The expansion of heterocyclic rings

Of the reactions in which pyrroles and indoles are reported to undergo ring expansion, the example investigated initially - the conversion of 2-carbamyl-2-cyano-dihydroindole to 3-carbamyl-2-hydroxyquinoline - proved to be incorrect. The supposed dihydroindole compound (a reduction product of alpha-cyano-o-nitrocinnamamide) was actually 2-amino-3-carbamylquinoline (Section A). The general reaction whereby pyrroles and indoles are converted by trihalomethanes/base to 2-pyrrole and 3-indole aldehydes, and 3-halopyridines and quinolines was next examined (Section B). Three instances of the isolation of a dichloromethyl pyrrolenine or indolenine and its subsequent conversion to a pyridine or quinoline are recorded in the literature. The dichloromethyl derivative had therefore been suggested to be an intermediate for both aldehyde formation and the ring expansion. From paper chromatographic experiments the ring expansion of 3-dichloromethyl-2:3-dimethylindolenine to 3-chloro-2:4-dimethylquinoline does not appear to occur.But a product whose picrate corresponds, by analysis, to that of 3-ethoxy-2:4-dimethylquinoline (and not to 2:3-dimethylindolenine-3-aldehyde or its diethyl acetal derivative) has been obtained from the action of sodiumethoxide on 3-dichloromethyl-2:3-dimethylindolenine. This suggests that the ring expansion does occur here, possibly by means of a labile intermediary, produced during solvolysis of the dichloromethyl group. A mechanism: has been suggested, and also one for the 'direct' conversion of pyrroles and indoles to pyridines and quinolines.A preliminary kinetic investigation of the reactionof sodium ethoxide on the dichloromethyl derivative was begun.Several 2-aminoquinolines and their N-oxides, and some 3-substituted2:4-dimethylquinolines were availablefrom the work recorded in Sections A and B. The spectra ofthe N-oxides in ethanol, and aqueous hydrochloric acid andsodium hydroxide, were measured (Section C). Spectra ofthe other derivatives were measured in the first twosolvents. As previously observed, the N-oxides show abathochromic effect in ethanol and alkali, but have thesame absorption as the corresponding quinolines in acid. The general characteristics of the 2:4-dimethylquinoline series conform with published results.<p

Position Measurements with Micro-Channel Plates and Transmission lines using Pico-second Timing and Waveform Analysis

The anodes of Micro-Channel Plate devices are coupled to fast transmission lines in order to reduce the number of electronics readout channels, and can provide two-dimension position measurements using two-ends delay timing. Tests with a laser and digital waveform analysis show that resolutions of a few hundreds of microns along the transmission line can be reached taking advantage of a few pico-second timing estimation. This technique is planned to be used in Micro-channel Plate devices integrating the transmission lines as anodes

Introducing v0.5 of the AI Safety Benchmark from MLCommons

This paper introduces v0.5 of the AI Safety Benchmark, which has been created by the MLCommons AI Safety Working Group. The AI Safety Benchmark has been designed to assess the safety risks of AI systems that use chat-tuned language models. We introduce a principled approach to specifying and constructing the benchmark, which for v0.5 covers only a single use case (an adult chatting to a general-purpose assistant in English), and a limited set of personas (i.e., typical users, malicious users, and vulnerable users). We created a new taxonomy of 13 hazard categories, of which 7 have tests in the v0.5 benchmark. We plan to release version 1.0 of the AI Safety Benchmark by the end of 2024. The v1.0 benchmark will provide meaningful insights into the safety of AI systems. However, the v0.5 benchmark should not be used to assess the safety of AI systems. We have sought to fully document the limitations, flaws, and challenges of v0.5. This release of v0.5 of the AI Safety Benchmark includes (1) a principled approach to specifying and constructing the benchmark, which comprises use cases, types of systems under test (SUTs), language and context, personas, tests, and test items; (2) a taxonomy of 13 hazard categories with definitions and subcategories; (3) tests for seven of the hazard categories, each comprising a unique set of test items, i.e., prompts. There are 43,090 test items in total, which we created with templates; (4) a grading system for AI systems against the benchmark; (5) an openly available platform, and downloadable tool, called ModelBench that can be used to evaluate the safety of AI systems on the benchmark; (6) an example evaluation report which benchmarks the performance of over a dozen openly available chat-tuned language models; (7) a test specification for the benchmark

Building a multi-scaled geospatial temporal ecology database from disparate data sources: fostering open science and data reuse

Although there are considerable site-based data for individual or groups of ecosystems, these datasets are widely scattered, have different data formats and conventions, and often have limited accessibility. At the broader scale, national datasets exist for a large number of geospatial features of land, water, and air that are needed to fully understand variation among these ecosystems. However, such datasets originate from different sources and have different spatial and temporal resolutions. By taking an open-science perspective and by combining site-based ecosystem datasets and national geospatial datasets, science gains the ability to ask important research questions related to grand environmental challenges that operate at broad scales. Documentation of such complicated database integration efforts, through peer-reviewed papers, is recommended to foster reproducibility and future use of the integrated database. Here, we describe the major steps, challenges, and considerations in building an integrated database of lake ecosystems, called LAGOS (LAke multi-scaled GeOSpatial and temporal database), that was developed at the sub-continental study extent of 17 US states (1,800,000 km² ). LAGOS includes two modules: LAGOS[subscript]GEO , with geospatial data on every lake with surface area larger than 4 ha in the study extent (~50,000 lakes), including climate, atmospheric deposition, land use/cover, hydrology, geology, and topography measured across a range of spatial and temporal extents; and LAGOS[subscript]LIMNO , with lake water quality data compiled from ~100 individual datasets for a subset of lakes in the study extent (~10,000 lakes). Procedures for the integration of datasets included: creating a flexible database design; authoring and integrating metadata; documenting data provenance; quantifying spatial measures of geographic data; quality-controlling integrated and derived data; and extensively documenting the database. Our procedures make a large, complex, and integrated database reproducible and extensible, allowing users to ask new research questions with the existing database or through the addition of new data. The largest challenge of this task was the heterogeneity of the data, formats, and metadata. Many steps of data integration need manual input from experts in diverse fields, requiring close collaboration.Keywords: LAGOS, Integrated database, Data harmonization, Database Ecoinformatics, Macrosystems ecology, Landscape limnology, Water qualityKeywords: LAGOS, Integrated database, Ecoinformatics, Data harmonization, Water quality, Data sharing, Landscape limnology, Macrosystems ecology, Database documentation, Data reus

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe