An exergy analysis of an advanced hypersonic vehicle, a scramjet, is presented and discussed with a twofold scope. First, to perfect the exergy approach to the design and optimization of aerospace ...propulsion systems: the exergy flow diagram can provide aircraft engineers and system designers with additional insight on the avoidable and unavoidable systemic losses, thus allowing for effective design improvements. Second, to explore limits and merits of two different fuelling solutions for a scramjet-powered aircraft. Two configurations are critically compared: one with a direct H
2 injection and one with an on-board kerosene reformer. The present study treats the scramjet-propelled plane as a Large Complex Energy System (“LCES”), and applies system balances (mass, energy, exergy) to calculate the relevant losses. The exergy analysis confirms that the introduction of an on-board reformer is advantageous from the point of view of the thrust efficiency (with a gain of 3 percentage points with respect to the H
2-fuelled engine) and, more importantly, from the point of view of a more correct use of the available resources (the fuel in the tanks). Another advantage of the on-board reforming is that the higher value of the volumetric-specific impulse allows for reducing the fuel tank size. All calculations have been performed with CAMEL
®, a modular simulator for energy conversion processes conceived and developed in the last decade by the Authors’ group at the Mechanical and Aeronautical Engineering Department of the University of Roma 1 “La Sapienza”. Some additional component models have been studied and implemented, and a specific tool dedicated to the analysis of propulsion systems has been created and integrated in the simulation package.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The monoclonal antibodies anti-programmed death protein-1 (anti-PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head ...and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti-PD-1-
anti-PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.
We did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1-based, PD-1-based, and standard chemotherapy. Treatments were indirectly compared with anti-PD-L1-based therapy.
The network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti-PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti-PD-1-based therapy appeared to be effective in smoker patients and in human papilloma-negative (HPV) patients. Conversely, anti-PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.
This is the first NMA study that aimed to indirectly compare anti-PD-1- and anti-PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.
Abstract
Background
Seroprevalence and the proportion of people with neutralizing activity (functional immunity) against SARS-CoV-2 variants were high in early 2022. In this prospective, population- ...based, multi-region cohort study, we assessed the development of functional and hybrid immunity (induced by vaccination and infection) in the general population during this period of high incidence of infections with Omicron variants.
Methods
We randomly selected and assessed individuals aged ≥16 years from the general population in southern (n = 739) and north-eastern (n = 964) Switzerland in March 2022. We assessed them again in June/July 2022, supplemented with a random sample from western (n = 850) Switzerland. We measured SARS-CoV-2 specific IgG antibodies and SARS-CoV-2 neutralizing antibodies against three variants (ancestral strain, Delta, Omicron).
Results
Seroprevalence remained stable from March 2022 (97.6%, n = 1894) to June/July 2022 (98.4%, n = 2553). In June/July, the percentage of individuals with neutralizing capacity against ancestral strain was 94.2%, against Delta 90.8% and against Omicron 84.9%, and 50.6% developed hybrid immunity. Individuals with hybrid immunity had highest median levels of anti-spike IgG antibodies titres 4518 World Health Organization units per millilitre (WHO U/mL) compared with those with only vaccine- (4304 WHO U/mL) or infection- (269 WHO U/mL) induced immunity, and highest neutralization capacity against ancestral strain (hybrid: 99.8%, vaccinated: 98%, infected: 47.5%), Delta (hybrid: 99%, vaccinated: 92.2%, infected: 38.7%) and Omicron (hybrid: 96.4%, vaccinated: 79.5%, infected: 47.5%).
Conclusions
This first study on functional and hybrid immunity in the Swiss general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less so for the general population.
Two-dimensional borophene nanosheets are sensitive to oxygen, which has hindered their development and use in scientific research and subsequent applications. Conventional methods of borophene ...synthesis are based on its epitaxial growth on single-crystal metal substrates by using molecular beam epitaxy (MBE). The electron deficiency of boron atoms in the borophene structure has made the use of metal substrates in the growth process inevitable. Hence, a method to stabilize the borophene sheets for further applications seems necessary. In this work, the oxidation arrangement of Al-activated chemical vapor deposition (CVD) of borophene sheets was investigated via scanning photoemission microscopy (SPEM). This method allows the investigation of oxidation ordering via its high spatial resolution and elemental sensitivity. The results indicate the persistence of the borophene χ3 (and some β12) phase after exposure to air. The formation of boron oxide is primarily limited to the Al aggregated islands and the edges while maintaining the borophene configuration intact. Our results show that the electronic exchange between the Al aggregates and the interface of boron atoms at the edges of the borophene sheet can prevent the oxidation process and preserve the borophene sheets for long periods. The lower oxidation tendency of the Al-saturated borophene was confirmed via density functional theory calculation, showing a lower oxygen binding energy on Al/borophene compared with that of the metal-free borophene. The oxidation-resistive borophene can be exploited in innovative high-efficiency catalytic, electronic, and sensing devices.
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IJS, KILJ, NUK, PNG, UL, UM
INVESTIGATING THE Ep, i –Eiso CORRELATION Amati, Lorenzo; Dichiara, Simone
Acta polytechnica (Prague, Czech Republic : 1992),
12/2013, Volume:
53, Issue:
A
Journal Article
Peer reviewed
Open access
The correlation between the spectral peak photon energy, Ep, and the radiated energy or luminosity (i.e., the “Amati relation” and other correlations derived from it) is one of the central and most ...debated topics in GRB astrophysics, with implications for physics and the geometry of prompt emission, the identification and understanding of various classes of GRBs (short/long, XRFs,sub-energetic), and GRB cosmology. Fermi is exceptionally suited to provide, also in conjunction with Swift observations, a significant step forward in this field of research. Indeed, one of the main goals of Fermi/GBM is to make accurate measurements of Ep, by exploiting its unprecedented broad energy band from ~8 keV to ~30MeV; in addition, for a small fraction of GRBs, the LAT can extend the spectral measurements up to the GeV energy range, thus allowing a reliable estimate of the bolometric radiated energy/luminosity. We provide a review, an update and a discussion of the impact of Fermi observations in the investigation, understanding and testing of the Ep,i –Eiso (“Amati”) relation.
Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients ...benefit from immunotherapy, which highlights the need to identify novel biomarkers to optimize treatment strategies. CD137
T cells have been identified as tumour-specific T cells correlated with immunotherapy responses in several solid tumours. In this study, we investigated the role of circulating CD137
T cells in (R/M) HNSCC patients undergoing pembrolizumab treatment. PBMCs obtained from 40 (R/M) HNSCC patients with a PD-L1 combined positive score (CPS) ≥1 were analysed at baseline via cytofluorimetry for the expression of CD137, and it was found that the percentage of CD3
CD137
cells is correlated with the clinical benefit rate (CBR), PFS, and OS. The results show that levels of circulating CD137
T cells are significantly higher in responder patients than in non-responders (
= 0.03). Moreover, patients with CD3
CD137
percentage ≥1.65% had prolonged OS (
= 0.02) and PFS (
= 0.02). Multivariate analysis, on a combination of biological and clinical parameters, showed that high levels of CD3
CD137
cells (≥1.65%) and performance status (PS) = 0 are independent prognostic factors of PFS (CD137
T cells,
= 0.007; PS,
= 0.002) and OS (CD137
T cells,
= 0.006; PS,
= 0.001). Our results suggest that levels of circulating CD137
T cells could serve as biomarkers for predicting the response of (R/M) HNSCC patients to pembrolizumab treatment, thus contributing to the success of anti-cancer treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) generates local accumulations of sequencing reads on the genome ("peaks"), which correspond to specific protein-DNA interactions or ...chromatin modifications. Peaks are detected by considering their total area above a background signal, usually neglecting their shapes, which instead may convey additional biological information. We present FunChIP, an R/Bioconductor package for clustering peaks according to a functional representation of their shapes: after approximating their profiles with cubic B-splines, FunChIP minimizes their functional distance and classifies the peaks applying a k-mean alignment and clustering algorithm. The whole pipeline is user-friendly and provides visualization functions for a quick inspection of the results. An application to the transcription factor Myc in 3T9 murine fibroblasts shows that clusters of peaks with different shapes are associated with different genomic locations and different transcriptional regulatory activity.
The package is implemented in R and is available under Artistic Licence 2.0 from the Bioconductor website (http://bioconductor.org/packages/FunChIP).
marco.morelli@iit.it.
Supplementary data are available at Bioinformatics online.
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