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Two seventh graders, Drew and Mia, spend their summer in Half Moon Bay, California, training for a half-marathon, and supporting each other as their families struggle with medical and financial problems.

The possibility that neutrinos may be their own antiparticles, unique among the known fundamental particles, arises from the symmetric theory of fermions proposed by Ettore Majorana in 1937 1 . Given the profound consequences of such Majorana neutrinos, among which is a potential explanation for the matter–antimatter asymmetry of the universe via leptogenesis 2 , the Majorana nature of neutrinos commands intense experimental scrutiny globally; one of the primary experimental probes is neutrinoless double beta (0 νββ ) decay. Here we show results from the search for 0 νββ decay of 130 Te, using the latest advanced cryogenic calorimeters with the CUORE experiment 3 . CUORE, operating just 10 millikelvin above absolute zero, has pushed the state of the art on three frontiers: the sheer mass held at such ultralow temperatures, operational longevity, and the low levels of ionizing radiation emanating from the cryogenic infrastructure. We find no evidence for 0 νββ decay and set a lower bound of the process half-life as 2.2 × 10 25  years at a 90 per cent credibility interval. We discuss potential applications of the advances made with CUORE to other fields such as direct dark matter, neutrino and nuclear physics searches and large-scale quantum computing, which can benefit from sustained operation of large payloads in a low-radioactivity, ultralow-temperature cryogenic environment. The CUORE experiment finds no evidence for neutrinoless double beta decay after operating a large cryogenic TeO 2 calorimeter stably for several years in an extreme low-radiation environment at a temperature of 10 millikelvin.

In the context of rising anthropogenic activities and world conflicts, there is an urgent need for energy supply, such as nuclear power from uranium minerals. Nonetheless, uranium is one of the most radioactive and hazardous metals due to its long half-life and chemical toxicity to living organisms, thus requiring advanced methods to clean uranium-contaminated waters and ecosystems. Silicate minerals, which constitute about 90% of the Earth's crust, have been widely studied as a means of removing radionuclides and heavy metals, including uranium, due to their abundance, low cost, and high efficiency. Here, we review uranium removal by silicate minerals, focusing on the sorption and reduction of uranium (VI) by silicate minerals with well-defined pore structures, including kaolinite, montmorillonite, silica, zeolites, and other natural or modified silicate minerals. The treatment process is influenced by the pH, uranium (VI) concentration, ionic strength, temperature, and the presence of carbon dioxide and organic ligands. In particular, the pore structure and surface charge of silicate minerals play critical roles in the sorption process, whereas the modification of silicate minerals and preparation of silicate mineral composites can substantially enhance the sorption of uranium (VI). The reduction of uranium (VI) produces sparingly soluble uranium (IV), which prevents the migration of uranium and facilitates the sorption process. Molecular dynamic simulations and density functional theory calculations can provide valuable insights into the mechanism of uranium (VI) sorption and reduction, especially when used in correlation with experimental studies. Future studies could focus on improving the alkali resistance and sorption selectivity of silica minerals for extracting uranium from seawater.

While the 2011 nuclear disaster in Japan forced residents out of their coastal Fukushima homes, transforming familiar ecologies into sites of estrangement, Naoko and neighbors remain invested in the material objects and spiritual relations of their houses, within and despite the logics of contamination. These desires to repair domestic livelihoods to nurture a sense of home (ie) and the idea of dying well (ii shinikata) challenge critical theories of nuclear fallout, which frame contamination’s impacts in terms of biopolitical logics and planetary scales. Thus, although contamination regiments the lives of residents through what I call a half-life politics, their practices of house-ing defy these strictures, as planetary contamination becomes experiential, ethnographic, and interscalar, and as people attempt to remake lives in an already injured and irradiated world. 2011 年東日本大震災に起因する東京電力福島第一発電所事故は近隣の森や 生態系を汚染し、多くの福島県浜通り地区の住民達を長期避難に追いやった。し かしながら住民の多くは汚染されなくなく避難した『家』との縁を切るのではな く、個々の考える『いい死に方』を求め汚染された家との物質的、精神的つながり 求め続けた。このような避難民の原子力事故後の行動は、人間と放射性物質の関 係性を生物的ダメージに特化して語るフォールアウト関連の学術的思考や、事故 後の政策に見られる汚染中心の『半減期的政治』とは異なる考え方の必要性を示 している。この論文は文化人類学的アプローチを使い、人はどのようにして『家』 を保持しようとする行動の中で自分以外のモノとのつながりを認知し、放射能汚 染の様々な規模　-その地域性や普遍性- を理解し、それと共存して行こうとす るのかという問いへの回答を探る。 Enquanto o desastre nuclear de 2011 no Japão forçou os residentes de Fukushima a abandonar suas casas, transformando ecologias familiares em locais de estranhamento, Naoko e seus vizinhos continuam a investir em objetos e em relações espirituais com as suas casas agora emolduradas pela lógica da contaminação. O desejo de recuperar o sentido de lar (ie) e a ideia de morrer bem (ii shinikata) desafia as teorias críticas da contaminação radioativa que maiormente enfatizam o seu impacto em termos biopolíticos e em escala planetária. Assim, embora a contaminação regule o dia a dia dos moradores através do que eu chamo de half-life politics, suas práticas de house-ing desafiam essas restrições. A etnografia revela a contaminação planetária como sendo experiencial e interescalar, e mostra as pessoas refazendo as suas vidas em um mundo já irradiado e ferido. Mientras el desastre nuclear de 2011 en Japón obligó a los residentes de Fukushima a abandonar sus hogares, transformando ecologías familiares en lugares de extrañamiento, Naoko y sus vecinos siguen invirtiendo en objetos y en relaciones espirituales con sus casas ahora envueltas en la lógica de la contaminación. Los deseos de recuperar el sentido de hogar (ie) y la idea de morir bien (ii shinikata) desafían las teorías críticas sobre la contaminación radioactiva que en su mayoría enfatizan los impactos biopolíticos y la escala planetaria. Así, aunque la contaminación regula el cotidiano a través de lo que llamo half-life politics, las prácticas de house-ing desafían estas restricciones. La etnografía revela a la contaminación planetaria como experiencial e interescalar y muestra a las personas rehaciendo sus vidas en un mundo ya herido e irradiado.

Background Degradation rate is a fundamental aspect of mRNA metabolism, and the factors governing it remain poorly characterized. Understanding the genetic and biochemical determinants of mRNA half-life would enable more precise identification of variants that perturb gene expression through post-transcriptional gene regulatory mechanisms. Results We establish a compendium of 39 human and 27 mouse transcriptome-wide mRNA decay rate datasets. A meta-analysis of these data identified a prevalence of technical noise and measurement bias, induced partially by the underlying experimental strategy. Correcting for these biases allowed us to derive more precise, consensus measurements of half-life which exhibit enhanced consistency between species. We trained substantially improved statistical models based upon genetic and biochemical features to better predict half-life and characterize the factors molding it. Our state-of-the-art model, Saluki, is a hybrid convolutional and recurrent deep neural network which relies only upon an mRNA sequence annotated with coding frame and splice sites to predict half-life ( r =0.77). The key novel principle learned by Saluki is that the spatial positioning of splice sites, codons, and RNA-binding motifs within an mRNA is strongly associated with mRNA half-life. Saluki predicts the impact of RNA sequences and genetic mutations therein on mRNA stability, in agreement with functional measurements derived from massively parallel reporter assays. Conclusions Our work produces a more robust ground truth for transcriptome-wide mRNA half-lives in mammalian cells. Using these revised measurements, we trained Saluki, a model that is over 50% more accurate in predicting half-life from sequence than existing models. Saluki succinctly captures many of the known determinants of mRNA half-life and can be rapidly deployed to predict the functional consequences of arbitrary mutations in the transcriptome.

Stable isotopes of carbon, nitrogen, and sulfur are used as ecological tracers for a variety of applications, such as studies of animal migrations, energy sources, and food web pathways. Yet uncertainty relating to the time period integrated by isotopic measurement of animal tissues can confound the interpretation of isotopic data. There have been a large number of experimental isotopic diet shift studies aimed at quantifying animal tissue isotopic turnover rate λ (%·day(-1), often expressed as isotopic half-life, ln(2)/λ, days). Yet no studies have evaluated or summarized the many individual half-life estimates in an effort to both seek broad-scale patterns and characterize the degree of variability. Here, we collect previously published half-life estimates, examine how half-life is related to body size, and test for tissue- and taxa-varying allometric relationships. Half-life generally increases with animal body mass, and is longer in muscle and blood compared to plasma and internal organs. Half-life was longest in ecotherms, followed by mammals, and finally birds. For ectotherms, different taxa-tissue combinations had similar allometric slopes that generally matched predictions of metabolic theory. Half-life for ectotherms can be approximated as: ln (half-life) = 0.22*ln (body mass) + group-specific intercept; n = 261, p<0.0001, r2 = 0.63. For endothermic groups, relationships with body mass were weak and model slopes and intercepts were heterogeneous. While isotopic half-life can be approximated using simple allometric relationships for some taxa and tissue types, there is also a high degree of unexplained variation in our models. Our study highlights several strong and general patterns, though accurate prediction of isotopic half-life from readily available variables such as animal body mass remains elusive.

Abstract Background Bexagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. A pilot study has shown that bexagliflozin can decrease dependence on exogenous insulin in cats with diabetes mellitus (DM). Objective To evaluate the safety and effectiveness of bexagliflozin as a monotherapy for DM in previously untreated cats. Animals Eighty-four client-owned cats. Methods Historically controlled prospective open-label clinical trial. Cats were dosed PO with 15 mg bexagliflozin once daily for 56 days, with a 124-day extension to evaluate safety and treatment effect durability. The primary endpoint was the proportion of cats experiencing a decrease in hyperglycemia and improvement in clinical signs of hyperglycemia from baseline on day 56. Results Of 84 enrolled cats, 81 were evaluable on day 56, and 68 (84.0%) were treatment successes. Decreases in mean serum glucose, fructosamine, and β-hydroxybutyrate (β-OHB) concentrations were observed, and investigator assessments of cat neurological status, musculature, and hair coat quality improved. Owner evaluations of both cat and owner quality of life were favorable. The fructosamine half-life in diabetic cats was found to be 6.8 days. Commonly observed adverse events included emesis, diarrhea, anorexia, lethargy, and dehydration. Eight cats experienced serious adverse events, 3 of which led to death or euthanasia. The most important adverse event was euglycemic diabetic ketoacidosis, diagnosed in 3 cats and presumed present in a fourth. Conclusion and Clinical Importance Bexagliflozin decreased hyperglycemia and observed clinical signs in cats newly diagnosed with DM. As a once-daily PO medication, bexagliflozin may simplify management of DM in cats.

Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, singlewalled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ($^{111}ln$) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.

Half-life ( t 1/2 ) is the oldest but least well understood pharmacokinetic parameter, because most definitions are related to hypothetical 1-compartment body models that don’t describe most drugs in humans. Alternatively, terminal half-life ( t 1/2,z ) is utilized as the single defining t 1/2 for most drugs. However, accumulation at steady state may be markedly over predicted utilizing t 1/2, z . An apparent multiple dosing half-life ( t 1/2, app ) was determined from peak and trough steady-state ratios and found to be significantly less than reported terminal t 1/2 s for eight orally dosed drugs with t 1/2,z values longer than one day. We define a new parameter, “operational multiple dosing half-life” ( t 1/2, op ), as equal to the dosing interval at steady-state where the maximum concentration at steady-state is twice the maximum concentration found for the first dose. We demonstrate for diazepam that the well-accepted concept that t 1/2,z representing the great majority of the AUC will govern accumulation can be incorrect. Using oral diazepam, we demonstrate that t 1/2, op is remarkably sensitive to the absorption t 1/2 , even when this absorption t 1/2 is much less than t 1/2,z, and describe the relevance of this in designing extended release dosage forms. The t 1/2, op is compared with previously proposed half-lives for predicting accumulation.

Monoclonal antibodies (mAbs) have emerged as a major class of therapeutic agents on the market. To date, approximately 80 mAbs have been granted marketing approval. In 2018, 12 new mAbs were approved by the FDA, representing 20% of the total number of approved drugs. The majority of mAb therapeutics are for oncological and immunological/infectious diseases, but these are expanding into other disease areas. Over 100 monoclonal antibodies are in development, and their unique features ensure that these will remain a part of the therapeutic pipeline. Thus, the therapeutic value and the elucidation of their pharmacological properties supporting clinical development of these large molecules are unquestioned. However, their utilization as pharmacological tools in academic laboratories has lagged behind their small molecule counterparts. Early therapeutic mAbs targeted soluble cytokines, but now that mAbs also target membrane‐bound receptors and have increased circulating half‐life, their pharmacology is more complex. The principles of pharmacology have enabled the development of high affinity, potent and selective small molecule therapeutics with reduced off‐target effects and drug‐drug interactions. This review will discuss how the same basic principles can be applied to mAbs, with some important differences. Monoclonal antibodies have several benefits, such as fewer off‐target adverse effects, fewer drug‐drug interactions, higher specificity, and potentially increased efficacy through targeted therapy. Modifications to decrease the immunogenicity and increase the efficacy are described, with examples of optimizing their pharmacokinetic properties and enabling oral bioavailability. Increased awareness of these advances may help to increase their use in exploratory research and further understand and characterize their pharmacological properties.