Exploring cavities in Type II porous liquids with xenon

The porous topology of Type II Porous Liquids (PLs), prepared using Noria-OEt as an empty molecular host dissolved in 15-crown-5 solvent, is investigated with 129Xe NMR Spectroscopy. Xenon NMR parameters, such as chemical shifts and T1 relaxation times, measured in PLs solutions prepared at various Noria-OEt concentrations, are related to the intrinsic microporous structure of the material. The experimental data are interpreted on the basis of a multiple-site model for xenon atoms within the multiple PLs cavities. Diffusion NMR experiments show a similar mobility of xenon in PLs compared with the pure solvent.(c) 2022 Elsevier B.V. All rights reserved

The Great Lakes Hydrography Dataset: Consistent, Binational Watersheds for the Laurentian Great Lakes Basin

Ecosystem‐based management of the Laurentian Great Lakes, which spans both the United States and Canada, is hampered by the lack of consistent binational watersheds for the entire Basin. Using comparable data sources and consistent methods, we developed spatially equivalent watershed boundaries for the binational extent of the Basin to create the Great Lakes Hydrography Dataset (GLHD). The GLHD consists of 5,589 watersheds for the entire Basin, covering a total area of approximately 547,967 km2, or about twice the 247,003 km2 surface water area of the Great Lakes. The GLHD improves upon existing watershed efforts by delineating watersheds for the entire Basin using consistent methods; enhancing the precision of watershed delineation using recently developed flow direction grids that have been hydrologically enforced and vetted by provincial and federal water resource agencies; and increasing the accuracy of watershed boundaries by enforcing embayments, delineating watersheds on islands, and delineating watersheds for all tributaries draining to connecting channels. In addition, the GLHD is packaged in a publically available geodatabase that includes synthetic stream networks, reach catchments, watershed boundaries, a broad set of attribute data for each tributary, and metadata documenting methodology. The GLHD provides a common set of watersheds and associated hydrography data for the Basin that will enhance binational efforts to protect and restore the Great Lakes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134077/1/jawr12435_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134077/2/jawr12435.pd

Forum on immune digital twins: a meeting report

Medical digital twins are computational models of human biology relevant to a given medical condition, which can be tailored to an individual patient, thereby predicting the course of disease and individualized treatments, an important goal of personalized medicine. The immune system, which has a central role in many diseases, is highly heterogeneous between individuals, and thus poses a major challenge for this technology. If medical digital twins are to faithfully capture the characteristics of a patient's immune system, we need to answer many questions, such as: What do we need to know about the immune system to build mathematical models that reflect features of an individual? What data do we need to collect across the different scales of immune system action? What are the right modeling paradigms to properly capture immune system complexity? In February 2023, an international group of experts convened in Lake Nona, FL for two days to discuss these and other questions related to digital twins of the immune system. The group consisted of clinicians, immunologists, biologists, and mathematical modelers, representative of the interdisciplinary nature of medical digital twin development. A video recording of the entire event is available. This paper presents a synopsis of the discussions, brief descriptions of ongoing digital twin projects at different stages of progress. It also proposes a 5-year action plan for further developing this technology. The main recommendations are to identify and pursue a small number of promising use cases, to develop stimulation-specific assays of immune function in a clinical setting, and to develop a database of existing computational immune models, as well as advanced modeling technology and infrastructure

One moment, please: can the speed and quality of political contact affect democratic health

Contact between politicians and their constituents is the cornerstone of democracies globally but an area of scholarship that remains relatively underdeveloped. Political contact can help convey authority, provide legitimacy and facilitate governance. This article goes beyond the assumption that representatives need to communicate more with the public and suggests, instead, that the quality of contact matters. Focusing on four processes by which citizens can contact their representatives (face-to-face, by letter, email or social media), we employ an experimental vignette methodology to test whether the character and timeliness of politicians’ responses to citizen communication affects two indicators of democratic health: (a) the latter’s satisfaction with political contact and (b) their likelihood to re-contact representatives. Our findings provide evidence that personalised communication and to a smaller extent, speed of response, can influence citizen satisfaction and their likelihood of re-engagement. This suggests politicians can improve these indicators of democratic health by adjusting the style of political contact and communication

Randomized Trial of Letrozole Following Tamoxifen as Extended Adjuvant Therapy in Receptor-Positive Breast Cancer: Updated Findings from NCIC CTG MA.17

Background: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patient

Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer

Background Malignant melanoma is an aggressive tumor of the skin and seems to be resistant to current therapeutic approaches. Melanocytic transformation is thought to occur by sequential accumulation of genetic and molecular alterations able to activate the Ras/Raf/MEK/ERK (MAPK) and/or the PI3K/AKT (AKT) signalling pathways. Specifically, mutations of B-RAF activate MAPK pathway resulting in cell cycle progression and apoptosis prevention. According to these findings, MAPK and AKT pathways may represent promising therapeutic targets for an otherwise devastating disease. Result Here we show a computational model able to simulate the main biochemical and metabolic interactions in the PI3K/AKT and MAPK pathways potentially involved in melanoma development. Overall, this computational approach may accelerate the drug discovery process and encourages the identification of novel pathway activators with consequent development of novel antioncogenic compounds to overcome tumor cell resistance to conventional therapeutic agents. The source code of the various versions of the model are available as S1 Archive

Twisting in the Wind: Monumental Weathervanes in Classical Antiquity

Monumental weathervanes have been overlooked as a tiny but important genre of ancient bronze sculpture. This is the first collective study of all three definite examples: the so-called ‘triton’ on the Tower of the Winds in Athens, a copy of this somewhere in Rome, and the winged female ‘Anemodoulion’ on the Bronze Tetrapylon in Constantinople. I propose to identify the intended subjects of these sculptures as the weather-deities Aiolos and Iris, thereby restoring a part of each monument’s original meaning that was unknown to the authors of our ancient written accounts. I also suggest that monumental weathervanes were first invented in Hellenistic Alexandria, which may explain why the Tower of the Winds shared the octagonal design of the Pharos, and why the Anemodoulion was mounted upon a bronze pyramidion

Self-love and sociability: the ‘rudiments of commerce’ in the state of nature

Istvan Hont’s classic work on the theoretical links between the seventeenth-century natural jurists Hugo Grotius and Samuel Pufendorf and the eighteenth-century Scottish political economists remains a popular trope among intellectual and economic historians of various stamps. Despite this, a common criticism levelled at Hont remains his relative lack of engagement with the relationship between religion and economics in the early modern period. This paper challenges this aspect of Hont’s narrative by drawing attention to an alternative, albeit complementary, assessment of the natural jurisprudential heritage of eighteenth-century British political economy. Specifically, the article attempts to map on to Hont’s thesis the Christian Stoic interpretation of Grotius and Pufendorf which has gained greater currency in recent years. In doing so, the paper argues that Grotius and Pufendorf’s contributions to the ‘unsocial sociability’ debate do not necessarily lead directly to the Scottish school of political economists, as is commonly assumed. Instead, it contends that a reconsideration of Grotius and Pufendorf as neo-Stoic theorists, particularly via scrutiny of their respective adaptations of the traditional Stoic theory of oikeiosis, steers us towards the heart of the early English ‘clerical’ Enlightenment