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Investigators build a better targeted drug therapy using the power of computation

Antibody drug conjugates (ADCs) —cancer drugs that are designed to target and destroy cancerous tissue while leaving healthy cells intact — to represent a long sought-after advancement in cancer therapy. ADCs work by attaching a cancer drug to an antibody that is unique to a specific type of tissue, allowing ADCs to deliver treatment directly to the site of a tumor rather than throughout the body.

To date, five ADCs have received Federal Drug Administration approval for treating cancer and 56 drug companies  are developing ADCs. And many companies are giving full support to make their research in ADC more convenient and diverse, such as Biochempeg , which has developed a series of peptides with discrete PEG chain which mitigates aggregation & immunogenicity in ADC.
However, ADCs currently have significant limitations. They can have unpredictable effects and may be unstable, losing their payloads and producing toxicity. Investigators from Brigham and Women’s Hospital set out to design more stable and predictable ADCs by using computer simulations to predict and plan out how drug payload and antibody can stay linked to each other. The team tested out their predictions in human and mouse plasma and in a model of human lung adenocarcinoma. Their findings are published in  Nature Biomedical Engineering .

Shiladitya Sengupta, Ph.D., associate professor of medicine at the Division of Engineering in Medicine at the Brigham, said „The goal of this technology is to empower currently used antibodies in cancer treatment. . „We designed a LEGO-like linker that just clicks a drug payload to any antibody we want. That means we can deliver a drug specifically to any tissue that expresses the target of the antibody.“

Sengupta and colleagues used computational docking molecular simulations to create a prototype that could link an antibody and drug payload. They mapped the binding sites to determine how ligand-drug pairs would bind to different antibodies. They synthesized various components and showed that when they were incubated together, they could self-assemble into ADCs, like magnets that find one another. Inspired by this observation, the team named this approach MAGNET ADCs, which stands for multivalent and affinity-guided antibody empowerment technology.

The team reports that MAGNET ADCs could be generated rapidly and did not require modifying antibodies. The MAGNET ADCs showed long-term stability in plasma, lasting 14 days and showing low toxicity. The team tested MAGNET ADCs in a model for human lung cancer, but the authors note that this technology could be adapted to a variety of therapeutic or diagnostic uses.

„We envisage that the MAGNET-ADC approach can be extended to a wide range of therapeutic molecules as well as diagnostics, with potential uses beyond the treatment of cancer,“ the authors write.

For a street style heel

Toning shoes don’t just come in sneaker form, though. These days, you can get toning shoes in nowadays shape and size. There are toning wedges and toning sandals, toning running shoes and toning tennis trainers. What’s next? Toning stilettos? A number of only belief! Wondering what your options are really? Curious as to what’s your toning sneaker? Not sure which is the toning shoe for you’ll? Read on to get the down and dirty on the bandwagon everyone is jumping referring to.

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Coal preparation portable crusher plant

The portable crusher plant is one of the most widely used mobile crushing systems. The portable crusher plant can be seen everywhere in the fields of construction, road repair, mining and water conservancy. As a large-scale mobile equipment, the portable crusher plant is priced reasonably, and many users are very new to this efficient crushing system. However, in practical applications, the repair and maintenance of the crushing station is sloppy, which is directly related to the quality of production.

Many users are looking for a portable crusher plant. Before buying a product, let’s take a look at the daily maintenance measures of the portable crusher plant, which is crucial for the normal operation of the equipment. Before the operation of the coal-moving mobile crushing plant, firstly, the equipment should be thoroughly inspected and the lubricating oil should be added. Especially for some small and medium-sized equipment, it is necessary to regularly add grease and lubricating oil to reduce the equipment parts in production. And the friction of materials to improve production efficiency.

In large-scale coal-fired mobile crushing plant equipment, if crushing equipment such as cone crusher and jaw crusher are used during operation, a forced lubrication system is generally required at this time. When the crushing station is running, the operator needs to observe the changes in oil quantity, oil temperature and oil pressure at regular intervals in order to make timely adjustments. At the same time, the user should pay attention to the noise and vibration of the equipment when paying attention to the quotation of the portable crusher plant. If the abnormality is found, it should be stopped and the equipment should be operated after the repair is completed.

The price of the portable crusher plant is generally reasonable. For the operator, in addition to paying attention to the above points, the output rate and quality of the finished product should be observed from time to time. If it finds a deviation, it should stop in time for maintenance. At ordinary times, the coal-moving portable crusher plant should be regularly scheduled for minor repairs, medium repairs and overhauls, and the vulnerable parts should be replaced in time to ensure normal production.

The mobile coal crushing station is a widely used one in the crushing station and plays an irreplaceable role in modern production. However, in the specific production process, various failures will occur due to various reasons, which requires all operators to carry out a comprehensive inspection of the equipment in time, timely repair of the vulnerable parts or a more slippery. Only when these maintenance is completed, the user can purchase safe crushing stations to ensure safe production and efficient production.

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Pay focus how far up you bring your golf club on a back move. The club’s shaft should be parallel to the ground. If the shaft is finished parallel to your ground, you increase the likelihood of making an unhealthy shot.

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The spongy nature and lack of arch support found in many flip flops, can cause the feet to roll inward, causing pain and injury to the arch as well as plantar fasciitis and if you are not already flat footed, you can actually develop this symptom by wearing poorly made flip flops. Of course there are the more obvious hazards of wearing open or uncovered footwear. When driving, flip flops can impair a driver’s control, especially if they fall off and become lodged underneath the brake or accelerator pedal. Other common injuries include stubbed toes, cuts, bruises, and insect bites. Not to mention dirty feet!!

Follow these tips, remember the rules of thumb and you will Golden Goose get more mileage out of your wardrobe than you ever imagined for this unpredictable season!

Ochranné rukavice proti proříznutí

Účinná ochrana rukou znamená nalézt dokonalou rovnováhu mezi spolehlivou ochranou a pohodlím při nošení. Pouze ochranné rukavice, které uživatel skutečně nosí, pomáhají předcházet úrazům a chránit ruce.

Ochranné rukavice proti proříznutí značky uvex, které jsou založené na nejnovější generaci patentované technologie uvex Bamboo TwinFlex® Technology, stanovují nový standard v oblasti ochrany, pohodlí, flexibility, citu při úchopu a hospodárnosti. Na míru šitá třída komfortu s robustní ochranou proti proříznutí přispívá ke zvýšení přijatelnosti nošení zejména při náročných činnostech, protože jedinečná kombinace přírodního vlákna a bambusu s moderními ochrannými vlákny zajišťuje vysoké pohodlí při nošení a dobré klimatické vlastnosti při zachování vysoké ochrany.
Při výběru vhodných ochranných rukavic je nutné zohlednit celou řadu faktorů. Společnost uvex připravila přehledný návod, který prostřednictvím praktických symbolů umožňuje vybrat ochranné rukavice pro konkrétní oblasti použití. Jedná se zejména o identifikaci a přiřazení možných rizik, stanovení individuálních požadavků na ochranné rukavice a definice okolního prostředí.
Mezi inovativní výrobky pro efektivní ochranu proti proříznutí patří například robustní ochranné rukavice uvex D500 foam s velmi vysokou třídou ochrany D. Vysoká ochrana proti oděru navíc prodlužuje životnost, díky čemuž jsou tyto rukavice obzvlášť hospodárné. Do potravinářského průmyslu jsou vhodné například všestranné rukavice uvex phynomic C5 s nejlepší citlivostí při úchopu, navíc jsou dermatologicky testované.
Pokud si nejste jisti, které rukavice jsou pro vaše pracovníky nejvhodnější, obraťte se na odborné pracovníky společnosti uvex.
Značku uvex v České republice zastupuje společnost UVEX Safety CZ, k.s. v Rychnově nad Kněžnou. V nabídce této společnosti jsou nejen ochranné pracovní rukavice, ale i kompletní sortiment OOPP značky uvex.

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