Thermal Analyses for Induction Sintering of Powder Metal Compacts up to Sintering Temperature

Induction sintering is developed as an alternative method to conventional sintering in order to sinter iron-based powder metal (PM) compacts. In this study, the 12 kW power and 30 kHz frequency induction-sintering machine is used for 3 wt.% copper-mixed iron. The effects of different shapes and sizes of the induction coil, and temperature differences on the PM compacts up to sintering temperature are investigated; these parameters are determined both theoretically and experimentally during induction sintering. Iron-based PM compacts are sintered at 1120°C. Induction sintering of iron-based PM compacts are simulated using a program to examine the effects of magnetic flux and temperature distribution in the sample over time. The results are compared with the experimental studies.Индукционное спекание было разработано как альтернатива обычному спеканию, чтобы спекать прессовки порошковых материалов (ПМ) на основе железа. В данной работе использована индукционная агломерационная машина мощностью 12 кВт и частотой 30 кГц для спекания смеси железа с 3 масс.% меди. Исследованы влияния различных форм и размеров индукционных катушек, разниц температур на брикеты ПМ вплоть до температуры спекания; эти параметры были исследованы как теоретически, так и экспериментально во время индукционного спекания. Брикеты ПМ на основе железа спекались при 1120°C. Индукционное спекание брикетов ПМ на основе железа также смоделировано с использованием программы, которая исследует влияние магнитного потока и распределения температуры в образце со временем. Результаты сопоставлены с результатами экспериментальных исследований.Індукційне спікання було розроблено як альтернатива звичайному спіканню, щоб спікати брикети порошкових матеріялів (ПМ) на основі заліза. В даній роботі використано індукційну аґломераційну машину потужністю у 12 кВт і частотою у 30кГц для спікання суміші заліза з 3 ваг.% міді. Досліджено впливи різних форм і розмірів індукційної шпулі, ріжниць температур на брикети ПМ аж до температури спікання; ті параметри було досліджено як теоретично, так й експериментально під час індукційного спікання. Брикети ПМ на основі заліза спікалися при 1120°C. Індукційне спікання брикетів ПМ на основі заліза також модельовано з використанням програми, яка досліджує впливи магнетного потоку та розподілу температури у зразку з часом. Результати порівняно з результатами експериментальних досліджень

Spatial variability of precipitation regimes over Turkey

Turkish annual precipitation regimes are analysed to provide large-scale perspective and redefine precipitation regions. Monthly total precipitation data are employed for 107 stations (1963–2002). Precipitation regime shape (seasonality) and magnitude (size) are classified using a novel multivariate methodology. Six shape and five magnitude classes are identified, which exhibit clear spatial structure. A composite (shape and magnitude) regime classification reveals dominant controls on spatial variability of precipitation. Intra-annual timing and magnitude of precipitation is highly variable due to seasonal shifts in Polar and Subtropical zones and physiographic factors. Nonetheless, the classification methodology is shown to be a powerful tool that identifies physically-interpretable precipitation regions: (1) coastal regimes for Marmara, coastal Aegean, Mediterranean and Black Sea; (2) transitional regimes in continental Aegean and Southeast Anatolia; and (3) inland regimes across central and Eastern Anatolia. This research has practical implications for understanding water resources, which are under ever growing pressure in Turkey

Compressive Response of Polycrystalline NiCoMnGa High-Temperature Meta-magnetic Shape Memory Alloys

The effects of the addition of quaternary element, Co, to polycrystalline NiMnGa alloys on their magnetic and shape memory properties have been investigated. NiCoMnGa polycrystalline alloys have been found to demonstrate good shape memory and superelasticity behavior under compression at temperatures greater than 100 °C with about 3% transformation strain and low-temperature hysteresis. It is also possible to train the material to demonstrate a large two-way shape memory effect

Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases

Activation of androgen receptor (AR) may play a role in the development of castration resistant prostate cancer. Two intracellular tyrosine kinases, Ack1 (activated cdc42-associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals. However, the upstream signals that activate these kinases and lead to AR activation are incompletely characterized. In this study, we investigated AR phosphorylation in response to non-androgen ligand stimulation using phospho-specific antibodies. Treatment of LNCaP and LAPC-4 cells with epidermal growth factor (EGF), heregulin, Gas6 (ligand binding to Mer receptor tyrosine kinase and activating Ack1 downstream), interleukin (IL)-6 or bombesin stimulated cell proliferation in the absence of androgen. Treatment of LNCaP and LAPC-4 cells with EGF, heregulin, or Gas6 induced AR phosphorylation at Tyr-267; IL-6 or bombesin treatment did not. AR phosphorylation at Tyr-534 was induced by treatment with EGF, IL-6 or bombesin, but not by heregulin or Gas6. siRNA-mediated knockdown of Ack1 or Src showed that Ack1 mediates heregulin- and Gas6-induced AR Tyr-267 phosphorylation whereas Src mediates Tyr-534 phosphorylation induced by EGF, IL-6, and bombesin. Dasatinib, a Src inhibitor, blocked EGF-induced Tyr-534 phosphorylation. In addition, we show dasatinib also inhibited Ack1 kinase. Dasatinib inhibited heregulin-induced Ack1 kinase activity and AR Tyr-267 phosphorylation. Dasatinib inhibited heregulin-induced AR-dependent reporter activity. Dasatinib also inhibited heregulin-induced expression of endogenous AR target genes. Dasatinib inhibited Ack1-dependent colony formation and prostate xenograft tumor growth in castrated mice. Interestingly, Ack1 or Src knockdown or dasatinib did not inhibit EGF-induced AR Tyr-267 phosphorylation or EGF-stimulated AR activity, suggesting the existence of an additional tyrosine kinase that phosphorylates AR at Tyr-267. These data suggest that specific tyrosine kinases phosphorylate AR at distinct sites and that dasatinib may exert anti-tumor activity in prostate cancer through inhibition of Ack1

Effect of fulvic acids on lead-induced oxidative stress to metal sensitive Vicia faba L. plant

Lead (Pb) is a ubiquitous environmental pollutant capable to induce various morphological, physiological, and biochemical functions in plants. Only few publications focus on the influence of Pb speciation both on its phytoavailability and phytotoxicity. Therefore, Pb toxicity (in terms of lipid peroxidation, hydrogen peroxide induction, and photosynthetic pigments contents) was studied in Vicia faba plants in relation with Pb uptake and speciation. V. faba seedlings were exposed to Pb supplied as Pb(NO3)2 or complexed by two fulvic acids (FAs), i.e. Suwannee River fulvic acid (SRFA) and Elliott Soil fulvic acid (ESFA), for 1, 12, and 24 h under controlled hydroponic conditions. For both FAs, Pb uptake and translocation by Vicia faba increased at low level (5 mg l−1), whereas decreased at high level of application (25 mg l−1). Despite the increased Pb uptake with FAs at low concentrations, there was no influence on the Pb toxicity to the plants. However, at high concentrations, FAs reduced Pb toxicity by reducing its uptake. These results highlighted the role of the dilution factor for FAs reactivity in relation with structure; SRFA was more effective than ESFA in reducing Pb uptake and alleviating Pb toxicity to V. faba due to comparatively strong binding affinity for the heavy metal

Mutation of Androgen Receptor N-Terminal Phosphorylation Site Tyr-267 Leads to Inhibition of Nuclear Translocation and DNA Binding

Reactivation of androgen receptor (AR) may drive recurrent prostate cancer in castrate patients. Ack1 tyrosine kinase is overexpressed in prostate cancer and promotes castrate resistant xenograft tumor growth and enhances androgen target gene expression and AR recruitment to enhancers. Ack1 phosphorylates AR at Tyr-267 and possibly Tyr-363, both in the N-terminal transactivation domain. In this study, the role of these phosphorylation sites was investigated by characterizing the phosphorylation site mutants in the context of full length and truncated AR lacking the ligand-binding domain. Y267F and Y363F mutants showed decreased transactivation of reporters. Expression of wild type full length and truncated AR in LNCaP cells increased cell proliferation in androgen-depleted conditions and increased colony formation. However, the Y267F mutant of full length and truncated AR was defective in stimulating cell proliferation. The Y363F mutant was less severely affected than the Y267F mutant. The full length AR Y267F mutant was defective in nuclear translocation induced by androgen or Ack1 kinase. The truncated AR was constitutively localized to the nucleus. Chromatin immunoprecipitation analysis showed that it was recruited to the target enhancers without androgen. The truncated Y267F AR mutant did not exhibit constitutive nuclear localization and androgen enhancer binding activity. These results support the concept that phosphorylation of Tyr-267, and to a lesser extent Tyr-363, is required for AR nuclear translocation and recruitment and DNA binding and provide a rationale for development of novel approaches to inhibit AR activity

Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental delay, severe to profound intellectual disability, muscle weakness and abnormal tone, autistic features, behavioral abnormalities, and variable dysmorphisms. The variants disrupt highly conserved residues across the protein. Functional experiments, including in silico analysis of the protein structure, in vitro assessment of cell surface expression, and in vitro knockdown, revealed potential mechanisms of pathogenicity of the variants, including loss of protein function and decreased neurite outgrowth. Our data indicate that appropriate expression of NTNG2 plays an important role in neurotypical development

The unexpected resurgence of Weyl geometry in late 20-th century physics

Weyl's original scale geometry of 1918 ("purely infinitesimal geometry") was withdrawn by its author from physical theorizing in the early 1920s. It had a comeback in the last third of the 20th century in different contexts: scalar tensor theories of gravity, foundations of gravity, foundations of quantum mechanics, elementary particle physics, and cosmology. It seems that Weyl geometry continues to offer an open research potential for the foundations of physics even after the turn to the new millennium.Comment: Completely rewritten conference paper 'Beyond Einstein', Mainz Sep 2008. Preprint ELHC (Epistemology of the LHC) 2017-02, 92 pages, 1 figur

Association of Toll-like receptor 4 (TLR4) with chronic plaque type psoriasis and psoriatic arthritis.

Family studies have provided overwhelming evidence for an underlying genetic component to psoriasis. Toll-like receptors (TLRs) are key transmembrane proteins in both the innate and adaptive immune responses which are known to be integral processes in psoriasis. Recent functional studies support this notion having suggested a role for TLR4 in the pathogenesis of psoriasis. Furthermore a missense polymorphism in the TLR4 gene has been associated with a number of autoimmune conditions, including Crohn diseases, making TLR4 a viable candidate gene for investigation. The aim of this study was to investigate polymorphisms across the TLR4 region with a high-density single nucleotide polymorphism (SNP) panel in a large cohort of patients with chronic plaque type psoriasis. Twenty SNPs were successfully genotyped using Sequenom iPLEX Gold platform in 2826 UK chronic plaque type psoriasis patients including subgroup data on presence of confirmed psoriatic arthritis (n = 1839) and early-onset psoriasis (n = 1466) was available. Allele frequencies for psoriasis patients were compared against imputed Wellcome Trust Case Control Consortium controls (n = 4861). Significant association was observed between a missense variant rs4986790 of TLR4 (Asp229Gly) and plaque type psoriasis (p = 2 × 10(-4)) which was also notable in those with psoriatic arthritis (p = 2 × 10(-4)) and early-onset psoriasis (p = 8 × 10(-4)). We present data suggestive of an association between a functional variant and an intronic variant of TLR4 and chronic plaque type psoriasis and psoriatic arthritis. However, validation of this association in independent cohorts will be necessary