We present the result of an experiment to measure the electric dipole moment (EDM) of the neutron at the Paul Scherrer Institute using Ramsey's method of separated oscillating magnetic fields with ...ultracold neutrons. Our measurement stands in the long history of EDM experiments probing physics violating time-reversal invariance. The salient features of this experiment were the use of a ^{199}Hg comagnetometer and an array of optically pumped cesium vapor magnetometers to cancel and correct for magnetic-field changes. The statistical analysis was performed on blinded datasets by two separate groups, while the estimation of systematic effects profited from an unprecedented knowledge of the magnetic field. The measured value of the neutron EDM is d_{n}=(0.0±1.1_{stat}±0.2_{sys})×10^{-26} e.cm.
We report on a search for ultralow-mass axionlike dark matter by analyzing the ratio of the spin-precession frequencies of stored ultracold neutrons and Hg199 atoms for an axion-induced oscillating ...electric dipole moment of the neutron and an axion-wind spin-precession effect. No signal consistent with dark matter is observed for the axion mass range 10−24≤ma≤10−17eV . Our null result sets the first laboratory constraints on the coupling of axion dark matter to gluons, which improve on astrophysical limits by up to 3 orders of magnitude, and also improves on previous laboratory constraints on the axion coupling to nucleons by up to a factor of 40.
Abstract
Background
Malignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor ...receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern.
Methods
Here, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas.
Results
EGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations.
Conclusions
Our findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.
Background and Purpose
The transcription factor NF‐κB orchestrates many pro‐inflammatory signals and its inhibition is considered a promising strategy to combat inflammation. Here we report the ...characterization of the natural product plumericin as a highly potent inhibitor of the NF‐κB pathway with a novel chemical scaffold, which was isolated via a bioactivity‐guided approach, from extracts of Himatanthus sucuuba, an Amazonian plant traditionally used to treat inflammation‐related disorders.
Experimental Approach
A NF‐κB luciferase reporter gene assay was used to identify NF‐κB pathway inhibitors from H. sucuuba extracts. Monitoring of TNF‐α‐induced expression of the adhesion molecules VCAM‐1, ICAM‐1 and E‐selectin by flow cytometry was used to confirm NF‐κB inhibition in endothelial cells, and thioglycollate‐induced peritonitis in mice to confirm effects in vivo. Western blotting and transfection experiments were used to investigate the mechanism of action of plumericin.
Key Results
Plumericin inhibited NF‐κB‐mediated transactivation of a luciferase reporter gene (IC50 1 μM), abolished TNF‐α‐induced expression of the adhesion molecules VCAM‐1, ICAM‐1 and E‐selectin in endothelial cells and suppressed thioglycollate‐induced peritonitis in mice. Plumericin exerted its NF‐κB pathway inhibitory effect by blocking IκB phosphorylation and degradation. Plumericin also inhibited NF‐κB activation induced by transfection with the constitutively active catalytic subunit of the IκB kinase (IKK‐β), suggesting IKK involvement in the inhibitory action of this natural product.
Conclusion and Implications
Plumericin is a potent inhibitor of NF‐κB pathways with a new chemical scaffold. It could be further explored as a novel anti‐inflammatory lead compound.
Automatic processing of IR sequences is a desirable target in Thermal Non-Destructive Evaluation (TNDE) of materials. Unfortunately, this task is made difficult by the presence of many undesired ...signals that corrupt the useful information detected by the IR camera. In this paper the Principal Component Analysis (PCA) is used to process IR image sequences to extract features and reduce redundancy by projecting the original data onto a system of orthogonal components. As a thermographic sequence contains information both in space and time, the way of applying the PCA to these data cannot be straightforwardly borrowed from typical applications of the PCA where the information is mainly spatial (e.g. remote sensing, face recognition). This peculiarity has been analysed and the results are reported. Finally, in addition to the use of the PCA as an unsupervised method, its use in a “learning and measuring” configuration is considered.
It has been proposed that there could be a mirror copy of the standard model particles, restoring the parity symmetry in the weak interaction on the global level. Oscillations between a neutral ...standard model particle, such as the neutron, and its mirror counterpart could potentially answer various standing issues in physics today. Astrophysical studies and terrestrial experiments led by ultracold neutron storage measurements have investigated neutron to mirror-neutron oscillations and imposed constraints on the theoretical parameters. Recently, further analysis of these ultracold neutron storage experiments has yielded statistically significant anomalous signals that may be interpreted as neutron to mirror-neutron oscillations, assuming nonzero mirror magnetic fields. The neutron electric dipole moment collaboration performed a dedicated search at the Paul Scherrer Institute and found no evidence of neutron to mirror-neutron oscillations. Thereby, the following new lower limits on the oscillation time were obtained: τnn′>352 s at B′=0 (95% C.L.), τnn′>6s for 0.4μT<B′<25.7μT (95% C.L.), and τnn′/cosβ>9s for 5.0μT<B′<25.4μT (95% C.L.), where β is the fixed angle between the applied magnetic field and the local mirror magnetic field, which is assumed to be bound to the Earth. These new constraints are the best measured so far around B′∼10μT and B′∼20μT.
Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries ...collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.
Introduction
Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established.
Methods
CPT-SIOP-2000 (NCT00500890) was an international registry for all CPT nesting a ...chemotherapy randomization for high-risk CPT with Carboplatin/Etoposide/Vincristine (CarbEV) versus Cyclophosphamide/Etoposide/Vincristine (CycEV). Patients older than three years were recommended to receive irradiation: focal fields for non-metastatic CPC, incompletely resected atypical choroid plexus papilloma (APP) or metastatic choroid plexus papilloma (CPP); craniospinal fields for metastatic CPC/APP and non-responsive CPC. High risk was defined as choroid plexus carcinoma (CPC), incompletely resected APP, and all metastatic CPT. From 2000 until 2010, 158 CPT patients from 23 countries were enrolled.
Results
For randomized CPC, the 5/10 year progression free survival (PFS) of patients on CarbEV (n = 20) were 62%/47%, respectively, compared to 27%/18%, on CycEV (n = 15), (intention-to-treat, HR 2.6, p = 0.032). Within the registry, histological grading was the most influential prognostic factor: for CPP (n = 55) the 5/10 year overall survival (OS) and the event free survival (EFS) probabilities were 100%/97% and 92%/92%, respectively; for APP (n = 49) 96%/96% and 76%/76%, respectively; and for CPC (n = 54) 65%/51% and 41%/39%, respectively. Without irradiation, 12 out of 33 patients with CPC younger than three years were alive for a median of 8.52 years. Extent of surgery and metastases were not independent prognosticators.
Conclusions
Chemotherapy for Choroid Plexus Carcinoma is feasible and effective. CarbEV is superior to CycEV. A subset of CPC can be cured without irradiation.
Hypothalamic syndrome Müller, Hermann L; Tauber, Maithé; Lawson, Elizabeth A ...
Nature reviews. Disease primers,
04/2022, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Hypothalamic syndrome (HS) is a rare disorder caused by disease-related and/or treatment-related injury to the hypothalamus, most commonly associated with rare, non-cancerous parasellar masses, such ...as craniopharyngiomas, germ cell tumours, gliomas, cysts of Rathke's pouch and Langerhans cell histiocytosis, as well as with genetic neurodevelopmental syndromes, such as Prader-Willi syndrome and septo-optic dysplasia. HS is characterized by intractable weight gain associated with severe morbid obesity, multiple endocrine abnormalities and memory impairment, attention deficit and reduced impulse control as well as increased risk of cardiovascular and metabolic disorders. Currently, there is no cure for this condition but treatments for general obesity are often used in patients with HS, including surgery, medication and counselling. However, these are mostly ineffective and no medications that are specifically approved for the treatment of HS are available. Specific challenges in HS are because the syndrome represents an adverse effect of different diseases, and that diagnostic criteria, aetiology, pathogenesis and management of HS are not completely defined.
Paediatric low-grade gliomas (also known as pLGG) are the most common type of CNS tumours in children. In general, paediatric low-grade gliomas show clinical and biological features that are distinct ...from adult low-grade gliomas, and the developing paediatric brain is more susceptible to toxic late effects of the tumour and its treatment. Therefore, response assessment in children requires additional considerations compared with the adult Response Assessment in Neuro-Oncology criteria. There are no standardised response criteria in paediatric clinical trials, which makes it more difficult to compare responses across studies. The Response Assessment in Pediatric Neuro-Oncology working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop consensus recommendations for response assessment in paediatric low-grade gliomas. Final recommendations were based on literature review, current practice, and expert opinion of working group members. Consensus recommendations include imaging response assessments, with additional guidelines for visual functional outcomes in patients with optic pathway tumours. As with previous consensus recommendations, these recommendations will need to be validated in prospective clinical trials.
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