Miracle-dz/UniFAR-FTUs huggingface dataset:
Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas

Our analyses of cathepsin H activity levels and protein forms in human colorectal cancers compared to matched control mucosa support the concept that altered proteinase expression patterns may reflect both cancer stage and site. Cathepsin H-specific activity was significantly increased in colorectal cancers compared to control mucosa (P = 0.003; n = 77). Highest specific activities and cancer/normal ratios (C/N) for activity were measured in Dukes' B and C stage carcinomas, cancers involved in local spread and invasion to lymph nodes. In contrast, cathepsin B and L activities analysed in the same paired extracts had been shown to be most frequently elevated in earlier stage carcinomas (Dukes' A and B), confirming that cathepsin H demonstrates a distinct pattern of expression during colorectal cancer progression. Although cathepsin H activities were most commonly elevated in Dukes' C cancers at all colon sites, both specific activity and C/N ratios were significantly higher for cancers of the left colon compared to other colon locations. A subset of 43 paired extracts analysed on Western blots also revealed consistent changes in cathepsin H protein forms in cancers. Normal mucosa typically showed a strong protein doublet at 31 and 29 kDa while cancers demonstrated decreased expression or total loss of the 31 kDa protein (90% of cases), equal or increased expression of the 29-kDa protein (67% of cases) and the new appearance or up-regulation of a cathepsin H band at 22 kDa (78% of cases). C/N ratios for cathepsin H enzyme activity correlated significantly with C/N ratios for the 29 kDa mature single-chain protein form (P< 0.001), with increased activity most commonly associated with elevated expression of 29-kDa cathepsin H but also with up-regulation of the 22-kDa band, suggesting a shift to more fully processed, mature active cathepsin H protein forms in cancers. Changes in cathepsin H expression were also detected by immunohistochemistry as elevated cathepsin H staining in tumour epithelial cells. © 2000 Cancer Research Campaign
Trace: Tennessee Research and Creative Exchange Development of Form and Function in Peripheral Auditory Structures of the Zebrafish (danio Rerio) a N. Popper Recommended Citation Development of Form and Function in Peripheral Auditory Structures of the Zebrafish (danio Rerio) A)

Investigations of the development of auditory form and function have, with a few exceptions, thus far been largely restricted to birds and mammals, making it difficult to postulate evolutionary hypotheses. Teleost fishes represent useful models for developmental investigations of the auditory system due to their often extensive period of posthatching development and the diversity of auditory specializations in this group. Using the auditory brainstem response and morphological techniques we investigated the development of auditory form and function in zebrafish ͑Danio rerio) ranging in size from 10 to 45 mm total length. We found no difference in auditory sensitivity, response latency, or response amplitude with development, but we did find an expansion of maximum detectable frequency from 200 Hz at 10 mm to 4000 Hz at 45 mm TL. The expansion of frequency range coincided with the development of Weberian ossicles in zebrafish, suggesting that changes in hearing ability in this species are driven more by development of auxiliary specializations than by the ear itself. We propose a model for the development of zebrafish hearing wherein the Weberian ossicles gradually increase the range of frequencies available to the inner ear, much as middle ear development increases frequency range in mammals.
3-D Characterization of Global and Local Microstructural Effects on Spall Damage in Shock Loaded FCC Metals: Experimental and Modeling

Global and local microstructural weak links for spall damage were investigated using 3-D characterization in polycrystalline (PC) and multicrystalline (MC) copper samples, respectively. All samples were shocked via flyer-target plate experiments using a laser drive at low pressures (2–6 GPa). The flyer plates measured approximately 500 μm thick and 8 mm in diameter and the target plates measured approximately 1000 μm thick and 10 mm in diameter. Electron Backscattering Diffraction (EBSD) and optical microscopy were used to determine to presence of voids and relate them to the surrounding microstructure. Statistics on the strength of grain boundaries (GBs) was conducted by analyzing PC samples and collecting the misorientation across GBs with damage present, and it was found that a misorientation range of 25–50° is favorable for damage. Statistics were also taken of copper PC samples that had undergone different heat treatments and it was found that although the 25–50° range is less dominant, it is still favorable for damage nucleation. Removal of initial plastic strain via heat treatments and an increase in Σ3 CSL boundaries, indicative of strong annealing twins, also led to an increased amount of transgranular damage. 3-D X-ray tomography data were used to investigate the shape of the voids present in untreated, as received and heat treated samples. It was found that the as received sample contained a higher amount of “disk”, or, “sheet-like” voids indicative of intergranular damage, whereas the heat treated samples had a higher fraction of spherical shaped voids, indicative of transgranular damage. MC samples were used to study microstructural weak links for spall damage because the overall grain size is much larger than the average void size, making it possible to determine which GBs nucleated damage. Simulations and experimental analysis of damage sites with large volumes indicate that high Taylor factor mismatches with respect to the crystallographic grain GB normal is the primary cause for the nucleation of damage at a GB interface and a low Taylor factor along the shock direction in either grain drives void growth perpendicular to the GB. Cases where experimental results show damage and simulation results show no damage are attributed to the presence of an intrinsic microstructural weak link, such as an incoherent twin boundary.Copyright © 2013 by ASME
Structure and Reciprocity in Technology-Centered Q&A Communities

In this paper we examine the network structure of the MythTV mailing list, an online technology Q&A user community, and we use time-series analysis techniques to study users’ reciprocity behavior in this community. We find that the amount of help users provide is strongly correlated to the amount of help they receive. Further, by conducting the Granger Causality test on the time series data of active users’ activity, we find that the amount of help given is actually the reason why one gets a lot of help. This finding corresponds to the concept of directed reciprocity in social networks and provides insights into social dynamics in technology-centered online communities.
Contribution to the Prediction of the Fold Code: Application to Immunoglobulin and Flavodoxin Cases

Background Folding nucleus of globular proteins formation starts by the mutual interaction of a group of hydrophobic amino acids whose close contacts allow subsequent formation and stability of the 3D structure. These early steps can be predicted by simulation of the folding process through a Monte Carlo (MC) coarse grain model in a discrete space. We previously defined MIRs (Most Interacting Residues), as the set of residues presenting a large number of non-covalent neighbour interactions during such simulation. MIRs are good candidates to define the minimal number of residues giving rise to a given fold instead of another one, although their proportion is rather high, typically [15-20]% of the sequences. Having in mind experiments with two sequences of very high levels of sequence identity (up to 90%) but different folds, we combined the MIR method, which takes sequence as single input, with the “fuzzy oil drop” (FOD) model that requires a 3D structure, in order to estimate the residues coding for the fold. FOD assumes that a globular protein follows an idealised 3D Gaussian distribution of hydrophobicity density, with the maximum in the centre and minima at the surface of the “drop”. If the actual local density of hydrophobicity around a given amino acid is as high as the ideal one, then this amino acid is assigned to the core of the globular protein, and it is assumed to follow the FOD model. Therefore one obtains a distribution of the amino acids of a protein according to their agreement or rejection with the FOD model. Results We compared and combined MIR and FOD methods to define the minimal nucleus, or keystone, of two populated folds: immunoglobulin-like (Ig) and flavodoxins (Flav). The combination of these two approaches defines some positions both predicted as a MIR and assigned as accordant with the FOD model. It is shown here that for these two folds, the intersection of the predicted sets of residues significantly differs from random selection. It reduces the number of selected residues by each individual method and allows a reasonable agreement with experimentally determined key residues coding for the particular fold. In addition, the intersection of the two methods significantly increases the specificity of the prediction, providing a robust set of residues that constitute the folding nucleus.
Progression of the phenotype of transformed cells after growth stimulation of cells by a human papillomavirus type 16 gene function

Alteration of the growth properties of the established murine fibroblast cell lines NIH 3T3 and 3Y1 was studied in monolayer cultures and in cells suspended in semisolid medium after introduction of a cloned human papillomavirus type 16 (HPV16) DNA. HPV 16 DNA stimulated both cell lines to grow beyond their saturation densities in monolayer cultures without any apparent morphological changes or tendency to pile up. These cells were also stimulated to grow in soft agar. Since essentially all the cells that received the viral gene were stimulated to grow, the growth-stimulatory activity of HPV16 appeared to be due to the direct effect of a viral gene function. The NIH 3T3 cells showed an additional change in growth properties upon prolonged incubation of dense monolayers of cells containing the HPV16 DNA; morphologically recognizable dense foci appeared at a frequency of about 10(-3). These cells, when cloned from the foci, grew more rapidly in soft agar than the parental cells and were morphologically transformed. In other words, there were two sequential steps in cell transformation induced by HPV16. Practically all the viral DNAs were present in the cells as large rearranged multimers and were integrated into host chromosomal DNA. There was no obvious difference in the state of viral DNA in the cells of the original clone or the three subclones derived from it as dense foci. There was no difference in the amount or the number of viral RNA species expressed in the cells at these two stages. The secondary changes in the growth properties of NIH 3T3 cells appear to be due to some cellular alterations.
Classification of Two Class Motor Imagery Tasks Using Hybrid GA-PSO Based K-Means Clustering

Transferring the brain computer interface (BCI) from laboratory condition to meet the real world application needs BCI to be applied asynchronously without any time constraint. High level of dynamism in the electroencephalogram (EEG) signal reasons us to look toward evolutionary algorithm (EA). Motivated by these two facts, in this work a hybrid GA-PSO based K-means clustering technique has been used to distinguish two class motor imagery (MI) tasks. The proposed hybrid GA-PSO based K-means clustering is found to outperform genetic algorithm (GA) and particle swarm optimization (PSO) based K-means clustering techniques in terms of both accuracy and execution time. The lesser execution time of hybrid GA-PSO technique makes it suitable for real time BCI application. Time frequency representation (TFR) techniques have been used to extract the feature of the signal under investigation. TFRs based features are extracted and relying on the concept of event related synchronization (ERD) and desynchronization (ERD) feature vector is formed.
Aphasia due to a right hemisphere tumor in a right‐handed man

IN COMMENTING on the role of the “minor hemisphere” of the brain in speech, MacDonald Critchleyl notes the “rare appearance of aphasia after lesions of the right hemisphere in subjects who have shown no personal nor familial evidence of sinistrality whatsoever. ” We have recently cared for such a patient during the last stages of a fatal illness. Consideration of his case, and a review of the literature on this problem, has led us to some unconventional speculations which we hope may be provocative.
Clinically Relevant Molecular Subtypes in Leiomyosarcoma

Purpose: Leiomyosarcoma is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for leiomyosarcoma. Recognition of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 leiomyosarcomas, we identified three molecular subtypes in leiomyosarcoma. The current study was performed to determine whether the existence of these subtypes could be confirmed in independent cohorts. Experimental Design: Ninety-nine cases of leiomyosarcoma were expression profiled with 3′end RNA-Sequencing (3SEQ). Consensus clustering was conducted to determine the optimal number of subtypes. Results: We identified 3 leiomyosarcoma molecular subtypes and confirmed this finding by analyzing publically available data on 82 leiomyosarcoma from The Cancer Genome Atlas (TCGA). We identified two new formalin-fixed, paraffin-embedded tissue-compatible diagnostic immunohistochemical markers; LMOD1 for subtype I leiomyosarcoma and ARL4C for subtype II leiomyosarcoma. A leiomyosarcoma tissue microarray with known clinical outcome was used to show that subtype I leiomyosarcoma is associated with good outcome in extrauterine leiomyosarcoma while subtype II leiomyosarcoma is associated with poor prognosis in both uterine and extrauterine leiomyosarcoma. The leiomyosarcoma subtypes showed significant differences in expression levels for genes for which novel targeted therapies are being developed, suggesting that leiomyosarcoma subtypes may respond differentially to these targeted therapies. Conclusions: We confirm the existence of 3 molecular subtypes in leiomyosarcoma using two independent datasets and show that the different molecular subtypes are associated with distinct clinical outcomes. The findings offer an opportunity for treating leiomyosarcoma in a subtype-specific targeted approach. Clin Cancer Res; 21(15); 3501–11. ©2015 AACR.
Structured Operational Semantics for Graph Rewriting

Process calculi and graph transformation systems provide models of reactive systems with labelled transition semantics. While the semantics for process calculi is compositional, this is not the case for graph transformation systems, in general. Hence, the goal of this article is to obtain a compositional semantics for graph transformation system in analogy to the structural operational semantics (SOS) for Milner's Calculus of Communicating Systems (CCS). The paper introduces an SOS style axiomatization of the standard labelled transition semantics for graph transformation systems. The first result is its equivalence with the so-called Borrowed Context technique. Unfortunately, the axiomatization is not compositional in the expected manner as no rule captures "internal" communication of sub-systems. The main result states that such a rule is derivable if the given graph transformation system enjoys a certain property, which we call "complementarity of actions". Archetypal examples of such systems are interaction nets. We also discuss problems that arise if "complementarity of actions" is violated.
Infectomic Analysis of Gene Expression Profiles of Human Brain Microvascular Endothelial Cells Infected with Cryptococcus neoformans

In order to dissect the pathogenesis of Cryptococcus neoformans meningoencephalitis, a genomic survey of the changes in gene expression of human brain microvascular endothelial cells infected by C. neoformans was carried out in a time-course study. Principal component analysis (PCA) revealed significant fluctuations in the expression levels of different groups of genes during the pathogen-host interaction. Self-organizing map (SOM) analysis revealed that most genes were up- or downregulated 2 folds or more at least at one time point during the pathogen-host engagement. The microarray data were validated by Western blot analysis of a group of genes, including β-actin, Bcl-x, CD47, Bax, Bad, and Bcl-2. Hierarchical cluster profile showed that 61 out of 66 listed interferon genes were changed at least at one time point. Similarly, the active responses in expression of MHC genes were detected at all stages of the interaction. Taken together, our infectomic approaches suggest that the host cells significantly change the gene profiles and also actively participate in immunoregulations of the central nervous system (CNS) during C. neoformans infection.
Reliability and Validity of Mechanical Response Tissue Analysis in Composite and Human Tibiae

The purpose of this study was to assess the validity, as well as to test novel approaches to improving the reliability, of mechanical response tissue analysis (MRTA). Twenty composite tibiae underwent MRTA testing on three separate days to determine intraand inter-day reliability of bending stiffness. The bones were then subjected to three-point bending tests to directly determine elastic modulus. Withinand between-day reliability of tibial bending stiffness with MRTA was moderate (CV = 24%) and poor (CV = 74%), respectively. No relationship was observed between the two testing methods due to the wide variation in tibial bending stiffness values with MRTA. The second part of the study sought to determine withinand between-day reliability of MRTA in young women with the current testing protocol and compare the results with those from newly-designed protocols. Twelve women (23 ± 2 yr, 162 ± 7 cm, 57 ± 7kg, 19 ± 4 % fat) were tested for tibial bending stiffness with MRTA over 5 days. The current protocol was compared to protocols where day-to-day subject positioning was quantified, subjects were tested in a supine position, and various bending stiffness prediction models were used. Within(CV = 20%) and between-day (CV = 19%) reliability of tibial bending stiffness with MRTA was moderate using the original methodology. Modifications to this protocol either resulted in similar or worse reliability.
The SUMO-targeted ubiquitin ligase subunit Slx5 resides in nuclear foci and at sites of DNA breaks

The Slx5/Slx8 protein complex, a heterodimeric SUMO-targeted ubiquitin ligase, plays an important role in genomic integrity. Slx5/Slx8 is believed to interact with sumoylated proteins that reside in the nuclei of budding yeast cells. In this complex, Slx5, owing to at least two SUMO interacting motifs (SIMs), has been proposed to be the targeting subunit of the Slx8 ubiquitin ligase. However, little is known about the exact subnuclear localization and targets of Slx5/Slx8. In this study we show that Slx5, but not Slx8, forms prominent nuclear foci. The formation of these foci depends on SUMO and a SIM in Slx5. Therefore, we investigated the subnuclear localization and potential chromatin association of Slx5. Using co-localization studies in live cells and fixed chromatin, we were able to localize Slx5 to DNA damage induced foci of Rad52 and Rad9, two proteins involved in the cellular response to DNA damage. Subsequent chromatin immunoprecipitation (ChIP) studies revealed that Slx5 is associated with HO endonuclease induced chromosome breaks. Surprisingly, real-time PCR analysis of Slx5 ChIPs revealed that the level of Slx5 at HO breaks in an slx8 deletion background is reduced about 4-fold. These results indicate that the DNA-damage targeting of Slx5/Slx8 depends on formation of the heterodimer and that this occurs at a subset of nuclear foci also containing DNA damage repair and checkpoint factors.
Active flexible rods with embedded SMA fibers

Embedding of shape memory alloy (SMA) fibers in slender flexible bodies results in shape changes of the host medium, whenever shape recovery of the SMA fibers takes place. The shape change of a cylindrical rod with a single off-axis embedded SMA fiber is modeled. The distributed axial compressive force and bending moment due to phase transformation in the SMA fiber is evaluated using an approximate analytical model and the deformed shape of the flexible rod is found by solving the equations of equilibrium of the rod. The stability analysis for the linearized theory is carried out and the critical value of the phase transformation induced strain for buckling is evaluated.
Treatment of dystrophinopathic cardiomyopathy: review of the literature and personal results

Cardiomyopathy is an almost universal finding in boys affected by Duchenne muscular dystrophy (DMD). Myocardial changes, as a result of the lack of dystrophin, consist of cell membrane degradation, interstitial inflammation, fatty replacement and fibrosis. Dystrophinopathic cardiomyopathy generally starts as a preclinical or intermediate stage, with evolution toward advanced stages characterized by ventricle enlargement but also by symptoms and signs of heart failure (dyspnoea, peripheral edema and liver enlargement). However in few patients the dilation could be the first manifestation of the heart involvement. The ability to detect overt cardiomyopathy increases with age, such that more than 80% of boys older than 18 years will have abnormal systolic function. Several drugs have been employed with the aim to contrast the evolution of cardiomyopathy toward stages of severe congestive heart failure. A review of cardiac treatment in DMD and personal experience are reported and discussed.
Middle East Respiratory Syndrome Infection Control and Prevention Guideline for Healthcare Facilities

Middle East Respiratory Syndrome (MERS) is an acute viral respiratory illness with high mortality caused by a new strain of betacoronavirus (MERS-CoV). Since the report of the first patient in Saudi Arabia in 2012, large-scale outbreaks through hospital-acquired infection and inter-hospital transmission have been reported. Most of the patients reported in South Korea were also infected in hospital settings. Therefore, to eliminate the spread of MERS-CoV, infection prevention and control measures should be implemented with rigor. The present guideline has been drafted on the basis of the experiences of infection control in the South Korean hospitals involved in the recent MERS outbreak and on domestic and international infection prevention and control guidelines. To ensure efficient MERS-CoV infection prevention and control, care should be taken to provide comprehensive infection control measures including contact control, hand hygiene, personal protective equipment, disinfection, and environmental cleaning.
A new N-level high voltage inversion system

This paper deals with a new multi-level high voltage source inverter using GTO thyristors. Recently, a multi-level approach seems to be best suited for implementing high voltage conversion systems because it leads to harmonic reduction and safely deals with high power conversion systems independent of the dynamic switching characteristics of each power semiconductor device. However, a conventional multi-level inverter has some problems; namely voltage unbalance between DC link capacitors and overvoltages across the inner switching devices. Therefore, the authors propose a novel structure of a multilevel inverter in order to improve these problems. <<ETX>>