Mechanical flange forming in steel and copper foil

Flange forming is a process which is wide spread in macro range for blanks with thicknesses from less than 1?mm up to several millimeters. Flange formed geometries are used as preforms for threads but also as device to give guidance and contact face to bolts and axles in sheet metal. A great advantage of flange forming compared to other machining processes is low process cycle time combined with high material utilization. Thus, a reasonable repertoire of knowledge has been gained for flange forming in macro range. Due to ongoing miniaturization of today??s products, flange forming is an interesting process applicable in micro range as well whereas size effects do not generally allow transfer of process limits from macro to micro range. Therefore the maximum flaring ratio for flange forming in micro range for sheet metal foil of 10?C25???m for a stainless steel 1.4301 and Copper E-Cu58 is investigated and compared with results in macro range. It is shown that the maximum flaring ratio decreases with decreasing sheet metal thickness. The resulting flange heights of experiments are compared with theoretical estimations which show a good accordance.     

Screening for Cytochrome P450 Reactivity by Harnessing Catalase as Reporter Enzyme

The big screen : We have devised a high‐throughput screening method for organic peroxide‐dependent P450 reactivity by taking advantage of a previously undescribed activity of catalase, which was used as reporter enzyme. This two‐step assay, followed by liquid chromatography/mass spectrometry analyses, allowed the facile identification of several new substrates for bacterial P450 enzymes.

     

Energy dissipation in laser-based free form heading: a numerical approach

Cold forming generally allows the fast generation of parts with very low tolerances. In addition, mechanical properties are improved, if work hardening materials are used. Transferring the cold forming process to micro range leads to a decrease in the maximum achievable upset ratio so that the forming process becomes inefficient. Therefore, a laser-based free form heading process has been developed to generate preforms which can be calibrated in a secondary cold forming step. The achievable upset ratios reach values of several hundreds instead of 2.1 which is common for single step mechanical upsetting. In this article, heat losses arising in the material accumulation process using laser-based free form heading are analyzed and discussed. For this purpose, the process is modeled within the framework of continuum mechanics and simulated by a finite element method. By using a numerical approach, a systematic study on heat losses is performed in order to identify the influence of radiation, heat transfer due to convection and thermal conduction during laser irradiation time. The simulation results, which are validated with experimental data, show that the radiation is the most important mechanism reducing the efficiency of the accumulation process.     

Coupling Interrupted Fischer and Multicomponent Joullié-Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics

The generation of peptidomimetic substructures for medicinal chemistry purposes requires effective and divergent synthetic methods. We present in this work an efficient flow process that allows quick modulation of reagents for Joullié-Ugi multicomponent reaction, using spiroindolenines as core motifs. This sterically hindered imine equivalent could successfully be diversified using various isocyanides and amino acids in generally good space-time yields. A telescoped flow process combining interrupted Fischer reaction for spiroindolenine synthesis and subsequent Joullié-Ugi-type modification resulted in product formation in very good overall yield in less than 2 hours compared to 48 hours required in batch mode. The developed protocol can be seen as a general tool for rapid and facile generation of peptidomimetic compounds. We also showcase preliminary biological assessments for the prepared compounds.     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.     

Disambiguating Visual Motion by Form-Motion Interaction—a Computational Model

The neural mechanisms underlying motion segregation and integration still remain unclear to a large extent. Local motion estimates often are ambiguous in the lack of form features, such as corners or junctions. Furthermore, even in the presence of such features, local motion estimates may be wrong if they were generated near occlusions or from transparent objects. Here, a neural model of visual motion processing is presented that involves early stages of the cortical dorsal and ventral pathways. We investigate the computational mechanisms of V1-MT feedforward and feedback processing in the perception of coherent shape motion. In particular, we demonstrate how modulatory MT-V1 feedback helps to stabilize localized feature signals at, e.g. corners, and to disambiguate initial flow estimates that signal ambiguous movement due to the aperture problem for single shapes. In cluttered environments with multiple moving objects partial occlusions may occur which, in turn, generate erroneous motion signals at points of overlapping form. Intrinsic-extrinsic region boundaries are indicated by local T-junctions of possibly any orientation and spatial configuration. Such junctions generate strong localized feature tracking signals that inject erroneous motion directions into the integration process. We describe a simple local mechanism of excitatory form-motion interaction that modifies spurious motion cues at T-junctions. In concert with local competitive-cooperative mechanisms of the motion pathway the motion signals are subsequently segregated into coherent representations of moving shapes. Computer simulations demonstrate the competency of the proposed neural model.