Wind-tunnel/flight correlation study of aerodynamic characteristics of a large flexible supersonic cruise airplane (XB-70-1). 3: A comparison between characteristics predicted from wind-tunnel measurements and those measured in flight

A program was undertaken by NASA to evaluate the accuracy of a method for predicting the aerodynamic characteristics of large supersonic cruise airplanes. This program compared predicted and flight-measured lift, drag, angle of attack, and control surface deflection for the XB-70-1 airplane for 14 flight conditions with a Mach number range from 0.76 to 2.56. The predictions were derived from the wind-tunnel test data of a 0.03-scale model of the XB-70-1 airplane fabricated to represent the aeroelastically deformed shape at a 2.5 Mach number cruise condition. Corrections for shape variations at the other Mach numbers were included in the prediction. For most cases, differences between predicted and measured values were within the accuracy of the comparison. However, there were significant differences at transonic Mach numbers. At a Mach number of 1.06 differences were as large as 27 percent in the drag coefficients and 20 deg in the elevator deflections. A brief analysis indicated that a significant part of the difference between drag coefficients was due to the incorrect prediction of the control surface deflection required to trim the airplane

The ultracool dwarf DENIS-P J104814.7-395606. Chromospheres and coronae at the low-mass end of the main-sequence

We have obtained an XMM-Newton observation and a broad-band spectrum from the ultraviolet to the near infrared with X-Shooter for one of the nearest M9 dwarfs, DENIS-P J1048-3956 (4pc). We integrate these data by a compilation of activity parameters for ultracool dwarfs from the literature with the aim to advance our understanding of these objects by comparing them to early-M type dwarf stars and the Sun. Our deep XMM-Newton observation has led to the first X-ray detection of DENIS-P J1048-3956 (log Lx = 25.1) as well as the first measurement of its V band brightness (V = 17.35mag). Flux-flux relations between X-ray and chromospheric activity indicators are here for the first time extended into the regime of the ultracool dwarfs. The approximate agreement of DENIS-P J1048-3956 and other ultracool dwarfs with flux-flux relations for early-M dwarfs suggests that the same heating mechanisms work in the atmospheres of ultracool dwarfs, albeit weaker as judged from their lower fluxes. The observed Balmer decrements of DENIS-P J1048-3956 are compatible with optically thick plasma in LTE at low, nearly photospheric temperature or optically thin LTE plasma at 20000K. Describing the decrements with CaseB recombination requires different emitting regions for Halpha and the higher Balmer lines. The high observed Halpha/Hbeta flux ratio is also poorly fitted by the optically thin models. We derive a similarly high value for the Halpha/Hbeta ratio of vB10 and LHS2065 and conclude that this may be a characteristic of ultracool dwarfs. We add DENIS-P J1048-3956 to the list of ultracool dwarfs detected in both the radio and the X-ray band. The Benz-Guedel relation between radio and X-ray luminosity of late-type stars is well-known to be violated by ultracool dwarfs. We speculate on the presence of two types of ultracool dwarfs with distinct radio and X-ray behavior.Comment: accepted for publication in Astronomy & Astrophysic

Applications of infrared thermography in sports. A review

La termografía infrarroja (TI) registra el calor irradiado de un cuerpo, que es emitido en un rango del espectro electromagnético que la visión humana no es capaz de identificar. La respuesta térmica depende de una serie de ajustes fisiológicos específicos como la homeostasis corporal y salud del deportista, lo cual permite establecer interesantes aplicaciones en el deporte. El objetivo de este trabajo ha sido revisar la literatura en torno a las aplicaciones de la TI en el ámbito del deporte, y proponer las características óptimas del registro en relación al evaluado, las condiciones ambientales y la cámara utilizada. Concluimos que la principal contribución de la TI en el ámbito del deporte es ayudar a identificar signos de lesión antes de que la lesión se produzca, permitiéndonos actuar de manera preventiva durante el proceso de entrenamientoInfrared thermography (IRT) records the radiant heat of a body, which is emitted in the range of the electromagnetic spectrum that human vision is not able to identify. The thermal response depends on a number of specific physiological adjustments as body homeostasis and athlete’s health, which allow us to establishing interesting applications in sport. The aim of this study was to review the literature on IRT applications in sports, and to propose the optimal characteristics of the register in terms of the subject, the environmental conditions and the camera used. We conclude that the main contribution of IRT in the field of sport is to help identify signs of injury before it occurs, allowing us to act proactively along the training proces

Interleukin-2 therapy in patients with HIV infection

BACKGROUND Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. METHODS We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. RESULTS In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT. CONCLUSIONS Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].

Differential effects of HIF2α antagonist and HIF2α silencing in renal cancer and sensitivity to repurposed drugs

Background In clear cell renal cell carcinoma, 80% of cases have biallelic inactivation of the VHL gene, leading to constitutive activation of both HIF1α and HIF2α. As HIF2α is the driver of the disease promoting tumour growth and metastasis, drugs targeting HIF2α have been developed. However, resistance is common, therefore new therapies are needed. Methods We assessed the effect of the HIF2α antagonist PT2385 in several steps of tumour development and performed RNAseq to identify genes differentially expressed upon treatment. A drug screening was used to identify drugs with antiproliferative effects on VHL-mutated HIF2α-expressing cells and could increase effectiveness of PT2385. Results PT2385 did not reduce cell proliferation or clonogenicity but, in contrast to the genetic silencing of HIF2α, it reduced in vitro cell invasion. Many HIF-inducible genes were down-regulated upon PT2385 treatment, whereas some genes involved in cell migration or extracellular matrix were up-regulated. HIF2α was associated with resistance to statins, addition to PT2385 did not increase the sensitivity. Conclusions: this study shows key differences between inhibiting a target versus knockdown, which are potentially targetable

The epidemiology of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in community-living seniors: protocol of the MemoVie cohort study, Luxembourg

BACKGROUND: Cognitive impairment and Alzheimer’s disease (AD) are increasingly considered a major public health problem. The MemoVie cohort study aims to investigate the living conditions or risk factors under which the normal cognitive capacities of the senior population in Luxembourg (≥ 65 year-old) evolve (1) to mild cognitive impairment (MCI) – transitory non-clinical stage – and (2) to AD. Identifying MCI and AD predictors undeniably constitutes a challenge in public health in that it would allow interventions which could protect or delay the occurrence of cognitive disorders in elderly people. In addition, the MemoVie study sets out to generate hitherto unavailable data, and a comprehensive view of the elderly population in the country. METHODS/DESIGN: The study has been designed with a view to highlighting the prevalence in Luxembourg of MCI and AD in the first step of the survey, conducted among participants selected from a random sample of the general population. A prospective cohort is consequently set up in the second step, and appropriate follow-up of the non-demented participants allows improving the knowledge of the preclinical stage of MCI. Case-control designs are used for cross-sectional or retrospective comparisons between outcomes and biological or clinical factors. To ensure maximal reliability of the information collected, we decided to opt for structured face to face interviews. Besides health status, medical and family history, demographic and socio-cultural information are explored, as well as education, habitat network, social behavior, leisure and physical activities. As multilingualism is expected to challenge the cognitive alterations associated with pathological ageing, it is additionally investigated. Data relative to motor function, including balance, walk, limits of stability, history of falls and accidents are further detailed. Finally, biological examinations, including ApoE genetic polymorphism are carried out. In addition to standard blood parameters, the lipid status of the participants is subsequently determined from the fatty acid profiles in their red blood cells. The study obtained the legal and ethical authorizations. DISCUSSION: By means of the multidisciplinary MemoVie study, new insights into the onset of cognitive impairment during aging should be put forward, much to the benefit of intervention strategies as a whole

PEGylated bottom-up synthesized graphene nanoribbons loaded with camptothecin as potential drug carriers

This work discusses the potential use of bottom-up synthesized graphene nanoribbons (GNRs) as nano-carriers for drug delivery systems (DDSs). GNRs have a high loading capacity for anticancer drugs due to their high specific surface area and non-covalent adsorption with hydrophobic anticancer drug molecules. Herein, we synthesized GNRs using a bottom-up approach, modified with PEG2000 (GNR-PEG) and PEG2000 carrying folic acid chains (GNR-PEG-FA), and then loaded with camptothecin (CPT). The targeting ability mediated by folic acid of the GNR derivative was evaluated using cellular assays, and the cytotoxicity of GNR systems loaded with CPT was assessed by in vitro studies. They suggest that the functionalization of GNR derivatives with folic acid significantly affects their interaction with cells expressing different levels of folic acid receptors. The authors also explore the possibility to employ GNRs in photothermal therapy (PTT). GNR-PEG and GNR-PEG-FA display minor or no toxicity in standard cell cultures, but they show remarkable thermal response upon NIR irradiation, causing complete loss of cell viability within a few hours of treatment. This work highlights the potential of GNRs as DDSs and emphasizes the importance of further research on their biocompatibility and as a platform for PTT

Decellularization of xenografted tumors provides cell-specific in vitro 3D environment

In vitro cell culture studies are common in the cancer research field, and reliable biomimetic 3D models are needed to ensure physiological relevance. In this manuscript, we hypothesized that decellularized xenograft tumors can serve as an optimal 3D substrate to generate a top-down approach for in vitro tumor modeling. Multiple tumor cell lines were xenografted and the formed solid tumors were recovered for their decellularization by several techniques and further characterization by histology and proteomics techniques. Selected decellularized tumor xenograft samples were seeded with the HCC1806 human triple-negative breast cancer (TNBC) basal-like subtype cell line, and cell behavior was compared among them and with other control 2D and 3D cell culture methods. A soft treatment using Freeze-EDTA-DNAse allows proper decellularization of xenografted tumor samples. Interestingly, proteomic data show that samples decellularized from TNBC basal-like subtype xenograft models had different extracellular matrix (ECM) compositions compared to the rest of the xenograft tumors tested. The in vitro recellularization of decellularized ECM (dECM) yields tumor-type–specific cell behavior in the TNBC context. Data show that dECM derived from xenograft tumors is a feasible substrate for reseeding purposes, thereby promoting tumor-type–specific cell behavior. These data serve as a proof-of-concept for further potential generation of patient-specific in vitro research models.Grant RTI2018-101708-A-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe. Grants RYC2018-025502-I and PRE2018-084542 are funded by MCIN/AEI/10.13039/501100011033 and by ESF Investing in your future. Grant MDM-2017-0720 Maria de Maeztu Units of Excellence Program funded by the Spanish State Research Agency. Grant KK-2019/00093 Elkartek program funded by Basque Government. Grant CICBMG_PhD_03_2021 funded by CICbiomaGUNE and Polymat. Grant CICBMG_PhD_05_2019 funded by CICbiomaGUNE and Polymat. 2019 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation, grant number IN[19]_CMA_BIO_0119. The BBVA Foundation accepts no responsibility for the opinions, statements, and contents included, which are entirely the responsibility of the authors

ParameciumDB in 2011: new tools and new data for functional and comparative genomics of the model ciliate Paramecium tetraurelia

ParameciumDB is a community model organism database built with the GMOD toolkit to integrate the genome and biology of the ciliate Paramecium tetraurelia. Over the last four years, post-genomic data from proteome and transcriptome studies has been incorporated along with predicted orthologs in 33 species, annotations from the community and publications from the scientific literature. Available tools include BioMart for complex queries, GBrowse2 for genome browsing, the Apollo genome editor for expert curation of gene models, a Blast server, a motif finder, and a wiki for protocols, nomenclature guidelines and other documentation. In-house tools have been developed for ontology browsing and evaluation of off-target RNAi matches. Now ready for next-generation deep sequencing data and the genomes of other Paramecium species, this open-access resource is available at http://paramecium.cgm.cnrs-gif.fr