Small, low cost, expendable turbojet engine. 2: Performance characteristics

A small experimental axial-flow turbojet engine was tested at sea level static conditions and over a range of simulated flight conditions to evaluate its performance as well as to demonstrate the feasibility of low-cost concepts utilized in its design. Testing was conducted at engine speeds as high as 37,000 rpm and at turbine inlet temperatures as high as 1,272 K. For maximum speed the engine produced a net thrust of 3,118 newtons at sea level static operation and 2,318 newtons at its cruise condition of M0 = 0.8 and 6,096 meters. Data obtained over a range of inlet Reynolds number indexes for nominal M0 of 0.38 revealed similar effects or trends on compressor characteristics of those previously established for much larger engines

Small, low-cost, expendable turbojet engine. 1: Design, fabrication, and preliminary testing

A small experimental axial-flow turbojet engine in the 2,669-Newton (600-lbf) thrust class was designed, fabricated, and tested to demonstrate the feasibility of several low-cost concepts. Design simplicity was stressed in order to reduce the number of components and machining operations. Four engines were built and tested for a total of 157 hours. Engine testing was conducted at both sea-level static and simulated flight conditions for engine speeds as high as 38,000 rpm and turbine-inlet temperatures as high as 1,255 K (1,800 F)

Caveolin-3 Directly Interacts with the C-terminal Tail of β-Dystroglycan IDENTIFICATION OF A CENTRAL WW-LIKE DOMAIN WITHIN CAVEOLIN FAMILY MEMBERS

Caveolin-3, the most recently recognized member of the caveolin gene family, is muscle-specific and is found in both cardiac and skeletal muscle, as well as smooth muscle cells. Several independent lines of evidence indicate that caveolin-3 is localized to the sarcolemma, where it associates with the dystrophin-glycoprotein complex. However, it remains unknown which component of the dystrophin complex interacts with caveolin-3. Here, we demonstrate that caveolin-3 directly interacts with b-dystroglycan, an integral membrane component of the dystrophin complex. Our results indicate that caveolin-3 co-localizes, co-fractionates, and coimmunoprecipitates with a fusion protein containing the cytoplasmic tail of b-dystroglycan. In addition, we show that a novel WW-like domain within caveolin-3 directly recognizes the extreme C terminus of b-dystroglycan that contains a PPXY motif. As the WW domain of dystrophin recognizes the same site within b-dystroglycan, we also demonstrate that caveolin-3 can effectively block the interaction of dystrophin with b-dystroglycan. In this regard, interaction of caveolin-3 with b-dystroglycan may competitively regulate the recruitment of dystrophin to the sarcolemma. We discuss the possible implications of our findings in the context of Duchenne muscular dystrophy

Le confessioni religiose tra libertà di vivere nella realtà dell'ordinamento statale e potere di creare norme giuridiche all'interno dello Stato. Il caso della Chiesa di Scientology.

L'A. si pone nella prospettiva di delineare il possibile significato della compresenza delle due distinte previsioni, l’una nell’art. 8, l’altra nell’art. 19 della Costituzione, a garanzia del fenomeno associativo religioso. La ricerca è stata redatta, fra l’altro, in considerazione della circostanza che, ad una prima sommaria lettura della Carta Costituzionale, il lettore potrebbe essere indotto a pensare che il fenomeno religioso, ed in particolare quello che si svolge in forma associata, goda di una maggiore preferenza, rispetto a quello che si esprime in forma individuale, per essere più volte disciplinato in Costituzione. Problema, questo, il quale non sembra abbia sinora ricevuto adeguato rilievo dalla dottrina ecclesiasticista che si è meritevolmente impegnata sul tema. Si è posto al riguardo l’interrogativo che nasce dalla presenza di due distinte previsioni costituzionali a garanzia del fenomeno associativo religioso: la prima contenuta nell’art. 8 il quale - com’è noto - regola con novità di linguaggio la posizione dei culti diversi dalla religione cattolica, garantisce alle confessioni religiose l’eguale libertà davanti alla legge, il diritto di organizzarsi secondo i propri statuti ed il potere di concludere intese con gli organi dello Stato; la seconda nell’art. 19 che riconosce la libertà di professare liberamente la propria fede religiosa in qualsiasi forma “individuale o associata”. In ordine ai numerosi problemi che la previsione costituzionale dell’art. 8 solleva, si è riflettuto soprattutto sul dubbio se la fattispecie in essa contemplata sia sostanzialmente ripetitiva e si risolva in un inutile duplicato di quanto disposto dall’art. 19 per la parte che riguarda tale aspetto, oppure se, con ciascuna di tali disposizioni, il legislatore costituzionale abbia voluto conferire uno specifico rilievo a due distinte sfere dell’esperienza giuridica con caratteristiche proprie, per struttura e sistemi di garanzie. L’analisi intrapresa ha interessato anche la ricostruzione della definizione giuridica di confessione religiosa, nonché l’accertamento del carattere confessionale della Chiesa di Scientology alla luce delle sentenze della giurisprudenza costituzionale e di legittimità

The botanical drug PBI-05204, a supercritical CO2 extract of Nerium oleander, sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy in vitro and in vivo

Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na+/K+-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties. Herein, the therapeutic properties of PBI-05204, an extract from Nerium oleander containing the CG oleandrin already studied in phase I and II clinical trials for cancer patients, were investigated, in vitro and in vivo, against FN- and FP-RMS cancer models. PBI-05204 induced growth arrest in a concentration dependent manner, with FP-RMS being more sensitive than FN-RMS, by differently regulating cell cycle regulators and commonly upregulating cell cycle inhibitors p21Waf1/Cip1 and p27Cip1/Kip1. Furthermore, PBI-05204 concomitantly induced cell death on both RMS types and senescence in FN-RMS. Notably, PBI-05204 counteracted in vitro migration and invasion abilities and suppressed the formation of spheroids enriched in CD133+ cancer stem cells (CSCs). PBI-05204 sensitized both cell types to RT by improving the ability of RT to induce G2 growth arrest and counteracting the RT-induced activation of both Non‐Homologous End‐Joining and homologous recombination DSBs repair pathways. Finally, the antitumor and radio-sensitizing proprieties of PBI-05204 were confirmed in vivo. Notably, both in vitro and in vivo evidence confirmed the higher sensitivity to PBI-05204 of FP-RMS. Thus, PBI-05204 represents a valid radio-sensitizing agent for the treatment of RMS, including the intrinsically radio-resistant FP-RMS

Clinically relevant radioresistant rhabdomyosarcoma cell lines: Functional, molecular and immune-related characterization

Background: The probability of local tumor control after radiotherapy (RT) remains still miserably poor in pediatric rhabdomyosarcoma (RMS). Thus, understanding the molecular mechanisms responsible of tumor relapse is essential to identify personalized RT-based strategies. Contrary to what has been done so far, a correct characterization of cellular radioresistance should be performed comparing radioresistant and radiosensitive cells with the same isogenic background. Methods: Clinically relevant radioresistant (RR) embryonal (RD) and alveolar (RH30) RMS cell lines have been developed by irradiating them with clinical-like hypo-fractionated schedule. RMS-RR cells were compared to parental isogenic counterpart (RMS-PR) and studied following the radiobiological concept of the "6Rs", which stand for repair, redistribution, repopulation, reoxygenation, intrinsic radioresistance and radio-immuno-biology. Results: RMS-RR cell lines, characterized by a more aggressive and in vitro pro-metastatic phenotype, showed a higher ability to i) detoxify from reactive oxygen species; ii) repair DNA damage by differently activating non-homologous end joining and homologous recombination pathways; iii) counteract RT-induced G2/M cell cycle arrest by re-starting growth and repopulating after irradiation; iv) express cancer stem-like profile. Bioinformatic analyses, performed to assess the role of 41 cytokines after RT exposure and their network interactions, suggested TGF-β, MIF, CCL2, CXCL5, CXCL8 and CXCL12 as master regulators of cancer immune escape in RMS tumors. Conclusions: These results suggest that RMS could sustain intrinsic and acquire radioresistance by different mechanisms and indicate potential targets for future combined radiosensitizing strategies

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber

Genetic Modifier Screens Reveal New Components that Interact with the Drosophila Dystroglycan-Dystrophin Complex

The Dystroglycan-Dystrophin (Dg-Dys) complex has a capacity to transmit information from the extracellular matrix to the cytoskeleton inside the cell. It is proposed that this interaction is under tight regulation; however the signaling/regulatory components of Dg-Dys complex remain elusive. Understanding the regulation of the complex is critical since defects in this complex cause muscular dystrophy in humans. To reveal new regulators of the Dg-Dys complex, we used a model organism Drosophila melanogaster and performed genetic interaction screens to identify modifiers of Dg and Dys mutants in Drosophila wing veins. These mutant screens revealed that the Dg-Dys complex interacts with genes involved in muscle function and components of Notch, TGF-β and EGFR signaling pathways. In addition, components of pathways that are required for cellular and/or axonal migration through cytoskeletal regulation, such as Semaphorin-Plexin, Frazzled-Netrin and Slit-Robo pathways show interactions with Dys and/or Dg. These data suggest that the Dg-Dys complex and the other pathways regulating extracellular information transfer to the cytoskeletal dynamics are more intercalated than previously thought

Evolution of silent myocardial ischaemia prevalence and cardiovascular disease risk factor management in Type 2 diabetes over a 10-year period: an observational study

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