Miracle-dz/UniFAR-FTUs huggingface dataset:
Exactly solvable 2D model for photon propagation in curved space: loss of interference and Bell inequality violation

We present an exact solution for the propagation of quantized massless scalar particles in a two-dimensional variation of the Alcubierre metric. Classical localized wavepacket solutions are derived using closed expressions for light-ray coordinates, and corresponding annihilation operators are constructed using the concept of locally positive and negative frequencies. The theory is used to describe the loss of fringe visibility in a single-photon interferometer, and the reduction of entanglement between two 2D photons, if one photon travels through a region with spacetime curvature. We derive an expansion of the field operator in terms of localized modes by means of an over-completeness relation. The quantization procedure also applies to massive and charged scalar fields in an n-dimensional globally hyperbolic spacetime.
Integrating top-down and bottom-up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone

Understanding the phenotypic and genetic architecture of reproductive isolation is a longstanding goal of speciation research. In many systems, candidate barrier traits and loci have been identified, but causal connections between them are rarely made. In this study, we combine ‘top-down’ and ‘bottom-up’ approaches with demographic modeling toward an integrated understanding of speciation across a monkeyflower hybrid zone. Previous work in this system suggests that pollinator-mediated reproductive isolation is a primary barrier to gene flow between two divergent red- and yellow-flowered ecotypes of Mimulus aurantiacus. Several candidate floral traits contributing to pollinator isolation have been identified, including a difference in flower color, which is caused primarily by a single large-effect locus (MaMyb2). Other anonymous SNP loci, potentially contributing to pollinator isolation, also have been identified, but their causal relationships remain untested. Here, we performed demographic analyses, which indicate that this hybrid zone formed by secondary contact, but that subsequent gene flow was restricted in a large fraction of the genome by barrier loci. Using a cline-based genome scan (our bottom-up approach), we demonstrate that candidate barrier loci are broadly distributed across the genome, rather than mapping to one or a few ‘islands of speciation. ’ A QTL analysis (our top-down approach) revealed most floral traits are highly polygenic, with little evidence that QTL co-localize, indicating that most traits are largely genetically independent. Finally, we find little convincing evidence for the overlap of QTL and candidate barrier loci, suggesting that some loci contribute to other forms of reproductive isolation. Our findings highlight the challenges of understanding the genetic architecture of reproductive isolation and reveal that barriers to gene flow aside from pollinator isolation may play an important role in this system.
Modeling Benefits, Costs, and Affordability of a Novel Gene Therapy in Hemophilia A

The objective was to undertake an early cost-effectiveness assessment of valoctocogene roxaparvovec (valrox; Roctavian) compared to factor (F)VIII prophylaxis or emicizumab (Hemlibra; Roche HQ, Bazel, Switzerland) in patients with severe Hemophilia A (HA) without FVIII-antibodies. We also aimed to incorporate and quantify novel measures of value such as treatment durability, maximum value-based price (MVBP) and break-even time (ie, time until benefits begin to offset upfront payment). We constructed a Markov model to model bleeds over time which were linked to costs and quality-of-life decrements. In the valrox arm, FVIII over time was estimated combining initial effect and treatment waning and then linked to bleeds. In FVIII and emicizumab arms, bleeds were based on trial evidence. Evidence and assumptions were validated using expert elicitation. Model robustness was tested via sensitivity analyses. A Dutch societal perspective was applied with a 10-year time horizon. Valrox in comparison to FVIII, and emicizumab showed small increases in quality-adjusted life years at lower costs, and were therefore dominant. Valrox’ base case MVBP was estimated at €2.65 million/treatment compared to FVIII and €3.5 million/treatment versus emicizumab. Mean break-even time was 8.03 years compared to FVIII and 5.68 years to emicizumab. Early modeling of patients with HA in The Netherlands treated with valrox resulted in estimated improved health and lower cost compared to prophylactic FVIII and emicizumab. We also demonstrated feasibility of incorporation of treatment durability and novel outcomes such as value-based pricing scenarios and break-even time. Future work should aim to better characterize uncertainties and increase translation of early modeling to direct research efforts.
Parents of Non-binary Children: Stories of Understanding and Support

ABSTRACT Parents of non-binary children undergo profound changes as they learn to first understand and then support their child. The question guiding this study was: what are the stories parents of non-binary children tell about how they came to understand and affirm their child? This narrative study provides a definition of non-binary gender, a review of peer-reviewed literature on therapy with children and adolescents who identify as transgender or non-binary, as well as narrative findings from three mothers of non-binary children ages 8 −11. Stories of parents confronting core beliefs, stepping into leadership, and feeling like they do not fit in or belong in ostensibly supportive spaces are presented. Relevance to narrative therapy is highlighted as well as the need for more research on family processes that enact support for transgender and non-binary children.
Endomembrane remodeling and dynamics in Salmonella infection

Salmonellae are bacteria that cause moderate to severe infections in humans, depending on the strain and the immune status of the infected host. These pathogens have the particularity of residing in the cells of the infected host. They are usually found in a vacuolar compartment that the bacteria shape with the help of effector proteins. Following invasion of a eukaryotic cell, the bacterial vacuole undergoes maturation characterized by changes in localization, composition and morphology. In particular, membrane tubules stretching over the microtubule cytoskeleton are formed from the bacterial vacuole. Although these tubules do not occur in all infected cells, they are functionally important and promote intracellular replication. This review focuses on the role and significance of membrane compartment remodeling observed in infected cells and the bacterial and host cell pathways involved.
Differential Effects of Parental and Self-Stigma on Intentions to Seek Counseling

Using hierarchical regression, the authors investigated the hypotheses that parental stigma and self-stigma would differentially and negatively predict intentions to seek counseling for European American (n = 318), Asian American (n = 153), and Asian international students. (n = 312). In this online cross-sectional study, parental stigma positively predicted intentions to seek counseling among Asian international students. The magnitude of this association was significantly greater than it was among European and Asian American students. As expected, self-stigma negatively predicted intentions to seek counseling among European and Asian American students. The magnitude of this association was significantly greater for European American students than it was for Asian international students, for whom self-stigma was not a significant predictor of intentions to seek counseling. This research suggests that the processes through which (a) stigma is felt and (b) stigma impacts psychological help seeking may be associated with one’s ethnicity and culture of origin.
Global Problems, Smart Solutions

Every four years since 2004, the Copenhagen Consensus Center has organized and hosted a high profile thought experiment about how a hypothetical extra $75 billion of development assistance money might best be spent to solve twelve of the major crises facing the world today. Collated in this specially commissioned book, a group of more than 50 experts make their cases for investment, discussing how to combat problems ranging from armed conflicts, corruption and trade barriers, to natural disasters, hunger, education and climate change. For each case, 'Alternative Perspectives' are also included to provide a critique and make other suggestions for investment. In addition, a panel of senior economists, including four Nobel Laureates, rank the attractiveness of each policy proposal in terms of its anticipated cost-benefit ratio. This thought-provoking book opens up debate, encouraging readers to come up with their own rankings and decide which solutions are smarter than others.
Using Noise Substitution for Backwards-Compatible Audio Codec Improvement

A method for representing error in perceptual audio coding as filtered noise is presented. Various techniques are compared for analyzing and re-synthesizing the noise representation. A focus is placed on improving the perceived audio quality with minimal data overhead. In particular, it is demonstrated that per-critical-band energy levels are sufficient to provide an increase in quality. Methods for including the coded error data in an audio file in a backwards-compatible manner are also discussed. The MP3 codec is treated as a case study, and an implementation of this method is presented.
Changes in Biomarkers of Tobacco Exposure among Cigarette Smokers Transitioning to ENDS Use: The Population Assessment of Tobacco and Health Study, 2013–2015

Limited data are available for how biomarkers of tobacco exposure (BOE) change when cigarette smokers transition to using electronic nicotine delivery systems (ENDS). Using biomarker data from Waves 1 (2013–2014) and 2 (2014–2015) of the PATH Study, we examined how mean BOE concentrations, including metabolites of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC) and metals, changed when 2475 adult smokers transitioned to using ENDS or quit tobacco products. Exclusive smokers who transitioned to dual use had a significant decrease in NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), but not nicotine metabolites, most PAHs, metals, or VOCs. Exclusive smokers who became dual users had significant reductions in total nicotine equivalents, NNAL, and 2CyEMA (acrylonitrile metabolite), but only in those who reduced cigarettes per day (CPD) by >=50%. Smokers who transitioned to exclusive ENDS use had significant reductions in most TSNAs, PAHs, and VOCs; however, nicotine metabolites did not decrease in dual users who became exclusive ENDS users. Smokers who quit tobacco use had significant decreases in nicotine metabolites, all TSNAs, most PAHs, and most VOCs. Cigarette smokers who became dual users did not experience significant reductions in most BOEs. Reductions were impacted by changes in CPD. However, transitioning from smoking to no tobacco or exclusive ENDS use was associated with reduced exposure to most BOEs measured. Future analyses could incorporate additional waves of PATH data and examine changes in biomarker exposure by ENDS device type and CPD.
Three-dimensional Structural Modeling (3D SM) and Joint Geophysical Characterization (JGC) of Hydrocarbon Reservoir: A Case Study of the Kadanwari field in Middle Indus Basin (MIB), Southeastern Pakistan

Complex structural geology generally leads to significant consequences for hydrocarbon reservoir exploration that needs a comprehensive methodology for complete comprehension. Despite a large number of existing wells in the Kadanwari field, Middle Indus Basin (MIB), southeastern Pakistan, the depositional environment of the Early Cretaceous stratigraphic sequence is still poorly understood, which has implications for regional geology as well as economic significance. To improve the understanding of depositional environment of complex heterogeneous reservoirs with associated 3D stratigraphic architecture, spatial distribution of facies and properties, and hydrocarbon prospects, a new methodology of three-dimensional structural modeling (3D SM) and joint geophysical characterization (JGC) is introduced in this research. JGC makes use of seismic interpretation-aided 3D SM, 3D seismic attributes analysis coupled with petrophysical modeling using 3D seismic reflection, and borehole data. Subsequently, the 3D SM reveals that the Kadanwari field experienced multiple stages of complex deformation dominated by NW to SW normal fault system, high relief horsts, half-graben, and graben structures. 3D SM and 3D fault system models (FSMs) further depict that the middle part of the sequence experienced more deformation compared to the surroundings of major faults with predominant oriented in S30°-45°E and N25°-35°W, azimuth as 148°–170° and 318°–345°, minimum (28°), mean (62°), and maximum (90°) dip angles. The applied variance edge attribute better portrays the inconsistency of the seismic data associated with faulting and estimated high reflection sediments presumed to be potential hydrocarbon traps. The high amplitude and loss of frequency anomalies of sweetness and root mean square (RMS) amplitude attributes represent cleaner and payable sand-rich shoreward facies revealing gas saturated sand, while relatively low amplitude and high-frequency anomalies indicate sandy shale, shale, and pro-delta facies, unfavorable zones for gas potential. The quantitative petrophysical modeling result shows that E sand interval has good effective porosity (∅ eff ) and hydrocarbon saturation (S hc ) compared to G sand interval. The derived average petrophysical properties, such as volume of shale (V shale ), average porosity (∅ avg ), ∅ eff , water saturation (S W ), and S hc of the E sand interval are 30.5%, 17.4%, 12.2%, 33.2%, 70.01%, respectively. The newly introduced 3D SM and JGC workflow is an effective tool for highlighting potential areas of high quality reservoir development.
Benchmarking Plane Waves Quantum Mechanical Calculations of Iron(II) Tris(2,2′-bipyridine) Complex by X-ray Absorption Spectroscopy

In this work, we used, for the first time, a computational Self-Consistent Field procedure based on plane waves to describe the low and high spin conformational states of the complex [Fe(bpy)3]2+. The results obtained in the study of the minimum energy structures of this complex, a prototype of a wide class of compounds called Spin Cross Over, show how the plane wave calculations are in line with the most recent studies based on gaussian basis set functions and, above all, reproduce within acceptable errors the experimental spectra of X-ray absorption near-edge structure spectroscopy (XANES). This preliminary study shows the capabilities of plane wave methods to correctly describe the molecular structures of metal-organic complexes of this type and paves the way for future even complex computational simulations based on the energy gradient, such as Nudge Elastic Band or ab-initio Born-Oppenheimer molecular dynamics.
Nuclear Lamins: Key Proteins for Embryonic Development

Simple Summary The biology of a multicellular organism is extremely complex, leaving behind a realm of compound yet systematic mechanisms still to be unraveled. The nucleus is a vital cellular organelle adapted to storing and regulating the hereditary genetic information. Dysregulation of the nucleus can have profound effects on the physiology and viability of cells. This becomes extremely significant in the context of development, where the whole organism arises from a single cell, the zygote. Therefore, even a mild aberration at this stage can have profound effects on the whole organism. However, studying the function of individual nuclear components at this point is exceptionally complicated because this phase is inherently under the control of maternal factors stored in the female germ cell, the egg. Here, we focus on the lamins, as essential nuclear components, and summarize the current knowledge of their role in development. Although scientists encounter challenges working with these miniscule yet key proteins, the demand to know more is increasing gradually due to the mutations caused in lamins leading to irreversible phenotypic conditions in humans. Abstract Lamins are essential components of the nuclear envelope and have been studied for decades due to their involvement in several devastating human diseases, the laminopathies. Despite intensive research, the molecular basis behind the disease state remains mostly unclear with a number of conflicting results regarding the different cellular functions of nuclear lamins being published. The field of developmental biology is no exception. Across model organisms, the types of lamins present in early mammalian development have been contradictory over the years. Due to the long half-life of the lamin proteins, which is a maternal factor that gets carried over to the zygote after fertilization, investigators are posed with challenges to dive into the functional aspects and significance of lamins in development. Due to these technical limitations, the role of lamins in early mammalian embryos is virtually unexplored. This review aims in converging results that were obtained so far in addition to the complex functions that ceases if lamins are mutated.
Effects of rain and foot disturbances on antlion (Myrmeleon immaculatus) pit size and relocation.

The purpose of this experiment was to determine the effects of rain and foot disturbances on the pit size and relocation preference of antlion larvae (Myrmeleon immaculatus). Antlions were placed in sand filled aquaria to build pits in a 24-hour period and pit size and location (exposed or sheltered) was measured. Rain and foot traffic treatments were performed and relocation and pit size was measured after a 24hour period. The mean pit diameter of the antlions exposed to treatments of dry and foot traffic were significantly larger than the mean pit diameter of antlions with the rain treatment. The number of antlions that relocated to shelter after the no treatment and foot traffic treatment was not significantly greater than the number of antlions that relocated to shelter after the treatment of rain. There was a greater proportion that chose shelter as the number of trials increased for no treatment and foot traffic treatment. There were significantly more pits built in dry conditions than wet conditions. In conclusion, pit size was related to disturbances of rain and foot, and pit size was larger within the trails with out treatment and with foot traffic and rain disturbances. I grant the Regents of the University of Michigan the non-exclusive right to retain, reproduce, and distribute my paper, titled in electronic formats and at no cost throughout the world. The University of Michigan may make and keep more than one copy of the Paper for purposes of security, backup, preservation and access, and may migrate the Paper to any medium or format for the purpose of preservation and access in the future.
Opportunities to Learn for Children With Autism Spectrum Disorders: Effects of the Perceived Efficacy of Teacher Practices and Drivers of Inclusion

One of the factors linked to the successful inclusion of children with autism spectrum disorder (ASD) is the idea that the attitudes of teaching professionals are related to the perceived efficacy of educational practices. The aim of this study was to explore the relationships between the perceived efficacy of a set of practices specifically aimed at children with ASD and the perceived drivers and attitudes toward their full inclusion. We estimated a structural equation model that included socioprofessional variables of the 454 teachers taking part in the study. The results show that greater efficacy of the practices implemented with children with ASD results in more positive attitudes toward the education of these children in inclusive settings. Similarly, drivers of inclusion also improve teachers’ attitudes toward these children. The findings suggest the need to improve teacher training and provide teachers with the resources necessary to adapt their practices to all children.
Modulation of DNA Damage Response by SAM and HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase (SAMHD1) Determines Prognosis and Treatment Efficacy in Different Solid Tumor Types

Simple Summary Ample evidence exists connecting dNTP pool dysregulation to cancer and genomic instability. SAMHD1, the unique dNTP triphosphohydrolase described in humans, has been proposed to play a key role in hematological cancers, although its value in advanced solid tumors has not yet been explored. Moreover, it has been proposed that SAMHD1 might fulfill the requirements of a driver gene in tumor development or might promote a so-called mutator phenotype. Here, we show that low SAMHD1 expression tumors show better prognosis in breast, ovarian, and lung advanced cancer. Moreover, low SAMHD1 expression is a positive predictive factor in lung and ovarian cancer treated with platin derivates and/or antimetabolites. In vitro evaluation of its underlying mechanism revealed that SAMHD1 KO cells presented enhanced susceptibility to DNA damage and subsequent induction of apoptosis of tumor cells. Our results provide strong evidence of the clinical importance of SAMHD1, becoming an interesting target for the development of personalized cancer treatments. Abstract SAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase with important roles in the control of cell proliferation and apoptosis, either through the regulation of intracellular dNTPs levels or the modulation of the DNA damage response. However, SAMHD1′s role in cancer evolution is still unknown. We performed the first in-depth study of SAMHD1′s role in advanced solid tumors, by analyzing samples of 128 patients treated with chemotherapy agents based on platinum derivatives and/or antimetabolites, developing novel in vitro knock-out models to explore the mechanisms driving SAMHD1 function in cancer. Low (or no) expression of SAMHD1 was associated with a positive prognosis in breast, ovarian, and non-small cell lung cancer (NSCLC) cancer patients. A predictive value was associated with low-SAMHD1 expression in NSCLC and ovarian patients treated with antimetabolites in combination with platinum derivatives. In vitro, SAMHD1 knock-out cells showed increased γ-H2AX and apoptosis, suggesting that SAMHD1 depletion induces DNA damage leading to cell death. In vitro treatment with platinum-derived drugs significantly enhanced γ-H2AX and apoptotic markers expression in knock-out cells, indicating a synergic effect of SAMHD1 depletion and platinum-based treatment. SAMHD1 expression represents a new strong prognostic and predictive biomarker in solid tumors and, thus, modulation of the SAMHD1 function may constitute a promising target for the improvement of cancer therapy.