Miracle-dz/UniFAR-FTUs huggingface dataset:
Learning methods for melanoma recognition

Melanoma is the most deadly skin cancer. Early diagnosis is a challenge for clinicians. Current algorithms for skin lesions' classification focus mostly on segmentation and feature extraction. This article instead puts the emphasis on the learning process, testing the recognition performance of three different classifiers: support vector machine (SVM), artificial neural network and k‐nearest neighbor. Extensive experiments were run on a database of more than 5000 dermoscopy images. The obtained results show that the SVM approach outperforms the other methods reaching an average recognition rate of 82.5% comparable with those obtained by skilled clinicians. If confirmed, our data suggest that this method may improve classification results of a computer‐assisted diagnosis of melanoma. © 2010 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 20, 316–322, 2010
NADPH Oxidase NOX4 Mediates Stellate Cell Activation and Hepatocyte Cell Death during Liver Fibrosis Development

A role for the NADPH oxidases NOX1 and NOX2 in liver fibrosis has been proposed, but the implication of NOX4 is poorly understood yet. The aim of this work was to study the functional role of NOX4 in different cell populations implicated in liver fibrosis: hepatic stellate cells (HSC), myofibroblats (MFBs) and hepatocytes. Two different mice models that develop spontaneous fibrosis (Mdr2−/−/p19ARF−/−, Stat3Δhc/Mdr2−/−) and a model of experimental induced fibrosis (CCl4) were used. In addition, gene expression in biopsies from chronic hepatitis C virus (HCV) patients or non-fibrotic liver samples was analyzed. Results have indicated that NOX4 expression was increased in the livers of all animal models, concomitantly with fibrosis development and TGF-β pathway activation. In vitro TGF-β-treated HSC increased NOX4 expression correlating with transdifferentiation to MFBs. Knockdown experiments revealed that NOX4 downstream TGF-β is necessary for HSC activation as well as for the maintenance of the MFB phenotype. NOX4 was not necessary for TGF-β-induced epithelial-mesenchymal transition (EMT), but was required for TGF-β-induced apoptosis in hepatocytes. Finally, NOX4 expression was elevated in patients with hepatitis C virus (HCV)-derived fibrosis, increasing along the fibrosis degree. In summary, fibrosis progression both in vitro and in vivo (animal models and patients) is accompanied by increased NOX4 expression, which mediates acquisition and maintenance of the MFB phenotype, as well as TGF-β-induced death of hepatocytes.
Modeling the motion of a hot, turbulent gas

This paper describes a new animation technique for modeling the turbulent rotational motion that occurs when a hot gas interacts with solid objects and the surrounding medium. The method is especially useful for scenes involving swirling steam, rolling or billowing smoke, and gusting wind. It can also model gas motion due to fans and heat convection. The method combines specialized forms of the equations of motion of a hot gas with an efficient method for solving volumetric differential equations at low resolutions. Particular emphasis is given to issues of computational efficiency and ease-of-use of the method by an animator. We present the details of our model, together with examples illustrating its use.
Chromoblastomycosis Caused by Fonsecaea pedrosoi

We report herein a case of chromoblastomycosis caused by Fonsecaea (F.) pedrosoi in a 39-year-old male, who showed multiple, asymptomatic, scaly erythematous plaques on the left shin for 12 months. Histopathologically, chronic granulomatous inflammation and either sclerotic or muriform cells were observed. The fungal culture produced typical black colonies of F. pedrosoi. The DNA sequence of the internal transcribed spacer (ITS) region of the clinical sample was 100% match to that of F. pedrosoi IFM 47061 (GenBank accession number AB240943). The patient was treated with 200 mg of itraconazole daily, for 3 months. Skin lesions were improved. In Korea, only 9 cases of chromoblastomycosis, including this case, have been reported until now. The etiologic agent was F. pedrosoi in the majority of cases (6/9;67%). The incidence of chromoblastomycosis was slightly higher in female, and the upper limbs were more affected than the lower limbs in patients.
Sex-specific associations between screen time and lipoprotein subfractions.

BACKGROUND Time spent in sedentary activities (such as watching television) has previously been associated with several risk factors for cardiovascular disease (CVD) such as increased low-density lipoprotein cholesterol (LDL-C). Little is known about associations with lipoprotein subfractions. Using television and computer screen time in hours per day as a measure of sedentary time, we examined the association of screen time with lipoprotein subfractions. METHODS Data were used from men and women forming the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study population. Mixed linear models specified lipoprotein measures as the outcome, and screen time as the predictor for fourteen lipoprotein subfraction measures, and included age, smoking status, pedigree, and fat, carbohydrate daily alcohol and energy intake as covariates. Analyses were run separately for men (n = 623) and women (n = 671). A step-down Bonferroni correction was applied to results. The analysis was repeated for significant results (p < .05), additionally controlling for body mass index (BMI) and moderate and vigorous physical activity. RESULTS Linear models indicated that screen time was associated with five lipoprotein parameters in women: the concentration of large VLDL particles (p = .01), LDL particle number (p = .01), concentration of small LDL particles (p = .04), the concentration of large HDL particles (p = .04), and HDL diameter (p = .02). All associations remained after controlling for moderate or vigorous physical activity and BMI. CONCLUSIONS We show that sedentary time is associated with lipoprotein measures, markers of cardiometabolic disease, independently of physical activity and BMI, in women but not men.
Regulation of Coronary Blood Flow during Individual Diastoles in the Dog

Data derived from instantaneous diastolic coronary artery pressure-flow relationships in the dog have suggested that diastolic coronary vascular resistance may be constant and coronary vasoregulation unimportant during individual diastoles. We tested these hypotheses by using constant pressure perfusion to determine the pattern of coronary blood flow during single diastoles under steady state conditions and when coronary vascular resistance was actively changing. In 20 closed-chest, anesthetized dogs, long diastoles of constant cycle length were obtained by vagal nerve stimulation during simultaneous right ventricular pacing. Cholinergic vasodilation was prevented with intracoronary atropine. There were no differences between early and late diastolic flows (P > 0.8) for cycle lengths of 0.5 to 5 seconds and flows ranging from 40 to 125 ml/min per 100 g. When coronary resistance was actively altered with adenosine, brief coronary inflow occlusions, or abrupt changes in heart rate, diastolic flow varied continuously during each beat (13.0 ± 1.1 (SD) to 33.4 ± 5.4 ml/min per 100 g per sec). In 10 additional animals, instantaneous diastolic coronary artery pressure-flow relations obtained with initial diastolic resistance constant were compared with those obtained when resistance was actively changing. Despite a changing diastolic resistance, the resulting pressure-flow curves remained linear. Values for slope and zero flow pressure were increased during vasoconstriction (P < 0.001) and decreased during vasodilation (P < 0.001). We conclude that, during constant pressure perfusion, coronary vascular resistance is constant during diastole, and when coronary resistance is actively changing, regulation of coronary blood flow occurs continuously during individual diastoles. Furthermore, instantaneous diastolic coronary artery pressure-flow relations may be linear despite changes in coronary vasomotor tone, and thus cannot be used to estimate resistance or back pressure in such cases.
The Zirconia Ceramic: Strengths and Weaknesses

Metal ceramic restorations were considered the gold standard as reliable materials. Increasing demand for esthetics supported the commercialization of new metal free restorations. A growing demand is rising for zirconia prostheses. Peer-reviewed articles published till July 2013 were identified through a Medline (Pubmed and Elsevier). Emphasizing was made on zirconia properties and applications. Zirconia materials are able to withstand posterior physiologic loads. Although zirconia cores are considered as reliable materials, these restorations are not problem free.
Age and Sex Differences in the Treatment of Patients with Initial Acute Myocardial Infarction: A Community-Wide Perspective

Purpose: The goal of this observational study was to examine overall and age-specific differences between women and men in the use of five beneficial cardiac medications in patients hospitalized with acute myocardial infarction (AMI) from a community-wide perspective. The objectives of our study were to determine whether women are treated differently than men and whether age acts as a potential effect modifier of any observed associations. Subjects: A total of 2,461 women and 3,454 men with validated AMI comprised the study sample. Methods: Our study was an observational investigation of metropolitan Worcester (Mass., USA) residents who were hospitalized with initial AMI in all area hospitals during 12 1-year periods between 1975 and 1999. Four age-specific subgroups (<55, 55–64, 65–74 and ≧75 years) were studied. Results: Differences in the use of angiotensin-converting enzyme (ACE) inhibitors, aspirin, β-blockers, lipid-lowering medications and thrombolytic agents during hospitalization for AMI were examined. The results of a multivariable regression analysis indicated that women were significantly less likely to receive aspirin and ACE inhibitors as compared to men. There were no significant gender differences in the prescribing of the other cardiac medications. Increasing age in both women and men was associated with a reduced likelihood of receiving effective cardiac therapies including aspirin, β-blockers, lipid-lowering therapy and thrombolytic agents. Conclusions: These data suggest that the reasons for the marked age-related differences, in men and women, in the use of cardiac medications be more systematically explored. Previously observed gender differences in the management of patients with AMI essentially no longer exist.
Phosphorylation of Threonine Residue 276 Is Required for Acute Regulation of Serotonin Transporter by Cyclic GMP*

Cellular protein kinases, phosphatases, and other serotonin transporter (SERT) interacting proteins participate in several signaling mechanisms regulating SERT activity. The molecular mechanisms of protein kinase G (PKG)-mediated SERT regulation and the site of transporter phosphorylation were investigated. Treatment of rat midbrain synaptosomes with 8-bromo-cGMP increased SERT activity, and the increase was selectively blocked by PKG inhibitors. The Vmax value for serotonin (5-HT) transport increased following cGMP treatment. However, surface biotinylation studies showed no change in SERT surface abundance following PKG activation. 32P metabolic labeling experiments showed increased SERT phosphorylation in the presence of cGMP that was abolished by selectively inhibiting PKG. Phosphoamino acid analysis revealed that cGMP-stimulated native SERT phosphorylation occurred only on threonine residues. When added to CHO-1 cells expressing SERT, 8-bromo-cGMP stimulated 5-HT transport and SERT phosphorylation. Mutation of SERT threonine 276 to alanine completely abolished cGMP-mediated stimulation of 5-HT transport and SERT phosphorylation. Although the T276A mutation had no significant effect on 5-HT transport or SERT protein expression, mutation to aspartate (T276D) increased the level of 5-HT uptake to that of cGMP-stimulated 5-HT uptake in wild-type SERT-expressing cells and was no longer sensitive to cGMP. These findings provide the first identification of a phosphorylation site in SERT and demonstrate that phosphorylation of Thr-276 is required for cGMP-mediated SERT regulation. They also constitute the first evidence that in the central nervous system PKG activation stimulates endogenous SERT activity by a trafficking-independent mechanism.
A Stem-Cell Based Bioassay to Critically Assess the Pathology of Dysfunctional Neuromuscular Junctions

Pluripotent stem cells can be directed to differentiate into motor neurons and assessed for functionality in vitro. An emerging application of this technique is to model genetically inherited diseases in differentiated motor neurons and to screen for new therapeutic targets. The neuromuscular junction (NMJ) is essential to the functionality of motor neurons and its dysfunction is a primary hallmark of motor neuron disease. However, mature NMJs that possess the functional and morphological characteristics of those formed in vivo have so far not been obtained in vitro. Here we describe the generation and analysis of mature NMJs formed between embryonic stem cell-derived motor neurons (ESCMNs) and primary myotubes. We compared the formation and maturation of NMJs generated by wild-type (NCAM+/+) ESCMNs to those generated by neural cell adhesion molecule null (NCAM-/-) ESCMNs in order to definitively test the sensitivity of this assay to identify synaptic pathology. We find that co-cultures using NCAM-/- ESCMNs replicate key in vivo NCAM-/- phenotypes and reveal that NCAM influences neuromuscular synaptogenesis by controlling the mode of synaptic vesicle endocytosis. Further, we could improve synapse formation and function in NCAM-/- co-cultures by chronic treatment with nifedipine, which blocks an immature synaptic vesicle recycling pathway. Together, our results demonstrate that this ESCMN/myofiber co-culture system is a highly sensitive bioassay for examining molecules postulated to regulate synaptic function and for screening therapeutics that will improve the function of compromised NMJs.
Analysis of Codon Usage Patterns in Herbaceous Peony (Paeonia lactiflora Pall.) Based on Transcriptome Data

Codon usage bias, which exists in many genomes, is mainly determined by mutation and selection. To elucidate the genetic features and evolutionary history of herbaceous peony (Paeonia lactiflora), a well-known symbol of prosperity in China, we examined synonymous codon usage in 24,216 reconstructed genes from the P. lactiflora transcriptome. The mean GC content was 44.4%, indicating that the nucleotide content of P. lactiflora genes is slightly AT rich and GC poor. The P. lactiflora genome has a wide range of GC3 (GC content at the third synonymous codon position) distribution, with a significant correlation between GC12 and GC3. ENC (effective number of codons) analysis suggested that mutational bias played a major role in shaping codon usage. Parity Rule 2 (PR2) analysis revealed that GC and AU were not used proportionally. We identified 22 “optimal codons”, most ending with an A or U. Our results suggested that nucleotide composition mutation bias and translational selection were the main driving factors of codon usage bias in P. lactiflora. These results lay the foundation for exploring the evolutionary mechanisms and heterologous expression of functionally-important proteins in P. lactiflora.
Quantum Kolmogorov complexity based on classical descriptions

We develop a theory of the algorithmic information in bits contained in an individual pure quantum state. This extends classical Kolmogorov complexity to the quantum domain retaining classical descriptions. Quantum Kolmogorov complexity coincides with the classical Kolmogorov complexity on the classical domain. Quantum Kolmogorov complexity is upper-bounded and can be effectively approximated from above under certain conditions. With high probability, a quantum object is incompressible. Upper and lower bounds of the quantum complexity of multiple copies of individual pure quantum states are derived and may shed some light on the no-cloning properties of quantum states. In the quantum situation complexity is not subadditive. We discuss some relations with "no-cloning" and "approximate cloning" properties.
AβPP processing results in greater toxicity per amount of Aβ1-42 than individually expressed and secreted Aβ1-42 in Drosophila melanogaster

ABSTRACT The aggregation of the amyloid-β (Aβ) peptide into fibrillar deposits has long been considered the key neuropathological hallmark of Alzheimer's disease (AD). Aβ peptides are generated from proteolytic processing of the transmembrane Aβ precursor protein (AβPP) via sequential proteolysis through the β-secretase activity of β-site AβPP-cleaving enzyme (BACE1) and by the intramembranous enzyme γ-secretase. For over a decade, Drosophila melanogaster has been used as a model organism to study AD, and two different approaches have been developed to investigate the toxicity caused by AD-associated gene products in vivo. In one model, the Aβ peptide is directly over-expressed fused to a signal peptide, allowing secretion of the peptide into the extracellular space. In the other model, human AβPP is co-expressed with human BACE1, resulting in production of the Aβ peptide through the processing of AβPP by BACE1 and by endogenous fly γ-secretase. Here, we performed a parallel study of flies that expressed the Aβ1-42 peptide alone or that co-expressed AβPP and BACE1. Toxic effects (assessed by eye phenotype, longevity and locomotor assays) and levels of the Aβ1-42, Aβ1-40 and Aβ1-38 peptides were examined. Our data reveal that the toxic effect per amount of detected Aβ1-42 peptide was higher in the flies co-expressing AβPP and BACE1 than in the Aβ1-42-expressing flies, and that the co-existence of Aβ1-42 and Aβ1-40 in the flies co-expressing AβPP and BACE1 could be of significant importance to the neurotoxic effect detected in these flies. Thus, the toxicity detected in these two fly models seems to have different modes of action and is highly dependent on how and where the peptide is generated rather than on the actual level of the Aβ1-42 peptide in the flies. This is important knowledge that needs to be taken into consideration when using Drosophila models to investigate disease mechanisms or therapeutic strategies in AD research. Summary: In Drosophila, the proteotoxic effect of Aβ1-42 is highly dependent on how and where the peptide is generated, rather than on the peptide level in the flies, with implications for Alzheimer's disease research.
3-way Networks: Application of Hypergraphs for Modelling Increased Complexity in Comparative Genomics

We present and develop the theory of 3-way networks, a type of hypergraph in which each edge models relationships between triplets of objects as opposed to pairs of objects as done by standard network models. We explore approaches of how to prune these 3-way networks, illustrate their utility in comparative genomics and demonstrate how they find relationships which would be missed by standard 2-way network models using a phylogenomic dataset of 211 bacterial genomes.
The Nuclear Factor κB Family Member RelB Facilitates Apoptosis of Renal Epithelial Cells Caused by Cisplatin/Tumor Necrosis Factor α Synergy by Suppressing an Epithelial to Mesenchymal Transition–Like Phenotypic Switch

Cis-diamminedichloroplatinum(II) (cisplatin)–induced renal proximal tubular apoptosis is known to be preceded by actin cytoskeleton reorganization, in conjunction with disruption of cell-matrix and cell-cell adhesion. In the present study, we show that the proinflammatory cytokine tumor necrosis factor α (TNF-α) aggravated these cisplatin-induced F-actin and cell adhesion changes, which was associated with enhanced cisplatin-induced apoptosis of immortalized proximal tubular epithelial cells. TNF-α–induced RelB expression and lentiviral small hairpin RNA (shRNA)-mediated knockdown of RelB, but not other nuclear factor κB members, abrogated the synergistic apoptosis observed with cisplatin/TNF-α treatment to the level of cisplatin-induced apoptosis. This protective effect was associated with increased stress fiber formation, cell-matrix, and cell-cell adhesion in the shRNARelB (shRelB) cells during cisplatin/TNF-α treatment, mimicking an epithelial-to-mesenchymal phenotypic switch. Indeed, gene array analysis revealed that knockdown of RelB was associated with upregulation of several actin regulatory genes, including Snai2 and the Rho GTPase proteins Rhophilin and Rho guanine nucleotide exchange factor 3 (ARHGEF3). Pharmacological inhibition of Rho kinase signaling re-established the synergistic apoptosis induced by combined cisplatin/TNF-α treatment of shRelB cells. In conclusion, our study shows for the first time that RelB is required for the cisplatin/TNF-α–induced cytoskeletal reorganization and apoptosis in renal cells by controlling a Rho kinase–dependent signaling network.
Know Thyself: NK-Cell Inhibitory Receptors Prompt Self-Tolerance, Education, and Viral Control

Natural killer (NK) cells provide essential protection against viral infections. One of the defining features of this lymphocyte population is the expression of a wide array of variable cell surface stimulatory and inhibitory NK receptors (sNKR and iNKR, respectively). The iNKR are particularly important in terms of NK-cell education. As receptors specific for MHC class I (MHC I) molecules, they are responsible for self-tolerance and adjusting NK-cell reactivity based on the expression level of self-MHC I. The end result of this education is twofold: (1) inhibitory signaling tunes the functional capacity of the NK cell, endowing greater potency with greater education, and (2) education on self allows the NK cell to detect aberrations in MHC I expression, a common occurrence during many viral infections. Many studies have indicated an important role for iNKR and MHC I in disease, making these receptors attractive targets for manipulating NK-cell reactivity in the clinic. A greater understanding of iNKR and their ability to regulate NK cells will provide a basis for future attempts at translating their potential utility into benefits for human health.
Dependently typed programming in Agda

Dependently typed languages have for a long time been used to describe proofs about programs. Traditionally, dependent types are used mostly for stating and proving the properties of the programs and not in defining the programs themselves. An impressive example is the certified compiler by Leroy (2006) implemented and proved correct in Coq (Bertot and Castéran 2004). Recently there has been an increased interest in dependently typed programming, where the aim is to write programs that use the dependent type system to a much higher degree. In this way a lot of the properties that were previously proved separately can be integrated in the type of the program, in many cases adding little or no complexity to the definition of the program. New languages, such as Epigram (McBride and McKinna 2004), are being designed, and existing languages are being extended with new features to accomodate these ideas, for instance the work on dependently typed programming in Coq by Sozeau (2007). This talk gives an overview of the Agda programming language (Norell 2007), whose main focus is on dependently typed programming. Agda provides a rich set of inductive types with a powerful mechanism for pattern matching, allowing dependently typed programs to be written with minimal fuss. To read about programming in Agda, see the lecture notes from the Advanced Functional Programming summer school (Norell 2008) and the work by Oury and Swierstra (2008). In the talk a number of examples of interesting dependently typed programs chosen from the domain of programming language implementation are presented as they are implemented in Agda.