Miracle-dz/UniFAR-FTUs huggingface dataset:
The N-Terminal Domain That Distinguishes Yeast from Bacterial RNase III Contains a Dimerization Signal Required for Efficient Double-Stranded RNA Cleavage

ABSTRACT Yeast Rnt1 is a member of the double-stranded RNA (dsRNA)-specific RNase III family identified by conserved dsRNA binding (dsRBD) and nuclease domains. Comparative sequence analyses have revealed an additional N-terminal domain unique to the eukaryotic homologues of RNase III. The deletion of this domain from Rnt1 slowed growth and led to mild accumulation of unprocessed 25S pre-rRNA. In vitro, deletion of the N-terminal domain reduced the rate of RNA cleavage under physiological salt concentration. Size exclusion chromatography and cross-linking assays indicated that the N-terminal domain and the dsRBD self-interact to stabilize the Rnt1 homodimer. In addition, an interaction between the N-terminal domain and the dsRBD was identified by a two-hybrid assay. The results suggest that the eukaryotic N-terminal domain of Rnt1 ensures efficient dsRNA cleavage by mediating the assembly of optimum Rnt1-RNA ribonucleoprotein complex.
Posterior retinal contour in adult human anisomyopia.

PURPOSE It is well documented that myopia is associated with an increase in axial length or, more specifically, in vitreous chamber depth. Whether the transverse dimensions of the eye also increase in myopia is relevant to further understanding of its development. METHODS The posterior retinal surface was localized in two-dimensional space in both eyes of young adult white and Taiwanese-Chinese iso- and anisomyopes (N = 56), from measured keratometry, A-scan ultrasonography, and central and peripheral refraction (+/-35 degrees) data, with the aid of a computer modeling program designed for this purpose. Anisomyopes had 2 D or more interocular difference in their refractive errors, with mean values in their more myopic eyes of -5.57 D and in their less myopic eyes of -3.25 D, similar to the means of the two isomyopic groups. The derived retinal contours for the more and less myopic eyes were compared by way of investigating ocular shape changes that accompany myopia, in the posterior region of the vitreous chamber. The presence and size of optic disc crescents were also investigated as an index of retinal stretching in myopia. RESULTS Relative to the less myopic eyes of anisometropic subjects, the more myopic eyes were more elongated and also distorted into a more prolate shape in both the white and Chinese groups. However, the Chinese eyes showed a greater and more uniform relative expansion of the posterior retinal surface in their more myopic eyes, and this was associated with larger optic disc crescents. The changes in the eyes of whites displayed a nasal-temporal axial asymmetry, reflecting greater enlargement of the nasal retinal sector. CONCLUSIONS Myopia is associated with increased axial length and a prolate shape. This prolate shape is consistent with the proposed idea that axial and transverse dimensions of the eye are regulated differently. The observations that ocular shape changes are larger but more symmetrical in Chinese eyes than in eyes of whites warrant further investigation.
Development of the Likelihood of Low Glucose (LLG) Algorithm for Evaluating Risk of Hypoglycemia

Objective: The objective was to develop an analysis methodology for generating diabetes therapy decision guidance using continuous glucose (CG) data. Methods: The novel Likelihood of Low Glucose (LLG) methodology, which exploits the relationship between glucose median, glucose variability, and hypoglycemia risk, is mathematically based and can be implemented in computer software. Using JDRF Continuous Glucose Monitoring Clinical Trial data, CG values for all participants were divided into 4-week periods starting at the first available sensor reading. The safety and sensitivity performance regarding hypoglycemia guidance “stoplights” were compared between the LLG method and one based on 10th percentile (P10) values. Results: Examining 13 932 hypoglycemia guidance outputs, the safety performance of the LLG method ranged from 0.5% to 5.4% incorrect “green” indicators, compared with 0.9% to 6.0% for P10 value of 110 mg/dL. Guidance with lower P10 values yielded higher rates of incorrect indicators, such as 11.7% to 38% at 80 mg/dL. When evaluated only for periods of higher glucose (median above 155 mg/dL), the safety performance of the LLG method was superior to the P10 method. Sensitivity performance of correct “red” indicators of the LLG method had an in sample rate of 88.3% and an out of sample rate of 59.6%, comparable with the P10 method up to about 80 mg/dL. Conclusions: To aid in therapeutic decision making, we developed an algorithm-supported report that graphically highlights low glucose risk and increased variability. When tested with clinical data, the proposed method demonstrated equivalent or superior safety and sensitivity performance.
Obstacle Avoidance Approaches for Autonomous Underwater Vehicle: Simulation and Experimental Results

Autonomous underwater vehicles (AUVs) operate in unknown underwater environments and must be able to avoid submerged obstacles such as cliffs, wrecks, and seabed changes. This paper proposes a methodology for obstacle avoidance by AUVs that are equipped with forward-looking sonars (FLSs). The data collected from two FLSs placed in horizontal and vertical orientation are processed in real time to provide obstacle detection information in the xz- and xy-planes, respectively. Due to the necessity of maintaining constant height when employing sidescan sonar (SSS) and lower energy consumption, horizontal avoidance maneuvers are preferred over vertical ones. For the horizontal obstacle avoidance, a two-layer obstacle avoidance algorithm (OAA) contains two different processes, an OAA based on Bandler and Kohout (BK) product of fuzzy relation used as a preplanning method and a reactive approach based on potential field and edge detection methods. The preplanning technique has a clear advantage on a line segment of the path, and the reactive method is more efficient on a curved segment. In case a horizontal approach cannot find a path to safely avoid the obstacle, the reactive vertical approach is activated. A seabed gradient detection technique that allows prediction of seabed and altitude changes up to 40 m ahead of the AUV is presented. Simulation and experimental results clearly demonstrate that the proposed methodology enables AUVs to navigate safely through obstacles and provide crucial information about the seafloor terrain changes.
Stabilization of blood homocysteine in an epidemiological setting

The major problem in the determination of homocysteine (Hcy), which is thought to be a risk factor in colorectal cancer, is the rise in its concentration if blood is not centrifuged immediately after collection. We assess the interference of 3-deazaadenosine (which inhibits conversion of S-adenosylhomocysteine into Hcy within the erythrocyte), using the fluorescence polarization immunoassay (FPIA) assay, the stabilizing effect of 3-deazaadenosine and the impact of temperature on Hcy stabilization. To assess interference of 3-deazaadenosine, 12 blood samples were extracted; two aliquots were obtained from each and one of them was added 3-deazaadenosine (50 μmol/l). To assess the stabilizing value of 3-deazaadenosine, as well as the effect of temperature, two blood samples were extracted from 24 volunteers. One of the tubes was immediately placed on ice and centrifuged (reference concentration). To the second tube was immediately added 3-deazaadenosine (50 μmol/l), producing six aliquots, three of which were kept at room temperature (25°C) for 1, 4 and 6 hours, the other three kept at 37°C. The mean values (standard deviation) obtained for methodological interference were: 7.32 (3.58) μmol/l without stabilizer, and 7.11 (3.61) μmol/l with stabilizer. There were no statistically significant differences (P = 0.104) and intraclass correlation coefficient was 0.989, suggesting no methodological interference. We did not find any significant differences regarding our reference value in the samples kept at room temperature during the interval studied. A high Pearson correlation coefficient was obtained. Nevertheless, in those samples kept at 37°C, a slight increase was observed in the 4-hour period (P = 0.009). The addition of 3-deazaadenosine may avoid problems in the critical pre-analytical phase in the Hcy measurement. There is no interference with the FPIA assay, nor any dilution effect, and new reference values are not necessary.
Early posthatch thermal stress affects breast muscle development and satellite cell growth and characteristics in broilers

&NA; Heat or cold stress, can disrupt well‐being and physiological responses in birds. This study aimed to elucidate the effects of continuous heat exposure in the first 2 wk of age on muscle development in broilers, with an emphasis on the pectoralis muscle satellite cell population. Chicks were reared for 13 d under either commercial conditions or a temperature regime that was 5°C higher. Body and muscle weights, as well as absolute muscle growth were lower in heat‐exposed chicks from d 6 onward. The number of satellite cells derived from the experimental chicks was higher in the heat‐treated group on d 3 but lower on d 8 and 13 compared to controls. This was reflected in a lower number of myonuclei expressing proliferating nuclear cell antigen in cross sections of pectoralis major muscle sampled on d 8. However, a TUNEL assay revealed similar cell survival in both groups. Mean myofiber diameter and distribution were lower in muscle sections sampled on d 8 and 13 in heat‐treated versus control group, suggesting that the lower muscle growth is due to changes in muscle hypertrophy. Oil‐Red O staining showed a higher number of satellite cells with lipids in the heat‐treated compared to the control group on these days. Moreover, lipid deposition was observed in pectoralis muscle cross sections derived from the heat‐treated chicks on d 13, whereas the controls barely exhibited any lipid staining. The gene and protein expression levels of CCAAT/enhancer binding protein &bgr; in pectoralis muscle from the heat‐treated group were significantly higher on d 13 than in controls, while myogenin levels were similar. The results suggest high sensitivity of muscle progenitor cells in the early posthatch period at a time when they are highly active, to chronic heat exposure, leading to impaired myogenicity of the satellite cells and increased fat deposition.
Evaluating the effectiveness of proactive telephone counselling for smoking cessation in a randomized controlled trial.

AIM To evaluate the effectiveness of repeated-contact proactive telephone counselling for smoking cessation in a UK setting. DESIGN Randomized controlled trial. SETTING The Quitline, an established national telephone counselling service available throughout the UK. PARTICIPANTS AND INTERVENTION A total of 1,457 callers to the Quitline in 2000 and 2001 were allocated randomly to a Control group to receive usual care or to a Repeated Contact group to be offered five proactive calls in addition to usual care. MEASUREMENTS Prolonged abstinence and 24-hour point-prevalent abstinence 6 and 12 months after recruitment, quit attempts and 24-hour periods of abstinence in non-quitters. FINDINGS No significant differences were found between the Repeated Contact and Control groups on prolonged or point-prevalent abstinence. On an intention-to-treat basis, 9.5% of the Control group were abstinent for longer than 6 months at the 12-month follow-up, compared with 9.3% of the Repeated Contact group; 18.9% and 20.2%, respectively, were point-prevalent abstinent at the 6-month follow-up. Significantly more non-quitters in the Control group made a quit attempt in the first 6 months following recruitment than in the Repeated Contact group (62.6%/56.1%, P < 0.05). CONCLUSIONS Proactive telephone counselling did not significantly increase abstinence rates, and appeared to decrease quit attempts, in callers to the Quitline. A non-structured, client-led counselling protocol and insufficient pre-quit motivational counselling could account for the lack of effect.
A retrospective study assessing the incidence, risk factors and comorbidities of pamidronate-related necrosis of the jaws in multiple myeloma patients.

BACKGROUND Bone necrosis of the jaws is a newly recognized complication associated with the use of bisphosphonates. The true incidence of this complication is unknown and the pathophysiology is controversial. The purpose of this study was to determine the incidence of jaw necrosis among a homogeneous population of multiple myeloma patients receiving the bisphosphonate pamidronate, to investigate risk factors and comorbidities that increase the risk and to characterize the radiographic changes on conventional dental radiographs in terms of type and frequency. MATERIALS AND METHODS The study was a retrospective review of medical and dental charts and databases in the medical oncology and dental departments at Princess Margaret Hospital, a tertiary cancer centre in Toronto. Two patient sample sizes were used, n = 655 for assessment of the incidence and n = 120 for analysis of the risk factors and comorbidities. RESULTS The incidence was estimated at 3.2% (95% confidence interval). The following risk factors were found to be statistically significant: longer duration of pamidronate therapy (P < 0.001), dental extractions (P < 0.001), cyclophosphamide therapy (P < 0.014), prednisone therapy (P < 0.014), erythropoietin therapy (P = 0.006), low hemoglobin levels (P < 0.001), renal dialysis (P < 0.016) and advanced age (P < 0.001). Radiographic changes produced by the necrotic bone were less evident than the clinically exposed bone.
Ischemia-Modified Albumin and Atherosclerosis in Patients With Familial Mediterranean Fever

The constriction of vessels due to atherosclerotic lesions causes hypoxia/ischemia and oxidative changes resulting in transformation of free albumin to ischemia-modified albumin (IMA) in the circulation and increased carotid intima–media thickness (cIMT). We investigated the reliability of IMA increase in evaluating atherosclerosis in patients with familial Mediterranean fever (FMF) compared with cIMT. Patients with FMF (n = 58) diagnosed by the Tel-Hashomer criteria in attack-free period and 38 healthy people were included in the study. Patient demographics as well as the clinical and laboratory characteristics of the healthy controls and patients with FMF were noted. The IMA levels and cIMT in patients with FMF were 0.30 ± 0.09 absorbance units (ABSUs) and 1.12 ± 0.27 mm, respectively, and in the control group, IMA levels and cIMT were 0.25 ± 0.07 ABSU and 0.74 ± 0.26 mm, respectively. The IMA levels and cIMT were significantly higher in patients with FMF than in controls (P = .020 and P < .0001, respectively). The IMA values showed positive correlation with cIMT in patients with FMF(r = .302, P = .041). Our results reveal that IMA—an oxidative stress marker—may be an indicator of atherosclerosis in patients with FMF. This finding deserves further investigation.
Modelling, Simulation and Fault Diagnosis of the Three-Phase Inverter Using Bond Graph

In this paper, a bond graph fault diagnosis methodology applied to a three-phase inverter is presented. A qualitative approach is used, which is based on signal amplitude behavior analysis when a fault in the system is presented. For a complete bond graph modelling of the three-phase inverter, sub-models for each power switches are used. Considerations about switching devices from the bond graph point of view are made in order to cope the simulation aspect and, at the same time, to avoid causality problems in the qualitative diagnosis approach employed. We include both open-circuit and short-circuit faults on power switches.
Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for Caesarean section.

BACKGROUND During spinal anaesthesia for Caesarean section, the optimal phenylephrine regimen and the optimal blood pressure (BP) to which it should be titrated are undetermined. The ideal regimen would balance efficacy for maintaining uteroplacental perfusion pressure against potential for uteroplacental vasoconstriction, both of which may affect fetal acid-base status. We compared phenylephrine infusion regimens based on three different BP thresholds. METHODS After intrathecal injection, we infused phenylephrine 100 microg min(-1) for 2 min. Then, until delivery, we infused phenylephrine whenever systolic BP (SBP), measured every 1 min, was below a randomly assigned percentage of baseline: 100% (Group 100, n=25), 90% (Group 90, n=25) or 80% (Group 80, n=24). We compared umbilical blood gases, Apgar scores and maternal haemodynamics and symptoms. RESULTS Patients in Group 100 had fewer episodes [median 0 (range 0-8)] of hypotension (SBP <80% baseline) compared with Group 80 [5 (0-18)] and Group 90 [2 (0-7)] (P<0.001 in each instance). Total dose of phenylephrine was greater in Group 100 [median 1520 microg (interquartile range 1250-2130 microg)] compared with Group 90 [1070 (890-1360) microg] and Group 80 [790 (590-950) microg]. Umbilical arterial pH was greater in Group 100 [mean 7.32 (95% confidence interval 7.31-7.34)] than in Group 80 [7.30 (7.28-7.31)] (P=0.034). No patient had umbilical arterial pH <7.2. In Group 100, 1/24 (4%) patients had nausea or vomiting compared with 4/25 (16%) in Group 90 and 10/25 (40%) in Group 80 (P=0.006). CONCLUSIONS For optimal management, phenylephrine should be titrated to maintain maternal BP at near-baseline values.
Induction of Syncytia by Neuropathogenic Murine Leukemia Viruses Depends on Receptor Density, Host Cell Determinants, and the Intrinsic Fusion Potential of Envelope Protein

ABSTRACT Infection by the neuropathogenic murine leukemia virus (MLV) TR1.3 results in hemorrhagic disease that correlates directly to in vivo syncytium formation of brain capillary endothelial cells (BCEC). This phenotype maps to amino acid 102 in the envelope (Env) protein of TR1.3. Substitution of glycine (G) for tryptophan (W) at this position (W102G Env) in the nonpathogenic MLV FB29 induces both syncytium formation and neurologic disease in vivo. Using an in vitro gene reporter cell fusion assay, we showed that fusion either with murine NIH 3T3 cells or with nonmurine target cells that expressed receptors at or below endogenous murine levels mirrored that seen in BCEC in vivo. In these instances only TR1.3 and W102G Env induced cell fusion. In contrast, when receptor levels on nonmurine cells were raised above endogenous murine levels, FB29 Env was as fusogenic as the neuropathogenic TR1.3 and W102G Env. These results indicate that TR1.3 Env and W102G Env are intrinsically more fusogenic than FB29 Env, that the induction of fusion requires a threshold number of receptors that is greater for FB29 Env than for TR1.3 or W102G Env, and that receptor density on murine NIH 3T3 cells and BCEC is below the threshold for FB29-dependent fusion. Surprisingly, receptor density on NIH 3T3 cells could not be increased by stable expression of exogenous receptors, and FB29-dependent fusion was not observed in NIH 3T3 cells that transiently expressed elevated receptor numbers. These results suggest that an additional undefined host cell factor(s) may limit both receptor expression and fusion potential in murine cells.
Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection.

Infection with the liver fluke, Opisthorchis viverrini, is a causative agent of cholangiocarcinoma. One possible contributing factor in this carcinogenesis is the chronic, local generation of nitric oxide by inflammatory cells expressing inducible nitric oxide synthase and the production of N-nitroso compounds via the reaction between amines and nitrosating agents derived from nitric oxide. Our previous studies provided evidence that nitric oxide synthesis is elevated during human liver fluke infection. Here we present data on the same sample of men which definitively demonstrates increased nitrosation of proline and thioproline (thiazolidine-4-carboxylic acid) among infected men compared to uninfected control subjects on a low nitrate diet. This difference was specifically abolished by co-administration of ascorbic acid with proline and by elimination of parasites by praziquantel treatment. Multivariate statistical models demonstrate the importance of salivary thiocyanate levels to variation in the nitrosation of proline among uninfected individuals, but not among those with current fluke infection. This suggests that considerable generation of nitrosating agents (N203/N204) in infected people may be occurring via oxidation of arginine by nitric oxide synthase in inflamed tissue which is thiocyanate insensitive. Analyses revealed positive associations between N-nitrosoproline excretion and nitrate/nitrite levels in urine, plasma and saliva and with usual alcohol intake; with variation in these trends between groups. In conclusion, we have confirmed the relationship between O.viverrini infection and enhanced endogenous nitrosation, showing evidence of its extragastric site. New information is also provided on the determinants of N-nitrosamino acid excretion in men on a controlled low nitrate diet without smoking, conditions which reduce exogenous sources of nitrosating agents.
Clinical management of rivaroxaban-treated patients

Introduction: Until recently, only vitamin K antagonists (VKAs) were used for long-term anticoagulation. New oral anticoagulants, with pharmacokinetic and pharmacodynamic characteristics different to VKAs, are now available for some indications. Rivaroxaban (Xarelto®) is an oral Factor Xa inhibitor approved in many countries for long-term treatment of patients with atrial fibrillation or venous thromboembolism. This article is addressed to all professionals involved in the management of treated patients to highlight the characteristics of rivaroxaban and provide practical guidance on management of treated patients. Areas covered: This article is based on a consensus of specialists involved in the management of anticoagulant treatment, including thrombosis experts, cardiologists, neurologists, emergency medicine specialists, and general practitioners. The authors performed a nonsystematic review of the literature, and expressed guidance statements based on the results of the review as well as personal experience. Expert opinion: Availability of new anticoagulant drugs, including rivaroxaban, is an important step forward to allow easier, more effective, and safer long-term anticoagulation in patients in whom adequate anticoagulation is currently denied due to the limitations of VKAs. However, given their totally new properties, associated risks, and expected broad clinical use, expert professionals and manufacturers must urgently tackle a series of issues.