Miracle-dz/UniFAR-FTUs huggingface dataset:
E4orf4 induces PP2A- and Src-dependent cell death in Drosophila melanogaster and at the same time inhibits classic apoptosis pathways

Significance Expression of the adenovirus protein E4orf4 alone in cultured mammalian cells prompts noncanonical apoptosis that is more efficient in oncogene-transformed cells than in normal cells. Here, E4orf4 activity in a whole organism (Drosophila melanogaster) is described, leading to three significant conclusions: (i) E4orf4-induced cell death is an evolutionarily conserved process; (ii) E4orf4 induces a distinctive mode of cell death, differing from well-characterized cell death mechanisms; and (iii) E4orf4 activates cell death but concomitantly inhibits it, thus minimizing damage to normal tissues. The last finding suggests a possible explanation for the differential effect of E4orf4 in normal and cancer cells. The adenovirus E4orf4 protein regulates the progression of viral infection, and when expressed alone in mammalian tissue culture cells it induces protein phosphatase 2A (PP2A)-B55– and Src-dependent cell death, which is more efficient in oncogene-transformed cells than in normal cells. This form of cell death is caspase-independent, although it interacts with classic caspase-dependent apoptosis. PP2A-B55–dependent E4orf4-induced toxicity is highly conserved in evolution from yeast to mammalian cells. In this work we investigated E4orf4-induced cell death in a whole multicellular organism, Drosophila melanogaster. We show that E4orf4 induced low levels of cell killing, caused by both caspase-dependent and -independent mechanisms. Drosophila PP2A-B55 (twins/abnormal anaphase resolution) and Src64B contributed additively to this form of cell death. Our results provide insight into E4orf4-induced cell death, demonstrating that in parallel to activating caspase-dependent apoptosis, E4orf4 also inhibited this form of cell death induced by the proapoptotic genes reaper, head involution defective, and grim. The combination of both induction and inhibition of caspase-dependent cell death resulted in low levels of tissue damage that may explain the inefficient cell killing induced by E4orf4 in normal cells in tissue culture. Furthermore, E4orf4 inhibited JNK-dependent cell killing as well. However, JNK inhibition did not impede E4orf4-induced toxicity and even enhanced it, indicating that E4orf4-induced cell killing is a distinctive form of cell death that differs from both JNK- and Rpr/Hid/Grim-induced forms of cell death.
Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers.

AIM To assess the effect of Schisandra sphenanthera extract (SchE) on the pharmacokinetics of tacrolimus in healthy volunteers. METHODS Twelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 13 days. Pharmacokinetic investigations of oral tacrolimus administration at 2 mg were performed both before and at the end of the SchE treatment period. Whole blood tacrolimus concentrations were determined by enzyme-linked immunosorbent assay. Estimated pharmacokinetic parameters before and with SchE were calculated with noncompartmental techniques. RESULTS Following administration of SchE, the average percentage increases of individual increases in AUC, AUMC and C(max) of tacrolimus were 164.2% [95% confidence interval (CI) 70.1, 258.4], 133.1% (95% CI 49.5, 261.3) and 227.1% (95% CI 155.8, 298.4), respectively (P < 0.01 or 0.05). On average, there was a 36.8% (95% CI 13.4, 60.2) increase in tacrolimus t(max) (P < 0.01). The average percentage decreases in CL/F and V/F were 49.0% (95% CI 31.1, 66.9) and 53.7% (95% CI 40.1, 67.4), respectively (P < 0.01). CONCLUSIONS SchE can increase the oral bioavailability of tacrolimus. The results of this study will add important information to the interaction area between drugs and herbal products.
Prevalence of oral lesions and the effects of HAART in adult HIV patients attending a tertiary hospital in Lagos, Nigeria

Background: Oral lesions have been reported to be early clinical features of HIV infection. The objective of this study was to establish the prevalence of oral lesions and the management outcome using HAART in HIV Seropositive patients attending a tertiary hos- pital in Lagos, Nigeria. Methods: This was a prospective study in 114 newly diagnosed adult HIV infected patients (not on antiretroviral therapy), who attended the PEPFAR clinic at Lagos University Teaching Hospital. They were assessed for oral lesions which were evaluated using EEC/WHO—Classification on the diagnostic criteria for oral lesions in HIV. Data were collected using an interviewer administered questionnaire. Oral examination was carried out and oral lesions detected were recorded. Presence or absence of oral lesions was evaluated following 3 months use of HAART. Results: 114 patients were enrolled into the study, 49(43.0%) males and 65(57.0%) females, with age range of 18-63 years. 42 (36.8%) presented with oral lesions, 19 (45.2%) of which had multiple lesions. Oral Candidiasis which accounted for 47.7% was the most common oral lesion observed followed by Oral Hairy Leukoplakia (21.6%) and oral hyperpigmentation (10.8%). Pseudomembraneous Candidiasis was the most common variant of oral Candidiasis seen. Prevalence of oral lesions was significantly associated with low CD4 count and high viral load. Eighty four percent (84%) of oral lesions disappeared following 3 months of HAART treatment. Conclusion: Oral lesions are common features of HIV and a marker for progression of the disease to AIDS. There was significant reduction in oral lesions following 3 months treatment with HAART.
Angiotensin II Type 1 Receptor Antagonist Candesartan as an Angiogenic Inhibitor in a Xenograft Model of Bladder Cancer

Purpose: There have been several studies on the antitumor activity of angiotensin II type 1 receptor (AT1R) antagonists. In this study, we evaluated the efficacy of the AT1R antagonist candesartan in bladder cancer. Experimental Design: For the study in vitro, human bladder cancer cells (KU-19-19) were cultured with or without angiotensin II and candesartan. Various cytokines and cell viability were analyzed. For the study in vivo, a tumor xenograft model was prepared in nude mice using KU-19-19 cells. Mice were given candesartan daily by oral gavage. Microvessel density, expression of vascular endothelial growth factor (VEGF), and apoptosis were assessed. Results: Candesartan did not induce direct toxicity in KU-19-19 cells, but VEGF and interleukin-8 were significantly lower in candesartan-treated cells (2.55 ± 0.25 and 6.58 ± 0.48 pg/103 cells) than in the angiotensin II–treated control cells (3.16 ± 0.42 and 7.91 ± 0.69 pg/103 cells). In mice, candesartan both at doses of 2 and 10 mg/kg/d significantly suppressed tumor growth in mice (35.4% and 33.5% reduction in tumor volume). Microvessel density was significantly decreased by candesartan (9.8 ± 2.8 per field) compared with the control group (17.6 ± 6.0 per field), and VEGF expression was significantly suppressed by this AT1R antagonist. However, candesartan did not induce apoptosis of cancer cells in the tumor. Conclusions: Specific blockade of AT1R prevented bladder tumor growth by inhibiting angiogenesis. However, its antitumor effect was not due to direct toxicity. Because AT1R antagonists are widely used to treat hypertension, and a 2 mg/kg/d dose level of candesartan is clinically achievable, this AT1R antagonist could also be used to treat bladder cancer.
Chemical and Molecular Characterization of Biofilm on Metal Surfaces

Sonak and Bhosle, 1995). As compared to this a few researchers have used molecular approach to assess the development of biofilm (White and Benson, 1984; Khandekar and Johns, 1991; Bhosle and Wagh, 1997). We have used a multi-parameter approach based on biological, chemical, biochemical and molecular constituents to assess development of conditioning film and biofilm on metal surfaces (Bhosle et al., 1989; Bhosle et al., 1990; Sonak and Bhosle, 1995; Bhosle and Wagh, 1997, D’Souza and Bhosle, 2003). This chapter is a compilation of relevant information to understand the dynamics, nature and sources of biofilm organic matter developed on metal surfaces.
Hypertension and the risk of mild cognitive impairment.

OBJECTIVE To explore whether hypertension is associated with the risk of mild cognitive impairment (MCI), an intermediate stage of dementia, because there are conflicting data relating hypertension to the risk of Alzheimer disease. DESIGN AND SETTING Prospective community-based cohort study conducted in northern Manhattan. Multivariate proportional hazards regression analyses were used, relating hypertension to incident all-cause MCI, amnestic MCI, and nonamnestic MCI in 918 persons without prevalent MCI at baseline followed up for a mean of 4.7 years. RESULTS There were 334 cases of incident MCI, 160 cases of amnestic MCI, and 174 cases of nonamnestic MCI during 4337 person-years of follow-up. Hypertension was associated with an increased risk of all-cause MCI (hazard ratio, 1.40; 95% confidence interval, 1.06-1.77; P = .02) and nonamnestic MCI (hazard ratio, 1.70; 95% confidence interval, 1.13-2.42; P = .009) after adjusting for age and sex. Both associations were slightly attenuated in models additionally adjusting for stroke and other vascular risk factors. There was no association between hypertension and the risk of amnestic MCI (hazard ratio, 1.10; 95% confidence interval, 0.79-1.63; P = .49). Consistent with this association, hypertension was related with the slope of change in an executive ability score, but not with memory or language score. There was no effect modification of the association between hypertension and MCI by APOEepsilon4 genotype or use of antihypertensive medication. CONCLUSIONS A history of hypertension is related to a higher risk of MCI. The association seems to be stronger with the nonamnestic than the amnestic type of MCI in the elderly. These findings suggest that prevention and treatment of hypertension may have an important impact in lowering the risk of cognitive impairment.
The Rubinstein-Taybi Syndrome: Familial and Dermatoglyphic Data

Since Rubinstein and Taybi [1] described the syndrome which now bears their names, there have been over 100 cases reported in the literature. In 1968, Rubinstein [2] reviewed 114 cases which either had been published or had been reported to him directly. The main clinical features are mental retardation, broad thumbs and great toes, a characteristic facies, and a high arched palate. A number of other clinical features which are present in the patients in varying frequencies are listed in Rubinstein [2] and Padfield et al. [3]. Most of the published reports describe the clinical features of the cases in some detail together with a number of investigations carried out on the patients such as chromosomal analyses, various biochemical tests, and pregnancy and family histories. No common etiological factor has emerged for this syndrome. Since 17 patients had already been diagnosed and studied clinically in this center and the series was larger than most others reported, it seemed worthwhile to study some parameters in their first-degree relatives. An attempt was made, therefore, to estimate the frequency of this syndrome among the sibs of our patients and, in addition, those of published patients. The means and distributions of parental ages for these families were compared with a control population. The dermatoglyphics in the parents and sibs of the Rubinstein-Taybi patients were examined in the present study. Unusual dermatoglyphics have been reported in patients with the syndrome [3-5], but there have been no reports on the frequencies of dermatoglyphic patterns in relatives of the patients.
Space, time and nature: exploring the public reception of biotechnology in New Zealand

Nature is widely acknowledged to be a fluid, contested, material-semiotic construction, historically and spatially grounded. This is certainly the case for New Zealand, where a number of constructions of nature have been mobilized as a means to make judgments over the viability of particular biotechnologies that have entered into public debate. In this paper, we utilize Mikhail Bakhtin’s space-time matrix, the chronotope, to explore a series of complementary nature-narratives that have been mobilized as a moral basis for making judgments over the acceptability of a series of exemplars of novel biotechnologies that were presented to participants in eleven national focus groups. We argue that it is the specific space-time manipulations that characterize these sometimes overlapping narrative constructions that are used to justify reactions to novel biotechnologies.
Stepping down asthma treatment: how and when

Purpose of review Guidelines suggest that asthma medication should be reduced once asthma control is sustained. Moderate-dose inhaled corticosteroids (ICS) can typically be reduced, but questions remain about the lowest effective ICS dose and the role of non-ICS controllers in treatment reduction. Long-acting beta agonist (LABA) safety concerns have created controversy about how to step down patients on ICS/LABA therapy. This review will focus on the current status of these issues. Recent findings Intermittent ICS treatment, often in fixed combination with short-acting beta agonist, is an emerging strategy for control of mild asthma. Addition of leukotriene modifiers, LABAs, and omalizumab to ICS can allow for reduced ICS dosing. Doses of ICS that control symptoms may be inadequate to control exacerbations. Reducing ICS dose before discontinuing LABAs may be the more effective approach for patients on combination therapy. Summary Use of non-ICS controllers allows for ICS dose reduction with superior outcomes. Tapering of ICS prior to LABA discontinuation may be the favored approach for patients on ICS/LABA therapy, but an understanding of long-term outcomes and further safety data are required. The lowest ICS dose that adequately controls both asthma impairment and risk remains to be determined.
Chinchilla and Murine Models of Upper Respiratory Tract Infections with Respiratory Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. While the primary infection is the most serious, reinfection of the upper airway throughout life is the rule. Although relatively little is known about either RSV infection of the upper respiratory tract or host mucosal immunity to RSV, recent literature suggests that RSV is the predominant viral pathogen predisposing to bacterial otitis media (OM). Herein, we describe mouse and chinchilla models of RSV infection of the nasopharynx and Eustachian tube. Both rodent hosts were susceptible to RSV infection of the upper airway following intranasal challenge; however, the chinchilla proved to be more permissive than the mouse. The chinchilla model will likely be extremely useful to test the role of RSV in bacterial OM and the efficacy of RSV vaccine candidates designed to provide mucosal and cytotoxic T-lymphocyte immunity. Ultimately, we hope to investigate the relative ability of these candidates to potentially protect against viral predisposal to bacterial OM.
Comparison of tongue interface with keyboard for control of an assistive robotic arm

This paper demonstrates how an assistive 6 DoF robotic arm with a gripper can be controlled manually using a tongue interface. The proposed method suggests that it possible for a user to manipulate the surroundings with his or her tongue using the inductive tongue control system as deployed in this study. The sensors of an inductive tongue-computer interface were mapped to the Cartesian control of an assistive robotic arm. The resulting control system was tested manually in order to compare manual control of the robot using a standard keyboard and using the tongue interface. Two healthy subjects controlled the robotic arm to precisely move a bottle of water from one location to another. The results shows that the tongue interface was able to fully control the robotic arm in a similar manner as the standard keyboard resulting in the same number of successful manipulations and an average increase in task duration of up to 30% as compared with the standard keyboard.
A 150-MS/s 8-b 71-mW CMOS time-interleaved ADC

A pipelined analog-to-digital converter (ADC) architecture suitable for high-speed (150 MHz), Nyquist-rate A/D conversion is presented. At the input of the converter, two parallel track-and-hold circuits are used to separately drive the sub-ADC of a 2.8-b first pipeline stage and the input to two time-interleaved residue generation paths. Beyond the first pipeline stage, each residue path includes a cascade of two 1.5-b pipeline stages followed by a 4-b "backend" folding ADC. The full-scale residue range at the output of the pipeline stages is half that of the converter input range in order to conserve power in the operational amplifiers used in each residue path. An experimental prototype of the proposed ADC has been integrated in a 0.18-/spl mu/m CMOS technology and operates from a 1.8-V supply. At a sampling rate of 150 MSample/s, it achieves a peak SNDR of 45.4 dB for an input frequency of 80 MHz. The power dissipation is 71 mW.
Long-term follow-up of the anterior lumbar interbody fusion procedure.

PURPOSE To evaluate the long-term clinical results and the effectiveness of the anterior lumbar interbody fusion procedure. METHODS Between 1999 and 2005, 60 ALIFs were performed in 59 patients. Mean age was 41.1 years. Clinically, patients were evaluated at a mean follow-up of 9.5 years using the Visual Analogue Scale grading scale, the Oswestry Disability score and the SF-36 questionnaire. RESULTS Preoperative and postoperative clinical evaluation scores of 38 patients were available. Nineteen patients were lost to follow-up, and 2 patients died during the follow-up. The fusion rate was 84%. Mean preoperative VAS-score for back pain was 6.69 (±2.15) ; in the long term, the mean VAS-score was 4.95 (±2.95), which was a significant improvement. (p<0.01). The postoperative ODI-score was 36.11 (±22.32), while the preoperative ODI-score was 59.31 (±17.16), which demonstrates a significant improvement. According to the SF-36, mild to good results were observed. CONCLUSIONS The ALIF procedure can offer significant pain relief and improved function if a strict indication policy is followed.
Photometric Variability and Rotation in Magnetic White Dwarfs

We present a search for long term (months—years) photometric variability in a sample of ten isolated magnetic white dwarfs using observations taken with the Liverpool Robotic Telescope between March 2005 and January 2007. These stars had previously been found to be photometrically stable on short (hours—one week) timescales [1]. We construct differential light curves for each target and then use CLEAN and Lomb‐Scargle periodograms to determine any periodicity that may be present. Photometric variability is detected in two of the targets during the observed timescale—G 240–72 and G 227–28. We find no variability in the remaining eight targets above the 1% level. Finally, we search for any correlations between the spin periods and intrinsic physical properties of magnetic white dwarfs, such as the magnetic field strength, temperature, mass and age.
Design a co-processor for Output Probability Calculation in speech recognition

In the CHMM (Continuous Hidden Markov Model) based speech recognition algorithm, Output Probability Calculation (OPC) is the most computation-intensive part. To reduce power consumption and design cost, this paper presents a custom-designed co-processor to implement OPC. The standard SRAM interface of the co-processor allows it to be controlled by various micro-controllers. The co-processor has been implemented in standard-cell based approach and manufactured in 0. 18µm UMC technology. Tested with a 358-state 3-mixture 27-feature 800-word HMM, the co-processor operates at 10MHz to meet real-time requirement. The power consumption of this co-processor is 1.6mW, and the die size is 1.18mm2.
Proficiency testing for the evaluation of the ability of European Union-National Reference laboratories to determine aflatoxin M1 in milk at levels corresponding to the new European Union legislation

In 1992, the European Union set up a network of National Reference Laboratories and charged the Community Reference Laboratory with the responsibility to design a proficiency testing scheme for assessing the analytical ability of laboratories involved in the official control of aflatoxin M1 in milk. Since 1996, two exercises of proficiency testing have been performed on samples of milk powder and liquid milk at various levels of aflatoxin M1 contents. The trials were conducted according to ISO Guide 43, in particular for the homogeneity testing of sample batches and for the calculation of laboratory z-scores. The National Reference Laboratories officially designated by their governments participated in this programme. Samples were naturally-contaminated milk obtained by feeding cows with aflatoxin B1-contaminated feed. The levels of aflatoxin M1 in the samples ranged from 0.2 to 0.7 microg/kg in milk powder and from 0.05 to 0.07 microg/l in liquid milk. These levels were chosen as being close to the European Union-regulated limit of 0.05 microg of aflatoxin M1 per litre. The results produced by laboratories were compiled and statistically analysed to detect any outlying results and to calculate the individual z-scores. Except for one laboratory in each exercise, all laboratories exhibited acceptable or questionable z-scores. The interlaboratory relative standard deviation for reproducibility (RSDR) obtained for both 1996 and 1998 exercises were in the range 15.7-30.3%. Compared with other published studies, this indicates a very good precision for the performance of this laboratory network in the analysis of traces of aflatoxin M1 in milk.
The impact of megakaryocyte proliferation of the evolution of myelofibrosis. Histological follow-up study in 186 patients with chronic myeloid leukaemia.

A histological study on sequential bone marrow biopsies in patients with chronic myeloid leukaemia (CML) was performed. We wished to answer the question as to whether a different content of megakaryopoiesis in the bone marrow of CML patients has a prognostic significance for the development of myelofibrosis during the course of disease. In addition, the significance of possible changes in the quantity of megakaryopoiesis in this process was assessed. In 186 patients who had no fibre increase at first diagnosis, the rate of subsequent myelofibrosis varied from 19% for the common or granulocytic subtype (CML.CT) to 40% for patients with features of megakaryocytic increase (CML.MI). No significant differences were found either in the rapidity of progression to fibrosis or in the final rate of osteomyelosclerosis. Whereas in CML.MI most patients (75%) showed an increase of fibres only, this was accompanied by an additional increase of megakaryocytes in CML.CT, changing the histological pattern from CML.CT to . MI or . MP, respectively. The data therefore revealed a correlation between fibre increase and subtyping of CML as suggested by the Hannover classification of chronic myeloproliferative diseases. Subtypes of CML with megakaryocytic increase could be shown to present a "pre-myelofibrotic" stage of disease and may therefore be conceived as a particular pathway of acceleration.