Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of tapasin and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma lesions with reduced survival of patients.

PURPOSE The purpose of this research was to assess the frequency and clinical significance of antigen processing machinery component and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma (SCC) lesions. EXPERIMENTAL DESIGN Formalin-fixed, paraffin-embedded tumor biopsy specimens at pretreatment status from 70 Japanese patients with maxillary sinus SCC were examined for HLA class I antigen and endoplasmic reticulum chaperone molecule expression using an immunohistochemical method. Furthermore, the results of immunohistochemical staining of the lesions were correlated with their histopathological characteristics and with the clinical course of the disease. RESULTS Calnexin, ERp57, calreticulin, tapasin, and HLA class I antigens were down-regulated in 13, 13, 24, 69, and 78% of the 70 lesions tested, respectively. Both tapasin and HLA class I antigen expression were significantly correlated with the number of infiltrating CD3(+) T cells into tumor lesions (P < 0.01); furthermore, tapasin expression was significantly correlated with tumor differentiation (P = 0.024). Tapasin expression was correlated with that of HLA class I antigens (P < 0.01). Furthermore, tapasin and HLA class I antigen down-regulation in SCC lesions was significantly associated with reduced survival of patients (P = 0.01 and P = 0.002, respectively). Multivariate Cox proportional hazards model analysis identified HLA class I antigen down-regulation as an independent prognostic marker. CONCLUSIONS Tapasin expression appears to be associated with HLA class I antigen expression in primary maxillary sinus SCC lesions. Furthermore, defects in tapasin and HLA class I antigen expression in primary maxillary sinus SCC lesions may play a role in the clinical course of the disease, because these defects were associated with poor prognosis.
Simulation of the growth of the 3D Rayleigh-Taylor instability in supernova remnants using an expanding reference frame

Context. The Rayleigh-Taylor instabilities that are generated by the deceleration of a supernova remnant during the ejecta-dominated phase are known to produce finger-like structures in the matter distribution that modify the geometry of the remnant. The morphology of supernova remnants is also expected to be modified when efficient particle acceleration occurs at their shocks. Aims: The impact of the Rayleigh-Taylor instabilities from the ejecta-dominated to the Sedov-Taylor phase is investigated over one octant of the supernova remnant. We also study the effect of efficient particle acceleration at the forward shock on the growth of the Rayleigh-Taylor instabilities. Methods: We modified the Adaptive Mesh Refinement code RAMSES to study with hydrodynamic numerical simulations the evolution of supernova remnants in the framework of an expanding reference frame. The adiabatic index of a relativistic gas between the forward shock and the contact discontinuity mimics the presence of accelerated particles. Results: The great advantage of the super-comoving coordinate system adopted here is that it minimizes numerical diffusion at the contact discontinuity, since it is stationary with respect to the grid. We propose an accurate expression for the growth of the Rayleigh-Taylor structures that smoothly connects the early growth to the asymptotic self-similar behaviour. Conclusions: The development of the Rayleigh-Taylor structures is affected, although not drastically, if the blast wave is dominated by cosmic rays. The amount of ejecta that reaches the shocked interstellar medium is smaller in this case. If acceleration were to occur at both shocks, the extent of the Rayleigh-Taylor structures would be similar but the reverse shock would be strongly perturbed.
Fatal cerebral malaria: a venous efflux problem

Most Plasmodium falciparum-infected children with cerebral malaria (CM) die from respiratory arrest, but the underlying pathology is unclear. Here we present a model in which the ultimate cause of death from CM is severe intracranial hypertension. Dynamic imaging of mice infected with P. berghei ANKA, an accepted model for experimental CM, revealed that leukocyte adhesion impairs the venous blood flow by reducing the functional lumen of postcapillary venules (PCV). The resulting increase in intracranial pressure (ICP) exacerbates cerebral edema formation, a hallmark of both murine and pediatric CM. We propose that two entirely different pathogenetic mechanisms—cytoadherence of P. falciparum-infected erythrocytes in pediatric CM and leukocyte arrest in murine CM—result in the same pathological outcome: a severe increase in ICP leading to brainstem herniation and death from respiratory arrest. The intracranial hypertension (IH) model unifies previous hypotheses, applies to human and experimental CM alike, eliminates the need to explain any selective recognition mechanism Plasmodium might use to target multiple sensitive sites in the brain, and explains how an intravascular parasite can cause so much neuronal dysfunction.
Numerical modeling of geosynthetic-reinforced earth structures and geosynthetic-soil interactions

Nowadays geosynthetics have been used as a routine reinforcement in earth structures such as mechanically stabilized earth (MSE) walls, column-supported embankments, soil slopes, and paved/unpaved roads. In those applications, reinforcement mechanisms of the geosynthetics are vaguely described as confinement, interlocking, and load shedding respectively but not fully understood. The uncertainties of the mechanisms have been reflected as overconservativeness, inconsistence and empiricism in current design methods of those applications. Various researches have been widely carried on to investigate the mechanisms of reinforcement of the above mentioned applications, especially the geosynthetic-soil interactions and then quantitatively consider them into design methods. Numerical modeling characterized as costand timesaving, is preferred in many circumstances. An appropriate modeling strategy is vital to yield reliable results. This paper reviewed and summarized the modeling techniques used to model modular-block MSE walls, reinforced embankments/slopes, and reinforced paved/unpaved roads, which include conventional continuum modeling based on constitutive relationships as well as micro-mechanical modeling based on Newton’s law of motion, i.e., modeling the soil mass as an assembly of soil particles governed by universal physics principles. The review of conventional continuum modeling includes constitutive models for soils, geosynthetics and other components (e.g., modular blocks), interface models for contacts between dissimilar materials, and simulation of construction, while the review of the micro-mechanical modeling is extended to the principle of the micro-mechanical modeling and how the micro-mechanical modeling is implemented to model the geosynthetic-soil interaction by using the most popular micro-mechanical schemePFC as an example. The objective of this paper is to provide a state-of-art review of the various numerical modeling techniques and consequently promote the usage of numerical modeling in research and practice of geosynthetic-reinforced earth structures.
RECRUITMENT PATTERNS AND CONTRACTILE PROPERTIES OF FAST MUSCLE- FIBERS ISOLATED FROM ROSTRAL AND CAUDAL MYOTOMES OF THE SHORT- HORNED SCULPIN

Muscle action during swimming and the contractile properties of isolated muscle fibres were studied in the short-horned sculpin Myoxocephalus scorpius at 5°C. Semi-steady swimming, startle responses and prey-capture events were filmed with a high-speed video at 200 frames s-1, using fish 22–26 cm in total length (L). Electromyographical (EMG) recordings, synchronised with the video, were made from fast muscle in rostral and caudal myotomes at points 0.40L and 0.80L along the body. Fast muscle fibres were first recruited at tail-beat frequencies of 3.7-4.2 Hz, corresponding to a swimming speed of 1.7 L s-1. Electrical activity in the muscles occurred during 16–38 % of each tail- beat cycle regardless of frequency. Muscle fibres were activated during the lengthening phase of the cycle. In caudal myotomes, the onset of the muscle activity occurred at a phase of 75–105° at 3.7 Hz, decreasing to approximately 50° at frequencies greater than 4.5 Hz (0° phase was defined as the point at which muscle fibres passed through their resting lengths in the stretch phase of the cycle; a full cycle is 360°). Prey capture was a stereotyped behaviour consisting of a preparatory movement, a powerstroke at 7–9 Hz and a glide of variable duration. The delay between the activation of muscle fibres in rostral and caudal myotomes during prey capture and startle responses was approximately 10 ms. Fast muscle fibres isolated from rostral and caudal myotomes were found to have similar isometric contractile properties. Maximum tetanic stress was 220 kN m-2, and half-times for force development and relaxation were approximately 50 ms and 135 ms respectively. Power output was measured by the ‘work loop’ technique in muscle fibres subjected to sinusoidal length changes at the range of frequencies found during swimming. Under optimal conditions of strain and stimulation, muscle fibres from rostral and caudal myotomes produced similar levels of work (3.5 J kg-1) and generated their maximum power output of 25–30 W kg-1 at the tail-beat frequencies used in swimming (4–8 Hz). Progressively delaying the onset of stimulation relative to the start of the strain cycle resulted in an initial modest increase, followed by a decline, in the work per cycle. Maximum positive work and net negative work were done at stimulus phase values of 20–50° and 120–140° respectively. The EMG and swimming studies suggest that fast muscle fibres in both rostral and caudal myotomes do net positive work under most conditions.
Hepatitis C Lipo-Viro-Particle from Chronically Infected Patients Interferes with TLR4 Signaling in Dendritic Cell

Background Hepatitis C virus (HCV) can be purified from serum of chronically-infected patients in the form of Lipo-Viro-Particles (LVP), which are triglycerid-rich lipoprotein-like particles containing viral RNA and proteins. Since LVP is a constant feature of chronically infected patients, we asked whether purified LVP could interfere with the immune response by acting directly on dendritic cell (DC) function. Methods and Findings We have analyzed the impact of LVP on the maturation monocyte-derived DC induced by TLR3 or TLR4 ligands. Following incubation with LVP, immature DC supported weak transient HCV-RNA replication and type I IFN synthesis. This, however, did not lead to viral particle production nor to maturation of DC. LVP-treatment prior to TLR3 stimulation by polyI:C only enhanced the secretion of IL-12, IL-6 and TNFα yielding typical mature DC. In contrast, LVP-treated DC activated by the TLR4 ligand LPS yielded phenotypically mature DC with reduced capacity to secrete both pro- and anti-inflammatory cytokines. Their ability to stimulate allogeneic T lymphocytes was strongly affected since activated T cells produced IL-5 and IL-13 instead of IFNγ. Addition of IFNα prevented the effect of LVP on DC function. Restoration of IFNγ secretion by T cells was obtained by blocking ERK activation in DC, while induction of IL-5 and IL-13 secretion was inhibited by blocking the p38-MAPK pathway in DC. Conclusions LVP can interfere with TLR4-triggered maturation of DC, inducing a shift in DC function that stimulates Th2 cells instead of Th1, by a mechanism that is ERK- and p38-MAPK-dependent. The effect of LVP on DC polarization was reversed by IFNα, providing an additional rationale for the interferon therapy of chronically-infected patients. By acting on TLR4 pathway with LVP, HCV may thus exploit a natural protective mechanism of the liver and the intestine normally used to control inflammation and immunity to commensal microorganisms.
Targeting Intracellular Calcium Signaling ([Ca2+]i) to Overcome Acquired Multidrug Resistance of Cancer Cells: A Mini-Overview

Cancer is a main public health problem all over the world. It affects millions of humans no matter their age, gender, education, or social status. Although chemotherapy is the main strategy for the treatment of cancer, a major problem limiting its success is the intrinsic or acquired drug resistance. Therefore, cancer drug resistance is a major impediment in medical oncology resulting in a failure of a successful cancer treatment. This mini-overview focuses on the interdependent relationship between intracellular calcium ([Ca2+]i) signaling and multidrug resistance of cancer cells, acquired upon treatment of tumors with anticancer drugs. We propose that [Ca2+]i signaling modulates gene expression of multidrug resistant (MDR) genes which in turn can be modulated by epigenetic factors which in turn leads to modified protein expression in drug resistant tumor cells. A precise knowledge of these mechanisms will help to develop new therapeutic strategies for drug resistant tumors and will improve current chemotherapy.
Longitudinal Detection of Prion Shedding in Saliva and Urine by Chronic Wasting Disease-Infected Deer by Real-Time Quaking-Induced Conversion

ABSTRACT Chronic wasting disease (CWD) is an emergent, rapidly spreading prion disease of cervids. Shedding of infectious prions in saliva and urine is thought to be an important factor in CWD transmission. To help to elucidate this issue, we applied an in vitro amplification assay to determine the onset, duration, and magnitude of prion shedding in longitudinally collected saliva and urine samples from CWD-exposed white-tailed deer. We detected prion shedding as early as 3 months after CWD exposure and sustained shedding throughout the disease course. We estimated that the 50% lethal dose (LD50) for cervidized transgenic mice would be contained in 1 ml of infected deer saliva or 10 ml of urine. Given the average course of infection and daily production of these body fluids, an infected deer would shed thousands of prion infectious doses over the course of CWD infection. The direct and indirect environmental impacts of this magnitude of prion shedding on cervid and noncervid species are surely significant. IMPORTANCE Chronic wasting disease (CWD) is an emerging and uniformly fatal prion disease affecting free-ranging deer and elk and is now recognized in 22 U.S. states and 2 Canadian provinces. It is unique among prion diseases in that it is transmitted naturally through wild populations. A major hypothesis to explain CWD's florid spread is that prions are shed in excreta and transmitted via direct or indirect environmental contact. Here we use a rapid in vitro assay to show that infectious doses of CWD prions are in fact shed throughout the multiyear disease course in deer. This finding is an important advance in assessing the risks posed by shed CWD prions to animals as well as humans.
Epstein-Barr virus DNA is amplified in transformed lymphocytes

Leukocytes isolated from two adult donors who lacked detectable antibodies to antigens associated with Epstein-Barr virus were exposed to an average of 0.02 to 0.1 DNA-containing particles of Epstein-Barr virus per cell and immediately clones in agarose. Within about 30 generations all transformed cell clones contained between 5 and 800 copies of viral DNA per cell. Only 1 in 10(4) to less than 1 in 10(5) of the cells of each clone release virus, and the frequency of release did not correlate with the average number of copies of viral DNA in the cells of each clone. One clone that had an average of five copies of viral DNA per cell was recloned, and the average number of copies in four of six subclones increased 15-to 50-fold while the subclones were being propagated sufficiently to study them. These results indicate that Epstein-Barr virus DNA can undergo amplification relative to cell DNA at different times after it transforms cells.
Credibility of various plastometric methods in simulation of hot rolling of the steel round bar

P. Kawulok, R. Kawulok, I. Schindler, S. Rusz, J. Kliber VŠB – Technical University of Ostrava, Faculty of Metallurgy and Materials Engineering, Czech Republic P. Unucka Material and Metallurgical Research Ltd., Czech Republic K. M. Čmiel Třinecké železárny a.s. , Czech Republic Rolling of round bar made of steel 32CrB4 was simulated physically. The interrupted torsion test led to the fi nal microstructure with coarser grains, however, thanks to comparatively large dimensions of the sample this type of experiment was not so sensitive to the cooling rate of the fi nal cooling as compression test. Too high temperature of the end of controlled cooling of the samples after compression test led to partial self-quenching of the investigated material. Decelerated cooling below the temperature of the start of martensitic transformation led in both applied types of compression tests to the parameters of the resulting microstructure and hardness closest to the parameters obtained after laboratory rolling.
Outcome of primary cutaneous anaplastic large cell lymphoma: a 20‐year British Columbia Cancer Agency experience

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30+ lymphoproliferative disorder with excellent outcomes reported despite frequent cutaneous relapses. Limited information exists on the development of systemic lymphoma. The British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database was searched to identify all adults diagnosed with PCALCL from 1993 to 2013. From 2005, the BCCA endorsed radiotherapy (RT) alone for limited stage with data failing to support chemotherapy. Forty‐seven patients were identified with a male predominance (n = 31, 66%), median age of 64 years and predominantly limited stage (n = 40, 85%). Median follow‐up was 8·4 years. The 5‐year time to progression (TTP) was 58% (64% limited versus 29% advanced stage). The 5‐year disease‐specific survival (DSS) and overall survival was 86% and 75%, respectively. In an as‐treated analysis, the 5‐year DSS for limited stage patients was similar comparing RT to combined modality treatment or chemotherapy alone but the 5‐year TTP favoured RT (82% vs. 33%, P = 0·004). The 5‐year cumulative risk of developing systemic lymphoma was 14%. Our results confirm the favourable prognosis of PCALCL despite a high relapse rate. Limited stage patients treated with RT alone have excellent outcomes. There is a small risk of systemic lymphoma in PCALCL.
The Trypanosoma brucei cAMP phosphodiesterases TbrPDEBl and TbrPDEB2: flagellar enzymes that are essential for parasite virulence

Cyclic nucleotide specific phosphodiesterases (PDEs) are pivotal regulators of cellular signaling. They are also important drug targets. Besides catalytic activity and substrate specificity, their subcel‐lular localization and interaction with other cell components are also functionally important. In contrast to the mammalian PDEs, the significance of PDEs in protozoal pathogens remains mostly unknown. The genome of Trypanosoma brucei, the causative agent of human sleeping sickness, codes for five different PDEs. Two of these, TbrPDEBl and TbrPDEB2, are closely similar, cAMP‐specific PDEs containing two GAF‐do‐mains in their N‐terminal regions. Despite their similarity, these two PDEs exhibit different subcellular localizations. TbrPDEB1 is located in the flagellum, whereas TbrPDEB2 is distributed between flagellum and cytoplasm. RNAi against the two mRNAs revealed that the two enzymes can complement each other but that a simultaneous ablation of both leads to cell death in bloodstream form trypanosomes. RNAi against Tbr‐PDEB1 and TbrPDEB2 also functions in vivo where it completely prevents infection and eliminates ongoing infections. Our data demonstrate that TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE‐inhibitor based trypanocidal drugs. Furthermore, they are compatible with the notion that the flagellum of T. brucei is an important site of cAMP signaling. —Oberholzer, M. , Marti, G. , Baresic, M. , Kunz, S. , Hemphill, A. , Seebeck, T. The Trypanosoma brucei cAMP phosphodiesterases TbrPDEB1 and TbrPDEB2: flagellar enzymes that are essential for parasite virulence. FASEB J. 21, 720–731 (2007)
Alternative methodologies in studies on business failure : do they produce better results than the classical statistical methods ?

Over the last 35 years, the topic of company failure prediction has developed to a major research domain in corporate finance. Academic researchers from all over the world have been developing a gigantic number of corporate failure prediction models, based on various types of modelling techniques. Besides the classical cross-sectional statistical methods, which have produced numerous failure prediction models, researchers have also been using several alternative methods for analysing and predicting business failure. To date, a clear overview and discussion of the application of alternative methods in corporate failure prediction is still lacking. Moreover, frequently, different designations or names are used for one method. Therefore, this study aims to provide a clear overview of the alternative research methods, attributing each of them a fixed designation. More in particular, this paper extensively elaborates on the most popular methods of survival analysis, machine learning decision trees and neural networks. Furthermore, it discusses several other alternative methods, which can be considered to have a certain value added in the empirical literature on business failure: the fuzzy rules-based classification model, the multi-logit model, the CUSUM model, dynamic event history analysis, the catastrophe theory and chaos theory model, multidimensional scaling, linear goal programming, the multi-criteria decision aid approach, rough set analysis, expert systems and self-organizing maps. This paper discusses the main features of these methods and their specific assumptions, advantages and disadvantages and it gives an overview of a number of academically developed corporate failure prediction models. Several issues viewed in isolation by earlier studies are here considered together, which is of major importance for gaining a clear insight into the possible alternative methods of corporate failure modelling and their corresponding features. A second aim of this paper is to find an answer to the question whether the more sophisticated, alternative modelling methods produce better performing failure prediction models than the rather simple classical statistical methods. The analysis of the conclusions of a large number of empirical studies comparing the classification results and/or the prediction abilities of failure prediction models based on different techniques seems to indicate that we may question the benefits to be gained from using the more sophisticated alternative methods.