Miracle-dz/UniFAR-FTUs huggingface dataset:
Virtual Biopsy – Image to Image translation of Optical Coherence Tomography (OCT) images to H&E Histology like images

Histological Haematoxylin and Eosin stained (H&E) images are the gold standard for various clinical assessments, including cancer detection, tumour margin detection, and disease diagnosis. Non-invasive optical imaging modalities, such as optical coherence tomography (OCT), permit label-free, micron-scale 3D imaging of biological tissue micro structure with significant depth (1-2 millimeters) and large fields-of-view, but are difficult to interpret and correlate with clinical ground truth without specialized training. Here we introduce the concept of a virtual biopsy, by using generative neural networks to synthesize virtual H&E sections from OCT images.
MINIATURE EXOPLANET RADIAL VELOCITY ARRAY (MINERVA) I. DESIGN, COMMISSIONING, AND FIRST SCIENCE RESULTS

The MINiature Exoplanet Radial Velocity Array (MINERVA) is a US-based observational facility dedicated to the discovery and characterization of exoplanets around a nearby sample of bright stars. MINERVA employs a robotic array of four 0.7 m telescopes outfitted for both high-resolution spectroscopy and photometry, and is designed for completely autonomous operation. The primary science program is a dedicated radial velocity survey and the secondary science objective is to obtain high precision transit light curves. The modular design of the facility and the flexibility of our hardware allows for both science programs to be pursued simultaneously, while the robotic control software provides a robust and efficient means to carry out nightly observations. In this article, we describe the design of MINERVA including major hardware components, software, and science goals. The telescopes and photometry cameras are characterized at our test facility on the Caltech campus in Pasadena, CA, and their on-sky performance is validated. New observations from our test facility demonstrate sub-mmag photometric precision of one of our radial velocity survey targets, and we present new transit observations and fits of WASP-52b—a known hot-Jupiter with an inflated radius and misaligned orbit. The process of relocating the MINERVA hardware to its final destination at the Fred Lawrence Whipple Observatory in southern Arizona has begun, and science operations are expected to commence within 2015. Subject headings: telescopes — methods: observational — techniques: radial velocity — techniques: photometric — stars: planetary systems — stars: individual (WASP-52)
Manganese hyperaccumulation from non-contaminated soil in Chengiopanax sciadophylloides Franch. et Sav. and its correlation with calcium accumulation

Abstract The objective of this study was to explore the ability of Chengiopanax sciadophylloides Franch. et Sav. to hyperaccumulate manganese (Mn). We were particularly interested in (1) Mn uptake ability relative to soil-Mn availability, (2) the potential use of this species in phytomining, and (3) potential key physiological factors associated with Mn hyperaccumulation ability. Among plants sampled from 17 locations in their native Japan provenance, the maximum foliar Mn concentration was 23,000 mg kg−1 dry weight (dw; mean: 11,000 mg kg−1). Soils from all sites examined contained low to normal Mn concentrations. There were no significant relationships detected between several soil factors and foliar Mn concentrations, although we found a strong positive correlation between foliar Mn and calcium (Ca) concentrations. Half of the foliar Mn was readily extractable with water, and almost all Mn was extractable with hydrochloric acid (HCl). Furthermore, a highly purified Mn compound was precipitated from leaf ash solutions when pH was adjusted to 8–10. We demonstrated that C. sciadophylloides has an extraordinary Mn-accumulating ability in non-contaminated soil and that Ca accumulation is correlated with Mn hyperaccumulation. We also showed that collecting Mn from C. sciadophylloides is easy and straightforward. We discuss the potential for using the plant in Mn phytomining.
Rapid responses in bovine milk fatty acid composition and phenol content to various tanniferous forages

Bovine milk and dairy products are widely consumed and routinely considered staples in many countries. Some dietary phenolic compounds are transferrable to bovine milk and may exert benefits for human health. Recognised benefits include protection against oxidative damage (Alenisan et al., 2017), prevention of chronic diseases (Vuazour et al., 2010) and inhibition of oxidative stress and cell destruction associated with degenerative diseases and with modern lifestyles (Willcox et al., 2004). Additionally, antioxidant effects of phenols help prevent oxidative scavenging of free radicals in dairy products, prolonging shelf life (Alenisan et al., 2017). Also, specific fatty acids (FA) have been clinically documented to have particular health promoting effects. These include α-linolenic acid (C18:3 n‒3; ALA) and rumenic acid (cis-9, trans-11 C18:2; RA) – one of the notably beneficial conjugated linoleic acid isomers caused by ruminal biohydrogenation (Białek et al., 2017). Benefits include decreased inflammation, prevention of a number of diseases, optimal cell signalling and increased immune function (German and Dillard, 2006; Białek et al., 2017). Other FA such as linoleic acid (C18:2 n‒6; LA), are explicit in modern diets and may cause adverse effects when consumed in disproportionate amounts (Calder, 2015). ABSTRACT. Milk and dairy products considerably contribute to the nutritional value of human diets. In order to benefit human nutrition bovine milk fatty acid composition and phenol content are effectively manipulated by the cow’s diet. However, response times taken for these alterations to occur have not been quantified. In the present study, fatty acid composition and phenol content of the milk were evaluated after three days of feeding six cows six different diets, supplemented with six different tanniferous plants (hazel, silver birch, blackcurrant, grape vine, wood avens and rosebay willow with total tannin concentrations of 26, 36, 42, 52, 55 and 79 g/kg dry matter, respectively). Lucerne was applied as the low-phenol control diet. Substantial changes in total phenols and fatty acids were found in milk samples after just three days. Proportions of cis-9 trans-11 C18:2 and trans-11 C18:1 declined by 29 and 68%, respectively, in comparison to milk from cows fed lucerne, indicating a definitive ruminal biohydrogenation response. However, there were no significant effects between test plants and lucerne when comparing C18:3 n-3 and C18:2 n-6 proportions in milk fat. So, it was demonstrated that phenols and certain individual fatty acids in bovine milk can be rapidly modified by adding specific tanniferous plants to the diet. Received: 4 August 2020 Revised: 20 October 2020 Accepted: 30 November 2020
Polymerization in Surfactant Liquid Crystalline Phases

We report the formation of cross-linked polysiloxane particles having rodlike and sheetlike morphologies by condensation of monomers in organized liquid crystalline mesophases of nonionic surfactants. The characteristic diffraction pattern obtained from the liquid crystalline surfactant assembly is preserved during polymer synthesis. The polymer colloids are rodlike when synthesized in a hexagonal mesophase and are sheetlike when synthesized in a lamellar mesophase. Interestingly, the size of the polymer particles is on the order of micrometers, viz. 3 orders of magnitude larger than the characteristic size of the surfactant mesophase. Thus, the polymers phase separate from the liquid crystalline phase during polymerization, and organize to resemble the mesophase geometry. The polymer particles are organized so as to minimize the elastic distortion of the surfactant mesophase after they phase separate. We speculate that the observed particle morphologies are formed due to the slow kinetics of polycondensa.
DeepCrossCancer Identiﬁes Similar Cancer Patients Across Cancers

The treatment decisions for a cancer patient are typically based on the patient’s diagnosed 5 cancer type. With the characterization of cancer tumors at the molecular level, there have been reports of patients that bear molecular similarities to other patients that are diagnosed with other cancer types. Motivated from these observations, we aim at discovering cross-cancer patients, which we deﬁne as patients whose tumors are more similar to patient tumors diagnosed with another cancer type. Our framework, DeepCrossCancer, identiﬁes a core set of cross-cancer patients that always co-cluster with the other patient 10 from another cancer type. The input to DeepCrossCancer is the transcriptomic proﬁles of the patient tumors, the age, and gender of the patient. To solve the clustering problem, we propose a semi-supervised deep learning-based clustering method in which the clustering task is supervised by cancer type labels and the survival times of the patients. Applying the method to patient data from nine different cancers, we discover 20 cross-cancer patients. By analyzing the predictive genes of the cross-cancer patients and other 15 genomic information available for the patient such as somatic mutations and copy number variations, we identify striking similarities across these patients validating their similarities. The detection of cross-cancer patients opens up possibilities for transferring clinical decisions across patients at a single patient level. DeepCrossCancer is available at https://github.com/Tastanlab/DeepCrossCancer .
Combining single- and repeated-visit occupancy models to make the best of monitoring surveys

A major challenge in applied ecology consists in integrating knowledge from different datasets to produce robust ecological indicators. To estimate species distribution, occupancy models are a flexible framework that can accommodate several datasets obtained from different sampling methods. However, repeating visits at sampling sites is a prerequisite for using standard occupancy models, which may limit their use. Under certain conditions, detection/non-detection data collected during single visit can be analysed with occupancy models. To date however, single-visit occupancy models have never been used to combine several different datasets. Here, we developed an approach that combines multi-method and single-visit occupancy models. As a case study, we estimated the distribution of Bottlenose dolphins (Tursiops truncatus) over the North-western Mediterranean Sea by combining 24,624 km of aerial surveys and 21,464 km of at-sea monitoring. We compared the outputs of single-vs. repeated-visit multi-method occupancy models, and that of single-method occupancy models. Multi-method models allowed a better sampling coverage in both coasts and high seas and provided a better precision for occupancy estimates than single-method occupancy models using aerial surveys or at-sea surveys in isolation. Overall, single- and repeated-visit multi-method occupancy models produced similar inference about the distribution of bottlenose dolphins. This suggests that single-visit occupancy models provide robust occupancy estimates, which open promising perspectives for the use of non-standardized datasets. Synthesis and applications: Single-visit multi-method occupancy models can help making the best out of ecological monitoring programs by optimizing cost effectiveness through the formal combination of datasets.
Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin with tubulin degradation effect

A novel binding site on α-tubulin shows promise as a target for a new generation of anticancer drugs. Microtubules, composed of αβ-tubulin heterodimers, have remained popular anticancer targets for decades. Six known binding sites on tubulin dimers have been identified thus far, with five sites on β-tubulin and only one site on α-tubulin, hinting that compounds binding to α-tubulin are less well characterized. Cevipabulin, a microtubule-active antitumor clinical candidate, is widely accepted as a microtubule-stabilizing agent by binding to the vinblastine site. Our x-ray crystallography study reveals that, in addition to binding to the vinblastine site, cevipabulin also binds to a new site on α-tubulin. We find that cevipabulin at this site pushes the αT5 loop outward, making the nonexchangeable GTP exchangeable, which reduces the stability of tubulin, leading to its destabilization and degradation. Our results confirm the existence of a new agent binding site on α-tubulin and shed light on the development of tubulin degraders as a new generation of antimicrotubule drugs targeting this novel site.
The potential of parrotfish faeces in replenishing reefs with coral-associated microbiome

Sparisoma viride is the most abundant parrotfish in the Caribbean and is considered as the most important excavator due to corallivore behaviour. Parrotfishes are a keystone group that favour the growth and resilience of coral reefs removing macroalgae and structuring the benthic communities. The microbial symbiotic communities are involved in multiple functions related to nutrition and immunity maintaining corals health. Because S. viride scrape coral tissues, the skeleton and the algae on coral, it could be important reservoirs or vectors of microorganism for the corals through the faeces dispersion, however, the role of parrotfishes as reservoirs are poorly studied. Establishing microbial communities present in parrotfish faeces will contribute to understand the ecological impact of parrotfishes in coral resilience. We investigated the composition of disseminated bacteria and the extent to which the cell integrity of dinoflagellate photosymbionts (Symbiodiniaceae) is maintained in the faeces and compare with sediments and water column controls. Then, we analysed diversity and structure of bacterial communities at family level and search similarities between faeces of the study and coral associated microbiome reported in the literature. Similar levels of structural integrity and photosynthetic health of Symbidiodinaceae cells were found in both faeces and reef sediments. Besides, the sediments microbiome echoes the parrotfish faecal microbiome by sharing high diversity and a similar bacterial community composition. Several bacterial families were present in parrotfish faeces and in coral microbiome reported in the literature highlighting the dispersal potential of parrotfishes replenishing coral reefs. Despite the sampling limitations, these findings uncover the potential role of the excavator parrotfish in enriching environmental reservoirs, especially reef sediments, with coral-associated bacteria and photosynthetic microalgae. Parrotfishes could reinforce the coral microbiome and facilitate coral symbiont acquisition, key features critical to maintaining the fitness of one of the most threatened ecosystems on Earth. This finding could be considered as a first step in uncovering a mechanism for reef-microbiome maintenance.
Cholesterol biosensor based on rf sputtered zinc oxide nanoporous thin film

Cholesterol oxidase (ChOx) has been immobilized onto zinc oxide (ZnO) nanoporous thin films grown on gold surface. A preferred c-axis oriented ZnO thin film with porous surface morphology has been fabricated by rf sputtering under high pressure. Optical studies and cyclic voltammetric measurements show that the ChOx∕ZnO∕Au bioelectrode is sensitive to the detection of cholesterol in 25–400mg∕dl range. A relatively low value of enzyme’s kinetic parameter (Michaelis-Menten constant) ∼2.1mM indicates enhanced enzyme affinity of ChOx to cholesterol. The observed results show promising application of nanoporous ZnO thin film for biosensing application without any functionalization.
Deep Ensemble Model for Classification of Novel Coronavirus in Chest X-Ray Images

The novel coronavirus, SARS-CoV-2, can be deadly to people, causing COVID-19. The ease of its propagation, coupled with its high capacity for illness and death in infected individuals, makes it a hazard to the community. Chest X-rays are one of the most common but most difficult to interpret radiographic examination for early diagnosis of coronavirus-related infections. They carry a considerable amount of anatomical and physiological information, but it is sometimes difficult even for the expert radiologist to derive the related information they contain. Automatic classification using deep learning models can help in better assessing these infections swiftly. Deep CNN models, namely, MobileNet, ResNet50, and InceptionV3, were applied with different variations, including training the model from the start, fine-tuning along with adjusting learned weights of all layers, and fine-tuning with learned weights along with augmentation. Fine-tuning with augmentation produced the best results in pretrained models. Out of these, two best-performing models (MobileNet and InceptionV3) selected for ensemble learning produced accuracy and FScore of 95.18% and 90.34%, and 95.75% and 91.47%, respectively. The proposed hybrid ensemble model generated with the merger of these deep models produced a classification accuracy and FScore of 96.49% and 92.97%. For test dataset, which was separately kept, the model generated accuracy and FScore of 94.19% and 88.64%. Automatic classification using deep ensemble learning can help radiologists in the correct identification of coronavirus-related infections in chest X-rays. Consequently, this swift and computer-aided diagnosis can help in saving precious human lives and minimizing the social and economic impact on society.
Modeling the Binding Mechanism of Remdesivir, Favilavir, and Ribavirin to SARS-CoV-2 RNA-Dependent RNA Polymerase

Recent efforts to repurpose drugs to combat COVID-19 have identified Remdesivir as a candidate. It acts on the RNA-dependent, RNA polymerase (RdRp) of the SARS-CoV-2 virus, a protein complex responsible for mediating replication of the virus’s genome. However, its exact action mechanism, and that of other nucleotide analogue inhibitors, is not known. In this study, we examine at the molecular level the interaction of this drug and that of similar nucleotide analogue inhibitors, ribavirin and favilavir, by relying on atomistic molecular simulations and advanced sampling. By analyzing the binding free energies of these different drugs, it is found that all of them bind strongly at the active site. Surprisingly, however, ribavirin and favilavir do not bind the nucleotide on the complementary strand as effectively and seem to act by a different mechanism than remdesivir. Remdesivir exhibits similar binding interactions to the natural base adenine. Moreover, by analyzing remdesivir at downstream positions of the RNA, we also find that, consistent with a “delayed” termination mechanism, additional nucleotides can be incorporated after remdesivir is added, and its highly polar 1′-cyano group induces a set of conformational changes that can affect the normal RdRp complex function. By analyzing the fluctuations of residues that are altered by remdesivir binding, and comparing them to those induced by lethal point mutations, we find a possible secondary mechanism in which remdesivir destabilizes the protein complex and its interactions with the RNA strands.
Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood–brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats’ plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15–30 nm), positive charge (5–9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2–6-fold and 1.3–7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.
PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid β-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdipoR2

Adiponectin plays multiple critical roles in modulating various physiological processes by binding to its receptors. The functions of PEG-BHD1028, a potent novel peptide agonist to AdipoRs, was evaluated using in vitro and in vivo models based on the reported action spectrum of adiponectin. To confirm the design concept of PEG-BHD1028, the binding sites and their affinities were analyzed using the SPR (Surface Plasmon Resonance) assay. The results revealed that PEG-BHD1028 was bound to two heterogeneous binding sites of AdipoR1 and AdipoR2 with a relatively high affinity. In C2C12 cells, PEG-BHD1028 significantly activated AMPK and subsequent pathways and enhanced fatty acid β-oxidation and mitochondrial biogenesis. Furthermore, it also facilitated glucose uptake by lowering insulin resistance in insulin-resistant C2C12 cells. PEG-BHD1028 significantly reduced the fasting plasma glucose level in db/db mice following a single s.c. injection of 50, 100, and 200 μg/Kg and glucose tolerance at a dose of 50 μg/Kg with significantly decreased insulin production. The animals received 5, 25, and 50 μg/Kg of PEG-BHD1028 for 21 days significantly lost their weight after 18 days in a range of 5–7%. These results imply the development of PEG-BHD1028 as a potential adiponectin replacement therapeutic agent.