Closed Aromatic Tubes-Capsularenes

In this study, we describe a synthetic method for incorporating arenes into closed tubes that we name capsularenes. First, we prepared vase-shaped molecular baskets 4–7. The baskets comprise a benzene base fused to three bicycle[2.2.1]heptane rings that extend into phthalimide (4), naphthalimide (6), and anthraceneimide sides (7), each carrying a dimethoxyethane acetal group. In the presence of catalytic trifluoroacetic acid (TFA), the acetals at top of 4, 6 and 7 change into aliphatic aldehydes followed by their intramolecular cyclization into 1,3,5-trioxane (1H NMR spectroscopy). Such ring closure is nearly a quantitative process that furnishes differently sized capsularenes 1 (0.7×0.9 nm), 8 (0.7×1.1 nm;) and 9 (0.7×1.4 nm;) characterized by X-Ray crystallography, microcrystal electron diffraction, UV/Vis, fluorescence, cyclic voltammetry, and thermogravimetry. With exceptional rigidity, unique topology, great thermal stability, and perhaps tuneable optoelectronic characteristics, capsularenes hold promise for the construction of novel organic electronic devices

Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems

We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12]6−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line-shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex [MTO⊂1]− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets

Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems

We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12]6−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line-shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex [MTO⊂1]− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets

VERITAS: Status and Highlights

The VERITAS telescope array has been operating smoothly since 2007, and has detected gamma-ray emission above 100 GeV from 40 astrophysical sources. These include blazars, pulsar wind nebulae, supernova remnants, gamma-ray binary systems, a starburst galaxy, a radio galaxy, the Crab pulsar, and gamma-ray sources whose origin remains unidentified. In 2009, the array was reconfigured, greatly improving the sensitivity. We summarize the current status of the observatory, describe some of the scientific highlights since 2009, and outline plans for the future.Comment: Presented at the 32nd ICRC, Beijing, 201

Pengaruh Pemberian Ketotifen terhadap Jumlah Sel Fibroblas dan Kepadatan Sel Kolagen pada Luka Insisi Tikus Wistar

Ingga Hadian, S-501202027. PENGARUH PEMBERIAN KETOTIFEN TERHADAP JUMLAH SEL FIBROBLAS DAN KEPADATAN SEL KOLAGEN PADA LUKA INSISI TIKUS WISTAR. Pembimbing I : DR. Untung Alfianto, dr, Sp.Bs, Pembimbing II : dr. Ardana Tri Arianto. Msi. Med. Sp.An-KNA. Program studi Magister Kedokteran Keluarga, Minat Utama Ilmu Biomedik, Fakultas Kedokteran Universitas Sebelas Maret, Surakarta, 2016. Latar Belakang : Sel mast merupakan salah satu yang berperan dalam proses inflamasi pada penyembuhan luka. Sel mast dikaitkan dengan kejadian luka kronis, sehingga sel mast diduga ikut memelihara proses inflamasi secara berlebihan. Hambatan pada degranulasi sel mast diharapkan akan mempercepat penyembuhan luka yang ditandai dengan meningkatnya jumlah sel fibroblas dan kepadatan sel kolagen. Ketotifen mampu mengurangi dreganulasi sel Mast dan mengurangi pelepasan Histamin, protease sel Mast, myeloperoxidase, leukotriens, PAF dan bermacam-macam Prostaglandin. Ketotifen juga menghambat agregasi polimorfonuklear serta mengurangi respon inflamasi dan mempercepat migrasi fibroblas di fase proliferasi. Tujuan :Mengetahui perbedaan jumlah sel fibroblas dan kepadatan sel kolagen pada tikus wistar yang diberikan Ketotifen oral dosis 0.3 mg/kg dibandingkan plasebo pada penyembuhan luka insisi tikus wistar. Metode : Penelitian ini termasuk true eksperimental laboratorik dengan desain Randomized Controlled Trial yang menggunakan tikus wistar sebagai obyek penelitian. 14 tikus Wistar dibagi dalam 2 kelompok, masing masing kelompok terdiri atas 7 tikus Wistar. Kelompok 1 merupakan kelompok kontrol yang dilakukan insisi sepanjang 2cm pada kulit punggung tikus dan diberikan plasebo per oral selama 6 hari. Kelompok 2 merupakan kelompok perlakuan yang dilakukan insisi sepanjang 2cm pada kulit punggung tikus dan diberikan Ketotifen 0,3 mg/kgBB per oral setiap 12 jam selama 6 hari. Analisis data untuk membandingkan rerata antar kedua kelompok yaitu kelompok perlakuan dan kelompok kontrol menggunakan uji independent samples t-test, dengan tingkat kemaknaan p < 0,05 (dikatakan bermakna secara statistik). Hasil : Pada kelompok kontrol didapatkan rerata persentase kepadatan sel kolagen sebesar 26,05 %, sedangkan pada kelompok Ketotifen didapatkan rerata persentase kepadatan sel kolagen sebesar 36,13 %. Untuk jumlah sel fibroblas pada kelompok kontrol didapatkan rerata sebesar 423 per lapang pandang, sedangkan pada kelompok Ketotifen didapatkan rerata sebesar 555,43 per lapang pandang. Kesimpulan : Ketotifen mempercepat penyembuhan luka ditandai dengan peningkatan sel fibroblas dan sel kolagen. Kata Kunci : Sel Mast, Ketotifen, Sel fibroblas, Serabut Kolagen. ABSTRACT Ingga Hadian, S-501202027. EFFECTS OF KETOTIFEN ON FIBROBLAST CELL COUNT AND COLLAGEN DENSITY ON INCISED WISTAR RATS. DR. Untung Alfianto, dr., Sp.BS, dr. Ardana Tri Arianto, Msi, Med, Sp.An-KNA. Background: Mast cells have a pivotal role in every healing process that involves inflammation of the cells, usually in wounds of chronic nature. If the degranulation process of the mast cells are inhibited, the healing process of the wound will accelerate, indicated by a raise in fibroblast cells and collagen density. Ketotifen are shown to inhibit the degranulation process and decreasing the release of histamin, mast cells proteases, myeloperoxidases, leukotriens, PAF, and various prostaglandins. Ketotifen can also inhibit the aggregation of polymorphonuclear cells, increasing the rate of fibroblast migration in the proliferation phase. This study was aimed to identify the effects of ketotifen on fibroblast cell count and collagen density tested on a wistar rats model. Methods: This study was a true laboratoric experimental study with randomized controlled trial using wistar rats model as objects. 14 rats were divided into two groups, each group contained seven rats. The first group was the control group, where the rats were incised 2 cm above the back skin, and were given per oral placebo for 6 days. The second group were given the same treatment, only the rats were given ketotifen 0.3 mg/kg per oral, every 12 hours lasting 6 days. The data were then collected and tested with independent sample t-test, with p value less than 0,05 is statistically significant. Results: In the control group, the mean percentage of the thickest collagen density were marked at 26.05%, whereas in the treatment group collagen density were marked at 36.13%. The mean fibroblast cell count were marked at 423 and 555.43 each viewing field, on the control group and the treatment group respectively. Conclusion: Ketotifen can accelerate the healing process, marked by the significant increase in collagen density and fibroblast cell count. Keywords: mast cells, ketotifen, fibroblast cells, collagen fibers

Behavioral responses of terrestrial mammals to COVID-19 lockdowns

DATA AND MATERIALS AVAILABILITY : The full dataset used in the final analyses (33) and associated code (34) are available at Dryad. A subset of the spatial coordinate datasets is available at Zenodo (35). Certain datasets of spatial coordinates will be available only through requests made to the authors due to conservation and Indigenous sovereignty concerns (see table S1 for more information on data use restrictions and contact information for data requests). These sensitive data will be made available upon request to qualified researchers for research purposes, provided that the data use will not threaten the study populations, such as by distribution or publication of the coordinates or detailed maps. Some datasets, such as those overseen by government agencies, have additional legal restrictions on data sharing, and researchers may need to formally apply for data access. Collaborations with data holders are generally encouraged, and in cases where data are held by Indigenous groups or institutions from regions that are under-represented in the global science community, collaboration may be required to ensure inclusion.COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals’ 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.The Radboud Excellence Initiative, the German Federal Ministry of Education and Research, the National Science Foundation, Serbian Ministry of Education, Science and Technological Development, Dutch Research Council NWO program “Advanced Instrumentation for Wildlife Protection”, Fondation Segré, RZSS, IPE, Greensboro Science Center, Houston Zoo, Jacksonville Zoo and Gardens, Nashville Zoo, Naples Zoo, Reid Park Zoo, Miller Park, WWF, ZCOG, Zoo Miami, Zoo Miami Foundation, Beauval Nature, Greenville Zoo, Riverbanks zoo and garden, SAC Zoo, La Passarelle Conservation, Parc Animalier d’Auvergne, Disney Conservation Fund, Fresno Chaffee zoo, Play for nature, North Florida Wildlife Center, Abilene Zoo, a Liber Ero Fellowship, the Fish and Wildlife Compensation Program, Habitat Conservation Trust Foundation, Teck Coal, and the Grand Teton Association. The collection of Norwegian moose data was funded by the Norwegian Environment Agency, the German Ministry of Education and Research via the SPACES II project ORYCS, the Wyoming Game and Fish Department, Wyoming Game and Fish Commission, Bureau of Land Management, Muley Fanatic Foundation (including Southwest, Kemmerer, Upper Green, and Blue Ridge Chapters), Boone and Crockett Club, Wyoming Wildlife and Natural Resources Trust, Knobloch Family Foundation, Wyoming Animal Damage Management Board, Wyoming Governor’s Big Game License Coalition, Bowhunters of Wyoming, Wyoming Outfitters and Guides Association, Pope and Young Club, US Forest Service, US Fish and Wildlife Service, the Rocky Mountain Elk Foundation, Wyoming Wild Sheep Foundation, Wild Sheep Foundation, Wyoming Wildlife/Livestock Disease Research Partnership, the US National Science Foundation [IOS-1656642 and IOS-1656527, the Spanish Ministry of Economy, Industry and Competitiveness, and by a GRUPIN research grant from the Regional Government of Asturias, Sigrid Rausing Trust, Batubay Özkan, Barbara Watkins, NSERC Discovery Grant, the Federal Aid in Wildlife Restoration act under Pittman-Robertson project, the State University of New York, College of Environmental Science and Forestry, the Ministry of Education, Youth and Sport of the Czech Republic, the Ministry of Agriculture of the Czech Republic, Rufford Foundation, an American Society of Mammalogists African Graduate Student Research Fund, the German Science Foundation, the Israeli Science Foundation, the BSF-NSF, the Ministry of Agriculture, Forestry and Food and Slovenian Research Agency (CRP V1-1626), the Aage V. Jensen Naturfond (project: Kronvildt - viden, værdier og værktøjer), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy, National Centre for Research and Development in Poland, the Slovenian Research Agency, the David Shepherd Wildlife Foundation, Disney Conservation Fund, Whitley Fund for Nature, Acton Family Giving, Zoo Basel, Columbus, Bioparc de Doué-la-Fontaine, Zoo Dresden, Zoo Idaho, Kolmården Zoo, Korkeasaari Zoo, La Passarelle, Zoo New England, Tierpark Berlin, Tulsa Zoo, the Ministry of Environment and Tourism, Government of Mongolia, the Mongolian Academy of Sciences, the Federal Aid in Wildlife Restoration act and the Illinois Department of Natural Resources, the National Science Foundation, Parks Canada, Natural Sciences and Engineering Research Council, Alberta Environment and Parks, Rocky Mountain Elk Foundation, Safari Club International and Alberta Conservation Association, the Consejo Nacional de Ciencias y Tecnología (CONACYT) of Paraguay, the Norwegian Environment Agency and the Swedish Environmental Protection Agency, EU funded Interreg SI-HR 410 Carnivora Dinarica project, Paklenica and Plitvice Lakes National Parks, UK Wolf Conservation Trust, EURONATUR and Bernd Thies Foundation, the Messerli Foundation in Switzerland and WWF Germany, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions, NASA Ecological Forecasting Program, the Ecotone Telemetry company, the French National Research Agency, LANDTHIRST, grant REPOS awarded by the i-Site MUSE thanks to the “Investissements d’avenir” program, the ANR Mov-It project, the USDA Hatch Act Formula Funding, the Fondation Segre and North American and European Zoos listed at http://www.giantanteater.org/, the Utah Division of Wildlife Resources, the Yellowstone Forever and the National Park Service, Missouri Department of Conservation, Federal Aid in Wildlife Restoration Grant, and State University of New York, various donors to the Botswana Predator Conservation Program, data from collared caribou in the Northwest Territories were made available through funds from the Department of Environment and Natural Resources, Government of the Northwest Territories. The European Research Council Horizon2020, the British Ecological Society, the Paul Jones Family Trust, and the Lord Kelvin Adam Smith fund, the Tanzania Wildlife Research Institute and Tanzania National Parks. The Eastern Shoshone and Northern Arapahoe Fish and Game Department and the Wyoming State Veterinary Laboratory, the Alaska Department of Fish and Game, Kodiak Brown Bear Trust, Rocky Mountain Elk Foundation, Koniag Native Corporation, Old Harbor Native Corporation, Afognak Native Corporation, Ouzinkie Native Corporation, Natives of Kodiak Native Corporation and the State University of New York, College of Environmental Science and Forestry, and the Slovenia Hunters Association and Slovenia Forest Service. F.C. was partly supported by the Resident Visiting Researcher Fellowship, IMéRA/Aix-Marseille Université, Marseille. This work was partially funded by the Center of Advanced Systems Understanding (CASUS), which is financed by Germany’s Federal Ministry of Education and Research (BMBF) and by the Saxon Ministry for Science, Culture and Tourism (SMWK) with tax funds on the basis of the budget approved by the Saxon State Parliament. This article is a contribution of the COVID-19 Bio-Logging Initiative, which is funded in part by the Gordon and Betty Moore Foundation (GBMF9881) and the National Geographic Society.https://www.science.org/journal/sciencehj2023Mammal Research InstituteZoology and Entomolog

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)