Miracle-dz/UniFAR-FTUs huggingface dataset:
Biliverdin reductase: A major physiologic cytoprotectant

Bilirubin, an abundant pigment that causes jaundice, has long lacked any clear physiologic role. It arises from enzymatic reduction by biliverdin reductase of biliverdin, a product of heme oxygenase activity. Bilirubin is a potent antioxidant that we show can protect cells from a 10,000-fold excess of H2O2. We report that bilirubin is a major physiologic antioxidant cytoprotectant. Thus, cellular depletion of bilirubin by RNA interference markedly augments tissue levels of reactive oxygen species and causes apoptotic cell death. Depletion of glutathione, generally regarded as a physiologic antioxidant cytoprotectant, elicits lesser increases in reactive oxygen species and cell death. The potent physiologic antioxidant actions of bilirubin reflect an amplification cycle whereby bilirubin, acting as an antioxidant, is itself oxidized to biliverdin and then recycled by biliverdin reductase back to bilirubin. This redox cycle may constitute the principal physiologic function of bilirubin.
Varenicline in the routine treatment of tobacco dependence: a pre-post comparison with nicotine replacement therapy and an evaluation in those with mental illness.

AIMS To compare the effectiveness of varenicline with nicotine replacement for smoking cessation and to evaluate the safety and effectiveness of varenicline in people with mental illness. DESIGN Evaluation of consecutive routine cases before and after the introduction of varenicline. SETTING National Health Service (NHS) tobacco dependence clinic in London, UK. PARTICIPANTS A total of 412 cases receiving routine care. INTERVENTION Seven group support sessions over 6 weeks with either nicotine replacement therapy (NRT) (n = 204) or varenicline (n = 208). MEASUREMENTS Verified abstinence 4 weeks after quit day, severity of withdrawal symptoms, incidence and severity of adverse drug symptoms, cost per patient treated and cost per successful short-term quitter. FINDINGS Short-term cessation rates were higher with varenicline than NRT (odds ratio = 1.70, 95% confidence interval = 1.09-2.67). Varenicline was equally effective in those with and without mental illness. Craving to smoke, but not adverse mood, was less severe with varenicline than NRT. The cost per quitter was similar for varenicline and NRT. There was a higher incidence of adverse drug symptoms among those taking varenicline, but these were tolerated by most smokers. There was no evidence that varenicline exacerbated mental illness. CONCLUSIONS In this setting and with group support varenicline appears to improve success rates over those achieved with NRT, and is equally effective and safe in those with and without a mental illness.
IL-12 como marcador predictivo de severidad del Dengue

Investigaciones previas han sugerido que las citocinas TH1 predominan en casos de fiebre del dengue (FD) y las TH2 en casos de fiebre hemorragica del dengue (FHD). La IL-12 es un importante factor de diferenciacion de celulas TH1. Con base a lo expuesto, se investigo mediante ensayo inmunoenzimatico (ELISA) los niveles sericos de IL-12 en pacientes con diferentes presentaciones clinica de dengue [FD (n8), FHD (n=9)] e individuos controles sanos (n=10) de ambos sexos y edades similares. Los pacientes con dengue tuvieron concentraciones de IL-12 significativamente mayores a las encontradas en los individuos controles (148,9±121,2 pg/mL vs 63,6±22 pg/mL, respectivamente; p<0,001). Las concentraciones de IL-12 en los pacientes con FD fueron significativamente mayores a las encontradas en los casos de FHD (226,8±134,9 pg/mL vs 79,6±44,5 pg/mL, respectivamente; p<0,001). No hubo diferencias significativas (p<0,1) entre las concentraciones de IL-12 encontradas en pacientes con FHD y los individuos controles. La frecuencia de sueros positivos para IL-12 en los pacientes con FD fue mayor que en aquellos con FHD (75% vs 11,1%, respectivamente; valor de corte en ELISA: 129,7 pg/mL). Las concentraciones promedio de IL-12 en los pacientes con FD alcanzaron los niveles mas altos 3 - 5 dias despues del inicio de la fiebre y disminuyeron en la medida que evoluciono la enfermedad, manteniendose por encima del valor de corte 6 - 7 dias despues del inicio de la fiebre. En conclusion, los pacientes con FD demostraron niveles sericos elevados de IL-12 durante la fase aguda de la enfermedad, sugiriendo la posibilidad de ser considerarla como marcador inmunologico de severidad del dengue
Finite time attitude control of double tethered satellites system in deep space

A finite time attitude control law incorporating a disturbance observer is proposed for double tethered satellites system (2-TSS) with a variable length tether in deep space. For each single tethered satellite, a disturbance observer combining with the theory of Extended State Observer (ESO) is firstly utilized to precisely estimate the synthesis of external bounded disturbances and parameter uncertainties. The stability of the observer is analyzed so that the observation errors are globally uniformly ultimately bounded and finally converge to a small neighborhood. Then to realize attitude control with high precision and fast response in finite time, a finite time attitude control law is proposed through designing a fast nonsingular sliding mode surface with a specific switching function. The Lyapunov stability analysis is performed to show that the system states are finite time stable and that the sliding mode surface can reach a small region of origin. Finally, numerical simulations demonstrate the effectiveness of proposed control schemes with disturbance observer.
Real-time simulation of BLDC-based wind turbine emulator using RT-LAB

A novel wind turbine emulator (WTE) based on a torque controlled Brushless DC (BLDC) motor is presented, which can emulate the steady-state and dynamic characteristics of an actual wind turbine. Variable wind speeds, turbine inertia and torque oscillation caused by tower shadow and wind shear are all considered in the construction of the actual wind turbine model and the torque controlled BLDC model . A PI regulator is employed to make sure that the output torque of BLDC tracks the reference torque. The simulation results based on RT-LAB real-time simulation platform verify the validity of the proposed WTE.
Heart rate variability decreased by coronary artery surgery has no prognostic value

Background Decreased heart rate variability (HRV) may predict cardiac death after myocardial infarction (MI). Coronary artery bypass grafting (CABG) strongly decreases HRV, but improves survival. The aim of the study was to determine the prognostic value of HRV decreased by coronary surgery. Design and methods Four-year follow-up was performed in 175 consecutive patients with HRV decreased by CABG (51) or MI (124). Mortality and secondary events rate were analysed. Decreased HRV, defined by the standard deviation of mean RR interval (SDNN) < 100 ms, was detected by a routine 24-h Holter electrocardiogram at admission to stationary rehabilitation 3 weeks to 3 months after acute MI or CABG. Two groups did not differ except by age; CABG patients were younger (56 versus 64 years, P<0.01), but this did not influence differences in survival (NS). Results HRV was lower among CABG patients than among MI patients (SDNN = 66 ± 20ms versus 77 ± 14 ms; P<0.001), but cumulative survival and event-free survival were much better in the CABG group than in the MI group. During a 46 ± 20 months follow-up, there were 10% new events in the CABG and 43% in the MI group (P<0.001). Mortality was 8% in the CABG and 33% in the MI group (log-rank=3.6; P<0.001). Unlike in the MI group, HRV was not different between survivors and non-survivors in the CABG group. Conclusions In contrast to the strong prognostic potential of HRV in patients with MI, decreased HRV has no prognostic significance in patients who have undergone CABG surgery.
Starting a carotid artery stenting program is safe

Background: Little is known on the performance of newly initiated carotid artery stenting (CAS) programs. The safety of the procedure is being questioned following the publication of the EVA‐3S trial, a study criticized for the limited interventional experience required to enroll patients. Methods: Within a newly started academic CAS program, patient data and outcomes were collected prospectively. The outcomes of the first 100 consecutive patients treated are reported. A CAS‐fellowship‐trained interventionalist was involved in all procedures. All patients underwent clinical assessment by a neurologist before and after the procedure, and serial ECG and cardiac enzymes were routinely obtained. Primary outcome measures included 30‐day major adverse events (MAE), defined as death, stroke, or myocardial infarction, while on follow‐up deaths and ipsilateral strokes were added. Results: Between July 2003 and November 2006, 92 patients had a single internal carotid artery treated, while 7 underwent staged bilateral CAS. In one patient, the procedure was aborted prior to lesion treatment. The 30‐day MAE rate per procedure was 1.9% (one major and one minor stroke). By a mean follow‐up of 16 months (range 2–42 months), one patient had died of refractory heart failure, while one patient had a minor ipsilateral stroke and three had minor contralateral strokes, corresponding to total MAE per patient of 4%. The rate of any stroke or death was 7%. The rate of restenosis ≥50% per lesion by ultrasound was 3.8%. Conclusion: This single center experience suggests that it is safe to start a CAS program following dedicated fellowship. © 2008 Wiley‐Liss, Inc.
Barley grain with adhering hulls is controlled by an ERF family transcription factor gene regulating a lipid biosynthesis pathway

In contrast to other cereals, typical barley cultivars have caryopses with adhering hulls at maturity, known as covered (hulled) barley. However, a few barley cultivars are a free-threshing variant called naked (hulless) barley. The covered/naked caryopsis is controlled by a single locus (nud) on chromosome arm 7HL. On the basis of positional cloning, we concluded that an ethylene response factor (ERF) family transcription factor gene controls the covered/naked caryopsis phenotype. This conclusion was validated by (i) fixation of the 17-kb deletion harboring the ERF gene among all 100 naked cultivars studied; (ii) two x-ray-induced nud alleles with a DNA lesion at a different site, each affecting the putative functional motif; and (iii) gene expression strictly localized to the testa. Available results indicate the monophyletic origin of naked barley. The Nud gene has homology to the Arabidopsis WIN1/SHN1 transcription factor gene, whose deduced function is control of a lipid biosynthesis pathway. Staining with a lipophilic dye (Sudan black B) detected a lipid layer on the pericarp epidermis only in covered barley. We infer that, in covered barley, the contact of the caryopsis surface, overlaid with lipids to the inner side of the hull, generates organ adhesion.
Emergency physician accuracy in interpreting electrocardiograms with potential ST-segment elevation myocardial infarction: Is it enough?

Background: Electrocardiogram (ECG) interpretation is widely performed by emergency physicians. We aimed to determine the accuracy of interpretation of potential ST-segment elevation myocardial infarction (STEMI) ECGs by emergency physicians. Methods: Thirty-six ECGs resulted in putative STEMI diagnoses were selected. Participants were asked to focus on whether or not the ECG in question met the diagnostic criteria for an acutely blocked coronary artery causing a STEMI. Based on the coronary angiogram, a binary outcome of accurate versus inaccurate ECG interpretation was defined. We computed the overall sensitivity, specificity, accuracy and 95% confidence intervals (95%CIs) for ECG interpretation. Data on participant training level, working experience and place were collected. Results: 135 participants interpreted 4603 ECGs. Overall sensitivity to identify ‘true’ STEMI ECGs was 64.5% (95%CI: 62.8–66.3); specificity in determining ‘false’ ECGs was 78% (95%CI: 76–80.1). Overall accuracy was modest (69.1, 95%CI: 67.8–70.4). Higher accuracy in ECG interpretation was observed for attending physicians, participants working in tertiary care hospitals and those more experienced. Conclusion: The accuracy of interpretation of potential STEMI ECGs was modest among emergency physicians. The study supports the notion that ECG interpretation for establishing a STEMI diagnosis lacks the necessary sensitivity and specificity to be considered a reliable ‘stand-alone’ diagnostic test.
Highly Diversified Molecular Evolution of Downstream Transcription Start Sites in Rice and Arabidopsis1[W][OA]

Alternative usage of transcription start sites (TSSs) is one of the key mechanisms to generate gene variation in eukaryotes. Here, we show diversified molecular evolution of TSSs in remotely related flowering plants, rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana), by comprehensive analyses of large collections of full-length cDNAs and genome sequences. We determined 45,917 representative TSSs within 23,445 loci of rice and 35,313 TSSs within 16,964 loci of Arabidopsis, about two TSSs per locus in either species. The nucleotide features around TSSs displayed distinct patterns when the most upstream TSSs were compared with downstream TSSs. We found that CG-skew and AT-skew were clearly different between upstream and downstream TSSs, and that this difference was commonly observed in rice and Arabidopsis. Relative entropy analysis revealed that the most upstream TSSs had retained canonical cis elements, whereas downstream TSSs showed atypical nucleotide features. Expression patterns were distinguishable between upstream and downstream TSSs. These results indicate that plant TSSs were generally diversified in downstream regions, resulting in the development of new gene expression patterns. Furthermore, our comparative analysis of TSS variation between the species showed a positive correlation between TSS number and gene conservation. Rice and Arabidopsis might have evolved novel TSSs in an independent manner, which led to diversification of these two species.
The Papain Inhibitor (SPI) of Streptomyces mobaraensis Inhibits Bacterial Cysteine Proteases and Is an Antagonist of Bacterial Growth

ABSTRACT A novel papain inhibitory protein (SPI) from Streptomyces mobaraensis was studied to measure its inhibitory effect on bacterial cysteine protease activity (Staphylococcus aureus SspB) and culture supernatants (Porphyromonas gingivalis, Bacillus anthracis). Further, growth of Bacillus anthracis, Staphylococcus aureus, Pseudomonas aeruginosa, and Vibrio cholerae was completely inhibited by 10 μM SPI. At this concentration of SPI, no cytotoxicity was observed. We conclude that SPI inhibits bacterial virulence factors and has the potential to become a novel therapeutic treatment against a range of unrelated pathogenic bacteria.
Nectin‐dependent localization of ZO‐1 at puncta adhaerentia junctions between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of adult mouse hippocampus

Nectin and afadin constitute a novel intercellular adhesion system that organizes adherens junctions in cooperation with the cadherin‐catenin system in epithelial cells. Nectin is a Ca2+‐independent immunoglobulin‐like adhesion molecule and afadin is an actin filament (F‐actin)‐binding protein that connects nectin to the actin cytoskeleton. At the puncta adhaerentia junctions (PAs) between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of the adult mouse hippocampus, the nectin‐afadin system also colocalizes with the cadherin‐catenin system and has a role in the formation of synapses. ZO‐1 is another F‐actin‐binding protein that localizes at tight junctions (TJs) and connects claudin to the actin cytoskeleton in epithelial cells. The nectin‐afadin system is able to recruit ZO‐1 to the nectin‐based cell–cell adhesion sites in nonepithelial cells that have no TJs. In the present study, we investigated the localization of ZO‐1 in the mouse hippocampus. Immunofluorescence and immunoelectron microscopy revealed that ZO‐1 also localized at the PAs between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of the adult mouse hippocampus, as described for afadin. ZO‐1 colocalized with afadin during the development of synaptic junctions and PAs. Microbeads coated with the extracellular fragment of nectin, which interacts with cellular nectin, recruited both afadin and ZO‐1 to the bead–cell contact sites in cultured rat hippocampal neurons. These results indicate that ZO‐1 colocalizes with nectin and afadin at the PAs and that the nectin‐afadin system is involved in the localization of ZO‐1. J. Comp. Neurol. 460:514–524, 2003. © 2003 Wiley‐Liss, Inc.
Quantitative Biochemical and Ultrastructural Comparison of Mitochondrial Permeability Transition in Isolated Brain and Liver Mitochondria: Evidence for Reduced Sensitivity of Brain Mitochondria

Opening of the mitochondrial permeability transition pore has increasingly been implicated in excitotoxic, ischemic, and apoptotic cell death, as well as in several neurodegenerative disease processes. However, much of the work directly characterizing properties of the transition pore has been performed in isolated liver mitochondria. Because of suggestions of tissue-specific differences in pore properties, we directly compared isolated brain mitochondria with liver mitochondria and used three quantitative biochemical and ultrastructural measurements of permeability transition. We provide evidence that brain mitochondria do not readily undergo permeability transition upon exposure to conditions that rapidly induce the opening of the transition pore in liver mitochondria. Exposure of liver mitochondria to transition-inducing agents led to a large, cyclosporin A-inhibitable decrease in spectrophotometric absorbance, a loss of mitochondrial glutathione, and morphologic evidence of matrix swelling and disruption, as expected. However, we found that similarly treated brain mitochondria showed very little absorbance change and no loss of glutathione. The absence of response in brain was not simply due to structural limitations, since large-amplitude swelling and release of glutathione occurred when membrane pores unrelated to the transition pore were formed. Additionally, electron microscopy revealed that the majority of brain mitochondria appeared morphologically unchanged following treatment to induce permeability transition. These findings show that isolated brain mitochondria are more resistant to induction of permeability transition than mitochondria from liver, which may have important implications for the study of the mechanisms involved in neuronal cell death.
ANTIEPILEPTIC DRUGS IN THE TREATMENT OF NEUROPATHIC PAIN: DRUG‐TO‐DRUG INTERACTION IN ELDERLY PEOPLE

500 MU per 2.5 mL of saline. The appropriate conversion factor of Botox:Dysport varies from 1:3 to 1:6 MU in studies using these agents in dystonia. The different potency of these agents in treating sialorrhea in PD is unknown. Therefore, given a conversion factor of 1:6 MU, our dosage of 80 MU appeared to be similar to that used in the report by Nóbrega et al. Moreover, our study showed that BTX-A decreased the volume and the frequency of sialorrhea, as demonstrated in other studies, whereas in the study by Nóbrega et al., only the volume was reduced. We agree with Nóbrega et al. on the possibility that in patients with PD, sialorrhea may be secondary to swallowing disorders, although in our study, the effect of the toxin on drooling frequency was less relevant than that on the volume, and it may be linked to the severity of PD in our patients, which was not specified in the report by Nóbrega et al. Finally, another important issue to discuss may be the duration of effectiveness of treatment with BTX-A in Parkinsonian-related sialorrhea. Some patients treated with BTX-A develop secondary immune resistance or do not obtain effective control of symptoms. Therefore, given the efficacy and safety of botulinum toxin type B (BTX-B) also in the management of sialorrhea in PD, we propose switching therapy from BTXA to BTX-B in patients who are nonresponders or poor responders to BTX-A.
Contrasting effects of angiotensin converting inhibitor and alpha‐1‐antagonist on albuminuria in insulin‐dependent diabetes mellitus patients with nephropathy

Abstract. Objective. The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha‐1 (α‐1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin‐dependent diabetes mellitus patients with nephropathy.
Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints

The uppermost superficial surface layer of articular cartilage, the ‘lamina splendens’ which provides a very low friction lubrication surface in articular joints, was investigated using atomic force microscopy (AFM). Complementary specimens were also observed under SEM at −10 °C without dehydration or sputter ion coating. Fresh adult pig osteochondral specimens were prepared from the patellas of pig knee joints and digested with the enzymes, hyaluronidase, chondroitinase ABC and alkaline protease. Friction coefficients between a pyrex glass plate and the osteochondral specimens digested by enzymes as well as natural (undigested) specimens were measured, using a thrust collar apparatus. Normal saline, hyaluronic acid (HA) and a mixture of albumin, globulin, HA (AGH) were used as lubrication media. The surface irregularities usually observed in SEM studies were not apparent under AFM. The articular cartilage surface was resistant to hyaluronidase and also to chondroitinase ABC, but a fibrous structure was exhibited in alkaline protease enzymes‐digested specimens. AFM analysis revealed that the thickness of the uppermost superficial surface layer of articular cartilage was between 800 nm and 2 μm in adult pig articular cartilage. The coefficient of friction (c.f.) was significantly higher in chondroitinase ABC and alkaline protease enzymes digested specimens. Generally, in normal saline lubrication medium, c.f. was higher in comparison to HA and AGH lubrication media. The role of the uppermost, superficial surface layer of articular cartilage in the lubrication mechanism of joints is discussed.
Acute Hypoxia Induces HIF-Independent Monocyte Adhesion to Endothelial Cells through Increased Intercellular Adhesion Molecule-1 Expression: The Role of Hypoxic Inhibition of Prolyl Hydroxylase Activity for the Induction of NF-κB

Myeloid cells recruited to sites of bacterial inflammation are exposed to low oxygen tension, hypoxia, and high concentrations of inflammatory cytokines that significantly affect myeloid cell function. Therefore, we analyzed the direct consequences of acute and severe hypoxia on monocytic adhesion to the endothelium in coculture experiments. Marked upregulation of monocytic ICAM-1, but no other monocytic adhesion molecule, was responsible for an ≈50-fold increase in adhesion of the monocytic cells THP-1 to human and rat endothelial cells. ICAM-1 expression was rapidly induced after the onset of severe hypoxia, but it decreased after 4 h. Knockdown of ICAM-1 by siRNA in endothelial and monocytic cells abolished the adhesion, indicating that ICAM-1 expression on both cell types was indispensable for hypoxia-induced adhesion of monocytes to the endothelium. siRNA-mediated knockdown of hypoxia inducible factor (HIF)-1α, HIF-2α, and the NF-κB family member p65 revealed that hypoxic upregulation of ICAM-1 resulted from hypoxic NF-κB induction but not from activation of HIFs. Within the leukocyte-adhesion cascade, our results provide evidence for prolyl hydroxylase-dependent but HIF-independent activation of hypoxia-induced monocyte–endothelial adhesion and assign a new function to monocytic ICAM-1 under acute hypoxic conditions.