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The perennial rhizomatous weed Cirsium arvense(L.) Scop. is difficult to manage on semiarid organic farms. Our objective was to quantify the impact of eight 4‐year crop sequences crossed with standard‐ and reduced‐tillage on C. arvenseoccurrence (presence/absence), stem density, and aboveground biomass at two semiarid sites in Montana. The sequences represented a range of crop competition from high (multiple years of perennial forage [alfalfa, Medicago sativaL.]) to low (2 years of continuous fallow), with intermediate sequences consisting of different annual species. Final‐year spring wheat (Triticum aestivumL. emend. Thell.) was planted in all sequences to determine impacts on subsequent cash crop production. Through time, alfalfa and double fallow sequences reduced C. arvensedensity and biomass where it was established, although its invasion into new areas increased in the double fallow. Final‐year C. arvenseoccurrence and stem density were lower in the alfalfa sequence compared with six and four annual crop sequences, respectively (p< 0.05). Final year C. arvensebiomass was higher at one site than the other, although not in the double fallow sequence. Wheat grain yields differed in response to crop sequences at the two sites: at one site, grain yield was lowest in the alfalfa sequence, especially when standard‐tillage was used, while yields were highest in the alfalfa and double fallow sequences at the other site. Using perennial forages in semiarid organic systems can be effective for managing C. arvense, but subsequent cash crop yield may be depressed. Consecutive years of alfalfa or tilled fallow reduced Cirsium arvense.Wheat yield was elevated following consecutive years of fallow.Alfalfa‐induced wheat yield depression occurred at the site where severe drought persisted.Reduced‐tillage practices provided the same Cirsium arvensecontrol as standard‐tillage practices.

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.

Pulse crops, including lentil (Lens culinarisMedik.) and pea (Pisum sativumL.), can improve the sustainability of Northern Great Plains cropping systems, largely through biological N fixation. Greater N fixation amounts can help producers to increase yield while decreasing N fertilizer inputs for the following crop. There may be potential to breed greater N‐fixing pulse varieties, yet little is known about varietal differences in N fixation. Nitrogen fixation of pea and lentil varieties was quantified at two sites in Montana from 2019 to 2021 using an N difference approach and the 15N natural abundance method. Riveland and CDC Richlea were frequently high N‐fixing lentil varieties, both fixing ca. 130 kg N ha−1in the site‐year with the most favorable growing conditions. No pea variety had consistently greater N fixation than others, despite N fixation ranging from 88 to 135 kg N ha−1in one site‐year among varieties. Nitrogen fixation by lentil had an inverse relationship with days to flowering but was not correlated with days to maturity. Nitrogen fixation by pea was positively correlated with days to maturity but was not correlated with days to flowering. Breeding lentil and pea for high N fixation by selecting high N‐fixing varieties is likely difficult, as varieties performed differently under variable environmental conditions. Breeding efforts based on traits, such as days to flowering, could be more successful. There were more positive correlations between N fixation parameters and seed yield for pea than for lentil, suggesting that breeding for greater yields could increase N fixation for pea but not lentil. Variation in environmental conditions strongly influenced N fixation by lentil and pea varieties.Differences in N fixation among varieties were up to 21 kg N ha−1for lentil and 47 kg N ha−1for pea.Two lentil varieties often fixed more N than others, while no pea varieties performed consistently well.Breeding lentil for shorter days to flower could increase N fixation, suggested by an inverse relationship.Breeding pea for greater yield or longer days to maturity could increase N fixation, suggested by positive relationships.

Cover crops during summer fallow have been rarely researched in the semiarid northern Great Plains. This study was conducted during 2012–2019 at four Montana locations and included four functional groups (Brassica family, fibrous‐rooted crops, legumes, and tap‐rooted crops). Eleven treatments included sole functional groups, a Full Mix, the Full Mixminus each functional group, pea, and chemical fallow. Wheat (Triticum aestivumL.) was grown after each cover crop year with three nitrogen (N) fertilizer rates. Cover crops were terminated with herbicide at first flower stage of pea (Pisum sativumL.) 57 to 66 days after planting. Shoot biomass averaged 2.0 Mg ha−1over eight site‐years representative of dryland farming in Montana. Using equal overall plant densities, treatments with six species averaged 13% greater biomass than two species. Measured at termination to a 0.9‐m depth, Fallowheld greater soil water than cover crop treatments, with Fallowaveraging 57 mm greater than the Full Mix. Soil nitrate averaged 49 kg N ha−1greater after Fallowthan the Full Mix; the Legumetreatment averaged 26 kg N ha−1greater than the Minus Legumetreatment. Wheat yield on Fallowaveraged 0.85 Mg ha−1greater than the Full Mixin 5 of 10 site‐years, mainly at the driest site‐years. The Legumetreatment elevated wheat protein over the Minus Legumetreatment by an average of 15 g kg−1. Cover crops grown during summer fallow reduced soil nitrate‐N, soil water, and wheat yields compared with chemical fallow, especially in the major wheat growing region of north central Montana. Soil improvement via cover crop growth is an uncertain trade‐off with soil water and nitrogen use.May–June rainfall best predicted cover crop biomass (Y =757 + 12.4X; Adj. R2= 0.72; p< 0.01).Cover crop treatments that included six crop species averaged 13% greater biomass than those with only two species.An eight‐species cover crop mix averaged 57 mm less soil water and 49 kg ha−1less soil N compared with fallow.Wheat yield on fallow averaged 0.85 Mg ha−1(22%) greater than cover crops for 5 of 10 site‐years.

Deciphering the cell-state transitions underlying immune adaptation across time is fundamental for advancing biology. Empirical in vivo genomic technologies that capture cellular dynamics are currently lacking. We present Zman-seq, a single-cell technology recording transcriptomic dynamics across time by introducing time stamps into circulating immune cells, tracking them in tissues for days. Applying Zman-seq resolved cell-state and molecular trajectories of the dysfunctional immune micro-environment in glioblastoma. Within 24 hours of tumor infiltration, cytotoxic natural killer cells transitioned to a dysfunctional program regulated by TGFB1 signaling. Infiltrating monocytes differentiated into immunosuppressive macrophages, characterized by the upregulation of suppressive myeloid checkpoints Trem2, Il18bp, and Argl, over 36 to 48 hours. Treatment with an antagonistic anti-TREM2 antibody reshaped the tumor microenvironment by redirecting the monocyte trajectory toward pro-inflammatory macrophages. Zman-seq is a broadly applicable technology, enabling empirical measurements of differentiation trajectories, which can enhance the development of more efficacious immunotherapies. [ABSTRACT FROM AUTHOR]

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After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges. Here we describe OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. After 1 h of warm ischaemia, OrganEx application preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs. Commensurately, single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes. Our analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal. [ABSTRACT FROM AUTHOR]

We consider the problem of indefinitely preserving information based on the assumption that the information is divided into segments called records. Each record is subject to radioactive (exponential) decay but also may be copied. It is shown that a slow, logarithmic growth rate in the number of copies is adequate to ensure that the record survives forever with nonzero probability. Such a growth rate, moreover, is sufficient to ensure a similar survival of every record in an expanding hierarchy such as a library or a mind that consists of a growing collection of records, or even a growing collection of record hierarchies of lower order. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the results of adjunctive Er,Cr:YSGG laser therapy with scaling and root planing (SRP) as compared with SRP alone in the treatment of moderate to severe periodontitis. Fifteen adults (aged 27 to 65 years) with 90 nonadjacent sites probing ≥ 5 mm were treated in split‐mouth design with SRP and laser therapy versus SRP alone. Probing pocket depth (PPD), gingival recession (GR), clinical attachment level (CAL), plaque, and bleeding on probing were collected at baseline, 1, 3, 6, 9, and 12 months. Patient reported outcomes were measured to assess pain, sensitivity, and satisfaction. Clinical improvements were similar for test and control sites with no statistically significant difference. At 12 months, the average PPD reduced from 6.1 to 4.2 mm for test and 6.2 to 4.3 mm for control sites. GR increased by 0.4 mm at test and control sites. CAL increased from 6.8 to 5.3 mm for test and 6.9 to 5.5 mm for control sites. Clinical outcomes were stratified by baseline PPD ( = 5, = 6 and ≥7 mm) and analyzed for number of sites that reduced (≤4 mm). No significant difference was observed when the baseline PPD was 5 or 6 mm. Test sites with baseline PPD ≥7 mm demonstrated a statistically significant difference in the percentage of reduced sites when compared with controls at nine (P= 0.001) and 12 months (P= 0.044). Adjunctive Er,Cr:YSGG laser therapy with SRP provides similar clinical improvement in the treatment of moderate‐severe periodontitis as SRP alone and may offer some advantage for deeper (≥7 mm) pockets.

This article describes the current and possible future processes the Military Health System (MHS) uses to identify, assess, and select the medical-surgical products used to treat patients in peacetime and [...]

This study investigates common features of a set of diverse schools’ responses to the initial school lockdown period during the pandemic in 2020, with a focus on practices supporting learning, inclusion and wellbeing. It comprises a collective case study of four Australian schools that were selected based on their reputation for impactful support of students and teachers during the emergency remote teaching period. Methods included interviews and focus groups with school leaders, teachers and students. The schools had widely differing contexts, technology access and student needs. Despite these varied contexts, the findings provided important insights into common practices supporting effective remote teaching. Emerging principles of effective practice illuminate ways forward to mitigate the significant risks accompanying emergency remote teaching, and guide practices in a variety of school contexts.

A longstanding goal of biology is to identify the key genes and species that critically impact evolution, ecology, and health. Network analysis has revealed keystone species that regulate ecosystems and master regulators that regulate cellular genetic networks. Yet these studies have focused on pairwise biological interactions, which can be affected by the context of genetic background and other species present, generating higher-order interactions. The important regulators of higher-order interactions are unstudied. To address this, we applied a high-dimensional geometry approach that quantifies epistasis in a fitness landscape to ask how individual genes and species influence the interactions in the rest of the biological network. We then generated and also reanalyzed 5-dimensional datasets (two genetic, two microbiome). We identified key genes (e.g., the rbs locus and pykF) and species (e.g., Lactobacilli) that control the interactions of many other genes and species. These higher-order master regulators can induce or suppress evolutionary and ecological diversification by controlling the topography of the fitness landscape. Thus, we provide a method and mathematical justification for exploration of biological networks in higher dimensions. [ABSTRACT FROM AUTHOR]

Microglia, the innate immune cells of the brain, influence Alzheimer's disease (AD) progression and are potential therapeutic targets. However, microglia exhibit diverse functions, the regulation of which is not fully understood, complicating therapeutics development. To better define the transcriptomic pheno-types and gene regulatory networks associated with AD, we enriched for microglia nuclei from 12 AD and 10 control human dorsolateral prefrontal cortices (7 males and 15 females, all aged >60 years) before single-nucleus RNA sequencing. Here we describe both established and previously unrecognized mi-croglial molecular phenotypes, the inferred gene networks driving observed transcriptomic change, and apply trajectory analysis to reveal the putative relationships between microglial phe-notypes. We identify microglial phenotypes more prevalent in AD cases compared with controls. Further, we describe the heterogeneity in microglia subclusters expressing homeostatic markers. Our study demonstrates that deep profiling of microglia in human AD brain can provide insight into microglial transcriptional changes associated with AD. [ABSTRACT FROM AUTHOR]

Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite its regulatory role and elevated function in ovarian and other solid tumors, another tumor-enriched death receptor called Fas (CD95) remained undervalued in cancer immunotherapy until recently, when its role in off-target tumor killing by CAR-T therapies was imperative. By comprehensively analyzing structure studies in the context of the binding epitope of FasL and various preclinical Fas agonist antibodies, we characterize a highly significant patch of positively charged residue epitope (PPCR) in its cysteine-rich domain 2 of Fas. PPCR engagement is indispensable for superior Fas agonist signaling and CAR-T bystander function in ovarian tumor models. A single-point mutation in FasL or Fas that interferes with the PPCR engagement inhibited apoptotic signaling in tumor cells and T cells. Furthermore, considering that clinical and immunological features of the autoimmune lymphoproliferative syndrome (ALPS) are directly attributed to homozygous mutations in FasL, we reveal differential mechanistic details of FasL/Fas clustering at the PPCR interface compared to described ALPS mutations. As Fas-mediated bystander killing remains vital to the success of CAR-T therapies in tumors, our findings highlight the therapeutic analytical design for potentially effective Fas-targeting strategies using death ag-onism to improve cancer immunotherapy in ovarian and other solid tumors. [ABSTRACT FROM AUTHOR]

Wheat (Triticumspp.) dominates dryland grain crop production in the North American Great Plains and other regions with semi‐arid steppe climates. A common practice is to alternate winter or spring wheat with a 14‐ to 21‐mo fallow period to allow for soil‐water recharge, despite economic inefficiencies and environmental degradation. Replacing fallow with non‐cereal grain and seed crops often reduces future wheat yields due to increased water stress during grain fill. The use of annual forages may not have the disadvantages associated with grain and seed crops. The objective of this review was to determine benefits and challenges of incorporating annual forages into dryland wheat systems in semi‐arid steppe climates, using the Great Plains within the United States as a model system. Results indicate that: (a) cool‐ and warm‐season, annual grass and broadleaf species can be grown for forage across the region; (b) forage production will be less risky than grain and seed crop production under predicted climate‐change scenarios; (c) grazing annual forages may offer advantages (e.g., nutrient cycling, improved soil structure, added revenue from livestock) over mechanically harvesting annual forages; (d) the lack of infrastructure and local markets impede the use of annual forages to diversify wheat‐based cropping systems in the region; and (e) limited networking among researchers hinders the advancement in knowledge on how annual forages can be used to improve dryland wheat system resilience.

A method is proposed, in principle, for restoring lost information which cannot be recovered or rediscovered from the environment by any process usually conceived within the scope of archaeology. This includes future archaeological methods that may be developed. Instead, the lost information is recreated de novo using a quantum-random process. An assumption of a multiple-worlds cosmology provides that different, lost versions of the missing information are recreated across parallel branches of reality, so that overall, there is no violation of information conservation and the restorations are all authentic. Refinements including partial restoration and use of probability weights are explored. [ABSTRACT FROM AUTHOR]

48 Cryonics / 1st Quarter 2021 www.alcor.org Revival Update Scientific Developments Supporting Revival Technologies Reported by R. Michael Perry, Ph.D. MP-Pt(IV): A MAOB-sensitive mitochondrial-specific prodrug for treating glioblastoma. By contrast, inhibiting the ISR by mutating the eIF2 phosphorylation site, genetically and pharmacologically inhibiting the ISR kinases, or mimicking reduced p-eIF2 with the ISR inhibitor ISRIB, enhances long-term memory in health and disease. Furthermore, ISRIB treatment reverses spatial memory deficits and ameliorates working memory in old mice. We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. [Extracted from the article]

The S-MIX is a quantitative cryonics cases outcome metric to calculate the total ischemic exposure of a patient. In this brief exposition, R. Michael Perry and Aschwin De Wolf introduce this metric and the issues involved in calculating it for a cryonics case involving several distinct procedures. [ABSTRACT FROM AUTHOR]

Rotating summer fallow with wheat (Triticumspp.) is done in dryland grain farming at upper latitudes to stabilize yields over time and to prevent crop failure. However, summer fallow is costly since weeds must be controlled and crops are not grown. Replacing summer fallow with grain crops can generate low economic returns. Previous research indicated that annual cool‐season forages can be substituted for summer fallow in dryland cropping systems. Our objective was to determine if annual warm‐season species were suited for forage production in monocultures and polycultures in the U.S. northern Great Plains. Dry matter (DM) production by 20 warm‐ and cool‐season crop monocultures and 4 polycultures was determined across six environments during 2016, and by 25 warm‐ and cool‐season crop monocultures and polycultures across four environments from 2016 through 2018. Maize (Zea maysL.) monoculture produced forage DM in amounts equal to, or greater than, those produced by other warm‐ and cool‐season crop treatments (P< 0.05). Maize DM production averaged 2.5 to 5.7 Mg ha−1, depending on the study and environment. Sorghum (Sorghum bicolorL.), foxtail millet [Setaria italica(L.) P. Beauv.] and sunflower (Helianthus annuusL.) also produced relatively large amounts of forage DM. Polycultures failed to produce more DM than monocultures consistently (P> 0.40). These results indicate that maize and other warm‐season crops are adapted for dryland forage production in cool regions at upper latitudes. Additional research is needed to determine the impacts of annual warm‐season forages on grain yield in a forage‐wheat crop sequence.

High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset.