bluuebunny/crossref_metadata_2025 huggingface dataset:
GPCR structure and function relationship: identification of a biased apelin receptor mutant
Authors: Ban Ting , Li Xun , Ma Xiaochuan , Yang Hui , Song Yunpeng , Sun Yaping , Shen Michelle , Li Na , Zhang Mei-Yun , Ma Yingli , Zhong Wenge , Zhang Mingqiang , Hu Liaoyuan A.
Published: November 2018

Biased ligands of G protein-coupled receptors (GPCRs) may have improved therapeutic benefits and safety profiles. However, the molecular mechanism of GPCR biased signaling remains largely unknown. Using apelin receptor (APJ) as a model, we systematically investigated the potential effects of amino acid residues around the orthosteric binding site on biased signaling. We discovered that a single residue mutation I109A (I1093.32) in the transmembrane domain 3 (TM3) located in the deep ligand-binding pocket was sufficient to convert a balanced APJ into a G protein signaling biased receptor. APJ I109A mutant receptor retained full capabilities in ligand binding and G protein activation, but was defective in GRK recruitment, β-arrestin recruitment, and downstream receptor-mediated ERK activation. Based on molecular dynamics simulations, we proposed a molecular mechanism for biased signaling of I109A mutant receptor. We postulate that due to the extra space created by I109A mutation, the phenyl group of the last residue (Phe-13) of apelin rotates down and initiates a cascade of conformational changes in TM3. Phe-13 formed a new cluster of hydrophobic interactions with the sidechains of residues in TM3, including F1103.33 and M1133.36, which stabilizes the mutant receptor in a conformation favoring biased signaling. Interruption of these stabilizing interactions by double mutation F110A/I109A or M113A/I109A largely restored the β-arrestin-mediated signaling. Taken together, we describe herein the discovery of a biased APJ mutant receptor and provide detailed molecular insights into APJ signaling selectivity, facilitating the discovery of novel therapeutics targeting APJ.
Rational engineering of a malate dehydrogenase for microbial production of 2,4-dihydroxybutyric acid via homoserine pathway
Authors: Frazão Cláudio J.R. , Topham Christopher M. , Malbert Yoann , François Jean Marie , Walther Thomas
Published: November 2018

A synthetic pathway for the production of 2,4-dihydroxybutyric acid from homoserine (HMS), composed of two consecutive enzymatic reaction steps has been recently reported. An important step in this pathway consists in the reduction in 2-keto-4-hydroxybutyrate (OHB) into (l)-dihydroxybutyrate (DHB), by an enzyme with OHB reductase activity. In the present study, we used a rational approach to engineer an OHB reductase by using the cytosolic (l)-malate dehydrogenase from Escherichia coli (Ec-Mdh) as the template enzyme. Structural analysis of (l)-malate dehydrogenase and (l)-lactate dehydrogenase enzymes acting on sterically cognate substrates revealed key residues in the substrate and co-substrate-binding sites responsible for substrate discrimination. Accordingly, amino acid changes were introduced in a stepwise manner into these regions of the protein. This rational engineering led to the production of an Ec-Mdh-5E variant (I12V/R81A/M85E/G179D/D86S) with a turnover number (kcat) on OHB that was increased by more than 2000-fold (from 0.03 up to 65.0 s−1), which turned out to be 7-fold higher than that on its natural substrate oxaloacetate. Further kinetic analysis revealed the engineered enzyme to possess comparable catalytic efficiencies (kcat/Km) between natural and synthetic OHB substrates (84 and 31 s−1 mM−1, respectively). Shake-flask cultivation of a HMS-overproducing E. coli strain expressing this improved OHB reductase together with a transaminase encoded by aspC able to convert HMS to OHB resulted in 89% increased DHB production as compared with our previous report using a E. coli host strain expressing an OHB reductase derived from the lactate dehydrogenase A of Lactococcus lactis.
NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma
Authors: Jing Ji-sheng , Li Hongbo , Wang Shun-cai , Ma Jiu-ming , Yu La-qing , Zhou Hua
Published: November 2018

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.
Enhanced transfection of a macromolecular lignin-based DNA complex with low cellular toxicity
Authors: Ho Yoon Khei , Kai Dan , Tu Geraldine Xue En , Deen G. Roshan , Too Heng Phon , Loh Xian Jun
Published: November 2018

Cationic polymers remain attractive tools for non-viral gene transfer. The effectiveness of these vectors rely on the ability to deliver plasmid DNA (pDNA) into the nucleus of cells. While we have previously demonstrated the potential of Lignin-PGEA-PEGMA as a non-viral gene delivery vector, alterations of cellular phenotype and cytotoxicity were observed post transfection. The present study aims to explore transfection conditions for high efficiency and low toxicity of the Lignin-PGEA-PEGMA based gene delivery system. Cellular toxicity was significantly reduced by using the centrifugation protocol, which enables rapid deposition of DNA complexes. Replacement of media post centrifugation resulted in minimal exposure of cells to excess polymers, which were toxic to cells. At an optimized DNA amount (500–750 ng) and molar ratios of nitrogen (N) in polymer to phosphate (P) in pDNA (N/P = 30–40), with the use of a novel transfection enhancer that facilitates endosomal escape and nuclear trafficking, the efficiency of gene delivery was increased significantly 24 h post transfection. The present study demonstrated an appropriately optimized protocol that enabled the utility of a novel cationic polymer blend with a mixture of fusogenic lipids and a histone deacetylate inhibitor in non-viral transfection, thereby providing an attractive alternative to costly commercial gene carriers.
Association between three genetic variants in kallikrein 3 and prostate cancer risk
Authors: Ding Wei-Hong , Ren Ke-Wei , Yue Chuang , Zou Jian-Gang , Zuo Li , Zhang Li-Feng , Bai Yu , Okada Atsushi , Yasui Takahiro , Mi Yuan-Yuan
Published: November 2018

Background: Epidemiological studies have assessed the association between kallikrein 3 (KLK3) polymorphisms and prostate cancer (PCa) susceptibility. However, published data on this association are somewhat inconclusive. Methods: Articles investigating the association between three KLK3 (rs1058205, rs2735839, and rs266882) variants and PCa susceptibility were searched from online databases, which included 35,838 patients and 36,369 control participants. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to demonstrate the strength of the association. We also utilized ELISA to detect serum expression of KLK3. In addition, in silico tools were adopted to evaluate the relationship of KLK3 expression and PCa survival time. Results: The overall results indicated that polymorphism T>C of rs1058205 was associated with decreased risk of PCa (allele contrast: OR = 0.75, 95% CI = 0.64–0.88, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.42–0.81, Pheterogeneity < 0.001), particularly in Caucasian population (allele contrast: OR = 0.77, 95% CI = 0.65–0.91, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.41–0.82, Pheterogeneity < 0.001). No association was observed between the polymorphism A>G of rs2735839 and risk of PCa. In addition, no association was observed between polymorphism A>G of rs266882 and risk of PCa. Serum KLK3 levels in PCa patients carrying CC/CT genotypes were statistically lower than those carrying TT genotypes. Conclusion: This meta-analysis suggests that rs1058205 polymorphism of KLK3 is a risk factor for PCa development, polymorphism T>C of rs1058205 is associated with decreased susceptibility to PCa particularly in Caucasian population.
An updated association between TNF-α -238G/A polymorphism and gastric cancer susceptibility in East Asians
Authors: Zhao Hongpeng , Liu Lixia , Liu Bo , Wang Yanmin , Li Feng , Yu Haihua
Published: November 2018

Polymorphisms in the tumor necrosis factor α (TNF-α) gene are emerging as key determinants of gastric diseases. The TNF-α-238G/A single-nucleotide polymorphism (SNP) is the most extensively studied. However, this association is inconsistent amongst different populations. We therefore conducted an updated meta-analysis to obtain a more precise estimate of the association of TNF-α-238G/A polymorphism with gastric cancer (GC) risk. A comprehensive search of PubMed, Embase, Chinese (CNKI and WanFang) databases was performed to identify relevant studies through 5 May 2018. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. Fourteen studies were included in our meta-analysis involving 2999 cases and 4685 controls. There was no significant association between TNF-α-238G/A polymorphism and GC risk in the overall populations. In the subgroup analysis, we found that TNF-α-238G/A polymorphism was associated with the increased risk of GC amongst Asians, especially in Chinese, but not in Caucasians. Subgroup analysis by genotyping methods revealed increased risk for other methods. In conclusion, our present meta-analysis shows that TNF-α-238G/A polymorphism is associated with the risk of GC in East Asian individuals.
Ceres’ opposition effect observed by the Dawn framing camera
Authors: Schröder Stefan E. , Li Jian-Yang , Rayman Marc D. , Joy Steven P. , Polanskey Carol A. , Carsenty Uri , Castillo-Rogez Julie C. , Ciarniello Mauro , Jaumann Ralf , Longobardo Andrea , McFadden Lucy A. , Mottola Stefano , Sykes Mark , Raymond Carol A. , Russell Christopher T.
Published: November 2018

Context. The surface reflectance of planetary regoliths may increase dramatically towards zero phase angle, a phenomenon known as the opposition effect (OE). Two physical processes that are thought to be the dominant contributors to the brightness surge are shadow hiding (SH) and coherent backscatter (CB). The occurrence of shadow hiding in planetary regoliths is self-evident, but it has proved difficult to unambiguously demonstrate CB from remote sensing observations. One prediction of CB theory is the wavelength dependence of the OE angular width.

Aims. The Dawn spacecraft observed the OE on the surface of dwarf planet Ceres. We aim to characterize the OE over the resolved surface, including the bright Cerealia Facula, and to find evidence for SH and/or CB. It is presently not clear if the latter can contribute substantially to the OE for surfaces as dark as that of Ceres.

Methods. We analyze images of the Dawn framing camera by means of photometric modeling of the phase curve.

Results. We find that the OE of most of the investigated surface has very similar characteristics, with an enhancement factor of 1.4 and a full width at half maximum of 3° (“broad OE”). A notable exception are the fresh ejecta of the Azacca crater, which display a very narrow brightness enhancement that is restricted to phase angles <0.5° (“narrow OE”); suggestively, this is in the range in which CB is thought to dominate. We do not find a wavelength dependence for the width of the broad OE, and lack the data to investigate the dependence for the narrow OE. The prediction of a wavelength-dependent CB width is rather ambiguous, and we suggest that dedicated modeling of the Dawn observations with a physically based theory is necessary to better understand the Ceres OE. The zero-phase observations allow us to determine Ceres’ visible geometric albedo as pV = 0.094 ± 0.005. A comparison with other asteroids suggests that Ceres’ broad OE is typical for an asteroid of its spectral type, with characteristics that are primarily linked to surface albedo.

Conclusions. Our analysis suggests that CB may occur on the dark surface of Ceres in a highly localized fashion. While the results are inconclusive, they provide a piece to the puzzle that is the OE of planetary surfaces.
La voix et la parole des adultes implantés cochléaires : enquêtes sur le ressenti des adultes implantés et les représentations des orthophonistes
Authors: Courtade Noémie , Borel Stéphanie
Published: November 2018

Cette étude interroge de façon croisée orthophonistes et patients sur la production de la voix et de la parole des adultes implantés
cochléaires. Deux questionnaires ont été élaborés et les réponses de 186 adultes implantés et 150 orthophonistes ont été analysées.
Les principales diffi cultés exprimées par les patients concernent l’intensité pour les adultes post-linguaux et l’articulation de la parole
pour les adultes pré/péri-linguaux. Cependant, ces caractéristiques vocales semblent peu gênantes. À l’inverse, les orthophonistes
pointent des diffi cultés chez leurs patients et sont en demande d’outils d’évaluation et de rééducation vocales spécifi ques à la surdité.
Recovery of germanium from acid leach solutions of zinc refinery residue using an oxime extractant of HBL101
Authors: Cheng Baohai , Zhang Ting’an , Zhang Kuifang , Cao Zuoying , Zeng Li
Published: November 2018

An oxime extractant of HBL101 was used to extract germanium from acid leach solutions of zinc refinary residues. The effect of acidity on extraction was investigated. Germanium was extracted from a sulphate acid solution with not too high acidity (1.0∼1.2 mol/L H2SO4), while zinc, cadmium, iron, gallium and arsenic were not extracted. Only small amount of copper was co-extracted. The germanium was readily stripped from the loaded organic solution with NaOH solutions. After germanium stripping, the co-extracted copper can be stripped using 2 mol/L H2SO4 while the extractant regenerated for recycling. The system was optimised in terms of organic composition and conditions of extraction and stripping and further characterised in terms of extraction and stripping kinetics and distribution isotherms. More than 98.5% of germanium was extracted in five-stage counter current extraction using an organic system of 30% HBL101 and 70% sulphonated kerosene and a feed containing 0.25 g/L Ge and 113 g/L H2SO4 with an A/O ratio of 4:1 at 25 °C for 20 min. The loaded organic containing 0.905 g/L Ge was stripped using 3.75 mol/L NaOH solution in five-stage counter current stripping with an A/O ratio of 1:4 at 25 °C for 25 min to selectively strip germanium followed by using 2 mol/L H2SO4 to strip co-extracted copper for recycling. The concentration of Ge in strip liquor reached 3.56 g/L.
GROSSE Bewegungen im Alltag – Behandlungskonzept für Menschen mit Parkinson
Authors: Geheb Katrin , Diaubalick Anne
Published: November 2018

Das LSVT-BIG-Konzept erscheint zunächst durch seine extrovertierten Übungen ungewohnt. Menschen mit Morbus Parkinson können dadurch jedoch den für ihre Erkrankung typischen kleinen Bewegungen entgegenwirken. Damit lassen sich Sturzprophylaxe, Selbstständigkeit im Alltag und individuelle Ziele erreichen.
Prevalence of Persistent Pain after Total Knee Arthroplasty and the Impact of Neuropathic Pain
Authors: Hasegawa Masahiro , Tone Shine , Naito Yohei , Wakabayashi Hiroki , Sudo Akihiro
Published: November 2018

The present study aimed to define the prevalence of pain persisting after total knee arthroplasty (TKA) and determine the impact of neuropathic pain. Knee pain after TKA was evaluated in 154 patients (222 knees with osteoarthritis) using a numerical rating scale (NRS) and followed up for a mean of 4.7 years. The patients were classified according to whether they had no or mild pain (NRS ≤ 3), or moderate-to-severe pain (NRS > 3), and then assigned to groups with nociceptive, unclear, or neuropathic pain based on responses to painDETECT questionnaires. Risk factors for these types of pain were determined. The ratio of patients with moderate-to-severe pain was 28% (62 knees). Thirteen patients (21 knees; 9%) experienced unclear pain. Patients with moderate-to-severe or unclear pain had malalignment and lower Knee Society knee scores. In conclusion, a significant number of patients experienced moderate-to-severe and unclear pain after TKA. Moderate-to-severe pain was associated with unclear pain.
Performance loss analysis and design space optimization of perovskite solar cells
Authors: Agarwal Sumanshu , Nair Pradeep R.
Published: November 2018

While the performance enhancement witnessed in the field of perovskite solar cells over the recent years has been impressive, a detailed analysis of various loss mechanisms is required for further performance optimization. Here, we address the same through numerical simulations of optical and electrical characteristics. We quantify various losses like optical losses (5%–6%), recombination losses (3%–4%), and resistive losses against the Auger recombination induced practical efficiency limits. Through this, we identify schemes to reduce these losses and hence lead to an increase in efficiency. In addition, we find that the optimum thickness of the perovskite (with material parameters comparable to MAPbI3-xClx and Eg = 1.55 eV) for solar cell fabrication is around 300 nm (comparable to the well-established value); however, the same could be as large as 900 nm for a trap free perovskite (∼ms as the minority carrier Shockley-Read-Hall recombination lifetime). The analyses also enable us to provide the design charts that could lead to >25% efficient perovskite solar cells on the planar structure.
Dissipative instability of longitudinal wave in interaction between spiral electron beam and warm collisional magnetized plasma
Authors: Jouhary M. , Khorashadizadeh S. M. , Barati Moqadam Niyat M. , Niknam A. R.
Published: November 2018

The dissipative instability of longitudinal waves due to the interaction of a relativistic spiral electron beam with a magnetized plasma is analytically investigated using the Bhatnagar-Gross-Krook kinetic theory, in which the thermal and collisional effects are taken into account. The dispersion relation of the longitudinal wave is derived, using the dielectric permittivity tensor of the plasma. The frequency spectrum and growth rate of the instability are calculated by solving the dispersion relation in both strongly and weakly magnetized plasmas. It is shown that the growth rate of the instability increases with the beam velocity.
Drop hammer with high-speed thermal imaging
Authors: Men Zhiwei , Bassett Will P. , Suslick Kenneth S. , Dlott Dana D.
Published: November 2018

The drop hammer test is the easiest way to assess the sensitivity of explosive materials, but drop hammer results for low-velocity impacts have not been able to explain how explosives will react to other kinds of initiating stimuli. In order to do that, we have to understand the fundamental mechanisms of drop hammer initiation and how they differ from other initiation methods. For this reason, there is interest in instrumented drop hammers that help reveal what the drop hammer does at a fundamental level. We have developed a drop hammer that combines two types of mid-wavelength infrared (MWIR) imagers that, when operated simultaneously, can detect both the rapid explosion and slower combustion from impact-initiated polymer-bonded explosives with high time (1 μs) and space (15 μm) resolution. Results are presented that show how to vibration isolate the drop hammer to minimize MWIR image shaking during impact and to quantify the noise floor for MWIR temperature determinations via optical pyrometry. Experiments were performed on polymer-encased crystals of RDX ([CH2–NNO2]3) and HMX ([CH2–NNO2]4). Our experiments showed that drop-hammer initiated explosions occur in two phases with roughly 100 μs between explosions. Drop-hammer initiation is compared to an ultrasonic hammer, which initiates explosions by rapid frictional rubbing of the explosive surfaces against the surrounding polymer. The explosion rise time is faster with the drop hammer because the drop hammer inputs energy throughout the explosive volume, whereas the ultrasonic hammer produces localized heating and much more heat at the explosive surface.
Effects of mobile charged defects on current–voltage behavior in resistive switching memories based on organic–inorganic hybrid perovskite
Authors: Roy Arijit , Jang Ho Won , Cha Pil-Ryung
Published: November 2018

I–V characteristics that are commonly observed in resistive switching memories based on organic or organic–inorganic hybrid materials are investigated using a drift–diffusion model. The characteristic current deflection region at a specific voltage in a high-resistance-state (HRS) is predicted using the drift-diffusion model and compared with the experimental results of methylammonium lead iodide (MALI, CH3NH3PbI3). The accumulation of oppositely charged defects in the Debye layers is found to play a dominant role in determining the shape of the I–V curve in the HRS. The magnitude of the applied voltage at which the deflection in the current occurred is decreased by increasing the voltage sweep rate. This result is attributed to the time-dependent migration of charged defects from the Debye layers to the bulk of the switching materials.
Note: Calibration of majority isotopes for enriched and depleted uranium fission chambers by using the elimination method with fast neutrons
Authors: Qin J. G. , An L. , Lu X. X. , Zhu T. H. , Jiang L. , Wang M. , Yang B.
Published: November 2018

Calibrated miniature pulse fission chambers (MPFCs) can be used for absolute measurement of the fission reaction rate in neutronic experiments. Absolute measurements require the effective number of fissionable atoms (ENFAs) in the coating of the chambers. An elimination method was proposed to calibrate the MPFCs embodying highly enriched and depleted uranium, using 14.75 MeV fast neutrons from the D–T reaction. The ENFAs of 235U in enriched uranium MPFC and 238U in depleted uranium MPFC are 8.39 × 1018 and 9.55 × 1018, with the uncertainties of 5.27% and 4.76%, respectively.
Angular streaking of betatron X-rays in a transverse density gradient laser-wakefield accelerator
Authors: Ma Y. , Seipt D. , Dann S. J. D. , Streeter M. J. V. , Palmer C. A. J. , Willingale L. , Thomas A. G. R.
Published: November 2018

In a plasma with a transverse density gradient, laser wavefront tilt develops gradually due to phase velocity differences in different plasma densities. The wavefront tilt leads to a parabolic trajectory of the plasma wakefield and hence the accelerated electron beam, which leads to an angular streaking of the emitted betatron radiation. In this way, the temporal evolution of the betatron X-ray spectra will be converted into angular “streak,” i.e., having a critical energy-angle correlation. An analytical model for the curved trajectory of a laser pulse in a transverse density gradient is presented. This gives the deflection angle of the electron beam and the betatron X-rays as a function of the plasma and laser parameters, and it was verified by particle-in-cell simulations. This angular streaking could be used as a single-shot diagnostic technique to reveal the temporal evolution of betatron X-ray spectra and hence the electron acceleration itself.
Characteristics of UV-induced bulk damage in large-aperture fused silica from full-sized beam tests
Authors: Tian Ye , Yuan Xiaodong , Hu Dongxia , Zhu Qihua , Han Wei
Published: November 2018

Laser-induced bulk damage in fused silica is studied on a large-aperture laser system with 6 J/cm2, 5-ns shot sequences at 351 nm. The lateral dimension of bulk damage is found to propagate exponentially with shot number in a wide range of growth rates, similar to the stochastic trend as displayed by rear-surface damage. Resemblance in the morphology between bulk and surface damage is revealed offline by microscopic observations. Arising from the accumulated effect of fluence variation, the repetitive laser exposures tend to create an increased number of bulk damage, the tendency of which is applied to evaluate the number of damage initiations via simulations.
New Products
Authors: Mandelis Andreas
Published: November 2018

In order to supplement manufacturers’ information, this Department will welcome the submission by our readers of brief communications reporting measurements on the physical properties of materials which supersede earlier data or suggest new research applications.
Ecological impacts of the little fire ant (Wasmannia auropunctata) in Tahiti
Authors: Bousseyroux Alice , Blanvillain Caroline , Darius Timeri , Vanderwoude Casper , Beaune David
Published: November 2018

The little fire ant (Wasmannia auropunctata) is one of the worst invasive exotic species of the world. Its pantropical expansion is explosive; the ant has been present in Tahiti for more than 20 years. This study is the first to be carried out in Tahiti to assess its ecological impacts. The ecological richness of three invaded environments located in or close to the Key Biodiversity Areas (Maruapo, Papehue, Hopuetamai and Orofero Valleys) was compared with that of adjoining uninvaded sites, in a xerophytic site of ferns and a rainforest in the bottom of a valley for invertebrates and finally a canyon and its cliffs for avifauna. At the last site, one bank is infested and the other bank is free of W. auropunctata. Invertebrates and birds were examined respectively by pitfall traps and observation points. The effects of W. auropunctata were significantly negative at each study site, and species diversity in infested sites was one-third of that in uninfested sites. For arthropods, the phytophages, omnivores, detritivores, predators and other ants were the most affected. Significantly fewer birds also frequented the infested shoreline, particularly endemic birds such as the Tahiti monarch (81% non-infested shoreline observation) and the Society fruit-dove in comparison with the adjacent non-infested shoreline. Moreover, Tahiti monarchs (which are territorial) were established in three territories located at the bottom of the infested zone or close to it in 2016. These birds have now deserted the areas colonised by W. auropunctata. Our results suggest that W. auropunctata is a serious threat to Tahitian terrestrial biodiversity, and related ecosystem services.
Multiple prebiotic metals mediate translation
Authors: Bray Marcus S. , Lenz Timothy K. , Haynes Jay William , Bowman Jessica C. , Petrov Anton S. , Reddi Amit R. , Hud Nicholas V. , Williams Loren Dean , Glass Jennifer B.
Published: November 2018

Significance

Ribosomes are found in every living organism, where they are responsible for the translation of messenger RNA into protein. The ribosome’s centrality to cell function is underscored by its evolutionary conservation; the core structure has changed little since its inception ∼4 billion years ago when ecosystems were anoxic and metal-rich. The ribosome is a model system for the study of bioinorganic chemistry, owing to the many highly coordinated divalent metal cations that are essential to its function. We studied the structure, function, and cation content of the ribosome under early Earth conditions (low O2, high Fe2+, and high Mn2+). Our results expand the roles of Fe2+and Mn2+in ancient and extant biochemistry as cofactors for ribosomal structure and function.
Chromatin modifiers Mdm2 and RNF2 prevent RNA:DNA hybrids that impair DNA replication
Authors: Klusmann Ina , Wohlberedt Kai , Magerhans Anna , Teloni Federico , Korbel Jan O. , Altmeyer Matthias , Dobbelstein Matthias
Published: November 2018

Significance

Accurate DNA replication is a prerequisite for cell proliferation and genetic stability, but obstacles to smooth replication fork progression are frequent. The oncogenic activity of Mdm2 has been largely ascribed to its ability of antagonizing the tumor suppressor p53. This report, however, points out a p53-independent activity of Mdm2 in suppressing R loops, a structure that includes DNA:RNA hybrids and has recently emerged as a key obstacle to DNA replication. Accordingly, Mdm2 is required for sustaining DNA replication. Our results also reveal that Mdm2 and the polycomb repressor complexes act in parallel to not only modify histones but also support DNA replication. Thus, chromatin modifiers that were traditionally implicated in transcription regulation are enabling unperturbed DNA replication as well.
Folding pathway of an Ig domain is conserved on and off the ribosome
Authors: Tian Pengfei , Steward Annette , Kudva Renuka , Su Ting , Shilling Patrick J. , Nickson Adrian A. , Hollins Jeffrey J. , Beckmann Roland , von Heijne Gunnar , Clarke Jane , Best Robert B.
Published: November 2018

Proteins that fold cotranslationally may do so in a restricted configurational space, due to the volume occupied by the ribosome. How does this environment, coupled with the close proximity of the ribosome, affect the folding pathway of a protein? Previous studies have shown that the cotranslational folding process for many proteins, including small, single domains, is directly affected by the ribosome. Here, we investigate the cotranslational folding of an all-β Ig domain, titin I27. Using an arrest peptide-based assay and structural studies by cryo-EM, we show that I27 folds in the mouth of the ribosome exit tunnel. Simulations that use a kinetic model for the force dependence of escape from arrest accurately predict the fraction of folded protein as a function of length. We used these simulations to probe the folding pathway on and off the ribosome. Our simulations—which also reproduce experiments on mutant forms of I27—show that I27 folds, while still sequestered in the mouth of the ribosome exit tunnel, by essentially the same pathway as free I27, with only subtle shifts of critical contacts from the C to the N terminus.
Flavonols control pollen tube growth and integrity by regulating ROS homeostasis during high-temperature stress
Authors: Muhlemann Joëlle K. , Younts Trenton L. B. , Muday Gloria K.
Published: November 2018

Significance

Plant sexual reproduction is required for seed and fruit production and is highly sensitive to elevated temperatures, suggesting that climate change may have profound agricultural impacts through inhibition of this process. During reproduction, pollen tubes must navigate long distances through floral tissues to fertilize ovules. We demonstrate that high-temperature stress increases levels of reactive oxygen species in pollen tubes, which inhibits pollen tube growth. We report that specialized metabolites of the flavonol class prevent reactive oxygen species from reaching inhibitory levels at normal and increased temperatures, thereby promoting pollen viability and pollen tube growth. These results indicate that flavonols enhance reproduction, particularly during heat stress, and could confer protection to plants against the negative effects of climate change.
Introduction
Authors: Uth Melanie , García García Marco
Published: November 2018

Despite numerous theoretical approaches and empirical analyses, it is not entirely clear how different focus types and constructions are realized and interpreted in individual Romance languages. Due to the complexity of this linguistic area, an interdisciplinary and cross-linguistic approach seems most appropriate for exploring the topic further. This introductory article gives an overview of the core problems related to focus realization in Romance, such as methodological incongruences, differences regarding the conceptualization of focus categories, and nonobservance of diatopic variation. Moreover, it gives an outline of the present volume and situates the contributions with respect to the aforementioned issues.
Prosodic nuclear patterns in narrow and broad focus utterances
Authors: Martín-Butragueño Pedro , Vázquez Érika Mendoza
Published: November 2018

The main goal of this chapter is to discuss some of the nuclear pitch accents in the domain of broad and narrow foci in Central Mexican Spanish (CMS). Starting with a reconsideration of previous descriptions, the aim is to offer a unified vision of some of the main findings. It is hypothesized that focus marking is a phenomenon of variable and not categorical nature. Moreover, it is shown that focus marking competes with other pragmatic goals also using prosody as a relevant cue; and that focus marking is differentiated according to certain social, identity-related and stylistic factors. In this regard, we illustrate the variation of focus marking in different datasets, as well as the role of the expressive and the communicative functions of the foci. Intonational, pragmatic and sociolinguistic factor groups have been examined via up & down logistic regression models. Moreover, we show that the different tendencies of the observed intonational structures correlate with three speech styles and with some aspects of social stratification in CMS. Finally, the discussion presents a preliminary constraint model on focus domain marking in CMS that synthesizes some of the generalizations derived from the data.
Developing strategies for encoding additive and contrastive relations in French and German child narratives
Authors: Dimroth Christine , Benazzo Sandra
Published: November 2018

Speakers of French and German differ in their preferred choice of information components for establishing contrastive and additive discourse relations. Whereas French speakers tend to relate and compare discourse entities to each other across utterances, German speakers prefer to relate and compare assertions. The current study explores at which age French and German children (ages 4, 7, and 10) acquire the preferred discourse organizational principles of their respective languages. In order to disentangle typical properties of children’s discourse at a certain age from features reflecting the acquisition of language-specific preferences, the same set of elicited production data is compared across languages and age groups. Results show that despite common developmental trends, the principles underlying additive and contrastive discourse relations in German are acquired earlier than those in French. Whereas the relatively uniform German pattern can be seen as a continuation of earlier stages of acquisition, the French pattern is slightly more complex: There is more variation in the input and the prototypical integration of the relevant devices requires certain morpho-syntactic structures to be mastered first. From age 7 onward, child learners of both languages hone in on their target language’s preferred discourse structure.
Focus, prosody, and subject positions in L3 Spanish
Authors: Gabriel Christoph , Grünke Jonas
Published: November 2018

This paper investigates the acquisition of focus-induced word order variation by German learners of L3 Spanish, thereby comparing monolingual learners and multilinguals who speak Italian or European Portuguese (EP) as a heritage language in addition to their dominant language. Special attention is given to the position of focused subjects ([F S]) in non-complex declaratives. In accordance with Rothman’s (2010, 2011) Typological Primacy Model (TPM), we hypothesize that the multilingual learners behave more target-like than the monolinguals given that Italian and EP are typologically closer to Spanish than German and pattern with the target language with respect to the post-verbal position of [F S] in sentences lacking an overt object determiner phrase (DP). Based on elicited production data and a grammaticality judgment task, it is shown that the multilingual learners have only a slight advantage over the monolinguals, depending on their metalinguistic knowledge. This suggests that the predictions made by the TPM do not necessarily hold for the special case of foreign language learning by heritage speakers.
The rise of heritage and religious tourism to sacred sites in Oman.
Authors: Kessler K. , Raj R.
Published: November 2018

This chapter first discusses the close connection of heritage and religious tourism in the Sultanate of Oman with particular emphasis on historical and religious accounts. It then presents key religious sites, which, if promoted and developed appropriately, could increase the heritage tourism potential of Oman following the main objectives of the Ministry of Tourism's strategy.
Spiritual tourism in sufism in south Asia.
Authors: Hasnu S. A. F. , Saad Aslam Saad Aslam
Published: November 2018

This chapter identifies the importance of pilgrimage in Sufism and describes spiritual tourism and its different types in Islam, namely, Hajj/Umrah, Rihla and ziyara. Visiting graves of spiritual, pious individuals for spiritual development is ziyara. One such grave site in Peshawar, Pakistan, is described.
Religious tourism: the beginning of a new era with special reference to India.
Authors: Rumki Bandyopadhyay Rumki Bandyopadhyay , Kushagra Rajendra Kushagra Rajendra
Published: November 2018

This chapter focuses on the growth and development of religious tourism, with a focus on India. A focus on the potential in India for religious tourism highlights a diversity of religions and religious practices that are geographically and culturally disparate, and a society that exhibits many differentiations. The chapter discusses policy frameworks, infrastructure development, and tourist satisfaction, among other potential emerging needs.
Pilgrimage and historical tourism on West Java: learning about history.
Authors: Hellman J.
Published: November 2018

This chapter provides a broad introduction to pilgrimage on Java. The aim is to familiarize the reader with Javanese traditions of learning about self and society through travel. To illustrate this, the ethnographic focus is on a group of pilgrims who visit the sacred site of a local ancestor to learn more about themselves and the ancient Sundanese kingdom of Pajajaran.
To own the sacred, to control the people: a case study of the MahāBodhi Temple Complex in Bodhgayā, India.
Authors: Joshi N.
Published: November 2018

This chapter uses the Mahābodhi Temple complex, which is both a Buddhist and Hindu pilgrimage site, as an example to illustrate the inextricable interrelatedness between a sacred place and identity politics. It also highlights how the religious attention and gaze on historic structures and events of a particular cultural group often limits understanding of a place as a shared resource. The Mahābodhi Temple is an example of the (re)construction of a sacred space, which rapidly became transformed from a shared multivalent site into a fiercely contested sacred site with a significant support from the Orientalist construct of Buddhism.
Ancient, classical and modern biotechnology.
Authors: Brankov T. , Lovre K.
Published: November 2018

This chapter presents a description of the historical evolution of biotechnology and how biotechnology reflects human history. Definitions of biotechnology, genetic engineering, genetically modified (GM) organisms and GM food are given.
Genetically modified foods in the light of food regimes.
Authors: Brankov T. , Lovre K.
Published: November 2018

This chapter describes how transgenic technology issues can be understood in the light of food regime concepts and lead to different experience with genetically modified organisms (GMOs) in different countries. It discusses GMO neoregulation in the USA, the European Union (with particular reference to Spain), Brazil, Russia, China, India, South Africa and Serbia within a broader context, as an integral part of general agricultural policy. It provides a brief description of these countries' agricultural performances, agricultural supports and trade relations.
Food security and GMOs.
Authors: Brankov T. , Lovre K.
Published: November 2018

This chapter examines food security at the global and regional levels and assesses the effects of the cultivation of GMOs (transgenic crops) on world hunger. It is revealed that the gap in agricultural productivity between the rich and the poor has deepened in the last 20 years. Without reducing this gap it is not possible to solve global hunger. It is argued that unlike the Green Revolution that was designed to help small farmers in developing countries but was also suitable for large-scale farms, the Gene Revolution led by multinational companies will never reach small farmers.
Is GMO farming an eco-friendly choice?
Authors: Brankov T. , Lovre K.
Published: November 2018

This chapter discusses whether transgenic technology is an environmentally friendly technology. It analyses pesticide and fertilizer usage and efficiency over a period spanning 5 decades, with a clear distinction between before and after the adoption of transgenic technology. In addition, a comparison of pesticide consumption trends between genetically modified crop producing and nonproducing countries is made.
Different agonists induce distinct single-channel conductance states in TRPV1 channels
Authors: Canul-Sánchez Jesús Aldair , Hernández-Araiza Ileana , Hernández-García Enrique , Llorente Itzel , Morales-Lázaro Sara L. , Islas León D. , Rosenbaum Tamara
Published: November 2018

The TRPV1 ion channel is a membrane protein that is expressed in primary afferent nociceptors, where it is activated by a diverse array of stimuli. Our prior work has shown that this channel is activated by lysophosphatidic acid (LPA), an unsaturated lysophospholipid that is produced endogenously and released under certain pathophysiological conditions, resulting in the sensation of pain. Macroscopic currents activated by saturating concentrations of LPA applied to excised membrane patches are larger in magnitude than those activated by saturating concentrations of capsaicin, which causes near-maximal TRPV1 open probability. Here we show that activation of TRPV1 by LPA is associated with a higher single-channel conductance than activation by capsaicin. We also observe that the effects of LPA on TRPV1 are not caused by an increase in the surface charge nor are they mimicked by a structurally similar lipid, ruling out the contribution of change in membrane properties. Finally, we demonstrate that the effects of LPA on the unitary conductance of TRPV1 depend upon the presence of a positively charged residue in the C terminus of the channel, suggesting that LPA induces a distinct conformational change.
International comparison CCQM-K116: 10 μmol mol-1 water vapour in nitrogen
Authors: Brewer P J , Gieseking B , Ferracci V F , Ward M , Wijk J van , Veen A M H van der , Lima A A , Augusto C R , Oh S H , Kim B M , Lee S , Konopelko L A , Kustikov Y , Shimosaka T , Niederhauser B , Guillevic M , Pascale C , Zhou Z , Wang D , Hu S
Published: November 2018

The measurement of trace amounts of water in process gases is of paramount importance to a number of manufacturing processes. Water is considered to be one of the most difficult impurities to remove from gas supply systems and there is strong evidence that the presence of water contamination in semiconductor gases has a measurable impact on the quality and performance of devices. Consequently, semiconductor manufacturers are constantly reducing target levels of water in purge and process gases. As the purity of gases improves, the problem of quantifying contamination and ensuring that the gases are within specification at the point of use becomes more challenging. There are several established techniques for detecting trace water vapour in process gases. These include instruments based on the chilled mirror principle which measures the dew-point of the gas and the quartz crystal adsorption principle which measures the adsorption of water vapour into a crystal with a hygroscopic coating. Most recently, spectroscopic instruments such as those employing cavity ring-down spectroscopy (CRDS) have become available. The calibration of such instruments is a difficult exercise because of the very limited availability of accurate water vapour standards. This CCQM key comparison aims to assess the analytical capabilities of laboratories for measuring the composition of 10 μmol mol-1 water vapour in nitrogen.

KEY WORDS FOR SEARCH

Metrology, traceability, water vapour, process gas, advance manufacturing

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Effect of Fly Ash Content and Applied Load On Wear Behaviour of AA6063 Aluminium Alloy
Authors: Razzaq Alaa Mohammed , Majid Dayang Laila , Manan Nor Hafizah , Ishak Mohamad R. , Basheer Uday M.
Published: November 2018

The AA6063 alloy reinforced with 0, 2, 4 and 6 wt. % of fly ash (FA) particulate composites were produced by the compocasting technique. In this study, the effect of FA content and sliding speed on the wear behaviour of AA6063-FA composite was investigated. The wear was carried out by using pin on disc apparatus against rough steel counterface. These wear tests were conducted at applied load of 24.5, 49 and 73.5 N respectively with the constant sliding speed (150 rpm) and sliding time (10 minutes). In the results, it has been observed that upon addition of FA particles, the wear resistance of AA6063 -FA composites was enhanced. The wear rate reduced with the increase in the content of FA particles. While the wear rate increased with increase in the applied load.