2,274 research outputs found
Synthesis, Conformation and Antiproliferative Activity of Isothiazoloisoxazole 1,1-dioxides
Sixteen new isothiazoloisoxazole 1,1-dioxides, one new isothiazolotriazole and one new isothiazolopyrazole have been synthesised by using 1,3-dipolar cycloadditions to isothiazole 1,1-dioxides. One sub-set of these isothiazoloisoxazoles showed low μM activity against a human breast carcinoma cell line, whilst a second sub-set plus the isothiazolotriazole demonstrated an interesting restricted rotation of sterically hindered bridgehead substituents. A thiazete 1,1-dioxide produced from one of the isothiazole 1,1-dioxides underwent conversion into an unknown 1,2,3-oxathiazolin-2-oxide upon treatment with Lewis acids, but was inert towards 1,3-dipoles and cyclopropenones. Six supporting crystal structures are included
Reply to Comment on: Hawking radiation from ultrashort laser pulse filaments
A comment by R. Schutzhold et al. raises possible concerns and questions
regarding recent measurements of analogue Hawking radiation. We briefly reply
to the opinions expressed in the comment and sustain that the origin of the
radiation may be understood in terms of Hawking emission
Herpes simplex virus type 1 and Alzheimer’s disease : link and potential impact on treatment
Introduction: Alzheimer\u2019s disease (AD), the most common form of dementia worldwide, is a multifactorial disease with a still unknown etiology. Herpes simplex virus 1 (HSV-1) has long been suspected to be one of the factors involved in the pathogenesis of the disease. Areas covered: We review the literature focusing on viral characteristics of HSV-1, the mechanisms this virus uses to infect neural cells, its interaction with the host immune system and genetic background and summarizes results and research that support the hypothesis of an association between AD and HSV-1. The possible usefulness of virus-directed pharmaceutical approaches as potential treatments for AD will be discussed as well. Expert opinion: We highlight crucial aspects that must be addressed to clarify the possible role of HSV-1 in the pathogenesis of the disease, and to allow the design of new therapeutical approaches for AD
Identification of the first enantiopure Rac1–Tiam1 protein–protein interaction inhibitor and its optimized synthesis via phosphine free remote group directed hydroarylation
A phospine free hydroarylation reaction applied to norbornene derivatives is described for the first time and was exploited for the regioselective gram scale synthesis of AR-148, a known Rac1\u2013Tiam1 PPI inhibitor. Umpolung conversion of the nitro group into free amine allowed the regiocontrol of the key arylation step via a long range effect. The effect of AR-148 in comparison with its enantiomers on Rac1 activation of has been evaluated and ( 12)AR-148 has been identified as the first enantiomerically pure inhibitor of Rac1\u2013Tiam1 PPI
Circulatory miR-223-3p Discriminates Between Parkinson’s and Alzheimer’s Patients
MiR-223-3p is involved in the regulation of a broad range of cellular processes and in many types of pathological processes as cancer, autoimmune and inflammatory diseases. MiR-223-3p has been indicated as negative regulator of NLRP3 protein, a key protein of inflammasome. The chronic inflammasome activation, an underlying feature of neurodegenerative disorders, is induced by misfolded protein aggregates, including amyloid-beta and alpha-synuclein, resulting in pro-inflammatory cytokines secretion and propagating of neuroinflammation. The aim of the study was to analyze whether circulatory miR-223-3p could be used as biomarker in neurodegeneration and to clarify its possible relationship with inflammasome activation. miR-223-3p concentration was evaluated in serum of Alzheimer\u2019s (AD) and Parkinson\u2019s disease (PD) or mild cognitive impairment (MCI) patients and healthy controls (HC). Compared to HC, miR-223-3p serum concentration was reduced in MCI and AD, but up-regulated in PD (p < 0.0001), and it decreased progressively from MCI to moderate (p < 0.0001) to severe AD (p = 0.0016). Receiver operating characteristic analysis showed that miR-223-3p concentration discriminates between AD, PD and MCI vs. HC, as well as between AD and PD. miR-223-3p serum concentration discriminates between AD/MCI and PD, suggesting that this molecule could be a potential non-invasive biomarker for differential diagnosis and prognosis of these neurodegenerative conditions
The Origin of Massive Compact Galaxies: Lessons from IllustrisTNG
We investigate the formation and evolution of z=0 massive compact galaxies
(MCGs) in the IllustrisTNG cosmological simulation. We found that, as in
observations, MCGs are mainly old (median age Gyr), have
super-solar metallicities (median ) and are
-enhanced (median ). The age distribution extends
to younger ages, however, and a few MCGs are as young as Gyr. In
general, MCGs assemble their mass early and accrete low angular momentum gas,
significantly increasing their mass while growing their size much slower. A
small fraction of MCGs follow another evolutionary path, going through a
compaction event, with their sizes shrinking by 40% or more. The accretion of
low angular momentum gas leads to enhanced SMBH growth, and MCGs reach the
threshold SMBH mass of - when kinetic
AGN feedback kicks in and quenches the galaxy - earlier than non-compact
galaxies. Comparing MCGs to a sample of median-sized quiescent galaxies matched
in effective velocity dispersion, we find that their accretion histories are
very different. 71% of MCGs do not merge after quenching compared to 37% of
median-sized quiescent galaxies. Moreover, tracing these populations back in
time, we find that at least a third of median-sized quiescent galaxies do not
have a compact progenitor, underscoring that both dry mergers and progenitor
bias effects are responsible for the differences in the kinematics and stellar
population properties of MCGs and median-sized quiescent galaxies.Comment: 15 pages, 15 figures (not including appendices). Accepted for
publication in the Monthly Notices of the Royal Astronomical Societ
Palladium-catalyzed domino carbopalladation/5-exo-allylic amination of \u3b1-amino allenamides: an efficient entry to enantiopure imidazolidinones
Allenamides of alpha-amino acids were converted into enantiopure 2-vinylimidazolidin-4-ones by a carbopalladation/exo-cyclization process. The products were obtained in 2.5:1-5.5:1 dr, with 94-99% ee. The palladium-catalyzed carbonylative cyclization of the same substrates afforded enone structures. Starting from properly substituted allenamides, an intramolecular carbopalladation followed by intramolecular amination gave rise to tricyclic fused-ring imidazolidinones
Screening for carriage of carbapenem-resistant Enterobacteriaceae in settings of high endemicity: A position paper from an Italian working group on CRE infections
A variety of national and international guidelines exist around the management of carbapenem resistant Enterobacteriaceae (CREs), but some of these are several years old and do not reflect current epidemiology and they also do not necessarily give pragmatic advice around active surveillance of CREs in countries with a high burden of cases and limited resources. This paper aims to provide a best practice position paper to guide active surveillance in a variety of scenarios in these settings, and discusses which patients should be screened, what methods could be used for screening, and how results might influence infection prevention interventions
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