bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity of snow density and specific surface area measured by microtomography to different image processing algorithms
Authors: Hagenmuller Pascal , Matzl Margret , Chambon Guillaume , Schneebeli Martin
Published: January 2016

Abstract. Microtomography can measure the X-ray attenuation coefficient in a 3D volume of snow with a spatial resolution of a few microns. In order to extract quantitative characteristics of the microstructure, such as the specific surface area (SSA), from these data, the grayscale image first needs to be segmented into a binary image of ice and air. Different numerical algorithms can then be used to compute the surface area of the binary image. In this paper, we report on the effect of commonly used segmentation and surface area computation techniques on the evaluation of density and specific surface area. The evaluation is based on a set of 38 X-ray tomographies of different snow samples without impregnation, scanned with an effective voxel size of 10 and 18 μm. We found that different surface area computation methods can induce relative variations up to 5 % in the density and SSA values. Regarding segmentation, similar results were obtained with sequential and energy-based approaches provided the associated parameters are correctly chosen. The voxel size also appears to affect the values of density and SSA, but because images with the higher resolution also show the higher noise level, it was not possible to draw a definitive conclusion on this effect of resolution. Finally, practical recommendations concerning the processing of X-ray tomographic images of snow are provided.
Brief communication: On area- and slope-related thickness estimates and volume calculations for unmeasured glaciers
Authors: Haeberli W.
Published: January 2016

Abstract. Area- and slope-related techniques have been used to estimate thicknesses and to calculate volumes of unmeasured glaciers on the basis of glacier outlines and corresponding glacier surface areas in glacier inventories. The present communication critically reflects key aspects involved with the application of these approaches to field data. Area-related empirical statistics are known to only provide order-of-magnitude estimates if applied to individual glaciers or glacier ensembles spanning less than several orders of magnitude. Even at this scale, however, problems exist with respect to calibration/validation, error propagation, artefacts (immediate mass loss in case of coalescing/disintegrating composite glaciers) and shortcomings (no detection of ice below sea level or below lake levels on land in view of glacier contributions to sea-level rise). 3-D-flux/stress/slope-related approaches and numerical models are better constrained by calibration/validation with field measurements. They help with overcoming the problems of 2-D-area-related statistics in that they allow for calculating detailed glacier bed topographies at all scales, from individual glaciers to global ensembles. Corresponding results are available today and can be further improved.
Effects of agricultural practices on soil and microbial biomass carbon, nitrogen and phosphorus content: a preliminary case study
Authors: Amaral F. , Abelho M.
Published: January 2016

Abstract. In this study we assessed the C : N : P ratios in soil and soil microbial biomass subject to conventional farming and three different organic farming practices. The results showed that microbial biomass was P-limited in soils subject to conventional farming and to organic farming with alfalfa green manure. Organic farming with compost amendment showed the best results in terms of microbial biomass carbon, nitrogen and phosphorus (CNP).
Pre-Service Teachers’ Belief Sources about Learning and Teaching: An Exploration with the Consideration of the Educational Programme Nature
Authors: Debreli Emre
Published: January 2016

It is often said that beliefs determine the ways teachers think and act in classrooms. There is now strong evidence that teachers’ beliefs are formed during their previous education as students, and that they exert a powerful influence throughout their careers. However, only little has yet been done on the teacher education programmes’ influence on teachers’ beliefs, especially by taking the programme nature into consideration. The present study attempted to explore whether it is the previous learning experiences or the teacher education programme that influenced teachers’ belief formation. Data were collected from sixteen ELT pre-service teachers in a university in Northern Cyprus through semi-structured interviews. Findings revealed that programme nature had a significant influence on pre-service teachers’ belief formation compared to the influence of their previous learning experiences. Other sources of beliefs were also identified. Implications for teacher education are discussed.
The Questionnaire of Marital Conflicts: A Confirmatory Factor Analysis (CFA)
Authors: Boostanipoor Alireza , Zaker Bagher Sanai
Published: January 2016

The family provides a healthy context for growth and reform. The function of the family is to support the character formation of its members while creating among them the sense of belonging. There have always been several views about the family with healthy and unhealthy functions. What is present in all these views is that a healthy family is a family in which the spouses are in a healthy and effective relationship. However, most of the couples who attend counseling centers state that their main problems are relationship problems and conflicts. So, there have been always necessary to have a tool for measuring the concept of conflict and its dimensions in every cultural context. To meet this need, the questionnaire of marital conflict has been provided which primary from involves 42 questions in 7 subscales; which, in the present research, it has been tried, to evaluate another one of the main dimensions of marital conflict, decreased effective contact, by adding 12 questions to the primary questionnaire. Then, on its confirmatory factor analysis, the present questionnaire was filled out by 270 participants. The results are indicative of optimal psychometric properties (α=0.96), and accepted clinical and scholarly applications.
The Paradox of Bureaucratic Collaboration Government Bureaucracies in Robust Collaboration with the Public
Authors: Fox Carie , Murphy Philip
Published: January 2016

When a government agency engages in robust public participation, it puts bureaucratic culture at risk. Yet agencies do, sometimes, engage successfully in collaboration. The Paradox of Bureaucratic Collaboration suggests that an agency will be willing to engage in robust collaboration if the temporary disruption to bureaucratic systems helps the agency to become more perfectly bureaucratic in the long run. By applying systems perspectives to bureaucracy, this paper assists collaboration designers and would-be participants to understand when bureaucracies might not—or should not—collaborate robustly, to identify the opportunities for robust collaboration that prove the exception and, where robust collaboration is viable, to minimize bureaucratic risk while maximizing overall collaboration benefits.
Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally
Authors: Wasson Jadiel A , Simon Ashley K , Myrick Dexter A , Wolf Gernot , Driscoll Shawn , Pfaff Samuel L , Macfarlan Todd S , Katz David J
Published: January 2016

Somatic cell nuclear transfer has established that the oocyte contains maternal factors with epigenetic reprogramming capacity. Yet the identity and function of these maternal factors during the gamete to embryo transition remains poorly understood. In C. elegans, LSD1/KDM1A enables this transition by removing H3K4me2 and preventing the transgenerational inheritance of transcription patterns. Here we show that loss of maternal LSD1/KDM1A in mice results in embryonic arrest at the 1-2 cell stage, with arrested embryos failing to undergo the maternal-to-zygotic transition. This suggests that LSD1/KDM1A maternal reprogramming is conserved. Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults. These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes. These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development.
Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications
Authors: Harb Kawssar , Magrinelli Elia , Nicolas Céline S , Lukianets Nikita , Frangeul Laura , Pietri Mariel , Sun Tao , Sandoz Guillaume , Grammont Franck , Jabaudon Denis , Studer Michèle , Alfano Christian
Published: January 2016

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features.
Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin
Authors: Theodosiou Marina , Widmaier Moritz , Böttcher Ralph T , Rognoni Emanuel , Veelders Maik , Bharadwaj Mitasha , Lambacher Armin , Austen Katharina , Müller Daniel J , Zent Roy , Fässler Reinhard
Published: January 2016

Integrins require an activation step prior to ligand binding and signaling. How talin and kindlin contribute to these events in non-hematopoietic cells is poorly understood. Here we report that fibroblasts lacking either talin or kindlin failed to activate β1 integrins, adhere to fibronectin (FN) or maintain their integrins in a high affinity conformation induced by Mn2+. Despite compromised integrin activation and adhesion, Mn2+ enabled talin- but not kindlin-deficient cells to initiate spreading on FN. This isotropic spreading was induced by the ability of kindlin to directly bind paxillin, which in turn bound focal adhesion kinase (FAK) resulting in FAK activation and the formation of lamellipodia. Our findings show that talin and kindlin cooperatively activate integrins leading to FN binding and adhesion, and that kindlin subsequently assembles an essential signaling node at newly formed adhesion sites in a talin-independent manner.
An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells
Authors: Walter Marius , Teissandier Aurélie , Pérez-Palacios Raquel , Bourc'his Déborah
Published: January 2016

DNA methylation is extensively remodeled during mammalian gametogenesis and embryogenesis. Most transposons become hypomethylated, raising the question of their regulation in the absence of DNA methylation. To reproduce a rapid and extensive demethylation, we subjected mouse ES cells to chemically defined hypomethylating culture conditions. Surprisingly, we observed two phases of transposon regulation. After an initial burst of de-repression, various transposon families were efficiently re-silenced. This was accompanied by a reconfiguration of the repressive chromatin landscape: while H3K9me3 was stable, H3K9me2 globally disappeared and H3K27me3 accumulated at transposons. Interestingly, we observed that H3K9me3 and H3K27me3 occupy different transposon families or different territories within the same family, defining three functional categories of adaptive chromatin responses to DNA methylation loss. Our work highlights that H3K9me3 and, most importantly, polycomb-mediated H3K27me3 chromatin pathways can secure the control of a large spectrum of transposons in periods of intense DNA methylation change, ensuring longstanding genome stability.
Guanylate binding proteins directly attack Toxoplasma gondii via supramolecular complexes
Authors: Kravets Elisabeth , Degrandi Daniel , Ma Qijun , Peulen Thomas-Otavio , Klümpers Verena , Felekyan Suren , Kühnemuth Ralf , Weidtkamp-Peters Stefanie , Seidel Claus AM , Pfeffer Klaus
Published: January 2016

GBPs are essential for immunity against intracellular pathogens, especially for Toxoplasma gondii control. Here, the molecular interactions of murine GBPs (mGBP1/2/3/5/6), homo- and hetero-multimerization properties of mGBP2 and its function in parasite killing were investigated by mutational, Multiparameter Fluorescence Image Spectroscopy, and live cell microscopy methodologies. Control of T. gondii replication by mGBP2 requires GTP hydrolysis and isoprenylation thus, enabling reversible oligomerization in vesicle-like structures. mGBP2 undergoes structural transitions between monomeric, dimeric and oligomeric states visualized by quantitative FRET analysis. mGBPs reside in at least two discrete subcellular reservoirs and attack the parasitophorous vacuole membrane (PVM) as orchestrated, supramolecular complexes forming large, densely packed multimers comprising up to several thousand monomers. This dramatic mGBP enrichment results in the loss of PVM integrity, followed by a direct assault of mGBP2 upon the plasma membrane of the parasite. These discoveries provide vital dynamic and molecular perceptions into cell-autonomous immunity.
Cyanobacteria use micro-optics to sense light direction
Authors: Schuergers Nils , Lenn Tchern , Kampmann Ronald , Meissner Markus V , Esteves Tiago , Temerinac-Ott Maja , Korvink Jan G , Lowe Alan R , Mullineaux Conrad W , Wilde Annegret
Published: January 2016

Bacterial phototaxis was first recognized over a century ago, but the method by which such small cells can sense the direction of illumination has remained puzzling. The unicellular cyanobacterium Synechocystis sp. PCC 6803 moves with Type IV pili and measures light intensity and color with a range of photoreceptors. Here, we show that individual Synechocystis cells do not respond to a spatiotemporal gradient in light intensity, but rather they directly and accurately sense the position of a light source. We show that directional light sensing is possible because Synechocystis cells act as spherical microlenses, allowing the cell to see a light source and move towards it. A high-resolution image of the light source is focused on the edge of the cell opposite to the source, triggering movement away from the focused spot. Spherical cyanobacteria are probably the world’s smallest and oldest example of a camera eye.
Experimental observation of spin-to-charge current conversion at non-magnetic metal/Bi2O3 interfaces
Authors: Karube Shutaro , Kondou Kouta , Otani YoshiChika
Published: January 2016

Here, we demonstrate interfacial spin-to-charge current conversion by means of spin pumping from a ferromagnetic permalloy (Py: Ni80Fe20) to a Cu/Bi2O3 interface. A clear peak owing to the spin-to-charge current conversion was observed in the voltage spectrum of a Py/Cu/Bi2O3 trilayer film, whereas no peak was observed in Py/Cu and Py/Bi2O3 bilayer films. We also found that the conversion coefficient strongly depended on the Cu thickness, reflecting the thickness-dependent momentum relaxation time for the Cu layer.
Room-temperature hard coating of ultrananocrystalline diamond/nonhydrogenated amorphous carbon composite films on tungsten carbide by coaxial arc plasma deposition
Authors: Naragino Hiroshi , Egiza Mohamed , Tominaga Aki , Murasawa Koki , Gonda Hidenobu , Sakurai Masatoshi , Yoshitake Tsuyoshi
Published: January 2016

Ultrananocrystalline diamond (UNCD)/nonhydrogenated amorphous carbon (a-C) composite films were deposited on unheated WC containing Co by coaxial arc plasma deposition. The hardness of the film is 51.3 GPa, which is comparable with the highest values of hard a-C films deposited on nonbiased substrates. The deposited film is approximately 3 µm thick, which is one order larger than that of hard a-C films. The internal compressive stress is 4.5 GPa, which is evidently smaller than that of comparably hard a-C films. The existence of a large number of grain boundaries in the UNCD/a-C film might play a role in the release of the internal stress.
Development of a compact compression test stage for synchrotron radiation micro-Laue diffraction measurements of long-period stacking-ordered phases in Mg–Zn–Y alloys
Authors: Kimura Shigeru , Kajiwara Kentaro , Shimura Takayoshi
Published: January 2016

We have developed a compact compression test stage for synchrotron radiation (SR) micro-Laue diffraction (MLD) measurements to investigate the deformation behavior of Mg–Zn–Y alloys with long-period stacking-ordered (LPSO) structures. The stage can compress a small sample with a size of 0.3 × 0.3 × 1.0 mm3. The loading can be changed from 0 to 100 N. Using this compression test stage, MLD experiments were performed on a directionally solidified Mg85Zn6Y9 alloy polycrystal with a single 18R-type LPSO phase. We succeeded in revealing the change in the grain boundaries with increasing compression loading.
MRP1 mediates folate transport and antifolate sensitivity in Plasmodium falciparum
Authors: Rijpma Sanna R. , van der Velden Maarten , Bilos Albert , Jansen Robert S. , Mahakena Sunny , Russel Frans G. M. , Sauerwein Robert W. , van de Wetering Koen , Koenderink Jan B.
Published: January 2016

Multidrug resistance‐associated proteins (MRP) of Plasmodium falciparum have been associated with altered drug sensitivity. Knowledge on MRP substrate specificity is indispensible for the characterization of resistance mechanisms and identifying its physiological roles. An untargeted metabolomics approach detected decreased folate concentrations in red blood cells infected with schizont stage parasites lacking expression of MRP1. Furthermore, a tenfold decrease in sensitivity toward the folate analog methotrexate was detected for parasites lacking MRP1. PfMRP1 is involved in the export of folate from parasites into red blood cells and is therefore a relevant factor for efficient malaria treatment through the folate pathway.
Submesoscale streamers exchange water on the north wall of the Gulf Stream
Authors: Klymak Jody M. , Shearman R. Kipp , Gula Jonathan , Lee Craig M. , D'Asaro Eric A. , Thomas Leif N. , Harcourt Ramsey R. , Shcherbina Andrey Y. , Sundermeyer Miles A. , Molemaker Jeroen , McWilliams James C.
Published: January 2016

The Gulf Stream is a major conduit of warm surface water from the tropics to the subpolar North Atlantic. Here we observe and simulate a submesoscale (<20 km) mechanism by which the Gulf Stream exchanges water with subpolar water to the north. Along isopycnals, the front has a sharp compensated temperature‐salinity contrast, with distinct mixed water between the two water masses 2 and 4 km wide. This mixed water does not increase downstream despite substantial energy available for mixing. A series of streamers detrain this water at the crest of meanders. Subpolar water replaces the mixed water and resharpens the front. The water mass exchange accounts for a northward flux of salt of 0.5–2.5 psu m2 s−1, (large‐scale diffusivity O (100 m2 s−1)). This is similar to bulk‐scale flux estimates of 1.2 psu m2 s−1 and supplies fresher water to the Gulf Stream required for the production of 18° subtropical mode water.
Ice‐melt rates during volcanic eruptions within water‐drained, low‐pressure subglacial cavities
Authors: Woodcock D. C. , Lane S. J. , Gilbert J. S.
Published: January 2016

Subglacial volcanism generates proximal and distal hazards including large‐scale flooding and increased levels of explosivity. Direct observation of subglacial volcanic processes is infeasible; therefore, we model heat transfer mechanisms during subglacial eruptions under conditions where cavities have become depressurized by connection to the atmosphere. We consider basaltic eruptions in a water‐drained, low‐pressure subglacial cavity, including the case when an eruption jet develops. Such drained cavities may develop on sloping terrain, where ice may be relatively shallow and where gravity drainage of meltwater will be promoted. We quantify, for the first time, the heat fluxes to the ice cavity surface that result from steam condensation during free convection at atmospheric pressure and from direct and indirect radiative heat transfer from an eruption jet. Our calculations indicate that the direct radiative heat flux from a lava fountain (a “dry” end‐member eruption jet) to ice is c. 25 kW m−2 and is a minor component. The dominant heat transfer mechanism involves free convection of steam within the cavity; we estimate the resulting condensation heat flux to be c. 250 kW m−2. Absorption of radiation from a lava fountain by steam enhances convection, but the increase in condensing heat flux is modest at c. 25 kW m−2. Overall, heat fluxes to the ice cavity surface are likely to be no greater than c. 300 kW m−2. These are comparable with heat fluxes obtained by single phase convection of water in a subglacial cavity but much less than those obtained by two‐phase convection.
Combining GOSAT XCO2 observations over land and ocean to improve regional CO2 flux estimates
Authors: Deng Feng , Jones Dylan B. A. , O'Dell Christopher W. , Nassar Ray , Parazoo Nicholas C.
Published: January 2016

We used the GEOS‐Chem data assimilation system to examine the impact of combining Greenhouse Gases Observing Satellite (GOSAT) XCO2 data over land and ocean on regional CO2 flux estimates for 2010–2012. We found that compared to assimilating only land data, combining land and ocean data produced an a posteriori CO2 distribution that is in better agreement with independent data and fluxes that are in closer agreement with existing top‐down and bottom‐up estimates. Adding XCO2 data over oceans changed the tropical land regions from a source of 0.64 Pg C/yr to a sink of −0.60 Pg C/yr and produced a corresponding reduction in the estimated sink in northern and southern land regions by 0.49 Pg C/yr and 0.80 Pg C/yr, respectively. This highlights the importance of improved observational coverage in the tropics to better quantify the latitudinal distribution of the terrestrial fluxes. Based only on land XCO2 data, we estimated a strong source in northern tropical South America, which experienced wet conditions in 2010–2012. In contrast, with the land and ocean data, we estimated a sink for this wet region in the north, and a source for the seasonally dry regions in the south and east, which is consistent with our understanding of the impact of moisture availability on the carbon balance of the region. Our results suggest that using satellite data with a more zonally balanced observational coverage could help mitigate discrepancies in CO2 flux estimates; further improvement could be expected with the greater observational coverage provided by the Orbiting Carbon Observatory‐2.
Evidence for nonuniform permafrost degradation after fire in boreal landscapes
Authors: Minsley Burke J. , Pastick Neal J. , Wylie Bruce K. , Brown Dana R. N. , Andy Kass M.
Published: January 2016

Fire can be a significant driver of permafrost change in boreal landscapes, altering the availability of soil carbon and nutrients that have important implications for future climate and ecological succession. However, not all landscapes are equally susceptible to fire‐induced change. As fire frequency is expected to increase in the high latitudes, methods to understand the vulnerability and resilience of different landscapes to permafrost degradation are needed. We present a combination of multiscale remote sensing, geophysical, and field observations that reveal details of both near‐surface (<1 m) and deeper (>1 m) impacts of fire on permafrost. Along 11 transects that span burned‐unburned boundaries in different landscape settings within interior Alaska, subsurface electrical resistivity and nuclear magnetic resonance data indicate locations where permafrost appears to be resilient to disturbance from fire, areas where warm permafrost conditions exist that may be most vulnerable to future change, and also areas where permafrost has thawed. High‐resolution geophysical data corroborate remote sensing interpretations of near‐surface permafrost and also add new high‐fidelity details of spatial heterogeneity that extend from the shallow subsurface to depths of about 10 m. Results show that postfire impacts on permafrost can be variable and depend on multiple factors such as fire severity, soil texture, soil moisture, and time since fire.
S‐Alkyl mercapturic acids (methyl mercapturic acid, ethyl mercapturic acid, n‐propyl mercapturic acid und iso‐propyl mercapturic acid) in urine [Biomonitoring Methods, 2015]
Authors: Eckert E. , Göen T. , Hartwig A. ,   MAK Commission
Published: January 2016

The analytical method permits simultaneous determination of various alkyl mercapturic acids in urine. For determination, the urine samples are buffered to pH = 2.5, spiked with isotope labeled internal standards (d3‐MeMA, d5‐EtMA, d7‐PrMA and d7‐iPrMA), processed using online solid phase extraction (online SPE) and analyzed. For that purpose the analytes are enriched on a C18 preconcentration column [Restricted Access Material (RAM) phase] and separated from most of the matrix. Subsequently, the analytes are transferred in backflush mode from the RAM phase to the analytical column, separated chromatographically and finally subjected to tandem mass spectrometric detection. For quantification, a calibration is carried out using standard solutions in pooled urine which are processed and analyzed in the same way as the samples to be analyzed.
3‐Iodo‐2‐propynyl butylcarbamate (IPBC) [MAK Value Documentations, 2011]
Authors: Laube B. , Bartsch R. , Grebenstein R. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated 3‐iodo‐2‐propynyl butylcarbamate (IPBC) to establish a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail.

IPBC is irritating to the eyes and respiratory tract and has a skin sensitizing potential. New data have substantiated the previous designation with “Sh”.

In a 5‐day aerosol inhalation study in rats, hyperplasia, squamous metaplasia and necrosis of the underlying cartilage of the larynx were observed at 1 mg/m3and above. These effects were observed to an increased extent in the 13‐week study, in which the NOAEC was 0.23 mg/m3and the LOAEC 0.3 mg/m3. Since the laryngeal irritation is the most sensitive endpoint, a MAK value of 0.1 mg/m3(0.01 ml/m3) is established. IPBC has been attributed Peak Limitation Category I for local effects with an excursion factor of 2, since there was no direct sensory irritation but rather a tissue alteration and the NOAEC of the 5‐day study was 3 times the MAK value.

In rats IPBC caused no tumours in an oral 2‐year carcinogenicity study. Increased number of liver adenomas in male mice might have been caused by liver enzyme induction. Available studies in vitro and in vivo provided no evidence of a specific genotoxic effect. Therefore IPBC is not classified as carcinogen or germ cell mutagen.

In rats and mice, there was a sufficiently high difference between the oral NOAEL for developmental toxicity scaled to a concentration at the work place and the MAK value. Therefore IPBC is classified in Pregnancy Risk Group C.

Skin contact will not significantly contribute to the systemic toxicity of 3‐iodo‐2‐propynyl butylcarbamate.
Mercury and inorganic mercury compounds [MAK Value Documentations, 2011]
Authors: Meischner V. , Schriever-Schwemmer G. , Reuter U. , Greim H. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of mercury and inorganic mercury compounds of 0.1 mg Hg/m3, considering all toxicological endpoints. For mercury and inorganic mercury compounds biological monitoring (biological tolerance or BAT value) is indicated to correlate exposure and inner burden. Based on the reduction of the BAT value to 25 µg mercury/g creatinine in 2007, the MAK value is reduced to 0.02 mg/m3(calculated as mercury). Due to the systemic effects and the long half‐life, classification in Peak Limitation Category II with excursion factor 8 is retained.

Mercury and inorganic mercury compounds remain classified as possibly carcinogenic to humans as epidemiological studies show no conclusive carcinogenicity of mercury. However, in male rats at high doses squamous cell papillomas develop in the forestomach, and in male mice renal tubular adenomas and carcinomas increase. The mode of action and the relevance of these findings to humans is still unknown.

Inorganic mercury compounds are clastogenic in vitro, and the clastogenic effect could be confirmed in one animal study starting at 2 mg/kg body weight, which is at least 500 times above the MAK value of 0.02 mg/m3. Therefore mercury and inorganic mercury compounds are not classified in a category for Germ Cell Mutagens.

Data in humans are inconsistent and data in animals are insufficient to obtain a reliable statement as to whether the MAK value of 0.02 mg/m3protects from prenatal toxicity. Thus, mercury and inorganic mercury compounds are classified in Pregnancy Risk Group D.

Skin contact may contribute significantly to systemic toxicity and mercury and inorganic mercury compounds are designated with an “H” notation.

Sensitization and contact allergic reactions to mercury or inorganic mercury compounds in humans have been confirmed in other publications. Data on respiratory sensitization are not available. Mercury and its inorganic compounds continue to be designated with “Sh”, but not with “Sa”.
Methacrylsäure [MAK Value Documentation in German language, 2016]
Authors: Wiench K. , Bartsch R. , Leibold E. , Jahnke G. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Methacrylic acid

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of methacrylic acid of 5 ml/m3, considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effects of methacrylic acid are goblet cell hyperplasia/hypertrophy in the respiratory epithelia and reduced body weight gain in rats, which is probably a secondary effect of the irritation at 350 ml/m3in a 90‐day study. Since 2014 the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, the NOAEC of 100 ml/m3corresponds to a work place air concentration of 33 ml/m3. As the goblet cell hyperplasia is judged to be adaptive and its incidence is not significantly increased, the MAK value is elevated to 50 ml/m3. Since local effects are critical, the assignment to Peak Limitation Category I and the excursion factor 2 are confirmed. Studies with the read‐across methyl methacrylate which is cleaved to methacrylic acid show that damage to the embryo or foetus is unlikely when the MAK value for methacrylic acid is observed, and the assignment to Pregnancy Risk Group C is confirmed. Methacrylic acid and methyl methacrylate are not genotoxic. Carcinogenicity studies with methacrylic acid are lacking but methyl methacrylate is not carcinogenic. Skin contact does not contribute significantly to systemic toxicity and sensitization is not expected.
Isopropyl benzene (cumene) [MAK Value Documentations, 2013]
Authors: Jahnke G. , Hamann I. , Laube B. , Greim H. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated isopropyl benzene to derive a maximum concentration at the work place (MAK value), considering all toxicity endpoints. Available publications are described in detail. Isopropyl benzene caused adenomas in the nose of rats, and in mice adenomas and carcinomas in the lungs and adenomas in the liver. Genotoxic effects do not seem to be responsible for the carcinogenicity. Concerning the lung tumours of mice, it is assumed that ring hydroxylated metabolites stimulate cell proliferation, which can lead to tumour formation. In humans, the metabolism of aromatic molecules in the respiratory tissues is not yet clarified in detail and therefore carcinogenic effects of isopropyl benzene in humans cannot be excluded. Isopropyl benzene is therefore classified in Carcinogen Category 3B. Isopropyl benzene is not genotoxic, therefore, the derivation of a MAK value is possible. In agreement with the procedures used by the Commission, a MAK value of 10 ml/m
3
was set, derived from a calculated BMDL of 35 ml/m
3
for liver weight increase in the 14‐week study with rats and from the calculated BMDL of 42 ml/m
3
for nasal adenomas in the 2‐year study in rats. On the basis of the mainly systemic effects, the classification in Peak Limitation Category II is retained. The half‐life in humans is considerably longer than 2 hours, so that the excursion factor of 4 is also retained. No foetotoxic or teratogenic effects were found in rats and rabbits up to 1200 and 2300 ml/m
3
, respectively. As the difference between the NOAEC for developmental toxicity and the MAK value is sufficiently large, damage to the embryo or foetus is unlikely when the MAK value is observed. The assignment to Pregnancy Group C is confirmed. Skin contact may contribute significantly to systemic toxicity and the designation with an “H” notation is retained. Sensitisation is not expected based on the result of a maximisation test.
Reasons for Treatment Choices in Knee and Hip Osteoarthritis: A Qualitative Study
Authors: Selten Ellen M. , Vriezekolk Johanna E. , Geenen Rinie , van der Laan Willemijn H. , van der Meulen‐Dilling Roelien G. , Nijhof Marc W. , Schers Henk J. , van den Ende Cornelia H.
Published: January 2016

Objective

Conservative treatment modalities in osteoarthritis (OA) of the hip or knee are underused, whereas the demand for surgery is rising substantially. To improve the use of conservative treatment modalities, a more in‐depth understanding of the reasons for patients’ treatment choices is required. This study identifies the reasons for choice of treatment in patients with hip or knee OA.

Methods

Semistructured in‐depth interviews with 24 OA patients were held. Stratified purposive sampling was used to enrich data variation. Interviews were transcribed verbatim and subsequently coded using a thematic approach. Two independent researchers reflected on, compared, discussed, and adjusted the coding.

Results

Various treatment modalities were discussed by respondents: medication, exercise, physical therapy, injections, surgery, complementary, and alternative treatment. Four key themes underlying the choice for or against a treatment modality for OA were identified: 1) treatment characteristics: expectations about its effectiveness and risks, the degree to which it can be personalized to a patient's needs and wishes, and the accessibility of a treatment; 2) personal investment in terms of money and time; 3) personal circumstances: age, body weight, comorbidities, and previous experience with a treatment; and 4) support and advice from the patient's social environment and health care providers.

Conclusion

The 4 identified key themes enhance the insight of health care providers into the widespread reasons influencing patients’ treatment choices for knee or hip OA. This knowledge can be used in clinical practice to aid shared decision making, which may lead to optimized treatment choices for both conservative and surgical treatment.
Racial and Ethnic Disparities in the Pregnancies of Women With Systemic Lupus Erythematosus
Authors: Clowse Megan E. B. , Grotegut Chad
Published: January 2016

Objective

Both systemic lupus erythematosus (SLE; lupus) and pregnancy individually have significant racial disparities, with black women experiencing higher rates of complications, yet no large studies have focused on the impact of race/ethnicity on pregnancy outcomes among women with lupus.

Methods

Using the Nationwide Inpatient Sample (NIS) for 2008–2010, pregnancy delivery discharges were identified and pregnancy outcomes were compared for women with lupus by maternal race/ethnicity. Adjusted odds ratios were used to compare pregnancy outcomes between black and white or Hispanic and white women with lupus.

Results

In this period, the NIS included 13,553 deliveries with lupus and 12,510,565 deliveries without lupus. Compared to white women with lupus, black and Hispanic women had higher rates of chronic hypertension, chronic renal failure, pneumonia, and acute renal failure. There was a high degree of pregnancy complication in all women with lupus, but especially in black and Hispanic women, with more than 40% cesarean‐section delivery; preterm labor in 14.3% of white, 24.7% of black (odds ratio [OR] 1.97), and 20.6% of Hispanic (OR 1.56) deliveries; and preeclampsia and gestational hypertension in almost 20% of black and Hispanic pregnancies. After adjustment for predictors of pregnancy outcomes and racial differences in nonlupus pregnancy, black and Hispanic women with lupus had higher than expected rates of preeclampsia, preterm labor, and fetal growth restriction.

Conclusion

Black and Hispanic women with lupus have disproportionately poor pregnancy outcomes. This study suggests that identifying the key causes of these differences and targeting interventions to the women of greatest need is an essential next step.
Sensitivity to Change and Minimal Important Differences of the LupusQoL in Patients With Systemic Lupus Erythematosus
Authors: McElhone Kathleen , Abbott Janice , Sutton Chris , Mullen Montana , Lanyon Peter , Rahman Anisur , Yee Chee‐Seng , Akil Mohammed , Bruce Ian N. , Ahmad Yasmeen , Gordon Caroline , Teh Lee‐Suan
Published: January 2016

Objective

As a health‐related quality of life (HRQOL) measure, the LupusQoL is a reliable and valid measure for adults with systemic lupus erythematosus (SLE). This study evaluates the responsiveness and minimal important differences (MIDs) for the 8 LupusQoL domains.

Methods

Patients experiencing a flare were recruited from 9 UK centers. At each of the 10 monthly visits, HRQOL (LupusQoL, Short Form 36 health survey [SF‐36]), global rating of change (GRC), and disease activity using the British Isles Lupus Assessment Group 2004 index were assessed. The responsiveness of the LupusQoL and the SF‐36 was evaluated primarily when patients reported an improvement or deterioration on the GRC scale and additionally with changes in physician‐reported disease activity. MIDs were estimated as mean changes when minimal change was reported on the GRC scale.

Results

A total of 101 patients were recruited. For all LupusQoL domains, mean HRQOL worsened when patients reported deterioration and improved when patients reported an improvement in GRC; SF‐36 domains showed comparable responsiveness. Improvement in some domains of the LupusQoL/SF‐36 was observed with a decrease in disease activity, but when disease activity worsened, there was no significant change. LupusQoL MID estimates for deterioration ranged from −2.4 to −8.7, and for improvement from 3.5 to 7.3; for the SF‐36, the same MID estimates were −2.0 to −11.1 and 2.8 to 10.9, respectively.

Conclusion

All LupusQoL domains are sensitive to change with patient‐reported deterioration or improvement in health status. For disease activity, some LupusQoL domains showed responsiveness when there was improvement but none for deterioration. LupusQoL items were derived from SLE patients and provide the advantage of disease‐specific domains, important to the patients, not captured by the SF‐36.
A phosphorus‐containing phenolic derivative and its application in benzoxazine resins: Curing behavior, thermal, and flammability properties
Authors: Huo Siqi , Wang Jun , Yang Shuang , Zhang Bin , Tang Yushan
Published: January 2016

In this work, flame‐retardant benzoxazine resins were prepared by copolymerization of bisphenol A based benzoxazine (BA‐a) and a phosphorous‐containing phenolic derivative (DOPO‐HPM). The curing behavior, thermal stability, and flame resistance of BA‐a/DOPO‐HPM composites were studied by differential scanning calorimeter (DSC), thermogravimetric analysis (TGA), limited oxygen index (LOI) measurement, UL94 test, and cone calorimeter. The DSC results indicated that DOPO‐HPM catalyzed the curing reaction because of its acidity. The TGA results revealed that the BA‐a/DOPO‐HPM thermosets possessed higher decomposition temperatures (T5%) and char yields than that of BA‐a. The combustion tests indicated that the flame retardant properties of BA‐a/DOPO‐HPM thermosets were enhanced. The BA‐a/DOPO‐HPM‐20 sample acquired the highest LOI value of 32.6% and UL94 V‐0 rating. Moreover, the average of heat release rate (av‐HRR), peak of heat release rate (pk‐HRR), average of effective heat of combustion (av‐EHC) and total heat release (THR) of BA‐a/DOPO‐HPM‐20 were decreased by 24.6%, 53.1%, 14.9%, and 22.1%, respectively, compared with BA‐a. The attractive performance of BA‐a/DOPO‐HPM blends was attributed to the molecular structure of DOPO‐HPM composed of DOPO group with excellent flame‐retardant effect and phenolic hydroxyl group with catalysis. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43403.
Identification of IRX1 as a Risk Locus for Rheumatoid Factor Positivity in Rheumatoid Arthritis in a Genome‐Wide Association Study
Authors: Julià Antonio , Blanco Francisco , Fernández‐Gutierrez Benjamín , González Antonio , Cañete Juan D. , Maymó Joan , Alperi‐López Mercedes , Olivè Alex , Corominas Héctor , Martínez‐Taboada Víctor , González-Álvaro Isidoro , Fernandez‐Nebro Antonio , Erra Alba , Sánchez‐Fernández Simón , Alonso Arnald , López‐Lasanta María , Tortosa Raül , Codó Laia , Lluis Gelpi Josep , García‐Montero Andrés C. , Bertranpetit Jaume , Absher Devin , Myers Richard M. , Tornero Jesús , Marsal Sara
Published: January 2016

Objective

Rheumatoid factor (RF) is a well‐established diagnostic and prognostic biomarker in rheumatoid arthritis (RA). However, ∼20% of RA patients are negative for this anti‐IgG antibody. To date, only variation at the HLA–DRB1 gene has been associated with the presence of RF. This study was undertaken to identify additional genetic variants associated with RF positivity.

Methods

A genome‐wide association study (GWAS) for RF positivity was performed using an Illumina Quad610 genotyping platform. A total of 937 RF‐positive and 323 RF‐negative RA patients were genotyped for >550,000 single‐nucleotide polymorphisms (SNPs). Association testing was performed using an allelic chi‐square test implemented in Plink software. An independent cohort of 472 RF‐positive and 190 RF‐negative RA patients was used to validate the most significant findings.

Results

In the discovery stage, a SNP in the IRX1 locus on chromosome 5p15.3 (SNP rs1502644) showed a genome‐wide significant association with RF positivity (P = 4.13 × 10−8, odds ratio [OR] 0.37 [95% confidence interval (95% CI) 0.26–0.53]). In the validation stage, the association of IRX1 with RF was replicated in an independent group of RA patients (P = 0.034, OR 0.58 [95% CI 0.35–0.97] and combined P = 1.14 × 10−8, OR 0.43 [95% CI 0.32–0.58]).

Conclusion

To our knowledge, this is the first GWAS of RF positivity in RA. Variation at the IRX1 locus on chromosome 5p15.3 is associated with the presence of RF. Our findings indicate that IRX1 and HLA–DRB1 are the strongest genetic factors for RF production in RA.
Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti–High‐Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease
Authors: Rodríguez‐Carrio Javier , López‐Mejías Raquel , Alperi‐López Mercedes , López Patricia , Ballina‐García Francisco J. , González‐Gay Miguel Á. , Suárez Ana
Published: January 2016

Objective

Paraoxonase 1 (PON‐1) is a high‐density lipoprotein (HDL)–associated antioxidant enzyme that plays an important role in HDL‐mediated cardioprotection. Although genetic polymorphisms are known to modulate PON-1 activity, its involvement in cardiovascular disease (CVD) in rheumatoid arthritis (RA) is controversial, suggesting that other factors may modulate its function. Since anti‐HDL antibodies have been found to be related to an impaired lipid profile and occurrence of CVD in RA, this study was undertaken to examine the associations between PON-1 activity, anti‐HDL antibodies, and CVD according to PON1 genetic variants in patients with RA.

Methods

Serum PON-1 activity, using paraoxon as substrate, and IgG anti‐HDL antibodies were quantified in 212 RA patients and 110 healthy controls. The PON1 rs662 genotype (Q>R) was determined with TaqMan probes. An additional group of 13 biologics‐naive patients with RA was prospectively followed up for 3 months.

Results

PON‐1 activity was decreased in RA patients compared to healthy controls (P = 0.005), and an effect of the rs662 genotype was noted in both groups, with Q/Q homozygotes exhibiting the lowest PON‐1 activity. The distribution of rs662 genotypes did not differ between RA patients and healthy controls (P = 0.215). In patients carrying the Q/Q genotype, anti‐HDL antibodies were associated with impaired PON‐1 activity (P = 0.010), and levels of anti‐HDL antibodies were associated with decreased HDL levels (r = −0.680, P < 0.001) and higher prevalence of cardiovascular events, as determined in univariate and multivariate models. Furthermore, change in anti‐HDL antibody levels upon tumor necrosis factor blockade was an independent predictor of improved PON‐1 activity (β = −0.369, 95% confidence interval −0.669, −0.069; P = 0.024).

Conclusion

PON‐1 activity is impaired in RA in association with the rs662 genotype and anti‐HDL antibodies, the latter being recognized as a pivotal player in the link between rs662 and CVD in patients with RA.
Synthesis of Peptides by Silver‐Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies
Authors: Hutton Craig A. , Shang Jing , Wille Uta
Published: January 2016

The mechanism of the recently described N→C direction peptide synthesis through silver‐promoted coupling of N‐protected amino acids with thioacetylated amino esters was explored by using density functional theory. Calculation of the potential energy surfaces for various pathways revealed that the reaction proceeds through silver‐assisted addition of the carboxylate to the thioamide, which is followed by deprotonation and silver‐mediated extrusion of sulfur as Ag2S. The resulting isoimide is the key intermediate, which subsequently rearranges to an imide through a concerted pericyclic [1,3]‐acyl shift (O–sp2N 1,3‐acyl migration). The proposed mechanism clearly emphasises the requirement of two equivalents of AgI and basic reaction conditions, which is in full agreement with the experimental findings. Alternative rearrangement pathways involving only one equivalent of AgI or through O–sp3N 1,3‐acyl migration can be excluded. The computations further revealed that peptide couplings involving thioformamides require significant conformational changes in the intermediate isoformimide, which slow down the rearrangement process.