A revisited and general Kane’s formulation applied to very flexible multibody spacecraft

Abstract. Current space missions require predicting the spacecraft dynamics with considerable reliability. Among the various components of a spacecraft, subsystems like payload, structures, and power depend heavily on the dynamic behavior of the satellite during its operational life. Therefore, to ensure that the results obtained through numerical simulations correspond to the actual behavior, an accurate dynamical model must be developed. In this context, an implementation of Kane’s method is presented to derive the dynamical equations of a spacecraft composed of both rigid and flexible bodies connected via joints in tree topology. Starting from the kinematics of two generic interconnected bodies, a systematic approach is derived and the recursive structure of the equations is investigated. The Kane’s formulation allows a relatively simple derivation of the equation of motion while obtaining the minimum set of differential equations, which implies lower computational time. On the other hand, this formulation excludes reaction forces and torques from the dynamical equations. Nevertheless, in this work a strategy to compute them a posteriori without further numerical integrations is presented. Flexibility is introduced through the standard modal decomposition technique, so that modal shapes obtained by FEA software can be directly utilized to characterize the elastic motion of the flexible bodies. A spacecraft composed of a rigid bus and several flexible appendages is modeled and numerical simulations point out that this systematic method is very effective for this illustrative example

Allelic Variants of HLA-C Upstream Region, PSORS1C3, MICA, TNFA and Genes Involved in Epidermal Homeostasis and Barrier Function Influence the Clinical Response to Anti-IL-12/IL-23 Treatment of Patients with Psoriasis

Several biologic therapies have been developed to treat moderate-to-severe psoriasis, with patients exhibiting different clinical benefits, possibly due to the heterogeneity of pathogenic processes underlying their conditions. Ustekinumab targets the IL-12/IL-23-p40 subunit and inhibits type-1 and type-17 T-cell responses. Although ustekinumab is effective as both short- and long-term treatment, therapeutic response varies considerably among patients. Ustekinumab biosimilars will be commercialized in the very next future, likely broadening the use of this drug in the treatment of psoriasis patients. Our pharmacogenomic study evaluated the influence of 417 single-nucleotide polymorphisms (SNPs) in psoriasis-risk alleles on the clinical response to ustekinumab in a cohort of 152 patients affected by moderate-to-severe plaque-type psoriasis. Differences in SNP pattern characterizing HLA-Cw6(+) or HLA-Cw6(-) patients, showing high or low responses to ustekinumab, were also analysed. We identified twelve SNPs in HLA-C upstream region (rs12189871, rs4406273, rs9348862 and rs9368670), PSORS1C3 (rs1265181), MICA (rs2523497), LCE3A-B intergenic region (rs12030223, rs6701730), CDSN (rs1042127, rs4713436), CCHCR1 (rs2073719) and in TNFA (rs1800610) genes associated with excellent response to ustekinumab. We also found that HLA-Cw6(+) and HLA-Cw6(-) patients carried out distinct patterns of SNPs associated with different clinical responses. The assessment of HLA-C alleles, together with other genetic variants, could be helpful for defining patients who better benefit from anti-IL-12/IL-23 therapy

Dynamics of concurrent and sequential Central European and Scandinavian heatwaves

In both 2003 and 2018 a heatwave in Scandinavia in July was followed by a heatwave in Central Europe in August. Whereas the transition occurred abruptly in 2003, it was gradual in 2018 with a 12-day period of concurrent heatwaves in both regions. This study contrasts these two events in the context of a heatwave climatology to elucidate the dynamics of both concurrent and sequential heatwaves. Central European and, in particular, concurrent heatwaves are climatologically associated with weak pressure gradient (WPG) events over Central Europe, which indicate the absence of synoptic activity over this region. One synoptic pattern associated with such events is Scandinavian blocking. This pattern is at the same time conducive to heatwaves in Scandinavia, thereby providing a mechanism by which Scandinavian and Central European heatwaves can co-occur. Further, the association of WPG events with Scandinavian blocking constitutes a mechanism that allows heatwaves to grow beyond the perimeter of the synoptic system from which they emanated. A trajectory analysis of the source regions of the low-level air incorporated in the heatwaves indicates rapidly changing air mass sources throughout the heatwaves in both regions, but no recycling of heat from one heatwave to the other. This finding is line with a composite analysis indicating that transitions between Scandinavian and Central European heatwaves are merely a random coincidence of heatwave onset and decay

Arithmetically Cohen-Macaulay Bundles on complete intersection varieties of sufficiently high multidegree

Recently it has been proved that any arithmetically Cohen-Macaulay (ACM) bundle of rank two on a general, smooth hypersurface of degree at least three and dimension at least four is a sum of line bundles. When the dimension of the hypersurface is three, a similar result is true provided the degree of the hypersurface is at least six. We extend these results to complete intersection subvarieties by proving that any ACM bundle of rank two on a general, smooth complete intersection subvariety of sufficiently high multi-degree and dimension at least four splits. We also obtain partial results in the case of threefolds.Comment: 15 page

Evaluating Native American Bird Use and Bird Assemblage Variability along the Oregon Coast

Native American use of birds on the Oregon coast is not well known and has never been synthesized to present a regional understanding. We rectify this by analyzing data from 26 zooarchaeological assemblages, including three previously unpublished bird assemblages: Umpqua/Eden (35DO83), Whale Cove (35LNC60), and the Dunes Site (35CLT27). We employ a series of non-parametric randomization tests to directly evaluate patterns of taxonomic diversity, correlations with nearby breeding colonies, and broader procurement strategies discussed in ethnohistorical accounts. We compare the assemblages to contemporary surveys of naturally beached birds as observed by COASST (Coastal Observation Seabird Survey Team) and evaluate whether archaeological specimens were scavenged from the beach. While 71% of the identified bird remains belong to just three families (Anatidae, Alcidae, and Procellariidae), closer analysis reveals the incredible diversity of birds used by Oregon coast Native Americans. The assemblages vary considerably in terms of taxonomic diversity and composition, leading us to conclude that people used birds opportunistically, likely incorporating multiple strategies, including hunting, collecting beached carcasses and targeting cormorant colonies. We hope that the methods and approaches employed here will inspire other archaeologists to devote more attention to bird assemblages, and how their study can inform conservation efforts

Biodiversity Studies for Sustainable Lagoon: Thermophilic and Tropical Fish Species vs. Endemic Commercial Species at Mellah Lagoon (Mediterranean, Algeria)

Lagoons play an important socio-economic role and represent a precious natural heritage at risk from fishing pressure and chemical and biological pollution. Our research focused on better understanding the discrimination of fish biodiversity, the detection of non-indigenous species, and the valorization of commercial indigenous species at Mellah lagoon (Algeria). Taxonomic characterization and barcoding for all fish species and Inkscape schematic drawings for the most common species are provided. A total of 20 families and 37 species were recorded. The thermophilic species Coris julis, Thalassoma pavo, and Aphanius fasciatus and tropical species such as Gambusia holbrooki and Parablennius pilicornis were identified. Numerous Mediterranean species of socio-economic importance are highlighted, and detailed information is summarized for the lagoon’s sustainability. This short-term evaluation goes hand in hand with long-term programs documenting the interaction between indigenous and non-indigenous species in the lagoon and will allow the development of a provisional relationship model for future studies. Thermophilic and tropical species patterns in the Mellah lagoon are presented. Taken together, we provide useful data that can guide future investigations and may become a potential management tool for achieving the Sustainable Development Goals and protecting species with large socio-economic roles from potential thermal stress impact

The Assertive Brain : Anterior Cingulate Phosphocreatine plus Creatine Levels Correlate With Self-Directedness in Healthy Adolescents

Despite various advances in the study of the neurobiological underpinnings of personality traits, the specific neural correlates associated with character and temperament traits are not yet fully understood. Therefore, this study aims to fill this gap by exploring the biochemical basis of personality, which is explored with the temperament and character inventory (TCI), during brain development in a sample of adolescents. Twenty-six healthy adolescents (aged between 13 and 21 years; 9 males and 18 females) with behavioral and emotional problems underwent a TCI evaluation and a 3T single-voxel proton magnetic resonance spectroscopy (1H MRS) acquisition of the anterior cingulate cortex (ACC). Absolute metabolite levels were estimated using LCModel: significant correlations between metabolite levels and selective TCI scales were identified. Specifically, phosphocreatine plus creatine (PCr+Cre) significantly correlated with self-directedness, positively, and with a self-transcendence (ST), negatively, while glycerophosphocholine plus phosphocholine (GPC+PC) and myo-inositol negatively correlated with ST. To the best of our knowledge, this is the first study reporting associations of brain metabolites with personality traits in adolescents. Therefore, our results represent a step forward for personality neuroscience within the study of biochemical systems and brain structures

Midkine mediates intercellular crosstalk between drug-resistant and drug sensitive neuroblastoma cells in vitro and in vivo

Resistance to cytotoxic agents has long been known to be a major limitation in the treatment of human cancers. Although many mechanisms of drug resistance have been identified, chemotherapies targeting known mechanisms have failed to lead to effective reversal of drug resistance, suggesting that alternative mechanisms remain undiscovered. Previous work identified midkine (MK) as a novel putative survival molecule responsible for cytoprotective signaling between drug-resistant and drug-sensitive neuroblastoma, osteosarcoma and breast carcinoma cells in vitro. In the present study, we provide further in vitro and in vivo studies supporting the role of MK in neuroblastoma cytoprotection. MK overexpressing wild type neuroblastoma cells exhibit a cytoprotective effect on wild type cells when grown in a co-culture system, similar to that seen with doxorubicin resistant cells. siRNA knockdown of MK expression in doxorubicin resistant neuroblastoma and osteosarcoma cells ameliorates this protective effect. Overexpression of MK in wild type neuroblastoma cells leads to acquired drug resistance to doxorubicin and to the related drug etoposide. Mouse studies injecting various ratios of doxorubicin resistant or MK transfected cells with GFP transfected wild type cells confirm this cytoprotective effect in vivo. These findings provide additional evidence for the existence of intercellular cytoprotective signals mediated by MK which contribute to chemotherapy resistance in neuroblastoma

Potential clinical implications of CD4+CD26high T cells for nivolumab treated melanoma patients

Background Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients’ outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe of-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will beneft from anti-PD-1 treatment avoiding unwanted side efects. However, the strength of CD26 expression on CD4+ T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies. Methods The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multiparametric fow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4+CD26high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4+CD26high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients. Results Circulating CD4+CD26high T cells were signifcantly reduced in melanoma patients compared to healthy subjects (p=0.001). In addition, a signifcant association was observed between a low baseline percentage of CD4+CD26high T cells (<7.3%) and clinical outcomes, measured as overall survival (p=0.010) and progression-free survival (p=0.014). Moreover, patients with clinical beneft from nivolumab therapy had signifcantly higher frequencies of circulating CD4+CD26high T cells than patients with non-clinical beneft (p=0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4+CD26high T cells was correlated with Disease Control Rate (p=0.014) and best Overall Response Rate (p=0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4+CD26high T cells were signifcantly higher in comparison with the frequencies measured at W0 (p<0.0001), aligning the cell counts with the ranges seen in the blood of healthy subjects

Basal and one-month differed neutrophil, lymphocyte and platelet values and their ratios strongly predict the efficacy of checkpoint inhibitors immunotherapy in patients with advanced BRAF wild-type melanoma

Background To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM). Methods We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Delta) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve. Results At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p &lt; 0.001), neutrophils (p &lt; 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Delta platelets (p = 0.039), Delta WBC (p &lt; 0.001), and Delta neutrophils (p = 0.020), and with lower Delta lymphocytes (p &lt; 0.001). Moreover, higher Delta NLR and Delta PLR identified patients with worse PFS, OS and DCR. In the multivariable model, only Delta NLR influenced PFS (p = 0.004), while OS resulted affected by higher Delta WBC (p &lt; 0.001) and lower Delta lymphocytes (p = 0.038). Higher Delta WBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and Delta NLR, normal LDH/lower Delta NLR showed a higher PFS than high LDH/higher Delta NLR (20 vs 5 months). Moreover, normal LDH/higher Delta lymphocytes had a higher OS than high LDH/lower Delta lymphocytes (50 vs. 10 months). Conclusions Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data. © 2022, The Author(s)