs affecting the protein might be a novel alternative to the available therapies, particularly in those patients who suffer from chronic kidney disease along with high blood pressure.
Protein in the envelope enclosing the cell nucleus
A research team led by Prof. Einar Hallberg at the Department of Life Sciences at Sdertrn University in Sweden has discovered a new protein in the inner membrane of the cell nucleus. This protein, which may play an important role in cell division, now provides a new piece of the puzzle to study in cancer research. The protein normally exists in the membrane envelope that surrounds the cell nucleus. During cell division, it becomes part of the process that distributes the chromosomes evenly between the daughter cells the so-called mitotic spindle. Hence, the protein is named spindle-associated membrane protein 1 (Samp1).
The distribution of chromosomes during cell division is extremely rigidly regulated; the slightest error can lead to the development of tumours. Hence, Samp1 will now be a key piece of the puzzle to study in cancer research.
The research team discovered in their study that Samp1 protein has connections to the cell skeleton outside the cell nucleus. This takes place between cell divisions, when the protein is in the inner membrane of the cell nucleus. It is possible that Samp1 plays a major role when mechanical signals from the outside of the cell are transmitted to the genes in the cell nucleus. The researchers are now focusing on investigating the role Samp1 might have in the transmission of mechanical signals from the outside of the cell to the genes.
Enzyme fights mutated protein in Parkinsons disease
An enzyme that naturally occurs in the brain helps destroy the mutated protein, which is the most common cause of inherited Parkinsons disease, report researchers from Southwestern Medical Centre, University of Texas, the United States. Their study, using human cells, provides a focus for further research into halting the action of the mutated protein. The particular mutation that the researchers studied affects a protein, which is named LRRK2, whose function is not well understood. In its normal form, LRRK2 appears to have multiple sites where other molecules can attach themselves. Several mutations can affect the protein, and some cause Parkinsons disease.
The current theory is that the mutation leads to increased function of LRRK2 and to the formation of abnormal clumps of proteins inside brain nerve cells. The cells eventually die from these effects. In the current study, the researchers used cultured human kidney cells and found that LRRK2 and a protein called CHIP are robustly associated with each other. Further testing showed that CHIP and LRRK2 could bind to each other either directly, or indirectly via a third molecule that acts as a bridge.
When CHIP was bound to either the normal or mutant form of LRRK2, levels of LRRK2 in the cell decreased, the researchers found. This occurred because the cells increased the rate at which they destroyed LRRK2. CHIP may be a useful therapeutic target for treatments to break down LRRK2 in people with Parkinsons, said Dr. Matthew Goldberg, assistant professor of neurology and psychiatry and senior author of the paper.
Protein regulates movement of mitochondria in brain cells
United States scientists have identified a protein in the brain that plays a key role in the function of mitochondria the part of the cell that supplies energy, supports cellular activity and wards off threats from disease. We know that in some disease states that mitochondria function is modified, so understanding how their activity is modulated is important to understanding how the brain responds to a pathological state, said University of Rochester Medical Centre neurologist Dr. David Rempe, the lead author of the study.
Mitochondria are cellular power plants that generate most of the cells supply of adenosine triphosphate (ATP), which is used as a source of chemical energy. While mitochondria are present in all of the bodys cells, some cells because of their size and purpose need to transport them to distant sites within the cell to maintain proper function. Neurons are at a disadvantage in terms of their anatomy, said Dr. Rempe. They put out enormous arms of axons and dendrites and they have to keep supplying nutrients and everything down these arms. The supply line is very long.
The supply line includes mitochondria that the cell must also push down the axons and dendrites to provide energy to these parts of the cell, help with the transmission of signals, as well as generally maintain cellular health. Dr. Rempe and his colleagues have discovered a protein that plays a critical role in regulating the movement or transport of mitochondria in neuron cells. The protein, which they dubbed hypoxia upregulated mitochondrial movement regulator (HUMMR), is produced in a state of low oxygen called hypoxia. HUMMR is induced by another protein called hypoxic inducible factor 1 alpha (HIF-1), which is responsible for triggering several processes in the cell which help it function in a low oxygen environment.
The scientists observed that when HUMMR was expressed at lower than normal levels, a greater number of the mitochondria began to abandon their posts along the cells dendrites and axon and return to the cell body proper. One of the keys to identifying the function of HUMMR has been the appreciation in that the body operates at a relatively low oxygen level. While the air we breath consists of approximately 20 per cent of oxygen, the cells in the brain sit at somewhere between 2-5 per cent of oxygen. This creates a normal state of hypoxia in the brain. However, the concentration of oxygen in the brain can drop even further in instances such as a stroke, when blood flow to a portion of the brain is cut off. This decrease in oxygen promotes the expression of HUMMR which, in turn, mobilizes mitochondria.
Honey more effective than antibiotics
In the first study of its kind, researchers at the University of Sydney, Australia, have found proof that some honeys can be more effective than antibiotics in treating surface wounds and infections. Unlike antibiotics, which only work on some bacteria, the honeys worked on all the infectious bugs tested, including one that was resistant to 13 different antibiotics. Critically, the bacteria did not adapt and develop resistance to the honey as they do with antibiotics. The honeys tested by the researchers were variations of Manuka honey and jelly bush honey, from New Zealand and Australia, respectively, both of which are currently available in medicinal versions, but are not widely used in hospitals.
Our research is the first to clearly show that these honey-based products could in many cases replace antibiotic creams on wounds and equipment such as catheters. Using honey as an intermediate treatment could also prolong the life of antibiotics, said Associate Professor Dr. Dee Carter from the University of Sydneys School of Molecular and Microbial Biosciences. The common denominator in the honeys tested is that they are all produced by bees that feed on Leptospermum plants, commonly known as tea trees, found in Australia and New Zealand.
The honeys worked on pathogens known to have a high level of acquired and/or intrinsic resistance, including superbugs such as methicillin-resistant Staphyloccocus aureaus, said Dr. Carter. We dont quite know how these honeys prevent and kill infections, but a compound in them called methylglyoxal seems to interact with a number of other unknown compounds in honey to prevent infectious bacteria developing new strains that are resistant to it.
Cerebrospinal fluid for early detection of Alzheimers disease
It is possible to identify patients who run a high risk of developing Alzheimers disease and the dementia associated with it, even in patients with minimal memory impairment, according to recent research at the Sahlgrenska Academy, University of Gothenburg, Sweden. The typical pattern of biomarkers known as the CSF AD profile can be seen in the cerebrospinal fluid (CSF) of patients even with very mild memory deficiencies, long before these can be detected by other tests.
The patients who had the typical changes in biomarker profile of the CSF had a risk of deterioration that was 27 times higher than the control group, says Prof. Kaj Blennow of the Academy. The researchers also found that all patients with mild cognitive impairment who deteriorated and developed Alzheimers disease had these alterations in the biomarker profile of their CSF. They also showed a relationship between the profile of biomarkers and other typical signs of the disease, such as the presence of the gene APOE e4 and atrophy of the hippocampus, which is the part of the brain cortex that controls memory.
Ovarian transplantation proves a success
A new technique for transplanting the ovaries of women is reported to have produced excellent results in women whose ovaries have been frozen because of cancer treatment. Dr. Pascal Piver, Manager of the IVF Centre at Limoges University Hospital, France, said that his teams technique worked to restore ovarian function quickly and already one patient from his clinic had had a baby and another had become pregnant.
Dr. Piver and colleagues set out to tackle one of the biggest problems of ovarian transplantation: the low response to stimulation caused by insufficient vascularization of the transplanted tissue. For a woman to become pregnant, the ovaries need to be responsive to the action of hormones that cause them to release eggs each month. If the blood supply to the ovaries is insufficient, this will not happen, even though the transplant may look as though it has been successful, Dr. Piver said. To overcome this problem they carried out a two-stage procedure, first grafting small pieces of the frozen ovarian tissue in the ovarian and peritoneal areas three days before the real transplant. The first graft encourages the growth of blood vessels and paves the way for the ovary to become fully functioning in a shorter time scale than would be possible if all the tissue were to be transplanted at the same time.
The researchers have so far utilized this technique with two patients who had been treated for cancer and had their ovaries frozen. The first patient was treated for sickle cell anaemia, and the second patient for periarteritis nodosa, an inflammation of medium-sized arteries, which become swollen and damaged from attack by rogue immune cells. This is the first time that a pregnancy has been obtained after a ten-year gap between ovarian cryopreservation and grafting, Dr. Piver claimed.
Light therapy offers new hope for breast cancer patients
Scientists led by world-renowned breast cancer expert, Mr. Mo Keshtgar, have used photodynamic therapy (PDT) as non-invasive breast cancer treatment. PDT uses light to destroy cancer cells, and possibly offers an alternative to radiotherapy in some cases. PDT works by giving the patient a drug that makes the target area sensitive to light. The drug is activated when light a low-power red laser is beamed at the area. The process starves the cancerous cells of oxygen, causing them to die.
Trials will be conducted at the Royal Free Hospital in London, the United Kingdom, where Mr. Keshtgar has been working with a technical and scientific team. The treatment is already available for some other cancers such as skin cancer (non-melanoma) and oral cancer. But the Royal Free team is the first to apply it to breast cancer. Trials are also underway with PDT for prostate and bile duct and pancreatic cancer.
New discovery to aid treatment of kidney disease
Researchers from Boston University School of Medicine and University of Louisville in the United States, in collaboration with their colleagues from the University of Nice Sophia-Antipolis in France, have identified a target antigen, PLA2R, in patients with idiopathic membranous nephropathy (IMN). The discovery has implications for the diagnosis and treatment of IMN, which involves the thickening and dysfunction of glomeruli, the filtering parts of the kidneys. It is caused when antibodies attack the glomeruli causing large amounts of protein to leak into the urine. Until now, the diagnosis of IMN required a kidney biopsy, as there are no blood or urine tests to distinguish it from other causes of kidney disease. This is because up until now the protein that is the target of the circulating auto-antibodies has never been identified.
To identify the target antigen in patients with this condition, the researchers used circulating antibodies from adults with this disease to detect normal glomerular proteins. Subsequent analysis using mass spectrometry and confirmation using protein-specific reagents allowed for the identification and characterization of the predominant protein detected by these circulating antibodies.
Direct link between smoking and brain damage
New research has suggested a direct link between smoking and brain damage. Researchers, led by Dr. Debapriya Ghosh and Dr. Anirban Basu from National Brain Research Centre (NBRC), India, have found that a tobacco compound, known as NNK, provokes white blood cells in the central nervous system to attack healthy cells, leading to severe neurological damage. NNK is a pro-carinogen, a chemical substance that becomes carcinogenic when it is altered by the metabolic process of the body. While NNK does not appear to harm brain cells directly, the research team believes it may cause neuro-inflamation, a condition that leads to disorders like multiple sclerosis.
The team employed blot analysis techniques that showed that the introduction of NNK increased pro-inflammatory signalling proteins, pro-inflammatory effector proteins and other stress-related proteins. Levels of pro-inflammatory cytokines, which act as molecular messengers between cells, were also increased. This confirmed that NNK provokes an exaggerated response from the brains immune cells, known as microglia, which start to attack healthy brain cells rather than the unhealthy cells they are supposed to attack.
Scientists produce GM crops without foreign genes
Scientists have unveiled a new way of altering the genetic sequence of a crop to produce a desired trait without needing to introduce foreign genes. The technique could be less controversial than conventional genetic modification because it does not involve transferring a gene from another species. Scientists used a set of enzymes to subtly change a tobacco plants DNA to make it herbicide resistant. The enzymes known as zinc finger nucleases can be engineered in the lab to target specific genes, introducing changes known to cause the desired trait. There has been no efficient way of making such changes to plant genes until now.
Dr. Daniel Voytas, Director of the University of Minnesota Centre for Genome Engineering, the United States, and the lead author of the study says: We changed a few letters in the genetic code of a native plant gene and made the plant resistant to herbicide. The researchers hope the technique will revolutionize how crops are genetically modified. Dr. Voytas says the technique requires only standard molecular biology laboratories and competence in introducing DNA into plants resources that are available in many parts of the developing world.
Protein that triggers plant cell division
For diversity of life to be possible, the cells that make up the living things must be just as varied. Parent cells must be able to divide in ways that create daughter cells that are different from each other, a process called asymmetric division. Scientists know how this happens in animals, but the process in plants has been a mystery. Now biologists at the Stanford University, the United States, have found a plant protein, called BASL, that plays a key role in asymmetric division. In plant cells where the protein is absent, the cells do not divide. This is crucial information, says Dr. Dominique Bergmann, an assistant professor of biology, to understand unique ways of plants of making the different types of cells in their bodies. Dr. Bergmann and colleagues tracked BASL in epidermal cells of Arabidopsis, a small plant used for genetic studies. By following where in the cell BASL resides during successful asymmetric cell divisions, they have discovered that BASL behaves like many of the proteins vital for animal asymmetric cell divisions, even though BASLs structure doesnt look like any of them.
The scientists tracked BASL by adding a fluorescent tag monitoring it under the microscope. They found that the protein behaved in some ways like proteins involved in asymmetric animal cell division. After the division, only one cell inherited BASL at the cell periphery and this helped the two daughter cells become different. When the instructions to make BASL were artificially put into any other cell in the plant, those cells (which normally wouldnt be able to make BASL) not only made BASL, but the protein was found in both the nucleus and a small region at the periphery. This proved that all plant cells have within them the ability to put proteins in specialized areas, said Dr. Bergmann. This is something scientists assumed must be true because it was a necessary step for asymmetric cell division.
Dr. Bergmann said that it was not surprising to find that plants used a different protein for their divisions because of the way their cells are built. Furthermore, the process of plant cell division is structurally different from animal cell division. Unlike animal cells, plant cells have stiff cell walls and cannot divide the way animal cells do. A plant cell actually has to build a new wall from the inside out in order to divide, said Dr. Bergmann.
A gene helps confer drought tolerance in maize
Scientists from the multinational agri-business giant Monsanto Company, the United States, and the global chemicals major BASF, Germany, have discovered that a naturally occurring gene can help maize (corn) plants combat drought conditions and confer yield stability during periods of inadequate water supplies. The companies will use the gene in their first-generation drought-tolerant corn product, which is designed to provide yield stability to farmers. The companies claim that the product would be the first biotechnology-derived drought-tolerant crop in the world. The drought-tolerant corn contains the cspB gene from Bacillus subtilis. CspB codes for an RNA chaperone, which are commonly occurring protein molecules that bind to RNAs and facilitate their function.
The gene was first identified in bacteria subjected to cold stress conditions and further research has demonstrated that cspB helps plants cope with drought stress. In corn, cspB works by helping the plant maintain growth and development during times of water scarcity. A corn plant is particularly vulnerable to drought during reproductive growth stages. By mitigating the impact of drought on the plant, cspB helps provide yield stability. Improved yield stability is of significant value to farmers faced with unpredictable rainfall.
Safety tests for GM rice that fights allergy
In a first-of-its-kind advance towards the next generation of genetically modified foods intended to improve consumers health, researchers in Japan have reported that a new transgenic rice designed to fight a common pollen allergy appears safe in animal studies. The researchers from the Transgenic Crop Research and Development Centre of National Institute of Agrobiological Sciences, and the Forestry Science Laboratory of Nippon Paper Industries Company, describe the development of a transgenic rice plant that is genetically engineered to fight allergies to Japanese cedar pollen, a growing public health problem in Japan that affects about 20 per cent of the population.
In laboratory studies, the scientists fed a steamed version of the transgenic rice and a non-transgenic version to a group of macaque monkeys every day for 26 weeks. At the end of the study period, the test animals did not show any health problems, in a demonstration that the allergy-fighting rice may be safe for consumption, the researchers say. Analysis of blood from monkeys showed that, with few exceptions, there were no significant differences in hematological or biochemical values between the two groups. Neither pathological symptoms nor histopathological abnormalities were observed. Thus, the scientists concluded that oral administration of transgenic rice that contains T-cell epitopes from Japanese cedar pollen allergens has no adverse effects.
Plants can produce specific microbicide
Scientists have developed an anti-HIV microbicide that can be mass-produced in plants in quantities large enough to make it affordable for people in developing countries. The microbicide, which has been found to prevent HIV transmission in cells, is a combination of two promising microbicide compounds monoclonal antibody b12 and the protein cyanovirin-N. Together the compounds are more potent at neutralizing HIV than its single components, said Dr. Amy Sexton, lead author of the study and a researcher at the University of Melbourne, Australia.
The researchers also showed that the microbicide can be mass-produced by transferring the gene constructed for the microbicide into tobacco plant cells. This way the plant expresses the gene and produces the microbicide in the same way it produces its own proteins, says Dr. Sexton. Scaling-up production simply requires growing acres of the plants from genetically modified seeds, she adds. Microbicide gels and creams are a great hope for female-initiated protection from HIV/AIDS but so far trials have had mixed results.
Scientists create drought-resistant tomato
Scientists at the University of Arkansas at Little Rock (UALR), the United States, are developing a tomato plant hearty enough to grow in space and survive droughts and diseases. Our transgenic plants are able to survive without water for three weeks, says Dr. Mariya Khodakovskaya, UALR Assistant Professor of Applied Science. She says her genetically modified cherry red tomatoes are darker and bigger than the regular ones. It also has more lycopene and antioxidants, and produces more sugar and more fructose.
The experiment has gone beyond earth. It was the first transgenic tomato tested in outer space. The long-term goal was to create a new food source for astronauts, says Dr. Khodakovskaya. But more than providing fresh produce for astronauts on extended missions, the research has important implications for developing crops that are resistant to drought and other stresses while improving the nutritional value of food.
Salt-tolerant crops one step closer to reality
An international team of scientists has developed salt-tolerant plants using a new type of genetic modification (GM), bringing salt-tolerant cereal crops a step closer to reality. The research team, based at the University of Adelaide in Australia, has used a new GM technique to contain salt in parts of the plant where it does less damage. The work has been led by researchers from the Australian Centre for Plant Functional Genomics and the University of Adelaides School of Agriculture, Food and Wine, in collaboration with the Department of Plant Sciences at the University of Cambridge, United Kingdom.
Salinity affects the growth of plants worldwide, particularly in irrigated land where one-third of the worlds food is produced. And it is a problem that is only going to get worse, as pressure to use less water increases and quality of water decreases, says the teams leader, Prof Mark Tester, from the School of Agriculture, Food and Wine at the University of Adelaide and the Australian Centre for Plant Functional Genomics (ACPFG).
Prof. Tester says his team used the technique to keep salt as sodium ions (Na+) out of the leaves of a model plant species. The scientists modified genes specifically around xylem, the plants water conducting pipes, so that salt is removed from the transpiration stream before it gets to the shoot. This reduces the amount of toxic Na+ build-up in the shoot and so increases the plants tolerance to salinity, Prof. Tester says. In doing so, the researchers have enhanced a process used naturally by plants to minimize the movement of Na+ to the shoot. They used GM technique to amplify the process, helping plants to do what they already do. The team is now in the process of transferring the technology to crops such as rice, wheat and barley.
Trends in Stem Cell Biology and Technology
The study of stem cell research is gaining the attention from a growing, mult-idisciplinary community of scientists. Trends in Stem Cells Biology and Technology serves this growing community, as it reveals new aspects of stem cell research by specifically covering studies focused on spermatogonial stem cells, uniparental embryonic stem cell lines, the generation of gametes from stem cells, reprogramming germ cells to stem cells, genetic reprogramming of nuclear and somatic cells, tissue engineering and mechano-transduction of stem cells, and the development of stem cell technologies for the treatment of deafness, heart disease, corneal injury and diabetes.
Contact: Customer Service Centre, Springer GmbH, Haberstrasse 7, 69126, Heidelberg, Germany. Tel: +49 (6221) 345 4301; Fax: +49 (6221) 345 4229; E-mail: firstname.lastname@example.com.
Gene Therapy of Cancer: Methods and Protocols
This second edition fully updates the publication with expert coverage of established and novel protocols involving both experimental and clinical approaches to cancer gene therapy. It contains overviews of new concepts and strategies with chapters on regulatory and ethical issues, developments, problems and possible limitations of design, and production of gene therapeutics as well as translational issues. The chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step rendition of protocols, and notes on troubleshooting and avoiding known pitfalls.
Cutting edge and authoritative, Gene Therapy of Cancer: Methods and Protocols is an ideal guide for all those who wish to explore the fast-paced and critical study of non-viral, viral, experimental and clinical cancer gene therapy.
Contact: Customer Service Centre, Springer GmbH, Haberstrasse 7, 69126, Heidelberg, Germany. Tel: +49 (6221) 345 4301; Fax: +49 (6221) 345 4229; E-mail: firstname.lastname@example.com.


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Exclusive: Southern, Glazer's Sign Letter Of Intent To Form Strategic AllianceOctober 22, 2015
The middle tier's consolidation wave is rolling again. Just days after Charmer-Sunbelt and Wirtz Beverage Group joined forces, SND has learned that Southern Wine & Spirits and Glazer's have signed a letter of intent to form a strategic alliance.
A Southern-Glazer's union would bring together the country's first- and fourth-largest spirits and wine wholesalers, respectively, to create a distribution force of unmatched scope and reach. The two wholesalers' combined revenue surpasses $16 billion, and they collectively operate in more than 40 U.S. states.
Despite the fact that Southern and Glazer's are giants in their own right, they have little geographical overlap. While the Miami-based Southern operates in 35 markets and the Dallas-based Glazer's in 15, they only have seven markets in common. SWS is strongest on the coasts—California, Florida and New York comprise more than 60% of its revenues—while Glazer's is particularly formidable in the country's interior, with Texas, Louisiana and Missouri its three biggest markets.
This isn't the first time Southern and Glazer's have agreed to partner. In August 2008, the companies announced that they intended to merge their operations in a new venture called Southern Glazer's Distributors of America. But that deal fell through roughly a year later.
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Tagged : distributors, Glazer's, Glazer's Distributing, Southern Wine & Spirits, Southern Wine & Spirits of America
Get your first look at 2018 data and 2019 projections for the wine and spirits industries. Order your 2019 Impact Databank Reports. Click here.

subset: commoncrawl


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Teams Meet in Bramley
Gift of the Givers Medical, Search and Rescue Teams always review our response capability after any big mission, in this case the Mozambique Floods. In depth discussions are held by our multifaceted team to increase speed and efficiency for the next mission. To be totally self sufficient for water rescue another R1 million of specialised equipment was purchased.


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Searched for: author:"Pozzi, P."
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Adaptive optics plug-and-play setup for high-resolution microscopes with multi-actuator adaptive lensQuintavalla, M. (author), Pozzi, P. (author), Verhaegen, M.H.G. (author), Bijlsma, H.K. (author), Verstraete, H.R.G.W. (author), Bonora, S. (author)Adaptive Optics (AO) has revealed as a very promising technique for high-resolution microscopy, where the presence of optical aberrations can easily compromise the image quality. Typical AO systems however, are almost impossible to implement on commercial microscopes. We propose a simple approach by using a Multi-actuator Adaptive Lens (MAL)...conference paper 2018


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Ayr, Carrick and Cumnock MP Bill Grant joined Cold Feet actress Fay Ripley and Marie Curie nurses to launch this year's Marie Curie Great Daffodil appeal.
The money raised will help the charity be there for more people living with any terminal illness, providing them and their loved ones with vital care and support at the most difficult time of their lives.
Bill is encouraging local people to help the charity raise more money than ever before by simply giving a donation and wearing a Marie Curie daffodil pin:
"Chances are, we all know someone who's been affected by a terminal illness, so it's absolutely crucial that families have the care and support they need at such a difficult time. I hope that as many people as possible wear a daffodil this March and understand that in doing so, they are making a huge difference for people living with a terminal illness and their loved ones."


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Homes are affordable, but buyers still stymied
(MoneyWatch) Homes are more affordable than they've been in decades, according to data released Wednesday by the National Association of Realtors. In fact, 2012 is likely to go down as a record year for home affordability.
NAR's home affordability index stood at 198.2 in November, and the trade association predicts a record high of 194 for all of 2012. The previous record was set in 2011, when the index hit 186; NAR began keeping the records in 1970.
Home affordability is based on median home price, median family income and average mortgage interest rates. An index of 100 represents the point where a median-income household has exactly enough income to qualify for the purchase of a median-priced existing single-family home, with 20 percent down and 25 percent of income devoted to mortgage payments.
The current level of affordability means a median-income household has twice as much buying power, setting a new record in 2012. Housing experts are optimistic that homes will remain highly affordable in 2013.
- 5 ways to boost the value of your home
- Who are today's wealthiest homebuyers?
- U.S. housing market finally ready for take-off?
"Rising home prices and a gradual uptrend in mortgage interest rates will offset improvements in family income, but 2013 will likely be the third best on record in terms of household buying power," said NAR chief economist Lawrence Yun in a statement. "A window of opportunity remains open for buyers who can qualify for a mortgage."
Low home prices and mortgage interest rates are big perks for buyers who can get financing, but they also prove that the housing market is still struggling to recover. Although home prices are generally trending upward, many homeowners still find themselves with houses worth less than what they bought them for. That's largely due to the fact that properties are appraised against comparable homes that are more affordable than ever.
Even homeowners who aren't "underwater" on their homes are perched on the edge of their own personal "fiscal cliff." According to a recent survey sponsored by home warranty company TotalProtect, a staggering 61.5 percent of homeowners would be devastated financially by a home repair that cost less than $2,000.
That means if a furnace or water heater gives out, an electrical system malfunctions or a plumbing line breaks, most homeowners would experience a significant financial setback. In some cases, it could take years for them to pay off the repairs -- plus interest.
Even buyers who can afford homes and the repairs that go with them may still run into trouble. Tight lending restrictions kept many would-be buyers out of the market in 2012, and this trend could continue well into the new year if murky lending requirements remain in place.
Until banks are willing to lend and consumers feel more confident spending money, the housing recovery will continue to crawl. With would-be buyers running into financing headaches and homeowners afraid that the slightest home repair could ruin their finances, it's clear that the housing market remains in need of fixing.


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Transform your living space with beautiful Monument Wallpapers
Want to refurbish your home interiors? If the answer is yes, then there can be nothing better than a bright and beautiful monument themed wallpaper. At Marshalls, we offer a wide range of best quality monument wallpaper for walls that can add a lot to the interiors of your home or office. Our wallpapers are sure to make a difference to your space, offering it an elegant and unique transformation.
You can choose the perfect option from our range of monument wall coverings online and make any plain and gloomy looking space pop up. These wallpapers can be ideal for your bedroom, dining room or even the living room. Whether you like the leaning tower of Pisa, the Eiffel Tower or the Taj Mahal, you can just browse through our range of hundreds of monument wallpapers to find what you like.
Our attractive monument wall coverings are sure to give life to any space in your home or office. If you love a particular monument and you've visited it multiple times, then what better way to look at it every day than having a wallpaper in your bedroom, living room or even the bathroom.


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2019 Volkswagen Jetta
Turn heads left and right.
If you're in the market for a sedan that offers outstanding efficiency without sacrificing your own driving enjoyment, then buy or lease a 2019 Volkswagen Jetta. The 2019 Jetta is powered by a turbocharged engine and delivers smooth handling at every turn. Plus, you'll benefit from innovative entertainment and safety technologies while on the road. Visit our Volkswagen dealership in Schenectady, NY, to buy or lease a 2019 VW Jetta sedan today.
2019 Volkswagen Jetta Interior & Technology
The 2019 Volkswagen Jetta is a family-friendly sedan that offers first-class features that all of your passengers will love. The new 2019 Jetta interior provides you with a wide range of innovative technologies, like the standard Composition Color touchscreen sound system with a 6.5-inch color display. The standard Volkswagen Car-Net® App-Connect system also makes it easy to use your favorite apps on the go thanks to Apple CarPlay™ and Android Auto™ compatibility. Upgrade 2019 Jetta trims and you'll find stellar options like leather seating surfaces and an 8-inch touchscreen navigation system that help you enjoy every ride around Upstate New York. You can also add unique two-tone leatherette seating surfaces and amenities like 10-color interior ambient lighting to help create a more welcoming environment. More standard and optional 2019 VW Jetta interior features and technologies can include:
- Bluetooth® technology with audio streaming
- Climatronic® dual-zone automatic climate control
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2019 Volkswagen Jetta Engine Specs & Safety
Cruise around Schenectady and beyond in true style by getting behind the wheel of a new 2019 Jetta sedan. The new 2019 VW Jetta engine offers up to 40 highway mpg* so that you can take on big trips without having to refuel at every stop, plus it provides the turbocharged performance you need to soar down every straightaway. The 2019 Jetta model also provides standard peace of mind thanks to driver-assistive features like a Rear View Camera System and seven stability-enhancing systems. Move up to popular Jetta trim levels like the new 2019 Jetta SE trim, and you'll gain features like a Blind Spot Monitor and Rear Traffic Alert. Add in other driver-assistive technologies like Lane Departure Warning and High Beam Control technology to gain a greater sense of security on every trip. Your 2019 Jetta engine specs and safety features can include:
- 1.4-liter TSI® 4-cylinder turbocharged engine with 147 hp and 184 lb-ft of torque
- 6-speed manual transmission
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- Driving Mode Selection
- XDS® Cross Differential System
- Forward Collision Warning
- Autonomous Emergency Braking


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Next morning: Date to be advised
If you would like to be notified when another Dharmakids class is to be held, click here and complete the contact form - please put "DHARMAKIDS" in the comment field. Once we have something scheduled we will be in contact by email.
The Dharmakids program is ideally for school aged children between 5 & 9 years old.
In these classes we will introduce basic Buddhist teachings and meditations using stories, discussions and simple activities.
Classes will be held once each term, when our schedule permits. A parent or guardian must remain with the child during the class and regsitration is essential.
Please email confirmation of the number of children attending and their ages .
Suggested donation (on the day) $10 per family


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Nygård, during a press conference at his unique house at Nygård Cay in Lyford Cay, presented Gibson with a cheque for $10,000 for the Acklins Regatta August 1-4. It's expected that the regatta site at Spring Point will be named in honour of Gibson.
Nygård said when he was contacted by Gibson, he couldn't turn him down because "he's the King." Nygård, however, said that having financed countless sporting activities over the years, he's hoping that there can be a similar system put in place like the one he initiated for the 'Golden Girls' in their lead up to the 2000 Olympic Games.
Nygård matched the amount that was raised by the general public and the total funds was used to assist the various sporting programmes over a period of time. It was estimated that some $250,000 was raised at the time.
Additionally, Nygård has made a contribution to just about every regatta held in the country. He noted that Gibson has been responsible for getting him to assist the regattas, but when he was approached this time, he couldn't turn down his friend.
Nygård's contribution came on the heels of hosting the historic Independence Day Regatta at Clifton Pier on Independence Day. Nygård made a contribution of more than $50,000 towards the hosting of the regatta that
was headed by Rev Dr Philip McPhee.
Accepting the cheque, Gibson said the contribution will go a long way in making it a good "Christmas" for the people of Acklins. Gibson said he knows he can count on Nygård to assist in the manner that he has done over the years. WEDNESDAY, JULY 17, 2013 $10,000 For Acklins Regatta Thanks to Peter Nygård
Also on hand for the presentation was V Alfred Gray, member of parliament for MICAL, which includes Acklins. Gray is also the minister of agriculture, marine resources and local government, which has the responsibility for regattas.
"King Eric, who is legendary, is from Acklins and this year the organizers have chosen to honour him by renaming the regatta site after him," Gray said. "King Eric is deserving of all that we can say about him."
As a consultant in his ministry, Gray said he's appreciative of the contribution that Gibson has made to regattas and even though his steps are much slower than they were, his mouth is still very loud.
"It's always good to give honour to those who deserve it while they are able to appreciate it," Gray said. "Every
now and again, we need to stop and show how much we appreciate people. So I want to congratulate King Eric on the site being named after him."
Gray went a bit further and said that while every dollar counts, it takes about $75,000 to stage the regatta in Acklins and he's appreciative of whatever support he receives because the Bahamas Government can't fund all of the regattas that are being held.
"He doesn't have to do this. He is a Bahamian, a wealthy Bahamian, but a lot of people around him are also sharing the same thing. They are Bahamians too," he said. "How many of them come forward and make a contribution. This is a nation building. It's not about Nygård. It's not about the government. It's about contributing to a country of which you belong and you're a citizen. I'm talking about every Bahamian, especially those who are wealthy and can do something."
Gray said he is packed and ready to go to Acklins and he encouraged the Bahamian public to join him next weekend when they honour Gibson. But for those persons who can't make the trip, Gray encouraged them to travel and participate in any of the other regattas being held in the other Family Islands.


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AXIAL AX31310 .040 Clear Retro Trophy Truck Body Description
FEATURES: Molded from.040 (1.02mm) clear polycarbonate plastic Fits the Yeti SCORE Trophy truck Retro design features include a 1960s era roofline,. INCLUDES: Axial TT-380 SCORE Retro Truck Body Trim and Sponsor Decals Precut Vinyl Window Masks Black Plastic Light Buckets and Body Trim. REQUIRES: Body scissors and reamer Polycarbonate safe spray or brush-on paint. The product is manufactured in CHINA.


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Terms and conditions
The terms and conditions were last reviewed at the 08th of May 2019
School information
Højskolen Østersøen
Flensborgvej 48-50
6200 Aabenraa
Tlf.: +45 7462 4700
E-mail: email@example.com
CVR nr. 15756349
1. Conditions
The student receives instruction, excursions, etc. according to the times stated in the course program. Højskolen Østersøen reserves the right to change the program. Any changes may be due to illness or general force majeure. The school undertakes to find equivalent activities as a replacement. After registering, the student receives a confirmation of participation by mail. Approx. one month before the start of the course, the student will receive a practical letter by mail or letter with information about the course.
2. Enrollment
Enrollment takes place either by Højskolen Østersøen's website web registration (www.hojoster.dk or by telephone inquiry. The registration is termed binding. The student receives written confirmation by mail.
3. Payment terms
Rates and payment terms are provided together with the description of each course. All prices are listed in Euros (Euro). All amounts are exempt from VAT, cf. VAT rules for education.
It is possible to pay with Visa or bank transfer.
Half of the tuition fee must be paid for the registration to apply. Upon cancellation, the intuition fee is not refunded. In case of an interrupted stay, payment must be made for the week started plus four weeks. If you don't get a visa you will get a full refund of your money.
Your Folk High School stay is paid as followed:
- Half of the tuition fee immediately
- The rest of the tuition fee is paid the latest two months before the course start
- Registration is only valid when the college has confirmed it and when half of the tuition fee has been paid.
- We strongly recommend cancellation insurance on all our courses (cannot be purchased through the college)
- No fees are charged for online payments.
- If the 2nd tuition is not paid on time, Højskolen Østersøen contacts the student either per. e-mail or phone with a reminder of payment.
Online payment security
No account or credit card information is stored when paying online. All data communication in connection with the electronic payment is done via a third party, a secure payment solution (Bambora formerly E-pay), a so-called encrypted SSL connection according to regulations from NETS.
4. Return
The general law of 14 days' right of withdrawal on goods and services purchased online is not applicable to Folk High School courses. If you cancel your registration, your registration will be canceled and our normal repayment rules for paid-in amounts will enter into force.
5. Complaints
Any complaints about errors/problems during payment or your stay can be directed to email@example.com
6. Reservations
Reservations are made for print / key errors and for sold out courses; deviations from the written as well as the displayed images.
7. Cancellation of courses
We serve the right to cancel courses if there are too few registrations or due to illness. In the event of cancellation, it will be possible to move the student's registration to another course with vacant seats or get the money returned. The student will be contacted by email or telephone in case of cancellation. We cannot guarantee that canceled courses will be created at a later date. The course fee will only be refunded in case of cancellation or relocation of the course.


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Setting Translation Checks
Translations missing key elements such as a variable or link could potentially break your website or app. To help prevent this, Transifex automatically checks every translation against a set of conditions. Whenever a condition is not met, e.g. an HTML element is missing, the translator will be shown either a warning or error message telling them what needs to be fixed. Translators can still save a translation when there's a warning. But if there's an error, they'll need to address the issue before they'll be able to save the translation.
Customizing translation checks
Each file format has a set of translation checks on by default. You can change whether a failed check results in an error or warning, or turn off a check all together.
To customize translation checks:
Go to your Organization Settings from the main navigation.
Click on Translation Checks in the left menu.
Click on a file format to see the checks available for that file format.
Click on the toggles next to each rule to change whether a check should show a warning, error message, or be off.
Hit Save to confirm the changes.
You can always restore the translation check settings by clicking the Set to default checks next to the Save button.
Checking for custom variables
If you use custom variables in your code, you can set up custom translation checks and make sure it's left untouched in the translation. This is done by adding a custom check for a file format, and specifying the characters your custom variables start and end with.
To do this:
Head to the Translation Checks settings page.
Click on the file format you want to add custom checks for.
Click Set up placeholder delimiters.
In the popup, specify the characters your custom variable starts and ends with.
Click Add placeholder so as to finish adding this check. You can add more if you like by creating more placeholders.
When adding multiple placeholder delimiters, keep in mind that the delimiters are executed in the order they are added.
In the following example both placeholders will be executed. However if the order was reversed then only the first expression will be executed.
Like the default checks, you can change whether a failed check results in an error or warning, or turn it off all together.


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There are no items in your basket.
You can get FREE Standard Delivery (1-3 days via First Class) for orders placed online today. We also offer a DPD Express Next Day service for £4.95. For more details, please view our Delivery Information page. Please note: We try our best to dispatch In-stock items the same day if ordered before 3pm.
If you are not totally satisfied with your purchase for any reason, you have the right to cancel your order within 14 working days from date of delivery, and we will provide you with a credit or refund. Please view our Returns Information for further details.
- This sign notifies about the presence of eye wash facility and help people locate the station with complete ease.
- This sign is made with sturdy materials of 1mm rigid plastic and self adhesive vinyl to boost up its lastingness.


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The Client
Leonard Cheshire Disability is a large UK charity that supports individuals to live, learn and work as independently as they choose, whatever their ability.
The Project
I was approached my Leonard Cheshire Disability to help them build a micro-site (a separate site to the main website) for their centenary celebrations. This website would showcase 100 stories of the impact made by the charity, and would also fit in with a re-branding project that was being done at the same time.
The Result
I built an interactive, mobile-friendly site from a provided design using WordPress as a content management system. I used the Isotope masonry library for a dynamic block layout and Turbolinks to make the site behave more like a single-page application without full page reloads when moving around.
I also advised on how the design could be tweaked for better website performance, and we used some modern web development techniques to get the design to work whilst maintaining performance.
The client particularly liked the video training material that I put together for them to help work with the site, saying that these videos were:
"…really clear and very useful. I've not worked with a developer who produces things like this before!"


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Tag: statement loafers
Your 5 Faves This Week 💗
June 22, 2017
1. Harrow White with Navy Cap Your absolute favourites this week are our timeless Harrow ballerinas in cool white with navy toe cap. Pair with your favourite summer dress our your fave pair of shorts for the perfect summer outfit. SHOP NOW 2. Chelsea Blue & Orange Runner up this week […]
Fashion Blogger Street Style x Cocorose London
February 24, 2016
Spanish blogger Oli Cobi #StrikesACocopose in her fun and fabulous statement loafers. Made using supple 3D leather, these foldable shoes are smart and quirky – simply perfect for any occasion. Happy Cocorosing! xx
Fashion Blogger Street Style x Cocorose London
November 9, 2015
Fashion blogger Julia Lundin goes back to black, highlighting her pucker Farringdon kissing lips loafer and giving her classic shift outfit a fun yet grown up twist. Our luxe foldable loafers are the ultimate in comfort, function and style. Ideal for urban lifestyles, they can be worn from office to cocktails and are perfect for travelling and commuting […]
Festival Feet
July 24, 2015
Whether you're dancing through summer festivals, drinking cocktails on the beach or Pimms in your local park, Cocoroses are your best companions this summer. Our Diffusion range comes with adorable matching travel purses, which allows you to #CocoroseIt any place, any time. Happy Cocorosing xx
As Seen On Update
May 14, 2015
Happy Thursday, Cocorosers! We've had some fantastic fashion bloggers #CocorosingIt all over the world and we wanted to make sure that you got to see some of their lovely pictures. Click the names above to check out their blogs and the images to see what shoe's they're loving. Jo Fletcher Jasmin Fatschild Sophia Salaroli Happy […]
Ahoy, Cocorosers!
April 8, 2015
Get your feet ready for The Boat Race this Saturday with our super cute and stylish Carnaby statement loafers with nautical applique. Click here to get Your sailor-style – also loved by Blogger Jo from Lost in the Haze. _____________________________________________________ Cocorose It to the Kings Road We're happy to announce that we'll be popping up […]
Sweet Easter Treat!
March 27, 2015
Cocorosers, we're really happy to be giving you the chance to win our adorable Carnaby loafers plus artisan du chocolat's delicious chocolate rainbow! You'll be automatically entered into our competition with every order placed from today until Easter Sunday. So snap your perfect spring pair now or get a surprise for your loved ones! ____________________________________________________________ […]


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This global law firm with a strong brand presence in Asia, is seeking a Senior BD Manager in Hong Kong/ Singapore. This role is responsible for developing BD and marketing strategy for the Transactional practice groups across Asia Pacific.
Working with partners and reporting into the overall Director of BDMC Asia-Pacific, you will implement strategy and business plans in order to increase revenue and profitability of client relationships. You will also take lead on key cross-border and cross-practice regional initiatives. Key areas of focus will include opportunity spotting, pipeline development, pricing strategy and market profitability.
This is a leadership role where you will also manage 2-3 team members.
Who should apply?
To be successful in your application, you will be an experienced business development manager, having previously worked in professional services and bringing some team management experience.
Covering 17 offices and 5 practice groups, this role has a large and cross-border portfolio and so could be a good career advancement opportunity for someone currently heading up a BD team in a smaller business.
You will have the capabilities and confidence to proactively develop and execute initiatives that best position the firm to achieve superior outcomes. You will be collaborative, commercially minded, a strategic thinker and possess exceptional communication, influencing and BD campaign management skills.
Job Details
+44 (0) 20 7332 6339[email protected]


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Independent Financial Advice:
Based in Doncaster, South Yorkshire we are a leading team of Independent Financial Adviser's who work to develop long term relationships with our clients. We specialize in RETIREMENT & INVESTMENT PLANNING and our IFA's have over 50 years of experience between them. We excel in the following areas:
- Retirement Planning
- Portfolio Planning
- Investments
- Pensions inc SSAS/SIPP & Income Drawdown
- Annuities
- Protection - Personal & Business
- Mortgages
- Equity Release
- Long Term Care Insurance
WE ARE AUTHORISED & REGULATED BY THE Financial Conduct Authority AND THE COMPANY AND IT'S ADVISERS ARE BOUND BY THE F.C.A'S RULES. THOSE WHO ADVISE ON LIFE ASSURANCE, PENSIONS, OR UNIT TRUST PRODUCTS ARE EITHER INDEPENDENT ADVISERS OR REPRESENTATIVES OF ONE COMPANY. YOUR ADVISER IS INDEPENDENT AND WILL ACT ON YOUR BEHALF IN ADVISING YOU ON LIFE ASSURANCE, PENSIONS OR UNIT TRUST PRODUCTS. BECAUSE YOUR ADVISER IS INDEPENDENT HE OR SHE CAN ADVISE YOU ON THE PRODUCTS OF DIFFERENT COMPANIES.
We confirm that we shall be pleased to advise you in connection with your Life Assurance, Pension, Unit Trust and Unit Trust PEP arrangements.
When we have arranged any investments for which you have given instructions we will not give you any further advice unless you request it, but will be glad to advise you at any time you ask us to do so.
We normally require written instructions before we act on a client's behalf, however, we may at our discretion accept verbal instructions. You, or we, may terminate our authority to act on your behalf at any time, without penalty. Notice of this termination must be given in writing.
Details of how we take our remuneration are enclosed in the accompanying 'Key Facts About the Costs of Our Services' document.
D J Cooke (Life & Pensions) Ltd has two partners or directors who are engaged in the day-to-day conduct of investment business. They are David J Cooke and Paul A Cuffling and can be contacted at: D J Cooke (Life & Pensions) Ltd , 32/34 Church Street, Conisbrough, Doncaster, DN12 3HR, 01709 863318/864414. Our FCA number is 120927.
D. J. Cooke (Life & Pensions) Ltd do not handle client money. We never accept a cheque made out to us (unless it is a cheque in settlement of charges or disbursements for which we have sent you a bill) or handle cash. We will make arrangements for all your investments to be registered in your name unless you first instruct us otherwise in writing. We will forward to you all documents showing ownership of your investments as soon as practicable after we receive them; where a number of documents relating to a series of transactions is involved, we will normally hold each document unless the series is complete and then forward them to you.
We undertake not to transact any business on your behalf in which we may have a personal interest, unless such an interest has been disclosed to you in writing, nor will we transact any business on your behalf, in which another of our clients has such an interest, unless such an interest is disclosed to you in writing, and your consent obtained.
We keep records of our business transactions for at least six years and you have the right to inspect our records relating to your transactions.
For your further information we would confirm that this company maintains professional indemnity insurance.
If you wish to register a complaint, please write to: DJ Cooke (Life & Pensions) Ltd, 32-34 Church Street, Conisbrough, Doncaster, DN12 3HR or telephone 01709-864414. A summary of our internal complaints handling procedures for the reasonable and prompt handlingof complaints is available on request and if you cannot settle your complaint with us, you may be entitled to refer it to the Financial Ombudsman Service at:
or by contacting them on 08000234567.
Yours sincerely,
Directors - D. J. COOKE P.A. CUFFLING
Click here for a free initial consultation
Free Consultation
You can have a free initial consultation. There's no fee, no catch and no obligation on your part.


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Rejoice this yr's Lunar New 12 months with selfmade Gà Sốt Cam – a easy, tasty low-cost Vietnamese dish of scrumptious orange hen with aromatic lemongrass.
Proceed studying"Vietnamese Orange Rooster with Lemongrass"
Vietnamese Orange Rooster with Lemongrass – Gà Sốt Cam
20 minutes preparation
20 minutes cooking
Massive wok
Small knife
Chopping boards
Two small frying pans (or clear and reuse one)
four meals preparation bowls
Slotted spoons
700g hen thigh fillets
250ml recent orange juice
2 garlic cloves
1 shallot
5 spring onion
1 tbsp chopped ginger
1 tbsp salt
1 tbsp sugar
1 tsp lemon pepper*
1 tsp floor white pepper*
2 tbsp potato flour (or cornflour)
1 tbsp minced lemongrass
four tbsp gentle soy sauce
1 tbsp toasted sesame oil
2 tbsp sesame seeds
Groundnut oil for frying
* – improve to 2 tsp for a extra intense flavour.
Making ready the Substances
Clear hen thighs, take away fats. Lower into bite-size items, place in a bowl. Coat hen items with potato flour, then salt, white and lemon peppers.
Slice the spring onion white root thinly lengthways. Slice the spring onion inexperienced stalks into small items.
Finely chop the shallot and ginger. Crush the garlic gloves.
Cooking the Dish
Warmth a small quantity of groundnut oil in a wok. Stir fry shallot, white spring onion, ginger and garlic till tender. Take away with a slotted spoon and put aside, leaving oil within the wok.
Add hen items to the wok, sprinkle with sugar. Stir fry till the hen items are golden throughout.
Return cooked aromatics (shallot, spring onion, ginger and garlic) to wok. Pour the orange juice into the wok and simmer on a low warmth, stirring sometimes.
In the meantime in a separate pan, warmth a small quantity of groundnut oil. Fry the minced lemongrass for one minute then add the soy sauce and sesame oil, fry for an additional minute. Then add pan contents into the wok.
Simmer and stir the contents of the wok till the orange sauce has decreased by half, round 10-12 minutes.
Take away hen items with a slotted spoon and place into bowls. Sprinkle with sliced inexperienced spring onion stalks and sesame seeds.
Decant the sauce from the wok in a aspect bowl for pouring or dipping.
Cooking with a Large Inexperienced Egg
This may be cooked utilizing a Large Inexperienced Egg. Observe this information for wok cooking on the Egg. Stir fry the aromatics and hen with the wok low and shut to fireplace ring, then elevate as much as simmer.
The lemongrass, soy sauce and sesame oil combination will be cooked in a separate pan. Take away and canopy the primary wok with a dome while doing this to retain the warmth.
Hints, Suggestions and Photos
Minced lemongrass is out there from supermarkets and Asian meals shops.
There's a first rate quantity of exercise on the finish to get the dish assembled. It's value studying by way of all the methodology earlier than beginning.
The tactic will be sped up through the use of two woks concurrently for first two steps.
Put the rice on to cook dinner when the lemongrass combination is added to the wok. This leads to the rice being prepared concurrently the hen.
Sprinkle pomegranate seeds on the rice for sweetness and ornament.


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Handmade Fleece HandleTug
Dog Toys
If you've seen similar Handle Tugs you may notice that some of them are loosely braided, and the cut edges of the fleece are turned out. I make every effort to turn in the rough edges, and braid my tugs as tightly as possible, in order to make them durable and attractive.
All but a few of my tugs start with the same width fabrics, but there are often variations in length. All tugs are $6.00, unless otherwise noted after the item number.
I only purchase remnants, or sale fabrics to make these tugs, to keep the price reasonable. The fabric is cut in the stretchy direction with the exception of one group of tugs made in greys and white. These were cut in the non-stretchy direction, and are even stronger than the regular ones. I have four left to sell, and they are $7.00 each.
Again, these are for
interactive & motivational play
. Please use responsibly and don't leave dog unattended with his or her HandleTug. With proper use you can expect your dog to get a lot of pleasure from these toys.
I've added a few photos below as examples. Please disregard the numbers as many of these tugs may already be sold.
for a list of colors available, or for a custom color order


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Normally, in the process of carrying out a screen reorientation, the Android platform tears down the foreground activity and recreates it, restoring each of the view values in the activity's layout.
In an app you're working on, you notice that a view's value is not being restored after screen reorientation. What could be a likely cause of the problem that you should verify, at a minimum, about that particular view?
You should verify that it has a valid
id. In order for the Android system to restore the state of the views in your activity, each view must have a unique ID, supplied by the
android:id attribute.
More information is available here.


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How to submit a RTI Application?
You will need a proof, that your RTI application has been received by the PIO. The tested methods to submit a RTI application are:
- Personally, by hand: Please ensure that you get your copy of the application and proof of payment duly stamped, signed and dated, either by the PIO or by the inward department
- Registered Post AD: The AD card will act as proof of submission, after it is returned to you by the postal department. In case the AD card does not come back with a proper stamp, signature and date of receipt, follow up with the dispatching post office to get the AD card completed
- Speed Post (A postal department service): Once the application is sent by Speed Post, track it on http://www.indiapost.gov.in/Speednew/track.aspx and keep a print out of the delivery status carefully with you
Do not use ordinary post, private courier companies, etc. since these will not provide you with a confirmed proof of delivery.