Miracle-dz/UniFAR-FTUs huggingface dataset:
Btg2 Enhances Retinoic Acid-Induced Differentiation by Modulating Histone H4 Methylation and Acetylation

ABSTRACT Retinoic acid controls hematopoietic differentiation through the transcription factor activity of its receptors. They act on specific target genes by recruiting protein complexes that deacetylate or acetylate histones and modify chromatin status. The regulation of this process is affected by histone methyltransferases, which can inhibit or activate transcription depending on their amino acid target. We show here that retinoic acid treatment of hematopoietic cells induces the expression of BTG2. Overexpression of this protein increases RARα transcriptional activity and the differentiation response to retinoic acid of myeloid leukemia cells and CD34+ hematopoietic progenitors. In the absence of retinoic acid, BTG2 is present in the RARα transcriptional complex, together with the arginine methyltransferase PRMT1 and Sin3A. Overexpressed BTG2 increases PRMT1 participation in the RARα protein complex on the RARβ promoter, a target gene model, and enhances gene-specific histone H4 arginine methylation. Upon RA treatment Sin3A, BTG2, and PRMT1 detach from RARα and thereafter BGT2 and PRMT1 are driven to the cytoplasm. These events prime histone H4 demethylation and acetylation. Overall, our data show that BTG2 contributes to retinoic acid activity by favoring differentiation through a gene-specific modification of histone H4 arginine methylation and acetylation levels.
Postoperative Treatment With Topical Diclofenac Versus Topical Dexamethasone After Combined Phacotrabeculectomy With Mitomycin C

Objective:The objective of the study was to compare the efficacy and safety of topical dexamethasone sodium phosphate 0.1% (Sterodex) to diclofenac sodium 0.1% (Voltaren Ophthalmic) after combined phacotrabeculectomy with mitomycin C. Methods:This prospective, randomized, double-masked clinical trial includes 42 patients with glaucoma and cataract who underwent a combined phacotrabeculectomy. Patients were randomly assigned to postoperative treatment with topical diclofenac sodium 0.1% or topical dexamethasone phosphate 0.1%. Follow-up duration was 12 months and all examinations were masked. The main outcome measures were intraocular pressure (IOP), number of glaucoma medications, and bleb morphology. Results:Baseline characteristics of the diclofenac (n=21) and dexamethasone (n=21) patients were similar. Phacotrabeculectomy with both postoperative treatments was effective in reducing IOP, lowering the number of glaucoma medications and improving visual acuity at all follow-up points. The average number of medications taken by the dexamethasone group was significantly greater than the diclofenac group at 8 months (1.2±1.4 and 0.3±0.6, respectively, P=0.03). The mean bleb height of the diclofenac group was significantly higher than the dexamethasone group at 3 weeks (P=0.05), and the mean bleb width was significantly wider at 8 months (P=0.04). No significant group differences in IOP were found at any of the follow-up visits, although there was a clinical trend toward lower IOP values in the diclofenac group. Sixteen patients (76%) in the diclofenac group and 17 patients in the dexamethasone group (81%) completed 1 year of follow-up. Conclusions:In this preliminary study, diclofenac sodium is at least as good as topical dexamethasone phosphate for glaucoma patients undergoing two-site combined phacotrabeculectomy with mitomycin C.
Advances in Brief CDKN 2 A Germline Mutations in Individuals with Multiple Cutaneous Melanomas 1

Germ-line CDKN2A mutations are present in some kindreds with hereditary cutaneous melanoma, and in Sweden a founder mutation with an extra arginine in codon 113 (113insR) has been identified. We screened 80 individuals with at least two primary cutaneous melanomas, who were identified mainly by a search of a regional cancer registry, for germ-line CDKN2A mutations. In nine patients,CDKN2A alterations that may contribute to melanoma predisposition were detected. In six individuals with a family history of melanoma, the 113insR founder mutation was present. One patient, who also had a family history of melanoma, had a 24-bp deletion that included codons 62–69. Anin vitro binding assay established that the resulting mutant p16 protein was unable to bind cyclin-dependent kinase 4 and cyclin-dependent kinase 6. Two patients without a family history of melanoma hadCDKN2A alterations: (a) one had a mutation in the 5*noncoding sequence (214C/T); and (b) the other had an insertion of an extra T in codon 28, which results in a stop signal in codon 43. The median age at diagnosis of the first melanoma was significantly lower, the number of primary melanomas was significantly higher, and the presence of a family history of melanoma was significantly more common in patients with CDKN2A mutations than in those without germ-line mutations. The proportion of CDKN2A mutation carriers was significantly higher among patients treated for three or more primary melanomas compared with those with two tumors only. We conclude that mutation screening of individuals with multiple primary melanomas is a useful strategy to identify new melanoma kindreds with CDKN2A germ-line mutations.
Rod outer segment maintenance is enhanced in the presence of bFGF, CNTF and GDNF.

We employed a morphological assay of outer segment collapse to determine if growth factors or other supplements directly affect dissociated rod photoreceptors in vitro. The morphological changes in outer segments were correlated with the light responsiveness of rods. Time-lapse video microscopy was used to observe the collapse of rod outer segments from isolated single cells and small clumps of cells. A consistent pattern of outer segment collapse into the inner segment was observed, yielding a convenient assay of the effects of neurotrophic factors on photoreceptor functional maintenance. The functional state of rods, defined as light-responsiveness, was measured with suction electrode recordings and matched with the various stages of outer segment collapse. Ciliary neurotrophic factor (CNTF) and glial cell-line-derived neurotrophic factor (GDNF) at a high concentration, yielded statistically significant improvements in rat outer segment survival times. Basic fibroblast growth factor (bFGF), which rescues photoreceptors in several rodent models of retinal degeneration, produced a significant increase in survival time in the presence of the cofactor heparin. In 4 out of 10 cases using human tisue, bFGF also yielded a significant increase in survival times. When brain-derived neurotrophic factor (BDNF) was applied to rat rods, outer segment survival times did not change. Outer segments collapsed more quickly when either pigment epithelial cell derived factor (PEDF) or sugar N-acetyl D-galactosamine (NAD-gal) were present. Our results show that rod photoreceptors can respond to bFGF, GDNF and CNTF in vitro and provide evidence for a direct effect of these neurotrophic factors on rods. The rapid collapse of isolated photoreceptors in this model provides a convenient means for testing various neurotrophic agents and the induced cellular responses.
Effects of public posting on driving speed in Icelandic traffic.

We replicated a study by Van Houten, Nau, and Marini (1980) that had revealed reductions in vehicle speeding following the posting of percentages of drivers not speeding on a sign at roadside. Our subjects were drivers entering a residential area where the speed limit changed from 90 km/hr (55.9 mph) to 60 km/hr (37.3 mph). A total of 4,409 vehicle speeds were taken from two observation sessions per day for 20 consecutive weekdays. The intervention consisted of a single posting condition, in which a hypothetical daily percentage of drivers not speeding was posted on a feedback sign, followed by a double posting condition, in which a sign posting a best result was erected beyond the feedback sign. Results revealed a significant speed reduction from an average of 69.0 km/hr (42.9 mph) during baseline to 63.4 km/hr (39.4 mph) during single posting. Average speed during double posting was 62.9 km/hr (39.1 mph). The percentage of drivers exceeding 70 km/hr (43.5 mph) dropped from 41.0 during baseline to 20.5 during single posting. The significant speed reductions add to the generality of findings of similar studies in Canada and Israel and offer possible explanations for the failure of feedback posting to reduce speed in the U.S.
CYCLOSPORIN A IN PATIENTS AFFECTED BY CHRONIC IDIOPATHIC URTICARIA: A THERAPEUTIC ALTERNATIVE

Chronic Idiopathic Urticaria (CIU) is a cutaneous disorder for which there is no identifiable specific etiologic agent. Some recent evidences suggest that CIU might be an autoimmune disease. We analyzed immunological features occurring in CIU and evaluated effectiveness and tolerance of Cyclosporin A (CsA) treatment in patients unresponsive to antihistaminic treatment. Twenty patients with CIU were recruited after a selective diagnostic protocol and were divided into two groups. CsA was prescribed for group 1 and Prednisone for group 2 as control, for 8 weeks. Before and after the therapy we performed on all patients immunological studies. For all patients symptoms disappeared after a few days of therapy. Before therapy all patients showed activated B cells (CD19+CD23+ cells) and among B CD19+ cells, about 20% were CD5+ (cells that synthesize natural autoantibodies). After treatment with Prednisone in group 2, a significant reduction of CD4+ lymphocytes (p + 0,01) was observed. Our findings might support the CIU autoimmune pathogenetic hypothesis. The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and, at dosage used, side effects were rare, mild and reversible. Thus, CsA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments.
Polyprenyl Phosphate Biosynthesis inMycobacterium tuberculosis and Mycobacterium smegmatis

ABSTRACT Mycobacterium smegmatis has been shown to contain two forms of polyprenyl phosphate (Pol-P), while Mycobacterium tuberculosis contains only one. Utilizing subcellular fractions from M. smegmatis and M. tuberculosis, we show that Pol-P synthesis is different in these species. The specific activities of the prenyl diphosphate synthases in M. tuberculosis are 10- to 100-fold lower than those in M. smegmatis. In M. smegmatis decaprenyl diphosphate and heptaprenyl diphosphate were the main products synthesized in vitro, whereas in M. tuberculosis only decaprenyl diphosphate was synthesized. The data from both organisms suggest that geranyl diphosphate is the allylic substrate for two distinct prenyl diphosphate synthases, one located in the cell membrane that synthesizes ω,E,Z-farnesyl diphosphate and the other present in the cytosol that synthesizes ω,E,E,E-geranylgeranyl diphosphate. In M. smegmatis, the ω,E,Z-farnesyl diphosphate is utilized by a membrane-associated prenyl diphosphate synthase activity to generate decaprenyl diphosphate, and the ω,E,E,E-geranylgeranyl diphosphate is utilized by a membrane-associated activity for the synthesis of the heptaprenyl diphosphate. In M. tuberculosis, however, ω,E,E,E-geranylgeranyl diphosphate is not utilized for the synthesis of heptaprenyl diphosphate. Thus, the difference in the compositions of the Pol-P ofM. smegmatis and M. tuberculosis can be attributed to distinct enzymatic differences between these two organisms.
Use of two reporter dyes without interference in a single-tube rapid-cycle PCR: alpha(1)-antitrypsin genotyping by multiplex real-time fluorescence PCR with the LightCycler.

BACKGROUND alpha(1)-Antitrypsin is the major plasma serine protease inhibitor. Its deficiency is mainly associated with the alleles PI*S and PI*Z and can lead to obstructive lung disease in adults and to liver cirrhosis during childhood. METHODS A multiplex PCR method has been established that uses two sets of primers to amplify the gene regions covering the PI*S or PI*Z mutations sites. Mutation detection was performed on the LightCycler by melting curve analysis of detection probes labeled with two different fluorescent dyes, LC-Red640 and LC-Red705. RESULTS Unequivocal genotyping results were obtained for all investigated samples in an assay time of approximately 30 min. The color compensation procedure greatly improved the readability of the resulting diagnostic melting curves. CONCLUSIONS To our knowledge, this is the first report of simultaneous detection of two mutations in a single tube by PCR of genomic DNA and the use of two different reporter dyes with the LightCycler color compensation feature. This approach is a rapid, convenient, and economic alternative to other methods described to date for the detection of alpha(1)-antitrypsin deficiency alleles.
Canal-wall-down tympanoplasty with mastoidectomy for advanced cholesteatoma.

OBJECTIVE The objective of this study was to review 8.5 years of the senior author's experience with canal-wall-down mastoid surgery for extensive cholesteatoma with high-grade atelectasis and severely destructed ossicles. DESIGN A retrospective review was conducted. SETTING The setting was a tertiary care medical centre. METHODS Available records consulted included 104 canal-wall-down mastoidectomy for advanced-stage cholesteatomas between July 1984 and December 1992. MAIN OUTCOME MEASURES Recurrence, hearing results, and dry ear rate were analyzed. RESULTS The recurrence rate was 4 of 104 (3.8%), and 9.6% of subjects suffered from recurrent otorrhea. Thirty-seven of 104 (35.6%) achieved the closure of air-bone gap within 20 dB. The availability of stapes suprastructure influenced the postoperative hearing level significantly (p < .001). CONCLUSION Even in treating advanced cholesteatoma, canal-wall-down mastoidectomy provides a low recurrence rate, establishes a high dry ear rate, and preserves adequate hearing when the stapes suprastructure is available for reconstruction.
Scale, Scope, and Speed—Managing the Challenges of Multiproduct Manufacturing

An empirically grounded model characterizes the challenges of modern multiproduct manufacturing, where products that operate in highly contrasting economic environments run in one fab. Three product classes are taken into consideration-VLSI circuits for which unit sales prices are highly time dependent; specialty chips for which unit sales prices and total demand are specified a priori; and commodity components whose unit sales prices are low, predictable, and either flat or cyclical. The model calculates the impact of manufacturing cycle time on cost structure and the ability to generate revenue, and it simulates the economic consequences of a variety of production plans involving the three product classes. The findings of this paper suggest that an integrated approach to managing scale, scope, and fab cycle time can bring about dramatic increases in fab performance as measured by the net profit that the fab accumulates.
Time-Accuracy Functions for Determining Process and Person Differences: An Application To Cognitive Aging

A paradigm for the determination of time-accuracy functions (TAFs) for individual participants is introduced for two pairs of tasks differing in cognitive complexity, that is, word scanning vs cued recognition and figural scanning vs figural reasoning. TAFs can be used to test dissociations of cognitive processes beyond scale-related ambiguities of ordinal interactions. The approach is applied to examine the cognitive-aging hypothesis that a single slowing factor can account for interactions between adult age and cognitive task complexity. Twenty young and 20 old adults participated in 17 sessions. Presentation times required for 75, 87.5, and 100% accuracies were determined for each task with a variant of the psychophysical method of limits. Accuracy was fit by negatively accelerated functions of presentation time. State-trace analyses showed that different slowing factors are required for high- and low-complexity tasks. Relations to speed-accuracy and performance-resource functions are discussed.
Randomized Intervention Analysis and the Interpretation of Whole‐Ecosystem Experiments

Randomized intervention analysis (RIA) is used to detect changes in a ma- nipulated ecosystem relative to an undisturbed reference system. It requires paired time series of data from both ecosystems before and after manipulation. RIA is not affected by non-normal errors in data. Monte Carlo simulation indicated that, even when serial au- tocorrelation was substantial, the true P value (i.e., from nonautocorrelated data) was <. 05 when the P value from autocorrelated data was <. 01. We applied RIA to data from 12 lakes (3 manipulated and 9 reference ecosystems) over 3 yr. RIA consistently indicated changes after major manipulations and only rarely indicated changes in ecosystems that were not manipulated. Less than 3% of the data sets we analyzed had equivocal results because of serial autocorrelation. RIA appears to be a reliable method for determining whether a nonrandom change has occurred in a manipulated ecosystem. Ecological argu- ments must be combined with statistical evidence to determine whether the changes dem- onstrated by RIA can be attributed to a specific ecosystem manipulation.
Inhibition of Herpes Simplex Virus-Induced DNA Polymerase Activity and Viral DNA Replication by 9-(2-Hydroxyethoxymethyl) guanine and Its Triphosphate

The effect of the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) on herpes simplex virus type 1 DNA synthesis was examined. Acycloguanosine inhibited herpesvirus DNA synthesis in virus-infected cells. The synthesis of host cell DNA was only partially inhibited in actively growing cells at acycloguanosine concentrations several hundred-fold greater than the 50% effective dose for herpes simplex virus type 1. Studies using partially purified enzymes revealed that the triphosphate of this compound inhibited the virus-induced DNA polymerases (DNA nucleotidyltransferases) to a greater degree than the DNA polymerase of the host cell, that the inhibition was dependent upon the base composition of the template, and that the triphosphate was a better substrate for the virus-induced polymerases than for the alpha cellular DNA polymerases.
On the volatility of oxide defects: Activation, deactivation, and transformation

Recent studies have clearly shown that oxide defects are more complicated than typically assumed in simple two-state models, which only consider a neutral and a charged state. In particular, oxide defects can be volatile, meaning that they can be deactivated and re-activated at the same site with the same properties. In addition, these defects can transform and change their properties. The details of all these processes are presently unknown and poorly characterized. Here we employ time-dependent defect spectroscopy (TDDS) to more closely study the changes occurring at the defect sites. Our findings suggest that these changes are ubiquitous and must be an essential aspect of our understanding of oxide defects. Using density-functional-theory (DFT) calculations, we propose hydrogen-defect interactions consistent with our observations. Our results suggest that standard defect characterization methods, such as the analysis of random telegraph noise (RTN), will typically only provide a snapshot of the defect landscape which is subject to change anytime during device operation.
Tunable-Q Wavelet Transform Based Multivariate Sub-Band Fuzzy Entropy with Application to Focal EEG Signal Analysis

This paper analyses the complexity of multivariate electroencephalogram (EEG) signals in different frequency scales for the analysis and classification of focal and non-focal EEG signals. The proposed multivariate sub-band entropy measure has been built based on tunable-Q wavelet transform (TQWT). In the field of multivariate entropy analysis, recent studies have performed analysis of biomedical signals with a multi-level filtering approach. This approach has become a useful tool for measuring inherent complexity of the biomedical signals. However, these methods may not be well suited for quantifying the complexity of the individual multivariate sub-bands of the analysed signal. In this present study, we have tried to resolve this difficulty by employing TQWT for analysing the sub-band signals of the analysed multivariate signal. It should be noted that higher value of Q factor is suitable for analysing signals with oscillatory nature, whereas the lower value of Q factor is suitable for analysing signals with non-oscillatory transients in nature. Moreover, with an increased number of sub-bands and a higher value of Q-factor, a reasonably good resolution can be achieved simultaneously in high and low frequency regions of the considered signals. Finally, we have employed multivariate fuzzy entropy (mvFE) to the multivariate sub-band signals obtained from the analysed signal. The proposed Q-based multivariate sub-band entropy has been studied on the publicly available bivariate Bern Barcelona focal and non-focal EEG signals database to investigate the statistical significance of the proposed features in different time segmented signals. Finally, the features are fed to random forest and least squares support vector machine (LS-SVM) classifiers to select the best classifier. Our method has achieved the highest classification accuracy of 84.67% in classifying focal and non-focal EEG signals with LS-SVM classifier. The proposed multivariate sub-band fuzzy entropy can also be applied to measure complexity of other multivariate biomedical signals.
Family and sociodemographic influences on patterns of leaving home in Postwar Britain

We identify child-level and parent-level characteristics associated with children’s patterns of leaving home. We use a multilevel discrete-time hazards model to examine the impact of family and demographic factors at both levels, and utilize the Alternating Conditional Expectation algorithm optimally to transform the dependent and independent variables. We find that measured variables at both the child and the parent level have important influences, as do period and cohort factors. However, unmeasured parent-level factors have an influence on the departure of children that is broadly similar in magnitude to measured factors.
Clinical evaluation of a porcine acellular dermal matrix for the treatment of multiple adjacent class I, II, and III gingival recessions using the modified coronally advanced tunnel technique.

OBJECTIVE To evaluate the clinical efficacy of a new porcine acellular dermal matrix (PADM) for the treatment of Miller Class I, II, and III multiple gingival recessions using the modified coronally advanced tunnel technique (MCAT). METHOD AND MATERIALS Twelve nonsmoking, systemically healthy patients presenting at least two adjacent Miller Class I, II, or III gingival recessions (GR), with a minimal depth of 2 mm, were treated consecutively with MCAT in conjunction with PADM. At baseline and 12 months postoperatively, complete root coverage (CRC, eg 100% root coverage), mean root coverage (RC), recession depth, recession width, attached gingiva (AG), keratinized tissue (KT), periodontal pocket depths (PD), and clinical attachment level (CAL) were evaluated. The main outcome variable was CRC. RESULTS Postoperative healing was uneventful in all cases, without any matrix loss or exposure or infection. Statistically significant improvements (P < .0001) were observed 12 months postoperatively in 53 of the included 54 GR (98.15%). Twenty two recessions (40.74%) showed CRC while the mean RC measured 73.20 ± 27.71%. Mean GR reduction was 2.06 ± 1.18 mm while the gain of AG amounted to 0.84 ± 0.73 mm and of KT to 0.69 ± 0.51 mm, respectively. There were no statistically significant changes for PD at 12 months; CAL showed a significant decrease (P < .05) at 12 months from 3.77 ± 1.28 mm to 2.30 ± 1.02 mm. CONCLUSION PADM in conjunction with MCAT may be successfully utilized for the treatment of Miller Class I, II, and III multiple adjacent GR.