Influence of nitriding on the fatigue behavior and fracture micromechanisms of nodular cast Iron

Surface modification processes are increasingly used to fully exploit material potential in fatigue critical applications because fatigue strength is sensitive to surface conditions. Nitriding is extensively adopted with ferrous materials because it forms a hard and strong surface layer and a system ofsuperficial compressive residual stresses. Fatigue, however, is strongly dependent also on defects and inhomogeneity. When nitriding is applied to nodular cast iron (NCI), the relatively thin hardened layer (about 300 μm) contains graphite nodules (diameter of the order of 30 μm), casting defects and a heterogeneous matrix structure. The paper presents and discusses the influence of nitriding on the fatigue response and fracture mechanisms of NCI. A ferritic NCI and a synthetic melt with different content of effective ferrite were initially gas-nitrided. Then, (i) structural analysis of nitrided layers, (ii) fatigue testing with rotating bending specimens, and (iii) fatigue fracture surface inspection were performed. Performance and scatter in fatigue performance is discussed by selective inspection of fracture surfaces and identification fracture micromechanisms. A semiempirical model explains observed trends in test results and is used for the process optimization.Процессы модификации поверхности все более широко применяются для полного раскрытия возможностей материала в условиях высоких усталостных нагрузок, поскольку на усталостную прочность влияет состояние поверхности. Азотирование широко используют для обработки железосодержащих материалов, поскольку оно создает прочный поверхностный слой и поверхностные остаточные сжимающие напряжения. Усталость также существенно зависит от дефектов и неоднородности. При азотировании чугуна с шаровидным графитом в относительно тонком упрочненном слое (примерно 300 мкм) присутствуют шаровидные включения графита (диаметр порядка 30 мкм), дефекты литья и неоднородная структура основы. Рассматривается влияние азотирования на характеристики усталости и механизмы разрушения чугуна. Сначала проводили газовое азотирование ферритного чугуна и синтетического расплава с различным содержанием активного феррита. Затем выполняли структурный анализ азотированных слоев; испытание на сопротивление усталости путем кругового изгиба образца; контроль поверхности усталостного разрушения. Эффективность и разброс усталостных характеристик оценивали путем выборочного контроля поверхностей разрушения и идентификации микромеханизмов разрушения. Полуэмпирическая модель используется для оценки результатов испытаний и оптимизации процесса

A Conserved Function of C. elegans CASY-1 Calsyntenin in Associative Learning

BACKGROUND: Whole-genome association studies in humans have enabled the unbiased discovery of new genes associated with human memory performance. However, such studies do not allow for a functional or causal testing of newly identified candidate genes. Since polymorphisms in Calsyntenin 2 (CLSTN2) showed a significant association with episodic memory performance in humans, we tested the C. elegans CLSTN2 ortholog CASY-1 for possible functions in the associative behavior of C. elegans. METHODOLOGY/PRINCIPAL FINDINGS: Using three different associative learning paradigms and functional rescue experiments, we show that CASY-1 plays an important role during associative learning in C. elegans. Furthermore, neuronal expression of human CLSTN2 in C. elegans rescues the learning defects of casy-1 mutants. Finally, genetic interaction studies and neuron-specific expression experiments suggest that CASY-1 may regulate AMPA-like GLR-1 glutamate receptor signaling. CONCLUSION/SIGNIFICANCE: Our experiments demonstrate a remarkable conservation of the molecular function of Calsyntenins between nematodes and humans and point at a role of C. elegans casy-1 in regulating a glutamate receptor signaling pathway

Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia

Familial dysautonomia (FD) is a developmental neuropathy of the sensory and autonomous nervous systems. The IKBKAP gene, encoding the IKAP/hELP1 subunit of the RNA polymerase II Elongator complex is mutated in FD patients, leading to a tissue-specific mis-splicing of the gene and to the absence of the protein in neuronal tissues. To elucidate the function of IKAP/hELP1 in the development of neuronal cells, we have downregulated IKBKAP expression in SHSY5Y cells, a neuroblastoma cell line of a neural crest origin. We have previously shown that these cells exhibit abnormal cell adhesion when allowed to differentiate under defined culture conditions on laminin substratum. Here, we report results of a microarray expression analysis of IKAP/hELP1 downregulated cells that were grown on laminin under differentiation or non-differentiation growth conditions. It is shown that under non-differentiation growth conditions, IKAP/hELP1 downregulation affects genes important for early developmental stages of the nervous system, including cell signaling, cell adhesion and neural crest migration. IKAP/hELP1 downregulation during differentiation affects the expression of genes that play a role in late neuronal development, in axonal projection and synapse formation and function. We also show that IKAP/hELP1 deficiency affects the expression of genes involved in calcium metabolism before and after differentiation of the neuroblastoma cells. Hence, our data support IKAP/hELP1 importance in the development and function of neuronal cells and contribute to the understanding of the FD phenotype

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

Host-Adaptation of Francisella tularensis Alters the Bacterium's Surface-Carbohydrates to Hinder Effectors of Innate and Adaptive Immunity

The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase.SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg) and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host-adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice.F. tularensis undergoes host-adaptation which includes production of multiple capsular materials. These capsules impede recognition of bacterial outer membrane constituents by antibody, complement, and Toll-Like Receptor 2. These changes in the host-pathogen interface have profound implications for pathogenesis and vaccine development

Triadic awareness predicts partner choice in male–infant–male interactions in Barbary macaques

Social knowledge beyond one’s direct relationships is a key to successful maneuvering of the social world. Individuals gather information on the quality of social relationships between their group companions, which has been termed triadic awareness. Evidence of the use of triadic awareness in natural contexts is limited mainly to conflict management. Here we investigated triadic awareness in wild Barbary macaques (Macaca sylvanus) in the context of bridging interactions defined as male-infant-male interactions whereby a male (actor) presents an infant to another male (receiver) in order to initiate an affiliative interaction with that male. Analyses based on 1,263 hours of focal observations on ten infants of one wild social group in Morocco supported the hypothesis that males use their knowledge of the relationship between infants and other adult males when choosing a male as a partner for bridging interactions. Specifically, (i) the number of bridging interactions among initiator-infant-receiver triads was affected by the strength of the infant-receiver relationship and (ii) when two males were available as bridging partners, a male was more likely to be chosen as the receiver the stronger his social relationship with the infant in comparison to the other available male was. This demonstrates that non-human primates establish triadic awareness also of temporarily rather dynamic infant-male relationships and use it in naturally occurring affiliative context. Our results contribute to the discussion about the mechanism underlying the acquisition of triadic awareness and the benefits of its usage and lend support to hypotheses linking social complexity to the evolution of complex cognition

Near-surface structure and fatigue crack initiation mechanisms of as-built slm inconel 718

Challenging structural applications such as customized jet engine parts are increasingly fabricated by Selective Laser Melting (SLM) of Inconel 718 powder. The as-built surface quality of SLM parts is however inferior of the machined version and the fatigue behavior is negatively affected. The as-built fatigue response of SLM Inconel 718 was quantified here using three sets of directional specimens. Since the surface quality is influenced by powder characteristics, process parameters and layer-wise fabrication, fatigue results showed a directional contribution that was interpreted using metallography and fractography

On the link between as-built surface quality and fatigue behavior of additively manufactured Inconel 718

Inconel 718 is widely used in challenging structural applications because of its excellent high temperature mechanical properties. Selective Laser Melting (SLM) of Inconel 718 powder is increasingly used to fabricate customized parts for jet engines. The surface quality of SLM parts is influenced by powder characteristics, process parameters and the layer-wise fabrication. The as-built fatigue behavior is negatively affected by the inferior surface quality of SLM parts compared to machined version. Here the fatigue behavior of SLM Inconel 718 is investigated using specimens fabricated with two different SLM systems and different directions of applied stress with respect to build direction. Fatigue test results are interpreted in the light of metallographic and fractographic investigations

Influence of surface orientation and segmentation on the notch fatigue behavior of as-built DMLS Ti6Al4V

Design and qualification of load-bearing metal parts produced by the additive manufacturing technology is a critical issue. Such metal parts are complex in geometry with notches that are critical locations under fatigue loading. Notch surfaces are typically in the as-built state because post-fabrication surface finishing is not a viable approach in most applications. Here fatigue experiments using notched specimens produced according to different orientations with respect to build direction are presented and used to discuss the notch fatigue behavior of DMLS Ti6Al4V. Notch fatigue factors depend on the process itself and on fabrication details such as up-skin versus down-skin surface orientation, stair-stepping of the notch surface due to the layer-by-layer segmentation and intrinsic as-built surface roughness