Mesoproterozoic intraplate magmatic ‘barcode’ record of the Angola portion of the Congo Craton: Newly dated magmatic events at 1505 and 1110 Ma and implications for Nuna (Columbia) supercontinent reconstructions

In the Angola portion of the Congo Craton, the only Proterozoic large igneous province (LIP) dated prior to this study was the 1380–1370 Ma (Kunene Intrusive Complex and related units). U–Pb TIMS ages on baddeleyite from dolerite sills and gabbro-noritic dykes, has revealed two additional Mesoproterozoic intraplate events: at ca. 1505 and ca. 1110 Ma, that are each proposed to be part of the plumbing system for LIPs. The identification of these three Mesoproterozoic magmatic events (ca. 1505, 1380, and 1110 Ma) represent an initial magmatic ‘barcode’ for this portion of Congo Craton (and formerly connected São Francisco Craton), which can be compared with the magmatic ‘barcode’ record of other blocks to identify former nearest neighbors in the Precambrian supercontinent Nuna (also known as Columbia).Specifically, a 1502 ± 5 Ma U–Pb TIMS baddeleyite age has been obtained for the prominent Humpata dolerite sill which is part of a wider sill province in SW Angola portion of the Congo Craton. The combined presence of both 1505 Ma and 1380 Ma magmatism in the Congo–São Francisco reconstructed craton is a match with similar ages published for two intraplate magmatic provinces in northern Siberia and suggests a nearest-neighbor relationship in the supercontinent Nuna in which northern Siberia is juxtaposed adjacent to the western São Francisco portion of the reconstructed São Francisco–Congo Craton.In addition, a precise U–Pb TIMS baddeleyite age of 1110 ± 2.5 Ma was obtained for a prominent NNW–NNE trending gabbro-noritic (GN) dyke swarm in southeastern Angola, but this age is currently unknown in Siberia suggesting that the breakup of Congo–São Francisco Craton from Siberia happened earlier, perhaps in association with the 1380 Ma event. This 1110 Ma age is however, a precise match with that of the Umkondo large igneous province (LIP) of the Kalahari Craton, and also with mafic intraplate magmatism on other blocks such as the Bundelkhand Craton (India) and the Amazonian Craton. We provisionally consider these three cratons to have been nearest neighbors to the Congo–São Francisco Craton at this time and to have shared this 1110 Ma magmatic event as a LIP node. There is also an age match with the early part of the Keweenawan event (in the interior of the Laurentia); however, on previously discussed paleomagnetic grounds the Keweenawan event is likely to have been distant and unrelated (and on the other side of the Grenville orogen)

Nitroheterocyclic drugs cure experimental <i>Trypanosoma cruzi</i> infections more effectively in the chronic stage than in the acute stage

The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5-8 million people in Latin America. Chagas disease is characterised by an acute phase, which is partially resolved by the immune system, but then develops as a chronic life-long infection. There is a consensus that the front-line drugs benznidazole and nifurtimox are more effective against the acute stage in both clinical and experimental settings. However, confirmative studies have been restricted by difficulties in demonstrating sterile parasitological cure. Here, we describe a systematic study of nitroheterocyclic drug efficacy using highly sensitive bioluminescence imaging of murine infections. Unexpectedly, we find both drugs are more effective at curing chronic infections, judged by treatment duration and therapeutic dose. This was not associated with factors that differentially influence plasma drug concentrations in the two disease stages. We also observed that fexinidazole and fexinidazole sulfone are more effective than benznidazole and nifurtimox as curative treatments, particularly for acute stage infections, most likely as a result of the higher and more prolonged exposure of the sulfone derivative. If these findings are translatable to human patients, they will have important implications for treatment strategies

In Vitro and In Vivo High-Throughput Assays for the Testing of Anti-Trypanosoma cruzi Compounds

The treatment of Trypanosoma cruzi infection (the cause of human Chagas disease) remains a significant challenge. Only two drugs, both with substantial toxicity, are available and the efficacy of these dugs is often questioned – in many cases due to the limitations of the methods for assessing efficacy rather than to true lack of efficacy. For these reasons relatively few individuals infected with T. cruzi actually have their infections treated. In this study, we report on innovative methods that will facilitate the discovery of new compounds for the treatment of T. cruzi infection and Chagas disease. Utilizing fluorescent and bioluminescent parasite lines, we have developed in vitro tests that are reproducible and facile and can be scaled for high-throughput screening of large compound libraries. We also validate an in vivo screening test that monitors parasite replication at the site of infection and determines the effectiveness of drug treatment in less than two weeks. More importantly, results in this rapid in vivo test show strong correlations with those obtained in long-term (e.g. 40 day or more) treatment assays. The results of this study remove one of the obstacles for identification of effective and safe compounds to treat Chagas disease

14 Examples of How LLMs Can Transform Materials Science and Chemistry: A Reflection on a Large Language Model Hackathon

Chemistry and materials science are complex. Recently, there have been great successes in addressing this complexity using data-driven or computational techniques. Yet, the necessity of input structured in very specific forms and the fact that there is an ever-growing number of tools creates usability and accessibility challenges. Coupled with the reality that much data in these disciplines is unstructured, the effectiveness of these tools is limited. Motivated by recent works that indicated that large language models (LLMs) might help address some of these issues, we organized a hackathon event on the applications of LLMs in chemistry, materials science, and beyond. This article chronicles the projects built as part of this hackathon. Participants employed LLMs for various applications, including predicting properties of molecules and materials, designing novel interfaces for tools, extracting knowledge from unstructured data, and developing new educational applications. The diverse topics and the fact that working prototypes could be generated in less than two days highlight that LLMs will profoundly impact the future of our fields. The rich collection of ideas and projects also indicates that the applications of LLMs are not limited to materials science and chemistry but offer potential benefits to a wide range of scientific disciplines

Computational Identification of Uncharacterized Cruzain Binding Sites

Chagas disease, caused by the unicellular parasite Trypanosoma cruzi, claims 50,000 lives annually and is the leading cause of infectious myocarditis in the world. As current antichagastic therapies like nifurtimox and benznidazole are highly toxic, ineffective at parasite eradication, and subject to increasing resistance, novel therapeutics are urgently needed. Cruzain, the major cysteine protease of Trypanosoma cruzi, is one attractive drug target. In the current work, molecular dynamics simulations and a sequence alignment of a non-redundant, unbiased set of peptidase C1 family members are used to identify uncharacterized cruzain binding sites. The two sites identified may serve as targets for future pharmacological intervention

A biometric study on the relationships between the deep palmar arch and the superficial palmar arch, the distal wirst and palmar creases

The topographical localisation of the palmar arches is important in hand surgery.The aim of this study was to contribute with biometric data on their positions and to correlate this with the size of the palm. We studied 60 hands of 30 adult fixed cadavers of Brazilian origin, from both sexes and between the ages of 2l and 70 years. The arteries of 54 hands were injected with latex Neoprene. Before dissection the distance between distal wrist crease (DWC) and the proximal palmar digital crease of the middle finger (PDMC) was measured. Also, we recorded the distance between the DWC and the proximal and distal palmar creases (PPC, DPC). After dissecting the superficial palmar region, the distance between the superficial palmar arch (SPA) and the DWC was recorder. We then dissected the deep palmar arch (DPA). The average distance between the DPA and DWC was always measured in the midline of the palm. The average distance DWC-DPA was 33,7 &plusmn; 2.6 mm in the female and 36 &plusmn; 4,0 mm in the male. The difference was statistically significant. The average distance between DPA and the PPC was 24,2 &plusmn; 3.0 mm in the female and 27,1 &plusmn; 4,1 mm in the male; this difference was significant. In 83% of cases the DPA was proximal to the SPA and in l4,9% was distal to it. The linear regression test for the relation between DWC-PDMC and DWC-DPA was significant in the male and this fact allowed us to obtain the linear equation to predict the distance DWC-DPA. Other parameters were also considered. The results may be useful as a reference to radiologists as well as to surgeons

Identifying resort tourism market segments based on visitor demographics: a study

Abstract This paper reports the findings of a study conducted in Goa, India, with the objective of segmenting resort visitors based on demographics. Four distinguishable segments are identified: relaxing regulars, tasters, honeymooners and exploring novices. Noticeably, these segments also provide vital insights into resort tourist motivation. Differences among the segments are identified and recommendations for resort marketing are provided