Miracle-dz/UniFAR-FTUs huggingface dataset:
DNase I–hypersensitive sites enhance α1(I) collagen gene expression in hepatic stellate cells

Liver fibrosis is characterized by a dramatic increase in the expression of type I collagen. Several deoxyribonuclease (DNase) I–hypersensitive sites (HS) have been located in the distal 5′‐flanking region of the α1(I) collagen gene that are specific to collagen‐producing cells. To assess the role of the DNase I–HS in regulating α1(I) collagen gene expression in hepatic stellate cells (HSCs), 3 transgenic mouse lines expressing collagen‐α1(I) reporter genes were used (Krempen et al. Gene Expr 1999;8:151‐163). The pCol9GFP transgene contains the collagen gene promoter (−3122 to +111) linked to the green fluorescent protein (GFP) reporter gene. The pCol9GFP‐HS4,5 transgene contains HS4,5 and pColGFP‐HS8,9 contains HS8,9 positioned upstream of the collagen promoter in pCol9GFP. HSCs isolated from transgenic mice containing pCol9GFPHS4,5 and pColGFP‐HS8,9 showed earlier and higher GFP expression patterns than HSCs isolated from pCol9GFP mice. HSCs from pCol9GFP‐HS4,5 showed the highest levels of GFP expression and culture‐induced expression correlated with induction of the endogenous α1(I) collagen gene. After CCl4 administration, pCol9GFP‐HS4,5 mice showed increased GFP expression compared with pCol9GFP mice in both whole liver extracts and isolated HSCs. Several sites for DNA‐protein interactions in both HS4 and HS5 were identified that included a binding site for activator protein 1. In conclusion, DNase I–HS4,5 enhance expression of the α1(I) collagen gene promoter in HSCs both in vitro and in vivo after a fibrogenic stimulus. The collagen‐GFP transgenic mice provide a convenient and reliable model system to investigate the molecular mechanisms controlling increased collagen expression during fibrosis.
Influence of excess branched‐chain amino acid uptake by Streptococcus mutans in human host cells

Abstract Oral streptococci, including cariogenic bacterium Streptococcus mutans, comprise a large percentage of human supragingival plaque, which contacts both tooth surfaces and gingiva. Eukaryotic cells are able to take up macromolecules and particles, including bacteria, by endocytosis. Increasing evidence indicates endocytosis may be used as an entry process by bacteria. We hypothesized that some endocytosed bacteria might survive and obtain nutrients, such as amino acids, until they are killed. To verify this hypothesis, we focused on bacterial utilization of branched‐chain amino acids (BCAAs; isoleucine, leucine and valine) in host cells. A branched‐chain aminotransferase, IlvE (EC 2.6.1.42), has been suggested to play an important role in internal synthesis of BCAAs in S. mutans UA159. Therefore, we constructed an ilvE‐deficient S. mutans 109c strain and confirmed that it had similar growth behavior as reported previously. 14C radioactive leucine uptake assays showed that ilvE‐deficient S. mutans took up more leucine both inside and outside of host cells. We further clarified that a relative decrease of BCAAs in host cells caused enhanced endocytic and autophagic activity. In conclusion, S. mutans is endocytosed by host cells and may survive and obtain nutrients, such as BCAAs, inside the cells, which might affect cellular functions of host cells. Figure. No Caption available.
Pathology of hepatocellular carcinoma and its precursors using proton magnetic resonance spectroscopy and a statistical classification strategy

Aim: Apply the statistical classification strategy (SCS) to magnetic resonance spectroscopy (MRS) data from liver biopsies and test its potential to discriminate between normal liver, cirrhotic nodules and nodules of hepatocellular carcinoma with a high degree of accuracy. Methods: Liver tissue specimens from 54 patients undergoing either partial (hemi) or total hepatectomy were analysed by one‐dimensional proton MRS at 8.5 Tesla. Histologically, these specimens were confirmed as normal (n = 31), cirrhotic (n = 59), and hepatocellular carcinoma (HCC, n = 32). Diagnostic correlation was performed between the MR spectra and histopathology. An SCS was applied consisting of pre‐processing MR magnitude spectra to identify spectral regions of maximal discriminatory value, and cross‐validated linear discriminant analysis. Results: SCS applied to MRS data distinguished normal liver tissue from HCC with an accuracy of 100%. Normal liver tissue was distinguished from cirrhotic liver with an accuracy of 92% and cirrhotic liver was distinguished from HCC with an accuracy of 98%. Conclusions: SCS applied to proton MRS of liver biopsies provides a robust method to distinguish, with a high degree of accuracy, HCC from both cirrhotic and normal liver.
Public Service Quality Improvements: A Case for Exemption from IRB Review of Public Administration Research

Should the exemption from Institutional Review Board (IRB) evaluations currently in place for quality improvements research be extended to public administration research that addresses questions of improving the quality of public service delivery? As a means to both reduce the level of disdain held by a group of social science researchers for IRBs and to reduce the cost of review for minimal risk studies, I argue here that much of the current public administration research should also be exempted from normal processes of review by IRBs on the basis of their similarity to Quality Improvements (QI) research, a category of studies already granted exemption. This argument dovetails provisions currently in place for studies of public service and public benefit, but reframes these exemptions in the language of “quality improvements,” which may be a more comfortable language for IRBs concerned to demonstrate compliance for review of all fields. To expedite this argument into the practices of IRBs, I included a checklist that researchers could use to self-identify their studies as QI, not research as such.
Loss and recovery of liver regeneration in rats with fulminant hepatic failure.

We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P < 0. 01). During the first 36 hr, Group I rats had lower blood ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased in weight four times reaching 30% of the original liver mass, the transplant-bearing rats expired due to inability of the regenerating liver to support the rat.
Mapping of adenovirus 12 mRNA's transcribed from the transforming region

Adenovirus 12 mRNA's transcribed from the transforming region were analyzed and mapped on viral DNA by the nuclease S1 gel and diazobenzyloxymethyl paper blot techniques in cells transformed of adenovirus 12 DNA and in cells early and late after lytic infection with adenovirus 12. Two initiation sites of mRNA transcription and two kinds of splicing were found in each of early regions 1A and 1B. For early region 1A mRNA's, four species were found in lytically infected cells. Three of them were commonly found in cells transformed by either HindIII-G or EcoRI-C. Cells transformed by HindIII-G contained two additional 1A transcripts, which could be the 3' portions of chimeric mRNA's of cellular-viral or viral-viral sequences. Transcription in the 1B region diverged among the above cell lines. Early after lytic infection, no appreciable amount of 1B mRNA was detected, whereas two species of mRNA's, one corresponding to protein IX mRNA and another having splicing, were found at the late stage. In cells transformed by EcoRI-C, a distinct mRNA species with splicing was observed. Cells transformed by HindIII-G contained a transcript from the leftmost part of the 1B sequence at the 5' portion of chimeric mRNA species, suggesting the presence of tandem integration of viral DNA in the cells. Other mRNA species in the 1A and 1B regions were also detected in both transformed cell lines. The results are discussed in relation to the nucleotide sequence of the HindIII-G fragment of adenovirus 12 DNA.
Oral microbiome composition changes in mouse models of colitis

Oral mucosal pathologies are frequent in inflammatory bowel disease (IBD). Since host–microbiome interactions are implicated in the pathogenesis of IBD, in this study the potential for changes affecting the oral microbiome was evaluated using two complementary mouse models of colitis: either chemically (dextran sulfate sodium) or with Citrobacter rodentium infection.
The possible role of p53 and bcl-2 expression in cervical carcinomas and their premalignant lesions.

OBJECTIVE The purpose of this study was to assess the expression and clinical significance of bcl-2 and p53 in the progression of cervical neoplasias. METHODS One hundred seventy-one cervical specimens, consisting of normal cervical epithelium (n = 13), lesions with histological features of HPV infection (n = 14), CIN (cervical intraepithelial neoplasia) lesions (n = 63), and cervical carcinomas (n = 81) were examined immunohistochemically in paraffin sections. RESULTS Twenty-three specimens showed p53 expression [3/20 (15%) CIN III, 18/63 (29%) ISCC (invasive squamous cervical carcinoma), and 2/18 (11%) adenocarcinomas] while 63 cases expressed the bcl-2 gene [10/13 (77%) normal, 0/14(0%) condylomas, 6/23 (26%) CIN I, 9/20 (45%) CIN II, 15/20 (75%) CIN III, 18/63 (29%) ISCC, and 5/18 (28%) adenocarcinomas]. The expression of bcl-2 was found to increase in direct relation to the grade of CIN (P = 0.02) whereas such a trend was not observed for p53. p53 was not detected in normal or premalignant lesions (except 3 out of 20 cases of CIN III). There was no significant correlation between the expression of p53 and the histological type of cervical carcinoma, even though expression of p53 was higher in ISCC than in adenocarcinomas (29% vs 11%, respectively). In cervical cancer patients, expression of bcl-2 was correlated to a greater than 5-year survival (P < 0.01) while no prognostic significance of p53 expression was found. CONCLUSION Evaluation of bcl-2 expression may provide additional and independent prognostic information for the clinical course of the disease and therefore to be developed as a prognostic indicator for cervical cancer.
Do Online Gossipers Promote Brands?

Online gossip has been recognized as small talk on social networking sites (SNSs) that influences consumer behavior, but little attention has been paid to its role. This study makes three theoretical predictions: (a) propensity to gossip online leads to greater information value, entertainment value, and friendship value; (b) upon exposure to a high-involvement product, online gossipers are more willing to spread such information through electronic word-of-mouth (eWOM) in search of prestige or fame as a knowledge expert; and (c) this tendency will be more pronounced when they are connected with strong ties (rather than weak ties) and belong to a large network (rather than a small network). An experimental survey was conducted with a scenario method. In total, 818 general consumers participated in the survey. A multivariate analysis of variance (ANOVA) provides empirical support for prediction (1). With regard to predictions (2) and (3), a series of three-way and two-way between-subjective ANOVAs were performed. When a high-involvement product is promoted, gossipers, rather than nongossipers, are more willing to participate in eWOM on an SNS. Furthermore, a significant interaction effect indicates that online gossipers' willingness to particiapte in eWOM would be more pronounced if they belonged to a large network rather than a small network. However, when a low-involvement product is promoted, no interaction effect is found between online gossip and network size. In closing, theoretical and managerial implications are discussed, while important limitations are recognized.
The prostate‐specific G‐protein coupled receptors PSGR and PSGR2 are prostate cancer biomarkers that are complementary to α‐methylacyl‐CoA racemase

Immunohistochemistry (IHC) to detect α‐methylacyl‐CoA racemase (AMACR) expression can be useful in the diagnosis of small foci of prostate cancer on needle biopsy specimens, although it still has limitations in terms of both sensitivity and specificity. We have previously described the increased expression of two prostate‐specific G‐protein coupled receptors (PSGR and PSGR2) in human prostate cancer. To examine their potential usefulness as cancer biomarkers, we have evaluated their expression relative to AMACR in prostate cancer tissues.
Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo in the treatment of perennial allergic rhinitis

Abstract Objective: Bilastine is a non-sedating second-generation H1 antihistamine with proven efficacy and safety in the treatment of patients with seasonal allergic rhinitis and urticaria. The objective of this study was to demonstrate the efficacy and safety of bilastine in patients with perennial allergic rhinitis (PAR). Methods: In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, patients with symptomatic PAR (n = 650) from Argentina, Europe, and South Africa received bilastine 20 mg, cetirizine 10 mg, or placebo once daily for 4 weeks. The primary efficacy outcome was the mean area under the curve (AUC) of reflective total 6-symptom scores (rT6SS) from baseline visit to day 28 (D28). Secondary outcome measures included mean AUC of instantaneous total 6-symptom scores (iT6SS), and mean AUCs of reflective and instantaneous total 4-nasal symptom scores (T4NSS) and total 2-ocular symptom scores (T2OSS) from baseline to D28. An open-label extension phase evaluated the safety of bilastine 20 mg administered to patients (n = 513) for one year. Results: In the overall population no significant differences in efficacy outcomes were found between active treatments and placebo. On account of the high placebo response in South Africa, a post-hoc analysis was conducted. This analysis demonstrated that statistically significant differences existed between active treatments and placebo in the mean AUC of rT6SS (p < 0.05) and T4NSS (p < 0.02), respectively, from baseline to D28 visit for the intent-to-treat population in patients from Europe and Argentina, whereas the difference was not statistically significant in South Africa. Whether this is related to differences in the demographic or clinical characteristics of South African patients (they had PAR for longer and reported more severe symptoms) and/or the disease management process compared with their European and Argentinean counterparts warrants further investigation. Conclusions: A post-hoc analysis indicated that bilastine and cetirizine were similarly effective and more effective than placebo during a 4-week treatment period in patients with PAR. In addition, bilastine was shown to be safe and well-tolerated over a 1-year treatment period. Clinical trial registry number: NCT01127620.
Quantification of coronary artery calcification using ultrafast computed tomography: Reproducibility of measurements

BACKGROUND Ultrafast computed tomography (CT) is a non-invasive method of visualizing and quantifying coronary artery calcification; its reproducibility, however, has not been fully elucidated. METHODS To assess intra-observer, inter-observer, and inter-study reproducibility, 75 consecutive patients (51 men and 24 women) were studied. CT images were obtained using the volume mode of ultrafast CT (Imatron C-100). A total coronary calcification score (TCS) was calculated from the lesion area (> or = 2 pixels) and its peak CT density (> or = 130 HU). RESULTS There was no intra-observer variability in two experienced observers. The TCS provided by these observers disagreed in 18 out of 75 (24%) cases, and the differences were -5.1 +/- 53 (mean +/- SD) for TCS and 0.014 +/- 0.13 for In(1 + TCS). They resulted from either 10 incorrect identifications of small coronary branches, or eight variations in determination of the ostial margin. The former was much smaller than the latter in TCS (0.66 +/- 3.0 and -48 +/- 165, respectively), but both were quite similar in In(1 + TCS) (0.082 +/- 0.31, 0.017 +/- 0.22, respectively). Between two scans, 50 out of 75 patients (67%) had different TCS values. The mean differences (95% confidence interval) were 1.8 +/- 106 (-210 to 214) in TCS, and -0.015 +/- 0.46 (-0.94 to 0.91) in In(1 + TCS). Because the differences increased with the mean values, the determination of TCS assumed a constant variance with increasing mean level. A comparison of scan images indicated that partial volume effects were responsible for this constant variance. CONCLUSION Partial volume effects play a key role in producing the variability of TCS determination, and log transformation should be used to interpret TCS values. Thus, for clinical purposes, we recommend that two scans be performed in rapid succession, and that the average of these two scans be used to determine TCS.
Comparison of enterotoxic activities of heat-stable enterotoxins from class 1 and class 2 Escherichia coli of swine origin

Pig small intestine develops age-dependent resistance to some (class 2 strains) enterotoxigenic Escherichia coli while remaining susceptible to others (class 1 strains). This study tested the hypothesis that class 1 and class 2 strains produce different subtypes of heat-stable enterotoxin (ST). The dose-response curves of small intestine to crude ST preparations from a class 1 and a class 2 strain were compared in several species. In infant mice, the class 1 ST preparation was less active than the class 2 ST preparation, whereas in rabbits the preparations were equally potent. However, in 1-, 7-, and 14-week-old pigs, the class 1 ST preparation was more active than the class 2 preparation. At low doses, both preparations caused reduced absorption in pigs of all three age groups, and at high doses the class 1 preparation caused secretion in all three age groups. In contrast, at high doses the class 2 preparation caused secretion in 1-week-old pigs but only reduced absorption in older pigs. when class 1 and class 2 ST preparations were fractionated by methanol extraction, in both cases the mouse-negative, pig-positive activity was associated with the methanol-insoluble fraction and mouse-positive, pig-positive activity was associated with the methanol-soluble fraction. The results are consistent with a hypothesis that class 1 and class 2 strains of enterotoxigenic E. coli produce different subtypes of ST and that the response of pig intestine to ST varies with both age and toxin subtype.
UvA-DARE ( Digital Academic Repository ) Talk and Tools : The best of both worlds in mobile user interfaces for E-coaching

In this paper, a user interface paradigm, called Talk-and-Tools, is presented for automated e-coaching. The paradigm is based on the idea that people interact in two ways with their environment: symbolically and physically. The main goal is to show how the paradigm can be applied in the design of interactive systems that offer an acceptable coaching process. As a proof of concept, an ecoaching system is implemented that supports an insomnia therapy on a smartphone. A human coach was replaced by a cooperative virtual coach that is able to interact with a human coachee. In the interface of the system, we distinguish between a set of personalized conversations (BTalk^) and specialized modules that form a coherent structure of input and output facilities (BTools^). Conversations contained a minimum of variation to exclude unpredictable behavior but included the necessary mechanisms for variation to offer personalized consults and support. A variety of system and user tests was conducted to validate the use of the system. After a 6-week therapy, some users spontaneously reported the experience of building a relationship with the e-coach. It is concluded that the addition of a conversational component fills an important gap in the design of current mobile systems.
Effect of a serotonin agonist (sumatriptan) on the peptidergic innervation of the rat cerebral dura mater and on the expression of c‐fos in the caudal trigeminal nucleus in an experimental migraine model

The supratentorial cerebral dura of the albino rat is equipped with a rich sensory innervation including nociceptive axons and their terminals, which display intense calcitonin gene‐related peptide (CGRP) immunoreactivity both in the connective tissue and around blood vessels. Stereotactic electrical stimulation of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine model, induces marked increase and disintegration of club‐like perivascular CGRP‐immunopositive nerve endings in the dura. Intravenous administration of sumatriptan, prior to electrical stimulation, prevents disintegration of perivascular terminals and induces accumulation of CGRP in terminal and preterminal portions of peripheral sensory axons. Consequently, immunopositive terminals and varicosities increase in size; accumulation of axoplasmic organelles results in a “hollow” appearance of many varicosities. Since sumatriptan exerts its anti‐migraine effect by virtue of its agonist action on 5‐HT1D receptors, we suggest that sumatriptan prevents the release of CGRP from dural perivascular terminals by an action at 5‐HT1D receptors. In the caudal trigeminal nucleus electrical stimulation of the trigeminal ganglion induces, in interneurons, increased expression of the oncoprotein c‐fos which is not prevented by intravenous application of sumatriptan. Disparate findings regarding this effect are partly due to the fact that sumatriptan very poorly passes the blood‐brain barrier and partly to different experimental paradigms used by different authors. J. Neurosci. Res. 48:449–464, 1997. © 1997 Wiley‐Liss, Inc.