Revealing the beneficial effect of protease supplementation to high gravity beer fermentations using "-omics" techniques

<p>Abstract</p> <p>Background</p> <p>Addition of sugar syrups to the basic wort is a popular technique to achieve higher gravity in beer fermentations, but it results in dilution of the free amino nitrogen (FAN) content in the medium. The multicomponent protease enzyme Flavourzyme has beneficial effect on the brewer's yeast fermentation performance during high gravity fermentations as it increases the initial FAN value and results in higher FAN uptake, higher specific growth rate, higher ethanol yield and improved flavour profile.</p> <p>Results</p> <p>In the present study, transcriptome and metabolome analysis were used to elucidate the effect on the addition of the multicomponent protease enzyme Flavourzyme and its influence on the metabolism of the brewer's yeast strain Weihenstephan 34/70. The study underlines the importance of sufficient nitrogen availability during the course of beer fermentation. The applied metabolome and transcriptome analysis allowed mapping the effect of the wort sugar composition on the nitrogen uptake.</p> <p>Conclusion</p> <p>Both the transcriptome and the metabolome analysis revealed that there is a significantly higher impact of protease addition for maltose syrup supplemented fermentations, while addition of glucose syrup to increase the gravity in the wort resulted in increased glucose repression that lead to inhibition of amino acid uptake and hereby inhibited the effect of the protease addition.</p

Genie: A Generator of Natural Language Semantic Parsers for Virtual Assistant Commands

To understand diverse natural language commands, virtual assistants today are trained with numerous labor-intensive, manually annotated sentences. This paper presents a methodology and the Genie toolkit that can handle new compound commands with significantly less manual effort. We advocate formalizing the capability of virtual assistants with a Virtual Assistant Programming Language (VAPL) and using a neural semantic parser to translate natural language into VAPL code. Genie needs only a small realistic set of input sentences for validating the neural model. Developers write templates to synthesize data; Genie uses crowdsourced paraphrases and data augmentation, along with the synthesized data, to train a semantic parser. We also propose design principles that make VAPL languages amenable to natural language translation. We apply these principles to revise ThingTalk, the language used by the Almond virtual assistant. We use Genie to build the first semantic parser that can support compound virtual assistants commands with unquoted free-form parameters. Genie achieves a 62% accuracy on realistic user inputs. We demonstrate Genie's generality by showing a 19% and 31% improvement over the previous state of the art on a music skill, aggregate functions, and access control.Comment: To appear in PLDI 201

Innovative organotypic in vitro models for safety assessment: aligning with regulatory requirements and understanding models of the heart, skin, and liver as paradigms

The development of improved, innovative models for the detection of toxicity of drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new products safely to market in a cost-effective and timely manner. In addition, improvement in models to detect toxicity may reduce the incidence of unexpected post-marketing toxicity and reduce or eliminate the need for animal testing. The safety of novel products of the pharmaceutical, chemical, or cosmetics industry must be assured; therefore, toxicological properties need to be assessed. Accepted methods for gathering the information required by law for approval of substances are often animal methods. To reduce, refine, and replace animal testing, innovative organotypic in vitro models have emerged. Such models appear at different levels of complexity ranging from simpler, self-organized three-dimensional (3D) cell cultures up to more advanced scaffold-based co-cultures consisting of multiple cell types. This review provides an overview of recent developments in the field of toxicity testing with in vitro models for three major organ types: heart, skin, and liver. This review also examines regulatory aspects of such models in Europe and the UK, and summarizes best practices to facilitate the acceptance and appropriate use of advanced in vitro models

Ripple Texturing of Suspended Graphene Atomic Membranes

Graphene is the nature's thinnest elastic membrane, with exceptional mechanical and electrical properties. We report the direct observation and creation of one-dimensional (1D) and 2D periodic ripples in suspended graphene sheets, using spontaneously and thermally induced longitudinal strains on patterned substrates, with control over their orientations and wavelengths. We also provide the first measurement of graphene's thermal expansion coefficient, which is anomalously large and negative, ~ -7x10^-6 K^-1 at 300K. Our work enables novel strain-based engineering of graphene devices.Comment: 15 pages, 4 figure

Galaxy Zoo: dust and molecular gas in early-type galaxies with prominent dust lanes

We study dust and associated molecular gas in 352 nearby early-type galaxies (ETGs) with prominent dust lanes. 65% of these `dusty ETGs' (D-ETGs) are morphologically disturbed, suggesting a merger origin. This is consistent with the D-ETGs residing in lower density environments compared to the controls drawn from the general ETG population. 80% of D-ETGs inhabit the field (compared to 60% of the controls) and <2% inhabit clusters (compared to 10% of the controls). Compared to the controls, D-ETGs exhibit bluer UV-optical colours (indicating enhanced star formation) and an AGN fraction that is more than an order of magnitude greater (indicating higher incidence of nuclear activity). The clumpy dust mass residing in large-scale features is estimated, using the SDSS r-band images, to be 10^{4.5}-10^{6.5} MSun. A comparison to the total (clumpy + diffuse) dust masses- calculated using the far-IR fluxes of 15% of the D-ETGs that are detected by the IRAS- indicates that only ~20% of the dust resides in these large-scale features. The dust masses are several times larger than the maximum value expected from stellar mass loss, ruling out an internal origin. The dust content shows no correlation with the blue luminosity, indicating that it is not related to a galactic scale cooling flow. No correlation is found with the age of the recent starburst, suggesting that the dust is accreted directly in the merger rather than being produced in situ by the triggered star formation. Using molecular gas-to-dust ratios of ETGs in the literature we estimate that the median current and initial molecular gas fraction are ~1.3% and ~4%, respectively. Recent work suggests that the merger activity in nearby ETGs largely involves minor mergers (mass ratios between 1:10 and 1:4). If the IRAS-detected D-ETGs form via this channel, then the original gas fractions of the accreted satellites are 20%-44%. [Abridged]Comment: 11 pages, 18 figures, 1 table, MNRAS (Accepted for publication- 2012 March 19

Strong Inter-valley Electron-Phonon Coupling in Magic-Angle Twisted Bilayer Graphene

The unusual properties of superconductivity in magic-angle twisted bilayer graphene (MATBG) have sparked enormous research interest. However, despite the dedication of intensive experimental efforts and the proposal of several possible pairing mechanisms, the origin of its superconductivity remains elusive. Here, using angle-resolved photoemission spectroscopy with micrometer spatial resolution, we discover replicas of the flat bands in superconducting MATBG unaligned with its hexagonal boron nitride (hBN) substrate, which are absent in non-superconducting MATBG aligned with the hBN substrate. Crucially, the replicas are evenly spaced in energy, separated by 150 +- 15 meV, signalling the strong coupling of electrons in MATBG to a bosonic mode of this energy. By comparing our observations to simulations, the formation of replicas is attributed to the presence of strong inter-valley electron-phonon coupling to a K-point phonon mode. In total, the observation of these replica flat bands and the corresponding phonon mode in MATBG could provide important information for understanding the origin and the unusual properties of its superconducting phase.Comment: 17 pages, 4 figure

Quantitative Analysis and Diagnostic Significance of Methylated SLC19A3 DNA in the Plasma of Breast and Gastric Cancer Patients

Background: Previously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. Here, we aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma. Methodology/Principal Findings: SLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoter was evaluated by methylation-specific qPCR. SLC19A3 expression was significantly down-regulated in 80% (12/15) of breast tumors (P<0.005). Breast tumors had significant increase in methylation percentage when compared to adjacent non-tumor tissues (P<0.005). A robust and simple methylation-sensitive restriction enzyme digestion and real-time quantitative PCR (MSRED-qPCR) was developed to quantify SLC19A3 DNA methylation in plasma. We validated this biomarker in an independent validation cohort of 165 case-control plasma including 60 breast cancer, 45 gastric cancer patients and 60 healthy subjects. Plasma SLC19A3 methylated DNA level was effective in differentiating both breast and gastric cancer from healthy subjects. We further validated this biomarker in another independent blinded cohort of 78 plasma including 38 breast cancer, 20 gastric cancer patients and 20 healthy subjects. The positive predictive values for breast and gastric cancer were 90% and 85%, respectively. The negative predictive value of this biomarker was 85%. Elevated level in plasma has been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 100%. Conclusions: These results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for breast and gastric cancer diagnosis. © 2011 Ng et al.published_or_final_versio

A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Assessing inter-sectoral climate change risks: the role of ISIMIP

The aims of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) are to provide a framework for the intercomparison of global and regional-scale risk models within and across multiple sectors and to enable coordinated multi-sectoral assessments of different risks and their aggregated effects. The overarching goal is to use the knowledge gained to support adaptation and mitigation decisions that require regional or global perspectives within the context of facilitating transformations to enable sustainable development, despite inevitable climate shifts and disruptions. ISIMIP uses community-agreed sets of scenarios with standardized climate variables and socio-economic projections as inputs for projecting future risks and associated uncertainties, within and across sectors. The results are consistent multi-model assessments of sectoral risks and opportunities that enable studies that integrate across sectors, providing support for implementation of the Paris Agreement under the United Nations Framework Convention on Climate Change