Nonconjugated hydrocarbons, like bicyclo1.1.1pentane, bicyclo2.2.2octane, triptycene, and cubane are a unique class of rigid linkers. Due to their similarity in size and shape they are useful mimics ...of classic benzene moieties in drugs, so‐called bioisosteres. Moreover, they also fulfill an important role in material sciences as linear linkers, in order to arrange various functionalities in a defined spatial manner. In this Review article, recent developments and usages of these special, rectilinear systems are discussed. Furthermore, we focus on covalently linked, nonconjugated linear arrangements and discuss the physical and chemical properties and differences of individual linkers, as well as their application in material and medicinal sciences.
Rigid, linear, versatile, and increasingly in use are attributes of nonconjugating hydrocarbons, such as bicyclo1.1.1pentane, bicyclo2.2.2octane, triptycene, and cubane. This Review article details their fundamental properties, synthetic chemistry, and use as linker systems in materials sciences and drug development (see figure).
The burden of influenza is unevenly distributed, with more severe outcomes in children aged <5 years than older children and adults. In spite of this, immunisation policies for young children are far ...from universal. This article provides an overview of the published evidence on the burden of influenza in children worldwide, with a particular interest in the impact of pandemic influenza in 2009–2010 (caused by the H1N1pdm09 virus). In an average season, up to 9.8 % of 0- to 14-year olds present with influenza, but incidence rates can be markedly higher in younger children. Children aged <5 years have greater rates of hospitalisation and complications than their older counterparts, particularly if the children have co-existing illnesses; historically, this age group have had higher mortality rates from the disease than other children, although during the 2009–2010 pandemic the median age of those who died of influenza was higher than in previous seasons. Admissions to hospital and emergency departments appear to have been more frequent in children with H1N1pdm09 infections than during previous seasonal epidemics, with pneumonia continuing to be a common complication in this setting. Outcomes in children hospitalised with severe disease also seem to have been worse for those infected with H1N1pdm09 viruses compared with seasonal viruses. Studies in children confirm that vaccination reduces the incidence of seasonal influenza and the associated burden, underlining the importance of targeting this group in national immunisation policies.
Conclusions
: Children aged <5 years are especially vulnerable to influenza, particularly that caused by seasonal viruses, and vaccination in this group can be an effective strategy for reducing disease burden.
Homoarginine is an amino acid derivative that may increase nitric oxide availability and enhance endothelial function. The effect of the level of homoarginine on cardiovascular outcome and mortality ...is unknown.
We assessed cardiovascular and all-cause mortality according to homoarginine levels in a cohort of 3,305 subjects referred for coronary angiography from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study. After investigating the relation of homoarginine with kidney function and markers of endothelial dysfunction, we explored its effects on adverse outcomes in a second high-risk cohort of 1244 patients with type 2 diabetes mellitus receiving maintenance hemodialysis (4D study Die Deutsche Diabetes Dialyse Studie). In the LURIC study, mean serum homoarginine levels were 2.6+/-1.1 micromol/L. During a median follow-up of 7.7 years, 766 patients died. After adjustments for age and sex, patients in the lowest quartile (<1.85 micromol/L) had a >4-fold higher rate of dying of cardiovascular disease (hazard ratio 4.1, 95% confidence interval 3.0 to 5.7) than patients in the highest quartile (>3.1 micromol/L). Lower homoarginine levels were associated with lower estimated glomerular filtration rate and higher levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Hemodialysed patients had lower mean homoarginine levels of 1.2+/-0.5 micromol/L and experienced a 5-fold increased mortality rate compared with LURIC patients (608 deaths during a median follow-up of 4 years). Homoarginine consistently affected mortality, which was 2-fold higher in 4D study patients in the lowest quartile (<0.87 micromol/L) than in patients in the highest quartile (>1.4 micromol/L).
Homoarginine levels are independently associated with cardiovascular and all-cause mortality in patients referred for coronary angiography and in patients undergoing hemodialysis. Future studies are needed to elucidate the underlying pathomechanisms.
The spin of a planet arises from the accretion of angular momentum during its formation, but the details of this process are still unclear. In the Solar System, the equatorial rotation velocities ...and, consequently, spin angular momenta of most of the planets increase with planetary mass; the exceptions to this trend are Mercury and Venus, which, since formation, have significantly spun down because of tidal interactions. Here we report near-infrared spectroscopic observations, at a resolving power of 100,000, of the young extrasolar gas giant planet β Pictoris b (refs 7, 8). The absorption signal from carbon monoxide in the planet's thermal spectrum is found to be blueshifted with respect to that from the parent star by approximately 15 kilometres per second, consistent with a circular orbit. The combined line profile exhibits a rotational broadening of about 25 kilometres per second, meaning that β Pictoris b spins significantly faster than any planet in the Solar System, in line with the extrapolation of the known trend in spin velocity with planet mass.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mucin-related carbohydrates are overexpressed on the surface of cancer cells, providing a disease-specific target for cancer immunotherapy. Here, we describe the design and construction of ...peptide-free multivalent glycosylated nanoscale constructs as potential synthetic cancer vaccines that generate significant titers of antibodies selective for aberrant mucin glycans. A polymerizable version of the Tn-antigen glycan was prepared and converted into well-defined glycopolymers by Reversible Addition–Fragmentation chain Transfer (RAFT) polymerization. The polymers were then conjugated to gold nanoparticles, yielding ‘multicopy-multivalent’ nanoscale glycoconjugates. Immunological studies indicated that these nanomaterials generated strong and long-lasting production of antibodies that are selective to the Tn-antigen glycan and cross-reactive toward mucin proteins displaying Tn. The results demonstrate proof-of-concept of a simple and modular approach toward synthetic anticancer vaccines based on multivalent glycosylated nanomaterials without the need for a typical vaccine protein component.
Ultrasonic transducers are often used in the nuclear industry as sensors to monitor the health and process status of systems or the components. Some of the after-effects of the Fukushima Daiichi ...earthquake could have been eased if sensors had been in place inside the four reactors and sensed the overheating causing meltdown and steam explosions. The key element of ultrasonic sensors is the piezoelectric wafer, which is usually derived from lead-zirconate-titanate (Pb(Zr, Ti)O3, PZT). This material loses its piezoelectrical properties at a temperature of about 200 °C. It also undergoes nuclear transmutation. Bismuth titanate (Bi4Ti3O12, BiTi) has been considered as a potential candidate for replacing PZT at the middle of this temperature range, with many possible applications, since it has a Curie–Weiss temperature of about 650 °C. The aim of this article is to describe experimental details for operation in gamma and nuclear radiation concomitant with elevated temperatures and details of the performance of a BiTi sensor during and after irradiation testing. In these experiments, bismuth titanate has been demonstrated to operate up to a fast neutron fluence of 5 × 1020 n/cm2 and gamma radiation of 7.23 × 1021 (gamma/cm2). The results offer a perspective on the state-of the-art for a possible sensor for harsh environments of high temperature, Gamma radiation, and nuclear fluence.
For the first time, free base and N-methylated porphyrins have been utilized as bifunctional organocatalysts in Michael additions and it was found that distortion of the macrocycle is a vital ...prerequisite for their catalytic activity. Conformational design has been used to tailor the properties of nonplanar porphyrins with regards to availability of the N-H units for hydrogen bonding (distortion-dependent hydrogen bonding) and the basicity of the heterocyclic groups. NMR spectroscopic- and catalyst screening studies provided insight into the likely mode of catalyst action. This unprecedented use of free base and N-substituted porphyrins as organocatalysts opens a new functional role for porphyrins.
Genome-wide association studies have identified several hundred loci associated with type 2 diabetes mellitus (T2DM). Additionally, pathogenic variants in several genes are known to cause monogenic ...diabetes that overlaps clinically with T2DM. Whole-exome sequencing of related individuals with T2DM is a powerful approach to identify novel high-penetrance disease variants in coding regions of the genome. We performed whole-exome sequencing on four related individuals with T2DM - including one individual diagnosed at the age of 33 years. The individuals were negative for mutations in monogenic diabetes genes, had a strong family history of T2DM, and presented with several characteristics of metabolic syndrome. A missense variant (p.N2291D) in the type 2 ryanodine receptor (
gene was one of eight rare coding variants shared by all individuals. The variant was absent in large population databases and affects a highly conserved amino acid located in a mutational hotspot for pathogenic variants in Catecholaminergic polymorphic ventricular tachycardia (CPVT). Electrocardiogram data did not reveal any cardiac abnormalities except a lower-than-normal resting heart rate (< 60 bpm) in two individuals - a phenotype observed in CPVT individuals with
mutations. RyR2-mediated Ca
release contributes to glucose-mediated insulin secretion and pathogenic
mutations cause glucose intolerance in humans and mice. Analysis of glucose tolerance testing data revealed that missense mutations in a CPVT mutation hotspot region - overlapping the p.N2291D variant - are associated with complete penetrance for glucose intolerance. In conclusion, we have identified an atypical missense variant in the
gene that co-segregates with diabetes in the absence of overt CPVT.
For practical use in harsh radiation environments, we pose selection criteria for piezoelectric materials for non-destructive evaluation (NDE) and material characterization. Using these criteria, ...piezoelectric aluminum nitride is shown to be an excellent candidate. The results of tests on an aluminum-nitride- based transducer operating in a nuclear reactor are also presented. We demonstrate the tolerance of single-crystal piezoelectric aluminum nitride after fast and thermal neutron fluences of 1.85 x 10 18 neutron/cm 2 and 5.8 x 10 18 neutron/cm 2 , respectively, and a gamma dose of 26.8 MGy. The radiation hardness of AlN is most evident from the unaltered piezoelectric coefficient d33, which measured 5.5 pC/N after a fast and thermal neutron exposure in a nuclear reactor core for over 120 MWh, in agreement with the published literature value. The results offer potential for improving reactor safety and furthering the understanding of radiation effects on materials by enabling structural health monitoring and NDE in spite of the high levels of radiation and high temperatures, which are known to destroy typical commercial ultrasonic transducers.
We present calibrations for star formation rate (SFR) indicators in the ultraviolet, mid-infrared, and radio-continuum bands, including one of the first direct calibrations of 150 MHz as an SFR ...indicator. Our calibrations utilize 66 nearby star-forming galaxies with Balmer-decrement-corrected luminosities, which span five orders of magnitude in SFR and have absolute magnitudes of . Most of our photometry and spectrophotometry are measured from the same region of each galaxy, and our spectrophotometry has been validated with SDSS photometry, so our random and systematic errors are small relative to the intrinsic scatter seen in SFR indicator calibrations. We find that the Wide-field Infrared Space Explorer W4 (22.8 m), Spitzer 24 m, and 1.4 GHz bands have tight correlations with the Balmer-decrement-corrected H luminosity, with a scatter of only 0.2 dex. Our calibrations are comparable to those from the prior literature for L∗ galaxies, but for dwarf galaxies, our calibrations can give SFRs that are far greater than those derived from most previous literature.
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