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We always wonder how that “Eureka Moment” turns up…but truth may lie in the “High and Mighty”.


Cracked.com’s new book is now on sale. What follows is one of the classic articles that appear in the book, along with 18 new articles that you can’t read anywhere else.

Any dreadlocked white guys finding this article after Googling “Drugs Rule” should know that we’ve given this list about drugs a rule. To make the cut, an accomplishment has to be considered great by people who could pass a field sobriety test. So no Grateful Dead music. We’re sure someone somewhere has enjoyed the Dead perfectly sober, just as there are probably non-Christians who listen to Christian Rock. But we’re just as sure that in the grand scheme of things, those people don’t count.

In fact, because we’re masochists, we gave ourselves a strict no music policy, leaving us with … well, not a whole lot actually. Turns out most great things were accomplished by people who just said no, at least immediately prior to accomplishing them. Except for these five.

Metabolic plasticity allows cancer cells to adjust their metabolic phenotypes to adapt in hostile environments. There is an urgent need to understand the cross-talk between gene regulation and metabolic pathways underlying cancer metabolic plasticity. We establish a theoretical framework to decode the coupling of gene regulation and metabolic pathways. Our work characterizes a hybrid metabolic state where cells can use both glycolysis and oxidative phosphorylation (OXPHOS) and a possible metabolically inactive state where cells have low activity of both glycolysis and OXPHOS. We show that targeting both OXPHOS and glycolysis may be necessary to eliminate cancer aggressiveness. Our work serves as a platform to target abnormal metabolism in cancer by modulating both genes and metabolic pathways.

Metabolic plasticity enables cancer cells to switch their metabolism phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) during tumorigenesis and metastasis. However, it is still largely unknown how cancer cells orchestrate gene regulation to balance their glycolysis and OXPHOS activities. Previously, by modeling the gene regulation of cancer metabolism we have reported that cancer cells can acquire a stable hybrid metabolic state in which both glycolysis and OXPHOS can be used. Here, to comprehensively characterize cancer metabolic activity, we establish a theoretical framework by coupling gene regulation with metabolic pathways. Our modeling results demonstrate a direct association between the activities of AMPK and HIF-1, master regulators of OXPHOS and glycolysis, respectively, with the activities of three major metabolic pathways: glucose oxidation, glycolysis, and fatty acid oxidation.

The particle, which has been called X(2900), was detected by analyzing all the data LHCb has recorded so far from collisions at CERNs Large Hadron Collider.

The LHCb experiment at CERN has developed a penchant for finding exotic combinations of quarks, the elementary particles that come together to give us composite particles such as the more familiar proton and neutron. In particular, LHCb has observed several tetraquarks, which, as the name suggests, are made of four quarks (or rather two quarks and two antiquarks). Observing these unusual particles helps scientists advance our knowledge of the strong force, one of the four known fundamental forces in the universe. At a CERN seminar held virtually on August 12, LHCb announced the first signs of an entirely new kind of tetraquark with a mass of 2.9 GeV/c²: the first such particle with only one charm quark.

First predicted to exist in 1964, scientists have observed six kinds of quarks (and their antiquark counterparts) in the laboratory: up, down, charm, strange, top and bottom. Since quarks cannot exist freely, they group to form composite particles: three quarks or three antiquarks form “baryons” like the proton, while a quark and an antiquark form “mesons.”

A historic French brand is set to return with one of the most extreme hypercar designs ever. The new holders of the Delage brand are squarely focused on the Nurburgring lap record with the monstrous D12 and its 7.6-liter, naturally aspirated V12.

Miami-based French entrepreneur Laurent Tapie has leased the rights to the Delage name, with an option to buy, and is building the first Delage car in some 64 years. And how! With backing from “four deeply invested billionaires” according to an interview with Robb Report, he’s fulfilling his dream of an F1 car for the street.

The D12 is a wasp-waisted monster whose dart-shaped cabin is so separated from the front wheels that it might as well be an open-wheeler. Its colossal mid-mounted V12, developed in-house, will put power down through an eight-speed single-clutch transmission with an electric motor built in to form a hybrid system.

Innovation is key for developing the future of agriculture and sometimes it comes from unlikely places.

The NASA Artemis Mission is working to develop space exploration, but here on Earth, they are partnering with the University of California Berkeley to use Land Satellite Seven to benefit agriculture.

According to NASA Administrator Jim Bridenstine, “We can use that data from space and combine it with weather stations from Earth, and we can get very precise evapotranspiration measurements, down to a quarter of an acre. What that means is we can provide farmers with very specific irrigation plans.”

The technology is still in the testing phase but could one day make farming a little easier. “Imagine being a farmer and going out into your field with your iPhone, looking at it and having an app on there that tells you exactly what your irrigation needs to be for this quarter of an acre for this type of soil and this type of crop,” Bridenstine states.

NASA looks to partner with private businesses to bring new technologies to the market. “The challenge is land sat only has a revisit of two weeks,” he notes. “Weather changes a lot in two weeks; so, I think there is a future where a commercial company could create lots of satellites that could provide this data to farmers.”

Purpose: This was an open-label phase 1a study assessing the maximum tolerated dose (MTD), safety, and tolerability of CXCR4 peptide antagonist, LY2510924, administered in combination with durvalumab in patients with advanced refractory solid tumors.

Methods: Patients received LY2510924 at 20, 30, or 40 mg subcutaneous (SC) once daily in combination with durvalumab at 1500 mg intravenously (IV) on day 1 of each 28-day cycle. The primary objective was to assess the MTD and safety of LY2510924 SC daily in combination with durvalumab in patients with advanced (metastatic and/or unresectable) solid tumors. Secondary objectives included pharmacokinetics (PK) and the antitumor activity of LY2510924 in combination with durvalumab. Exploratory objectives were biomarker analysis, including pharmacodynamic markers, relevant to LY2510924 and durvalumab, including immune functioning, drug targets, cancer-related pathways, and the disease state.

Results: Nine patients (three each at 20, 30, and 40 mg) were enrolled in the study (eight patients with pancreatic cancer and one patient with rectal cancer). The majority of patients completed one or two cycles (100.0% ≥ 1 cycle; 88.9% ≥ 2 cycles) of LY2510924 and durvalumab. No dose limiting toxicities were reported. Most common (10%) treatment-emergent adverse events were injection-site reaction (44.4%), fatigue (33.3%), and increased white blood cell count (33.3%). PK parameters for combination were similar to those reported in previous studies when given as monotherapy. Best overall response of stable disease was observed in four (44.4%) patients and one patient had unconfirmed partial response.