335 research outputs found
Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma
JX-594 is an oncolytic vaccinia virus genetically modified to replicate selectively in tumor cells. Metronomic chemotherapy has shown preclinical synergy with oncolytic viruses. We report here the results of the METROMAJX which is a randomized phase II clinical trial investigating the combination of JX-594 combined with metronomic cyclophosphamide (arm 1) or metronomic cyclophosphamide (arm 2) in patients with advanced STS. A two-stage Simon design was used. JX-594 was administered intra-venously at the dose 1.109 every 2 weeks for the first 3 injections and then every 3 weeks. Cyclophosphamide was given orally at the dose of 50 mg BID 1 week on 1 week off. The primary endpoint was the 6-month non progression rate. 20 patients were included (arm 1:15, arm 2:5). The two most frequent toxicities were grade 1 fatigue and fever and grade 2 fatigue and grade 2 lymphopenia in arms 1 and 2, respectively. In arm 1, 12 patients were assessable for the efficacy analysis. None of them were progression-free at 6 months indicating that the first stage of the Simon's design was not satisfied. One patient out 4 assessable for efficacy was progression-free at 6 months in arm 2. High throughput analysis of sequential plasma samples revealed an upregulation of protein biomarkers reflecting immune induction such as CXCL10 and soluble CD8 antigen in arm 1. Systemic treatment with JX-594 is safe in patients with advanced STS. Further investigations are needed to improve immune response to oncolytic viruses and define their therapeutic potential in patients with STS
Multidifferential study of identified charged hadron distributions in -tagged jets in proton-proton collisions at 13 TeV
Jet fragmentation functions are measured for the first time in proton-proton
collisions for charged pions, kaons, and protons within jets recoiling against
a boson. The charged-hadron distributions are studied longitudinally and
transversely to the jet direction for jets with transverse momentum 20 GeV and in the pseudorapidity range . The
data sample was collected with the LHCb experiment at a center-of-mass energy
of 13 TeV, corresponding to an integrated luminosity of 1.64 fb. Triple
differential distributions as a function of the hadron longitudinal momentum
fraction, hadron transverse momentum, and jet transverse momentum are also
measured for the first time. This helps constrain transverse-momentum-dependent
fragmentation functions. Differences in the shapes and magnitudes of the
measured distributions for the different hadron species provide insights into
the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb
public pages
Study of the decay
The decay is studied
in proton-proton collisions at a center-of-mass energy of TeV
using data corresponding to an integrated luminosity of 5
collected by the LHCb experiment. In the system, the
state observed at the BaBar and Belle experiments is
resolved into two narrower states, and ,
whose masses and widths are measured to be where the first uncertainties are statistical and the second
systematic. The results are consistent with a previous LHCb measurement using a
prompt sample. Evidence of a new
state is found with a local significance of , whose mass and width
are measured to be and , respectively. In addition, evidence of a new decay mode
is found with a significance of
. The relative branching fraction of with respect to the
decay is measured to be , where the first
uncertainty is statistical, the second systematic and the third originates from
the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb
public pages
Ray Optics Analysis Explanation of Beam-Splitting Condition in Fabry-Pérot Antennas
International audienceThis paper presents a theoretical analysis where general and accurate formulas for the design of Fabry-Pérot antennas (FPA) are derived from a simple ray optics approach. The beam-splitting condition predicted from the leaky-wave (LW) theory is analyzed here from ray optics analysis. Excellent agreement is observed with the results obtained from the LW analysis in a significant frequency range. Thereby, these expressions allow to design FPAs accurately without performing dispersion analysis of the leaky modes inside the structure. Index Terms-Fabry-Pérot resonant cavity antennas, leaky wave antenna, ray optics analysis, splitting condition
Ray Optics Analysis Explanation of Beam-Splitting Condition in Fabry-Pérot Antennas
International audienceThis paper presents a theoretical analysis where general and accurate formulas for the design of Fabry-Pérot antennas (FPA) are derived from a simple ray optics approach. The beam-splitting condition predicted from the leaky-wave (LW) theory is analyzed here from ray optics analysis. Excellent agreement is observed with the results obtained from the LW analysis in a significant frequency range. Thereby, these expressions allow to design FPAs accurately without performing dispersion analysis of the leaky modes inside the structure. Index Terms-Fabry-Pérot resonant cavity antennas, leaky wave antenna, ray optics analysis, splitting condition
Non-quantum cryptanalysis of the noisy version of Aaronson–Christiano's quantum money scheme
International audienceAt STOC 2012, Aaronson and Christiano proposed a noisy and a noiseless version of the first public-key quantum money scheme endowed with a security proof. This paper addresses the so-called noisy hidden subspaces problem, on which the noisy version of their scheme is based. The first contribution of this work is a non-quantum cryptanalysis of the above-mentioned noisy quantum money scheme extended to prime fields F, with |F| ≠ 2, that runs in randomised polynomial time. This finding is supported with experimental results showing that, in practice, the algorithm presented is efficient and succeeds with overwhelming probability. The second contribution is a non-quantum randomised polynomial-time cryptanalysis of the noisy quantum money scheme over F2 succeeding with a certain probability for values of the noise lying within a certain range. This result disproves a conjecture made by Aaronson and Christiano about the non-existence of an algorithm that solves the noisy hidden subspaces problem over F2 and succeeds with such probability
Non‐quantum cryptanalysis of the noisy version of Aaronson–Christiano's quantum money scheme
PRRX1-rearranged mesenchymal tumors : Expanding the immunohistochemical profile and molecular spectrum of a recently described entity with the proposed revision of nomenclature
Since the publication of the 2020 World Health Organization classification of soft tissue and bone tumors, the classification of fibroblastic tumors has expanded to include a novel subset of tumors characterized by PRRX1::NCOA1/2 gene fusions. These tumors defy conventional classification and are morphologically distinct, characterized by a multi-nodular growth of bland spindle cells suspended in a myxo-collagenous stroma with mild cytologic atypia, staghorn-like vessels, and variable perivascular hyalinization. Mitotic activity is rare, and necrosis is not identified. Herein, we present six additional cases of PRRX1-rearranged mesenchymal tumors, including five cases with PRRX1::NCOA1 fusion and one case with PRRX1::KMT2D fusion. Three cases (3/6, 50%) demonstrated focal co-expression of S100 protein and SOX10, thereby expanding the immunohistochemical profile of this emerging entity. Like prior reported cases, there was no evidence of malignant behavior on short-term follow-up. The novel fusion, PRRX1::KMT2D, further expands the molecular spectrum of this entity and leads to a proposed revision of the provisional nomenclature to PRRX1-rearranged mesenchymal tumor to both accommodate non-NCOA1/2 fusion partners and allow for the possibility of partial neural or neuroectodermal differentiatio
Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models
Chordomas are rare, slow-growing tumors of the axial skeleton. These tumors are locally aggressive and refractory to conventional therapies. Radical surgery and radiation remain the first-line treatments. Despite these aggressive treatments, chordomas often recur and second-line treatment options are limited. The mechanisms underlying chordoma radioresistance remain unknown, although several radioresistant cancer cells have been shown to respond favorably to aldehyde dehydrogenase (ALDH) inhibition. The study of chordoma has been delayed by small patient cohorts and few available models due to the scarcity of these tumors. We thus created cellular 3D models of chordoma by using low-adherence culture systems. Then, we evaluated their radiosensitivity using colony-forming and spheroid size assays. Finally, we determined whether pharmacologically inhibiting ALDH increased their radiosensitivity. We found that 3D cellular models of chordoma (derived from primary, relapse, and metastatic tumors) reproduce the histological and gene expression features of the disease. The metastatic, relapse, and primary spheroids displayed high, medium, and low radioresistance, respectively. Moreover, inhibiting ALDH decreased the radioresistance in all three models
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