Naturally occurring diacetyl and 2,3-pentanedione concentrations associated with roasting and grinding unflavored coffee beans in a commercial setting

AbstractOver the last decade, concerns have been raised about potential respiratory health effects associated with occupational exposure to the flavoring additives diacetyl and 2,3-pentanedione. Both of these diketones are also natural components of many foods and beverages, including roasted coffee. To date, there are no published studies characterizing workplace exposures to these diketones during commercial roasting and grinding of unflavored coffee beans. In this study, we measured naturally occurring diacetyl, 2,3-pentanedione, and respirable dust at a facility that roasts and grinds coffee beans with no added flavoring agents. Sampling was conducted over the course of three roasting batches and three grinding batches at varying distances from a commercial roaster and grinder. The three batches consisted of lightly roasted soft beans, lightly roasted hard beans, and dark roasted hard beans. Roasting occurred for 37 to 41min, and the grinding process took between 8 and 11min. Diacetyl, 2,3-pentanedione, and respirable dust concentrations measured during roasting ranged from less than the limit of detection (<LOD) to 0.0039ppm, <LOD to 0.018ppm, and <LOD to 0.31mg/m3, respectively. During grinding, diacetyl, 2,3-pentanedione, and respirable dust concentrations ranged from 0.018 to 0.39ppm, 0.0089 to 0.21ppm, and <LOD to 1.7mg/m3, respectively. For any given bean/roast combination and sample location, diketone concentrations during grinding were higher than those measured during roasting. During grinding, concentrations decreased with increased distance from the source. Measured concentrations of both diketones were higher during grinding of soft beans than hard beans. The results indicate that airborne concentrations of naturally occurring diacetyl and 2,3-pentanedione associated with unflavored coffee processing: (1) are similar to the concentrations that have been measured in food flavoring facilities; (2) are likely to exceed some recommended short-term occupational exposure limits, but; (3) based on previous analyses of exposure response relationships in animal studies, are far below the concentrations that are expected to cause even minimal responses in the human respiratory tract

A Census of Early-phase High-mass Star Formation in the Central Molecular Zone

We present new observations of the C-band continuum emission and masers to assess high-mass (>8 ${M}_{\odot }$) star formation at early evolutionary phases in the inner 200 pc of the Central Molecular Zone (CMZ) of the Galaxy. The continuum observation is complete to free–free emission from stars above 10–11 ${M}_{\odot }$ in 91% of the covered area. We identify 104 compact sources in the continuum emission, among which five are confirmed ultracompact H ii regions, 12 are candidates of ultracompact H ii regions, and the remaining 87 sources are mostly massive stars in clusters, field stars, evolved stars, pulsars, extragalactic sources, or of unknown nature that is to be investigated. We detect class ii CH3OH masers at 23 positions, among which six are new detections. We confirm six known H2CO masers in two high-mass star-forming regions and detect two new H2CO masers toward the Sgr C cloud, making it the ninth region in the Galaxy that contains masers of this type. In spite of these detections, we find that current high-mass star formation in the inner CMZ is only taking place in seven isolated clouds. The results suggest that star formation at early evolutionary phases in the CMZ is about 10 times less efficient than expected from the dense gas star formation relation, which is in line with previous studies that focus on more evolved phases of star formation. This means that if there will be any impending, next burst of star formation in the CMZ, it has not yet begun

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy

CMZoom III: Spectral Line Data Release

We present an overview and data release of the spectral line component of the SMA Large Program, \textit{CMZoom}. \textit{CMZoom} observed $^{12}$CO(2-1), $^{13}$CO(2-1) and C$^{18}$O(2-1), three transitions of H$_{2}$CO, several transitions of CH$_{3}$OH, two transitions of OCS and single transitions of SiO and SO, within gas above a column density of N(H$_2$)$\ge 10^{23}$\,cm$^{-2}$ in the Central Molecular Zone (CMZ; inner few hundred pc of the Galaxy). We extract spectra from all compact 1.3\,mm \emph{CMZoom} continuum sources and fit line profiles to the spectra. We use the fit results from the H$_{2}$CO 3(0,3)-2(0,2) transition to determine the source kinematic properties. We find $\sim 90$\% of the total mass of \emph{CMZoom} sources have reliable kinematics. Only four compact continuum sources are formally self-gravitating. The remainder are consistent with being in hydrostatic equilibrium assuming that they are confined by the high external pressure in the CMZ. Based on the mass and density of virially bound sources, and assuming star formation occurs within one free-fall time with a star formation efficiency of $10\% - 75\%$, we place a lower limit on the future embedded star-formation rate of $0.008 - 0.06$\,M$_{\odot}$\,yr$^{-1}$. We find only two convincing proto-stellar outflows, ruling out a previously undetected population of very massive, actively accreting YSOs with strong outflows. Finally, despite having sufficient sensitivity and resolution to detect high-velocity compact clouds (HVCCs), which have been claimed as evidence for intermediate mass black holes interacting with molecular gas clouds, we find no such objects across the large survey area.Comment: 44 pages, 41 figure

BioTIME: A database of biodiversity time series for the Anthropocene.

MotivationThe BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables includedThe database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grainBioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).Time period and grainBioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurementBioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.Software format.csv and .SQL

A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection

We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor) and peginterferon alfa-2a/ribavirin (PR) in patients with genotype 1 chronic hepatitis C (CHC). This model, which was parameterized with on-treatment data from early phase clinical studies in treatment-naïve patients, prospectively predicted sustained virologic response (SVR) rates that were comparable to observed rates in subsequent clinical trials of regimens with different treatment durations in treatment-naïve and treatment-experienced populations. The model explains the clinically-observed responses, taking into account the IC50, fitness, and prevalence prior to treatment of viral resistant variants and patient diversity in treatment responses, which result in different eradication times of each variant. The proposed model provides a framework to optimize treatment strategies and to integrate multifaceted mechanistic information and give insight into novel CHC treatments that include direct-acting antiviral agents

Two-Photon Microscopy for Non-Invasive, Quantitative Monitoring of Stem Cell Differentiation

BACKGROUND: The engineering of functional tissues is a complex multi-stage process, the success of which depends on the careful control of culture conditions and ultimately tissue maturation. To enable the efficient optimization of tissue development protocols, techniques suitable for monitoring the effects of added stimuli and induced tissue changes are needed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present the quantitative use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a noninvasive means to monitor the differentiation of human mesenchymal stem cells (hMSCs) using entirely endogenous sources of contrast. We demonstrate that the individual fluorescence contribution from the intrinsic cellular fluorophores NAD(P)H, flavoproteins and lipofuscin can be extracted from TPEF images and monitored dynamically from the same cell population over time. Using the redox ratio, calculated from the contributions of NAD(P)H and flavoproteins, we identify distinct patterns in the evolution of the metabolic activity of hMSCs maintained in either propagation, osteogenic or adipogenic differentiation media. The differentiation of these cells is mirrored by changes in cell morphology apparent in high resolution TPEF images and by the detection of collagen production via SHG imaging. Finally, we find dramatic increases in lipofuscin levels in hMSCs maintained at 20% oxygen vs. those in 5% oxygen, establishing the use of this chromophore as a potential biomarker for oxidative stress. CONCLUSIONS/SIGNIFICANCE: In this study we demonstrate that it is possible to monitor the metabolic activity, morphology, ECM production and oxidative stress of hMSCs in a non-invasive manner. This is accomplished using generally available multiphoton microscopy equipment and simple data analysis techniques, such that the method can widely adopted by laboratories with a diversity of comparable equipment. This method therefore represents a powerful tool, which enables researchers to monitor engineered tissues and optimize culture conditions in a near real time manner

Ecosystem Processes and Human Influences Regulate Streamflow Response to Climate Change at Long-Term Ecological Research Sites

Analyses of long-term records at 35 headwater basins in the United States and Canada indicate that climate change effects on streamflow are not as clear as might be expected, perhaps because of ecosystem processes and human influences. Evapotranspiration was higher than was predicted by temperature in water-surplus ecosystems and lower than was predicted in water-deficit ecosystems. Streamflow was correlated with climate variability indices (e.g., the El Nino Southern Oscillation, the Pacific Decadal Oscillation, the North Atlantic Oscillation), especially in seasons when vegetation influences are limited. Air temperature increased significantly at 17 of the 19 sites with 20- to 60-year records, but streamflow trends were directly related to climate trends (through changes in ice and snow) at only 7 sites. Past and present human and natural disturbance, vegetation succession, and human water use can mimic, exacerbate, counteract, or mask the effects of climate change on streamflow, even in reference basins. Long-term ecological research sites are ideal places to disentangle these processes

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure