bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live Tissue Imaging to Elucidate Mechanical Modulation of Stem Cell Niche Quiescence
Authors: Yu Nicole Y.C. , O’Brien Connor A. , Slapetova Iveta , Whan Renee M. , Knothe Tate Melissa L. 
Published: July 2016

Abstract
The periosteum, a composite cellular connective tissue, bounds all nonarticular bone surfaces. Like Velcro, collagenous Sharpey's fibers anchor the periosteum in a prestressed state to the underlying bone. The periosteum provides a niche for mesenchymal stem cells. Periosteal lifting, as well as injury, causes cells residing in the periosteum (PDCs) to change from an immobile, quiescent state to a mobile, active state. The physical cues that activate PDCs to home to and heal injured areas remain a conundrum. An understanding of these cues is key to unlocking periosteum's remarkable regenerative power. We hypothesized that changes in periosteum's baseline stress state modulate the quiescence of its stem cell niche. We report, for the first time, a three-dimensional, high-resolution live tissue imaging protocol to observe and characterize ovine PDCs and their niche before and after release of the tissue's endogenous prestress. Loss of prestress results in abrupt shrinkage of the periosteal tissue. At the microscopic scale, loss of prestress results in significantly increased crimping of collagen of periosteum's fibrous layer and a threefold increase in the number of rounded nuclei in the cambium layer. Given the body of published data describing the relationships between stem cell and nucleus shape, structure and function, these observations are consistent with a role for mechanics in the modulation of periosteal niche quiescence. The quantitative characterization of periosteum as a stem cell niche represents a critical step for clinical translation of the periosteum and periosteum substitute-based implants for tissue defect healing.
Concise Review: Cell Surface N-Linked Glycoproteins as Potential Stem Cell Markers and Drug Targets
Authors: Boheler Kenneth R. , Gundry Rebekah L. 
Published: July 2016

Abstract
Stem cells and their derivatives hold great promise to advance regenerative medicine. Critical to the progression of this field is the identification and utilization of antibody-accessible cell-surface proteins for immunophenotyping and cell sorting—techniques essential for assessment and isolation of defined cell populations with known functional and therapeutic properties. Beyond their utility for cell identification and selection, cell-surface proteins are also major targets for pharmacological intervention. Although comprehensive cell-surface protein maps are highly valuable, they have been difficult to define until recently. In this review, we discuss the application of a contemporary targeted chemoproteomic-based technique for defining the cell-surface proteomes of stem and progenitor cells. In applying this approach to pluripotent stem cells (PSCs), these studies have improved the biological understanding of these cells, led to the enhanced use and development of antibodies suitable for immunophenotyping and sorting, and contributed to the repurposing of existing drugs without the need for high-throughput screening. The utility of this latter approach was first demonstrated with human PSCs (hPSCs) through the identification of small molecules that are selectively toxic to hPSCs and have the potential for eliminating confounding and tumorigenic cells in hPSC-derived progeny destined for research and transplantation. Overall, the cutting-edge technologies reviewed here will accelerate the development of novel cell-surface protein targets for immunophenotyping, new reagents to improve the isolation of therapeutically qualified cells, and pharmacological studies to advance the treatment of intractable diseases amenable to cell-replacement therapies.
Amplified spontaneous emission of phonons as a likely mechanism for density-dependent velocity saturation in GaN transistors
Authors: Khurgin Jacob B. , Bajaj Sanyam , Rajan Siddharth 
Published: July 2016

Abstract
We show that density-dependent velocity saturation in a GaN high electron mobility transistor (HEMT) can be related to the stimulated emission of longitudinal optical (LO) phonons. As the drift velocity of electrons increases, the drift of the Fermi distribution in reciprocal space results in population inversion and gain for the LO phonons. Once this gain reaches a threshold value, the avalanche-like increase in LO phonon emission causes a rapid loss of electron energy and momentum and leads to drift velocity saturation. Our simple model correctly predicts both the general trend of decreasing saturation velocity with increasing electron density, and the measured experimental values of saturation.
Development of a prototype T-shaped fast switching device for electron cyclotron current drive systems
Authors: Sekiguchi Kenji , Nagashima Koji , Honzu Toshihiko , Saigusa Mikio , Oda Yasuhisa , Takahashi Koji , Sakamoto Keishi 
Published: July 2016

Abstract
A T-shaped high-power switching device composed of circular corrugated waveguides with three ports and double dielectric disks made of sapphire was proposed as a fast switching device based on a new principle in electron cyclotron current drive systems. This switching device has the advantages of operating at a fixed frequency and being compact. The design of the prototype switch was obtained by numerical simulations using a finite-difference time-domain (FDTD) method. The size of these components was optimized for the frequency band of 170 GHz. Low-power tests were carried out in a cross-shaped model.
Quantification and attribution of errors in the simulated annual gross primary production and latent heat fluxes by two global land surface models
Authors: Li Jianduo , Wang Ying‐Ping , Duan Qingyun , Lu Xingjie , Pak Bernard , Wiltshire Andy , Robertson Eddy , Ziehn Tilo 
Published: July 2016

AbstractDifferences in the predicted carbon and water fluxes by different global land models have been quite large and have not decreased over the last two decades. Quantification and attribution of the uncertainties of global land surface models are important for improving the performance of global land surface models, and are the foci of this study. Here we quantified the model errors by comparing the simulated monthly global gross primary productivity (GPP) and latent heat flux (LE) by two global land surface models with the model‐data products of global GPP and LE from 1982 to 2005. By analyzing model parameter sensitivities within their ranges, we identified about 2–11 most sensitive model parameters that have strong influences on the simulated GPP or LE by two global land models, and found that the sensitivities of the same parameters are different among the plant functional types (PFT). Using parameter ensemble simulations, we found that 15%–60% of the model errors were reduced by tuning only a few (<4) most sensitive parameters for most PFTs, and that the reduction in model errors varied spatially within a PFT or among different PFTs. Our study shows that future model improvement should optimize key model parameters, particularly those parameters relating to leaf area index, maximum carboxylation rate, and stomatal conductance.
Substantial overnight reaeration by convective cooling discovered in pond ecosystems
Authors: Holgerson Meredith A. , Zappa Christopher J. , Raymond Peter A. 
Published: July 2016

AbstractTrends in freshwater dissolved oxygen (DO) reflect whole‐ecosystem properties and influence organismal survival and behavior. Here we show that small ponds have unique oxygen dynamics that differ from larger lakes. We discovered that ponds undersaturated in DO experienced substantial increases in oxygen concentration overnight. Nighttime increases in DO occurred on 45% of the nights sampled and resulted in DO saturation increasing 12‐fold (22% saturation) on average. Oxygen spikes were likely to occur when ponds became at least 1.8°C warmer than the air and later in the season when oxygen levels were low (<31% saturation) and the air was warm (≥5.8°C). We demonstrate that overnight increases in surface water DO resulted from atmospheric oxygen invasion as opposed to internal production. Convective cooling enhanced turbulence and air‐water gas exchange, leading to intense bursts of oxygen invasion during nighttime hours. This mechanism has not been demonstrated before and has important implications for the biogeochemistry of these systems, as well as understanding how organisms survive in hypoxic small ponds.
Addendum to 2‐Butoxyethanol (Ethylene glycol monobutyl ether) [BAT Value Documentation, 2009]
Authors: Angerer J. , Drexler H. , Hartwig A. ,   MAK Commission
Published: July 2016

2‐Butoxyethanol (Ethylene glycol monobutyl ether): Addendum BAT value documentation (2008)
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value at the work place (BAT value) for 2‐butoxyethanol (ethylene glycol monobutyl ether), considering butoxyacetic acid in urine to characterise the internal exposure. Available publications are described in detail.
In male and female individuals exposed to 2‐butoxyethanol, irritant effects to eyes, nose and throat as well as a disturbed taste, headaches and vomiting were observed. The main systemic adverse effects of 2‐butoxyethanol are on the haematopoietic system (haemolytic effects), followed by possible teratogenic and testicular effects. In addition, effects on the central nervous system, the liver and the kidneys were discussed. 2‐Butoxyethanol was classified in category 4 for carcinogenic substances. It can pass through the skin so biological monitoring is necessary.

Human studies on exposure and effects, however, are still not available. In more recent animal studies for the haemolytic effects a NOAEC of 25 ml 2‐butoxyethanol/m
3
after chronic exposure of rats was obtained. In vivo and in vitro data indicate that regarding to the haemolytic effects rats are more sensitive than humans. At 20 ml 2‐butoxyethanol/m
3
and the correlating BAT value of 100 mg butoxyacetic acid/l urine, no haemolytic effects are to be expected according to these recent studies. Also no other systemic effects are to be expected, as no prenatal toxicity was observed up to 100 ml 2‐butoxyethanol/m3 and no effects on male reproductive organs occurred even at 125 ml/m
3
(rats) or 250 ml/m
3
(mice). In addition, the correlation between 100 mg butoxyacetic acid/l urine and 20 ml 2‐butoxyethanol/m
3
is supported by a recently available study with individuals.

The previous BAT value of 100 mg free butoxyacetic acid/l urine*, which intended to protect against systemic effects (especially haemolytic effects), is therefore retained. The sampling time is at the end of exposure/shift after several previous shifts.
A considerable part of the absorbed 2‐butoxyethanol is excreted in the form of the glutamine conjugate of butoxyacetic acid, i. e. N‐butoxyacetyl glutamine varying intra‐ and inter‐individually. According to published data, about twice as much total butoxyacetic acid as free butoxyacetic acid is excreted. Therefore, a further BAT value of 200 mg butoxyacetic acid (after hydrolysis)/l urine* is established for the sum of free and conjugated butoxyacetic acid.
These BAT values apply for both 2‐butoxyethanol and 2‐butoxyethylacetate.
*no longer valid
Addendum zu Brommethan (Methylbromid) [BAT Value Documentation in German language, 2016]
Authors: Hallier E. , Müller M. , Drexler H. , Hartwig A. ,   MAK‐Kommission
Published: July 2016

Brommethan (Methyl bromide): Addendum BAT value documentation (2016)The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the “Biologischer Leitwert” (BLW) for methyl bromide, using bromide in serum/plasma to characterize the internal exposure. The critical effect of methyl bromide is a high acute and chronic neurotoxicity. It can pass through the skin so that biological monitoring is highly recommended.On the basis of results of a human study the occurrence of abnormal findings in the EEG is comparable for unexposed persons and persons with exposure to methyl bromide in concentrations below 12 mg bromide/l plasma. Thus the BLW value of 12 mg bromide/l plasma or serum was confirmed. The sampling time is at the end of exposure/shift after several previous shifts.
Merkaptursäuren des 2‐Chloroprens, des Epichlorhydrins und des 1,3‐Butadiens im Urin [Biomonitoring Methods in German Language, 2015]
Authors: Eckert E. , Göen T. , Hartwig A. ,   MAK Commission
Published: July 2016

AbstractThe analytical method permits simultaneous determination of the mercapturic acid of epichlorohydrin i.e. N‐acetyl‐S‐(3‐chloro‐2‐hydroxypropyl) cysteine (CHPMA) and of four mercapturic acids of 2‐chloroprene in urine: N‐acetyl‐S‐(4‐chloro‐3‐oxobutyl) cysteine (Cl‐MA I), N‐acetyl‐S‐(3‐chloro‐2‐hydroxy‐3‐butenyl) cysteine (Cl‐MA III), N‐acetyl‐S‐(4‐hydroxy‐3‐oxobutyl) cysteine (HOBMA) and N‐acetyl‐S‐(3,4‐dihydroxybutyl) cysteine (DHBMA). The mercapturic acids HOBMA and DHBMA are also formed after exposure to 1,3‐butadiene.For determination, the urine samples are buffered to pH 2.5, spiked with isotopelabeled internal standards (d3‐CHPMA, d3‐Cl‐MA I, d3‐Cl‐MA III, d3‐HOBMA and d7‐DHBMA), processed using online solid phase extraction (online SPE) and LC–MS/MS. For that purpose the analytes are enriched on a C18 pre‐concentration column [RAM (Restricted Access Material) phase]. 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. 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.
Hämoglobinaddukte von Ethylenoxid (N‐(2‐Hydroxyethyl)valin), Propylenoxid (N‐(2‐Hydroxypropyl)valin), Acrylnitril (N‐(2‐Cyanoethyl)valin), Acrylamid (N‐(2‐Carbonamidethyl)valin) und Glycidamid (N‐(2‐Hydroxy‐2‐carbonamidethyl)valin) [Biomonitoring Methods in German Language, 2015]
Authors: Schettgen T. , Müller J. , Ferstl C. , Angerer J. , Göen T. , Hartwig A. ,   MAK Commission
Published: July 2016

AbstractThe method permits the simultaneous quantification of the N‐terminal haemoglobin adducts N‐(2‐hydroxyethyl)valine (HEV), N‐(2‐hydroxypropyl)valine (HPV), N‐(2‐cyanoethyl)valine (CEV), N‐(2‐carbonamide ethyl)valine (AAV), and N‐(2‐hydroxy‐2‐carbonamide ethyl)valine (GAV) of the carcinogens ethylene oxide, propylene oxide, acrylonitrile, acrylamide, as well as of glycidamide the metabolite of acrylamide in blood.The adducts which are covalently bound to the N‐terminal valine of the globin chain are cleaved off from the globin chain by a modified Edman degradation. The resulting pentafluorophenyl thiohydantoine derivatives of the valine adducts are extracted with diethyl ether, purified and then subjected to tandem mass spectrometric detection. To protect the vicinal hydroxyl group of the glycidamide adduct, the modified Edman degradation is followed by a second derivatization using sulphuric acetone. For calibration, standards are prepared in non‐smoker pooled globin, adding solutions of dipeptide standards simulating the adduct‐bearing latter two N‐terminal amino acids of the haemoglobin chain. They are processed in the same way as the samples to be analyzed. As internal standards, solutions of isolated globin, which has prior been transformed with the deuterated compounds d3‐acrylo‐nitrile, d3‐acrylamide or d3‐propylene oxide, are used. As internal standard for glycidamide, the d8‐labeled, acetonized pentafluorophenyl thiohydantoine of the glycidamide valine adduct is used.
Di(2‐ethylhexyl) phthalate (DEHP) [MAK Value Documentation, 2015]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the mechanism of action, the effects after inhalation, the toxicity to fertility, the genotoxicity and carcinogenicity of di(2‐ethylhexyl) phthalate (DEHP). The literature has been searched for new studies relevant to the evaluation of these endpoints. Prenatal toxicity is not included in this evaluation.

A MAK value of 2 mg/m
3
for the inhalable fraction has been calculated by toxicokinetic extrapolation from the lowest oral NOAEL of 3.7 mg DEHP/kg body weight and day (90‐day rat study). At the LOAEL (38 mg/kg body weight and day) vacuolization of Sertoli cells was observed. The MAK value is markedly below the NOAEC of 50 mg/m
3
in a 28‐day rat inhalation study. The larynx was not investigated in this study. Although it might have been a possible target organ, because the structurally related dibutyl phthalate caused low grade squamous metaplasia in the larynx, this effect is regarded as adaptive.

As systemic toxicity is critical, DEHP is classified in Peak Limitation Category II. The effects are more likely attributable to monoethylhexyl phthalate (MEHP) or its further metabolites. As the initial half‐life of MEHP of 1.9 hours is decisive for the peak concentrations in the blood, an excursion factor of 2 has been established.
DEHP induced hepatocellular adenomas and carcinomas in rats and mice, as well as tumours originating from the enterochromaffin cells of the stomach and from the acinar and islet cells of the pancreas. A new long term study with male rats confirms the data. Since the documentation from 2002 no new mechanistic data or genotoxicity studies have become available which call into question the previous carcinogenicity evaluation. The classification in Carcinogen Category 4 is therefore retained.
As available data for DEHP and its metabolites in vitro and in vivo do not provide any clear evidence of genotoxic effects, DEHP is not classified in one of the categories for germ cell mutagens.
Dermal absorption can provide a relevant contribution to systemic toxicity. DEHP is therefore designated with an “H”. The substance is not sensitising to skin or airways.
N‐Cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt [MAK Value Documentation, 2013]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. A gavage study with rats given daily doses of the substance for 3 months yielded a NOAEL of 25 mg/kg body weight and day; effects on the blood and liver and mortality occurred at 50 mg/kg body weight and day. Based on this NOAEL, a MAK value of 10 mg/m
3
has been established for the inhalable fraction of N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt. The MAK value was derived from a systemic NOAEL; therefore, N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt is classified in Peak Limitation Category II with a default excursion factor of 2 as sufficient toxicokinetic data are not available. Calculations of dermal absorption based on in vitro studies show that dermal absorption would contribute substantially to the systemic toxicity. Therefore, N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt has been designated with an “H”. N‐Cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt is not genotoxic or carcinogenic and limited data show no sensitizing potential in mice. Because there are no studies on developmental toxicity of N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt, it is assigned to Pregnancy Risk Group D.
Dimethylsulfoxid [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

Dimethyl sulfoxide

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration of dimethyl sulfoxide at the workplace (MAK value) of 50 ml/m
3
, considering the endpoints local and systemic toxicity as well as developmental toxicity. In a 13‐week inhalation study the olfactory and respiratory epithelia and the pharynx of rats were the target tissues, and reduction of body weight gain, possibly secondary to the irritation, was seen. The NOAEC for these effects is 964 mg/m
3
(297 ml/m
3
, vapour). 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, a MAK value of 50 ml/m
3
can be calculated from this study, taking into account that a lower NOAEC has to be expected with chronic exposure. Therefore, the previous MAK value is retained. As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 2 are retained. The borderline increase in incidences of pups with dilated renal pelvis seen in the developmental toxicity study was not confirmed in a screening study with rats according to OECD Test Guideline 421. However, in rabbits dimethyl sulfoxide causes kidney malformations with a NOAEL of 300 mg/kg bw. Therefore, damage to the embryo or foetus cannot be excluded even when the MAK value is observed and dimethyl sulfoxide is assigned to Pregnancy Risk Group B.
Multiple Ionization of Free Ubiquitin Molecular Ions in Extreme Ultraviolet Free‐Electron Laser Pulses
Authors: Schlathölter Thomas , Reitsma Geert , Egorov Dmitrii , Gonzalez‐Magaña Olmo , Bari Sadia , Boschman Leon , Bodewits Erwin , Schnorr Kirsten , Schmid Georg , Schröter Claus Dieter , Moshammer Robert , Hoekstra Ronnie 
Published: July 2016

AbstractThe fragmentation of free tenfold protonated ubiquitin in intense 70 femtosecond pulses of 90 eV photons from the FLASH facility was investigated. Mass spectrometric investigation of the fragment cations produced after removal of many electrons revealed fragmentation predominantly into immonium ions and related ions, with yields increasing linearly with intensity. Ionization clearly triggers a localized molecular response that occurs before the excitation energy equilibrates. Consistent with this interpretation, the effect is almost unaffected by the charge state, as fragmentation of sixfold deprotonated ubiquitin leads to a very similar fragmentation pattern. Ubiquitin responds to EUV multiphoton ionization as an ensemble of small peptides.