Progress in Medical Sciences and Life Sciences, in general, require detailed knowledge of the complex biological processes that underlie the function of a cell, the organization and interplay of multicellular structures, and, eventually, of the whole organism. Such a basic understanding has an enormous impact on our life, as it is necessary to understand diseases and to develop better drugs and therapeutic protocols. The cell, be it a pathogenic bacterium or a motor neuron, could be thought of as the fundamental unit of Life. However, a closer look at its inner workings reveals a hugely complex machinery, made up of a multitude of small and large molecules. Membrane proteins and lipids interact with each other in an orderly manner, to create larger structures─membranes─that segregate the inner aqueous solution in different compartments─organelles─and control the diffusion of soluble components in a selective manner. Other proteins dynamically organize as fibrils, making the cytoskeleton, that ultimately allow the cell to maintain its integrity and to control its shape and motility. Inside, DNA, RNAs, and the ribosomes take care of storing and translating the genetically encoded information, while other associated proteins regulate such processes and define the cellular phenotype. The intracellular aqueous compartments are filled with a plethora of soluble ions, metabolites, and macromolecules, which make up the intricated biochemical and signaling pathways that make the cell self-sustaining and ultimately “alive”...

...NMR spectroscopy is the only one able to obtain information on the structure, the kinetics, and the thermodynamics of biological macromolecules at the atomic level, as it can observe them in native-like environments at physiological temperatures, and it can do so in a nondestructive manner. (6) Such a feature has always made NMR spectroscopy appealing for the study of small and large molecules not only in vitro, isolated from their physiological context, but directly inside intact living cells. Compared to other spectroscopic techniques, NMR suffers from an intrinsically low sensitivity; therefore, its applicability to cells was traditionally restricted to the observation of small, highly abundant molecules. Indeed, in the past century, cellular NMR studies were mostly focused on the analysis of cellular metabolism, for example, by exploiting the observation of phosphorus-containing molecules through 31P NMR, or by introducing 13C-labeled precursors for a metabolic flux analysis. In some cases, very abundant small macromolecules could be studied, often because of peculiar properties that made them stand out against the rest of the milieu, as it is the case for highly shifted signals of paramagnetic metalloproteins. Then, in the early 2000s, it became clear that modern NMR spectrometers, with a higher magnetic field and more sensitive hardware, could detect signals from isotopically labeled proteins inside the bacteria in which they were recombinantly expressed. (7) Shortly after, macromolecules─proteins at first, then nucleic acids─were delivered to eukaryotic cells. The cellular NMR approach, reborn as “in-cell NMR”, soon gained widespread recognition, in a time when the scientific community had realized the importance of performing biochemical and biophysical studies in physiologically relevant contexts, and huge advancements were being made in developing techniques, such as single-molecule Förster resonance energy transfer (FRET) and cryo-electron tomography, that would be able to characterize macromolecules in a cellular environment...

...This work provides a detailed overview of the development and applications of in-cell solution NMR approaches during the first ?20 years since its inception in the modern sense. We first describe the existing approaches for cell sample preparation, the various types and strategies for isotopic incorporation, and the NMR methods that can be applied to living cells. We then review the application of in-cell NMR to different biological questions: how the cellular environment affects the folding thermodynamics of a protein, its structural and dynamic properties, and its interactions with specific cellular partners; whether the structure of a folded protein in cells differs from that determined in vitro...

The band’s label saw its stock price plunge, and the possibility that the K-pop group won’t tour as pandemic restrictions ease threatens to reverberate through South Korea’s economy.

The fallout from BTS’s announcement on Tuesday that the K-pop juggernaut will be taking a break as members explore solo careers was immediate and drastic.

In just a day, the stock price of the group’s management label, HYBE, plummeted 28 percent to 139,000 won — or $108 — its lowest price since the company went public nearly two years ago, shedding $1.7 billion in market value. The stock price has barely moved since.

The drastic plunge underscores how South Korea’s best-selling boy band has become not only a cultural sensation but also a powerful stakeholder in South Korea’s economy.

Since the group’s debut in 2013, BTS has raked in billions of dollars through album sales, concert tickets and social media. Its YouTube channel alone, which is the 20th largest in the world, can generate up to $2 million a month. By 2020, the group was contributing $3.5 billion annually to the nation’s economy, according to the Hyundai Research Institute...

Again and again:

In the early hours after the shooting at a Tulsa medical center on Wednesday, the details were murky. Soon, it became clear that the death toll there was not going to be as nearly as high as the tolls from the recent shootings in Uvalde and Buffalo.

Four people were killed in Tulsa (in addition to the gunman), compared with 21 in Uvalde and 10 in Buffalo. But the Tulsa shooting is nonetheless horrific in its own way — not only for its victims and their families but also for what it says about gun violence in the United States.

Shootings that kill multiple people are so common in this country that they often do not even make national news. They are a regular feature of American life. Tulsa has become the latest example — yet another gun crime that seems almost ordinary here and yet would be extremely rare in any other country as wealthy as the U.S.

To give you a sense of how common these shootings are, we’re devoting the rest of the lead item of today’s newsletter to a list of every documented mass shooting in which a gunman has killed at least three people in the U.S. so far this year. (The Gun Violence Archive defines a mass shooting as any in which at least four people are shot, including survivors.)...

...2022, so far

Jan. 19, Baltimore: A man who worked for a gun violence reduction program was killed in an East Baltimore neighborhood, along with two others. A fourth person was injured.

Jan. 23, Milwaukee: Five men and a woman were found shot to death at a Park West neighborhood home. The police believe the attack targeted specific people.

Jan. 23, Inglewood, Calif.: The same day, a shooting at a birthday party killed four people, including two sisters, and wounded a fifth. The shooting was gang-related, the mayor said.

Jan. 29, St. Louis: A shooting near an intersection killed three young men and wounded a fourth. Police said they had no suspects.

Feb. 5, Corsicana and Frost, Texas: A 41-year-old man murdered his mother, his stepfather, his sons and the son of his ex-girlfriend in an overnight shooting. The man later fatally shot himself.

Feb. 28, Sacramento: A man shot dead his three daughters and their chaperone at a church during a court-approved visit. The children’s mother had a restraining order against the shooter, who killed himself.

March 12, Baltimore: A shooting in Northwest Baltimore killed three men in a car and wounded a fourth.

March 19, Fayetteville, N.C.: A Saturday night shootout in a hotel parking lot killed three people and wounded another three. The shooting may have been linked to a fight between motorcycle gangs.

March 19, Norfolk, Va.: Hours later, an argument outside a bar escalated into a shooting that killed three young bystanders. One of the victims was a 25-year-old newspaper reporter whose editor called her to cover the shooting, not realizing she had been killed.

April 3, Sacramento: At least five shooters fired more than 100 rounds a block from the State Capitol, killing six people — three men and three women — and wounding 12. The police described the shooting as gang-related.

April 20, Duluth, Minn.: A 29-year-old man who said he suffered from mental illness killed his aunt, uncle, two young cousins and their dog in their sleep. He later killed himself.

April 21, Mountain View, Ark.: A man killed his parents, another woman and her son at two homes half a mile apart in a rural community, the police say.

April 27, Biloxi, Miss.: A 32-year-old man killed the owner of the Broadway Inn Express motel and two employees in an argument over money. He fled to a neighboring town and fatally shot a fourth person. Police later found the gunman dead, barricaded inside a convenience store.

May 8, Clarkston, Ga.: Three people were shot to death and three others were wounded at a suburban Atlanta condo complex on a Sunday night.

May 14, Buffalo: An 18-year-old avowed white supremacist killed 10 people and wounded three more with an assault-style weapon in a live-streamed attack at a supermarket.

May 24, Uvalde, Texas: An 18-year-old gunman killed 19 students and two teachers at Robb Elementary School.

May 27, Stanwood, Mich.: A 51-year-old man allegedly killed his wife and her three young children at a home in Mecosta County before shooting himself, police said. The man remains in critical condition.

June 1, Tulsa, Okla.: A gunman killed his back surgeon, another doctor, a receptionist and a visitor at a medical building. He then killed himself.

As long as this list is, it’s also a very incomplete accounting of American gun violence. It doesn’t include the at least 60 shootings that left three people dead but don’t technically count as mass shootings (because fewer than four people were shot). It doesn’t count shootings that wounded people without killing anybody, like one in Milwaukee that injured 17 people. And it leaves out the individual gun homicides and suicides that make up a majority of the gun violence that kills more than 100 Americans on an average day.

Nuclear fuel debris filters manufactured by Westinghouse Electric Sweden AB using 3D printing technology have been installed at unit 2 of the Olkiluoto nuclear power plant in Finland and unit 3 of the Oskarshamn plant in Sweden.

Westinghouse created the StrongHold AM filter in close cooperation with plant operators Teollisuuden Voima Oyj (TVO) and OKG AB. It said the filters are fully manufactured through 3D printing techniques and offer enhanced capture features to prevent debris from entering the fuel assembly and potentially damaging the cladding, which could cause unplanned and expensive outages.

Additive manufacturing - or 3D printing - simplifies the manufacturing process by building a three-dimensional object from a computer-aided design model, usually by successively adding material layer by layer.

"As the first 3D-printed fuel debris filter for insertion in a nuclear power plant, the StrongHold AM marks a major milestone in our effort to further improve the boiling water reactor (BWR) fuel reliability by leveraging advances in manufacturing technology," said Carina Önneby, Westinghouse Vice President EMEA Fuel Delivery.

During a recent refuelling outage at the Olkiluoto 2 BWR, two fuel assemblies equipped with 3D-printed filters for exclusion of foreign material were loaded in the reactor.

"We can boast playing a pioneering role, even globally, in the utilisation of this new technology at nuclear power plants," said Fuel Procurement Team Leader Arttu Knuutila from TVO...

Gene therapy opens up new routes for the treatment of chronic disease by modulating gene expression in targeted cells through the delivery of nucleic acids. (1) Although viral delivery vectors can lead to high transfection efficiencies in animal models, their clinical applications are limited by potential immunogenicity and mutagenesis. (2,3) In addition, the limited size capacity of viral particles precludes the delivery of larger nucleic acids required for some gene therapies. (4) Therefore, the development of safe and effective nonviral gene delivery vectors has become an intense field of investigation at the interface of materials science and molecular biology. (2,3,5?11) In particular, polymer nanoparticles (or PNPs) offer a number of advantages for gene delivery compared to their lipid-based counterparts, including stability, ease of functionalization, and variability of properties. (12?16)

To serve as effective gene delivery vehicles, PNP vectors should be designed with four main characteristics. First, they should provide stable encapsulation of nucleic acids while protecting them from constituents in the extracellular environment; for example, both deoxyribonucleases (DNases) and ribonucleases (RNases) will bind and degrade exposed exogenic nucleic acids in the blood. (4,17,18) Second, PNP vectors should disperse in the bloodstream and deliver nucleic acids to target cells through passive or active targeting. (4,17,18) Third, they should facilitate cellular uptake followed by the release of nucleic acids to trigger the desired transfection events. (4,17,18) Finally, the vector material should be broken down and excreted by the patient with minimal toxicological effects. (4,17,18)

Drought in California could nearly halve the state’s hydroelectric generation this summer, pushing up wholesale power prices in the West, and forcing the state to rely on natural gas generation and out-of-state imports, the Energy Information Administration (EIA) projects in a new analysis.

The EIA suggests in a supplement to its May 2022–released Short-Term Energy Outlook that current drought conditions in the state potentially “have a significant impact” on power markets throughout the West from June through September 2022. That impact “could be different than in past years, given the state’s accelerating growth in intermittent generating capacity and reliance on imports,” which accounted for nearly one-third of California’s power supply in 2020, it said.

Conditions this summer are especially precarious given that California has experienced more frequent and intense drought conditions over the past decade—and it is currently grappling with a third continuous year of drought.

“During the 2022 water year, which began October 1, 2021, snowpack reached above-normal levels in December, but dry conditions then persisted through March. As of April 1, which typically marks the peak of snowpack, California’s snowpack had an equivalent water content of 6.9 inches, which is about 40% below the median value from 1991 through 2020,” the EIA explained. “Less snowpack means that, as temperatures warm in the spring, less snow will melt and flow into California’s reservoirs.”

Drought Widely Affecting Major Reservoirs
According to the California Department of Water Resources, every reservoir in California is suffering below-average conditions. These include reservoirs where some of the state’s largest hydropower generators are located, such as the 644-MW Edward C. Hyatt plant at Lake Oroville; the 300-MW New Melones plant at New Melones Lake; the 714-MW Shasta plant at Shasta Lake; the 140-MW Trinity pant at Trinity Lake; the 207-MW Folsom plant at Folsom Lake; and the 315-MW Colgate plant at New Bullards Bar Reservoir. The six plants, notably, are the focus of the EIA’s modeling in the May-released supplement. The six projects accounted for 22% of California’s total hydropower generation over the previous five years, the EIA notes...

Current conditions (as of June 1, 2022), at California’s major water supply reservoirs. Source: California Department of Water Resources.