Coil-On-Plug Ignition for Oxygen/Methane Liquid Rocket Engines in Thermal-Vacuum Environments

A coil-on-plug ignition system has been developed and tested for Liquid Oxygen (LOX)/liquid methane (LCH4) rocket engines operating in thermal vacuum conditions. The igniters were developed and tested as part of the Integrated Cryogenic Propulsion Test Article (ICPTA), previously tested as part of the Project Morpheus test vehicle. The ICPTA uses an integrated, pressure-fed, cryogenic LOX/LCH4 propulsion system including a reaction control system (RCS) and a main engine. The ICPTA was tested at NASA Glenn Research Center's Plum Brook Station in the Spacecraft Propulsion Research Facility (B-2) under vacuum and thermal vacuum conditions. A coil-on-plug ignition system has been developed to successfully demonstrate ignition reliability at these conditions while preventing corona discharge issues. The ICPTA uses spark plug ignition for both the main engine igniter and the RCS. The coil-on-plug configuration eliminates the conventional high-voltage spark plug cable by combining the coil and the spark plug into a single component. Prior to ICPTA testing at Plum Brook, component-level reaction control engine (RCE) and main engine igniter testing was conducted at NASA Johnson Space Center (JSC), which demonstrated successful hot-fire ignition using the coil-on-plug from sea-level ambient conditions down to 10(exp -2) torr. Integrated vehicle hot-fire testing at JSC demonstrated electrical and command/data system performance. Lastly, hot-fire testing at Plum Brook demonstrated successful ignitions at simulated altitude conditions at 30 torr and cold thermal-vacuum conditions at 6 torr. The test campaign successfully proved that coil-on-plug technology will enable integrated LOX/LCH4 propulsion systems in future spacecraft

The Effect of Adverse Supply Shocks on Monetary Policy and Output

The aim of the present research is to use a model economy built for Brazil, based on an optimizing dynamic general equilibrium model, in order to perform numerical simulations to derive the ability of the artificial economy to explain the impact of monetary policy interventions on short run economic performance in terms of the inflation rate, output gap, interest rate and level of economic activity in the face of an adverse supply shock. Alternative specification of monetary reaction functions are introduced into the model economy in order to perform a sensitivity analysis of derived impulse responses to those interventions facing the negative productivity shock. The preliminary results suggest that the introduction of habit persistence into the consumption hypothesis does not make much difference. However the introduction of different monetary reaction functions does alter the impulse response of output, inflation rate, and nominal interest rate. A common result is the decline in potential output for all models. Additionally, the only case where a reduction in the output gap is observed is when using the Taylor rule that takes into consideration the output gap and past interest rates with high persistence.

Učinak praha avokada, suncokretova ulja te različitih omjera voluminozne i koncentrirane krme u obroku na unos hrane, probavljivost hrane i proizvodnost mladih ovnova

The objective of this study was to evaluate the inclusion of avocado flour and sunflower oil as energy sources in different proportions, as well as different forage:concentrate ratios on the productive performance and feed intake of male rams, and the in vitro dry matter digestibility, organic matter digestibility and gas production. The intake was measured in diets containing avocado flour or sunflower oil with 60% forage: 40% concentrate, and in diets with different forage:concentrate ratios and 10% inclusion of avocado flour or sunflower oil. The daily weight gain was registered for 84 days, the in vitro dry matter digestibility was determined at 48 h, and the in vitro gas production was evaluated at 72 h. The partial production of gas at 24 hours, raw protein, raw fat, and ash were used to estimate the metabolizable energy and organic matter digestibility. Low levels of avocado flour and sunflower oil in the diet showed the highest intake, in vitro dry matter digestibility and in vitro gas production. Daily weight gains were 0.28 kg in avocado flour and 0.30 kg in sunflower oil diets, both at 10% inclusion and 40% forage: 60% concentrate. The inclusion of high levels of avocado flour or forage in the diet decreased the feed intake of male sheep. The best avocado flour level was 10% with 40% forage: 60% concentrate.Cilj rada bio je istražiti utjecaj različitih omjera između praha avokada i suncokretova ulja kao izvora energije, te različitih omjera između voluminozne i koncentrirane krme u obroku na unos hrane i proizvodnost mladih ovnova. Osim toga, in vitro istražena je probavljivost suhe tvari, probavljivost organske tvari i proizvodnja plina. Unos hrane mjeren je u obrocima koji su sadržavali prah avokada ili suncokretovo ulje uz omjer između voluminozne i koncentrirane krme od 60:40% ili u obrocima sa različitim omjerom voluminozne i koncentrirane krme uz dodatak 10% praha avokada ili suncokretova ulja. Dnevni prirast bilježen je tijekom 84 dana. Probavljivost suhe tvari in vitro određivana je 48 h, a proizvodnja plina in vitro 72 h od uzimanja uzoraka. Za određivanje metaboličke energije i probavljivosti organske tvari korišteni su parcijalna proizvodnja plina 24-ti sat, sirovi protein, sirova mast i pepeo. Niske razine praha avokada i suncokretova ulja u obroku rezultirale su najvišim unosom hrane te najvišom in vitro probavljivošću suhe tvari i in vitro proizvodnjom plina. Dnevni prirast bio je 0,28 kg u životinja kojima je davano 10% praha avokada, 0,30 kg u životinja kojima je davano 10% suncokretova ulja, pri čemu je omjer voluminozne i koncentrirane krme iznosio 40:60%. Dodavanje visokih razina praha avokada ili voluminozne krme u obrok dovelo je do nižeg unosa hrane kod mladih ovnova pa je zaključeno da je najpovoljnija razina dodanog praha avokada 10% uz omjer voluminozne i koncentrirane krme 40:60%

Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection

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Mesenchymal stem cells from Shwachman\u2013Diamond syndromepatients display normal functions and do not contribute tohematological defects

Shwachman\u2013Diamond syndrome (SDS) is a rare inherited disorder characterized by bone marrow (BM) dysfunction and exocrine pancreatic insufficiency. SDS patients have an increased risk for myelodisplastic syndrome and acute myeloid leukemia. Mesenchymal stem cells (MSCs) are the key component of the hematopoietic microenvironment and are relevant in inducing genetic mutations leading to leukemia. However, their role in SDS is still unexplored. We demonstrated that morphology, growth kinetics and expression of surface markers of MSCs from SDS patients (SDS-MSCs) were similar to normal MSCs. Moreover, SDS-MSCs were able to differentiate into mesengenic lineages and to inhibit the proliferation of mitogen-activated lymphocytes. We demonstrated in an in vitro coculture system that SDS-MSCs, significantly inhibited neutrophil apoptosis probably through interleukin-6 production. In a long-term coculture with CD34\ufe-sorted cells, SDS-MSCs were able to sustain CD34\ufe cells survival and to preserve their stemness. Finally, SDS-MSCs had normal karyotype and did not show any chromosomal abnormality observed in the hematological components of the BM of SDS patients. Despite their pivotal role in the hematopoietic stem cell niche, our data suggest that MSC themselves do not seem to be responsible for the hematological defects typical of SDS patients

CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia

Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway

Absent B Cells, agammaglobulinemia, and Hypertrophic Cardiomyopathy in Folliculin-interacting Protein 1 Deficiency

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity

Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondria! numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1(-/-) animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of I immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity.Molecular Technology and Informatics for Personalised Medicine and Healt