Microscale Cartesian Diver Activities

Because air has weight, it exerts pressure. The air in a room can weigh as much as 100 kilograms, which is the weight of a large person. Air can also be compressed into small containers, such as those used by underwater divers. Teachers can construct several toys called Cartesian divers which will rise and fall exactly as a diving bell does. The toys are called Cartesian because the principle of moving diving machines by air pressure was first explained by Rene Descartes, a 16th century mathematician. This exercise is divided up into four parts: A Cartesian Retriever, The Cartesian Helicopter, A Cartesian Counter and Cartesian Basketball

FOREIGN AGRICULTURAL POLICY AND FAR EAST FARM MARKETS

Agricultural and Food Policy,

Precision health in behaviour change interventions: A scoping review

Precision health seeks to optimise behavioural interventions by delivering personalised support to those in need, when and where they need it. Conceptualised a decade ago, progress toward this vision of personally relevant and effective population-wide interventions continues to evolve. This scoping review aimed to map the state of precision health behaviour change intervention research. This review included studies from a broader precision health review. Six databases were searched for studies published between January 2010 and June 2020, using the terms ‘precision health’ or its synonyms, and including an intervention targeting modifiable health behaviour(s) that was evaluated experimentally. Thirty-one studies were included, 12 being RCTs (39 %), and 17 with weak study design (55 %). Most interventions targeted physical activity (27/31, 87 %) and/or diet (24/31, 77 %), with 74% (23/31) targeting two to four health behaviours. Interventions were personalised via human interaction in 55 % (17/31) and digitally in 35 % (11/31). Data used for personalising interventions was largely self-reported, by survey or diary (14/31, 45 %), or digitally (14/31, 45 %). Data was mostly behavioural or lifestyle (20/31, 65 %), and physiologic, biochemical or clinical (15/31, 48 %), with no studies utilising genetic/genomic data. This review demonstrated that precision health behaviour change interventions remain dependent on human-led, low-tech personalisation, and have not fully considered the interaction between behaviour and the social and environmental contexts of individuals. Further research is needed to understand the relationship between personalisation and intervention effectiveness, working toward the development of sophisticated and scalable behaviour change interventions that have tangible public health impact

Unit 4-Dairy Calf Housing and Environment

This archival publication may not reflect current scientific knowledge or recommendations. Current information available from the University of Minnesota Extension: https://www.extension.umn.edu

546 Results from Phase Ib study of tebentafusp (tebe) in combination with durvalumab (durva) and/or tremelimumab (treme) in metastatic cutaneous melanoma (mCM)

BackgroundTebe, a T cell receptor fused to an anti-CD3 effector, can redirect T cells to target gp100+ cells and in Ph3, demonstrated overall survival (OS) benefit as monotherapy in metastatic uveal melanoma. In Ph2, any tumor shrinkage (44% of patients) was a better predictor of OS than response rate. In Ph1, Tebe had monotherapy activity in mCM, also a gp100+ tumor, with 1-year OS ~74% in PD-1 naïve mCM. A Ph1 dose escalation of tebe with durva (anti-PD-L1) and/or treme (anti-CTLA4) was conducted in pre-treated mCM [NCT02535078], with nearly all patients having prior PD1-treatment, and where recently reported therapies have 1-yr OS of ~55%.MethodsHeavily pre-treated HLA-A2+ mCM patients received weekly IV tebe alone (Arm 4) or with increasing doses of durva and/or treme (Arm 1–3) administered IV monthly starting day 15 of each cycle. Primary objective was to identify RP2D of combination therapy. Secondary objectives included adverse events (AE) and efficacy.Results112 pts received ≥1 tebe dose. Median age was 59, 77% were ECOG 0, and 37% were BRAFm (of which 71% received prior BRAFi/MEKi). 91% of pts were 2L+, while 74% were 3L+. 103 (92%) received prior PD-1 inhibitor, of which 87% also received prior ipilimumab. 43 pts received tebe + durva (Arm 1), 13 received tebe + treme (Arm 2), 29 received triplet therapy (Arm 3), and 27 received tebe alone (Arm 4). Maximum target doses of tebe (68 mcg) + durva (20 mg/kg) and treme (1 mg/kg) were tolerated. MTD was not formally identified for any arm. Two DLTs occurred: prolonged grade 3 rash (Arm 1) and grade 2 diarrhea leading to treatment delay (Arm 2). Related AEs that were Grade ≥3 or led to discontinuations were: 44%/0% (Arm 1), 23%/0% (Arm2), 38%/7% (Arm3), 26%/4% (Arm 4). There were no treatment-related deaths.In prior PD-1 pts, tumor shrinkage occurred in 36% and 1-yr OS was 68%. Of 51 evaluable PD-1 resistant pts (best response CR/PR/SD to prior PD1), tumor shrinkage occurred in 28% and 1-yr OS was 73% (figure 1). In 35 evaluable PD-1 refractory pts (prior best response PD), tumor shrinkage occurred in 49% and 1-yr OS was 61%. For 38 prior PD-1 pts who received ≥10mg/kg durva, 1-yr OS was 81%.Abstract 546 Figure 1% tumor change from baseline in evaluable patients with known response to prior PD1 exposureConclusionsTebe with anti-PD-L1 and/or anti-CTLA4 had an acceptable safety profile. Tebe + durva demonstrated durable tumor shrinkage and promising 1-yr OS rates in prior-PD1 treated mCM relative to recent reports.Trial RegistrationNCT02535078Ethics ApprovalThe institutional review board or independent ethics committee at each center approved the trial. The trial was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines

A measurement of the millimetre emission and the Sunyaev-Zel'dovich effect associated with low-frequency radio sources

We present a statistical analysis of the millimetre-wavelength properties of 1.4GHz-selected sources and a detection of the Sunyaev–Zel’dovich (SZ) effect associated with the haloes that host them. We stack data at 148, 218 and 277GHz from the Atacama Cosmology Telescope at the positions of a large sample of radio AGN selected at 1.4GHz. The thermal SZ effect associated with the haloes that host the AGN is detected at the 5σ level through its spectral signature, representing a statistical detection of the SZ effect in some of the lowest mass haloes (average M 200 ≈ 10 13 M. h −1 70 ) studied to date. The relation between the SZ effect and mass (based on weak lensing measurements of radio galaxies) is consistent with that measured by Planck for local bright galaxies. In the context of galaxy evolution models, this study confirms that galaxies with radio AGN also typically support hot gaseous haloes. Adding Herschel observations allows us to show that the SZ signal is not significantly contaminated by dust emission. Finally, we analyse the contribution of radio sources to the angular power spectrum of the cosmic microwave background

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma

Background: Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. Methods: In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. Results: A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported. Conclusions: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.). Copyright © 2021 Massachusetts Medical Society

Ancient DNA reveals interstadials as a driver of common vole population dynamics during the last glacial period

Aim Many species experienced population turnover and local extinction during the Late Pleistocene. In the case of megafauna, it remains challenging to disentangle climate change and the activities of Palaeolithic hunter-gatherers as the main cause. In contrast, the impact of humans on rodent populations is likely to be negligible. This study investigated which climatic and/or environmental factors affect the population dynamics of the common vole. This temperate rodent is widespread across Europe and was one of the most abundant small mammal species throughout the Late Pleistocene. Location Europe. Taxon Common vole (Microtus arvalis). Methods We generated a dataset comprised of 4.2 kb long fragment of mitochondrial DNA (mtDNA) from 148 ancient and 51 modern specimens sampled from multiple localities across Europe and covering the last 60 thousand years (ka). We used Bayesian inference to reconstruct their phylogenetic relationships and to estimate the age of the specimens that were not directly dated. Results We estimated the time to the most recent common ancestor of all last glacial and extant common vole lineages to be 90 ka ago and the divergence of the main mtDNA lineages present in extant populations to between 55 and 40 ka ago, which is earlier than most previous estimates. We detected several lineage turnovers in Europe during the period of high climate variability at the end of Marine Isotope Stage 3 (MIS 3; 57-29 ka ago) in addition to those found previously around the Pleistocene/Holocene transition. In contrast, data from the Western Carpathians suggest continuity throughout the Last Glacial Maximum (LGM) even at high latitudes. Main Conclusions The main factor affecting the common vole populations during the last glacial period was the decrease in open habitat during the interstadials, whereas climate deterioration during the LGM had little impact on population dynamics. This suggests that the rapid environmental change rather than other factors was the major force shaping the histories of the Late Pleistocene faunas.info:eu-repo/semantics/publishedVersio

Two-Component Elements Mediate Interactions between Cytokinin and Salicylic Acid in Plant Immunity

Recent studies have revealed an important role for hormones in plant immunity. We are now beginning to understand the contribution of crosstalk among different hormone signaling networks to the outcome of plant–pathogen interactions. Cytokinins are plant hormones that regulate development and responses to the environment. Cytokinin signaling involves a phosphorelay circuitry similar to two-component systems used by bacteria and fungi to perceive and react to various environmental stimuli. In this study, we asked whether cytokinin and components of cytokinin signaling contribute to plant immunity. We demonstrate that cytokinin levels in Arabidopsis are important in determining the amplitude of immune responses, ultimately influencing the outcome of plant–pathogen interactions. We show that high concentrations of cytokinin lead to increased defense responses to a virulent oomycete pathogen, through a process that is dependent on salicylic acid (SA) accumulation and activation of defense gene expression. Surprisingly, treatment with lower concentrations of cytokinin results in increased susceptibility. These functions for cytokinin in plant immunity require a host phosphorelay system and are mediated in part by type-A response regulators, which act as negative regulators of basal and pathogen-induced SA–dependent gene expression. Our results support a model in which cytokinin up-regulates plant immunity via an elevation of SA–dependent defense responses and in which SA in turn feedback-inhibits cytokinin signaling. The crosstalk between cytokinin and SA signaling networks may help plants fine-tune defense responses against pathogens

Power spectrum analysis of ionospheric fluctuations with the Murchison Widefield Array

Low-frequency, wide field-of-view (FOV) radio telescopes such as the Murchison Widefield Array (MWA) enable the ionosphere to be sampled at high spatial completeness. We present the results of the first power spectrum analysis of ionospheric fluctuations in MWA data, where we examined the position offsets of radio sources appearing in two data sets. The refractive shifts in the positions of celestial sources are proportional to spatial gradients in the electron column density transverse to the line of sight. These can be used to probe plasma structures and waves in the ionosphere. The regional (10–100 km) scales probed by the MWA, determined by the size of its FOV and the spatial density of radio sources (typically thousands in a single FOV), complement the global (100–1000 km) scales of GPS studies and local (0.01–1 km) scales of radar scattering measurements. Our data exhibit a range of complex structures and waves. Some fluctuations have the characteristics of traveling ionospheric disturbances, while others take the form of narrow, slowly drifting bands aligned along the Earth's magnetic field