Datasets and Benchmarks for Nanophotonic Structure and Parametric Design Simulations

Nanophotonic structures have versatile applications including solar cells, anti-reflective coatings, electromagnetic interference shielding, optical filters, and light emitting diodes. To design and understand these nanophotonic structures, electrodynamic simulations are essential. These simulations enable us to model electromagnetic fields over time and calculate optical properties. In this work, we introduce frameworks and benchmarks to evaluate nanophotonic structures in the context of parametric structure design problems. The benchmarks are instrumental in assessing the performance of optimization algorithms and identifying an optimal structure based on target optical properties. Moreover, we explore the impact of varying grid sizes in electrodynamic simulations, shedding light on how evaluation fidelity can be strategically leveraged in enhancing structure designs.Comment: 31 pages, 31 figures, 4 tables. Accepted at the 37th Conference on Neural Information Processing Systems (NeurIPS 2023), Datasets and Benchmarks Trac

Accumulation of promutagenic DNA adducts in the mouse distal colon after consumption of heme does not induce colonic neoplasms in the western diet model of spontaneous colorectal cancer

Author version made available in accordance with Publisher copyright policy.Scope: Red meat is considered a risk factor for colorectal cancer (CRC). Heme is considered to promote colonic hyperproliferation and cell damage. Resistant starch (RS) is a food that ferments in the colon with studies demonstrating protective effects against CRC. By utilizing the western diet model of spontaneous CRC, we determined if feeding heme (as hemin chloride) equivalent to a high red meat diet would increase colonic DNA adducts and CRC and whether RS could abrogate such effects. Methods and results: Four groups of mice: control, heme, RS and heme + RS were fed diets for 1 or 18 months. Colons were analyzed for apoptosis, proliferation, DNA adducts “8-hydroxy-2-deoxyguanosine” and “O6-methyl-2-deoxyguanosine” (O6MeG), and neoplasms. In the short term, heme increased cell proliferation (p < 0.05). Changes from 1 to 18 months showed increased cell proliferation (p<0.01) and 8-hydroxy-2-deoxyguanosine adducts (p < 0.05) in all groups, but only heme-fed mice showed reduced apoptosis (p < 0.01) and increasedO6MeGadducts (p<0.01). The incidence of colon neoplasms was not different between any interventions. Conclusion: We identified heme to increase proliferation in the short term, inhibit apoptosis over the long term, and increase O6MeG adducts in the colon over time although these changes did not affect colonic neoplasms within this mouse model.Funding for this project was provided by the National Health and Medical Research Council of Australia (Project number 535079).We would like to acknowledge the Royal Society of Edinburgh for funding a visit for Dr. SilviaGratz fromUKto Australia to carry out work associated with this project

Brief but Efficient: Acute HIV Infection and the Sexual Transmission of HIV

Background. We examined whether viral dynamics in the genital tract during the natural history of acute human immunodeficiency virus type 1 (HIV-1) infection could explain efficient heterosexual transmission of HIV. Methods. We measured HIV-1 concentration in blood and semen samples from patients with acute and long-term HIV-1 infection. We explored the effect of changes in viral dynamics in semen on the probability of transmission per coital act, using a probabilistic model published elsewhere. Results. Considered over time from infection, semen HIV-1 concentrations, in men with acute infection, increase and decrease in approximate parallel with changes occurring in blood. Modeling suggests that these acute dynamics alone are sufficient to increase probability of heterosexual transmission by 8-10-fold between peak (day 20 after infection, based on the model) and virologic set points (day 54 and later after infection). Depending on the frequency of coitus, men with average semen HIV-1 loads and without sexually transmitted diseases (STDs) would be expected to infect 7%-24% of susceptible female sex partners during the first 2 months of infection. The predicted infection rate would be much higher when either partner has an STD. Conclusions. Empirical biological data strongly support the hypothesis that sexual transmission by acutely infected individuals has a disproportionate effect on the spread of HIV-1 infection. Acute hyperinfectiousness may, in part, explain the current pandemic in heterosexual individual

Ultrathin compound semiconductor on insulator layers for high performance nanoscale transistors

Over the past several years, the inherent scaling limitations of electron devices have fueled the exploration of high carrier mobility semiconductors as a Si replacement to further enhance the device performance. In particular, compound semiconductors heterogeneously integrated on Si substrates have been actively studied, combining the high mobility of III-V semiconductors and the well-established, low cost processing of Si technology. This integration, however, presents significant challenges. Conventionally, heteroepitaxial growth of complex multilayers on Si has been explored. Besides complexity, high defect densities and junction leakage currents present limitations in the approach. Motivated by this challenge, here we utilize an epitaxial transfer method for the integration of ultrathin layers of single-crystalline InAs on Si/SiO2 substrates. As a parallel to silicon-on-insulator (SOI) technology14,we use the abbreviation "XOI" to represent our compound semiconductor-on-insulator platform. Through experiments and simulation, the electrical properties of InAs XOI transistors are explored, elucidating the critical role of quantum confinement in the transport properties of ultrathin XOI layers. Importantly, a high quality InAs/dielectric interface is obtained by the use of a novel thermally grown interfacial InAsOx layer (~1 nm thick). The fabricated FETs exhibit an impressive peak transconductance of ~1.6 mS/{\mu}m at VDS=0.5V with ON/OFF current ratio of greater than 10,000 and a subthreshold swing of 107-150 mV/decade for a channel length of ~0.5 {\mu}m

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Time interval from diagnosis to treatment of brain metastases with stereotactic radiosurgery is not associated with radionecrosis or local failure

IntroductionBrain metastases are the most common intracranial tumor diagnosed in adults. In patients treated with stereotactic radiosurgery, the incidence of post-treatment radionecrosis appears to be rising, which has been attributed to improved patient survival as well as novel systemic treatments. The impacts of concomitant immunotherapy and the interval between diagnosis and treatment on patient outcomes are unclear.MethodsThis single institution, retrospective study consisted of patients who received single or multi-fraction stereotactic radiosurgery for intact brain metastases. Exclusion criteria included neurosurgical resection prior to treatment and treatment of non-malignant histologies or primary central nervous system malignancies. A univariate screen was implemented to determine which factors were associated with radionecrosis. The chi-square test or Fisher’s exact test was used to compare the two groups for categorical variables, and the two-sample t-test or Mann-Whitney test was used for continuous data. Those factors that appeared to be associated with radionecrosis on univariate analyses were included in a multivariable model. Univariable and multivariable Cox proportional hazards models were used to assess potential predictors of time to local failure and time to regional failure.ResultsA total of 107 evaluable patients with a total of 256 individual brain metastases were identified. The majority of metastases were non-small cell lung cancer (58.98%), followed by breast cancer (16.02%). Multivariable analyses demonstrated increased risk of radionecrosis with increasing MRI maximum axial dimension (OR 1.10, p=0.0123) and a history of previous whole brain radiation therapy (OR 3.48, p=0.0243). Receipt of stereotactic radiosurgery with concurrent immunotherapy was associated with a decreased risk of local failure (HR 0.31, p=0.0159). Time interval between diagnostic MRI and first treatment, time interval between CT simulation and first treatment, and concurrent immunotherapy had no impact on incidence of radionecrosis or regional failure.DiscussionAn optimal time interval between diagnosis and treatment for intact brain metastases that minimizes radionecrosis and maximizes local and regional control could not be identified. Concurrent immunotherapy does not appear to increase the risk of radionecrosis and may improve local control. These data further support the safety and synergistic efficacy of stereotactic radiosurgery with concurrent immunotherapy

Divergent methyl-coenzyme M reductase genes in a deep-subseafloor Archaeoglobi

The methyl-coenzyme M reductase (MCR) complex is a key enzyme in archaeal methane generation and has recently been proposed to also be involved in the oxidation of short-chain hydrocarbons including methane, butane, and potentially propane. The number of archaeal clades encoding the MCR continues to grow, suggesting that this complex was inherited from an ancient ancestor, or has undergone extensive horizontal gene transfer. Expanding the representation of MCR-encoding lineages through metagenomic approaches will help resolve the evolutionary history of this complex. Here, a near-complete Archaeoglobi metagenome-assembled genome (MAG; Ca. Polytropus marinifundus gen. nov. sp. nov.) was recovered from the deep subseafloor along the Juan de Fuca Ridge flank that encodes two divergent McrABG operons similar to those found in Ca. Bathyarchaeota and Ca. Syntrophoarchaeum MAGs. Ca. P. marinifundus is basal to members of the class Archaeoglobi, and encodes the genes for β-oxidation, potentially allowing an alkanotrophic metabolism similar to that proposed for Ca. Syntrophoarchaeum. Ca. P. marinifundus also encodes a respiratory electron transport chain that can potentially utilize nitrate, iron, and sulfur compounds as electron acceptors. Phylogenetic analysis suggests that the Ca. P. marinifundus MCR operons were horizontally transferred, changing our understanding of the evolution and distribution of this complex in the Archaea

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought