Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of the Nkx2.5–Calr–p53 signaling pathway by hyperglycemia induces cardiac remodeling and dysfunction in adult zebrafish

ABSTRACT Hyperglycemia is an independent risk factor for diabetic cardiomyopathy in humans; however, the underlying mechanisms have not been thoroughly elucidated. Zebrafish (Danio rerio) was used in this study as a novel vertebrate model to explore the signaling pathways of human adult cardiomyopathy. Hyperglycemia was induced by alternately immersing adult zebrafish in a glucose solution or water. The hyperglycemic fish gradually exhibited some hallmarks of cardiomyopathy such as myocardial hypertrophy and apoptosis, myofibril loss, fetal gene reactivation, and severe arrhythmia. Echocardiography of the glucose-treated fish demonstrated diastolic dysfunction at an early stage and systolic dysfunction at a later stage, consistent with what is observed in diabetic patients. Enlarged hearts with decreased myocardial density, accompanied by decompensated cardiac function, indicated that apoptosis was critical in the pathological process. Significant upregulation of the expression of Nkx2.5 and its downstream targets calreticulin (Calr) and p53 was noted in the glucose-treated fish. High-glucose stimulation in vitro evoked marked apoptosis of primary cardiomyocytes, which was rescued by the p53 inhibitor pifithrin-μ. In vitro experiments were performed using compound treatment and genetically via cell infection. Genetically, knockout of Nkx2.5 induced decreased expression of Nkx2.5, Calr and p53. Upregulation of Calr resulted in increased p53 expression, whereas the level of Nkx2.5 remained unchanged. An adult zebrafish model of hyperglycemia-induced cardiomyopathy was successfully established. Hyperglycemia-induced myocardial apoptosis was mediated, at least in part, by activation of the Nkx2.5–Calr–p53 pathway in vivo, resulting in cardiac dysfunction and hyperglycemia-induced cardiomyopathy. Summary: Induction of hyperglycemia gives rise to cardiac apoptosis and dysfunction in adult zebrafish via the Nkx2.5–Calr–p53 signaling pathway, resulting in adult cardiomyopathy.
Design and implementation of a secure XML-based grid file storage system with reliability features

Grid computing represents a new challenge for enterprises looking for computing and storage resources. Business grid is the new frontier that, with the wide adoption of the notion of services, is paving the way through a real shift of the grid computing paradigm from the scientific to the commercial sector. This imposes among the others the solution of security issues, as well as the development of reliable mechanisms to access data. In this paper we address the problem of data fault tolerance in Grid through the adoption of the Redundant Residue Number System. From each file to be stored, a set of n elements is generated which are allocated to n + r different containers. If a disrupting event occurs, the r new elements will allow a correct reconstruction of the original file. The user will autonomously select both the fragmentation number and the degree of replication, that best fit his/her needs.
CONCURRENT ENGINEERING : Research and Applications A Model for Preliminary Design Procedures of Satellite Systems

The article describes a model for satellite systems preliminary design based on European Space Agency concurrent design approach. Space systems preliminary design aspects based on a concurrent engineering methodology are first briefly illustrated. A general description of a typical space system and its subsystems is provided and sizing criteria are provided for each subsystem. The design procedure is formalized according to Unified Modeling Language formalism. A description of the implementation of the model and some conclusive remarks are then included.
Effects of Operation Condition and Casting Strategy on Drainage Efficiency of the Blast Furnace Hearth

A mathematical model is developed to quantify the effect of operation conditions and casting strategy on residual amount of slag and metal in hearth. The model is validated by a physical scale model experiment. Calculated results show that the residual amount of slag increases in proportion to the square of production. The effect of hearth permeability on the residual amount of slag is larger than slag viscosity. Then high permeability is necessary under high productivity operation condition. Although a load is not small, increasing tapping rod diameter and shortening cast duration are the effective way to decease maximum slag level. High durability filling mud is necessary to keep cast duration.
Analysis and design considerations for a contactless power transfer system

Contactless power transfer (CPT) is a safe, convenient and reliable way of transferring power in many applications where there exists no physical contact between the source and the load. In this paper, general design criteria are described for efficient power transfer in a CPT system. The need for compensation has been discussed and general conditions for achieving bifurcation-free operation for each compensation topologies have been derived. Advantages of using Series-Series compensated topology over other topologies are discussed. Constant current and constant voltage modes of operation of Series-Series topology and conditions for these modes of operation are presented. An experimental CPT setup is built to validate the theory developed.
Monoclonal suppressor factor specific for lactate dehydrogenase B. I. Mechanism of interaction between the factor and its target cells

Hybridomas secreting a monoclonal T suppressor-effector factor (TseF) were produced by fusion of a lactate dehydrogenase B (LDHB)-specific long-term T suppressor-effector (Tse) cell line with the BW5147 thymoma. A short exposure (4 h) to TseF completely suppresses the antigen-specific and A-restricted proliferation of LDHB-primed Lyt-1+2- [possibly helper (Th)] cells. The action of TseF on Th cells, as that of the Tse cells themselves, is antigen-specific and A-restricted. The interaction of TseF with Th cells involves two binding events, of which one occurs via antigen bridge, and the other represents the recognition of a factor-derived Ak-like moiety by the anti-Ak receptor of Th cells. The Ak-like moiety of the TseF carries the determinants that serve as restriction elements for antigen recognition by Th cells, and additional determinants demonstrable by T cell-specific monoclonal "anti-Ak" antibodies, however, it lacks serologically detectable determinants of the B cell-derived A alpha A beta class II Mhc molecules.
Phosphoinositide‐3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation

The phosphatidylinositol‐3 kinase (PI3K) family of signaling enzymes plays a crucial role in leukocyte recruitment and activation and hence, likely regulates the induction and propagation phases of inflammation. However, little data have emerged showing a role for these processes in the resolution phase in models of in vivo inflammation. Here, we have evaluated the role of PI3K for the migration and survival of eosinophils in a model of allergic pleurisy in mice. Eosinophil accumulation in PI3Kγ‐deficient mice was inhibited at 48 h, as compared with wild‐type mice but not at earlier time‐points (6 and 24 h). Experiments with adoptive transfer of bone marrow showed that PI3Kγ in eosinophils but not in non‐bone marrow‐derived cells was required for their accumulation. Systemic treatment with PI3K inhibitors before antigen challenge prevented the recruitment of eosinophils. This was associated with decreased Akt phosphorylation, interleukin‐5 production, and eosinophil release from the bone marrow. Treatment with PI3K inhibitors 24 h after antigen challenge markedly cleared the accumulated eosinophils, an effect associated with inhibition of Akt phosphorylation and an increased number of apoptotic events. Altogether, our data demonstrate an important role of PI3Kγ for the maintenance of eosinophilic inflammation in vivo, whereas other isoforms of PI3K may be relevant for the recruitment process.
Pushing the limits of multicast in ad hoc networks

Focuses on the requirements of "better than best effort" (high hop-by-hop delivery guarantee) broadcasting in highly dynamic mobile multi-hop ad-hoc networks (MANETs). Our work is motivated by mission-critical applications, such as disaster relief and military operations. This class of applications is characterized by: (1) high delivery guarantee requirements, even in the presence of high mobility, and (2) a broadcast style of communication, where all nodes are receivers. Extensive simulations conducted on two different platforms show that, as node speeds, network traffic load and number of senders increase, the performance of existing multicast protocols (exemplified by ODMRP and MAODV) degrades in terms of packet delivery and overhead. In contrast, simple flooding, while clearly not a panacea, performs comparatively well and shows promise as a foundation for more specialized protocols for highly dynamic MANETs of the future.
Development and Validation of a Shear Punch Test Fixture

Abstract : An experimental shear punch assembly has been designed and fabricated for the evaluation of mechanical strength properties of metallic materials. The shear punch tester uses very small, thin specimens to evaluate shear behaviour of materials, the results of which can be correlated to tensile behaviour of the material. The apparatus provides a means of evaluating the mechanical properties of metal matrix composites (MMC) manufactured by friction stir processing (FSP) that are being developed as part of a Technology Investment Fund (TIF) project, as the volume of materials produced are too small for conventional tensile test methods. The shear punch apparatus has a similar basic design to those described in the literature; however a close-coupled compression force transducer and the direct measurement of specimen displacement response during the test procedure have been incorporated. This provides a direct measurement of both force and specimen displacement which improves the accuracy of the measured material response. This report also details the validation of the apparatus using 3xxx series aluminum specimens. The results indicate that for a given punch diameter and specimen thickness combination, the calculated effective yield stress, ultimate stress and strain are generally reproducible.
Flow patterns generated by oblate medusan jellyfish: field measurements and laboratory analyses

SUMMARY Flow patterns generated by medusan swimmers such as jellyfish are known to differ according the morphology of the various animal species. Oblate medusae have been previously observed to generate vortex ring structures during the propulsive cycle. Owing to the inherent physical coupling between locomotor and feeding structures in these animals, the dynamics of vortex ring formation must be robustly tuned to facilitate effective functioning of both systems. To understand how this is achieved, we employed dye visualization techniques on scyphomedusae (Aurelia aurita) observed swimming in their natural marine habitat. The flow created during each propulsive cycle consists of a toroidal starting vortex formed during the power swimming stroke, followed by a stopping vortex of opposite rotational sense generated during the recovery stroke. These two vortices merge in a laterally oriented vortex superstructure that induces flow both toward the subumbrellar feeding surfaces and downstream. The lateral vortex motif discovered here appears to be critical to the dual function of the medusa bell as a flow source for feeding and propulsion. Furthermore, vortices in the animal wake have a greater volume and closer spacing than predicted by prevailing models of medusan swimming. These effects are shown to be advantageous for feeding and swimming performance, and are an important consequence of vortex interactions that have been previously neglected.
Detecting Stations Cheating on Backoff Rules in 802.11 Networks Using Sequential Analysis

As the commercial success of the IEEE 802.11 protocol has made wireless infrastructure widely deployed, user organizations are increasingly concerned about the new vulnerabilities to their networks. While various security issues have been extensively studied, the threats posed by denial-of-service (DoS) attacks have not been fully exploited. In this paper, we consider DoS attacks posed by cheating on the backoff rules in the IEEE 802.11 DCF protocol and propose a scheme detecting such adversaries. Our scheme is based on the sequential hypothesis testing. We first develop analytical models for packet interarrival time distribution from each station in the network where multiple cheating stations co-exist. Using the characterization of this probability distribution, we develop an algorithm to detect cheating stations based on the throughout degradations observed at normal stations. Our simulation results show that the proposed algorithm only requires very small number of observations of packets with very small value (i.e., less than 0.1%) of false positive and false negative decisions. That is, our proposed algorithm performs significantly fast and also accurately.
Caspase-12 Silencing Attenuates Inhibitory Effects of Cigarette Smoke Extract on NOD1 Signaling and hBDs Expression in Human Oral Mucosal Epithelial Cells

Cigarette smoke exposure is associated with increased risk of various diseases. Epithelial cells-mediated innate immune responses to infectious pathogens are compromised by cigarette smoke. Although many studies have established that cigarette smoke exposure affects the expression of Toll-liked receptor (TLR), it remains unknown whether the nucleotide-binding oligomerization domain-containing protein 1 (NOD1) expression is affected by cigarette smoke exposure. In the study, we investigated effects of cigarette smoke extract (CSE) on NOD1 signaling in an immortalized human oral mucosal epithelial (Leuk-1) cell line. We first found that CSE inhibited NOD1 expression in a dose-dependent manner. Moreover, CSE modulated the expression of other crucial molecules in NOD1 signaling and human β defensin (hBD) 1, 2 and 3. We found that RNA interference-induced Caspase-12 silencing increased NOD1 and phospho-NF-κB (p-NF-κB) expression and down-regulated RIP2 expression. The inhibitory effects of CSE on NOD1 signaling can be attenuated partially through Caspase-12 silencing. Intriguingly, Caspase-12 silencing abrogated inhibitory effects of CSE on hBD1, 3 expression and augmented induced effect of CSE on hBD2 expression. Caspase-12 could play a vital role in the inhibitory effects of cigarette smoke on NOD1 signaling and hBDs expression in oral mucosal epithelial cells.
Collapse strength of longitudinal plate assemblies with dimple imperfections

This study considers the effects of dimple imperfections, i.e. imperfections caused by local accidents, on the ability of a plate assembly to resist compressive loads. Several different parameters for the plate were used, so that a relationship between these and the effect of the dimple imperfection could be developed. One such parameter was the position of the dimple imperfection on the plate. The study was based on finite element calculations. The results obtained were compared with the ones for the same panels without the dimple imperfections. It was found that the effect of the dimple imperfection is higher when positioned near the unloaded edge of the plate. It was also found that the effect on the collapse strength of this type of imperfection depends upon its amplitude and on the slenderness of the plate.
Influence of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone on serologic parameters and clinical course in lymphoma patients with autoimmune diseases.

BACKGROUND As patients with B-cell lymphomas suffering from an underlying autoimmune condition undergoing therapy with the CD20 antibody rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) offer the unique possibility of monitoring effects of therapy on various rheumatologic parameters, we have evaluated serologic autoimmune markers and the clinical outcome of patients with autoimmune diseases (ADs) who received lymphoma treatment with R-CHOP during the course of their disease. PATIENTS AND METHODS We have retrospectively analysed 13 patients with non-Hodgkin's lymphoma who concurrently suffered from ADs and were treated with the R-CHOP regimen. Subjective parameters along with rheumatoid factor (RF) and antinuclear antibodies (ANA) were serially measured. RESULTS The median levels of RF were 901 IU/ml [inter-quartile-range (IQR) 189-2520] before and 75 IU/ml (IQR 45-644) after therapy (P = 0.028). The median levels of ANA were 800 (IQR 140-2560) before and 100 (40-1280) after therapy (P = 0.027). Ten (77%) patients showed clinical improvement of their autoimmune symptoms, two (15%) reported no difference and one (7%) patient with rheumatoid arthritis-related worsening symptoms during therapy with R-CHOP. The autoimmune-related symptoms recurred after a median time of 7 weeks (IQR 6-8) in seven patients. In terms of lymphoma response, 11 patients achieved a complete remission and two a partial remission. CONCLUSIONS This analysis indicates that R-CHOP given for lymphoma treatment is also effective for therapy of concurrent rheumatoid diseases. Both rheumatoid parameters as well as clinical symptoms showed a significant decrease during treatment with this immunochemotherapy. The effects on the rheumatic diseases, however, seem to be of limited duration.
Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels

The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and bio‐molecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonary disease (COPD; n=219) cohorts when compared to controls (n=96). In these cohorts, a genome‐wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma population (P=1.17 × 10–7), which was also observed in a COPD population (combined P=5.04 × 10–12). Using a fluorescent assay, we demonstrated that serum KLKB1 enzymatic activity was driven by rs4253238 and is inverse to scuPAR levels. Biochemical analysis identified that KLKB1 cleaves scuPAR and negates scuPAR's effects on primary human bronchial epithelial cells (HBECs) in vitro. Chymotrypsin was used as a proproteolytic control, while basal HBECs were used as a control to define scuPAR‐driven effects. In summary, we reveal a novel post‐translational regulatory mechanism for scuPAR using a hypothesis‐free approach with implications for multiple human diseases. —Portelli, M. A. , Siedlinski, M. , Stewart, C. E. , Postma, D. S. , Nieuwenhuis, M. A. , Vonk, J. M. , Nurnberg, P., Altmuller, J., Moffatt, M. F. , Wardlaw, A. J., Parker, S. G. , Connolly, M. J., Koppelman, G. H. , Sayers, I. Genome‐wide protein QTL mapping identifies human plasma kallikrein as a post‐translational regulator of serum uPAR levels. FASEB J. 28, 923–934 (2014). www.fasebj. org
Process-variation aware mapping of real-time streaming applications to MPSoCs for improved yield

As technology scales, the impact of process variation on the maximum supported frequency (FMAX) of individual cores in a MPSoC becomes more pronounced. Task allocation without variation-aware performance analysis can result in a significant loss in yield, defined as the number of manufactured chips satisfying the application timing requirement. We propose variation-aware task allocation for real-time streaming applications modeled as task graphs. Our solutions are primarily based on the throughput requirement, which is the most important timing requirement in many real-time streaming applications. The three main contributions of this paper are: 1) Using data flow graphs that are well-suited for modeling and analysis of real-time streaming applications, we explicitly model task execution both in terms of clock cycles (which is independent of variation) and seconds (which does depend on the variation of the resource), which we connect by an explicit binding. 2) We present two approaches for optimizing the yield. The approaches give different results at different costs. 3) We present exhaustive and heuristic algorithms that implement the optimization approaches. Our variation-aware mapping algorithms are tested on models of real applications, and are compared to the mapping methods that are unaware of hardware variation. Our results demonstrate yield improvements of up to 50% with an average of 31%, showing the effectiveness of our approaches.
Feasibility analysis of vehicular dynamic spectrum access via queueing theory model

In this paper, we present a feasibility analysis for performing vehicular dynamic spectrum access across vacant television spectral channels via a queueing theory approach that is primarily based on a multi-server, multi-priority, preemptive queue. Queueing theory has been extensively employed in the open literature to model wireless multiple access architectures as well as analyze network performance in both wired and wireless communication frameworks. On the other hand, to the best of the authors' knowledge, there does not exist a queueing theory approach designed to analyze dynamic spectrum access networks on a system level, including the specific case of vehicular dynamic spectrum access (VDSA). Leveraging previously reported quantitative measurements obtained from a wireless spectrum measurement campaign conducted along a major interstate highway (I-90) located in Massachusetts, we modeled vacant TV channels as a multi-server queueing system in which available servers represent vacant channels. The servers become unavailable in a time/location-varying fashion such that they represent spatially occupied TV channels. Both M/M/m and M/G/m models are employed to evaluate the probability that a vehicle finds all channels busy, as well as to derive the expected waiting times and the expected number of channel switches. We also consider cases where there are multiple priority classes of service requests such as a channel request by a first-responder vehicle.