Saturday, 4 December 2010

Drug can extend life for multiple myeloma patients

Adding a second drug to standard chemotherapy treatment can help patients diagnosed with an aggressive type of bone marrow cancer live longer, according to a major study published online in the Lancet today.

Around 4,000 British people are diagnosed each year with multiple myeloma, a cancer that affects a type of white blood cell in the bone marrow called plasma cells. Average survival after diagnosis is just three to five years so new treatments are urgently needed.

Professor Gareth Morgan from The Institute of Cancer Research (ICR) and The Royal Marsden Hospital led a Phase III study of 1960 newly-diagnosed multiple myeloma patients comparing a zoledronic acid treatment called Zometa, developed by Novartis, with another standard approved treatment called clodronic acid. All patients were also given chemotherapy. The trial, known as the Medical Research Council (MRC) Myeloma IX study, ran from May 2003 until November 2007 with funding from the MRC and support from Novartis, Schering Health Care, Chugai, Pharmion, Celgene and Ortho Biotech.

Friday, 3 December 2010

Scientists unlock bacteria’s survival aid

Scientists have worked out how to control a protective mechanism found in many bacteria that helps them grow and stay alive.

In a finding that is hoped will help the future development of new antimicrobial drugs, researchers have revealed they are able to manipulate the protein or channel that protects E.coli, Salmonella, Legionella, which causes Legionnaires’ disease, and Pseudomonas, which can affect cystic fibrosis patients and sufferers of other chronic lung conditions.

All bacteria have channels that aid their survival by protecting them when they are threatened or under attack.

Last year Ian Booth and Tarmo Roosild at the University of Aberdeen, Nevada Cancer Institute in Las Vegas and the Salk Institute in San Diego published a paper that explained the mechanics of these channels, which stay shut if all is normal, but spring open to help protect bacteria against potential toxins.

Now these scientists, in collaboration with Stuart Conway at the University of Oxford, have taken their findings another step forward.

Thursday, 2 December 2010

Developing photonic crystal technology for diagnosis of cerebrovascular disease

The P3SENS consortium has been formed to develop an immunoassay detection device suitable for use in emergency-medicine, whether diagnosis is required in an ambulance, emergency room or as part of a rapid near-patient laboratory test in a hospital environment. It is anticipated that the combination of highly sensitive Photonic Crystals, a panel of clinically proven Bio-Recognition Elements and low-cost production technologies will result in a novel biosensor system which can make a real difference to Stroke patients worldwide.

At the core of the biosensor is a photonic chip, which due to the low cost requirements of Point of Care applications is to be fabricated from nano-composite polymeric materials, using highly scalable nano-imprint-lithography (NIL).

Phase 1 Study of Anti-CD19 Antibody in chronic lymphocytic leukemia

MorphoSys AG and Xencor Inc announced today that they have initiated Phase 1 testing of MOR208 (XmAb®5574), and the first patient has been dosed. MOR208 (XmAb5574) is a potent monoclonal anti-CD19 antibody to which MorphoSys recently gained worldwide access via an exclusive license and collaboration agreement with Xencor. The trial is designed to assess the drug's safety, tolerability, pharmacokinetic profile and preliminary anti-tumor activity in chronic lymphocytic leukemia (CLL) patients. The open-label, multi-dose, single-arm, dose-escalation study is estimated to enroll 30 patients suffering from relapsed or refractory CLL.

Streamlining in vitro research regenerative research

A UK company has developed a new technology that could streamline in vitro research and hold the key to dramatic advancements in the field of regenerative medicine.

Leading UK nanobiotechnology company, Orla Protein Technologies, has developed a unique biosurface technology which could offer a more efficient and cost effective solution for biomedical research, whilst highlighting exciting possibilities for the future of biomedical implants and ‘nanomedicine’.

Featured in a recent journal article by Newcastle University PhD student Elizabeth Mitchell and Dr Mark Birch of the university’s Musculoskeletal Research Group, Orla’s technology offers a very real alternative to current in vitro testing techniques, including those used for stem cell research.

Developing next generation modular bio-therapeutic manufacturing technology

G-Con Manufacturing, LLC and GE Healthcare, a unit of General Electric Company, announced today their intention to collaborate on the development of an industry-leading modular portable bio-process manufacturing solution for vaccines and therapeutics.

This collaboration combines GE Healthcare’s global presence and expertise in biopharmaceutical manufacturing technology with G-Con’s modular portable flexible clean-room technology. The collaboration will offer comprehensive GMP manufacturing solutions that are less expensive and quicker to build and maintain and easier to operate than any currently existing solution on the market.

Together, the companies have the capability to design, build and deliver turnkey advanced bio-therapeutic manufacturing facilities throughout the world, and will be able to meet the growing market for rapid access to biopharmaceutical manufacturing capabilities, whether in developing markets, or for increased speed in situations such as pandemic response.

“GE Healthcare is a global life sciences leader, and we are excited by the market-changing next generation therapeutic manufacturing innovations this collaboration will be able to produce,” said Dr. Barry Holtz, President of G-Con Manufacturing, LLC.

“This collaboration is part of GE Healthcare’s mission to increase speed and access, and reduce cost for developers and manufacturers of bio-therapeutics and vaccines around the world,” said Nigel Darby, Vice President, Biotechnologies, GE Healthcare. “This collaboration means we move further towards our vision of modular and possibly mobile flexible bio-pharmaceutical manufacturing facilities – the vaccine factory in a box.”

G-Con Manufacturing, LLC

Autoclave validation applications using wireless data loggers

Following its recent securing of a UK distribution agreement for DataTrace fully patented, high-tech data logging systems, Cherwell Laboratories has verified a rapid autoclave validation application.

DataTrace are self-contained, wireless, high precision, data loggers designed specifically for use in critical manufacturing, quality control and validation applications. Since no wiring is required, DataTrace probes can be readily used to measure temperature, humidity and pressure directly inside an autoclave for validation with full 21CFR11 compliance and minimal production downtime.

Traditional autoclave validation involves the complicated and time consuming task of introducing many thermocouple wires into an autoclave chamber. This can be extremely time consuming, not only in fitting the probes through a port, but also in placing them securely within the load. Such thermocouples also require qualification before and after use to identify any offset.

Improving plate washing for ELISpot assays

Tecan’s HydroFlex microplate washer has allowed hematologists at the Department of Oncology and Hematology, University of Modena and Reggio Emilia, Italy, to introduce automated washing for Enzyme-Linked ImmunoSpot (ELISpot) assays.

The laboratory performs detailed studies on the immune response of patients to viral, fungal and tumor antigens. Dr Giovanni Riva, a postdoctoral scientist at the laboratory, explained: “We are essentially performing clinical research studies, investigating the immune response in both peripheral blood and bone marrow samples, and have also expanded our field of research to include the study of polymorphisms, in an attempt to correlate genetic differences and disease.

“Our laboratory uses the Enzyme-Linked ImmunoSpot (ELISpot) assay, a very sensitive immunoassay, for the detection of secreted cytokines at the single cell level. The washing stages of the assay are critical, and when performed manually are very time consuming and labour intensive. We wanted to improve the methodology, and decided to change to automated washing using the HydroFlex plate washer. We now have a standardized, reproducible, automatic plate washing method, which frees staff time, allowing them to perform other tasks.”

Giovanni concluded: “The instrument has proved very reliable and is simple to use. We simply define the protocol for washing, insert a plate and then everything is done automatically. The HydroFlex is a great improvement to the ELISpot assay and our laboratory.”


Nexxis RM centralizes reporting for the whole lab

Labtronics Inc, a leader in laboratory automation, has released Nexxis RM (Report Manager), a new reporting tool that centralizes the reporting for all lab informatics systems into one central location.

Nexxis RM is a new type of lab informatics product that that produces files, print jobs and real time dashboards to make all of the lab's information available from a single source.

Nexxis RM is able to use and integrate information from instruments, LIMS and any other lab informatics system. It does this by centralizing information into standard formats and by having direct connections to other systems. It organizes data and then provides an advanced reporting process to turn the data into information.

Alvetex 3D cell culture technology among “Top 10 Life Science Innovations of 2010"

Reinnervate's alvetex, its 3D cell culture technology, is among the winners of The Scientist magazine’s “Top 10 Life Science Innovations of 2010”.

Alvetex is a highly porous material that provides a robust and inert scaffold for cells to grow and form complex 3D cell structures in the laboratory, mimicking the normal growth and formation of tissues in the body. The first of multiple presentations of alvetex, a 12 well plate, was launched in November 2010. Further presentations, including 6, 24, 48 and 96 well plates, are planned to launch over the next 12 months and are designed to allow researchers in academia and the pharmaceutical and related industries to construct 3D cell culture models for application in research into cell development, disease modelling and drug safety screening.

Wednesday, 1 December 2010

Experts shed Light on diabetes risk for South Asians

University of Glasgow academics have discovered one of the reasons why people of South Asian origin are more at risk of developing type 2 diabetes.

The new finding, published today in the journal PLoS ONE, is one which researchers hope will pave way for more studies into this area of type 2 diabetes.

According to lead author Dr Jason Gill, of the University’s Institute of Cardiovascular and Medical Sciences, South Asian muscles have a lower capacity to burn fat than Europeans which means they are more insulin resistant and so at greater risk of developing diabetes.

Large scale diabetes study

Oxford Gene Technology (OGT), provider of innovative clinical genetics and diagnostic solutions to advance molecular medicine, has today announced details of a major project with the University of Virginia Center for Public Health Genomics.

In a groundbreaking study, Professor Stephen Rich, Director of the centre, will utilise OGT’s Genefficiency aCGH microarray screening service to investigate the relationship between genome structural variation and susceptibility to type 1 (T1) diabetes.

Employing a unique array design developed from recent work exploring genome wide copy number variations (CNVs), the new study will utilise an extensive collection of over 10,000 patient samples in the hope of identifying CNVs associated with T1 diabetes. This will allow researchers to better predict disease susceptibility and highlight potential opportunities for therapeutic manipulation.

Graphene used to decode DNA

Genome sequencing will have a profound effect on our understanding of genetic biology and could usher in a day when doctor and patient are able to review individual genome sequences to fully personalise medical treatment.

As the X PRIZE FOUNDATION begins to receive nominations for its $10m prize for the first privately funded company that can accurately sequence 100 genomes in 10 days for less than $10,000 per genome, the science writer Philip Ball looks at the latest advances towards success in December Physics World’s lead feature.

Cervical cancer screening test set to save the lives of women all over the UK

The largest ever registrational study for a diagnostic product, involving more than 47,000 women shows that the cobas 4800 Human Papillomavirus (HPV) test from Roche, is able to improve the detection of pre-cancerous cells in women whose cervical smears tested normal.

The ATHENA (Addressing THE Need for Advanced) HPV Diagnostics trial demonstrated that more than 1 in 10 women in the trial aged 30 years and older who tested positive for HPV genotypes 16 and/or 18 by the cobas 4800 HPV test had cervical pre-cancer although their Pap1 smear was normal.

The conclusion is that genotypes 16 and 18 if tested positive are high-risk indicators of cervical cancer. The data points to the importance of genotyping to increase the accuracy of assessing the risk of cervical cancer, especially screening for the two high risk HPV genotypes 16 and 18, and underscores the limitations of relying on examining and assessing the appearance of cervical cells under a microscope as is the traditional method.

Latest generation of DNA and RNA folding

Integrated DNA Technologies (IDT), a leader in oligonucleotide synthesis, and Rensselaer Polytechnic Institute (RPI) today announced the launch of the UNAFold secondary structure prediction software at IDT. The software will be used to more accurately detect secondary structures within sequences submitted by customers, and will be made freely available through a web-based interface on IDT’s SciTools website.

SeqSolve: sequencing functional bioinformatics analysis software

Integromics, a leader in IT solutions for life sciences in the field of genomics and proteomics, today announced the availability of SeqSolve, a unique Next Generation Sequencing (NGS) functional bioinformatics analysis software designed for the use by scientists.

The SeqSolve analysis software, exclusively designed for Next Generation Sequencing, performs tertiary level analyzes for biologically relevant results. It has been designed with a high performance and robust computational core with a simple, but powerful user interface.

Finger length linked to prostate cancer risk

Men who have long index fingers are at lower risk of prostate cancer, a new study published today in the British Journal of Cancer has found.

The study led by The University of Warwick and The Institute of Cancer Research (ICR) found men whose index finger is longer than their ring finger were one third less likely to develop the disease than men with the opposite finger length pattern.

“Our results show that relative finger length could be used as a simple test for prostate cancer risk, particularly in men aged under 60,” Joint senior author Professor Ros Eeles from the ICR and The Royal Marsden NHS Foundation Trust says. “This exciting finding means that finger pattern could potentially be used to select at-risk men for ongoing screening, perhaps in combination with other factors such as family history or genetic testing.”

Tuesday, 30 November 2010

Chromatography data system platform enables more efficient use of laboratory data

Waters Corporation today introduced Waters Empower 3 Chromatography Data System (CDS), a scalable, enterprise-wide CDS platform that can be rapidly deployed to easily fit into existing corporate infrastructure.

“One of the most important challenges laboratory scientists and information technology managers face today is the need for data management standardization,” said Dr Rohit Khanna, Vice President of Marketing for Waters division. “Many of our customers are forced to support multiple laboratory software and informatics platforms amongst their many labs. This lack of consistency is often traced to a merger or acquisition, or perhaps legacy systems from multiple manufacturing and R&D sites. Regardless of the reason, these companies suffer from inefficiencies that directly affect their bottom line. Addressing this issue of standardization, Empower 3 CDS is designed to bring significant value to science driven organizations at the enterprise level.”

Customised clean room pass-through oven solves heat treating challenge for arterial stents

Carbolite, the UK manufacturer of standard laboratory and bespoke industrial ovens, has played a key role in helping to create a customised manufacturing solution for a leading producer of innovative arterial stents used by clinicians to treat cardiovascular disease.

The stent manufacturer approached Carbolite to create a class 10,000 clean room oven solution because it was looking for a customised design to meet its precise production requirements.

Although the stents only require heat treating to a maximum of 400°C the dimensions and temperature uniformity specifications of the oven posed a major technical challenge. The solution calls for a chamber nearly a metre and a half deep to be heated with a stability of better than ±1°C under steady state conditions coupled with temperature uniformity better than ±5°C. To ensure good temperature uniformity the oven is divided into three separately controlled zones. The main program controller is digitally linked to two slave controllers that automatically track the program set in the main controller.

Industry and academia team together on GluSense project to facilitate CNS target drug discovery

Cisbio Bioassays, member of IBA Group and global provider of HTRF (homogenous time resolved fluorescence) technology and services to facilitate drug discovery, today announced the launch of the GluSense research and development program in partnership with the Functional Genomics Institute of Montpellier, France. The project, financed by a grant of $1.2 million (€900 000) from France’s National Research Agency (ANR), will focus on the development of CNS drug discovery research tools.

Thermostatic laboratory chillers

Thermo Fisher Scientific Inc has launched the new Thermo Scientific Polar Series thermostatic laboratory chillers, the Accel 250 and Accel 500. The Polar Series has a temperature range from -10 to 80 °C, allowing users to select the optimal set-point for each application.

Thermostatic technology enables fast temperature ramping, and this delivers immediate heating and cooling for an extremely efficient workflow. Furthermore, the energy-saving mode in the Series makes it an environmentally-friendly option for any laboratory requiring precise temperature control. The Polar Series is ideal for an expansive range of applications, including chemical reaction control, separations, spectroscopy and surface science.

These easy-to-use laboratory chillers are programmable via an intuitive user interface, making it simple to set required temperature parameters. A compact footprint and minimal noise enable convenient in-lab placement, increasing laboratory efficiency. An internal reservoir and pump and cooling capacity options ensure extremely accurate temperature performance. The integrated fill port, drain and site tube design facilitates quick and easy operation. This range of CE- and CSA-compliant chillers has an intuitive plug and play design, eliminating any lengthy installation processes.

Thermo Fisher Scientific

Real-time inter-laboratory comparison quality reports

HORIBA Medical has introduced an upgrade to its external worldwide inter-laboratory quality control programme (QCP) for haematology and clinical chemistry analysers. QCP version II enables users to submit internal Quality Control (QC) results online to evaluate the accuracy and precision of their analysers via real-time peer group statistical reports from QCP. This intuitive online inter-laboratory comparison service for Proficiency Testing is also fully customisable.

Clinical case study on potential treatment for progressive multifocal leukoencephalopathy

Cytheris SA, a clinical-stage biopharmaceutical company focused on research and development of new therapies for immune modulation, today announced the publication of a case study report based on successful treatment of progressive multifocal leukoencephalopathy (PML) with combination therapy consisting of two investigational agents, Cytheris’ recombinant human interleukin-7 (CYT107) and CMX001, an investigational, oral broad-spectrum antiviral drug (Chimerix, Research Triangle Park, NC) in the Journal of Antimicrobial Chemotherapy. The combination therapy succeeded in eradicating the polyomavirus JC, the virus that causes PML, in less than two weeks following initiation of CYT107 treatment, and four weeks following the introduction of CMX001.

Progressive multifocal leukoencephalopathy (PML) is a rare and usually fatal neurological disease caused by the polyomavirus JC. The virus, first identified in 1971, multiplies in and destroys oligodendrocytes, which are cells of the brain that produce the myelin sheath surrounding neurons. Symptoms include loss of vision, impaired speech, paralysis, cognitive decline and weakness. There is no known cure for PML.

PEG resins for solid phase peptide synthesis

Biotage, a supplier of tools and technology for analytical and medicinal chemistry, announced the addition of ChemMatrix resins to its extensive offering of peptide synthesis and purification products. ChemMatrix is a patented 100% PEG resin from Matrix Innovation that offers substantial advantages over traditional PS and PEG based resins for solid phase peptide synthesis.

“Biotage is a leader in the global development of tools and technology for peptide synthesis and purification. Earlier this year, we introduced the SyroWave peptide synthesizer, more recently Resolux HPLC columns for peptides purification and now ChemMatrix resins.” says Scott Carr, VP of Commercial Operations. “Biotage truly delivers a total solution to professionals in this growing area of science.”

The ChemMatrix resin is a technological tool enabling synthesis of complex molecules from biological origin, peptides, oligionucleotides and small proteins typically used for therapeutic purposes. This resin is supplied as classical spherical beads, a tried and tested solution in the industry for almost 50 years but leverages today’s need for flexibility and exacting standards of quality and performance in the synthesis of especially difficult sequences.

There are many benefits to ChemMatrix, such as; exceptional stability, wide solvent compatibility, no leaching, optimum loading capacity allow users to achieve higher purities and yields of product, per gram of resin, especially in the case of difficult peptide sequences.


Transient gene expression

Evitria SA, a protein design and expression company, has achieved a major breakthrough in transient gene expression. Using Life Technologies’ Invitrogen FreeStyle CHO-S Cells, evitria scientists succeeded in obtaining titers exceeding 1 gram per litre in transient. evitria’s rapid protein expression platform now allows companies to perform their in vitro and in vivo studies with protein transiently produced in the same host system as used later for production of stable cell lines.

Comments Dr Sebastien Chenuet, Founder and Principal Investigator at evitria: “Today, CHO cells are the preferred host system for stable cell lines. Yet, many companies perform their initial in vitro and in vivo studies with protein transiently produced in HEK293 cells. We see the reason for that in the challenge to produce sufficient amounts of protein transiently in CHO cells. Going forward, evitria’s rapid protein expression platform will enable companies to perform their preclinical and clinical studies with the same host system. This is especially crucial in light of the extensive literature that stresses the importance of glycosylation on protein functionality.”

evitria SA

Automated filling of two-compartment Petri dishes

Using a MEDIAJET vario Automatic Media Preparation System from INTEGRA - leading Danish healthcare provider - Herlev Hospital has increased the efficiency and reliability of preparing its two-compartment agar plates.

For many applications, the amount of required agar can be reduced by using two-compartment Petri dishes. However, pouring biplates by hand is time-consuming and inefficient. The MEDIAJET fitted with biplate filling option is proven to offer an efficient and reliable solution for preparing two-compartment Petri dishes automatically.

LabLogic radiochromatography systems assist cancer antibody trials

The Cancer Sciences Division of Southampton University School of Medicine is using radio HPLC and radio TLC systems from LabLogic in the development and quality control of radio-labelled antibody conjugates undergoing clinical trials for treating haematological malignancies.

The HPLC system incorporates an Agilent quaternary pump, an auto-degasser and a thermostatically controlled column compartment. “We have had the equipment for ten months now, and it has proved to be a sensitive and reliable upgrade from our previous system,” says John Langford, head of the laboratory.

“It is always easy to use, whether we are measuring the gamma emissions of 111indium or the beta emissions of 90yttrium. And the speed and ease of use of LabLogic’s Laura radiochromatography software means that results are available immediately after the end of each run.

“We often correlate our results to ITLC for confirmation, and here we’re finding that the LabLogic radio-TLC scanner provides more detail than the ‘cut and count’ method. It makes it easier to locate peaks and discriminate between them and it uses the same Laura software, which is very convenient.”

LabLogic Systems Limited

Automated sample preparation of peptides designated for MALDI MS

A new application note from Agilent Automation Solutions describes a protocol for automated sample preparation and MALDI spotting developed with the protein analytics group of Dr. Lottspeich at the Max Planck Institute of Biochemistry in Martinsried, Germany.

The new protocol automates the sample preparation steps (cleansing and desalting) of peptides designated for mass spectrometry and the subsequent spotting onto a MALDI target plate using the Agilent Bravo Automated Liquid Handling Platform and C18 filled VeloTips from Glygen.

In order to get high quality peptide mass fingerprints in MALDI mass spectrometry, peptides must be concentrated and cleansed from impurities of previous steps.

In particular, salts and buffer components originating from the protein digests should be removed. There are several manual cleansing tools available. All are based on various chromatography media and require multiple aspiration/dispensing or mixing steps. While manual sample handling remains a tedious procedure and extremely difficult to standardize, automation of the routine has never been truly feasible on any automation platform due to several technical limitations.

In the application note the authors compare automated sample preparation for MALDI-MS analysis on the Agilent Bravo Automated Liquid Handling Platform with a traditional manual cleansing process using Millipore ZipTips. A protocol for the binding, washing, elution, and direct spotting onto MALDI targets was created using Agilent VWorks Automation Control software is described which can be adapted to various MALDI target plates, labware, and pipetting tasks.

 Results show that peptide mass fingerprints produced by the automatic workflow performed equally well or better than the manual process regarding signal intensity and protein sequence coverage.

As an additional benefit, the whole process is carried out in a reproducible and timesaving manner. The outcome of the experimentation shows that the automatic workup results in a better sequence coverage and Mascot score than both the tested manual workups.

The authors conclude that the Bravo Automated Liquid Handling Platform has been proven to be an effective tool for fully automated sample preparation with C18 VeloTips and subsequent MALDI target spotting processes.

Agilent Automation Solutions

Monday, 29 November 2010

PharmaNet appoints Chris Beaver as Director, Immunochemistry Services

PharmaNet Development Group Inc, a provider of clinical development services to pharmaceutical, biotechnology, generic drug and medical device companies, announces that Chris Beaver, PhD has joined the Company as Director, Immunochemistry Services. Dr Beaver is responsible for leading the immunochemistry team within the Company's bioanalytical laboratories and expanding its large molecule services, including assay development and sample analysis for biomarker, ELISA, radioimmunoassays, immunogenicity and cell-based assays.

AiCuris gains Bio.NRW research promotion

AiCuris GmbH & Co KG has been awarded a three-year research grant together with the Universities of Bochum, Düsseldorf and Bonn as well as the company Squarix (Marl). This grant is a part of the research promotion programme “Bio.NRW” by the Ministry of Innovation, Science and Research of North Rhine-Westphalia. AiCuris will obtain 833,582 Euro.

Reinnervate partners LGC for alvetex 3D cell culture technology

Reinnervate is partnering with LGC Standards for the non-exclusive distribution and sale of alvetex, its breakthrough 3D cell culture technology. LGC Standards is a division of LGC and a leading supplier of cutting-edge research tools to life science researchers across Europe.

In addition, the companies will be collaborating on the use of alvetex to generate realistic 3D cell models for drug discovery and development applications. For example, one key area of research has focused on the use of alvetex to generate liver cell cultures that closely mimic the structure and function of the same cells in the body. An accurate 3D model of the liver can allow researchers to examine the toxicity of new pharmaceuticals and be predictive of the effects of the these drugs in the body, while ultimately reducing the need for animal-based testing.

Management and analysis of mass spectrometry data

Integromics, a leader in IT solutions provision for life sciences in the field of genomics and proteomics, today announces that the Princeton Mass Spectrometry Center has purchased a license for the Integromics’ OmicsHub Proteomics solution.

The Princeton University Center will use OmicsHub as a key element in its strategy for data management and analysis of mass spectrometry (MS) data. Integromics will deploy the solution at Princeton and create a functional data analysis infrastructure by the end of 2010.