Data Analytics for Manufacturing Systems – A Data-Driven Approach for Process Optimization

In the course of digitalization many small and medium-sized companies face the challenge of using the existing database for process optimization in manufacturing. Furthermore, the demand-oriented expansion of the database is a great challenge. A lack of competencies, limited financial resources and historically grown data structures, which show a strong heterogeneity and lack of transparency, are the central obstacles. A specific approach, how data analytics projects for process optimization should be carried out in manufacturing, is presented. In particular, the question which sensors should be implemented to expand the database is answered. The approach is applied exemplarily for a manufacturing line

Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex

The mechanism and regulation of fusion between autophagosomes and lysosomes/vacuoles are still only partially understood in both yeast and mammals. In yeast, this fusion step requiresSNAREproteins, the homotypic vacuole fusion and protein sorting (HOPS) tethering complex, theRAB7GTPase Ypt7, and its guanine nucleotide exchange factor (GEF) Mon1-Ccz1. We and others recently identified Ykt6 as the autophagosomalSNAREprotein. However, it has not been resolved when and how lipid-anchored Ykt6 is recruited onto autophagosomes. Here, we show that Ykt6 is recruited at an early stage of the formation of these carriers through a mechanism that depends on endoplasmic reticulum (ER)-resident Dsl1 complex andCOPII-coated vesicles. Importantly, Ykt6 activity on autophagosomes is regulated by the Atg1 kinase complex, which inhibits Ykt6 through direct phosphorylation. Thus, our findings indicate that the Ykt6 pool on autophagosomal membranes is kept inactive by Atg1 phosphorylation, and once an autophagosome is ready to fuse with vacuole, Ykt6 dephosphorylation allows its engagement in the fusion event

The yeast LYST homolog Bph1 is a Rab5 effector and prevents Atg8 lipidation at endosomes

Lysosomes mediate degradation of macromolecules to their precursors for their cellular recycling. Additionally, lysosome-related organelles mediate cell type-specific functions. The Chédiak-Higashi syndrome is an autosomal, recessive disease, in which loss of the protein LYST causes defects in lysosomes and lysosome-related organelles. The molecular function of LYST, however, is largely unknown. Here, we dissected the function of the yeast LYST homolog, Bph1. We show that Bph1 is an endosomal protein, and an effector of the minor Rab5 isoform Ypt52. Strikingly, the bph1▵ mutant has lipidated Atg8 on their endosomes, which is sorted via late endosomes into the vacuole lumen under non-autophagy inducing conditions. In agreement, proteomics of bph1▵ vacuoles reveal an accumulation of Atg8, reduced flux via selective autophagy, and defective endocytosis. Additionally, bph1▵ cells have reduced autophagic flux under starvation conditions. Our observations suggest that Bph1 is a novel Rab5 effector that maintains endosomal functioning. When lost, Atg8 is lipidated at endosomes even during normal growth and ends up in the vacuole lumen. Thus, our results contribute to the understanding of the role of LYST-related proteins and associated diseases

Challenge of modelling GLORIA observations of upper troposphere-lowermost stratosphere trace gas and cloud distributions at high latitudes: A case study with state-of-The-Art models

Water vapour and ozone are important for the thermal and radiative balance of the upper troposphere (UT) and lowermost stratosphere (LMS). Both species are modulated by transport processes. Chemical and microphysical processes affect them differently. Thus, representing the different processes and their interactions is a challenging task for dynamical cores, chemical modules and microphysical parameterisations of state-of-the-art atmospheric model components. To test and improve the models, high-resolution measurements of the UT–LMS are required. Here, we use measurements taken in a flight of the GLORIA (Gimballed Limb Observer for Radiance Imaging of the Atmosphere) instrument on HALO (High Altitude and LOng Range Research Aircraft). The German research aircraft HALO performed a research flight on 26 February 2016 that covered deeply subsided air masses of the aged 2015/16 Arctic vortex, high-latitude LMS air masses, a highly textured region affected by troposphere-to-stratosphere exchange and high-altitude cirrus clouds. Therefore, it provides a challenging multifaceted case study for comparing GLORIA observations with state-of-the-art atmospheric model simulations in a complex UT–LMS region at a late stage of the Arctic winter 2015/16. Using GLORIA observations in this manifold scenario, we test the ability of the numerical weather prediction (NWP) model ICON (ICOsahedral Nonhydrostatic) with the extension ART (Aerosols and Reactive Trace gases) and the chemistry–climate model (CCM) EMAC (ECHAM5/MESSy Atmospheric Chemistry – fifth-generation European Centre Hamburg general circulation model/Modular Earth Submodel System) to model the UT–LMS composition of water vapour (H$_{2}$O), ozone (O$_{3}$), nitric acid (HNO$_{3}$) and clouds. Within the scales resolved by the respective model, we find good overall agreement of both models with GLORIA. The applied high-resolution ICON-ART set-up involving an R2B7 nest (local grid refinement with a horizontal resolution of about 20 km), covering the HALO flight region, reproduces mesoscale dynamical structures well. Narrow moist filaments in the LMS observed by GLORIA at tropopause gradients in the context of a Rossby wave breaking event and in the vicinity of an occluded Icelandic low are clearly reproduced by the model. Using ICON-ART, we show that a larger filament in the west was transported horizontally into the Arctic LMS in connection with a jet stream split associated with poleward breaking of a cyclonically sheared Rossby wave. Further weaker filaments are associated with an older tropopause fold in the east. Given the lower resolution (T106) of the nudged simulation of the EMAC model, we find that this model also reproduces these features well. Overall, trace gas mixing ratios simulated by both models are in a realistic range, and major cloud systems observed by GLORIA are mostly reproduced. However, we find both models to be affected by a well-known systematic moist bias in the LMS. Further biases are diagnosed in the ICON-ART O$_{3}$, EMAC H$_{2}$O and EMAC HNO$_{3}$ distributions. Finally, we use sensitivity simulations to investigate (i) short-term cirrus cloud impacts on the H$_{2}$O distribution (ICON-ART), (ii) the overall impact of polar winter chemistry and microphysical processing on O$_{3}$ and HNO$_{3}$ (ICON-ART and EMAC), (iii) the impact of the model resolution on simulated parameters (EMAC), and (iv) consequences of scavenging processes by cloud particles (EMAC). We find that changing the horizontal model resolution results in notable systematic changes for all species in the LMS, while scavenging processes play a role only in the case of HNO$_{3}$. We discuss the model biases and deficits found in this case study that potentially affect forecasts and projections (adversely) and provide suggestions for further model improvements

Mesoscale fine structure of a tropopause fold over mountains

We report airborne remote-sensing observations of a tropopause fold during two crossings of the polar front jet over northern Italy on 12 January 2016. The GLORIA (Gimballed Limb Observer for Radiance Imaging of the Atmosphere) observations allowed for a simultaneous mapping of temperature, water vapour, and ozone. They revealed deep, dry, and ozone-rich intrusions into the troposphere. The mesoscale fine structures of dry filaments at the cyclonic shear side north of the jet and tongues of moist air entraining tropospheric air into the stratosphere along the anticyclonic shear side south of the jet were clearly resolved by GLORIA observations. Vertically propagating mountain waves with recorded temperature residuals exceeding ±3 K were detected above the Apennines. Their presence enhanced gradients of all variables locally in the vicinity of the tropopause. The combination of H2O−O3 correlations with potential temperature reveals an active mixing region and shows clear evidence of troposphere-to-stratosphere and stratosphere-to-troposphere exchange. High-resolution short-term deterministic forecasts of ECMWF\u27s integrated forecast system (IFS) applying GLORIA\u27s observational filter reproduce location, shape, and depth of the tropopause fold very well. The fine structure of the mixing region, however, cannot be reproduced even with the 9 km horizontal resolution of the IFS, used here. This case study demonstrates convincingly the capabilities of linear limb-imaging observations to resolve mesoscale fine structures in the upper troposphere and lower stratosphere, validates the high quality of the IFS data, and suggests that mountain wave perturbations have the potential to modulate exchange processes in the vicinity of tropopause folds

Pyramid

Snapshot of the pyramid-master branch of Empyre , commit hash 6f56004e3f6f9f8630c6fb3bdfb0fed7479a6590 . Pyramid is an unreleased predecessor of the Empyre software package. This deposition mainly serves as a reference for research projects that are based on the unreleased Pyramid code

AP-3 vesicle uncoating occurs after HOPS-dependent vacuole tethering

Heterotetrameric adapter (AP) complexes cooperate with the smallGTPase Arf1 or lipids in cargo selection, vesicle formation, and budding at endomembranes in eukaryotic cells. While mostAPcomplexes also require clathrin as the outer vesicle shell, formation ofAP-3-coated vesicles involved in Golgi-to-vacuole transport in yeast has been postulated to depend on Vps41, a subunit of the vacuolarHOPStethering complex.HOPShas also been identified as the tether ofAP-3 vesicles on vacuoles. To unravel this conundrum of a dual Vps41 function, we anchored Vps41 stably to the mitochondrial outer membrane. By monitoringAP-3 recruitment, we now show that Vps41 can tetherAP-3 vesicles to mitochondria, yetAP-3 vesicles can form in the absence of Vps41 or clathrin. By proximity labeling and mass spectrometry, we identify the Arf1GTPase-activating protein (GAP) Age2 at theAP-3 coat and show that tethering, but not fusion at the vacuole can occur without complete uncoating. We conclude thatAP-3 vesicles retain their coat after budding and that their complete uncoating occurs only after tethering at the vacuole

Vps39 Interacts with Tom40 to Establish One of Two Functionally Distinct Vacuole-Mitochondria Contact Sites

The extensive subcellular network of membrane contact sites plays central roles in organelle biogenesis and communication, yet the precise contributions of the involved machineries remain largely enigmatic. The yeast vacuole forms a membrane contact site with mitochondria, called vacuolar and mitochondrial patch (vCLAMP). Formation of vCLAMPs involves the vacuolar Rab GTPase Ypt7 and the Ypt7-interacting Vps39 subunit of the HOPS tethering complex. Here, we uncover the general preprotein translocase of the outer membrane (TOM) subunit Tom40 as the direct binding partner of Vps39 on mitochondria. We identify Vps39 mutants defective in TOM binding, but functional for HOPS. Cells that cannot form vCLAMPs show reduced growth under stress conditions and impaired survival upon starvation. Unexpectedly, our mutant analysis revealed the existence of two functionally independent vacuole-mitochondria MCSs: one formed by the Ypt7-Vps39-Tom40 tether and a second one by Vps13-Mcp1, which is redundant with ER-mitochondrial contacts formed by ERMES

Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery

Lysosomes are essential for cellular recycling, nutrient signaling, autophagy, and patho-genic bacteria and viruses invasion. Lysosomal fusion is fundamental to cell survival and requiresHOPS, a conserved heterohexameric tethering complex. On the membranes to be fused, HOPSbinds small membrane- associated GTPases and assembles SNAREs for fusion, but how the complexfulfills its function remained speculative. Here, we used cryo-electron microscopy to reveal the struc-ture of HOPS. Unlike previously reported, significant flexibility of HOPS is confined to its extremities,where GTPase binding occurs. The SNARE-binding module is firmly attached to the core, therefore,ideally positioned between the membranes to catalyze fusion. Our data suggest a model for howHOPS fulfills its dual functionality of tethering and fusion and indicate why it is an essential part ofthe membrane fusion machinery

Mesoscale fine structure of a tropopause fold over mountains

We report airborne remote-sensing observations of a tropopause fold during two crossings of the polar front jet over northern Italy on 12 January 2016. The GLORIA (Gimballed Limb Observer for Radiance Imaging of the Atmosphere) observations allowed for a simultaneous mapping of temperature, water vapour, and ozone. They revealed deep, dry, and ozone-rich intrusions into the troposphere. The mesoscale fine structures of dry filaments at the cyclonic shear side north of the jet and tongues of moist air entraining tropospheric air into the stratosphere along the anticyclonic shear side south of the jet were clearly resolved by GLORIA observations. Vertically propagating mountain waves with recorded temperature residuals exceeding ±3K were detected above the Apennines. Their presence enhanced gradients of all variables locally in the vicinity of the tropopause. The combination of H2O − O3 correlations with potential temperature reveals an active mixing region and shows clear evidence of troposphere-to-stratosphere and stratosphere-to-troposphere exchange. High-resolution short-term deterministic forecasts of ECMWF's integrated forecast system (IFS) applying GLORIA's observational filter reproduce location, shape, and depth of the tropopause fold very well. The fine structure of the mixing region, however, cannot be reproduced even with the 9km horizontal resolution of the IFS, used here. This case study demonstrates convincingly the capabilities of linear limb-imaging observations to resolve mesoscale fine structures in the upper troposphere and lower stratosphere, validates the high quality of the IFS data, and suggests that mountain wave perturbations have the potential to modulate exchange processes in the vicinity of tropopause folds