Miracle-dz/UniFAR-FTUs huggingface dataset:
Commentary: assessment of non‐alcoholic fatty liver disease using serum total cell death and apoptosis markers – authors’ reply

We thank Miller and Dillon for their comments. Their first point was on the definition of non-alcoholic steatohepatitis (NASH) and whether some NASH patients might have non-alcoholic fatty liver disease activity score (NAS) below 5 points. Among 69 patients classified as NASH in our study, 32 (46%) had NAS over 5 points. While we agree with Miller and Dillon that the inclusion of less florid cases in the NASH group might lead to lower apparent diagnostic accuracy of the cytokeratin18-based cell death biomarkers, the meaning of NAS deserves clarification. According to current guidelines, NASH is a histological diagnosis based on global features of hepatic steatosis, inflammation and hepatocyte ballooning. In contrast, NAS is the unweighted sum of the scores of these 3 histological parameters. NAS was originally developed by the NASH Clinical Research Network (CRN) to assess treatment response in NASH trials. However, since its introduction, many hepatologists have mistaken its meaning and used a cut-off of 5 points to diagnose NASH. A number of subsequent studies suggest that this approach is inappropriate. When pathologists from the NASH CRN reviewed the histology and clinical data of 976 adult NAFLD patients, only 75% of patients with definite NASH had NAS above 5, and at least 29% of patients with NAS below 5 had NASH. In an independent study of 386 adult patients, NAS was again shown to have only moderate correlation with the diagnosis of NASH. 7 Finally, we agree that one of the important roles of new biomarkers of NASH is to monitor disease activity over time because serial liver biopsies are unrealistic outside research setting. 9 Further studies should be conducted to evaluate the performance of biomarkers against serial biopsies. This will eventually reduce the need for liver biopsy and improve patient care.
A Domain Decomposition Method With Nonconformal Meshes for Finite Periodic and Semi-Periodic Structures

We present a domain decomposition method as a preconditioner for Krylov-type solvers to model complex electromagnetic problems containing periodicities. The method reduces memory requirements by decomposing the original problem into several nonoverlapping sub-domains. The 1st order transmission condition is employed on interfaces between adjacent sub-domains to enforce continuity of electromagnetic fields and to ensure the sub-domain problems are well-posed. By following the spirit of duality paring a symmetric system is obtained. To reduce the computational burdens of the present method, the finite element tearing and interconnecting like algorithm is adopted. This algorithm results in the computation of the so-called "numerical" Green's function, which can be compressed efficiently via a rank-revealing matrix factorization algorithm. The final system matrix is solved by Krylov solvers instead of classical stationary solvers. To improve the convergence of iterative solvers, several robust implementation details are discussed and the choice of some popular Krylov-subspace solvers is studied through numerical examples.
A gene transfer vector-cell line system for complete functional complementation of adenovirus early regions E1 and E4

The improvements to adenovirus necessary for an optimal gene transfer vector include the removal of virus gene expression in transduced cells, increased transgene capacity, complete replication incompetence, and elimination of replication-competent virus that can be produced during the growth of first-generation adenovirus vectors. To achieve these aims, we have developed a vector-cell line system for complete functional complementation of both adenovirus early region 1 (E1) and E4. A library of cell lines that efficiently complement both E1 and E4 was constructed by transforming 293 cells with an inducible E4-ORF6 expression cassette. These 293-ORF6 cell lines were used to construct and propagate viruses with E1 and E4 deleted. While the construction and propagation of AdRSV beta gal.11 (an E1-/E4- vector engineered to contain a deletion of the entire E4 coding region) were possible in 293-ORF6 cells, the yield of purified virus was depressed approximately 30-fold compared with that of E1- vectors. The debilitation in AdRSV beta gal.11 vector growth was found to correlate with reduced fiber protein and mRNA accumulation. AdCFTR.11A, a modified E1-/E4- vector with a spacer sequence placed between late region 5 and the right inverted terminal repeat, efficiently expressed fiber and grew with the same kinetic profile and virus yield as did E1- vectors. Moreover, purified AdCFTR.11A yields were equivalent to E1- vector levels. Since no overlapping sequences exist in the E4 regions of E1-/E4- vectors and 293-ORF6 cell lines, replication-competent virus cannot be generated by homologous recombination. In addition, these second-generation E1-/E4- vectors have increased transgene capacity and have been rendered virus replication incompetent outside of the new complementing cell lines.
Specific Attitudes in Initial Interviews with Patients Having Different “Psychosomatic” Diseases

&NA; A specificity‐of‐attitude hypothesis, proposed by Grace and Graham,3 stated that there is a specific relation between the attitude towards a stressful stimulus and the disease which occurs in response to the stimulus. Two interview studies with hospitalized patients investigated whether attitudes predicted to be associated with diseases were more applicable to patients having the disease in question than to patients who did not have the disease. There were 16 patients with eight diseases in the first study, and 20 patients' with ten diseases in the second study. Half of the patients, matched for disease, were interviewed by a psychologist unfamiliar with the specific predictions of the hypothesis under investigation. The recorded interviews were edited to remove references identifying diseases and were submitted to two medical and two nonmedical judges. Judges selected from a list of 18 previously described attitudes the three attitudes most similar to those expressed in each interview. They also ranked all 18 attitudes in the order of their applicability to the patient. The percentage of predicted choices was significantly greater than the expected percentage in both studies, and in both the blind and the nonblind interviews. The average of correctly predicted choices in the two studies were 28 per cent and 45 per cent for. the blind interviews, and 38 per cent and 62 per cent for the nonblind interviews. Three judges chose the predicted attitudes significantly often from the interviews conducted blind and all four judges chose the predicted attitudes significantly often from the nonblind interviews. Judges showed significant agreement with one another and the nonmedical judges did as well as the medical. A particular attitude was ranked lower, i.e., was judged more applicable than others, when patients had the associated disease than when they had other diseases. The ranks for predicted attitude‐disease associations were significantly lower in the blind interviews of the second study and in the nonblind interviews of both studies. It was concluded that different psychosomatic diseases are associated with different attitudes. The association was demonstrated even when a naive interviewer and naive judges were employed.
Role of Fas Ligand in Ocular Tissue

The expression of Fas ligand (FasL) in the eye is an important factor in the maintenance of immune privilege. Although FasL expression in donor corneas contributes to prolonged survival of orthotopic corneal allografts in solid organ transplantation, FasL gene-transfected tissues reportedly lead to graft destruction through neutrophil recruitment. Differences in the effects of FasL have been attributed to different roles of soluble FasL (sFasL) and membrane FasL (mFasL). This is based on the presumption that the signals through sFasL and mFasL differ, with one causing apoptosis and the other activating inflammation. It was recently reported that inflammation caused by FasL was inhibited at an immune-privileged site, and therefore the effects of FasL may depend on differences in the anatomic sites where FasL-expressing cells are located. In this article, we discuss the role of sFasL and mFasL in ocular immune privilege.
A Note on “A Catalog of Biases in Questionnaires” [Response to Letter]

A Note on " A Catalog of Biases in Questionnaires " [Response to Letter] LETTER TO THE EDITOR Suggested citation for this article: Choi BCK, Pak AWP. A note on " A Catalog of Biases in Questionnaires " [response to letter]. Prev Chronic Dis [serial online] 2005 Apr [date cited]. In Reply: We would like to thank Dr Harrow (1) for pointing out a flawed example in our paper (2). As he notes, the recommended question should be: How many cigarettes do you smoke per day? [ ] None [ ] 1–4 [ ] 5–24 [ ] 25 or more The previously recommended category " 4 or less " was a typographical error. References 1. Harrow JJ. A note on " A Catalog of Biases in Questionnaires " [letter to editor]. or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
On designing circuit primitives for cortical processors with memristive hardware

Cortical processors, inspired by the neocortex, offer a promising paradigm to build the next generation of massively parallel, energy efficient, real-time information processing systems. Efforts in realizing a scalable cortical processor in hardware are hindered by stringent design requirements, including high degrees of connectivity, dense weight storage, robustness to variability, and complex hierarchical structures. Emerging memristive devices are proven to be effective in emulating the plasticity characteristics of the neocortex, including synaptic and non-synaptic plasticity, within a single device. In this paper, we review various approaches in designing and realizing memristive hardware primitives for cortical processors such as neurons, synapses, training functions. Scalability and associated challenges for large-scale network realization are also reviewed. Further, we discuss the application space of such processors.
A new approach in the BCI research based on fractal dimension as feature and Adaboost as classifier

High rate classification of imagery tasks is still one of the hot topics among the brain computer interface (BCI) groups. In order to improve this rate, a new approach based on fractal dimension as feature and Adaboost as classifier is presented for five subjects in this paper. To have a comparison, features such as band power, Hjorth parameters along with LDA classifier have been taken into account. Fractal dimension as a feature with Adaboost and LDA can be considered as alternative combinations for BCI applications.
From incubation to maturity inside parks: the evolution of local knowledge networks

This paper analyses the effect of the evolution of local knowledge networks on the innovative capacity of firms co-located. Using a network dynamic approach, this paper argues that the length of time that firms spend in a science park affects their local knowledge network. By the identification of three stages of local development - incubation, growth and maturity - this study provides new insights about the role of science parks in both increasing their innovative capacity and promoting the exchange of knowledge among co-located firms. In this sense, science parks have been increasingly considered as a nurturing environment for business start-ups and lead to the development of growth-oriented firms, not being a consensus about how the length of time the firm spends in the park may affect these benefits.
Novel clinical trial designs for the development of new antiretroviral agents

The resounding success of combination antiretroviral efficacy for both treatment-naïve and treatment-experienced patients – with 70–90% viral suppression rates in recent studies – has made registration trials for new agents challenging. With the inevitable specter of drug resistance, new agents must have a pathway to approval. The Forum for Collaborative HIV Research obtained input from concerned stakeholders including industry, clinical sciences, community advocacy, and regulatory sciences (Food and Drug Administration and European Medicines Agency) to discuss how safety and efficacy of new agents could be demonstrated. Recognizing the shortfalls of superiority or noninferiority trials in this environment, a new trial design for treatment-experienced patients, minimizing the risk for drug resistance but allowing full assessment of safety, was proposed. The antiviral efficacy of an active investigational drug would be assessed by comparison to placebo as an add-on to a failing regimen in a short, 10–14-day study followed by institution of an optimized background regimen (OBR) in both arms with investigational drug given to all patients. The follow-on stage would assess dose response, safety, durability of initial response, and development of resistance. Additionally, a second safety trial could be conducted comparing patients randomized to the investigational agent with a new OBR to those on a new OBR and placebo. Finally, approval decisions could consider other long-term safety endpoints. Exposing treatment-naïve patients to investigational agents remains a controversial issue; stakeholders have different interpretations of risk–benefit for trials in this population that necessitate careful consideration before initiating trials in them.
TAp73 Is a Downstream Target of p53 in Controlling the Cellular Defense against Stress*

TAp73 is a p53 tumor suppressor gene homologue that is known to be mainly involved in apoptosis. We report here that TAp73 is necessary for the cellular response to oxidative stress and that TAp73 functions as a downstream target of p53 in this process. We show that p53 physically interacts with the TAp73 promoter under stress conditions that lead to cell death. Particularly, p53 binds to a palindromic site in the TAp73 promoter, activates the promoter of TAp73, and selectively induces TAp73 transcription. TAp73 expression is highly increased under oxidative stress in a p53-dependent manner. Furthermore, knock-down of TAp73 expression inhibits the cellular apoptotic response to oxidative damage. In contrast, the ectopic expression of TAp73 in p53–/– mouse embryonic fibroblasts induces oxidative cell death. Our findings demonstrate that p53 is a direct transcriptional regulator of TAp73. Our data reveal a new pathway for cellular protection against oxidative damage and provide evidence that TAp73 is a stress-response gene and a downstream effector in the p53 pathway.
The effect of strain heterogeneities on Rb-Sr and Sm-Nd isotopic re-equilibration in minerals and rocks

Kombinierte mikrostrukturelle und mineralchemische Analysen der gesteinsbildenden Minerale Muskowit und Albit zeigen, dass ein bedeutender Anteil der Permischen Metapegmatite durch die Deformation beeinflusst wurde und dass dies mit signifikanten chemischen Alterationen einhergeht. Allerdings zeigen die Daten, dass Rb–Sr Isotopendaten von Muskowit offensichtlich nicht mit deren Hauptelementchemie korrelieren. Detaillierte Resultate der Rb–Sr Analyse von verschiedenen Korngrossen– und Magnetfraktionen von Muskowit stellen bestehende Modelle isotopischer Rehomogenisierung in Frage. Die Resultate demonstrieren einen wesentlichen Effekt von, vermutlich deformationsbezogenem, Verlust von Sr auf die 87Rb/86Sr Verhaltnise von Muskowit ohne eine signifikante 87Sr/86Sr Rehomogenisierung. Die Steigungen von Muskowit–internen `Errorchronen´ basierend auf bis zu 5 Korngrossen– und Magnetfraktionen, scheinen den Zeitpunkt des uberpragenden Events einzugrenzen. Ein anderer wesentlicher Punkt ist die Prasenz von mindestens einer Korngrosen– und Magnetfraktion, typischerweise jene mit den niedrigsten 87Rb/86Sr und 87Sr/86Sr Verhaltnisen, welche als Permotriassisches Bildungs– oder Abkuhlalter interpretiert wird. Zusammenfassend liefern die Untersuchungen von verschiedenen Korngrosen– und Magnetfraktionen von Muskowit einzelner Proben einen umfassenden Datensatz, welcher signifikante systematische Variationen im Rb–Sr Isotopensystem im Handstucksbereich dokumentiert. Ebenso zeigt diese Arbeit eine Abhangigkeit von Haupt– und Spurelement– und Isotopenverteilung von lokaler Deformation und effektiven Deformationsmechanismen.
Monte Carlo simulation using the PENELOPE code with an ant colony algorithm to study MOSFET detectors

In this work we have developed a simulation tool, based on the PENELOPE code, to study the response of MOSFET devices to irradiation with high-energy photons. The energy deposited in the extremely thin silicon dioxide layer has been calculated. To reduce the statistical uncertainties, an ant colony algorithm has been implemented to drive the application of splitting and Russian roulette as variance reduction techniques. In this way, the uncertainty has been reduced by a factor of ∼5, while the efficiency is increased by a factor of above 20. As an application, we have studied the dependence of the response of the pMOS transistor 3N163, used as a dosimeter, with the incidence angle of the radiation for three common photons sources used in radiotherapy: a 60Co Theratron-780 and the 6 and 18 MV beams produced by a Mevatron KDS LINAC. Experimental and simulated results have been obtained for gantry angles of 0o, 15o, 30o, 45o, 60o and 75o. The agreement obtained has permitted validation of the simulation tool. We have studied how to reduce the angular dependence of the MOSFET response by using an additional encapsulation made of brass in the case of the two LINAC qualities considered.
Diepitopic Construct of Functionally and Epitopically Complementary Peptides Enhances Immunogenicity, Reactivity with Glucosyltransferase, and Protection from Dental Caries

ABSTRACT Coimmunization with peptide constructs from catalytic (CAT) and glucan-binding (GLU) domains of glucosyltransferase (GTF) of mutans streptococci has resulted in enhanced levels of antibody to the CAT construct and to GTF. We designed and synthesized a diepitopic construct (CAT-GLU) containing two copies of both CAT (B epitope only) and GLU (B and T epitope) peptides. The immunogenicity of this diepitopic construct was compared with that of individual CAT and GLU constructs by immunizing groups of Sprague-Dawley rats subcutaneously in the salivary gland vicinity with the CAT-GLU, CAT, or GLU construct or by treating rats by sham immunization. Levels of serum immunoglobulin G (IgG) antibody to GTF or CAT in the CAT-GLU group were significantly greater than in GLU- or CAT-immunized groups. Immunization with CAT-GLU was compared to coimmunization with a mixture of CAT and GLU in a second rodent experiment under a similar protocol. CAT-GLU immunization resulted in serum IgG and salivary IgA responses to GTF and CAT which were greater than after coimmunization. Immunization with the diepitopic construct and communization with CAT and GLU constructs showed proliferation of T lymphocytes to GTF. Immunization with either the CAT or GLU construct has been shown to elicit significant protection in a rodent dental caries model. Similarly in this study, the enhanced response to GTF after immunization with the CAT-GLU construct resulted in protective effects on dental caries. Therefore, the CAT-GLU diepitopic construct can be a potentially important antigen for a caries vaccine, giving rise to greater immune response than after immunization with CAT, GLU, or a mixture of the two.
Advanced Technologies of Preventive Maintenance for Thermal Power Plants

OVERVIEW: Although thermal power generating facilities are aging, flexible operation in response to changes in the demand for electrical power is required. To extend the life and manage the maintenance of those facilities, advanced preventive maintenance technology is important. For that reason, Hitachi has been grappling with nondestructive inspection, life assessment technology, rationalization technology for scheduled inspections of the boilers, steam turbines, gas turbines and other machinery used in thermal power generation to strengthen preventive maintenance and increase the efficiency of maintenance. Recently, we have been developing products and services for advanced support for maintenance and preservation through the use of IT (information technology) and network technology, going beyond what has previously been available. Kiyoshi Shimomura, Dr. Eng. Hideaki Ishitoku Shigeo Sakurai, Dr. Eng. Fumiyuki Hirose
A Double-Blind, Crossover Assessment of the Sedative and Analgesic Effects of Intranasal Dexmedetomidine

BACKGROUND:The alpha2-receptor agonist, dexmedetomidine, provides sedation with facilitated arousal and analgesia with no respiratory depression. These properties render it potentially useful for anesthesia premedication, although parenteral administration is not practical in this setting. We designed this study to evaluate the sedative, anxiolytic, analgesic, and hemodynamic effects of dexmedetomidine administered intranasally in healthy volunteers. METHODS:Koch's design for crossover trials (three-treatment and two-period design) was adopted. The study was double-blind and there were three treatment groups: A (placebo), B (intranasal dexmedetomidine 1 &mgr;g/kg) and C (intranasal dexmedetomidine 1.5 &mgr;g/kg). Each of the 18 subjects participated in two study periods. The study drug was administered intranasally after baseline observations of modified Observer Assessment of Alertness/Sedation Scale, visual analog scale of sedation, bispectral index, visual analog scale of anxiety, pain pressure threshold measured by an electronic algometer, systolic blood pressure (SBP) and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation. These were repeated during the course of the study. RESULTS:Intranasal dexmedetomidine was well tolerated. Both 1 and 1.5 &mgr;g/kg doses equally produced significant sedation and decreases in bispectral index, SBP, diastolic blood pressure, and heart rate when compared with placebo (P < 0.05). The onset of sedation occurred at 45 min with a peak effect at 90–150 min. The maximum reduction in SBP was 6%, 23%, and 21% for Groups A, B, and C respectively. There was no effect on pain pressure threshold, oxygen saturation or respiratory rate. Anxiolysis could not be evaluated as no subjects were anxious at baseline. CONCLUSION:The intranasal route is effective, well tolerated, and convenient for the administration of dexmedetomidine. Future studies are required to evaluate the possible role of the noninvasive route of administration of dexmedetomidine in various clinical settings, including its role as premedication prior to induction of anesthesia.