Miracle-dz/UniFAR-FTUs huggingface dataset:
Design-based Stereology

In regulatory toxicology studies, qualitative histopathological evaluation is the reference standard for assessment of test article–related morphological changes. In certain cases, quantitative analysis may be required to detect more subtle morphological changes, such as small changes in cell number. When the detection of subtle test article–related morphological changes is critical to the decision-making process, sensitive quantitative methods are needed. Design-based stereology provides the tools for obtaining accurate, precise quantitative structural data from tissue sections. These tools have the sensitivity necessary to detect small changes by combining statistical sampling principles with geometric analysis of the tissue microstructure. It differs from other morphometric methods based on tissue section analysis by providing estimates that are statistically valid, truly three-dimensional, and referent to the entire organ. Further, because the precision of the stereological analysis procedure can be predicted, studies can be designed and powered to detect subtle, potentially toxicologically significant changes. Although stereological methods have not been widely applied in toxicologic pathology, recent advances have made it feasible to implement these methods in a regulatory toxicology setting, particularly methods for estimation of total cell number.
Normal Anatomy and Histology of the Adult Zebrafish

The zebrafish has been shown to be an excellent vertebrate model for studying the roles of specific genes and signaling pathways. The sequencing of its genome and the relative ease with which gene modifications can be performed have led to the creation of numerous human disease models that can be used for testing the potential and the toxicity of new pharmaceutical compounds. Many pharmaceutical companies already use the zebrafish for prescreening purposes. So far, the focus has been on ecotoxicity and the effects on embryonic development, but there is a trend to expand the use of the zebrafish with acute, subchronic, and chronic toxicity studies that are currently still carried out with the more conventional test animals such as rodents. However, before we can fully realize the potential of the zebrafish as an animal model for understanding human development, disease, and toxicology, we must first greatly advance our knowledge of normal zebrafish physiology, anatomy, and histology. To further this knowledge, we describe, in the present article, location and histology of the major zebrafish organ systems with a brief description of their function.
Fe Allocation in Liver during Early Stages of Endotoxemia in Fe-Overload Rats

The hypothesis of this study was that alterations in Fe distribution triggered by lipopolysaccharide (LPS) administration were affected in vivo by Fe overload. Lipopolysaccharide treatment by itself significantly decreased Fe content in serum and increased the blood NO-hemoglobin (NO-Hb) EPR signal and nitrotyrosine protein content in liver, as compared to values in control animals. Fe overload (produced by Fe-dextran ip administration) caused an increase, as compared to values in control animals, in Fe content in serum, and a significant enhancement in ferritin (Ft) content, Fe content in Ft, the labile Fe pool (LIP), and the protein carbonyl content in the liver. The simultaneous administration of LPS and Fe-dextran lead to a significant increase in the Fe content in serum, blood NO-Hb EPR signal, the content of Fe, Fe in Ft, LIP, protein carbonyl, and nitrotyrosine protein in liver, as compared to values in control animals. The data reported here indicate that the protective strategy against endotoxemia of sequestering serum Fe content is not fully operative under Fe overload conditions. However, the oxidative condition of the liver does not seem to be being affected, since endogenous mechanisms were able to regulate the amount of catalytically active Fe to the same levels observed after Fe-dextran administration, even in the presence of LPS, over the initial six-hour period.
Tesaglitazar, a Dual PPAR-α/γ Agonist, Hamster Carcinogenicity, Investigative Animal and Clinical Studies

Tesaglitazar was developed as a dual peroxisome proliferator–activated receptor (PPARα/γ). To support the clinical program, a hamster carcinogenicity study was performed. The only neoplastic findings possibly related to treatment with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the liver of male animals. A high-power, two-year investigative study with interim necropsies was performed to further elucidate these findings. Treatment with tesaglitazar resulted in changes typical for exaggerated PPARα pharmacology in rodents, such as hepatocellular hypertrophy and hepatocellular carcinoma, but not an increased frequency of hemangiosarcomas. At the highest dose level, there was an increased incidence of sinusoidal dilatation and hemangiomas. No increased endothelial cell (EC) proliferation was detected in vivo, which was confirmed by in vitro administration to ECs. Immunohistochemistry and gene expression analyses indicated increased cellular stress and vascular endothelial growth factor (VEGF) expression in the liver, which may have contributed to the sinusoidal dilatation. A two-fold increase in the level of circulating VEGF was detected in the hamster at all dose levels, whereas no effect on VEGF was observed in patients treated with tesaglitazar. In conclusion, investigations have demonstrated that tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect on vascular morphology in the liver.
Quantitative evaluation of improvement ratio of image S/N in the NMR phase-scrambled Fourier imaging technique

A phase-scrambled Fourier transform imaging technique with a signal description algorithm similar to a Fresnel transform algorithm, which can be implemented by adding some changes to a conventional MRI system, can reduce noise in the image area without degrading resolution and can improve the S/N ratio of an image, even if the noise properties are unknown. This study presents two image S/N-improvement methods in the phase-scrambled Fourier imaging technique and quantitatively compares the extent of improvement of the image S/N ratio of the two methods by computer simulations. The results show that both methods 1 and 2 improve the image S/N ratio by a factor of about 1.3 at the maximum without degrading resolution or creating artifacts. In addition, applying the improvement methods to NMR signals collected by the phase-scrambled Fourier transform imaging technique using the prototype MRI system that we have constructed confirms the same extent of improvement in the image S/N ratio as in the simulation results. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(12): 27–37, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10209
Neural-network prediction with noisy predictors

Very often the input variables for neural-network predictions contain measurement errors. In particular, this may happen because the original input variables are often not available at the time of prediction and have to be replaced by predicted values themselves. This issue is usually ignored and results in nonoptimal predictions. This paper shows that under some general conditions, the optimal prediction using noisy input variables can be represented by a neural network with the same structure and the same weights as the optimal prediction using exact input variables. Only the activation functions have to be adjusted. Therefore we can achieve optimal prediction without costly retraining of the neural network. We explicitly provide an exact formula for adjusting the activation functions in a logistic network with Gaussian measurement errors in input variables. This approach is illustrated by an application to short-term load forecasting.
AEthereal network on chip: concepts, architectures, and implementations

The continuous advances in semiconductor technology enable the integration of increasing numbers of IP blocks in a single SoC. Interconnect infrastructures, such as buses, switches, and networks on chips (NoCs), combine the IPs into a working SoC. Moreover, the industry expects platform-based SoC design to evolve to communication-centric design, with NoCs as a central enabling technology. In this article, we introduce the AEthereal NoC. The tenet of the AEthereal NoC is that guaranteed services (GSs) - such as uncorrupted, lossless, ordered data delivery; guaranteed throughput; and bounded latency - are essential for the efficient construction of robust SoCs. To exploit the NoC capacity unused by the GS traffic, we provide best-effort services.
Standards: The P1685 IP-XACT IP Metadata Standard

The paper aims to develop an XML-based standard for describing electronic intellectual property - that is, blocks of electronic logic suitable for inclusion in complex integrated circuits, commonly know as systems on chips (SoCs). This work, which is based on the Spirit Consortium's IP-XACT specification, has transferred to the IEEE for standardization. The IP-XACT specification provides a metadata schema for describing IP, enabling it to be compatible with automated integration techniques, and an API for tool access to this schema. Tools that implement the standard would be able to automatically interpret, configure, integrate, and manipulate IP blocks that are delivered with metadata that conforms to the proposed IP metadata description, and the IP-XACT APIs provides a standard method for linking multiple tools through a single exchange-metadata format. This automatic integration of tools and IP from multiple vendors creates an IP-XACT-enabled environment
Evaluation of interfractional variation of the centroid position and volume of internal target volume during stereotactic body radiotherapy of lung cancer using cone‐beam computed tomography

The purpose of this study was to determine interfractional variation of the centroid position and volume of internal target volume (ITV) during stereotactic body radiation therapy (SBRT) of lung cancer. From January 2014 to August 2014, a total of 32 patients with 37 primary or metastatic lung tumors were enrolled in our study. All patients received SBRT treatment in 4–5 fractions to a median dose of 48 Gy. Both 3D CT and 4D CT scans were used for radiotherapy treatment planning. 3D CBCT was acquired prior to treatment delivery to verify patient positioning. A total of 163 3D CBCT images were available for evaluation. 3D CBCT scans acquired for verification were registered with simulation CT scans. The ITVs were contoured on all verification 3D CBCT scans and compared to the initial gross target volume (GTV) or ITV in treatment planning system. GTV was based on 3D CT while ITV was based on both 3D CT and 4D CT. To assess the interfractional variation of ITV centroid position, we used vertebrae body adjacent to the tumor as reference point when performing the registration procedure. To eliminate the effect of time on tumor volume between simulation CT scan and the first fraction, the interfractional variation of ITV was evaluated from the first fraction to the last fraction. The overall 3D vector shift was 4.4±2.5 mm (range: 0.4−13.8 mm). The interfractional variation of ITV centroid position in superior‐inferior, anterior‐posterior, and left‐right directions were −0.7±2.7 mm, −1.4±3.4 mm, and −0.5±2.2 mm, respectively. No significant difference was observed between three directions (p=0.147). Large interfractional variations (≥5 mm) were observed in 12 fractions (9.3%) in superior‐inferior direction, 24 fractions (18.6%) in anterior‐posterior direction, and 5 fractions (3.9%) in left‐right direction. No time trend of tumor volume change measured in 3D CBCT was detected during four fractions (p=0.074). A significant (p=0.010) time trend was detected when evaluating the time trend of ITV change during 5 fractions and diameter was found to be significantly correlated with the ITV change (p=0.000). ITV did not show significant regression during SBRT treatment, but interfractional variation in the ITV centroid position was observed, especially in anterior‐posterior direction. An isotropic margin of 7 mm around ITV might be necessary for adequate coverage of interfractional variation of ITV centroid position, but only in case no soft tissue‐based setup is performed during SBRT treatment. PACS number(s): 87.55. dk
Current Practices in Preclinical Drug Development

The Health and Environmental Sciences Institute Cardiac Biomarkers Working Group surveyed the pharmaceutical development community to investigate practices in assessing hemostasis, including detection of hypocoagulable and hypercoagulable states. Scientists involved in discovery, preclinical, and clinical research were queried on laboratory evaluation of endothelium, platelets, coagulation, and fibrinolysis during safety assessment studies. Results indicated that laboratory assessment of hemostasis is inconsistent among institutions and not harmonized between preclinical and clinical studies. Hemostasis testing in preclinical drug safety studies primarily focuses on the risk of bleeding, whereas the clinical complication of thrombosis is seldom assessed. Our results reveal the need for broader utilization of biomarkers to detect altered hemostasis (e.g., endothelial and platelet activation) to improve preclinical safety assessments early in the drug development process. Survey respondents indicated a critical lack of validated markers of hypercoagulability and subclinical thrombosis in animal testing. Additional obstacles included limited blood volume, lack of cross-reacting antibodies for hemostasis testing in laboratory species, restricted availability of specialized hemostasis analyzers, and few centers of expertise in animal hemostasis testing. Establishment of translatable biomarkers of prothrombotic states in multiple species and strategic implementation of testing on an industry-wide basis are needed to better avert untoward drug complications in patient populations.
Use of unlabeled time series data in hidden Markov models

In this paper, the authors propose a method of assigning probabilistic class labels to unlabeled time-series data that can be collected inexpensively to use together with labeled data as training data in order to improve the performance of hidden Markov models (HMM) as classifiers. Conventional methods of using unlabeled data according to probabilistic class labels were only for static data. They could not deal with time-series data, which are used with HMMs. Therefore, the authors extended the conventional methods as follows. First, they formed extended tied-mixture hidden Markov models (ETM-HMMs) by mixing multiple HMMs that exist independently for each class. Then, they introduced the extended Baum-Welch (EBW) algorithm as the learning algorithm from time-series data in which labeled and unlabeled data coexist in the ETM-HMMs. The authors then assumed a situation in which there existed insufficient labeled training data and used the proposed method to perform classification experiments for Japanese sign language data and voice data. When unlabeled data were added to the labeled training data according to the proposed method, the classification error rate for Japanese sign language signs improved from 38.7% to 30.4%. Also, by making the model more detailed in addition to adding unlabeled data, the classification error rate for phonemes improved from 69.1% to 52.9%. © 2003 Wiley Periodicals, Inc. Syst Comp Jpn, 34(13): 1–12, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10537
Towards software-defined VANET: Architecture and services

Vehicular Ad Hoc Networks (VANETs) have in recent years been viewed as one of the enabling technologies to provide a wide variety of services, such as vehicle road safety, enhanced traffic and travel efficiency, and convenience and comfort for passengers and drivers. However, current VANET architectures lack in flexibility and make the deployment of services/protocols in large-scale a hard task. In this paper, we demonstrate how Software-Defined Networking (SDN), an emerging network paradigm, can be used to provide the flexibility and programmability to networks and introduces new services and features to today's VANETs. We take the concept of SDN, which has mainly been designed for wired infrastructures, especially in the data center space, and propose SDN-based VANET architecture and its operational mode to adapt SDN to VANET environments. We also discuss benefits of a Software-Defined VANET and the services that can be provided. We demonstrate in simulation the feasibility of a Software-Defined VANET by comparing SDN-based routing with traditional MANET/VANET routing protocols. We also show in simulation fallback mechanisms that must be provided to apply the SDN concept into mobile wireless scenarios, and demonstrate one of the possible services that can be provided by a Software-Defined VANET.
Optimal training of thresholded linear correlation classifiers

A closed-form solution for improved pattern recognition that reduces the training time to a single epoch (one presentation of each of the training patterns) is presented. It is shown that the corresponding hardware requirements are no greater than those for regular recognition under certain conditions. A simple example which shows that the generalization obtained with the closed-form method exceeds that obtained by a model that admits only diagonal transformations is discussed.
TH17 Cells Mediate Steroid-Resistant Airway Inflammation and Airway Hyperresponsiveness in Mice

McKinley L, Alcorn JF, Peterson A, et al. J Immunol . 2008;181(6):4089–4097 PURPOSE OF THE STUDY. To investigate the function of T-helper 17 (TH17) cells in the context of antigen-induced airway inflammation. METHODS. The authors examined the role of TH17 cells in asthma by using a mouse model in which severe combined immunodeficient (SCID) mice were challenged with ovalbumin. On day 0, ovalbumin-specific TH2 or TH17 cells were adoptively transferred into the SCID mice. The SCID mice were challenged …
Parameter estimation of the manifold growth model using Z-graph

The manifold growth model that unifies existing software reliability growth models can cover a wide range of accumulated fault data including various types of data which are difficult to treat with existing models. However, there are problems. For example, it sometimes takes a long time to solve transcendental equations to estimate parameters of the model, and the solution is difficult to obtain in some cases. This paper shows that the most important parameters of the differential equation that defines the manifold growth model can be easily estimated for the given data by using a "Z-graph" to express the Z-equation derived from the differential equation in a 2-dimensional graph. This paper also shows that the most appropriate type of software reliability growth model, or the most appropriate shape of curve, can be determined simply by observing a part of the data sequence from Z-graph, since Z-graph makes it possible that the variation of the value of parameters at any time can be recognized visually. Finally, the effectiveness of the Z-graph is shown by applying the Z-graph to both ideal and actual data.
Multidimensional Structural Credit Modeling under Stochastic Volatility

This paper extends the structural credit model with underlying stochastic volatility to a multidimensional framework. The model combines the Black/Cox framework with the Heston model interpreting the equity of a company as a down-and-out barrier call option on the company's assets. This implies a combination of local and stochastic volatility on the equity as well as other stylized features. In this paper, we allow for a correlation between the asset processes of different companies to incorporate dependency structures. An estimator for the correlation parameter is derived and tested in a recovery framework. With the help of this model, we examine the default risk of the two mortgage lenders Fannie Mae and Freddie Mac before their actual placement into federal conservatorship and show that their default risk severely increased during the financial crisis.
Acute pain management in trauma

Major trauma affects more than 20 000 people per annum in the UK. Some three quarters of these patients will experience moderate-to-severe pain either as a direct result of their injuries or during the course of their management. Acute pain is associated with activation of the stress response. Poorly treated pain can also result in considerable psychological stress, which can impact on ongoing treatment and rehabilitation post-injury. Additionally, pain may persist to become chronic pain — up to two-thirds of major trauma victims report ongoing pain severe enough to affect quality of life for several years after injury. Delivery of effective analgesia has been shown to reduce the adverse effects on outcome associated with undertreated pain.
Keyholes, correlations, and capacities of multielement transmit and receive antennas

Multielement system capacities are usually thought of as limited only by correlations between elements. It is shown here that degenerate channel phenomena called "keyholes" may arise under realistic assumptions which have zero correlation between the entries of the channel matrix H and yet only a single degree of freedom. Canonical physical examples of keyholes are presented. For outdoor environments, it is shown that roof edge diffraction is perceived as a "keyhole" by a vertical base array that may be avoided by employing instead a horizontal base array.
What Respondents Really Expect From Researchers

This article addresses the issue of falling response rates in telephone surveys. To better understand and maintain respondent goodwill, concepts of psychological contract and respondent expectations are introduced and explored. Results of the qualitative study show that respondent expectations are not only socially contingent but also ego-expressive, utilitarian, pleasurable, and epistemic by nature. Although results are reassuring in terms of commercialization of the psychological contract, they indicate some radical changes that are needed for the respondents to accept its continuation. The article discusses several practical and theoretical implications of such changes and suggests a series of corresponding propositions aimed at facilitating and inspiring future developments in this field.
Economic Evaluation of Continuing Care Interventions in the Treatment of Substance Abuse

The chronic and relapsing nature of substance abuse points to the need for continuing care after a primary phase of treatment. This article reviews the economic studies of continuing care, discusses research gaps, highlights some of the challenges of conducting rigorous economic evaluations of continuing care, and offers research guidelines and recommendations for future economic studies in this emerging field. Rigorous economic evaluations are needed by health care providers and policy makers to justify the allocation of scarce resources to continuing care interventions. The adoption of cost-effective continuing care services can reduce long-term consequences of addiction, thereby potentially increasing overall social welfare.