Search

Analytical modelling of deep drawing process is of value in preliminary process design to illustrate the influence of major variables including friction and strain hardening on punch loads, cup dimensions and process limits. In this study, analytical models including theoretical solution and a series of finite element models are developed to account for the influences of process parameters including friction coefficient, tooling geometry and material properties on deep drawing of metal cups. The accuracy of both the theoretical and finite element solutions is satisfactory compared with those from experimental work.

The aggregation of proteins as a result of intrinsic or environmental stress may be cytoprotective, but is also linked to pathophysiological states and cellular ageing. We analysed the principles of aggregate formation and the cellular strategies to cope with aggregates in Escherichia coli using fluorescence microscopy of thermolabile reporters, EM tomography and mathematical modelling. Misfolded proteins deposited at the cell poles lead to selective re-localization of the DnaK/DnaJ/ClpB disaggregating chaperones, but not of GroEL and Lon to these sites. Polar aggregation of cytosolic proteins is mainly driven by nucleoid occlusion and not by an active targeting mechanism. Accordingly, cytosolic aggregation can be efficiently re-targeted to alternative sites such as the inner membrane in the presence of site-specific aggregation seeds. Polar positioning of aggregates allows for asymmetric inheritance of damaged proteins, resulting in higher growth rates of damage-free daughter cells. In contrast, symmetric damage inheritance of randomly distributed aggregates at the inner membrane abrogates this rejuvenation process, indicating that asymmetric deposition of protein aggregates is important for increasing the fitness of bacterial cell populations.

This paper introduces a new argument into the theoretical literature on labor market effects of changes in working hours and labor force participation. We advance a general equilibrium model in which increased labor supply reduces unskilled unemployment via consumer demand: longer work hours and higher labor force participation imply higher incomes and less (leisure) time. In consequence, home production is reduced in favor of outsourcing domestic tasks to the market, shifting consumer demand toward unskill-intensive goods. Relative demand for unskilled labor rises and unemployment falls. Finally, we provide empirical support for the basic mechanisms of our model for Germany.

The increasing application of hydroforming for the production of automotive lightweight components is mainly due to the attainable advantages regarding part properties and improving technology of the forming equipment. However, the high pressure requirements during hydroforming decreases the costs benefit and make the part expensive. Another requirement of automotive industries is weight reduction and better crash performance. Thereby steel industries developed advanced high strength steels which have high strength, good formability and better crash performance. Even though the thickness of the sheet to form the component is reduced, the pressure requirement to form the part during expansion is still high during high pressure hydroforming. This paper details the comparison between high and low pressure tube hydroforming for the square cross-section geometry. It is determined that the internal pressure and die closing force required for low pressure tube hydroforming process is much less than that of high pressure tube hydroforming process. The stress and thickness distribution of the part during tube crushing were critically analysed. Further, the stress distribution and forming mode were studied in this paper. Also friction effect on both processes was discussed.

TIF-IA is a basal transcription factor of RNA polymerase I (Pol I) that is a major target of the JNK2 signaling pathway in response to ribotoxic stress. Using advanced fluorescence microscopy and kinetic modeling we elucidated the subcellular localization of TIF-IA and its exchange dynamics between the nucleolus, nucleoplasm and cytoplasm upon ribotoxic stress. In steady state, the majority of (GFP-tagged) TIF-IA was in the cytoplasm and the nucleus, a minor portion (7%) localizing to the nucleoli. We observed a rapid shuttling of GFP-TIF-IA between the different cellular compartments with a mean residence time of approximately 130 s in the nucleus and only approximately 30 s in the nucleoli. The import rate from the cytoplasm to the nucleus was approximately 3-fold larger than the export rate, suggesting an importin/exportin-mediated transport rather than a passive diffusion. Upon ribotoxic stress, GFP-TIF-IA was released from the nucleoli with a half-time of approximately 24 min. Oxidative stress and inhibition of protein synthesis led to a relocation of GFP-TIF-IA with slower kinetics while osmotic stress had no effect. The observed relocation was much slower than the nucleo-cytoplasmic and nucleus-nucleolus exchange rates of GFP-TIF-IA, indicating a time-limiting step upstream of the JNK2 pathway. In support of this, time-course experiments on the activity of JNK2 revealed the activation of the JNK kinase as the rate-limiting step.

In Acemoglu's model of directed technical change, the skill-premium increases in consequence of an increase in the relative supply of skilled labor. In this paper, I argue that other measures of wage inequality such as the Gini-coefficient do not necessarily rise as well. The Gini-coefficient depends positively on the skill-premium but the effect of an increase in the relative supply of skilled labor is ambiguous. A simulation of Acemoglu's model shows that the growth in the relative supply of skilled labor has led to increased wage inequality in the past but will lead to decreasing wage inequality in the future.

The biogenesis of endoplasmic reticulum (ER) exit sites (ERES) involves the formation of phosphatidylinositol-4 phosphate (PI4) and Sec16, but it is entirely unknown how ERES adapt to variations in cargo load. Here, we studied acute and chronic adaptive responses of ERES to an increase in cargo load for ER export. The acute response (within minutes) to increased cargo load stimulated ERES fusion events, leading to larger but less ERES. Silencing either PI4-kinase IIIalpha (PI4K-IIIalpha) or Sec16 inhibited the acute response. Overexpression of secretory cargo for 24 h induced the unfolded protein response (UPR), upregulated COPII, and the cells formed more ERES. This chronic response was insensitive to silencing PI4K-IIIalpha, but was abrogated by silencing Sec16. The UPR was required as the chronic response was absent in cells lacking inositol-requiring protein 1. Mathematical model simulations further support the notion that increasing ERES number together with COPII levels is an efficient way to enhance the secretory flux. These results indicate that chronic and acute increases in cargo load are handled differentially by ERES and are regulated by different factors.

Diffusion-mediated searching for interaction partners is an ubiquitous process in cell biology. Transcription factors, for example, search specific DNA sequences, signaling proteins aim at interacting with specific cofactors, and peripheral membrane proteins try to dock to membrane domains. Brownian motion, however, is affected by molecular crowding that induces anomalous diffusion (so-called subdiffusion) of proteins and larger structures, thereby compromising diffusive transport and the associated sampling processes. Contrary to the naive expectation that subdiffusion obstructs cellular processes, we show here by computer simulations that subdiffusion rather increases the probability of finding a nearby target. Consequently, important events like protein complex formation and signal propagation are enhanced as compared to normal diffusion. Hence, cells indeed benefit from their crowded internal state and the associated anomalous diffusion.

Functional diversity (FD) is an important component of biodiversity that quantifies the difference in functional traits between organisms. However, FD studies are often limited by the availability of trait data and FD indices are sensitive to data gaps. The distribution of species abundance and trait data, and its transformation, may further affect the accuracy of indices when data is incomplete. Using an existing approach, we simulated the effects of missing trait data by gradually removing data from a plant, an ant and a bird community dataset (12, 59, and 8 plots containing 62, 297 and 238 species respectively). We ranked plots by FD values calculated from full datasets and then from our increasingly incomplete datasets and compared the ranking between the original and virtually reduced datasets to assess the accuracy of FD indices when used on datasets with increasingly missing data. Finally, we tested the accuracy of FD indices with and without data transformation, and the effect of missing trait data per plot or per the whole pool of species. FD indices became less accurate as the amount of missing data increased, with the loss of accuracy depending on the index. But, where transformation improved the normality of the trait data, FD values from incomplete datasets were more accurate than before transformation. The distribution of data and its transformation are therefore as important as data completeness and can even mitigate the effect of missing data. Since the effect of missing trait values pool-wise or plot-wise depends on the data distribution, the method should be decided case by case. Data distribution and data transformation should be given more careful consideration when designing, analysing and interpreting FD studies, especially where trait data are missing. To this end, we provide the R package “traitor” to facilitate assessments of missing trait data.

Cellular fluids, e.g. the cytoplasm, are crowded with macromolecules at concentrations up to 400g/l. Macromolecular crowding influences transport processes and biochemical reactions [1]. A particular example for the latter is the opening and closing kinetics of DNA hairpins which we have studied by UV hyperchromicity and fluorescence correlation spectroscopy (FCS). Timing and steady state of this reaction are differentially altered by the crowders' excluded volume and by a crowding-induced viscoelasticity of the fluid that also causes an anomalous diffusion of the hairpin. As a result, we observed an increased fraction of closed DNA hairpins in viscoelastic crowded fluids [2,3], which compares favorably to a simple statistical model that considers both facets of crowding.Going beyond these observations, we have also investigated the spatial heterogeneity of cellular and biomimetic crowded fluids using the molecular rotor dye DASPMI as a reporter. On mesoscale, FCS experiments revealed that both, cells and biomimetic solutions, exhibit a comparable spatial heterogeneity of diffusion times and anomalies. On nanoscale, however, fluorescent lifetime imaging microscopy (FLIM) highlighted a considerably increased inhomogeneity of cellular fluids as compared to artificial solutions. Hence, crowding in cellular fluids has certain facets that are not well captured by biomimetic fluids.[1] Weiss, Int. Rev. Cell Mol. Biol., 307, 383-417 (2014).[2] Stiehl, Weidner-Hertrampf & Weiss, New J. Phys. 15 113010 (2013).[3] Stiehl, Weidner-Hertrampf & Weiss, Phys. Rev. E 91, 012703 (2015).

A coupled quantum dot--nanocavity system in the weak coupling regime of cavity quantumelectrodynamics is dynamically tuned in and out of resonance by the coherent elastic field of a $f_{\rm SAW}\simeq800\,\mathrm{MHz}$ surface acoustic wave. When the system is brought to resonance by the sound wave, light-matter interaction is strongly increased by the Purcell effect. This leads to a precisely timed single photon emission as confirmed by the second order photon correlation function $g^{(2)}$. All relevant frequencies of our experiment are faithfully identified in the Fourier transform of $g^{(2)}$, demonstrating high fidelity regulation of the stream of single photons emitted by the system., Comment: revised manuscript - to be published in Applied Physics Letters

We have used fluorescence correlation spectroscopy to determine the anomalous diffusion properties of fluorescently tagged gold beads in the cytoplasm and the nucleus of living cells. From the extracted mean-square displacement v(tau) approximately tau(alpha), we have determined the complex shear modulus G(omega) approximately omega(alpha) for both compartments. Without treatment, all tested cell lines showed a strong viscoelastic behavior of the cytoplasm and the nucleoplasm, highlighting the crowdedness of these intracellular fluids. We also found a similar viscoelastic response in frog egg extract, which tended toward a solely viscous behavior upon dilution. When cells were osmotically stressed, the diffusion became less anomalous and the viscoelastic response changed. In particular, the anomality changed from alpha approximately 0.55 to alpha approximately 0.66, which indicates that the Zimm model for polymer solutions under varying solvent conditions is a good empirical description of the material properties of the cytoplasm and the nucleoplasm. Since osmotic stress may eventually trigger cell death, we propose, on the basis of our observations, that intracellular fluids are maintained in a state similar to crowded polymer solutions under good solvent conditions to keep the cell viable.

The influence of temperature on the forming behavior of an aluminum/polypropylene/aluminum (APA) sandwich sheet was studied. Shear and tensile tests were performed to determine the mechanical properties of the laminate and the component materials as a function of process temperature. The forming limit diagram (FLD) of the laminate was established for two different temperatures, and its springback behavior was examined in four-point bend and channel bend tests. Cup forming tests were performed at various test temperatures to determine the limiting drawing ratio (LDR) and the tendency for wrinkling at these temperatures. Although there was only a minor influence of temperature on the mechanical properties and the FLD values of the laminate, the bend test results reveal that springback can be reduced by forming at higher temperature. The decreasing strength of the core material with rising process temperature led to an increased tendency of the laminate to wrinkle in the heated cup drawing tests.

We investigate the ultrafast optoelectronic properties of single Al0.3Ga0.7As/GaAs-core-shell-nanowires. The nanowires contain GaAs-based quantum wells. For a resonant excitation of the quantum wells, we find a picosecond photocurrent which is consistent with an ultrafast lateral expansion of the photogenerated charge carriers. This Dember-effect does not occur for an excitation of the GaAs-based core of the nanowires. Instead, the core exhibits an ultrafast displacement current and a photo-thermoelectric current at the metal Schottky contacts. Our results uncover the optoelectronic dynamics in semiconductor core-shell nanowires comprising quantum wells, and they demonstrate the possibility to use the low-dimensional quantum well states therein for ultrafast photoswitches and photodetectors.

Cellular membranes are typically decorated with a plethora of embedded and adsorbed macromolecules, e.g. proteins, that participate in numerous vital processes. With typical surface densities of 30,000 proteins per μm(2) cellular membranes are indeed crowded places that leave only few nanometers of private space for individual proteins. Here, we review recent advances in our understanding of protein crowding in membrane systems. We first give a brief overview on state-of-the-art approaches in experiment and simulation that are frequently used to study crowded membranes. After that, we review how crowding can affect diffusive transport of proteins and lipids in membrane systems. Next, we discuss lipid and protein sorting in crowded membrane systems, including effects like protein cluster formation, phase segregation, and lipid droplet formation. Subsequently, we highlight recent progress in uncovering crowding-induced conformational changes of membranes, e.g. membrane budding and vesicle formation. Finally, we give a short outlook on potential future developments in the field of crowded membrane systems. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog.

The rituximab extended schedule or retreatment trial (RESORT; E4402) was a phase 3 randomized prospective trial comparing maintenance rituximab (MR) versus a retreatment (RR) dosing strategy in asymptomatic, low tumour burden indolent lymphoma. A planned exploratory sub-study compared the two strategies for small lymphocytic (SLL) and marginal zone lymphomas (MZL). Patients responding to rituximab weekly × 4 were randomized to MR (single dose rituximab every 3 months until treatment failure) or RR (rituximab weekly × 4) at the time of each progression until treatment failure. The primary endpoint was time to treatment failure (TTTF). Patients with SLL (n = 57), MZL (n = 71) and unclassifiable small B-cell lymphoma (n = 3) received induction rituximab. The overall response rate (ORR) was 40% [95% confidence interval (CI) 31-49%; SLL ORR 22·8%; MZL ORR 52·1%]; all 52 responders were randomized. At a median of 4·3 years from randomization, treatment failure occurred in 18/23 RR and 15/29 MR. The median TTTF was 1·4 years for RR and 4·8 years for MR (P = 0·012); median time to first cytotoxic therapy was 6·3 years for RR and not reached for MR (P = 0·0002). Survival did not differ (P = 0·72). In low tumour burden SLL and MZL patients responding to rituximab induction, MR significantly improved TTTF as compared with RR.

Synthetic Aperture Radar (SAR) tomography has seen a strong evolution in the past years as it has shown to be a worthwhile tool for analysing data obtained with high range resolution interferometric SAR sensors at pixel size. In particular by transforming them into a 3-D, 4-D, and in general Multi-Dimensional SAR image. The resolution in the higher dimensions, for instance in elevation and time, depends on the size of the elevation aperture and on the temporal separation which will be spanned by the different repeat paths. However, for more recent space-borne SAR systems which has sub-meter range resolution, like COSMO-Skymed or TerraSAR-X, the orbital tracks are tightly controlled so that they show only a small variation. According to this, the tomographic resolution in elevation is an order of magnitude lower than in range or azimuth. This is normally not a problem as only the strongest reflector is of interest. However, for urban scenes or man made objects one can expect that each azimuth-range cell consists of a few point-like scatterers in the elevation direction. To resolve these scatterers super-resolution algorithms are required to improve the performance of tomographic tools. Due to the present of only a few scatterers we can use compressive sensing (CS) techniques for reconstructing the elevation for tomographic images. This paper presents an adapted CS method for 4-D tomographic SAR and compares it with classical matched filter. Super-resolution properties of the proposed CS is proven by results obtained from simulations and from real TerraSAR-X data.

Experimentally determined diffusion constants are often used to elucidate the size and oligomeric state of membrane proteins and domains. This approach critically relies on the knowledge of the size-dependence of diffusion. We have used mesoscopic simulations to thoroughly quantify the size-dependent diffusion properties of membrane inclusions. For small radii R , we find that the lateral diffusion coefficient D is well described by the Saffman-Delbruck relation, which predicts a logarithmic decrease of D with R . However, beyond a critical radius R c ≈ hη m /(2 η c ) ( h , bilayer thickness; η m/c , viscosity of the membrane/surrounding solvent) we observe significant deviations and the emergence of an asymptotic scaling D ∼ 1/ R 2 . The latter originates from the asymptotic hydrodynamics and the inclusion's internal degrees of freedom that become particularly relevant on short timescales. In contrast to the lateral diffusion, the size dependence of the rotational diffusion constant D r follows the predicted hydrodynamic scaling D r ∼ 1/ R 2 over the entire range of sizes studied here.

Alterations in endoplasmic reticulum (ER) cholesterol are fundamental for a variety of cellular processes such as the regulation of lipid homeostasis or efficient protein degradation. We show that reduced levels of cellular sterols cause a delayed ER-to-Golgi transport of the secretory cargo membrane protein ts-O45-G and a relocation to the ER of an endogenous protein cycling between the ER and the Golgi complex. Transport inhibition is characterized by a delay in the accumulation of ts-O45-G in ER-exit sites (ERES) and correlates with a reduced mobility of ts-O45-G within ER membranes. A simple mathematical model describing the kinetics of ER-exit predicts that reduced cargo loading to ERES and not the reduced mobility of ts-O45-G accounts for the delayed ER-exit and arrival at the Golgi. Consistent with this, membrane turnover of the COPII component Sec23p is delayed in sterol-depleted cells. Altogether, our results demonstrate the importance of sterol levels in COPII mediated ER-export.

Summary The COPII coat complex mediates the formation of transport carriers at specialized sites of the endoplasmic reticulum (ERES). It consists of the Sar1p GTPase and the Sec23/24p and the Sec13/31p subcomplexes [1–3]. Both stimulate the GTPase activity of Sar1p [4], which itself triggers coat disassembly. This built-in GAP activity makes the COPII complex in principle unstable and raises the question of how sufficient stability required for cargo capture and carrier formation is achieved. To address this, we analyzed COPII turnover at single ERES in living cells. The half times for Sar1p, Sec23p, and Sec24p turnover are 1.1, 3.7, and 3.9 s, respectively. Decreasing the amount of transport-competent cargo in the endoplasmic reticulum accelerates turnover of the Sec23/24p and slows down that of Sar1p. A mathematical model of COPII membrane turnover that reproduces the experimental in vivo FRAP kinetics and is consistent with existing in vitro data predicts that Sec23/24p remains membrane associated even after GTP hydrolysis by Sar1p for a duration that is strongly increased by the presence of cargo. We conclude that secretory cargo retains the COPII complex on membranes, after Sar1p release has occurred, and prevents premature disassembly of COPII during cargo sorting and transport carrier formation.

Phospholipases are a class of molecular machines that are involved in the active remodelling processes of biological membranes. These lipases are interfacially activated enzymes and in the specific case of phospholipase A(2) (PLA(2)) the enzyme catalyses the hydrolysis of di-acyl phospholipids into products of lysolipids and fatty acids, that dramatically change the physical properties of lipid membrane substrates. Using dissipative particle dynamics simulations on a simple coarse-grained bead-spring model of a fluid lipid bilayer in water, the mechanical and diffusive properties of the bilayer in the pure state and after the action of PLA(2) have been calculated. It is found that, in response to hydrolysis, the lipid membrane becomes mechanically softened and the various in-plane and trans-bilayer diffusional modes become enhanced. The results compare favourably with available experimental data.

The shear strain of the interlayer in the elastic regime for a Steel-Polymer-Steel (SPS) laminate material has been studied during bending to a constant curvature. An analytical model is developed and the influence of process parameters are analyzed. The tension in the cover sheets is also determined and, finally, a moment diagram is calculated. The results show that the moment in the SPS laminate is nonuniform along the bent strip even though the curvature is constant because of the tension and compression forces introduced in the cover sheets by the shear reaction force of the interlayer material.

A major challenge of software-defined radio (SDR) is to realize many giga operations per second of flexible baseband processing within a power budget of only a few hundred mW. A heterogeneous hardware architecture with the programmable vector processor EVP as key component can support WLAN, UMTS, and other standards. A detailed rationale for the EVP architecture, based on the analysis of a number of key algorithms, as well as implementation and benchmarking results are described.

Confocal fluorescence recovery after photobleaching (FRAP) is today the prevalent tool when studying the diffusional and kinetic properties of proteins in living cells. Obtaining quantitative data for diffusion coefficients via FRAP, however, is challenged by the fact that both bleaching and scanning take a finite time. Starting from an experimental case, it is shown by means of computer simulations that this intrinsic temporal limitation can lead to a gross underestimation of diffusion coefficients. Determining the binding kinetics of proteins to membranes with FRAP is further shown to be severely hampered by additional diffusional contributions, e.g. diffusion-limited binding. In some cases, the binding kinetics may even be masked entirely by diffusion. As current efforts to approach biological problems with biophysical models have to rely on experimentally determined model parameters, e.g. binding rates and diffusion constants, it is proposed that the accuracy in evaluating FRAP measurements can be improved by means of accompanying computer simulations.

The random movement of molecules (diffusion) is fundamental to most cellular processes, including enzymatic reactions, signalling, protein-protein interaction, as well as domain and pattern formation. Despite playing a central role, diffusion is, to a large extent, under-appreciated in the cell biology community. One reason for this is that diffusion is rather challenging to study in living cells. This article is intended to explain, at least in part, how we can go about studying diffusion of molecules in living cells, why it is important and how it provides us with important clues about biological systems. As the title 'In a mirror dimly' suggests, we do this by monitoring faint light emitted by fluorescent probes or proteins using advanced optics (e.g. mirrors) and electronics. The data are then fitted and interpreted with mathematical and physical models, providing a glimpse into the world of molecules.

Resident proteins of the exocytic pathway are maintained at various levels through coatomer protein I (COPI)-mediated recycling. Sorting of cargo by COPI requires GTP hydrolysis by ADP-ribosylation factor 1 (ARF-1). This small GTPase recruits coatomer onto Golgi membranes and upon hydrolysis, is thought to release coatomer back into the cytosol. This step requires the activating protein, ARFGAP1. By coupling sorting to a cargo-induced sequestering of ARFGAP1, we have formulated a kinetic proof-reading model that explains how a GTP hydrolysis-driven coat release can yield an active sorting event. The sorting scheme predicts a dependency on the amount of ARFGAP1 and explains the recent experimental findings that ARF-1 and COPI detach with different time constants from the Golgi membrane in vivo.

Generalizing a classic result by Polya concerning the zeros of successive derivatives of meromorphic functions in the complex plane, we study the accumulation set of zeros of successive derivatives of automorphic functions in the hyperbolic plane, as well as the connection between the automorphism group and the topology of this set in the Poincare disk model.

Few studies have examined the prevalence and severity of treatment-induced neuropathic symptoms in patients across different cancer types.This study aimed to report the prevalence of numbness/tingling (N/T) and neuropathic pain in patients with colorectal cancer (CRC) vs. other cancers, describe the prevalence of moderate-to-severe N/T by specific clinical variables, and examine factors associated with the presence of these symptoms.A total of 3106 outpatients with colorectal (n = 718), breast (n = 1544), lung (n = 524), or prostate (n = 320) cancer were enrolled at any point in their treatment. Assessments were conducted at the initial visit and 28-35 days later. Patients reported pain and N/T; clinicians reported mechanism of pain and ranked the top three symptoms causing difficulties.Moderate-to-severe N/T was higher in patients with CRC relative to other cancer types (25.8% vs. 17.1%, P0.001); 25% vs. 10.5% of clinicians rated N/T as a top three symptom for patients with CRC relative to other cancers (P0.001). The prevalence of neuropathic pain was comparable between patients with CRC and other cancers (P = 0.654). Patients with CRC, longer duration of cancer, prior therapy, on current therapy, older patients, and patients of black race experienced worse N/T.Patients with CRC experience significantly higher rates of N/T but comparable neuropathic pain, relative to patients with other cancers. Awareness of the prevalence and severity of neuropathic symptoms and their associated risk factors in this patient population is critical for both clinicians and patients.

Newly synthesized proteins are sorted into COPII-coated transport carriers at the endoplasmic reticulum (ER). Assembly of the COPII coat complex, which occurs at ER exit sites (ERES), is initiated by membrane association and GTP loading of SAR1, followed by the recruitment of the SEC23-SEC24 and SEC13-SEC31 subcomplexes. Both of these two subcomplexes stimulate GTP hydrolysis and coat disassembly. This inherent disassembly capacity of COPII complexes needs to be regulated to allow sufficient time for cargo sorting and transport carrier formation. By performing fluorescence recovery after photobleaching (FRAP) and mathematical modeling, we show that p150glued (also known as DCTN1), a component of the dynactin complex, stabilizes the COPII pre-budding complex on ER membranes in a microtubule-independent manner. Concentration of the secretory marker ts-O45-G at ERES is reduced in the presence of a C-terminal p150glued fragment that prevents binding of endogenous p150glued to SEC23. A similar cargo reduction is observed upon p150glued knockdown. Taken together, our data suggest that cargo concentration at ERES is regulated by p150glued to coordinate protein sorting and transport carrier formation with the subsequent long-range transport towards the Golgi complex along microtubules. © 2015. Published by The Company of Biologists Ltd.

Trophoblast stem cells (TSCs) represent the multipotent progenitors that give rise to the different cells of the embryonic portion of the placenta. Here, we analysed the expression of key TSC transcription factorsCdx2,Eomes, andElf5in the early developing placenta of mouse embryos and in cultured TSCs and reveal surprising heterogeneity in protein levels. We analysed persistence of TSCs in the early placenta and find that TSCs remain in the chorionic hinge until E9.5 and are lost shortly afterwards. To define the transcriptional signature of bona fide TSCs, we used inducible gain- and loss-of-function alleles ofEomesorCdx2, andEomesGFP, to manipulate and monitor the core maintenance factors of TSCs, followed by genome-wide expression profiling. Combinatorial analysis of resulting expression profiles allowed for defining novel TSC marker genes that might functionally contribute to the maintenance of the TSC state. Analyses by qRT-PCR andin situhybridisation validated novel TSC- and chorion-specific marker genes, such asBok/Mtd, Cldn26, Duox2, Duoxa2, Nr0b1, andSox21. Thus, these expression data provide a valuable resource for the transcriptional signature of bona fide and early differentiating TSCs and may contribute to an increased understanding of the transcriptional circuitries that maintain and/or establish stemness of TSCs.

In order to assess the rigor of research procedures (whether qualitative or quantitative) to appreciate a study’s results and to want to integrate them into the body of scholarly knowledge they need to be transparently relayed. Unlike in other disciplines or methods it is far from clear what the label ‘transparent research procedures’ constitutes in management field studies with adverse effects during write up revision and even after publication. To rectify this we review 365 field studies across seven major management journals 1997 2006 in order to develop a transparency index and link it to article impact. Overall transparency tends to increase impact across methods particularly with increasing article age. Moreover quantitative studies tend to be more transparent than qualitative studies although key transparency indicators were underutilized in either method.

Micro roll forming is a new processing technology to produce bipolar plates for Proton Exchange Membrane Fuel Cells (PEMFC) from thin stainless steel foil. To gain a better understanding of the deformation of the material in this process, numerical studies are necessary before experimental implementation. In general, solid elements with several layers through the material thickness are required to analyse material thinning in processes where the deformation mode is that of bending combined with tension, but this results in high computational costs. This pure solid element approach is especially time-consuming when analysing roll forming processes which generally involves feeding a long strip through a number of successive roll stands. In an attempt to develop a more efficient modelling approach without sacrificing accuracy, two solutions are numerically analysed with ABAQUS/Explicit in this paper. In the first, a small patch of solid elements over the strip width and in the centre of the "pre-cut" sheet is coupled with shell elements while in the second approach pure shell elements are used to discretize the full sheet. In the first approach, the shell element enables accounting for the effect of material being held in the roll stands on material flow while solid elements can be applied to analyse material thinning in a small discrete area of the sheet. Experimental micro roll forming trials are performed to prove that the coupling of solid and shell elements can give acceptable model accuracy while using shell elements alone is shown to result in major deviations between numerical and experimental results.

Roll forming enables the manufacturing of longitudinal components from materials that combine high strength with limited formability and is increasingly used in the automotive industry for the manufacture of structural and crash components. An extension of conventional roll forming is the Flexible Roll Forming (FRF) process where the rolls are no longer fixed in space but are free to move which enables the forming of components with variable cross section over the length of the part. Even though FRF components have high weight saving potential the technology has found only limited application in the automotive industry. A new flexible forming facility has recently been developed that enables proof of concept studies and the production of FRF prototypes before a full FRF line is built; this may lead to a wider uptake of the FRF technology in the automotive industry. In this process, the pre-cut blank is placed between two clamps and the whole set up moves back and forth; a forming roll that is mounted on a servo-controlled platform with six degrees of freedom forms the pre-cut blank to the desired shape. In this study an initial forming concept for the flexible roll forming of an automotive component with variable height is developed using COPRA® FEA RF. This is followed by performing experimental prototyping studies on the new concept forming facility. Using the optical strain measurement system Autogrid Compact, material deformation, part shape and wrinkling severity are analysed for some forming passes and compared with the numerical results. The results show that the numerical model gives a good representation of material behaviour and that with increasing forming severity wrinkling issues need to be overcome in the process.

Sensemaking has been identified as a central topic for understanding human behavior in organizations. Still, however, much of what we know about sensemaking addresses its cognitive dimension, even ...

Compared to innovators, past research has often found adaptors to be related to lower levels of creativity. However, drawing from theory on cognitive psychology in creative problem solving, our stu...