Coding polymorphisms in Casp5, Casp8 and DR4 genes may play a role in predisposition to lung cancer

Apoptosis plays a role in the elimination of DNA-damaged cells thus protecting the host from cancer development. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. We tested 19 coding apoptotic gene SNPs in 2-stage molecular epidemiological study. For the preliminary sorting of SNP candidates, we employed a “comparison of extremes” approach, where 111 patients with highly pronounced LC susceptibility (non-smokers or young-onset light smokers) were analyzed against 110 subjects with the evidence for LC tolerance (elderly tumor-free heavy smokers). Three genotypes demonstrated possible association with LC risk (Leu/Leu-homozygotes for Casp5 Val318Leu versus other genotypes: OR = 2.47 (95% CI: 1.07–5.69), p = 0.03; His-carriers for Casp8 His302Asp: OR = 2.26 (95% CI: 1.18–4.31), p = 0.02; Arg-carriers for DR4 Lys441Arg: OR = 1.89 (95% CI: 1.05–3.40), p = 0.03), and therefore were selected for the validation. The extended study included 2 case-control series, namely subjects from Russia (351 LC cases and 538 controls) and Moldova (296 LC cases and 295 controls). Interestingly, all three candidate genotypes consistently demonstrated OR above 1 both in Russian and in Moldovian groups. Although the combined Mantel–Haenszel analysis yet failed to reach statistical significance (OR = 1.22 (95% CI: 0.90–1.65), p = 0.21; OR = 1.17 (95% CI: 0.92–1.50), p = 0.21; OR = 1.19 (95% CI: 0.95–1.51), p = 0.14, respectively), the obtained data indicate that Casp5, Casp8 and DR4 gene polymorphisms may deserve consideration in large-scale case-control studies of LC risk modifiers.     

Investigation of the Metabolites of (S,S)-[11C]MeNER in Humans, Monkeys and Rats

Introduction  (S,S)-[¹¹C]MeNER ((S,S)-2-(α-(2-[¹¹C]methoxyphenoxy)benzyl)morpholine) is a positron emission tomography (PET) radioligand recently applied in clinical studies of norepinephrine transporters (NETs) in the human brain in vivo. In view of further assessment of the suitability of (S,S)-[¹¹C]MeNER as a NET radioligand, its metabolism and the identity of the in vivo radiometabolites of (S,S)-[¹¹C]MeNER are of great interest. Materials and Methods  Thus, PET studies were used to measure brain dynamics of (S,S)-[¹¹C]MeNER, and plasma reverse-phase radiochromatographic analysis was performed to monitor and quantify its rate of metabolism. Eighteen healthy human volunteers, five cynomolgus monkeys, and five rats were studied. Results and Discussion  In human subjects, the plasma radioactivity representing (S,S)-[¹¹C]MeNER decreased from 88 ± 5% at 4 min after injection to 82 ± 7% at 40 min, while a polar radiometabolite increased from 3 ± 3% to 16 ± 7% at the same time-points, respectively. A more lipophilic radiometabolite than (S,S)-[¹¹C]MeNER decreased from 9 ± 5% at 4 min to 1 ± 2% at 40 min. In monkeys, plasma radioactivity representing (S,S)-[¹¹C]MeNER decreased from 97 ± 2% at 4 min to 74 ± 7% at 45 min, with a polar fraction as the major radiometabolite. A more lipophilic radiometabolite than (S,S)-[¹¹C]MeNER, constituted 3 ± 2% of radioactivity at 4 min and was not detectable later on. In rats, 17 ± 4% of plasma radioactivity was parent radioligand at 30 min with the remainder comprising mainly a polar radiometabolite. (S,S)-[¹¹C]MeNER in rat brain and urine at 30 min after injection were 90% and 4%, respectively. On a brain regional level, parent radioligand ranged from 87.5 ± 3.9% (57.2 ± 14.2% SUV [standard uptake values, %injected radioactivity per mL multiplied with animal weight (in g)]; cerebellum) to 92.9 ± 1.8% (36.1 ± 4.7% SUV; striatum), with differential distribution of the radiometabolite in the cerebellum (6.7 ± 0.3% SUV) and the striatum (2.5 ± 0.3% SUV). Liquid chromatography-mass spectrometry analysis of rat urine identified a hydroxylation product of the methoxyphenoxy ring of (S,S)-MeNER as the main metabolite. In the brain, the corresponding main metabolite was the product from O-de-methylation of (S,S)-MeNER. PET measurements were performed in rats as well as in wild-type and P-gp-knock-out mice. In rats, the brain peak level of radioactivity was found to be very low (65%SUV). In mice, there was only a small difference in peak brain accumulation between P-gp knock-out and wild-type mice (145 vs. 125%SUV) with the following rank order of regional brain radioactivity: cerebellum × thalamus > cortical regions > striatum. Conclusion  It can be concluded that radiometabolites of (S,S)-[¹¹C]MeNER are of minor importance in rat and monkey brain imaging. The presence of a transient lipophilic radiometabolite in peripheral human plasma may induce complications with brain imaging, but its kinetics appear favorable in relation to the slow kinetics of (S,S)-[¹¹C]MeNER in humans.     

Lung, liver and bone cancer mortality in Mayak workers

Workers at the Mayak nuclear facility in the Russian Federation offer the only adequate human data for evaluating cancer risks from exposure to plutonium. Risks of mortality from cancers of the lung, liver and bone, the organs receiving the largest doses from plutonium, were evaluated in a cohort of 17,740 workers initially hired 1948-1972 using, for the first time, recently improved individual organ dose estimates. Excess relative risk (ERR) models were used to evaluate risks as functions of internal (plutonium) dose, external (primarily gamma) dose, gender, attained age and smoking. By December 31, 2003, 681 lung cancer deaths, 75 liver cancer deaths and 30 bone cancer deaths had occurred. Of these 786 deaths, 239 (30%) were attributed to plutonium exposure. Significant plutonium dose-response relationships (p < 0.001) were observed for all 3 endpoints, with lung and liver cancer risks reasonably described by linear functions. At attained age 60, the ERRs per Gy for lung cancer were 7.1 for males and 15 for females; the averaged-attained age ERRs for liver cancer were 2.6 and 29 for males and females, respectively; those for bone cancer were 0.76 and 3.4. This study is the first to present and compare dose-response analyses for cancers of all 3 organs. The unique Mayak cohort with its high exposures and well characterized doses has allowed quantification of the plutonium dose-response for lung, liver and bone cancer risks based on direct human data. These results will play an important role in plutonium risk assessment.     

Investigation of Technological and Load Intensity Parameters of the Finishing Process of Materials on Equipment with Tools Translational Kinematics

The regularities of the formation of the resulting raster tool trajectories based on Lissajous figures for the lapping process of planes are established. This makes it possible to maximize the cutting ability of the tool, which contributes to its more uniform wear and increased productivity and processing quality. Optimal parameters of productivity and roughness of the treated surface during lapping of zirconium ceramics are achieved through the use of ASM paste 28/20 µm. Based on Preston’s hypothesis, an exponential dependence of the change in the contact area during the lapping of planes of different initial shape of the macrorelief is obtained. The obtained theoretical and practical results of the study of the process of flat lapping with constant and variable clamping force of the treated surface to the surface of the tool. The influence of the force factor on the formation of the surface in the process of abrasive lapping has been established. Studies have been carried out and the main technological recommendations of precision surface treatment of workpieces based on hard, brittle ceramic material and bronze samples on equipment with a raster trajectory of the tool movement are presented. The optimal pressure value when processing ceramics should be considered 203–270 kPa (2.1–2.8 kg/cm²).     

Sub-Threshold Fabrication of Laser-Induced Periodic Surface Structures on Diamond-like Nanocomposite Films with IR Femtosecond Pulses

In the paper, we study the formation of laser-induced periodic surface structures (LIPSS) on diamond-like nanocomposite (DLN) a-C:H:Si:O films during nanoscale ablation processing at low fluences—below the single-pulse graphitization and spallation thresholds—using an IR fs-laser (wavelength 1030 nm, pulse duration 320 fs, pulse repetition rate 100 kHz, scanning beam velocity 0.04–0.08 m/s). The studies are focused on microscopic analysis of the nanostructured DLN film surface at different stages of LIPSS formation and numerical modeling of surface plasmon polaritons in a thin graphitized surface layer. Important findings are concerned with (i) sub-threshold fabrication of high spatial frequency LIPSS (HSFL) and low spatial frequency LIPSS (LSFL) under negligible surface graphitization of hard DLN films, (ii) transition from the HSFL (periods of 140 ± 30 and 230 ± 40 nm) to LSFL (period of 830–900 nm) within a narrow fluence range of 0.21–0.32 J/cm², (iii) visualization of equi-field lines by ablated nanoparticles at an initial stage of the LIPSS formation, providing proof of larger electric fields in the valleys and weaker fields at the ridges of a growing surface grating, (iv) influence of the thickness of a laser-excited glassy carbon (GC) layer on the period of surface plasmon polaritons excited in a three-layer system “air/GC layer/DLN film”.     

A Feasibility Study of High-Entropy Alloy Coating Deposition by Detonation Spraying Combined with Laser Melting

In this work, a new two-stage approach to the deposition of high-entropy alloy coatings is proposed. At the first stage, a composite precursor coating is formed by detonation spraying of the metal powder mixtures. At the second stage, the precursor coating is re-melted by a laser, and the formation of multi-component solid solution phases can be expected upon solidification. The feasibility of the proposed approach was validated using three different mixtures of Fe, Ni, Cu, Co and Al powders. It was shown that detonation spraying allows forming composite coatings with a uniform distribution of the lamellae of different metals. The results of the structural analysis of the laser-treated coatings suggest that complete alloying occurred in the melt and face-centered cubic solid solutions formed in the coatings upon cooling.     

Triterpene glycosides from Antarctic sea cucumbers. 1. Structure of liouvillosides A1, A2, A3, B1, and B2 from the sea cucumber Staurocucumis liouvillei: new procedure for separation of highly polar glycoside fractions and taxonomic revision

Five new triterpene glycosides, liouvillosides A1 (1), A2 (2), A3 (3), B1 (4), and B2 (5), have been isolated from the Antarctic sea cucumber Staurocucumis liouviellei along with the known liouvilloside A(6), isolated earlier from the same species, and hemoiedemosides A (7) and B (8), isolated earlier from the Patagonian sea cucumber Hemioedema spectabilis. The isolation was carried out using a new chromatographic procedure including application of ion-pair reversed-phase chromatography followed by chiral chromatography on a cyclodextrin ChiraDex column. The structures of the new glycosides were elucidated using extensive NMR spectroscopy (1H and 13C NMR spectrometry, DEPT, 1H-(1)H COSY, HMBC, HMQC, and NOESY), ESI-FTMS, and CID MS/MS, and chemical transformations. Glycosides 1-3 are disulfated tetraosides and glycosides 4 and 5 are trisulfated tetraosides. Glycosides 2 and 3 contain 3-O-methylquinovose, found for the first time as a natural monosaccharide in sea cucumber glycosides. On the basis of analyses of glycoside structures a taxonomic revision is proposed.     

Structure and Mechanical Properties of Cu–Al–Mn Alloys Fabricated by Electron Beam Additive Manufacturing

In this work, the method of electron beam additive manufacturing (EBAM) was used to fabricate a Cu-based alloy possessing a shape memory effect. Electron beam additive technology is especially relevant for copper and its alloys since the process is carried out in a vacuum, which makes it possible to circumvent oxidation. The main purpose of the study was to establish the influence of the printing parameters on the structure of the obtained products, their phase composition, mechanical properties, dry friction behavior, and the structure-phase gradient that formed in Cu–Al–Mn alloy samples during electron beam layer-by-layer printing. The results of the study allowed us to reveal that the structure-phase composition, the mechanical properties, and the tribological performance of the fabricated material are mainly affected by the magnitude of heat input during electron beam additive printing of Cu–Al–Mn alloy. High heat input values led to the formation of the β1′ + α decomposed structure. Low heat input values enabled the suppression of decomposition and the formation of an ordered 1 structure. The microhardness values were distributed on a gradient from 2.0 to 2.75 GPa. Fabricated samples demonstrated different behaviors in friction and wear depending on their composition and structure, with the value of the friction coefficient lying in the range between 0.1 and 0.175.     

Silicon-photonics focused ultrasound detector for minimally invasive optoacoustic imaging

One of the main challenges in miniaturizing optoacoustic technology is the low sensitivity of sub-millimeter piezoelectric ultrasound transducers, which is often insufficient for detecting weak optoacoustic signals. Optical detectors of ultrasound can achieve significantly higher sensitivities than their piezoelectric counterparts for a given sensing area but generally lack acoustic focusing, which is essential in many minimally invasive imaging configurations. In this work, we develop a focused sub-millimeter ultrasound detector composed of a silicon-photonics optical resonator and a micro-machined acoustic lens. The acoustic lens provides acoustic focusing, which, in addition to increasing the lateral resolution, also enhances the signal. The developed detector has a wide bandwidth of 84 MHz, a focal width smaller than 50 µm, and noise-equivalent pressure of 37 mPa/Hz^1/2 – an order of magnitude improvement over conventional intravascular ultrasound. We show the feasibility of the approach and the detector’s imaging capabilities by performing high-resolution optoacoustic microscopy of optical phantoms with complex geometries.     

Esmolol in Cardiac Surgery: A Randomized Controlled Trial

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