Cancer therapies that target specific molecular defects arising from mutations in tumor cells are currently the focus of much anticancer drug development. However, due to the absence of good targets and to the genetic variation in tumors, platinum-based chemotherapies are still the mainstay in the treatment of many cancers, including those that have a mutated version of the tumor suppressor gene p53.
P53 is mutated in a majority of cancers, which enables tumor cells to develop resistance to platinum-based chemotherapies. But these defects can still be exploited to selectively target tumor cells by targeting a second gene to take down the tumor cell, leveraging a phenomenon known as synthetic lethality.
Focused on understanding and targeting cell signaling in cancer, the laboratory of Michael Yaffe, the David H. Koch Professor Science and director of the MIT Center for Precision Cancer Medicine, seeks to identify pathways that are synthetic lethal with each other, and to develop therapeutic strategies that capitalize on that relationship. His group has already identified MK2 as a key signaling pathway in cancer and a partner to p53 in a synthetic lethal combination.
Now, working with a team of fellow researchers at MIT’s Koch Institute for Integrative Cancer Research, Yaffe’s lab added a new target, the gene XPA, to the combination. Appearing in Nature Communications, the work demonstrates the potential of “augmented synthetic lethality,” where depletion of a third gene product enhances a combination of targets already known to show synthetic lethality. Their work not only demonstrates the effectiveness of teaming up cancer targets, but also of the collaborative teamwork for which the Koch Institute is known.
P53 serves two functions: first, to give cells time to repair DNA damage by pausing cell division, and second, to induce cell death if DNA damage is too severe. Platinum-based chemotherapies work by inducing enough DNA damage to initiate the cell’s self-destruct mechanism. In their previous work, the Yaffe lab found that when cancer cells lose p53, they can re-wire their signaling circuitry to recruit MK2 as a backup pathway. However, MK2 only restores the ability to orchestrate DNA damage repair, but not to initiate cell death.
The Yaffe group reasoned that targeting MK2, which is only recruited when p53 function is absent, would be a unique way to create a synthetic lethality that specifically kills p53-defective tumors, by blocking their ability to coordinate DNA repair after chemotherapy. Indeed, the Yaffe Lab was able to show in pre-clinical models of non-small cell lung cancer tumors with mutations in p53, that silencing MK2 in combination with chemotherapy treatment caused the tumors to shrink significantly.
Although promising, MK2 has proven difficult to drug. Attempts to create target-specific, clinically viable small-molecule MK2 inhibitors have so far been unsuccessful. Researchers led by co-lead author Yi Wen Kong, then a postdoc in the Yaffe lab, have been exploring the use of RNA interference (siRNA) to stop expression of the MK2 gene, but siRNA’s tendency to degrade rapidly in the body presents new challenges.
Enter the potential of nanomaterials, and a team of nanotechnology experts in the laboratory of Paula Hammond, the David H. Koch Professor of Engineering, head of the MIT Department of Chemical Engineering, and the Yaffe group’s upstairs neighbor. There, Kong found a willing collaborator in then-postdoc Erik Dreaden, whose team had developed a delivery vehicle known as a nanoplex to protect siRNA until it gets to a cancer cell. In studies of non-small cell lung cancer models where mice were given the MK2-targeting nanocomplexes and standard chemotherapy, the combination clearly enhanced tumor cell response to chemotherapy. However, the overall increase in survival was significant, but relatively modest.
Meanwhile, Kong had identified XPA, a key protein involved in another DNA repair pathway called NER, as a potential addition to the MK2-p53 synthetic lethal combination. As with MK2, efforts to target XPA using traditional small-molecule drugs have not yet proven successful, and RNA interference emerged as the team’s tool of choice. The flexible and highly controllable nature of the Hammond group’s nanomaterials assembly technologies allowed Dreaden to incorporate siRNAs against both XPA and MK2 into the nanocomplexes.
Kong and Dreaden tested these dual-targeted nanocomplexes against established tumors in an immunocompetent, aggressive lung cancer model developed in collaboration between the laboratories of professor of biology Michael Hemann and Koch Institute Director Tyler Jacks. They let the tumors grow even larger before treatment than they had in their previous study, thus raising the bar for therapeutic intervention.
Tumors in mice treated with the dual-targeted nanocomplexes and chemotherapy were reduced by up to 20-fold over chemotherapy alone, and similarly improved over single-target nanocomplexes and chemotherapy. Mice treated with this regimen survived three times longer than with chemotherapy alone, and much longer than mice receiving nanocomplexes targeting MK2 or XPA alone.
Overall, these data demonstrate that identification and therapeutic targeting of augmented synthetic lethal relationships — in this case between p53, MK2 and XPA — can produce a safe and highly effective cancer therapy by re-wiring multiple DNA damage response pathways, the systemic inhibition of which may otherwise be toxic.
The nanocomplexes are modular and can be adapted to carry other siRNA combinations or for use against other cancers in which this augmented synthetic lethality combination is relevant. Beyond application in lung cancer, the researchers — including Kong, who is now a research scientist at the Koch Institute, and Dreaden, who is now an assistant professor at Georgia Tech and Emory School of Medicine — are working to test this strategy for use against ovarian and other cancers.
Written by Koch Institute
WD My Passport SSD (2020) Review
WD’s latest round of redesigns has spread throughout its portable storage lineup, replacing the bold, bright, sharp design-led identity with rounded edges, muted colours, and simpler plastic bodies. Whimsy has given way to practicality, which you might or might not be in favour of. The latest reimagined storage device is the WD My Passport SSD (2020), but in this case, the changes aren’t solely cosmetic. You get a huge bump in hardware specifications and speeds, keeping WD’s portable SSD lineup current and competitive. Here’s a review of the brand new WD My Passport SSD (2020).
WD My Passport SSD (2020) design and features
The older two-tone metal-and-plastic design might have been slightly impractical with its sharp corners and overall bulk, but it looked and felt very modern and premium. Now, you get a much more organic body, shaped somewhat like a thin bar of soap. It’s much flatter than before, with rounded sides and corners that make for an easy grip. This device will be comfortable in your hand as well as your pocket. It weighs only 45.7g.
The body is made of metal and there’s a swirly ridged pattern on the front as well as the rear. The USB Type-C port is off-centre on the bottom and there’s no activity LED. The raised WD logo feels rough and looks rather garish, but otherwise this is a simple, sober design that will fit in anywhere. You have a choice between Space Grey, Midnight Blue, and Gold. A red version appears to be available in other countries, but isn’t listed here.
Unlike some other portable SSDs (including models from Western Digital’s other brands, SanDisk and G-Technology), there’s no waterproofing or other form of protection from the elements. WD does mention shock and vibration resistance, which are inherent to SSDs, plus drop resistance for falls from up to 1.98m in height.
Perhaps unsurprisingly, the My Passport SSD (2020) is very similar in shape and size to the SanDisk Extreme V2 portable SSD, but doesn’t have an integrated handle, ruggedised coating, or IP rating.
You get a very short USB Type-C cable in the box, with a Type-C to Type-A adapter for broad compatibility. As we noted with the previous incarnation of the My Passport SSD, such an adapter is technically outside the official USB specification and so the cable and adapter both have notches to make sure they’re used with each other. That doesn’t physically stop you from using the entire cable, plus adapter, with another device though. This should be avoided, because some devices need to negotiate things like how much power is sent from one side to another, which cannot happen through a legacy USB port when such an adapter is used.
WD My Passport SSD (2020) price, specifications and performance
The biggest upgrade comes from the use of an NVMe SSD and bridge rather than the older SATA protocol. WD claims read and write speeds of 1050MBps and 1000MBps respectively – exactly the same as the Samsung SSD T7 Touch, and in line with the Sandisk Extreme Pro. You’ll need a PC with a USB 3.2 Gen2 (10Gbps) or Thunderbolt 3 port to be able to harness such speed.
The new My Passport SSD (2020) is available in 500GB, 1TB and 2TB capacities, priced officially at Rs. 8,999, Rs. 15,999, and Rs. 28,999 respectively. They are exclusive to Amazon during the festive sale period, and actual prices are quite a bit lower. They will be available offline from mid-November.
WD has implemented 256-bit AES hardware encryption. The company offers quite a lot of free software that you can download, including the capable Drive Utilities for general maintenance, WD Backup to set up simple backup routines, and WD Security to set up encryption with a password. You’re also encouraged to install WD Discovery, which is completely unnecessary and only exists to serve up ads and promotions for WD.
The 1TB review unit we’re testing today was formatted to exFAT by default. This works cross-platform, but if you’re planning to use Time Machine on a Mac, you’ll need to reformat the drive to HFS+ (or at least partition and format some of it). Windows’ Disk Management console reported 931.48GB of usable space.
All tests were run on an HP Spectre x360 13 laptop because of its Thunderbolt 3 ports. CrystalDiskMark 6 reported sequential read and write speeds of 913.9Mbps and 924.9Mbps respectively, which is not too far below WD’s official claim. More realistic random read and write speeds were 154.1Mbps and 163.8MBps respectively. While good by portable SSD standards, the My Passport SSD (2020)’s scores lag quite a way behind what the Samsung SSD T7 Touch and SanDisk Extreme Pro were able to achieve. The Anvil benchmark managed read and write scores of 2,186.6 and 1,921.12, for an overall score of 4,107.72.
The shell of the WD My Passport SSD (2020) did get quite warm when benchmarks were running and when large batches of files were being copied up and down in testing. This shouldn’t be much of a problem in everyday use, and there’s nothing else to complain about.
If you like bold, edgy design and products that make a statement, the new WD My Passport might be a bit of a disappointment. It looks unassuming and pedestrian compared to its predecessor; more like a bar of soap than a high-end tech product. Perhaps this is a signifier that portable SSDs aren’t just lifestyle accessories for only those who can afford them anymore, but are now perfectly mainstream commodity products.
The emerging new class of NVMe portable SSDs brings nearly twice the speed of previous-gen SATA models. Samsung still has the performance advantage, but WD isn’t too far behind now. Other than speed, you should choose your SSD based on whether you prioritise features such as AES encryption and ruggedisation. SSDs are also routinely discounted below their official MRPs, so if you do find a great deal on the WD My Passport SSD (2020) and it meets your requirements, you shouldn’t hesitate to pick one up.
WD My Passport SSD (2020)
Rs. 6,999 (500GB)
Rs. 12,999 (1TB)
Rs. 24,999 (2TB)
- NVMe-based, good read and write speeds
- Good value for money
- Compact and light
- Gets a bit warm when stressed
- No IP rating
- Performance: 4.5
- Value for Money: 4.5
- Overall: 4.5
Edge computing and IoT sensors help cities plug a leak in water bills
Tracking the health of pipes and water meters in real time helps cities catch water main breaks sooner and issue more accurate bills.
A Texas company is using edge computing and IoT sensors to help cities modernize crumbling water infrastructure and inaccurate water meters. The American Society of Civil Engineers has given the country’s drinking water system a D- for the last 10 years. Many components of city water systems date back to the Civil War era. Olea Edge Analytics is using 21st century technology to spot needed repairs and make sure water bills are accurate.
Dave Mackie, Olea Edge Analytics’ CEO, said the company combines edge computing with artificial intelligence and machine learning to help cities make more informed decisions.
“Our network operations center can remotely manage all of the endpoints across the city, prioritizing repair work, giving the ideal route and directions, and transmitted work plans and specifications to provide everything crews need for a right-first-time trip,” he said in a press release.
SEE: 5 Internet of Things (IoT) innovations (free Pdf) (TechRepublic)
Olea puts sensors on water meters and sends data about how much water is used to the cloud for analysis. The Smart Water Management Platform monitors the meters to look for water usage that isn’t showing up on monthly bills. Olea estimates that up to 40% of all high-volume commercial water meters are not capturing the full amount of water used.
As Brandon Vigliarolo wrote in “
,” Forrester predicts that this is the year that new business models will push edge computing “from science project to real value.” Forrester analysts said that cloud platforms, artificial intelligence, and the widespread proliferation of 5G will make these edge use cases more practical.
SEE: The future of IoT: 5 major predictions for 2021 (TechRepublic)
The Department of Watershed Management of the City of Atlanta is spending $3.9 million on a deal with Olea to measure water usage more accurately.
The COVID-19 pandemic has created a serious budget shortfall for many cities around the US. According to the National League of Cities, losses in sales tax and other revenue sources will cost cities $360 billion from this year through 2022.
Olea Edge Analytics produces products that use technology for revenue recovery. The company’s Vault Management platform allows utilities to manage assets and get alerts when something changes. A dashboard provides a high-level and operational view of workflows, including data about billing and consumption, maintenance, and safety. CityEdge uses blockchain, AI, and machine learning to spot problems in water infrastructure as soon as they happen.
“People are surprised to learn that they can make these simple repairs and turn that money into a catalyst for much-needed projects,” Mackie said in a press release. “Everyone is looking for an edge in funding, especially during these economic times.”
With the CityEdge product, a blockchain validates water usage from when it leaves the meter’s sensors to the moment it reaches the customer. The encrypted data in the ledger is distributed across every device in the network, increasing transparency and traceability. The platform also creates a digital twin of every meter on the network.
DKK 42 million for sustainable chip-based spectrometers
In a new four-year Grand Solutions project—supported by Innovation Fund Denmark with DKK 25 million—DTU and four companies will join forces in a consortium called NEXUS to develop the next generation of ultracompact spectrometers based on chip technology:
“We will quite simply make spectrometers in a radically different way that will make them both inexpensive and sustainable,” says the originator of the new Innovation Fund Denmark project, Associate Professor Søren Stobbe from DTU Fotonik. He continues:
“In NEXUS, we will develop the nanotechnology and the chip technology, as well as the modules that will be used to integrate the spectrometers in the industry already during the project. In short, we will make it possible to perform measurements in places where you cannot measure today. And because we can make the spectrometers small and inexpensive, it can also be good business for companies to choose the most environmentally friendly solution.”
Spectrometers to reduce waste at dairies
To begin with, NEXUS’ spectrometers will make a difference for dairies.
Dairies need spectrometers to measure the contents of protein, fat, and water in their milk. But the spectrometers currently available on the market are large and expensive, which means that the dairies only have a very limited number of them. So when, for example, the dairies are to produce a new batch of semi-skimmed milk, they rinse the pipes with milk to be sure of what they have in the pipes. This means that they send around 10,000 litres of milk directly into the sewers every day. This could be avoided if spectrometers were instead installed to measure what is in the pipes.
Jacob Riis Folkenberg—Vice President of Technology at FOSS, which makes food production equipment—is therefore convinced that the new optical spectroscopy technology has the potential to revolutionize the market:
“In addition to being a waste of time and energy, the 10,000 litres of milk going to waste every day also has a fairly high market value. If you can get the price of a spectrometer down, this will quickly turn into a really good business case for the dairies. We estimate that there is a market potential of three billion Danish kroner at the dairies alone,” he says.
The core of the NEXUS project is DTU’s patented chip technology.
“We have a prototype that works, but we don’t yet have the spectral resolution we need,” says Associate Professor at DTU Fotonik, Søren Stobbe, and continues:
“We need to develop a lot of stuff in the chip, and it must then be built into the whole technology that surrounds it. For it’s one thing to make a chip. But—in reality—a large part of the work is to integrate the chip with the surroundings.”
While DTU Fotonik is responsible for the development of the chip, the companies Beamfox Technologies ApS and ELIONIX INC will develop methods for nanofabrication of the chip. Ibsen Photonics A/S makes the modules in which the chip will be integrated, and FOSS makes the food production probes in which the modules will be installed and which can be used at the dairies.
Wind turbines, aircraft, and health monitoring on the mobile
The NEXUS project starts with the dairies, but the technology will also be relevant in many other contexts.
“The ultimate vision is to be able to make spectrometers so small and inexpensive that it can, for example, be worthwhile to build them into mobile phones. The spectrometer will be able to make a kind of primitive blood test, which could give you an indication of whether you need to see your doctor,” says Søren Stobbe.
“Another example is so-called optical interrogation monitors, which can be used to measure and predict the behaviour of large mechanical structures. They can be built into a bridge, a wind turbine blade, or an aeroplane wing, where they will then monitor whether the material begins to give off some strange vibrations. The area of application for spectrometers—if you can make them in this low price range—is gigantic.”
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