Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of heparin-binding epidermal growth factor-like growth factor in light-induced photoreceptor degeneration in mouse retina.

PURPOSE Although heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been reported to have protective effects against various neuronal cell damage, its role in the retina has not been elucidated. Here, we investigated its role in light-induced photoreceptor degeneration using retinas and ventral forebrain-specific Hb-egf knockout (KO) mice. METHODS Disruption of Hb-egf was confirmed by β-galactosidase (LacZ) staining and RT-PCR. Time-dependent changes in retinal HB-EGF were measured using quantitative RT-PCR and Western blotting. Retinal damage was induced by exposure to light. Recombinant human HB-EGF was injected intravitreally. Electroretinogram (ERG) and histological analyses were performed. To evaluate the effect of HB-EGF against light irradiation-induced cell death, 661W cells, a transformed mouse cone cell line, were used. RESULTS LacZ-positive cells were observed and Hb-egf deletion was confirmed in the retinas of Hb-egf KO mice. Hb-egf and pro-HB-EGF levels were increased after light exposure in wild-type (WT) mice. Exposure to light reduced the a- and b-wave amplitudes of the dark-adapted ERG, and also outer nuclear layer (ONL) thickness, in Hb-egf KO mice versus WT mice. Treatment with HB-EGF improved both the a- and b-wave amplitudes and the thickness of the ONL. The 661W cell death induced by light irradiation was exacerbated by Hb-egf knockdown. HB-EGF also protected against light-induced cell death and reduced reactive oxygen species (ROS) production in 661W cells. HB-EGF treatment improved the a-wave amplitudes and the thickness of the ONL in Hb-egf KO mice. CONCLUSIONS These data suggest that HB-EGF plays a pivotal role in light-induced photoreceptor degeneration. It therefore warrants investigation as a potential therapeutic target for such light-induced retinal diseases as age-related macular degeneration.
Age‐dependent changes in T cell homeostasis and SIV load in sooty mangabeys

Sooty mangabeys (Cercocebus atys) showed age‐dependent changes in T cell regeneration. Younger animals had a high percentage of CD4+ CD45RA+ T cells and a high concentration of T cell receptor excisional circles (TRECs) in peripheral blood, which indicated active thymopoiesis. In contrast, older animals had an increased T cell turnover, which suggested that most T cell production occurred in the periphery. In addition, the number of peripheral CD4+ T cells naturally decreased with age. Non‐pathogenic SIVsm infection did not significantly change the T cell proliferation rate or the TREC concentration, though it did cause a moderate loss of peripheral CD4+ T cells. The viral load correlated negatively with age, which could be accounted for by the reduced availability of CD4+ target cells in older mangabeys. Thus, the number of susceptible target cells may be a limiting factor in natural SIV infection.
Study of the effect exerted by fructo-oligosaccharides from yacon (Smallanthus sonchifolius) root flour in an intestinal infection model with Salmonella Typhimurium

Beneficial effects of prebiotics like inulin and fructo-oligosaccharides (FOS) have been proven in health and nutrition. Yacon (Smallanthus sonchifolius), an Andean crop, contains FOS (50–70 % of its dry weight) and, therefore, is considered a prebiotic. Commercial FOS can up-regulate total secretory IgA (S-IgA) in infant mice, prevent infection with Salmonella in swine or enhance immune response for Salmonella vaccine in a mouse model. Previously, we found that administration of yacon root flour regulates gut microbiota balance and has immunomodulatory effects without inflammatory responses. The aim of the present paper is to analyse if yacon prevents enteric infection caused by a strain of Salmonella enteritidis serovar Typhimurium (S. Typhimurium) in a mouse model. BALB/c mice were supplemented with yacon flour (45 d), challenged with S. Typhimurium and killed to study pathogen translocation, total and specific IgA production by ELISA, presence of IgA and other cytokines and Toll-like receptor 4 (TLR4) and clustor of differentiation 206 (CD206) receptors positive cells by immunofluorescence and histological changes. Yacon flour administration had a protective effect from 15 to 30 d of treatment. We found a peak of total S-IgA production without translocation of the pathogen for these periods. At 30 d, there was an increase in IL-6 and macrophage inflammatory proteins-1α+ cells and expression of the receptors CD206 and TLR4. Yacon flour did not have incidence in pathogen-specific S-IgA production. Longer periods (45 d) of administration had no protective effect. Therefore, yacon can prevent enteric infection caused by S. Typhimurium when given up to 30 d; this effect would be mediated by enhancing non-specific immunity, such as total S-IgA, that improves the immunological intestinal barrier.
Airn Transcriptional Overlap, But Not Its lncRNA Products, Induces Imprinted Igf2r Silencing

Long Noncoding RNAs The past 5 years have uncovered thousands of long (>100 nucleotides) noncoding RNAs (lncRNAs) outpacing our understanding of their functions and mechanisms in regulating the genome. Lee (p. 1435) reviews the known and suspected means by which these intriguing molecules control gene expression locally and at great distances, considers potential universal roles for lncRNAs, and warns that classifying these intriguing molecules may be quite challenging given their diversity. The very long noncoding RNA, Airn, silences the Igf2r (insulin-like growth factor 2 receptor) imprinted gene cluster in mammals. Latos et al. (p. 1469) show in mouse cells that, rather than recruiting enzymes that modify histones to repress the locus, it is the act of transcription of Airn (and not the Airn gene product) that results in the silencing. A very long noncoding RNA acts to silence its target gene cluster through transcriptional interference. Mammalian imprinted genes often cluster with long noncoding (lnc) RNAs. Three lncRNAs that induce parental-specific silencing show hallmarks indicating that their transcription is more important than their product. To test whether Airn transcription or product silences the Igf2r gene, we shortened the endogenous lncRNA to different lengths. The results excluded a role for spliced and unspliced Airn lncRNA products and for Airn nuclear size and location in silencing Igf2r. Instead, silencing only required Airn transcriptional overlap of the Igf2r promoter, which interferes with RNA polymerase II recruitment in the absence of repressive chromatin. Such a repressor function for lncRNA transcriptional overlap reveals a gene silencing mechanism that may be widespread in the mammalian genome, given the abundance of lncRNA transcripts.
THE SURVEY OF INCOME AND PROGRAM PARTICIPATION PRIVATE HEALTH INSURANCE AND THE UTILIZATION OF MEDICAL CARE BY THE ELDERLY No

In this study, we report that unobserved common factors are powerful explanation of the decision to have private health insurance and the use of medical care by elderly Medicare recipients. This indicates that unobserved factors leading some individuals to have private health insurance coverage to fill in the gaps in Medicare also cause these individuals to seek more medical care than other Medicare enrollees. Simultaneity is also significant between the decisions to have private health insurance in addition to Medicare coverage and to visit a doctor, but not between the decisions to have private health insurance and the number of doctor visits nor the use of hospital care. Other results indicate that health status and functional limitations are significant determinants of whether an individual has private health insurance and the decision to seek medical care and subsequent decisions concerning the levels of utilization. Other characteristics (age, sex, race, education, marital status, and region) are significant in the decision to have private health insurance, but less important in the utilization of medical care. Unlike prior studies in which health insurance coverage is not jointly estimated with use of medical care, we find that education and income have only an effect on use of medical care. Table A.1 Coefficients from Probits of Medicaid Enrollment
The role of the lateral hypothalamus and orexin in ingestive behavior: a model for the translation of past experience and sensed deficits into motivated behaviors

The hypothalamus has been recognized for its involvement in both maintaining homeostasis and mediating motivated behaviors. The present article discusses a region of the hypothalamus known as the lateral hypothalamic area (LHA). It is proposed that brain nuclei within the LHA including the dorsal region of the lateral hypothalamus (LHAd) and perifornical area (PeF) provide a link between neural systems that regulate homeostasis and those that mediate appetitive motivated behaviors. Functional and immunohistochemical data indicate that the LHA promotes many motivated behaviors including food intake, water intake, salt intake, and sexual behavior. Anatomical tracing experiments demonstrate that the LHA is positioned to receive inputs from brain areas involved in regulating body fluid and energy homeostasis. Regions within the LHA send dense projections to the ventral tegmental area (VTA), providing a pathway for the LHA to influence dopaminergic systems generally recognized to be involved in motivated behaviors and their reinforcement. Furthermore, the LHA contains neurons that synthesize orexin/hypocretin, a neuropeptide that promotes many appetitive motivated behaviors. The LHA also receives inputs from brain areas involved in reward-related learning and orexin neuron activation can become conditioned to environmental stimuli that are associated with rewards. Therefore, it is hypothesized that the LHA integrates signaling from areas that regulate body fluid and energy balance and reward-related learning. In turn, this information is “fed into” mesolimbic circuitry to influence the performance of motivated behaviors. This hypothesis may foster experiments that will result in an improved understanding of LHA function. An improved understanding of LHA function may aid in treating disorders that are associated with an excess or impairment in the expression of ingestive behavior including obesity, anorexia, impairments in thirst, salt gluttony, and salt deficiency.
Development of Bioadhesive Transdermal Bupivacaine Gels for Enhanced Local Anesthetic Action

Topical drug dosage forms such as ointments and creams can be easily removed through wetting, movement and contact. The new bioadhesive formulations with enhanced local anesthetic effects are needed for topical administration. The adhesive capacity of hydroxypropyl methylcellulose (HPMC) was determined by measuring the maximum detachment force and the adhesion work with an auto peeling tester. The release of drug from a HPMC gel was studied according to the drug concentration. Permeation study through the rat skin was performed at 37°C using phosphate buffer solution (pH = 7.4) as a receptor medium. To increase the skin permeation of bupivacaine from the HPMC gels, penetration enhancer such as the saturated and unsaturated fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were incorporated in the bupivacaine-HPMC gels. The local anesthetic effect of the formulated gel preparation was examined using a tail-flick analgesimeter. As the concentration of HPMC increased, the bioadhesive force and viscosity were increased. The rate of drug release was increased with increasing the drug concentration. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the most enhancing effects on drug permeation through the skin. In the rat tail flick test, the area under the efficacy curve of bupivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed a 2.36-fold increase in anesthetic activity compared to control gel without any additives. The bupivacaine gels containing both penetration enhancer and vasoconstrictor showed enhancement and prolonged efficacy compared to the control gel. To enhance the local anesthetic effects of bupivacaine, the transdermal bupivacaine gel formulation containing penetration enhancer and vasoconstrictor could be developed.
Rational Development of Histone Deacetylase Inhibitors as Anticancer Agents: A Review

The epigenome is defined by DNA methylation patterns and the associated post-translational modifications of histones. This histone code determines the expression status of individual genes dependent upon their localization on the chromatin. The histone deacetylases (HDACs) play a major role in keeping the balance between the acetylated and deacetylated states of chromatin and eventually regulate gene expression. Recent developments in understanding the cancer cell cycle, specifically the interplay with chromatin control, are providing opportunities for developing mechanism-based therapeutic drugs. Inhibitors of HDACs are under considerable exploration, in part because of their potential roles in reversing the silenced genes in transformed tumor cells by modulating transcriptional processes. This review is an effort to summarize the nonclinical and clinical status of HDAC inhibitors currently under development in anticancer therapy.
On the Roles of Corrosion Products in Local Cell Processes.

Abstract : This paper reviews work performed on the roles that corrosion products play in corrosion and materials degradation processes. Subject areas include: (1) 'wedging action' in which the tensile stresses required for crack propagation are generated by the formation of solid corrosion products within the crack cavity; (2) gas bubble formation and coalescence that eventually fills a major volume segment of a pit, crevice or crack; (3) an experimental determination and mathematical modeling of the local electrode potential and solution composition existing within active pits and crevices; (4) an analysis that shows the existence of a limiting electrode potential, E sub LIM, in a cavity and defines its value; (5) an analysis based on the E sub LIM concept and on known trends in concentrations of ionic species that provides a means for distinguishing between stress corrosion and hydrogen cracking in noble metal alloys.
An Experts' Perspective on Enterprise Architecture Goals, Framework Adoption and Benefit Assessment

In recent years, enterprise architecture (EA) management has become an intensively discussed approach in both industry and academia for managing the complexity of an enterprise from a holistic perspective. While there is a strong academic and practical interest in EA frameworks and EA modeling, there is a notable insecurity about the cost benefit ratio of EA. In this paper, we address this research problem with a qualitative research design. We conduct a series of semi-structured interviews with industry experts on enterprise architecture in order to identify classes of EA goals, corresponding EA frameworks adoption to achieve these goals and employed EA benefit assessment approaches. The findings point to, among others, a fairly stable set of EA goals that shift over time and EA frameworks that lack modularity and adjustment capabilities to easily customize towards these goals. This paper is part of an ongoing exploratory research that aims at researching which benefits emanate from EA.
A group intelligence-based asynchronous argumentation learning-assistance platform

Structured argumentation support environments have been built and used in scientific discourse in the literature. However, to the best our knowledge, there is no research work in the literature examining whether student’s knowledge has grown during learning activities with asynchronous argumentation. In this work, an intelligent computer-supported collaborative argumentation-based learning platform that detects whether the learners address the expected discussion issues is proposed. After each learner presents an argument, a term weighting method is adopted to derive input parameters of a one-class support vector machines classifier which determines if the learners’ arguments are related to the discussion topics. Notably, a peer review mechanism is established to improve the quality of the classifier. Besides, a feedback module is used to issue feedback messages to the learners if the learners have gone off on a tangent. The experimental results revealed that the students were benefited by the proposed learning-assistance platform.
Role of the 3′ tRNA-Like Structure in Tobacco Mosaic Virus Minus-Strand RNA Synthesis by the Viral RNA-Dependent RNA Polymerase In Vitro

ABSTRACT A template-dependent RNA polymerase has been used to determine the sequence elements in the 3′ untranslated region of tobacco mosaic virus RNA that are required for promotion of minus-strand RNA synthesis and binding to the RNA polymerase in vitro. Regions which were important for minus-strand synthesis were domain D1, which is equivalent to a tRNA acceptor arm; domain D2, which is similar to a tRNA anticodon arm; an upstream domain, D3; and a central core, C, which connects domains D1, D2, and D3 and determines their relative orientations. Mutational analysis of the 3′-terminal 4 nucleotides of domain D1 indicated the importance of the 3′-terminal CA sequence for minus-strand synthesis, with the sequence CCCA or GGCA giving the highest transcriptional efficiency. Several double-helical regions, but not their sequences, which are essential for forming pseudoknot and/or stem-loop structures in domains D1, D2, and D3 and the central core, C, were shown to be required for high template efficiency. Also important were a bulge sequence in the D2 stem-loop and, to a lesser extent, a loop sequence in a hairpin structure in domain D1. The sequence of the 3′ untranslated region upstream of domain D3 was not required for minus-strand synthesis. Template-RNA polymerase binding competition experiments showed that the highest-affinity RNA polymerase binding element region lay within a region comprising domain D2 and the central core, C, but domains D1 and D3 also bound to the RNA polymerase with lower affinity.
Investigation of the α−γ−α Phase Transformation in Steel: High-Temperature In Situ EBSD Measurements

A newly developed laser powered heating stage for commercial SEMs in combination with automated established electron backscatter diffraction (EBSD) data acquisition is presented. This novel experimental setup can be used to achieve more information about microstructure and orientation changes during grain growth, recrystallization, recovery, and phase transformations. First results on the α − γ − α phase transformation in steel within 886 ∘ C– 900 ∘ C are presented.
Pregnancy in the Woman with Epilepsy: Maternal and Fetal Outcomes

Pregnancy in women with epilepsy is associated with increased obstetric risks and increased adverse neonatal outcomes. Prior to conception, folic acid should be administered and the antiepileptic drug (AED) regimen should be optimized. Effective control of maternal seizures with the least risk to the fetus is the goal, preferably using AED monotherapy. Periodic monitoring of total and free AED levels is recommended. The "fetal anticonvulsant syndrome" has been described with all of the AEDs and includes major malformations, minor anomalies, microcephaly, cognitive impairment, intrauterine growth retardation, and infant mortality. The most common major malformations are cleft lip/palate, heart defects, and neural tube defects. Prenatal screening should be offered. Supplemental vitamin K(1) should be given to the mother and newborn to prevent neonatal hemorrhagic disorder. Careful planning and management of any pregnancy in women with epilepsy are essential to increase the likelihood of a healthy outcome for the mother and infant.
Lung Cancer Screening with Low-Dose CT in Female Never Smokers: Retrospective Cohort Study with Long-term National Data Follow-up

Purpose Because of growing concerns about lung cancer in female never smokers, chest low-dose computed tomography (LDCT) screening is often performed although it has never shown clinical benefits. We examinewhether or not female never smokers really need annual LDCT screening when the initial LDCT showed negative findings. Materials and Methods This retrospective cohort study included 4,365 female never smokers aged 40 to 79 years who performed initial LDCT from Aug 2002 to Dec 2007. Lung cancer diagnosis was identified from the Korea Central Cancer Registry Database registered until December 31, 2013. We calculated the incidence, cumulative probability, and standardized incidence ratio (SIR) of lung cancer by Lung Imaging Reporting and Data System (Lung-RADS) categories showed on initial LDCT. Results After median follow-up of 9.69 years, 22 (0.5%) had lung cancer. Lung cancer incidence for Lung-RADS category 4 was 1,848.4 (95% confidence interval [CI], 1,132.4 to 3,017.2) per 100,000 person-years and 16.4 (95% CI, 7.4 to 36.4) for categories 1, 2, and 3 combined. The cumulative probability of lung cancer for category 4 was 10.6% at 5 years and 14.8% at 10 years while they were 0.07% and 0.17% when categories 1, 2, and 3 were combined. The SIR for subjects with category 4 was 43.80 (95% CI, 25.03 to 71.14), which was much higher than 0.47 (95% CI, 0.17 to 1.02) for categories 1, 2, and 3 combined. Conclusion Considering the low risk of lung cancer development in female never smokers, it seems unnecessary to repeat annual LDCT screening for at least 5 years or even longer unless the initial LDCT showed Lung-RADS category 4 findings.
Computing the median with uncertainty

We consider a new model for computing with uncertainty. It is desired to compute a function f(X1,. . .,Xn), where X1, . , Xn are unknown but guaranteed to lie in specified intervals I1, . , In. It is possible to query the precise value of any Xj at a cost cj. The goal is to pin down the value of f to within a precision $\delta$ at a minimum possible cost. We focus on the selection function f which returns the value of the kth smallest argument. We present optimal offline and online algorithms for this problem.
The Emerging Role of Digital Technologies in Early Clinical Development

Pharmaceutical development is witnessing an increase in the use of digital technologies in the delivery of pharmaceutical substances, data generation, and data interpretation. These digital technologies offer the valuable benefits of speed, enhanced integration with various other components, visualization of a continuum, and improving precision of delivery or measurement. The adoption of these opportunities in early clinical development has been slow and sparse. This commentary analyzes these benefits, including the socialization and adoption of such practices.