Slurry and dry particle erosion wear properties of WC-10Co4Cr and Cr3C2-25NiCr hardmetal coatings deposited by HVOF and HVAF spray processes

Thermally sprayed hardmetal coatings were produced to provide improved erosion wear compared to conventional cast GX4CrNi13-4 martensitic steel (CA6NM) used in hydro turbine components. Sprayed coatings and reference materials were tested with high-speed slurry pot tester using either fine or coarse quartz as the erosive media. Additional erosion tests were carried out with centrifugal dry erosion tester. Tungsten carbide based coatings provided the highest wear resistance due to the high hardness and even distribution of the fine carbide particles. The cast 13-4 steel samples experienced up to 180 times higher wear rates in fine quartz slurry and up to 36 times higher wear rates in coarse slurry compared to the sprayed coatings

Properties of arc-sprayed coatings from Fe-based cored wires for high-temperature applications

Equipment of a thermal power plant is subjected to high temperature oxidation and wear. This raises operating costs through frequent repair of worn parts and high metal consumption. The paper proposes a possible solution to this problem through arc spraying of protective coatings. Cored wires of the Fe-Cr-C basic alloying system are used as a feedstock. Additional alloying by Al, B, Si, Ti and Y allows one to create wear- and heat-resistant coatings, which are an attractive substitute of more expensive Co- and Ni-based materials. © 2017 Author(s)

Levinneen suonikalvoston melanooman hoito on kautta Suomen kansainvälistä tasoa

Lähtökohdat : Silmän suonikalvoston levinneen melanooman (uveamelanooma) hoitosuositukset vaihtelevat. Keräsimme väestöpohjaisen aineiston, jonka avulla selvitimme, onko yliopistopiirien välillä eroa elossaoloajassa tai hoitolinjoissa. Menetelmät : Aineistona oli 338 potilasta, joiden emokasvain oli hoidettu keskitetysti Hyksissä ja joiden levinnyt tauti todettiin 1999–2016 ja hoidettiin hajautetusti eri sairaanhoitopiireissä. Potilaat jaoteltiin Suomessa kehitetyn levinneisyysluokituksen, ensilinjan hoidon ja yliopistosairaalapiirin mukaan. Tulokset : Oireenmukaista hoitoa sai 33 % potilasta ja aktiivista 67 %, yliopistosairaalapiireittäin 21–40 % ja 60–79 %. Vastaavat elossaoloajan mediaanit olivat 1,6 kk ja 12 kk ja koko kohortissa 9,0 kk. Aktiivisesti hoidetusta leikattiin 9 %. Hoitotutkimuksiin osallistui 4 % potilaista. ­Suotuisimmassa levinneisyysluokassa IVa (ennuste ≥ 12 kk) oireenmukaisesti ja aktiivisesti ­hoidettujen elossaoloajat olivat 12 kk ja 18 kk. Levinneisyysluokissa IVa ja IVb (6–12 kk) ­elossaoloajat yliopistopiireittäin olivat toisiinsa verrattavat (p = 0,90 ja 0,91). Luokassa IVc (< 6 kk) oli eroa, mutta se hävisi tarkemmassa analyysissä (p = 0,33). Päätelmät : Yliopistosairaalapiirien tulokset vastaavat toisiaan ja kansainvälistä tasoa.Peer reviewe

Over 2000-Fold Increased Production of the Leaderless Bacteriocin Garvicin KS by Increasing Gene Dose and Optimization of Culture Conditions

The leaderless bacteriocin Garvicin KS (GarKS) is a potent antimicrobial, being active against a wide range of important pathogens. GarKS production by the native producer Lactococcus garvieae KS1546 is, however, relatively low (80 BU/ml) under standard laboratory growth conditions (batch culture in GM17 at 30°C). To improve the production, we systematically evaluated the impact of different media and media components on bacteriocin production. Based on the outcomes, a new medium formulation was made that increased GarKS production about 60-fold compared to that achieved in GM17. The new medium was composed of pasteurized milk and tryptone (PM-T). GarKS production was increased further 4-fold (i.e., to 20,000 BU/ml) by increasing the gene dose of the bacteriocin gene cluster (gak) in the native producer. Finally, a combination of the newly composed medium (PM-T), an increased gene dose and cultivation at a constant pH 6 and a 50–60% dissolved oxygen level in growth medium, gave rise to a GarKS production of 164,000 BU/ml. This high production, which is about 2000-fold higher compared to that initially achieved in GM17, corresponds to a GarKS production of 1.2 g/L. To our knowledge, this is one of the highest bacteriocin production reported hitherto

Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors : modeling the function of an inactivating receptor mutation

Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein-protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.Peer reviewe

Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors : modeling the function of an inactivating receptor mutation

Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein-protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.Peer reviewe

Steroidogenic factor 1 (NR5A1) induces multiple transcriptional changes during differentiation of human gonadal-like cells

Peer reviewe

Complement in Human Pre-implantation Embryos: Attack and Defense

It is essential for early human life that mucosal immunological responses to developing embryos are tightly regulated. An imbalance of the complement system is a common feature of pregnancy complications. We hereby present the first full analysis of the expression and deposition of complement molecules in human pre-implantation embryos. Thus, far, immunological imbalance has been considered in stages of pregnancy following implantation. We here show that complement activation against developing human embryos takes place already at the pre-implantation stage. Using confocal microscopy, we observed deposition of activation products on healthy developing embryos, which highlights the need for strict complement regulation. We show that embryos express complement membrane inhibitors and bind soluble regulators. These findings show that mucosal complement targets human embryos, and indicate potential adverse pregnancy outcomes, if regulation of activation fails. In addition, single-cell RNA sequencing revealed cellular expression of complement activators. This shows that the embryonic cells themselves have the capacity to express and activate C3 and C5. The specific local embryonic expression of complement components, regulators, and deposition of activation products on the surface of embryos suggests that complement has immunoregulatory functions and furthermore may impact cellular homeostasis and differentiation at the earliest stages of life.Peer reviewe

DUX4 is a multifunctional factor priming human embryonic genome activation

Double homeobox 4 (DUX4) is expressed at the early pre-implantation stage in human embryos. Here we show that induced human DUX4 expression substantially alters the chromatin accessibility of non-coding DNA and activates thousands of newly identified transcribed enhance-like regions, preferentially located within ERVL-MaLR repeat elements. CRISPR activation of transcribed enhancers by C-terminal DUX4 motifs results in the increased expression of target embryonic genome activation (EGA) genes ZSCAN4 and KHDC1P1. We show that DUX4 is markedly enriched in human zygotes, followed by intense nuclear DUX4 localization preceding and coinciding Kith minor EGA. DUX4 knockdown in human zygotes led to changes in the EGA transcriptome but did not terminate the embryos. We also show that the DUX4 protein interacts with the Mediator complex via the C-terminal KIX binding motif. Our findings contribute to the understanding of DUX4 as a regulator of the non-coding genome.Peer reviewe