Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of the proapoptotic activity of huntingtin interacting protein 1 by Dyrk1 and caspase‐3 in hippocampal neuroprogenitor cells

Dual specific protein kinase Dyrks are thought to play a key role in the regulation of cell growth in a variety of cellular systems. Interestingly, human Dyrk1 is mapped to the Down's syndrome (DS) critical region on chromosome 21, and thought to be a candidate gene responsible for the mental retardation of DS patients. Huntingtin‐interacting protein 1 (Hip‐1), a proapoptotic mediator, is implicated as a molecular accomplice in the pathogenesis of Huntington's disease. In the present study we found that Dyrk1 selectively binds to and phosphorylates Hip‐1 during the neuronal differentiation of embryonic hippocampal neuroprogenitor (H19‐7) cells. The Dyrk1‐mediated phosphorylation of Hip‐1, in response to bFGF, resulted in the blockade of Hip‐1‐mediated neuronal cell death as well as the enhancement of neurite outgrowth. Furthermore, the addition of etoposide to proliferating H19‐7 cells caused the diminished binding of Hip‐1 to Dyrk1 and the levels of phosphorylated Hip‐1 remarkably decreased. Simultaneously, the dissociated Hip‐1 from Dyrk1 bound to caspase‐3 in response to etoposide, which led to its activation and consequently cell death in H19‐7 cells. These data suggest that the phosphorylation of Hip‐1 by Dyrk1 has a dual role in regulating neuronal differentiation and cell death. The interaction between Dyrk1 and Hip‐1 appeared to be differentially modulated by different kinds of stimuli, such as bFGF and etoposide in H19‐7 cells. © 2005 Wiley‐Liss, Inc.
A comparative confocal microscopy analysis after LASIK with the IntraLase femtosecond laser vs Hansatome microkeratome.

PURPOSE To evaluate and compare confocal microscopy findings between a femtosecond laser and a mechanical microkeratome. METHODS Eighteen eyes of nine patients underwent LASIK. Corneal flaps were created with the femtosecond laser in the right eyes and a mechanical microkeratome in the left eyes. The corneal flap interface was analyzed in all eyes with a confocal microscope at 1 week and 1 month postoperatively. RESULTS All eyes showed small reflective particles at the corneal flap interface. The mean number of reflective particles was not statistically significantly different at 1 week (P = .078) and 1 month (P = .28) using a femtosecond laser and a mechanical microkeratome. CONCLUSIONS Confocal microscopy findings at the corneal flap interface showed a similar number of particles using both systems.
Comparative Evaluation of the New Version of the INNO-LiPA Mycobacteria and GenoType Mycobacterium Assays for Identification of Mycobacterium Species from MB/BacT Liquid Cultures Artificially Inoculated with Mycobacterial Strains

ABSTRACT The performance of two DNA line probe assays, a new version of INNO-LiPA Mycobacteria (Innogenetics, Ghent, Belgium) and the GenoType Mycobacterium (Hain Diagnostika, Nehren, Germany), were evaluated for identification of mycobacterial species isolated from liquid cultures. Both tests are based on a PCR technique and designed for simultaneous identification of different mycobacterial species by reverse hybridization and line probe technology. The INNO-LiPA Mycobacteria v2 targeting the 16S-23S rRNA gene spacer region was developed for the simultaneous identification of 16 different mycobacterial species. The GenoType Mycobacterium, which targets the 23S rRNA gene, allows simultaneous identification of 13 mycobacterial species. Both tests were evaluated on 110 mycobacterial strains belonging to 22 different mycobacterial species (20 reference strains, 83 clinical strains, and 4 Mycobacterium kansasii strains isolated from tap water) that were previously inoculated into MB/BacT bottles. The sensitivity of both methods, defined as the number of positive results obtained with the Mycobacterium genus probe together with an interpretable result on the number of samples tested was 110 of 110 (100%) for INNO-LiPA and 102 of 110 (92.7%) for GenoType. For samples with interpretable results, INNO-LiPA was able to correctly identify 109 of 110 samples (99.1%), whereas the GenoType correctly identified 100 of 102 samples (98.0%). Both tests were easy to perform, rapid, and reliable when applied to mycobacterial identification directly from MB/BacT bottles.
Dietary essential oils improve the hepatic antioxidative status of broiler chickens

Abstract 1. A total of 200 male Ross 308 chickens were used to evaluate the effects of a standardised combination of essential oils including 5% carvacrol, 3% cinnamaldehyde and 2% capsicum oleoresin (XT 6930; Pancosma S.A., Geneva, Switzerland) on their performance, hepatic antioxidant concentration and caecal tonsils morphometry. 2. Two diets were offered to broiler chickens from d old to 21 d of age. The control diet (C) was slightly lower in metabolisable energy (12.13 MJ/kg ME) and crude protein (215 g/kg CP) than breeders’ recommendation. The second diet, made as XT 6930, was added on the top of the control diet at 100 mg/kg. Each diet was offered ad libitum to birds housed in one of 10 floor pens in a randomised complete block design. The birds were housed in 20 floor pens, 10 birds in each pen, and were allocated to 10 replicates of the two dietary treatments. 3. The concentration of antioxidants in the liver of the birds was determined using high-performance liquid chromatography (HPLC) at 21 d of age. Birds fed control diet only had lower weight and converted less efficiently feed to gain compared to birds fed essential oils-supplemented diet. Feed consumption was not affected by dietary treatments. The antioxidant data showed that supplemented essential oils improved the hepatic concentration of carotenoids and coenzyme Q10 when fed to broiler chickens. The morphometry of the caecal tonsils of the birds was not influenced by dietary treatments. 4. It can be concluded that that dietary combination of essential oils, including carvacrol, cinnamaldehyde and capsicum oleoresin, improved growth, feed efficiency and the hepatic concentration of carotenoids and coenzyme Q10 when fed to broiler chickens.
Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland following Staphylococcus aureus challenge and in response to milk accumulation

We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma and milk. The expression levels of IL1β and TNFα were markedly up-regulated in Staph. aureus-inoculated mammary tissue at 72 h, whilst IL6 was up-regulated to a lesser extent in a way which was not confined to the inoculated glands. APP expression was up-regulated at 48 and 72 h in both Staph. aureus-inoculated and teat-sealed mammary glands. These differences between cytokine and APP expression provide additional support for the contention that APPs are produced within the mammary tissue itself during inflammation, rather than in associated immune cells. We propose that measurement of cytokines and APP in combination might provide a tool for diagnostic discrimination between mastitis caused by pathogenic invasion and milk accumulation, and hence allow for better targeting of antibiotic therapy. In comparison with mammary expression, expression of cytokines in liver tissue was up-regulated to a similar or lesser extent, whilst expression of APP was up-regulated to a much greater extent. The first appearance of increased cytokine and APP concentrations in plasma and of milk amyloid A (MAA) in milk occurred in advance of the measurable up-regulation of expression, hence their origin cannot be stated with certainty.
Modelling effluent quality based on a real-time optical monitoring of the wastewater treatment process

ABSTRACT A novel optical monitoring device was used for imaging an activated sludge process in situ during a period of over one year. In this study, the dependencies between the results of image analysis and the process measurements were studied, and the optical monitoring results were utilized to predict the important quality parameters for the wastewater treatment process efficiency: suspended solids, biological oxygen demand, chemical oxygen demand, total nitrogen and total phosphorous in biologically treated wastewater. The optimal subsets of variables for each model were searched using five variable selection methods. It was shown that online optical analysis results have clear dependencies on some process variables and the purification result. The model based on optical monitoring and process variables from the early stage of the treatment process can be used to predict the levels of important quality parameters, and to show the quality of the biologically treated wastewater hours in advance. This study confirms that the optical monitoring method is a valuable tool for monitoring a wastewater treatment process and receiving new information in real time. Combined with predictive modelling, it has the potential to be used in process control, keeping the process in a stable operating condition and avoiding environmental risks.
Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri

Cytological screening for cervical cancer or its precursors using Papanicolaou's smear test (Pap test) has been highly efficient to reduce the morbidity and mortality of cervical cancer. However, evaluation of the Pap test relies on subjective diagnostic parameters and is affected by a high rate of false‐positive and false‐negative results. More objective diagnostic parameters to identify truly dysplastic or neoplastic cells in cervical smears as well as in cervical biopsy samples would therefore avoid insecurity for many patients and the high screening costs associated with repeated testing. Cervical dysplasia is induced by persistent infections through high‐risk types of human papillomaviruses (HPVs). Outgrowth of dysplastic lesions is triggered by increasing expression of two viral oncogenes, E6 and E7, which both interact with various cell cycle‐regulating proteins. Among these is the retinoblastoma gene product pRB, which is inactivated by E7. pRB inhibits transcription of the cyclin‐dependent kinase inhibitor gene p16INK4a. Increasing expression of the viral oncogenes in dysplastic cervical cells might thus be reflected by increased expression of p16INK4a. In line with this hypothesis, we observed marked overexpression of p16INK4a in all cervical intraepithelial neoplasm (CIN) I lesions (n = 47) except those associated with low‐risk HPV types (n = 7), all CIN II lesions (n = 32), all CIN III lesions (n = 60) and 58 of 60 invasive cervical cancers. In contrast, no detectable expression of p16INK4a was observed in normal cervical epithelium (n = 42), inflammatory lesions (n = 48) and low‐grade cervical lesions (CIN I) associated with low‐risk HPV types (n = 7). Dysplastic cells could also be identified in cervical smears using a specific p16INK4a monoclonal antibody. These data demonstrate that p16INK4a is a specific biomarker to identify dysplastic cervical epithelia in sections of cervical biopsy samples or cervical smears. © 2001 Wiley‐Liss, Inc.
Long-Term Effects of Carvedilol on Left Ventricular Function, Remodeling, and Expression of Cardiac Cytokines After Large Myocardial Infarction in the Rat

Carvedilol (20 mg/kg, bid) or vehicle was given to rats surviving a myocardial infarction (MI) 24 h (n = 409). In rats with large MI, carvedilol partially preserved left ventricular (LV) function and intrinsic myocardial contractility and reactivity to &bgr;-adrenergic stimulation. Carvedilol led to scar thickening, increased LV hypertrophy, and decreased cardiac fibrosis but did not prevent LV dilatation. Carvedilol reduced cardiac expression of interleukin-1&bgr; but did not prevent cardiac fetal gene re-expression or modify cardiac oxidative stress. Despite these beneficial effects, carvedilol decreased survival (38.8%, versus vehicle, 50.6%) due to excessive early mortality. Thus, post-MI carvedilol has many beneficial effects, however, in this study it increased post-MI mortality, perhaps due to excessive hypotension.
Experience of Audit Committee Members and Audit Quality

Abstract We investigate whether the experience of audit committee members is associated with audit quality. In order to comprehensively analyse the experience of audit committee members, we include audit committee member tenure, age and multiple-directorships in our analysis. Using observations from 2001 to 2012, we undertake analysis on 13,155 firm-year observations and find that all our proxies of audit committee member experience are positively associated with audit fees. A range of additional tests, including using discretionary accruals as an alternative measure of audit quality and differences-in-differences analysis, support our main findings and our results consequently make a number of contributions to both the literature and policy making. One possible policy contribution is that regulators may wish to consider audit committee characteristics representing experience when framing recommendations to improve audit quality and thereby, financial reporting by firms.
Subtype-specific Clinical Presentation, Medical Treatment and Family Impact of Influenza in Children 1–5 Years of Age Treated in Outpatient Practices in Germany During Three Postpandemic Years, 2013–2015

Background: Limited data on the influenza burden in pediatric outpatients are available, especially regarding direct comparison of the cocirculating (sub)types A(H1N1)pdm09, A(H3N2) and B. Methods: Children 1–5 years of age, unvaccinated against influenza and presenting with febrile acute respiratory infections (ARIs), were enrolled in 33 pediatric practices in Germany from 2013 to 2015 (January–May). Influenza was confirmed by multiplex polymerase chain reaction from pharyngeal swabs and (sub)typed. Results: In 805 children with ARI, influenza was the most frequently detected respiratory virus (n = 305; 37.9%). Of 217 influenza patients included, 122 (56.2%) were infected with A(H3N2), 56 (25.8%) with A(H1N1)pdm09 and 39 (18.0%) with B. Median age was 3.7 years [interquartile range (IQR), 2.1–4.8]; 11% had underlying conditions. Median fever duration was 4 days (IQR, 3–5), and the disease duration was 9 days (IQR, 7–12). Most frequent diagnoses were pharyngitis (26%), bronchitis (18%) and acute otitis media (10%). Children received mainly antipyretics (86%) and adrenergic nasal drops/spray (53%); 9% received antibiotics and 3% oseltamivir. Thirty-six percent required at least 1 additional practice visit; 1% was hospitalized. Median absences from childcare were 5 days (IQR, 3–7); parents lost 4 workdays (IQR, 2–6). Symptoms, severity and impact on the family were largely unrelated to (sub)type. However, patients with A(H1N1)pdm09 had fewer underlying conditions (P = 0.017), whereas patients with B more often had pharyngitis (P = 0.022), acute otitis media (P = 0.012) and stenosing laryngotracheitis (P = 0.007). Conclusions: Influenza was the most frequently detected viral pathogen in outpatient children with febrile, mostly uncomplicated ARI. In this setting, clinical manifestations and severity were similar across the (sub)types prevalent during the postpandemic seasons.
Institution of Basal-Bolus Therapy at Diagnosis for Children With Type 1 Diabetes Mellitus

OBJECTIVE. We studied whether the institution of basal-bolus therapy immediately after diagnosis improved glycemic control in the first year after diagnosis for children with newly diagnosed type 1 diabetes mellitus. METHODS. We reviewed the charts of 459 children ≥6 years of age who were diagnosed as having type 1 diabetes between July 1, 2002, and June 30, 2006 (212 treated with basal-bolus therapy and 247 treated with a more-conventional neutral protamine Hagedorn regimen). We abstracted data obtained at diagnosis and at quarterly clinic visits and compared groups by using repeated-measures, mixed-linear model analysis. We also reviewed the records of 198 children with preexisting type 1 diabetes mellitus of >1-year duration who changed from the neutral protamine Hagedorn regimen to a basal-bolus regimen during the review period. RESULTS. Glargine-treated subjects with newly diagnosed diabetes had lower hemoglobin A1c levels at 3, 6, 9, and 12 months after diagnosis than did neutral protamine Hagedorn-treated subjects (average hemoglobin A1c levels of 7.05% with glargine and 7.63% with neutral protamine Hagedorn, estimated across months 3, 6, 9, and 12, according to repeated-measures models adjusted for age at diagnosis and baseline hemoglobin A1c levels; treatment difference: 0.58%). Children with long-standing diabetes had no clinically important changes in their hemoglobin A1c levels in the first year after changing regimens. CONCLUSION. The institution of basal-bolus therapy with insulin glargine at the time of diagnosis of type 1 diabetes was associated with improved glycemic control, in comparison with more-conventional neutral protamine Hagedorn regimens, during the first year after diagnosis.
Dysregulated Metabotropic Glutamate Receptor-Dependent Translation of AMPA Receptor and Postsynaptic Density-95 mRNAs at Synapses in a Mouse Model of Fragile X Syndrome

Fragile X syndrome, a common form of inherited mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP), an mRNA binding protein that is hypothesized to regulate local mRNA translation in dendrites downstream of gp1 metabotropic glutamate receptors (mGluRs). However, specific FMRP-associated mRNAs that localize to dendrites in vivo and show altered mGluR-dependent translation at synapses of Fmr1 knock-out mice are unknown so far. Using fluorescence in situ hybridization, we discovered that GluR1/2 and postsynaptic density-95 (PSD-95) mRNAs are localized to dendrites of cortical and hippocampal neurons in vivo. Quantitative analyses of their dendritic mRNA levels in cultured neurons and synaptoneurosomes did not detect differences between wild-type and Fmr1 knock-out (KO) mice. In contrast, PSD-95, GluR1/2, and calcium/calmodulin-dependent kinase IIα (CaMKIIα) mRNA levels in actively translating polyribosomes were dysregulated in synaptoneurosomes from Fmr1 knock-out mice in response to mGluR activation. [35S]methionine incorporation into newly synthesized proteins similarly revealed impaired stimulus-induced protein synthesis of CaMKIIα and PSD-95 in synaptoneurosomes from Fmr1 KO mice. Quantitative analysis of mRNA levels in FMRP-specific immunoprecipitations from synaptoneurosomes demonstrated the association of FMRP with CaMKIIα, PSD-95, and GluR1/2 mRNAs. These findings suggest a novel mechanism whereby FMRP regulates the local synthesis AMPA receptor (AMPAR) subunits, PSD-95, and CaMKIIα downstream of mGluR-activation. Dysregulation of local translation of AMPAR and associated factors at synapses may impair control of the molecular composition of the postsynaptic density and consequently alter synaptic transmission, causing impairments of neuronal plasticity observed in Fmr1 knock-out mice and fragile X syndrome.
Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey

Summary. Streptococcus pneumoniae (S. pneumoniae) may cause severe and lethal infections months and years following stem cell transplantation (SCT). In a prospective survey over a 3·5‐year period, we assessed the incidence, risk factors and outcome for invasive pneumococcal infection (IPI) following SCT. Fifty‐one episodes of IPI were reported: 43 episodes after bone marrow transplantation (BMT) and 8 after peripheral blood stem cell transplantation (PBSCT); 35 after allogeneic SCT and 16 after autologous SCT. Seven IPI episodes, all bacteraemias, were defined as early, occurring 1–35 d (median 3 d) post transplantation. Forty‐four episodes were defined as late (≥ 100 d post SCT), occurring 4 months to 10 years (median 17 months) post transplantation. The incidences of early and late IPI were 2·03/1000 and 8·63/1000 transplantations respectively (P = 0·001). A higher incidence of late IPI was observed after BMT than after PBSCT (10·99 versus 3·23/1000; P < 0·01) and after allogeneic versus autologous SCT (12·20 versus 4·60/1000; P < 0·01). There was a higher estimated incidence of IPI in allogeneic patients with than in those without graft‐versus‐host disease (GVHD) (18·85 versus 8·25/1000; P = 0·015). The mortality rate was 20%, including 2/7 of early and 8/44 of late IPI. S. pneumoniae is a rare but important complication during the aplastic phase after SCT. In conclusion, S. pneumoniae is a significant cause of morbidity late post‐transplantation, especially in allogeneic patients, and particularly those with GVHD. The high IPI mortality rate, both early and late post‐transplantation, requires preventive approaches, mainly effective immunization.
Role of interferons in the treatment of severe acute respiratory syndrome

Severe acute respiratory syndrome (SARS) is caused by the SARS coronavirus (SCV). The disease appeared in the Guandong province of southern China in 2002. The epidemic affected > 8422 patients and caused 908 deaths in 29 countries on 5 continents. Several treatment modalities were tried with limited success to treat SARS and a variety of experimental drugs are under development. Type I interferons (IFNs-α/β) were suggested as potential candidates to treat SARS. Several animal and human coronaviruses, including SCV, were shown to be sensitive to IFNs both in vitro and in vivo. A pilot clinical report showed effectiveness of IFN-α for the treatment of SARS patients. This review summarises antiviral activities of IFNs with special regard to SARS, and reviews the published clinical and experimental data describing the use of IFNs for SARS.
Did the Teachers Destroy the School? Public Entrepreneurship as Creation and Adaptation

This article is based on a case study to explore a model of teacher governance and illustrate the distinct challenges of entrepreneurship in public education. In the Sedona Charter School, each classroom principal educator serves as instructional leader and resource leader. Principal educators adjust curricula, hire their teachers, determine salaries (including their own), and purchase classroom materials within the constraints of state funding. By conventional measures of market, financial, and performance accountability, the school succeeds, suggesting that this model can be replicated. Yet the school founders severed their relationship with the school and lobbied state authorities to close it, since, in their view, it violated its charter (process accountability). This case suggests that most innovative entrepreneurs may have difficulty adjusting to educational realities and must themselves be held accountable by parents and state authorities. The study further suggests that, as educational principals, parents and state regulators are more influenced by performance and financial accountability than by process accountability.