DiffusionCT: Latent Diffusion Model for CT Image Standardization

Computed tomography (CT) imaging is a widely used modality for early lung cancer diagnosis, treatment, and prognosis. Features extracted from CT images are now accepted to quantify spatial and temporal variations in tumor architecture and function. However, CT images are often acquired using scanners from different vendors with customized acquisition standards, resulting in significantly different texture features even for the same patient, posing a fundamental challenge to downstream studies. Existing CT image harmonization models rely on supervised or semi-supervised techniques, with limited performance. In this paper, we have proposed a diffusion-based CT image standardization model called DiffusionCT which works on latent space by mapping latent distribution into a standard distribution. DiffusionCT incorporates an Unet-based encoder-decoder and a diffusion model embedded in its bottleneck part. The Unet first trained without the diffusion model to learn the latent representation of the input data. The diffusion model is trained in the next training phase. All the trained models work together on image standardization. The encoded representation outputted from the Unet encoder passes through the diffusion model, and the diffusion model maps the distribution in to target standard image domain. Finally, the decode takes that transformed latent representation to synthesize a standardized image. The experimental results show that DiffusionCT significantly improves the performance of the standardization task.Comment: 6 pages, 03 figures and 01 table

A Theory of Cheap Control in Embodied Systems

We present a framework for designing cheap control architectures for embodied agents. Our derivation is guided by the classical problem of universal approximation, whereby we explore the possibility of exploiting the agent's embodiment for a new and more efficient universal approximation of behaviors generated by sensorimotor control. This embodied universal approximation is compared with the classical non-embodied universal approximation. To exemplify our approach, we present a detailed quantitative case study for policy models defined in terms of conditional restricted Boltzmann machines. In contrast to non-embodied universal approximation, which requires an exponential number of parameters, in the embodied setting we are able to generate all possible behaviors with a drastically smaller model, thus obtaining cheap universal approximation. We test and corroborate the theory experimentally with a six-legged walking machine. The experiments show that the sufficient controller complexity predicted by our theory is tight, which means that the theory has direct practical implications. Keywords: cheap design, embodiment, sensorimotor loop, universal approximation, conditional restricted Boltzmann machineComment: 27 pages, 10 figure

Evolution of gaseous disk viscosity driven by supernova explosion in star-forming galaxies at high redshift

Motivated by Genzel et al.'s observations of high-redshift star-forming galaxies, containing clumpy and turbulent rings or disks, we build a set of equations describing the dynamical evolution of gaseous disks with inclusion of star formation and its feedback. Transport of angular momentum is due to "turbulent" viscosity induced by supernova explosions in the star formation region. Analytical solutions of the equations are found for the initial cases of a gaseous ring and the integrated form for a gaseous disk, respectively. For a ring with enough low viscosity, it evolves in a slow processes of gaseous diffusion and star formation near the initial radius. For a high viscosity, the ring rapidly diffuses in the early phase. The diffusion drives the ring into a region with a low viscosity and start the second phase undergoing pile-up of gas at a radius following the decreased viscosity torque. The third is a sharply deceasing phase because of star formation consumption of gas and efficient transportation of gas inward forming a stellar disk. We apply the model to two $z\sim 2$ galaxies BX 482 and BzK 6004, and find that they are undergoing a decline in their star formation activity.Comment: To appear in ApJ, 5 figure

Competing biosecurity and risk rationalities in the Chittagong poultry commodity chain, Bangladesh

This paper anthropologically explores how key actors in the Chittagong live bird trading network perceive biosecurity and risk in relation to avian influenza between production sites, market maker scenes and outlets. They pay attention to the past and the present, rather than the future, downplaying the need for strict risk management, as outbreaks have not been reported frequently for a number of years. This is analysed as ‘temporalities of risk perception regarding biosecurity’, through Black Swan theory, the idea that unexpected events with major effects are often inappropriately rationalized (Taleb in The Black Swan. The impact of the highly improbable, Random House, New York, 2007). This incorporates a sociocultural perspective on risk, emphasizing the contexts in which risk is understood, lived, embodied and experienced. Their risk calculation is explained in terms of social consent, practical intelligibility and convergence of constraints and motivation. The pragmatic and practical orientation towards risk stands in contrast to how risk is calculated in the avian influenza preparedness paradigm. It is argued that disease risk on the ground has become a normalized part of everyday business, as implied in Black Swan theory. Risk which is calculated retrospectively is unlikely to encourage investment in biosecurity and, thereby, points to the danger of unpredictable outlier events

Understanding Urban Demand for Wild Meat in Vietnam: Implications for Conservation Actions

Vietnam is a significant consumer of wildlife, particularly wild meat, in urban restaurant settings. To meet this demand, poaching of wildlife is widespread, threatening regional and international biodiversity. Previous interventions to tackle illegal and potentially unsustainable consumption of wild meat in Vietnam have generally focused on limiting supply. While critical, they have been impeded by a lack of resources, the presence of increasingly organised criminal networks and corruption. Attention is, therefore, turning to the consumer, but a paucity of research investigating consumer demand for wild meat will impede the creation of effective consumer-centred interventions. Here we used a mixed-methods research approach comprising a hypothetical choice modelling survey and qualitative interviews to explore the drivers of wild meat consumption and consumer preferences among residents of Ho Chi Minh City, Vietnam. Our findings indicate that demand for wild meat is heterogeneous and highly context specific. Wild-sourced, rare, and expensive wild meat-types are eaten by those situated towards the top of the societal hierarchy to convey wealth and status and are commonly consumed in lucrative business contexts. Cheaper, legal and farmed substitutes for wild-sourced meats are also consumed, but typically in more casual consumption or social drinking settings. We explore the implications of our results for current conservation interventions in Vietnam that attempt to tackle illegal and potentially unsustainable trade in and consumption of wild meat and detail how our research informs future consumer-centric conservation actions

Modeling Chemical Interaction Profiles: II. Molecular Docking, Spectral Data-Activity Relationship, and Structure-Activity Relationship Models for Potent and Weak Inhibitors of Cytochrome P450 CYP3A4 Isozyme

Polypharmacy increasingly has become a topic of public health concern, particularly as the U.S. population ages. Drug labels often contain insufficient information to enable the clinician to safely use multiple drugs. Because many of the drugs are bio-transformed by cytochrome P450 (CYP) enzymes, inhibition of CYP activity has long been associated with potentially adverse health effects. In an attempt to reduce the uncertainty pertaining to CYP-mediated drug-drug/chemical interactions, an interagency collaborative group developed a consensus approach to prioritizing information concerning CYP inhibition. The consensus involved computational molecular docking, spectral data-activity relationship (SDAR), and structure-activity relationship (SAR) models that addressed the clinical potency of CYP inhibition. The models were built upon chemicals that were categorized as either potent or weak inhibitors of the CYP3A4 isozyme. The categorization was carried out using information from clinical trials because currently available in vitro high-throughput screening data were not fully representative of the in vivo potency of inhibition. During categorization it was found that compounds, which break the Lipinski rule of five by molecular weight, were about twice more likely to be inhibitors of CYP3A4 compared to those, which obey the rule. Similarly, among inhibitors that break the rule, potent inhibitors were 2–3 times more frequent. The molecular docking classification relied on logistic regression, by which the docking scores from different docking algorithms, CYP3A4 three-dimensional structures, and binding sites on them were combined in a unified probabilistic model. The SDAR models employed a multiple linear regression approach applied to binned 1D 13C-NMR and 1D 15N-NMR spectral descriptors. Structure-based and physical-chemical descriptors were used as the basis for developing SAR models by the decision forest method. Thirty-three potent inhibitors and 88 weak inhibitors of CYP3A4 were used to train the models. Using these models, a synthetic majority rules consensus classifier was implemented, while the confidence of estimation was assigned following the percent agreement strategy. The classifier was applied to a testing set of 120 inhibitors not included in the development of the models. Five compounds of the test set, including known strong inhibitors dalfopristin and tioconazole, were classified as probable potent inhibitors of CYP3A4. Other known strong inhibitors, such as lopinavir, oltipraz, quercetin, raloxifene, and troglitazone, were among 18 compounds classified as plausible potent inhibitors of CYP3A4. The consensus estimation of inhibition potency is expected to aid in the nomination of pharmaceuticals, dietary supplements, environmental pollutants, and occupational and other chemicals for in-depth evaluation of the CYP3A4 inhibitory activity. It may serve also as an estimate of chemical interactions via CYP3A4 metabolic pharmacokinetic pathways occurring through polypharmacy and nutritional and environmental exposures to chemical mixtures

Inter-specific hybridization underlies phenotypic variability in Daphnia populations

In the glacial lakes of the Palaearctic three species of Cladocera commonly coexist: Daphnia hyalina, D. galeata , and D. cucullata . Frequently these populations contain not only animals which are morphologically typical for the species but also individuals of an intermediate phenotype. Electrophoretic investigations of allozyme-patterns in morphologically typical individuals reveal that each species is fixed for a different allele at the GOT locus. Morphologically intermediate animals are heterozygous for the alleles of the two species which they resemble. The allelic pattern at other loci is also consistent with the assumption that morphological intermediates are formed via interspecific hybridization. Very few backcrosses between galeata-hyalina hybrids and their parent species are found, and there is no indication of gene flow between D. cucullata and the other species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47761/1/442_2004_Article_BF00378763.pd

Activation of Latent HIV Using Drug-Loaded Nanoparticles

Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the HDAC inhibitor sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. Taken together these data demonstrate the ability of nanotechnological approaches to provide improved methods for activating latent HIV and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV therapy

Mistreatment of university students most common during medical studies

BACKGROUND: This study concerns the occurrence of various forms of mistreatment by staff and fellow students experienced by students in the Faculty of Medicine and the other four faculties of the University of Oulu, Finland. METHODS: A questionnaire with 51 questions on various forms of physical and psychological mistreatment was distributed to 665 students (451 females) after lectures or examinations and filled in and returned. The results were analysed by gender and faculty. The differences between the males and females were assessed statistically using a test for the equality of two proportions. An exact two-sided P value was calculated using a mid-P approach to Fisher's exact test (the null hypothesis being that there is no difference between the two proportions). RESULTS: About half of the students answering the questionnaire had experienced some form of mistreatment by staff during their university studies, most commonly humiliation and contempt (40%), negative or disparaging remarks (34%), yelling and shouting (23%), sexual harassment and other forms of gender-based mistreatment (17%) and tasks assigned as punishment (13%). The students in the Faculty of Medicine reported every form of mistreatment more commonly than those in the Faculties of Humanities, Education, Science and Technology. Experiences of mistreatment varied, but clear messages regarding its patterns were to be found in each faculty. Female students reported more instances of mistreatment than males and were more disturbed by them. Professors, lecturers and other staff in particular mistreated female students more than they mistreated males. About half of the respondents reported some form of mistreatment by their fellow students. CONCLUSION: Students in the Faculty of Medicine reported the greatest amount of mistreatment. If a faculty mistreats its students, its success in the main tasks of universities, research, teaching and learning, will be threatened. The results challenge university teachers, especially in faculties of medicine, to evaluate their ability to create a safe environment conducive to learning

Shifts in timing and duration of breeding for 73 boreal bird species over four decades

Breeding timed to match optimal resource abundance is vital for the successful reproduction of species, and breeding is therefore sensitive to environmental cues. As the timing of breeding shifts with a changing climate, this may not only affect the onset of breeding but also its termination, and thus the length of the breeding period. We use an extensive dataset of over 820K nesting records of 73 bird species across the boreal region in Finland to probe for changes in the beginning, end, and duration of the breeding period over four decades (1975 to 2017). We uncover a general advance of breeding with a strong phylogenetic signal but no systematic variation over space. Additionally, 31% of species contracted their breeding period in at least one bioclimatic zone, as the end of the breeding period advanced more than the beginning. We did not detect a statistical difference in phenological responses of species with combinations of different migratory strategy or number of broods. Nonetheless, we find systematic differences in species responses, as the contraction in the breeding period was found almost exclusively in resident and short-distance migrating species, which generally breed early in the season. Overall, changes in the timing and duration of reproduction may potentially lead to more broods co-occurring in the early breeding season-a critical time for species' reproductive success. Our findings highlight the importance of quantifying phenological change across species and over the entire season to reveal shifts in the community-level distribution of bird reproduction.Peer reviewe