Negative experimental evidence for magneto-orbital dichroism - supplemental information

A light beam can carry both spin angular momentum (SAM) and orbital angular momentum (OAM). SAM is commonly evidenced by circular dichroism (CD) experiments {\em i. e.} differential absorption of left and right-handed circularly polarized light. Recent experiments, supported by theoretical work, indicate that the corresponding effect with OAM instead of SAM is not observed in chiral matter. Isotropic materials can show CD when subjected to a magnetic field (MCD). In Ref. ~\onlinecite{Mathevet2012} we report a set of experiments, under well defined conditions, searching for magnetic orbital dichroism (MOD), differential absorption of light as a function of the sign of its OAM. We experimentally demonstrate that this effect, if any, is smaller than a few $10^{-4}$ of MCD for the Nd:YAG $^4I_{9/2}\rightarrow^4F_{5/2}$ transition. This transition is essentially of electric dipole nature. We give an intuitive argument suggesting that the lowest order of light matter interaction leading to MOD is the electric quadrupole term. We give here more experimental details and extra measurements.Comment: 6 pages, 7 figures. Supplemental material for a publication in Optics Expres

Automatic End-To-End VMAT Treatment Planning for Rectal Cancers

BACKGROUND: The treatment planning process from segmentation to producing a deliverable plan is time-consuming and labor-intensive. Existing solutions automate the segmentation and planning processes individually. The feasibility of combining auto-segmentation and auto-planning for volumetric modulated arc therapy (VMAT) for rectal cancers in an end-to-end process is not clear. PURPOSE: To create and clinically evaluate a complete end-to-end process for auto-segmentation and auto-planning of VMAT for rectal cancer requiring only the gross tumor volume contour and a CT scan as inputs. METHODS: Patient scans and data were retrospectively selected from our institutional records for patients treated for malignant neoplasm of the rectum. We trained, validated, and tested deep learning auto-segmentation models using nnU-Net architecture for clinical target volume (CTV), bowel bag, large bowel, small bowel, total bowel, femurs, bladder, bone marrow, and female and male genitalia. For the CTV, we identified 174 patients with clinically drawn CTVs. We used data for 18 patients for all structures other than the CTV. The structures were contoured under the guidance of and reviewed by a gastrointestinal (GI) radiation oncologist. The predicted results for CTV in 35 patients and organs at risk (OAR) in six patients were scored by the GI radiation oncologist using a five-point Likert scale. For auto-planning, a RapidPlan knowledge-based planning solution was modeled for VMAT delivery with a prescription of 25 Gy in five fractions. The model was trained and tested on 20 and 34 patients, respectively. The resulting plans were scored by two GI radiation oncologists using a five-point Likert scale. Finally, the end-to-end pipeline was evaluated on 16 patients, and the resulting plans were scored by two GI radiation oncologists. RESULTS: In 31 of 35 patients, CTV contours were clinically acceptable without necessary modifications. The CTV achieved a Dice similarity coefficient of 0.85 (±0.05) and 95% Hausdorff distance of 15.25 (±5.59) mm. All OAR contours were clinically acceptable without edits, except for large and small bowel which were challenging to differentiate. However, contours for total, large, and small bowel were clinically acceptable. The two physicians accepted 100% and 91% of the auto-plans. For the end-to-end pipeline, the two physicians accepted 88% and 62% of the auto-plans. CONCLUSIONS: This study demonstrated that the VMAT treatment planning technique for rectal cancer can be automated to generate clinically acceptable and safe plans with minimal human interventions

Small-scale field evaluation of PermaNet ® Dual (a long-lasting net coated with a mixture of chlorfenapyr and deltamethrin) against pyrethroid-resistant Anopheles gambiae mosquitoes from Tiassalé, Côte d’Ivoire

Background: Due to the rapid expansion of pyrethroid-resistance in malaria vectors in Africa, Global Plan for Insecticide Resistance Management (GPIRM) has recommended the development of long-lasting insecticidal nets (LLINs), containing insecticide mixtures of active ingredients with different modes of action to mitigate resistance and improve LLIN efficacy. This good laboratory practice (GLP) study evaluated the efficacy of the chlorfenapyr and deltamethrin-coated PermaNet® Dual, in comparison with the deltamethrin and synergist piperonyl butoxide (PBO)-treated PermaNet® 3.0 and the deltamethrin-coated PermaNet® 2.0, against wild free-flying pyrethroid-resistant Anopheles gambiae sensu lato (s.l.), in experimental huts in Tiassalé, Côte d’Ivoire (West Africa). Methods: PermaNet® Dual, PermaNet® 3.0 and PermaNet® 2.0, unwashed and washed (20 washes), were tested against free-flying pyrethroid-resistant An. gambiae s.l. in the experimental huts in Tiassalé, Côte d’Ivoire from March to August 2020. Complementary laboratory cone bioassays (daytime and 3-min exposure) and tunnel tests (nightly and 15-h exposure) were performed against pyrethroid-susceptible An. gambiae sensu stricto (s.s.) (Kisumu strain) and pyrethroid-resistant An. gambiae s.l. (Tiassalé strain). Results: PermaNet® Dual demonstrated significantly improved efficacy, compared to PermaNet® 3.0 and PermaNet® 2.0, against the pyrethroid-resistant An. gambiae s.l. Indeed, the experimental hut trial data showed that the mortality and blood-feeding inhibition in the wild pyrethroid-resistant An. gambiae s.l. were overall significantly higher with PermaNet® Dual compared with PermaNet® 3.0 and PermaNet® 2.0, for both unwashed and washed samples. The mortality with unwashed and washed samples were 93.6 ± 0.2% and 83.2 ± 0.9% for PermaNet® Dual, 37.5 ± 2.9% and 14.4 ± 3.9% for PermaNet® 3.0, and 7.4 ± 5.1% and 11.7 ± 3.4% for PermaNet® 2.0, respectively. Moreover, unwashed and washed samples produced the respective percentage blood-feeding inhibition of 41.4 ± 6.9% and 43.7 ± 4.8% with PermaNet® Dual, 51.0 ± 5.7% and 9.8 ± 3.6% with PermaNet® 3.0, and 12.8 ± 4.3% and − 13.0 ± 3.6% with PermaNet® 2.0. Overall, PermaNet® Dual also induced higher or similar deterrence, exophily and personal protection when compared with the standard PermaNet® 3.0 and PermaNet® 2.0 reference nets, with both unwashed and washed net samples. In contrast to cone bioassays, tunnel tests predicted the efficacy of PermaNet® Dual seen in the current experimental hut trial. Conclusion: The deltamethrin-chlorfenapyr-coated PermaNet® Dual induced a high efficacy and performed better than the deltamethrin-PBO PermaNet® 3.0 and the deltamethrin-only PermaNet® 2.0, testing both unwashed and 20 times washed samples against the pyrethroid-susceptible and resistant strains of An. gambiae s.l. The inclusion of chlorfenapyr with deltamethrin in PermaNet® Dual net greatly improved protection and control of pyrethroid-resistant An. gambiae populations. PermaNet® Dual thus represents a promising tool, with a high potential to reduce malaria transmission and provide community protection in areas compromised by mosquito vector resistance to pyrethroids

A Real-Time Contouring Feedback Tool for Consensus-Based Contour Training

PURPOSE: Variability in contouring structures of interest for radiotherapy continues to be challenging. Although training can reduce such variability, having radiation oncologists provide feedback can be impractical. We developed a contour training tool to provide real-time feedback to trainees, thereby reducing variability in contouring. METHODS: We developed a novel metric termed localized signed square distance (LSSD) to provide feedback to the trainee on how their contour compares with a reference contour, which is generated real-time by combining trainee contour and multiple expert radiation oncologist contours. Nine trainees performed contour training by using six randomly assigned training cases that included one test case of the heart and left ventricle (LV). The test case was repeated 30 days later to assess retention. The distribution of LSSD maps of the initial contour for the training cases was combined and compared with the distribution of LSSD maps of the final contours for all training cases. The difference in standard deviations from the initial to final LSSD maps, ΔLSSD, was computed both on a per-case basis and for the entire group. RESULTS: For every training case, statistically significant ΔLSSD were observed for both the heart and LV. When all initial and final LSSD maps were aggregated for the training cases, before training, the mean LSSD ([range], standard deviation) was -0.8 mm ([-37.9, 34.9], 4.2) and 0.3 mm ([-25.1, 32.7], 4.8) for heart and LV, respectively. These were reduced to -0.1 mm ([-16.2, 7.3], 0.8) and 0.1 mm ([-6.6, 8.3], 0.7) for the final LSSD maps during the contour training sessions. For the retention case, the initial and final LSSD maps of the retention case were aggregated and were -1.5 mm ([-22.9, 19.9], 3.4) and -0.2 mm ([-4.5, 1.5], 0.7) for the heart and 1.8 mm ([-16.7, 34.5], 5.1) and 0.2 mm ([-3.9, 1.6],0.7) for the LV. CONCLUSIONS: A tool that uses real-time contouring feedback was developed and successfully used for contour training of nine trainees. In all cases, the utility was able to guide the trainee and ultimately reduce the variability of the trainee\u27s contouring

Automated Contouring and Planning in Radiation Therapy: What Is \u27Clinically Acceptable\u27?

Developers and users of artificial-intelligence-based tools for automatic contouring and treatment planning in radiotherapy are expected to assess clinical acceptability of these tools. However, what is \u27clinical acceptability\u27? Quantitative and qualitative approaches have been used to assess this ill-defined concept, all of which have advantages and disadvantages or limitations. The approach chosen may depend on the goal of the study as well as on available resources. In this paper, we discuss various aspects of \u27clinical acceptability\u27 and how they can move us toward a standard for defining clinical acceptability of new autocontouring and planning tools

Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry

Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT). Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant ( P < 0.05). Through fine-mapping, in six regions ( 3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13 ), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions ( 11q13, 16q12/TOX3 ), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality. Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry. Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1-11. ©2017 AACR

The combined immunodetection of AP-2α and YY1 transcription factors is associated with ERBB2 gene overexpression in primary breast tumors

INTRODUCTION: Overexpression of the ERBB2 oncogene is observed in about 20% of human breast tumors and is the consequence of increased transcription rates frequently associated with gene amplification. Several studies have shown a link between activator protein 2 (AP-2) transcription factors and ERBB2 gene expression in breast cancer cell lines. Moreover, the Yin Yang 1 (YY1) transcription factor has been shown to stimulate AP-2 transcriptional activity on the ERBB2 promoter in vitro. In this report, we examined the relationships between ERBB2, AP-2alpha, and YY1 both in breast cancer tissue specimens and in a mammary cancer cell line. METHODS: ERBB2, AP-2alpha, and YY1 protein levels were analyzed by immunohistochemistry in a panel of 55 primary breast tumors. ERBB2 gene amplification status was determined by fluorescent in situ hybridization. Correlations were evaluated by a chi2 test at a p value of less than 0.05. The functional role of AP-2alpha and YY1 on ERBB2 gene expression was analyzed by small interfering RNA (siRNA) transfection in the BT-474 mammary cancer cell line followed by real-time reverse transcription-polymerase chain reaction and Western blotting. RESULTS: We observed a statistically significant correlation between ERBB2 and AP-2alpha levels in the tumors (p < 0.01). Moreover, associations were found between ERBB2 protein level and the combined high expression of AP-2alpha and YY1 (p < 0.02) as well as between the expression of AP-2alpha and YY1 (p < 0.001). Furthermore, the levels of both AP-2alpha and YY1 proteins were inversely correlated to ERBB2 gene amplification status in the tumors (p < 0.01). Transfection of siRNAs targeting AP-2alpha and AP-2gamma mRNAs in the BT-474 breast cancer cell line repressed the expression of the endogenous ERBB2 gene at both the mRNA and protein levels. Moreover, the additional transfection of an siRNA directed against the YY1 transcript further reduced the ERBB2 protein level, suggesting that AP-2 and YY1 transcription factors cooperate to stimulate the transcription of the ERBB2 gene. CONCLUSION: This study highlights the role of both AP-2alpha and YY1 transcription factors in ERBB2 oncogene overexpression in breast tumors. Our results also suggest that high ERBB2 expression may result either from gene amplification or from increased transcription factor levels

Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor

Class B GPCRs can activate multiple signalling effectors with the potential to exhibit biased agonism in response to ligand stimulation. Previously, we highlighted key TM domain polar amino acids that were crucial for the function of the GLP-1 receptor, a key therapeutic target for diabetes and obesity. Using a combination of mutagenesis, pharmacological characterisation, mathematical and computational molecular modelling, this study identifies additional highly conserved polar residues located towards the TM helical boundaries of Class B GPCRs that are important for GLP-1 receptor stability and/or controlling signalling specificity and biased agonism. This includes (i) three positively charged residues (R3.30227, K4.64288, R5.40310) located at the extracellular boundaries of TMs 3, 4 and 5 that are predicted in molecular models to stabilise extracellular loop 2, a crucial domain for ligand affinity and receptor activation; (ii) a predicted hydrogen bond network between residues located in TMs 2 (R2.46176), 6 (R6.37348) and 7 (N7.61406 and E7.63408) at the cytoplasmic face of the receptor that is important for stabilising the inactive receptor and directing signalling specificity, (iii) residues at the bottom of TM 5 (R5.56326) and TM6 (K6.35346 and K6.40351) that are crucial for receptor activation and downstream signalling; (iv) residues predicted to be involved in stabilisation of TM4 (N2.52182 and Y3.52250) that also influence cell signalling. Collectively, this work expands our understanding of peptide-mediated signalling by the GLP-1 receptor

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 (-) (8)). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 (-) (10)) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 (-) (8)) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer