Solidification microstructure of centrifugally cast Inconel 625

Centrifugal casting is a foundry process allowing the production of near net-shaped axially symmetrical components. The present study focuses on the microstructural characterization of centrifugally cast alloys featuring different chemical compositions for the construction of spheres applied in valves made of alloy IN625 for operation at high pressure. Control of the solidification microstructure is needed to assure the reliability of the castings. Actually, a Ni-base superalloy such as this one should have an outstanding combination of mechanical properties, high temperature stability and corrosion resistance. Alloys such as IN625 are characterised by a large amount of alloying elements and a wide solidification range, so they can be affected by micro-porosity defects, related to the shrinkage difference between the matrix and the secondary reinforcing phases (Nb-rich carbides and Laves phase). In this study, the microstructure characterization was performed as a function of the applied heat treatments and it was coupled with a calorimetric analysis in order to understand the mechanism ruling the formation of micro-porosities that can assure alloy soundness. The obtained results show that the presence of micro-porosities is governed by morphology and by the size of the secondary phases, and the presence of the observed secondary phases is detrimental to corrosion resistance

Unravelling error sources in miniaturized NIR spectroscopic measurements: the case study of forages

The use of miniaturized NIR spectrometers is spreading over the scientific literature with a particular focus on developing methods as rapid and easy-to-use as possible and following the philosophy of green analytical chemistry. Several applications and studies are typically presented by comparing results obtained with benchtop instrumentation even when the analytical strategies are substantially different. Indeed, analytical applications that include the use of miniaturized instrumentation are subject to several sources of variability that need to be known at the time of method development. In this study, different statistical strategies were employed to understand the features and limitations of handheld NIR instruments. Because of the high interest in real applications, a common type of hygroscopic powder sample was selected: forages. A step-by-step methodology is presented to statistically address the different issues to consider in order to obtain realistic models when using miniaturized NIR spectrometers. We demonstrate how a careful evaluation of the sources of variability related to an experiment can help in the understanding of the system under study in order to obtain a more reliable development of the method and consciously choose the analytical parameters and strategies of analysis. The results were also compared with those achieved on the same dataset from a benchtop system in order to provide references analogous with those in the literature

Exposure to a Low Pathogenic A/H7N2 Virus in Chickens Protects against Highly Pathogenic A/H7N1 Virus but Not against Subsequent Infection with A/H5N1

Recent evidences have demonstrated that the presence of low pathogenic avian influenza viruses (LPAIV) may play an important role in host ecology and transmission of avian influenza viruses (AIV). While some authors have clearly demonstrated that LPAIV can mutate to render highly pathogenic avian influenza viruses (HPAIV), others have shown that their presence could provide the host with enough immunological memory to resist re-infections with HPAIV. In order to experimentally study the role of pre-existing host immunity, chickens previously infected with H7N2 LPAIV were subsequently challenged with H7N1 HPAIV. Pre-infection of chickens with H7N2 LAPIV conferred protection against the lethal challenge with H7N1 HPAIV, dramatically reducing the viral shedding, the clinical signs and the pathological outcome. Correlating with the protection afforded, sera from chickens primed with H7N2 LPAIV reacted with the H7-AIV subtype in hemagglutination inhibition assay and specifically with the N2-neuraminidase antigen. Conversely, subsequent exposure to H5N1 HPAIV resulted in a two days-delay on the onset of disease but all chickens died by 7 days post-challenge. Lack of protection correlated with the absence of H5-hemagglutining inhibitory antibodies prior to H5N1 HPAIV challenge. Our data suggest that in naturally occurring outbreaks of HPAIV, birds with pre-existing immunity to LPAIV could survive lethal infections with HA-homologous HPAIV but not subsequent re-infections with HA-heterologous HPAIV. These results could be useful to better understand the dynamics of AIV in chickens and might help in future vaccine formulations

Inactivation of CK1\u3b1 in multiple myeloma empowers drug cytotoxicity by affecting AKT and f-catenin survival signaling pathways

Recent evidence indicates that protein kinase CK1\u3b1 may support the growth of multiple myeloma (MM) plasma cells. Here, by analyzing a large cohort of MM cases, we found that high CK1\u3b1 mRNA levels are virtually associated with all MM patients. Moreover, we provided functional evidence that CK1\u3b1 activity is essential for malignant plasma cell survival even in the protective niche generated by co-cultures with bone marrow stromal cells. We demonstrated that CK1\u3b1 inactivation, while toxic for myeloma cells, is dispensable for the survival of healthy B lymphocytes and stromal cells. Disruption of CK1\u3b1 function in myeloma cells resulted in decreased Mdm2, increased p53 and p21 and reduced expression of \u3b2-catenin and AKT. These effects were mediated partially by p53 and caspase activity. Finally, we discovered that CK1\u3b1 inactivation enhanced the cytotoxic effect of both bortezomib and lenalidomide. Overall, our study supports a role for CK1\u3b1 as a potential therapeutic target in MM in combination with proteasome inhibitors and/or immunomodulatory drugs

Presence of specific antibodies against H7-, N1- and N2- evaluated by ELISA.

<p>Pooled sera from chickens were taken 15 days post-H7N2 LPAIV exposure and 10 days post-H7N1 HPAIV challenge and were tested for binding to (A) H7 hemagglutinin, (B) N1 or (C) N2 neuraminidases by ELISA.</p

Viral shedding from experimental infected chickens with H7N2 LPAIV and to subsequent infection with H7N1 HPAIV.

<p>Viral RNA shedding measured by RRT-PCR in swab samples (oropharyngeal and cloacal) at 1, 4, 7 and 12 days after (A) H7N2 LPAIV infection and (B) H7N1 HPAIV challenge. Results are expressed as inverted Ct-value and shown as means ± SD. The number of animals shedding/total birds is indicaed, except in those cases that the sheddin was 100%. Ct, cycle of threshold. Asterisk (*) indicates statistical significant differences (<i>P</i><0.05).</p

Experimental design.

<p>Thirty 2-week old SPF-chickens were randomly distributed into three groups. Animals received the first inoculum (day 0) and 2 weeks later (day 15), birds were challenged with the respective inoculum 2. Six birds from G1 and G2 were consecutively infected 2 weeks later (day 30) with the third inoculum.</p><p>Abbreviations: LPAIV = low pathogenic avian influenza virus; HPAIV = highly pathogenic avian influenza virus.</p>a<p>Chickens from G1 were inoculated intranasally with LPAIV A/<i>Anas plathyrhynchos</i>/Spain/1877/2009 (H7N2) (10^5.5 ELD₅₀). Birds from G2 and G3 received saline solution.</p>b<p>Chickens from G1 and G2 were intranasally challenged with HPAIV A/FPV/Rostock/34 (H7N1) (10^5.5 ELD₅₀) 15 days after the pre-exposure to H7N2 LPAIV. Birds from G3 received saline solution.</p>c<p>Chickens from G1 and G3 were inoculated intranasally with 10^4.5 ELD₅₀ of A/Great crested grebe/Basque Country/06.03249/2006 (H5N1) 15 days after the challenge with H7N1 HPAIV.</p

Serological status, as determined by hemagglutination inhibition, of chickens 15 days after experimental pre-exposure to H7N2 LPAIV^a and 10 days after challenge with H7N1 HPAIV^b.

<p>Sera from the animals were tested against H7 and H5 antigens.</p>a<p>Chickens were inoculated intranasally with A/<i>Anas plathyrhynchos</i>/Spain/1877/2009 (H7N2) (10^5.5 ELD₅₀). Serologic data from six randomly selected birds per group are presented.</p><p>Due to the lack of seroconversion, only four animals from the naïve group are represented in the table.</p>b<p>Chickens were challenged intranasally with A/FPV/Rostock/34 (H7N1) (10^5.5 of ELD₅₀) 15 days after the pre-exposure to H7N2 LPAIV.</p>c<p>HI titers ≥8 were considered positive.</p>d<p>HI using antigen against H7N3 subtype.</p>e<p>HI using antigen against H5N1 aubtype.</p>†<p> = succumbed to H7N1 HPAIV-infection.</p