Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues

ABSTRACT Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly 100% of the world population and causes severe respiratory disease in infants, the elderly, and immunocompromised patients. We previously showed that HMPV binds heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the viral fusion (F) protein. To characterize the features of this interaction critical for HMPV binding and the role of this interaction in infection in relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics, and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity by inhibiting binding to lung cells mediated by the F protein. Furthermore, analysis of a minilibrary of variably sulfated derivatives of Escherichia coli K5 polysaccharide mimicking the HS structure revealed that the highly O-sulfated K5 polysaccharides inhibited HMPV infection, identifying a potential feature of HS critical for HMPV binding. The peptide dendrimer SB105-A10, which binds HS, reduced binding and infection in an F-dependent manner, suggesting that occlusion of HS at the target cell surface is sufficient to prevent infection. HMPV infection was also inhibited by these compounds during apical infection of polarized airway tissues, suggesting that these interactions take place during HMPV infection in a physiologically relevant model. These results reveal key features of the interaction between HMPV and HS, supporting the hypothesis that apical HS in the airway serves as a binding factor during infection, and HS modulating compounds may serve as a platform for potential antiviral development. IMPORTANCE Human metapneumovirus (HMPV) is a paramyxovirus that causes respiratory disease worldwide. It has been previously shown that HMPV requires binding to heparan sulfate on the surfaces of target cells for attachment and infection. In this study, we characterize the key features of this binding interaction using heparan sulfate mimetics, identify an important sulfate modification, and demonstrate that these interactions occur at the apical surface of polarized airway tissues. These findings provide insights into the initial binding step of HMPV infection that has potential for antiviral development.
Phylogenetic position of Mixia osmundae inferred from 28S rDNA comparison.

Mixia osmundae has been uncertain based on morphological characters and 18S rDNA sequence comparison. Here we determined the D1/D2 region sequence of 28S rDNA of M. osmundae and compared it with those of other Urediniomycetes. The phylogenetic tree based on 28S rDNA comparison showed that M. osmundae was clustered with a monophyletic group consisting of three lineages: the Rhodosporidium/ Sporidiobolus, the Erythrobasidium/Sakaguchia, and Helicobasidium. The family Mixiaceae consists of only M. osmundae (Hawksworth et al., 1995). M. osmundae is parasitic on Osmunda japonica. This fungus grows as yeast on artificial media. M. osmundae was believed to be a member of the ascomycetes (Kramer, 1958; Mix, 1947) before evidence from both morphological characteristics and 18S rDNA sequence comparisons showed that it was a basidiomycete (Nishida et al., 1995). The 18S rDNA sequence comparison indicated that this fungus belonged to the Urediniomycetes group. The Urediniomycetes group is divided into four major clusters: the Erythrobasidium/Sakaguchia lineage, the Agaricostibum/Bensingtonia lineage, the Rhodosporidium/Sporidiobolus lineage, and the rusts/ Helicobasidium lineage (Sjamsuridzal et al., 1999; Swann and Taylor, 1995). However, the phylogenetic placement of M. osmundae within the Urediniomycetes group has been uncertain (Hamamoto and Nakase, 2000; Sjamsuridzal et al., 1999; Swann et al., 2001). Fell et al. (2000) sequenced the D1/D2 region of the 28S rDNA from most basidiomycetous yeasts and compared them. However, nobody has sequenced the D1/D2 region from M. osmundae. The strain that we sequenced in this study is M. osmundae IFO 32408 ( IAM 14511). The primers LROR, LR7 (Vilgalys and Hester, 1990), 5 -AGATGAAAAGAACTTTGAAAAGAGAG-3 , and 5 -GGTCCGTGTTTCAAGACGG-3 were used for the polymerase chain reaction and sequencing. The sequence was obtained directly from the amplified DNAs. We compared the 28S rDNA from M. osmundae with those from 51 other basidiomycetes. The sequences were aligned using CLUSTAL W (Thompson et al., 1994). The phylogenetic tree from Kimura 2-parameter distance estimation by the neighbor-joining method with 1,000 bootstrap analyses was constructed based on the multiple alignment using MEGA version 2.1 (Kumar et al., 2001). The maximum parsimony analysis was performed using the Close-Neighbor-Interchange heuristic search program of MEGA version 2.1 (Kumar et al., 2001). We used the given optional numbers. We determined the DNA sequence of a 600-nt region of the 28S rDNA from M. osmundae. The nucleotide sequence has been deposited in the interPhylogenetic position of Mixia osmundae inferred from 28S rDNA comparison
The Influence of Gene Expression Time Delays on Gierer – Meinhardt Pattern Formation Systems

There are numerous examples of morphogen gradients controlling long range signalling in developmental and cellular systems. The prospect of two such interacting morphogens instigating long range self-organisation in biological systems via a Turing bifurcation has been explored, postulated, or implicated in the context of numerous developmental processes. However, modelling investigations of cellular systems typically neglect the influence of gene expression on such dynamics, even though transcription and translation are observed to be important in morphogenetic systems. In particular, the influence of gene expression on a large class of Turing bifurcation models, namely those with pure kinetics such as the Gierer–Meinhardt system, is unexplored. Our investigations demonstrate that the behaviour of the Gierer–Meinhardt model profoundly changes on the inclusion of gene expression dynamics and is sensitive to the sub-cellular details of gene expression. Features such as concentration blow up, morphogen oscillations and radical sensitivities to the duration of gene expression are observed and, at best, severely restrict the possible parameter spaces for feasible biological behaviour. These results also indicate that the behaviour of Turing pattern formation systems on the inclusion of gene expression time delays may provide a means of distinguishing between possible forms of interaction kinetics. Finally, this study also emphasises that sub-cellular and gene expression dynamics should not be simply neglected in models of long range biological pattern formation via morphogens.
An integrated mobile agent framework for distributed network management†

Conventional network management based on simple network management protocol (SNMP) is often run in a centralized manner. The centralized management approach is limited to small-scale networks because it incurs excessive processing load and heavy network traffic in the management station. For scalability, this paper presents a new management framework that integrates mobile agents with the SNMP protocol. The mobile agent technology provides support for distributed network management. The integrated framework allows the network operators to deploy an appropriate management approach according to the characteristics of target networks and the nature of management activities. A quantitative latency model is developed for the mobile agent based approach. We have implemented a prototype of the framework based on an in-house developed Naplet mobile agent docking environment and the AdventNet SNMP package. We have experimented with the system in network interface performance monitoring and fault diagnosis applications. Experimental results demonstrate the advantages and disadvantages of centralized and distributed management approaches and the flexibility of the integrated framework and verify the accuracy of the latency model.
Haemodynamic effects of etomidate, propofol and electrical shock in patients undergoing implantable cardioverter-defibrillator testing.

BACKGROUND Anaesthetic drugs and internal electrical shock may alter the haemodynamic status of patients undergoing implantable cardioverter-defibrillator (ICD) testing. Comparative data on the mechanisms of etomidate and propofol-induced changes in haemodynamic parameters are inconsistent. Also the effects of ICD shock on haemodynamics have not been extensively studied. AIM To compare the haemodynamic effects of etomidate and propofol as well as electrical shock during ICD testing in a prospective, randomised trial. METHODS The study group consisted of 63 consecutive patients (mean age 66 ± 10 years, 51 males) who underwent ICD testing. Haemodynamic parameters were measured using impedance cardiography (Task Force Monitor Systems, CNSystems, Austria) before and after injection of etomidate (n = 30) or propofol (n = 33) as well as immediately after internal defibrillation of ventricular fibrillation (VF). Parameters measured included heart rate, systolic (sBP), diastolic (dBP) and mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR). RESULTS Propofol significantly decreased the values of all measured parameters (sBP: 123.4 ± 17.1 vs. 106.3 ± 18 mm Hg, p < 0.0001; dBP: 83.7 ± 12.2 vs. 74.1 ± 13.8 mm Hg, p < 0.0001; mBP: 93.9 ± 13.1 vs. 81.1 ± 16.1 mm Hg, p < 0.0001; SV: 61.1 ± 19.3 vs. 56.4 ± 15.7 mL, p < 0.003; CO: 4.51 ± 1.07 vs. 4.17 ± 0.73 L/min, p < 0.003; and TPR: 1,735.8 ± 532.6 vs. 1,573.9 ± 390.5 dyn×s/cm⁵), whereas the only significant change following etomidate infusion was a decrease in SV (60.6 ± 11 vs. 56.8 ± 10 mL, p < 0.022). The propofol-induced changes were similar in patients with reduced (< 40%) vs. preserved (≥ 40%) left ventricular ejection fraction (LVEF) and in patients in heart failure NYHA class 0-II vs. class III-IV. Induction of VF and internal electrical shock did not cause major haemodynamic changes apart from significant, albeit very modest, drops in dBP and mBP (77 ± 2 vs. 72.9 ± 18 mm Hg, p < 0.002, and 85.2 ± 17 vs. 81.8 ± 20 mm Hg, p < 0.017, respectively). There were no complications during ICD testing. CONCLUSIONS Propofol significantly decreased BP probably by both reducing CO and causing vasodilatation, whereas etomidate only slightly decreased dBP and mBP without affecting other parameters. Propofol-induced changes were independent of LVEF or NYHA class. Induction of VF and internal defibrillation did not cause clinically significant changes apart from very modest drops in dBP and mBP values.
Depression in Children and Adolescents with Cystic Fibrosis: Case Studies

Objective: Cystic fibrosis is an autosomal recessively inherited multi-system disorder of children and adults characterized by the obstruction and infection of airways presenting as a wide variety of symptoms. It has varying degrees of psychological impact on patients and their families, requiring numerous adjustments in their life styles. Newer sophisticated medical treatments of cystic fibrosis has led to an increase in life expectancy; however, the same kind of progress has not been made in the psychological interventions available to treat emotional disturbances. Method: We report three cases of children and adolescents with cystic fibrosis who were diagnosed with depression and treated with a combination of antidepressant medications and other psychosocial interventions. Results and Conclusions: Two of the three cases suggest that treatment with antidepressant medications has a positive influence on psychological outcomes. We further propose clinical studies to test efficacy, safety, and long-term effects of these medications in patients with cystic fibrosis.
Eustachian Tube Function and Retraction of the Tympanic Membrane

The medial displacement of the tympanic membrane or the retracted tympanic membrane is a common clinical finding. Also, retractions are looked upon as the precursor of middle ear cholesteatoma. In current otologic literature there seems to be some dispute whether the retractions of the tympanic membrane are caused by negative intratympanic air pressure or by shrinkage of middle ear adhesions pulling the tympanic membrane or part of it medially. In this study only ears with posterior/superior retractions of the tympanic membrane were investigated. Tympanometry revealed that only 33% of the ears did have middle ear pressure within ± 100 mm H2O. After insertion of a polyethylene tube through the tympanic membrane, the eustachian tube function was tested using the air pressure equalization technique. None of the ears could change the negative air pressure upon swallowing. Planometric measurements on the x-ray of the mastoid air cell system of the present material deviate from those of a normal material, indicating a significantly smaller air volume in the present material. It may be concluded that dysfunction of the eustachian tube and a small air volume of the mastoid are characteristic features of an ear with posterior/superior retraction of the tympanic membrane.
CSS performance analysis and optimisation based on soft decision fusion

A cooperative spectrum sensing CSS based on soft combine with decision fusion SC-DF-CSS is proposed and the detection performance is analysed further under the actual channel fading environment. The optimal algorithm to obtain the weighting vector for maximising the detection probability is given based on NP criterion. In order to reduce the complexity, the optimal algorithm for obtaining weighting vector based on modified deflection coefficient MDC is further given. The results show that only a little detection performance loss exists in SC-DF-CSS compared with CSS based on soft combine with data fusion, while the system bandwidth can be effectively saved by the former. In addition, it is also shown that the detection performance can be effectively improved by the optimal algorithm and the optimal algorithm based on MDC can achieve the same performance with the optimal algorithm based on NP criterion, which, however, reduces the computational complexity greatly.
Confirmatory population pharmacokinetic analysis for bapineuzumab phase 3 studies in patients with mild to moderate Alzheimer's disease

The population pharmacokinetics of bapineuzumab, a humanized monoclonal IgG1 antibody that was generated from a murine monoclonal antibody and binds specifically to amino acids 1 to 5 of the free N‐terminus of human amyloid‐beta peptide, were characterized in patients with mild‐to‐moderate alzheimer's disease in two Phase 3 studies (ELN115727‐301 and ELN115727‐302). A total of 8,040 serum concentration measurements were analyzed from 1,458 patients who received 6 doses of bapineuzumab intravenously once every 13 weeks. A confirmatory analysis was conducted using a prespecified two‐compartment model with first‐order elimination. After the primary covariate effect assessment, a reduced model was obtained. Based on the reduced model, the typical population values for clearance (CL) and volume (Vc) from the central compartment in a Caucasian subject with a standardized body weight of 70 kg were 0.17 L/day and 3.13 L, respectively. Bapineuzumab CL and Vc increased with body weight. Furthermore, CL was 15% higher in non‐Caucasian subjects; however, this was not considered clinically relevant. None of the other evaluated covariates had a meaningful impact on CL. The median terminal elimination half‐life was estimated to be approximately 29 days. Sensitivity analyses and bootstrapping results supported model stability.
Symptoms of Depression in Hearing Impaired Adults and Elderly : Importance of Hearing Aid Use

* PhD in Biomedical Gerontology by PUCRS – Speech Doctor and Gerontologist – Professor in the Phonoaudiology Course at ULBRA. ** Phonoaudiology Doctor. *** Post Doctorate Degree in ENT by Pittsburg University/USA – Adjunt Professor of ENT Discipline at ULBRA and of the Morphological Science Department at UFRGS. Head of Service of ENT and Head and Neck Surgery at Hospital Universitário ULBRA). **** Master Degree in Communication Disorder – UTP – Speech Doctor at Serviço de Alta Complexidade em Saúde Auditiva Hospital Universitário – ULBRA (University Hospital – Auditory Health).
Exercise for Breast Cancer Survivors

IN BRIEF: Exercise can have significant benefits for breast cancer survivors during and after treatment The general aerobic prescription is for moderate-intensity activity (50% to 75% heart rate reserve), 3 to 5 days per week, 20 to 60 minutes per session. Resistance training should also be incorporated into the programs. Psychological health is optimized by exercise that is enjoyable, develops new skills, incorporates social interaction, and takes place in a mind- and spirit-stimulating environment Conditions that warrant prescription modification include fatigue and nausea, cytopenias, lymphedema, and bone metastasis. Postcancer exercise is facilitated by instilling a positive attitude toward exercise, confidence in overcoming barriers, and a supportive social environment.
Three intervening galaxy absorbers towards GRB 060418: faint and dusty?

We present an analysis of three strong, intervening Mg II absorption systems (zabs= 0.603, 0.656, 1.107) towards the optical afterglow of gamma-ray burst (GRB) 060418. From high-resolution Ultraviolet and Visual Echelle Spectrograph (UVES) spectra we measure metal column densities and find that the highest redshift absorber exhibits a large amount of dust depletion compared with damped Lyman absorbers (DLAs) seen in quasi-stellar object (QSO) spectra. The intervening zabs= 1.107 absorber is also unusual in exhibiting a clear 2175-A bump, the first time this feature has been definitively detected in a GRB spectrum. The GRB afterglow spectrum is best fitted with a two-component extinction curve: a Small Magellanic Cloud (SMC) extinction law at z= 1.49 (the redshift of the host) with E(B−V) = 0.07 ± 0.01 and a Galactic extinction curve at z∼ 1.1 with E(B−V) = 0.08 ± 0.01. We also present a moderately deep New Technology Telescope (NTT) R-band image of the GRB 060418 field and spectroscopy of four galaxies within 1 arcmin. None of these objects has a redshift that matches any of the intervening absorbers, and we conclude that the galaxies responsible for the two intervening Mg ii absorbers at z∼ 0.6 have luminosities .
CORPORATE OWNERSHIP IN SPAIN

In this paper we analyse the structure of ownership in non-financial Spanish listed companies in the period 1996-2002, focussing on the control chain methodology. The results obtained show that the main shareholder’s control threshold stands at about 29% of the voting rights and that in 2002 families were the ultimate owners in 52.7% of the firms. On the other hand, the use of pyramid structures continues to increase. In 2002, 29.1% of the companies were controlled in this way, which means that the ratio of voting rights to cash flow rights for this year was 0.89.
Effects of the melatonin on the kidney of high fat diet fed obese rats: A stereological and histological approach

Obesity has become a major global health concern, and its incidence has increased sharply in recent years. It has been shown that obesity or metabolic syndrome is a strong and independent risk factor for cardiovascular disease that causes mortality and for the development of micro albuminuria and end-stage renal disease. Also, obesity should be considered the most important risk factor for chronic kidney disease because of its strong association with diabetes and hypertension, the two most common etiologies of end stage kidney disease. Melatonin has very close direct and indirect correlation with kidney functions. The aim of this study; was to examine effects of fatty diet induced obesity and melatonin on kidney in female rats by histological and stereological methods. This study was including 4 groups: Non-obese control, obese control, non-obese melatonin and obese-melatonin groups. Kidneys of all animals of groups were prepared and staining with Hematoxylin-eosin for stereological and light microscopic analysis. The volume of kidney was calculated Cavalieri methods and the number of glomeruli was analyzed by physical dissector. The volumes of the kidney cortex and medulla of control and obese groups were not seen significant difference among the groups. The mean numerical density of glomeruli for the obese group was significantly decreased in comparison to the control group. But melatonin treatment leads to a significant increase of glomeruli number in obese-melatonin group after fatty diet induced obesity. Glomeruli, vessels, tubules and interstitial structures were normal in the nonobese-control and nonobese-melatonin group. However, in the obese-control group, there was eosinophilic cytoplasm in distal and proximal tubules in the cortex. The hydropic degeneration in distal and proximal tubules was widely observed. Also the lumens of the tubules and Bowman’s space were enlarged and mononuclear cell infiltration was seen in the renal cortices of the obese rats. Degeneration in nephrons, including glomerulosclerosis and segmental necrosis was found. There was cellular debris in the cortex of the kidneys removed from the obese control group. After melatonin application no pathological finding was detected in light microscopical section of obese-melatonin group. Histological structure of kidneys of the rats in the obese-melatonin group was smilar to those of the healthy control ones in the nonobese-control group. These study provided that melatonin has a protective effect on the kidney structure in terms of morphometrical parameters which are number of glomeruli and glomerular morphology in fatty diet induced obese rat model.
A DNA Polymerase-α·Primase Cofactor with Homology to Replication Protein A-32 Regulates DNA Replication in Mammalian Cells*

α-Accessory factor (AAF) stimulates the activity of DNA polymerase-α·primase, the only enzyme known to initiate DNA replication in eukaryotic cells ( Goulian, M., Heard, C. J., and Grimm, S. L. (1990) J. Biol. Chem. 265, 13221-13230 ). We purified the AAF heterodimer composed of 44- and 132-kDa subunits from cultured cells and identified full-length cDNA clones using amino acid sequences from internal peptides. AAF-132 demonstrated no homologies to known proteins; AAF-44, however, is evolutionarily related to the 32-kDa subunit of replication protein A (RPA-32) and contains an oligonucleotide/oligosaccharide-binding (OB) fold domain similar to the OB fold domains of RPA involved in single-stranded DNA binding. Epitope-tagged versions of AAF-44 and -132 formed a complex in intact cells, and purified recombinant AAF-44 bound to single-stranded DNA and stimulated DNA primase activity only in the presence of AAF-132. Mutations in conserved residues within the OB fold of AAF-44 reduced DNA binding activity of the AAF-44·AAF-132 complex. Immunofluorescence staining of AAF-44 and AAF-132 in S phase-enriched HeLa cells demonstrated punctate nuclear staining, and AAF co-localized with proliferating cell nuclear antigen, a marker for replication foci containing DNA polymerase-α·primase and RPA. Small interfering RNA-mediated depletion of AAF-44 in tumor cell lines inhibited [methyl-3H]thymidine uptake into DNA but did not affect cell viability. We conclude that AAF shares structural and functional similarities with RPA-32 and regulates DNA replication, consistent with its ability to increase polymerase-α·primase template affinity and stimulate both DNA primase and polymerase-α activities in vitro.