Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving personalized prediction of cancer prognoses with clonal evolution models

Cancer occurs via an accumulation of somatic genomic alterations in a process of clonal evolution. There has been intensive study of potential causal mutations driving cancer development and progression. However, much recent evidence suggests that tumor evolution is normally driven by a variety of mechanisms of somatic hypermutability, known as mutator phenotypes, which act in different combinations or degrees in different cancers. Here we explore the question of how and to which degree different mutator phenotypes act in a cancer predict its future progression. We develop a computational paradigm using evolutionary tree inference (tumor phylogeny) algorithms to derive features quantifying single-tumor mutational preferences, followed by a machine learning frame-work to identify key features predictive of progression. We build phylogenies tracing the evolution of subclones of cells in tumor tissues using a variety of somatic genomic alterations, including single nucleotide variations, copy number alterations, and structural variations. We demonstrate that mutation preference features derived from the phylogenies are predictive of clinical outcomes of cancer progression – overall survival and disease-free survival – based on the analyses on breast invasive carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. We further show that mutational phenotypes have predictive power even after accounting for traditional clinical and driver-centric predictors of progression. These results confirm the power of mutational phenotypes as an independent class of predictive biomarkers and suggest a strategy for enhancing the predictive power of conventional clinical or driver-centric genomic features.
Palm (Arecaceae) Communities in the Brazilian Atlantic Forest: a Phytosociological Study

The aim of this study was to improve our understanding of the structure and composition of native palm communities in the Brazilian Atlantic Forest. This study was carried out at “Parque Estadual da Serra Furada” (PAESF), a protected area located in southern state of Santa Catarina. A palm community survey was carried out in Dense Ombrophilous Forest in five 20 m × 100 m sampling units, totaling 1ha. All palm individuals were measured, totaling 11,183 plants, belonging to four genera and five species: Bactris setosa Mart. , Euterpe edulis Mart. , Geonoma gamiova Barb.Rodr. , Geonoma schottiana Mart. and Syagrus romanzoffiana (Cham.) Glassman. Euterpe edulis was the most common species, contributing the most to all phytosociological parameters; however, relatively few large individuals were found. Our study demonstrates the limitations of traditional forest surveys that ignore smaller diameter palm species and highlights the importance of the role of this group in the floristic diversity, ecosystem function, environmental services and carbon dynamics.
Structural and molecular insight into the pH-induced low-permeability of the voltage-gated potassium channel Kv1.2 through dewetting of the water cavity

Understanding the gating mechanism of ion channel proteins is key to understanding the regulation of cell signaling through these channels. Channel opening and closing are regulated by diverse environmental factors that include temperature, electrical voltage across the channel, and proton concentration. Low permeability in voltage-gated potassium ion channels (Kv) is intimately correlated with the prolonged action potential duration observed in many acidosis diseases. The Kv channels consist of voltage-sensing domains (S1–S4 helices) and central pore domains (S5–S6 helices) that include a selectivity filter and water-filled cavity. The voltage-sensing domain is responsible for the voltage-gating of Kv channels. While the low permeability of Kv channels to potassium ion is highly correlated with the cellular proton concentration, it is unclear how an intracellular acidic condition drives their closure, which may indicate an additional pH-dependent gating mechanism of the Kv family. Here, we show that two residues E327 and H418 in the proximity of the water cavity of Kv1.2 play crucial roles as a pH switch. In addition, we present a structural and molecular concept of the pH-dependent gating of Kv1.2 in atomic detail, showing that the protonation of E327 and H418 disrupts the electrostatic balance around the S6 helices, which leads to a straightening transition in the shape of their axes and causes dewetting of the water-filled cavity and closure of the channel. Our work offers a conceptual advancement to the regulation of the pH-dependent gating of various voltage-gated ion channels and their related biological functions. Author Summary The acid sensing ion channels are a biological machinery for maintaining the cell functional under the acidic or basic cellular environment. Understanding the pH-dependent gating mechanism of such channels provides the structural insight to design the molecular strategy in regulating the acidosis. Here, we studied the voltage-gated potassium ion channel Kv1.2 which senses not only the electrical voltage across the channels but also the cellular acidity. We uncovered that two key residues E327 and H418 in the pore domain of Kv1.2 channel play a role as pH-switch in that their protonation control the gating of the pore in Kv1.2 channel. It offered a molecular insight how the acidity reduces the ion permeability in voltage-gated potassium channels.
The impact of variety of episodic contexts on the integration of novel words into semantic network

ABSTRACT The current study examined whether and how the variety of episodic contexts influences the integration of novel words into semantic network via thematic and taxonomic relations in a semantic priming task with event-related potential (ERP) technique. The novel words were acquired from discourses containing either single or multiple episodes. We found that corresponding concepts, targets thematic-related to learning episodes (Experiment 1) and taxonomic-related targets (Experiment 2) elicited semantic-priming N400s/LPCs effects compared to the unrelated targets in both conditions, whereas the targets thematic-related to unlearned episodes (Experiment 1) and feature-related targets (Experiment 2) elicited semantic-priming N400s/LPCs effects only in the multiple episodic condition. These results indicated that only the novel words learned from variable episodes could successfully prime thematically related words in unlearned episodes and feature-related words. Our findings suggest that the variety of episodic contexts contributes to establishing more stable and richer semantic representations of the novel words.
Fruit weight prediction models in Quercus based on some biometric parameters.

This study aimed at developing some mathematical models for the estimation of achene weight in oak based on fruit biometric parameters and at evaluating through principal component analysis (PCA) fruit size group affinity with biometric parameters. We studied fruits of two oak species, Quercus petraea and Quercus robur. At achene level, we determined such parameters as achene length (Al), middle achene diameter (MAD), achene basis diameter (Abd), achene tip diameter (Atd), and achene weight (Aw). At cupule level, we determined such parameters as cupule height (Ch), outer cupule diameter (Ocd), inner cupule diameter (Icd), cupule all thickness (Cwt), and cupule weight (Cw). We also calculated fruit size index (FSI). Regression analysis was used to find out equations as achene weight prediction models based on studied biometric parameters. The working process followed a logical pattern suggested a general working model. We obtained a linear equation for the estimation of achene weight based on Atd in Q. robur; all other achene weight prediction equations were of the second-degree polynomial type in both Q. robur and Q. petraea. The level of statistic safety in the estimation of fruit size ranged between R = 0.720 and R = 0.962 in Q. petraea and R = 0.376 to R = 0.928 in Q. robur, respectively. Based on biometric parameters, the fruits of the two species studied were grouped into seven size classes. The PCA analysis explained the variance based on PC1 as 92.573% and on PC2 as 6.2315% in Q. petraea and as 82.041% based on PC1 and as 16.032% based on PC2 in Q. robur. For size classes Qp1-Qp3 in Q. petraea and Qr1 in Q. robur, the least variation of any size parameter leads to achene size, while size classes Qp4 and Qr7, diameter variation significantly determines achene weight increase. In size classes Qp5-Qp7 and Qr2-Qr6, fruit length variation induces a significant fruit weight increase.
The effects of different fishmeal level diets with or without phytase supplementation on growth performance, body composition, digestibility, immunological and biochemical parameters of juvenile hybrid sturgeon (
 Acipenser baeri
 Brandt ♀ × 
 A. schrenckii
 Brandt ♂)

A 12‐week growth trial was conducted to evaluate the effect of low fishmeal and phytase replacing inorganic phosphorus on juvenile hybrid sturgeon (Acipenser baeri Brandt ♀ × A. schrenckii Brandt ♂). Four experimental diets were designed as FM100p, FM100, FM250p and FM250, which represented 10% and 25% fishmeal with or without phytase, respectively. The results showed that although growth parameters had no significant difference in all treatments, low fishmeal obviously decreased the culture cost of hybrid sturgeon. Lipid content of body composition was obviously increased in low fishmeal treatments (p < .05). The interaction of low fishmeal and phytase significantly enhanced apparent digestibility coefficients of crude protein (p < .05). Two‐way ANOVA analysis showed that input and output of phosphorus were significantly affected by fishmeal level, phytase and interaction of both factors (p < .05). For the immunological and hepatic function parameters, fishmeal level and phytase had significant effects on the activities of lysozyme, myeloperoxidase, malondialdehyde, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase (p < .05). The present study potentially justifies that a diet containing 10% fishmeal can be used for hybrid sturgeon. Moreover, replacement of monocalcium phosphate by phytase not only has no adverse effect on the growth of hybrid sturgeon, but also reduces phosphorus emission and protects aquaculture environment.
Adiponectin and related C1q/TNF-related proteins bind selectively to anionic phospholipids and sphingolipids

Significance Adiponectin, a member of the CTRP family of secreted proteins produced by adipose tissue, is thought to function as an endocrine hormone. An unusual feature of adiponectin is that it is present in high concentrations in circulation and thus may have noncanonical endocrine functions. Here we show that adiponectin as well as several other CTRPs and C1q family proteins bind anionic phospholipids, suggesting that their mode of action is opsonization of cells with specific plasma membrane phospholipid compositions. These findings suggest a new perspective on CTRP family function. Adiponectin (Acrp30) is an adipokine associated with protection from cardiovascular disease, insulin resistance, and inflammation. Although its effects are conventionally attributed to binding Adipor1/2 and T-cadherin, its abundance in circulation, role in ceramide metabolism, and homology to C1q suggest an overlooked role as a lipid-binding protein, possibly generalizable to other C1q/TNF-related proteins (CTRPs) and C1q family members. To investigate this, adiponectin, representative family members, and variants were expressed in Expi293 cells and tested for binding to lipids in liposomes using density centrifugation. Binding to physiological lipids were also analyzed using gradient ultracentrifugation, liquid chromatography-mass spectrometry, and shotgun lipidomics. Interestingly, adiponectin selectively bound several anionic phospholipids and sphingolipids, including phosphatidylserine, ceramide-1-phosphate, glucosylceramide, and sulfatide, via the C1q domain in an oligomerization-dependent fashion. Binding to lipids was observed in liposomes, low-density lipoproteins, cell membranes, and plasma. Other CTRPs and C1q family members (Cbln1, CTRP1, CTRP5, and CTRP13) also bound similar lipids. These findings suggest that adiponectin and CTRPs function not only as hormones, but also as lipid opsonins, as may other C1q family proteins.
Unveiling The Worldwide UV-Metaresistome: Metagenomic Analysis of Microbiomes Exposed to Different UV-B Regimes

During evolution, microorganisms exposed to high UV doses have developed a complex battery of physiological and molecular mechanisms to cope with UV stress and damage recently called as the UV-resistome. As a precedent, the UV-resistome was analyzed at the genomic and proteomic level in poly-extremophiles bacteria isolated from High-Altitude Andean Lakes. In this work, we go further by exploring the impact of UV-B radiation on microbiomes in different geographic regions across the globe. The abundance of photoprotection and DNA repair pathways in each microbiome was use to configure the world-wide UV-metaresistome. Metagenomics combined with georeferenced climate data indicated that the higher the UV-B dose suffered by the microbiome the higher the abundance and diversity of the UV-metaresistome genes. In contrast, a substantial depletion on microbial diversity was observed in higher irradiated environments. A positive correlation between CPF abundance and radiation intensity/photoperiod was detected. CPF genes were investigated in the global dataset, being present in most abundant organisms of communities, which are facing significant exposure to sunlight. Three extra clades not identified so far were reported together with a widespread occurrence of cryptochromes-related genes.
Examining Prospective Teachersr Mathematical Communication Skills in Statistics

The mathematical communication skill is an important thing to support the teachers’ role as facilitators in helping students to master 21st-century skills. The efforts to improve the skill must be well prepared since they are still as prospective teachers. The communication skill involves some aspects. Therefore, to improve the skill of prospective teachers, it must be identified what aspects need to be improved. This study aims to describe students' mathematical communication skills in Statistics. The mathematical communication skills in this study refer to the students' skills to 1) present the data or information into table or diagram correctly, 2) use mathematical terms, symbols/notations, charts, diagram, illustrations or formulas correctly, 3) solve the problems correctly and systematically, and 4) provide the correct reasons or explanations on the solution they got. The participants of this study are 35 students of Mathematics Education Department, Yogyakarta State University who enroll in Statistics course during September – December 2016. The data of this study are collected from the midterm exam and final exam of the semester. The research shows: 1) the students' mathematical communication skills in Statistics are at the medium level; 2) the ability to use correct mathematical terms, symbols/notations, charts, diagram, illustrations or formulas seems to be the lowest one among the four skills measured in this study; and 3) most students have difficulties in solving problems related to probability. The results indicate that the students' mathematical communication skills are serious issues that need to be addressed. Keywords— prospective math teachers, communication skills,
Relações filogenéticas do "clado das aves aquáticas", com ênfase nas "aves totipalmadas" (AVES: NATATORES AUT AEQUORNITHES)

18 Introduction.19 Material and Methods.24 Taxon sampling and survey.24 Cladistic analysis.27 Results.30 Description of characters.30 Parsimony analysis.56 Discussion.87 The ‘waterbird assemblage’: Natatores (sensu Livezey and Zusi 2007) or Aequornithes (sensu G. Mayr 2010). 87 The ‘pelagic assemblage’: Procellariimorphae (sensu Livezey and Zusi 2007) or Austrodyptornithes (sensu Yuri et al. 2013). 90 vii Podicipedidae and Phoenicopteridae.91 The wading birds and allies: storks, ibises, shoebill, and hamerkop.93 Phaethontidae.95 The ‘totipalmate birds’: Steganopodes and Suliformes.96 Concluding remarks.101 Acknowledgment.105 Resumo.105 References.106 Considerações finais.135 Referências. 138 Anexo 1.140 Anexo 2.144
SGK1 Attenuates Oxidative Stress-Induced Renal Tubular Epithelial Cell Injury by Regulating Mitochondrial Function

Mitochondrial dysfunction has been implicated in the early stages or progression of many renal diseases. Improving mitochondrial function and homeostasis has the potential to protect renal function. Serum- and glucocorticoid-induced kinase 1 (SGK1) is known to regulate various cellular processes, including cell survival. In this study, we intend to demonstrate the effect and molecular mechanisms of SGK1 in renal tubular cells upon oxidative stress injury and to determine whether regulation of mitochondrial function is implicated in this process. HK-2 cells were exposed to H2O2, and cell viability and apoptosis were dynamically detected by the CCK-8 assay and annexin-V/PI staining. The concentrations of cellular reactive oxygen species (ROS) and adenosine triphosphate (ATP) and the expression of the SGK1/GSK3β/PGC-1α signaling pathway were analyzed by flow cytometry or western blot. In addition, shRNA targeting SGK1 and SB216763 were added into the culture medium before H2O2 exposure to downregulate SGK1 and GSK3β, respectively. Cell viability and mitochondrial functions, including mitochondrial membrane potential (Δψm), Cytochrome C release, mtDNA copy number, and mitochondrial biogenesis, were examined. Protein levels and SGK1 activation were significantly stimulated by H2O2 exposure. HK-2 cells with SGK1 inhibition were much more sensitive to H2O2-induced oxidative stress injury than control group cells, as they exhibited increased apoptotic cell death and mitochondrial dysfunction involving the deterioration of cellular ATP production, ROS accumulation, mitochondrial membrane potential reduction, and release of Cytochrome C into the cytoplasm. Studies on SGK1 knockdown also indicated that SGK1 is required for the induction of proteins associated with mitochondrial biogenesis, including PGC-1α, NRF-1, and TFAM. Moreover, the deleterious effects of SGK1 suppression on cell apoptosis and mitochondrial function, including mitochondrial biogenesis, were related to the phosphorylation of GSK3β and partially reversed by SB216763 treatment. H2O2 leads to SGK1 overexpression in HK-2 cells, which protects human renal tubule cells from oxidative stress injury by improving mitochondrial function and inactivating GSK3β.
High speed multi-plane super-resolution structured illumination microscopy of living cells using an image-splitting prism

Super-resolution structured illumination microscopy (SR-SIM) can be conducted at video-rate acquisition speeds when combined with high-speed spatial light modulators and sCMOS cameras, rendering it particularly suitable for live cell imaging. If, however, three-dimensional (3D) information is desired, the sequential acquisition of vertical image stacks employed by current setups significantly slows down the acquisition process. In this work we present a multi-plane approach to SR-SIM that overcomes this slowdown via the simultaneous acquisition of multiple object planes, employing a recently introduced multi-plane image splitting prism combined with high-speed SR-SIM illumination. This strategy requires only the introduction of a single optical element and the addition of a second camera to acquire a laterally super-resolved three-dimensional image stack. We demonstrate the performance of multi-plane SR-SIM by applying this instrument to the dynamics of live mitochondrial network.
Tumor segmentation in fluorescent TNBC immunohistochemicalmultiplex images using deep learning

Breast cancer is among females the most frequently diagnosed cancer and the leading cause of cancer death. A subtype of breast cancer called triple negative breast cancer( TNBC) is known to be more aggressive, generally occur at younger age and even very small (<1cm) node-negative TNBC show recurrence within 5 years in 15% of cases if left untreated. For TNBC, several studies showed that the number of tumor-infiltraing lymphocytes (TIL) in hematoxylin and eosin (H&E) stained sections strongly correlates with disease free survival. Subtyping of lymphocytes could strongly help finding more powerful prognostic markers. However, standard H&E stained sections do not permit specific subtyping of lymphocytes and immunohistochemistry(IHC) allows very limited subtyping. New scanning systems, staining protocols and medical imaging analysis algorithms allows to gather spatial information of lymphocyte subtypes and to determine subtype positioning of lymfocytes in peri- or intertumoral regions. A first step towards this goal is to detect tumor regions to determine whether a lymfocyte is positioned perior intertumoral. Therefore, the aim of this thesis was to investigate the performance of convolutional networks to segment tumor regions in TNBC whole-slide multiplex IHC slides. Multiple experiments were conducted to investigate and maximize the performance. The data used for training was investigated and it was concluded that training a FCNN (fully convolutional neural network) using the DAPI and CK8-18 data channels together with a resolution of 0.96 �m�pi x and patch size of 128x128 resulted in the highest segmentation performance. Enriching the dataset with hard mining had no positive effects on the performance. Using the different architecture U-net resulted in similar results compared to that of a FCNN. A ’model averaging ensemble’ resulted in the highest segmentation performance with a F1 score of 0.83. It can be concluded that fully convolutional networks were able to segment tumor regions in triple negative and holds true for both FCNN and U-net architectures and can be used for the overarching aim of this research, namely extracting powerful prognostic information from intra- and peritumoral lymphocytes.
Complete chloroplast genome of a Chinese endemic species Corydalis trisecta Franch. (Papaveraceae)

Abstract Corydalis trisecta Franch. is an endemic plant found in China. In this study, we presented the first complete chloroplast genome of C. trisecta, which was assembled and characterized based on Illumina pair-end sequencing data. The complete chloroplast genome was 161,410 bp in length, with a GC content of 41.4% in total. Its structure contained a large single copy (LSC) region of 89,127 bp and a small single copy (SSC) region of 16,993 bp, which were separated by a pair of extremely inverted repeats (IRs) of 27,645 bp each, with GC content 39.8, 87.2, and 45.2%, respectively. The phylogenetic analysis indicated that C. triscta was sister to Lamprocapons spectabilis in Papaveraceae.