March 24, 2017

Critical step in cellular repair of damaged DNA identified which could be big for reversing aging and human trials will start within six months

UNSW researchers have identified a critical step in the molecular process that allows cells to repair damaged DNA – and it could mean big things for the future of anti-ageing drugs, childhood cancer survivors and even astronauts. It could lead to a revolutionary drug that actually reverses ageing, improves DNA repair and could even help NASA get its astronauts to Mars.

Their experiments in mice suggest a treatment is possible for DNA damage from ageing and radiation. It is so promising it has attracted the attention of NASA, which believes the treatment can help its Mars mission.

While our cells have an innate capability to repair DNA damage − which happens every time we go out into the sun, for example – their ability to do this declines as we age.

The scientists identified that the metabolite NAD+, which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair.

Treating mice with a NAD+ precursor, or “booster,” called NMN improved their cells’ ability to repair DNA damage caused by radiation exposure or old age.

“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said lead author Professor David Sinclair of UNSW School of Medical Sciences and Harvard Medical School Boston.

Human trials of NMN therapy will begin within six months.

“This is the closest we are to a safe and effective anti-aging drug that’s perhaps only three to five years away from being on the market if the trials go well,” says Sinclair, who maintains a lab at UNSW in Sydney.

Science - A conserved NAD+ binding pocket that regulates protein-protein interactions during aging

An anti-ageing pill could be on the horizon

For the past four years, Professor Sinclair and Dr Wu have been working on making NMN into a drug substance with their companies MetroBiotech NSW and MetroBiotech International.

The human trials will begin this year at Brigham and Women’s Hospital, in Boston.

The findings on NAD+ and NMN add momentum to the exciting work the UNSW Laboratory for Ageing Research has done over the past four years.

They’ve been looking at the interplay of a number of proteins and molecules and their roles in the ageing process.

They had already established that NAD+ could be useful for treating various diseases of ageing, female infertility and also treating side effects of chemotherapy.

In 2003, Professor Sinclair made a link between the anti-ageing enzyme SIRT1 and resveratrol, a naturally occurring molecule found in tiny quantities in red wine.

“While resveratrol activates SIRT1 alone, NAD+ boosters activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he says.

French election in May 2018 will decide the future of Europe

The fate of the EU could be decided April 23-May 7, when the French vote for a new president in their elections. If a pro-European candidate doesn’t win there, the European project may instead be forced into a long, cold winter, and nationalist, protectionist and populist agendas may once again take the upper hand.

The French presidential elections, run in two rounds on April 23 and May 7.

Le Pen is very likely to advance to the second-round final vote with Emmanuel Macron, the leading centrist candidate. Both politicians poll at about 25% currently, well ahead of other contenders. In the second round, Le Pen is expected receive only around 35% of the votes. That is well below the poll numbers of 2016’s seminal election winners: the “Leave” campaign in the U.K., and Donald Trump in the U.S. elections. But a terror attack or political bombshell might still make Le Pen a real contender in that final round on May 7.

The reasons for that are multifold, but the fact that France was the European focal point for terror attacks in recent years, and has for years had a complicated relation to immigrants, certainly plays a major role.

A possible election of Le Pen in France would be much more fatal to the European project than Brexit.

France was the EU’s Founding ‘Motor’

France, unlike the U.K., was a founding member of the EU just as The Netherlands was. But more than The Netherlands, it was also the real motor behind the European integration, together with Germany. French politicians, particularly former EU Commission President Jacques Delors, are credited with shaping the European institutions we know today. Others, such as former President Francois Mitterrand, laid the foundations for the Franco-German tandem.

It is more likely that a moderately pro-European candidate will win the French elections with a more or less comfortable margin (65% to 35% according to projections).

However, experts had also predicted that Brexit would fail and that Hillary Clinton would become president of the United States in a landslide.

US Navy working on mostly automated 'Magic Carpet' aircraft carrier landings starting in 2019

When Magic Carpet software and systems are switched on, the USNavy pilot no longer directly controls the flaps, throttle, and so on. Instead, he or she chooses a path and the computer makes the fine adjustments to get and stay on it. Affecting one aspect of flight — angle, speed, alignment, and so on — still affects the others, but the pilot can focus on one at a time while the computer keeps the others under control. The pilot remains a crucial part of the system.

The system is expected to be released in 2019. In fact, the Naval Aviation Enterprise leadership told NAVAIR to deliver the system as is earlier than that because it performed so well.

The system takes on many of the stressful aspects of aircraft carrier landing, like having to gauge the course of landing with the moving ship and all of the things the pilot has to consider while doing it, such as adding and reducing power, adjusting the pitch, yaw and roll.

The system improves safety and efficiency for the pilots, taking much of the stress of landing off the pilot and putting it on the system.

India has 300 million people without electricity and will soon have the world's third largest hypersonic wind tunnel

India has parts which are very advanced and parts that are completely undeveloped.

Of the world’s 1.3 billion people who live without access to power, a quarter — about 300 million — live in rural India in states such as Bihar. Nighttime satellite images of the sprawling subcontinent show the story: Vast swaths of the country still lie in darkness. “It’s a matter of shame that 68 years after independence we have not been able to provide a basic amenity like electricity,” ­Piyush Goyal, India’s minister of state for power, coal and new and renewable energy, said recently.

The Indian government has launched an ambitious project to supply 24-hour power to its towns and villages by 2022 — with plans for miles of new feeder lines, infrastructure upgrades and solar micro­grids for the remotest areas.

India's progress in Space

ISRO (India's space agency) on Monday commissioned two major facilities -- a Hypersonic Wind Tunnel and Shock Tunnel -- at the Vikram Sarabhai Space Centre in Thiruvananthapuram as part of its continuous and concerted efforts to minimise cost of access to space.

ISRO Chairman Kiran Kumar said commissioning of such facilities would provide adequate data for design and development of current and future space transportation systems in the country.

He said commissioning of the facility symbolizes the country's capability in establishing such world class facilities wherein technology from outside is restricted or not available.

The one meter Hypersonic Wind Tunnel and one meter Shock Tunnel have been established with a wide spectrum of simulation capabilities in terms of Mach number, Reynolds number and re-entry velocities, an official release said.

These facilities, indigenously designed, developed and 'Made in India' with the support of Indian industries, are the third largest in terms of size and simulation capability in the world, it said.

A few critical technologies, which are under embargo, have been jointly developed by ISRO and industries for realisation of these facilities.

VSSC Director Sivan in his presidential address said though excellent modeling capabilities exists with the advent of powerful computers, there was no other replacement for wind tunnel testing for aerodynamic characterisation.

The new facility would help aerodynamic characterisation of advanced space transportation systems, he said.

The facilities were dedicated in the memory of Satish Dhawan, a pioneer in the field and named as the Satish Dhawan Wind tunnel Complex.

ISRO is planning future missions such as Reusable Launch Vehicles, Two Stage to Orbit, Air Breathing propulsion systems and Human Space Flight Programme, the release added.

China exporting multi-trillion dollar investment infrastrcture led development to the world with One Belt One Road

One of the main factors driving the OBOR (One Belt One Road) effort is the slowdown in China’s own economy. The Communist Party is striving to transition away from growth led by investment and exports to development led by domestic consumer demand and services, and to keep growth at more sustainable levels than in the past. The government set a growth target of 6.5% in 2017 at the National People Congress in March, down from a 2016 target of 6.5% to 7%. In a sense, China is seeking to export the investment-led part of its economy, to help its own overbuilt heavy industries and provinces.

It will take a decade or more for the OBOR projects and construction to scale up to hundreds of billions of dollars per year where it will be a significant share of the business for major Chinese companies.

Compared to the size of China’s steel industry or other industries, it would take a very long time for demand from the projects to be big enough to make a difference, he says. “Many of the projects are far away from China, and some types of steel are worth transporting but not all kinds of steel. It would not help reduce excess capacity of cement because it is not economically viable to transport cement over such long distances,” Kuijs says. Bottelier, also, sees overcapacity as only a marginal factor in the OBOR plan.

Already, more than US$900 billion in projects are planned or underway, Fitch Ratings says in a report titled “China’s One Belt and One Road Initiative Brings Risks.” It says most funding will likely come from China’s policy banks, the Export and Import Bank of China, China Development Bank and its largest commercial banks. “We estimate that outstanding loans from Chinese banks total US$1.2 trillion, and a large portion of that has financed infrastructure projects involving Chinese state-owned enterprises,” the report says. China also has other major financial resources such as its sovereign wealth fund and foreign exchange reserves.

One project that got a head start was construction of a railway link from the port of Piraeus in Greece to Eastern Europe. Piraeus is a gateway to Europe for Chinese products, and major Chinese companies have been using the port to enter the European market. China, through its China Ocean Shipping Company, bought a 67% stake in the port’s Pier I from the Piraeus Port Authority SA in January 2016.

The Japan and U.S.-led Asian Development Bank says infrastructure development in Asia and the Pacific will exceed $22.6 trillion through 2030, or $1.5 trillion per year. In a recent report, “Meeting Asia’s Infrastructure Needs” issued in February, the estimate rises to more than $26 trillion, or $1.7 trillion a year when costs for climate change adaptation and mitigation are included. “This is a grand vision, and it may take a decade, but there is no rush. You cannot really put any number on the total investment,” says Rajiv Biswas, Singapore-based Asia-Pacific chief economist at IHS Global Insight.

Gene sequencing for rapid diagnosis of tuberculosis and prompt initiation of correct life saving treatment

British scientists have made a world-first breakthrough in the diagnosis of tuberculosis using gene sequencing. The diagnosis can be made in days instead of months. This will enable the prompt treatment with the correct drugs.

Researchers in Oxford and Birmingham say they can isolate different strains of the disease using a process called genome sequencing.

Health Secretary Jeremy Hunt said the breakthrough "will save lives".

Speedy diagnosis means patients can begin their recovery much quicker and also reduces the chances of the infection being spread.

Consultant microbiologist Dr Grace Smith said: "We're able to provide information on the species of the organism and the drugs to which it may be resistant if it's TB."

Public Health England says it is the first time anyone in the world has applied the technique on such a large scale.

The breakthrough comes after experts warned that a rise in drug-resistant strains of TB was threatening to derail efforts to eradicate the disease.

A new study found one in five global cases of the disease is now resistant to at least one major treatment drug.

Africa will triple its urban population 500 million to 1.5 billion in 2050 will need China to help avoid mass slumification

The proportion of Africans living in urban areas soared from 15 percent in 1960 to 40 percent in 2010. It's projected to hit 60 percent in 2050. Against that backdrop, the big challenge for government policymakers is how to harness urbanization for sustainable and inclusive growth.

"There is a high rate of rural-urban migration, and an increasing number of slums and squatter settlements in urban areas across Africa," Obitou says. "This kind of migration has brought shortages of adequate housing, basic infrastructure and services - in addition To contribute to overcrowding and congestion, and increasing exposure to environmental hazards. However, with proper planning, we will be able to manage our urbanization process.

Africa will go from 1.2 billion people today to about 2.5 billion in 2050.
The urban population will go from about 500 million today to 1.5 billion in 2050.

China, during its rapid urbanization, was able to successfully controlled the number of slums, for example.

In most of the African countries, extreme poverty is more prominent in rural areas than in urban centers; hence, urbanization seems to be an effective method for providing better services and livelihoods to millions of Africans - as abrations in China - he says.

According to the world Bank, a cornerstone of China's urbanization strategy has been the hukou or household registration system to control migration, and trying to channel migrants to small medium-sized cities.

Another key element is the devolution of public services and many administration functions to city governments. In 2005, Chinese citizens' degree of satisfaction with local governments rose to 72 percent - surplus higher than in many other countries, including the United States.

China can help Africa to strengthen its city management and planning, so that cities do a better job of looking ahead and improved congestion, pollution and the emergence of urban slums.

China will also likely expand its funding and construction of infrastructure and large scale construction processes in Africa.

Across Africa, Chinese companies are building highways, railways, sports stadiums, mass housing complexes, and sometimes entire cities.

But China isn’t just providing the manpower to fuel quickly urbanizing African cities. It is exporting its own version of urbanization, creating cities and economic zones that look remarkably similar to Chinese ones.

Since 2005, Chinese businesses have invested an estimated $120 billion in sub-Saharan Africa . And don't expect China's focus on Africa to decrease over the next decade.

According to South China Morning Post, China's central government and state-owned banks will help finance $1 trillion in projects in Africa through 2025 -- 70-80 percent of which will come from the Export-Import Bank of China -- with a specific focus on infrastructure projects.

Office of Naval Research shows new Navy BAE railgun test

The Office of Naval Research and Naval Surface Warfare Center, Dahlgren Division, conduct the first shot of the Railgun at the terminal range November 17, 2016.

There are also current tests of with an Army Howitzer is now firing a super high-speed, high-tech, electromagnetic Hyper Velocity Projectile.

Hypervelocity projectiles from regular howitzers and navy 5 inch guns would be mach 3 and have 60 to 100 mile range.
Full railguns are mach 6 to mach 10 weapons with a range up to 250 miles.
Regular navy guns with regular shells have to 10-35 mile range.

Two separate breakthroughs will combine for unlimited youthful blood for antiaging and immune system boosting transfusions

Two separate breakthroughs will combine for unlimited youthful blood for antiaging and immune system boosting transfusions
1. Immortalized cell lines can enable factory mass produced red blood cells
2. An activated protein can make blood youthful which boosts immune systems

This could be the first cells and tissue that could be immortalized and used for rejuvenation.

It could be possible to have regular resupply (two to four times per year or more often with automation) of youthful cells and tissues for health maintenance and as antiaging treatment. This would be combined with treatments to clear old cells more rapidly from the body.

Researchers have generated the first immortalised cell lines which allow more efficient manufacture of red blood cells. The team, from the University of Bristol and NHS Blood and Transplant, were able to manufacture red blood cells in a more efficient scale than was previously possible.

The results, published in Nature Communications, could, if successfully tested in clinical trials, eventually lead to a safe source of transfusions for people with rare blood types, and in areas of the world where blood supplies are inadequate or unsafe.

Previously, research in this field focused on growing donated stem cells straight into mature red blood cells. However that method presently produces small numbers of mature cells and requires repeat donations.

The world-leading team in Bristol have now developed a robust and reproducible technique which allows the production of immortalised erythroid cell lines from adult stem cells. These premature red cells can be cultured indefinitely, allowing larger-scale production, before being differentiated into mature red blood cells.

Dr Jan Frayne, from the University of Bristol’s School of Biochemistry, said: “Previous approaches to producing red blood cells have relied on various sources of stem cells which can only presently produce very limited quantities. By taking an alternative approach we have generated the first human immortalised adult erythroid line (Bristol Erythroid Line Adult or BEL-A), and in doing so, have demonstrated a feasible way to sustainably manufacture red cells for clinical use from in vitro culture.

NHS Blood and Transplant needs to collect 1.5 million units of blood each year to meet the needs of patients across England and the ongoing need for life saving blood donations remains. It would be many years before manufactured cells could be available on a large scale.

NHS Blood and Transplant announced plans for in-man trials of manufactured blood in 2015. This first trial will not use Bel-A cells. The first trial, due to start by the end of 2017, will use manufactured red cells from stem cells in a normal blood donation.

Continuously expanding cells – images of the immortalised early erythroid cells, labelled with number of days since immortalisation, demonstrating no change in morphology of the cells with extended time in continuous culture.

Nature Communications - An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells

Separate work makes blood young which boosts immune systems

Researchers examined the bone marrow in mice, they found that older animals have much lower levels of a protein called osteopontin. To see if this protein has an effect on blood stem cells, the team injected stem cells into mice that lacked osteopontin and found that the cells rapidly aged.

But when older stem cells were mixed in a dish with osteopontin and a protein that activates it, they began to produce white blood cells just as young stem cells do. This suggests osteopontin makes stem cells behave more youthfully. “If we can translate this into a treatment, we can make old blood young again,” Geiger says.

Geiger’s team is developing a drug containing osteopontin and the activating protein to encourage blood stem cells to behave more youthfully. “It should boost the immune system of elderly people,” he says.

Such a drug might have benefits beyond fighting infection and alleviating anaemia. The team also think the protein will boost levels of mother stem cells. Having only a small number of such cells has been linked to heart disease, so Geiger says there is a chance that boosting them may help prevent this.

Osteopontin might also be useful for treating age-linked blood disorders, such as myelodysplasias that involve dysfunctional cells, says Martin Pera of the Jackson Laboratory in Bar Harbor, Maine. “It is possible that rejuvenating bone marrow stem cells could help with these conditions,” he says.

Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

March 23, 2017

Traditional semiconductor CMOS scaling at end of roadmap in 2024 then it is neuromorphic, quantum and other new systems

Traditional semiconductor scaling is expected to reach an end by about 2024, according to a white paper from engineers working on a new version of the semiconductor roadmap. The good news is a wide variety of new kinds of devices, chip stacks and systems innovations promise to continue benefits in computing performance, power and cost.

“Die cost reduction has been enabled so far by concurrent scaling of poly pitch, metal pitch, and cell height scaling. This [will likely] continue until 2024,” according to one of nine white papers published today as part of the International Roadmap for Devices and Systems.

Beyond that date “there is no room for contact placement as well as worsening performance as a result of contacted poly pitch (CPP) scaling. It is projected that physical channel length would saturate around 12nm due to worsening electrostatics while CPP would saturate at 24nm to reserve sufficient CD (~11nm) for the device contact providing acceptable parasitics,” the white paper reported.

A preliminary version of a paper on new system architectures notes “many organizations are proposing remedies [to the end of Moore’s law] based on new device physics. Representative new devices include neuromorphic circuits, quantum qubits, spintronics, and many others. These new devices represent a significant broadening of the search space over the previous focus on CMOS and the microprocessor…[showing a wide] deviation from the current path.”

To enable such new architectures, the roadmap also includes a new section on applications benchmarks. It identifies 11 areas for tracking, spanning a broad range of computing styles.

A new section on system interconnects lays out broad challenges for both wired and wireless links. They include “increased use of germanium and III-V [materials] and possibly integration of these on silicon CMOS platforms” for advanced RF circuits.

The analysis of the future of semiconductors is here.

A preliminary paper that starts to scope out what comes after is here

CRISPR/Cas9 Reveals Cancer’s Synthetic Lethal Vulnerabilities

The CRISPR/Cas9 gene-editing system has been used to identify more than 120 synthetic-lethal gene interactions in cancer cells. These interactions could guide drug developers to new combination therapies that could selectively kill cancer cells and spare healthy cells.

Synthetic-lethal gene interactions may occur when certain pairs of mutated genes are present. When there is a mutation in either of these genes within a cell, the cell remains viable. But when there are mutations in both genes, the result is cell death. Synthetic-lethal gene interactions are especially important in the context of cancer therapies. If at least one of the genes in the interaction is specific to cancer, then a drug that inhibits the other gene would selectively kill only cancer cells.

The method appeared March 20 in the journal Nature Methods, in an article entitled “Combinatorial CRISPR–Cas9 Screens for De Novo Mapping of Genetic Interactions.”

“We developed a systematic approach to map human genetic networks by combinatorial CRISPR–Cas9 perturbations coupled to robust analysis of growth kinetics,” wrote the article’s authors. “We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction.”

In this article, the UC San Diego team described how they used the gene-editing technique CRISPR/Cas9 to simultaneously test for thousands of synthetic-lethal interactions. The researchers designed a CRISPR/Cas9 system with two guide RNAs: (1) one that targets a tumor suppressor gene that is commonly mutated in cancer and (2) one that targets a gene that could also be disrupted by a cancer drug. They deployed this system against 73 genes in three laboratory cell lines—human cervical cancer, lung cancer, and embryonic kidney cells. Then they measured cell growth and death.

“Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision,” the authors noted. “From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies.”

"The ovarian cancer drug olaparib works by synthetic lethality—it inhibits a gene that, when a BRCA gene is also mutated, kills just those cancer cells," said John Paul Shen, M.D., clinical instructor and postdoctoral fellow at UC San Diego School of Medicine and Moores UCSD Cancer Center. "Many other cancers could likely be treated this way as well, but we don't yet know which gene mutation combinations will be synthetic-lethal."

They are scaling their cancer genetic networks maps so they can systematically identify new combination therapies.

CRISPR gene therapy is enhancing t-cell immnotherapy treatment of cancer and treatments in people could be available within 2 to 3 years

Marcela V. Maus, M.D., Ph.D., of Harvard Medical School identified three important improvements that CRISPR gene editing could potentially bring to T-cell-based therapies.

1. being more-effective tumor responses.
2. the targeted nature of CRISPR-mediated CAR integration into the genome might “prove safer than random integration, which carries the potential risk of generating a harmful mutation,” Dr. Maus wrote.
3. It could enable off-the-shelf CAR T cells to be made that need not come from a patient's own T cells. This would enable easier and cheaper manufacture of CAR T cells.

New gene-editing technologies will likely lead to rapid improvement in antigen-targeted T-cell immunotherapies for cancer.

David Edgell, an associate professor of biochemistry at the University of Western Ontario, thinks CRISPR treatments could be available within the next two to three years, with modified T-cells used to treat some types of cancer (there are already clinical trials for lung cancer in China, and a similar one slated to take place at the University of Pennsylvania was approved last June by the National Institutes of Health

CAR T cells created with CRISPR were less likely to stop recognizing and attacking tumor cells after a certain time point, a phenomenon researchers call “exhaustion."

Based on three measures of exhaustion, less than 2% of CRISPR-created T cells showed signs of exhaustion, compared with up to half of conventionally engineered CAR T cells.

Using CRISPR, researchers have genetically engineered immune cells and improved the ability of these cells to kill cancer cells in mice.

The cells were modified to express proteins on their surfaces called chimeric antigen receptors (CARs), which enabled the cells to recognize and attack cancer cells that expressed the corresponding antigen.

In experiments with the mice, immune cells that had been engineered to express CARs using CRISPR were more effective at killing tumor cells than immune cells engineered using conventional methods.

Nature - Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection

LPP Fusion working on inpurities for Tungsten anode and in the summer will have experiments with new Beryllium Cathode

Hardric Labs in Massachusetts has reported to LPPFusion that its work on machining the new beryllium cathode is nearing completion and they expect to ship the finished piece in early March, only a few weeks behind their initial schedule. Since the beryllium anodes have already been received at the Middlesex NJ lab, we will soon have a complete set of beryllium electrodes ready for our next set of experiments. This will be an important milestone for the project, as our effort to obtain the beryllium electrodes began in mid-2014, as soon as our crowdfunding effort had raised the money needed for the new set. Beryllium is crucial to the next step in the experiment for two reasons. First, as a light element with an atomic charge, or “z”, of only 4, it will eliminate any high-z impurities in the plasma, optimizing FF-1’s performance. Second, beryllium is highly transparent to x-rays, so will be much better able to withstand the heavy x-ray flux from the plasmoid as we increase fusion yields.

Once our current experiments with tungsten are complete, we will still need two or three months to prepare for the beryllium experiments. For one thing, our vacuum chamber will need a new coating of titanium oxide to coat over any remaining tungsten in the chamber. But with the electrodes soon to be in hand, we can be confident that the next set of experiments will be under way in the summer.

The Tungsten experiments have slow going because of the need to remove impurities from the fusion chamber.

Beryllium cathode for next experiment being machined at Hardric Lab. In Mass

If this shoestring budget effort were to succeed they would be able to create superlow cost energy from nuclear fusion.

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