Recent advances regarding the synthetic chemistry of fluorinated aziridines, azetidines, pyrrolidines and their lactam/amino acid counterparts are presented. These heterocycles are of high importance ...both as building blocks for more complex structures and as active parts of medicinal chemistry-oriented compounds.
The synthetic methodologies and the potential biological targets of α-trifluoromethylated nitrogen heterocycles are presented.
Objective
Neutrophil extracellular traps (NETs) have been shown to promote thrombus formation. Little is known about the exact composition of thrombi that cause ischemic stroke. In particular, no ...information is yet available on the presence of NETs in cerebral occlusions. Such information is, however, essential to improve current thrombolytic therapy with tissue plasminogen activator (t‐PA). This study aimed at investigating the presence of neutrophils and more specifically NETs in ischemic stroke thrombi.
Methods
Sixty‐eight thrombi retrieved from ischemic stroke patients undergoing endovascular treatment were characterized by immunostaining using neutrophil markers (CD66b and neutrophil elastase) and NET markers (citrullinated histone H3 H3Cit and extracellular DNA). Neutrophils and NETs were quantified. In addition, extracellular DNA was targeted by performing ex vivo lysis of retrieved thrombi with DNase 1 and t‐PA.
Results
Neutrophils were detected extensively throughout all thrombi. H3Cit, a hallmark of NETs, was observed in almost all thrombi. H3Cit‐positive area varied up to 13.45% of total thrombus area. Colocalization of H3Cit with extracellular DNA released from neutrophils confirmed the specific presence of NETs. H3Cit was more abundant in thrombi of cardioembolic origin compared to other etiologies. Older thrombi contained significantly more neutrophils and H3Cit compared to fresh thrombi. Interestingly, ex vivo lysis of patient thrombi was more successful when adding DNase 1 to standard t‐PA.
Interpretation
Neutrophils and NETs form important constituents of cerebral thrombi. Targeting of NETs with DNase 1 might have prothrombolytic potential in treatment of acute ischemic stroke. Ann Neurol 2017;82:223–232
The ability of light to carry and deliver orbital angular momentum (OAM) in the form of optical vortices has attracted much interest. The physical properties of light with a helical wavefront can be ...confined onto two-dimensional surfaces with subwavelength dimensions in the form of plasmonic vortices, opening avenues for thus far unknown light-matter interactions. Because of their extreme rotational velocity, the ultrafast dynamics of such vortices remained unexplored. Here we show the detailed spatiotemporal evolution of nanovortices using time-resolved two-photon photoemission electron microscopy. We observe both long- and short-range plasmonic vortices confined to deep subwavelength dimensions on the scale of 100 nanometers with nanometer spatial resolution and subfemtosecond time-step resolution. Finally, by measuring the angular velocity of the vortex, we directly extract the OAM magnitude of light.
Pharmaceuticals and personal care products (PPCPs) garner increasing attention globally for both their usefulness as indicators of human waste and their potency as emerging organic toxicants. Three ...decades of rapid increase in PPCP study combined with an increasing number of PPCPs on the global market have created an opportunity (1) to review trends in diversity of compounds, sewage treatment techniques (STTs), and ecosystems investigated as well as (2) to identify knowledge gaps in the literature. We conducted a quantitative evidence synthesis of 6517 abstracts from primary articles in the environmental PPCP literature by examining relative abundance of specific PPCP classes, STTs, and ecosystem types. Our results demonstrate that non-prescription drugs and antibiotics dominated PPCP abstracts, appearing in 51% and 39% of reviewed abstracts, respectively, in comparison to hormones (18%), prescription drugs (18%), fragrances (0.3%), and antioxidants (0.0%), which can all elicit physiological and ecological responses even at low concentrations. References to centralized STTs (e.g., activated sludge, 37%) were more frequent than decentralized STTs (e.g., septic, 2%), despite decentralized STTs being common and frequently high impact sources of sewage pollution worldwide. Freshwater lotic systems (63%) were more prevalent than freshwater lentic (24%) and terrestrial (20%) systems. This discrepancy is notable because the longer residence times of lentic and terrestrial systems may enable PPCPs to concentrate and thus increase risk of biological consequences. These results highlight distinct opportunities to address knowledge gaps in the environmental PPCP literature, including underrepresented compounds (e.g., fragrances), sewage treatment techniques (e.g., septic systems), and ecosystem types (e.g., lakes).
Ischemic stroke is caused by a thromboembolic occlusion of cerebral arteries. Treatment is focused on fast and efficient removal of the occluding thrombus, either
intravenous thrombolysis or
...endovascular thrombectomy. Recanalization, however, is not always successful and factors contributing to failure are not completely understood. Although the occluding thrombus is the primary target of acute treatment, little is known about its internal organization and composition. The aim of this study, therefore, was to better understand the internal organization of ischemic stroke thrombi on a molecular and cellular level. A total of 188 thrombi were collected from endovascularly treated ischemic stroke patients and analyzed histologically for fibrin, red blood cells (RBC), von Willebrand factor (vWF), platelets, leukocytes and DNA, using bright field and fluorescence microscopy. Our results show that stroke thrombi are composed of two main types of areas: RBC-rich areas and platelet-rich areas. RBC-rich areas have limited complexity as they consist of RBC that are entangled in a meshwork of thin fibrin. In contrast, platelet-rich areas are characterized by dense fibrin structures aligned with vWF and abundant amounts of leukocytes and DNA that accumulate around and in these platelet-rich areas. These findings are important to better understand why platelet-rich thrombi are resistant to thrombolysis and difficult to retrieve
thrombectomy, and can guide further improvements of acute ischemic stroke therapy.
The goal of this paper is the construction of measures μ on ℝⁿ enjoying three conflicting but fortunately compatible properties: (i) μ is a sum of weighted Dirac masses on a locally finite set, (ii) ...the Fourier transform μ̂ of μ is also a sum of weighted Dirac masses on a locally finite set, and (iii) μ is not a generalized Dirac comb. We give surprisingly simple examples of such measures. These unexpected patterns strongly differ from quasicrystals, they provide us with unusual Poisson’s formulas, and they might give us an unconventional insight into aperiodic order.
Zika virus has acquired worldwide concern after a recent outbreak in Latin America that started in Brazil, with associated neurological conditions such as microcephaly in newborns from infected ...mothers. The virus is transmitted mainly by
Aedes aegypti
mosquitoes, but direct (sexual) transmission has been documented. We formulate a reaction diffusion model that considers spatial movement of humans and vectors, with local contact transmission of Zika virus. Vaccination is introduced as a control variable, giving immunity to susceptible humans, in order to characterize an optimal vaccination strategy that minimizes the costs associated with infections and vaccines. The optimal control characterization is obtained in terms of state and adjoint equations. Parameter estimation and numerical simulations are carried out using data for the initial 2015 Zika outbreak in the state of Rio Grande do Norte in Brazil. Several scenarios are considered and analyzed in terms of number of new infections and costs, showing that the optimal control application is successful, significantly reducing these quantities.
Random community genomes (metagenomes) are now commonly used to study microbes in different environments. Over the past few years, the major challenge associated with metagenomics shifted from ...generating to analyzing sequences. High-throughput, low-cost next-generation sequencing has provided access to metagenomics to a wide range of researchers.
A high-throughput pipeline has been constructed to provide high-performance computing to all researchers interested in using metagenomics. The pipeline produces automated functional assignments of sequences in the metagenome by comparing both protein and nucleotide databases. Phylogenetic and functional summaries of the metagenomes are generated, and tools for comparative metagenomics are incorporated into the standard views. User access is controlled to ensure data privacy, but the collaborative environment underpinning the service provides a framework for sharing datasets between multiple users. In the metagenomics RAST, all users retain full control of their data, and everything is available for download in a variety of formats.
The open-source metagenomics RAST service provides a new paradigm for the annotation and analysis of metagenomes. With built-in support for multiple data sources and a back end that houses abstract data types, the metagenomics RAST is stable, extensible, and freely available to all researchers. This service has removed one of the primary bottlenecks in metagenome sequence analysis - the availability of high-performance computing for annotating the data. http://metagenomics.nmpdr.org.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This review describes the recent advances made in difluoromethylation processes based on X-CF
2
H bond formation where X is C(sp), C(sp
2
), C(sp
3
), O, N or S, a field of research that has ...benefited from the invention of multiple difluoromethylation reagents. The last decade has witnessed an upsurge of metal-based methods that can transfer CF
2
H to C(sp
2
) sites both in stoichiometric and catalytic mode. Difluoromethylation of C(sp
2
)-H bond has also been accomplished through Minisci-type radical chemistry, a strategy best applied to heteroaromatics. Examples of electrophilic, nucleophilic, radical and cross-coupling methods have appeared to construct C(sp
3
)-CF
2
H bonds, but cases of stereoselective difluoromethylation are still limited. In this sub-field, an exciting departure is the precise site-selective installation of CF
2
H onto large biomolecules such as proteins. The formation of X-CF
2
H bond where X is oxygen, nitrogen or sulfur is conventionally achieved upon reaction with ClCF
2
H; more recently, numerous protocols have achieved X-H insertion with novel non-ozone depleting difluorocarbene reagents. All together, these advances have streamlined access to molecules of pharmaceutical relevance, and generated interest for process chemistry.
This review describes the conceptual advances that have led to the multiple difluoromethylation processes making use of well-defined CF
2
H sources.
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