ABSTRACT
The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.
Subject(s)
Databases, Chemical , Perfume/chemistry , Perfume/toxicity , Sesquiterpenes/analysis , Sesquiterpenes/toxicity , Animals , Consumer Product Safety , Drug Administration Routes , Endpoint Determination , Humans , No-Observed-Adverse-Effect Level , Perfume/administration & dosage , Risk Assessment , Sesquiterpenes/administration & dosage , Toxicity TestsABSTRACT
BACKGROUND: In extramammary Paget disease (EMPD), Paget cells are sometimes detected outside the clinical border (subclinical extension). However, the spreading pattern of Paget cells in subclinical extension remains unclear. In addition, the macroscopic appearances of lesions accompanied by subclinical extension are totally unknown. OBJECTIVES: To characterize the spreading pattern of Paget cells as well as the macroscopic appearance of lesions of EMPD with subclinical extension. METHODS: Nineteen patients with primary anogenital EMPD underwent mapping biopsies and excisional surgeries; biopsy samples were then taken at the periphery of well-demarcated lesions. Samples were transparentized and subjected to whole-mount immunostaining with anticytokeratin 7 antibody to label Paget cells. The histological border was evaluated in three dimensions by two-photon microscopy. The shape and location of the histological border were compared with those of the clinical border. RESULTS: In 21 samples taken at the lesion where subclinical extension was not shown by mapping biopsy, the shape and location of the histological border were almost identical to those of the clinical border. However, two samples exhibited small foci of Paget cells outside the clinical border, showing subclinically extended satellite lesions. In the two samples taken at the lesions where subclinical extension was shown by mapping biopsy, a continuous arrangement of Paget cells extending beyond the clinical border was identified. Subclinically extended Paget cells were detected solely outside hypopigmented patches with erythema. CONCLUSIONS: In EMPD, at least two patterns of subclinical extension exist: continuous and satellite lesions. Subclinical extension might exist preferentially outside hypopigmented patches with erythema.
Subject(s)
Anus Neoplasms/pathology , Paget Disease, Extramammary/pathology , Skin Neoplasms/pathology , Urogenital Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Dermoscopy/methods , Female , Humans , Hypopigmentation/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Paget Disease, Extramammary/surgery , Photons , Preoperative Care , Skin Neoplasms/surgerySubject(s)
Camphanes/toxicity , Perfume/toxicity , Propionates/toxicity , Toxicity Tests/methods , Animals , Camphanes/chemistry , Consumer Product Safety , DNA Damage/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Endpoint Determination , No-Observed-Adverse-Effect Level , Perfume/chemistry , Propionates/chemistry , Rats , Risk AssessmentSubject(s)
Cyclohexanes/toxicity , Perfume/toxicity , Toxicity Tests/methods , Animals , Consumer Product Safety , Cyclohexanes/chemistry , DNA Damage/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Endpoint Determination , No-Observed-Adverse-Effect Level , Perfume/chemistry , Rats , Risk AssessmentSubject(s)
Acetates/toxicity , Norbornanes/toxicity , Perfume/toxicity , Toxicity Tests/methods , Acetates/chemistry , Animals , Consumer Product Safety , DNA Damage/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Endpoint Determination , No-Observed-Adverse-Effect Level , Norbornanes/chemistry , Perfume/chemistry , Rats , Risk AssessmentABSTRACT
The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the suitable read across analog linalool (CAS # 78-70-6) show that this material is not genotoxic nor does it have skin sensitization potential and also provided a MOE > 100 for the local respiratory endpoint. The repeated dose, developmental and reproductive toxicity endpoints were completed using nerolidol (isomer unspecified, CAS # 7212-44-4) as a suitable read across analog, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework.
Subject(s)
Fatty Alcohols/toxicity , Perfume/toxicity , Toxicity Tests/methods , Animals , Consumer Product Safety , DNA Damage/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Endpoint Determination , Fatty Alcohols/chemistry , No-Observed-Adverse-Effect Level , Perfume/chemistry , Rats , Risk AssessmentABSTRACT
The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the suitable read across analog 2-ethylhexanol (CAS # 104-76-7) show that this material is not genotoxic. Data from the suitable read across analog isopropyl alcohol (CAS # 67-63-0) show that this material does not have skin sensitization potential. The local respiratory toxicity endpoint was completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (1.4 mg/day). The repeated dose toxicity endpoint was completed using 2-ethylhexanol (CAS # 104-76-7) and 1-heptanol, 2-propyl (CAS # 10042-59-8) as suitable read across analogs, which provided a MOE > 100. The developmental and reproductive toxicity endpoint was completed using 2-ethyl-hexanol (CAS # 104-76-7) and isobutyl alcohol (CAS # 78-83-1) as suitable read across analogs, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework.
Subject(s)
Hexanols/toxicity , Perfume/toxicity , Toxicity Tests/methods , Animals , Consumer Product Safety , DNA Damage/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Endpoint Determination , Hexanols/chemistry , No-Observed-Adverse-Effect Level , Perfume/chemistry , Rats , Risk AssessmentABSTRACT
The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the target material and the suitable read across analog 6-acetyl-1,1,2,4,4,7-hexamethyltetraline (CAS # 21145-77-7) show that this material is not genotoxic. Data from the suitable read across analog 6-acetyl-1,1,2,4,4,7-hexamethyltetraline (CAS # 21145-77-7) provided a MOE > 100 for the repeat dose and developmental toxicity endpoints. The reproductive and local respiratory toxicity endpoints were completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class II material (0.009 mg/kg/day and 0.47 mg/day, respectively). Data on the target material showed that this material is below the non-reactive DST for skin sensitization and did not have the potential for phototoxicity or photoallergenicity. The environmental endpoint was completed as described in the RIFM Framework.
Subject(s)
Ketones/toxicity , Naphthalenes/chemistry , Perfume/toxicity , Propane/chemistry , Propane/toxicity , Tetrahydronaphthalenes/toxicity , Toxicity Tests/methods , Animals , Consumer Product Safety , DNA Damage/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Endpoint Determination , Ketones/chemistry , No-Observed-Adverse-Effect Level , Perfume/chemistry , Propanols , Rats , Risk Assessment , Tetrahydronaphthalenes/chemistryABSTRACT
The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, as well as, environmental safety. Repeated dose toxicity was determined to have the most conservative systemic exposure derived NO[A]EL of 37.5 mg/kg/day. A gavage 13-week subchronic toxicity study conducted in mice resulted in a MOE of 5769 while considering 38.4% absorption from skin contact and 100% from inhalation. A MOE of >100 is deemed acceptable.
