Miracle-dz/UniFAR-FTUs huggingface dataset:
The microRNA spectrum in 12 body fluids.

BACKGROUND MicroRNAs (miRNAs) are small, noncoding RNAs that play an important role in regulating various biological processes through their interaction with cellular messenger RNAs. Extracellular miRNAs in serum, plasma, saliva, and urine have recently been shown to be associated with various pathological conditions including cancer. METHODS With the goal of assessing the distribution of miRNAs and demonstrating the potential use of miRNAs as biomarkers, we examined the presence of miRNAs in 12 human body fluids and urine samples from women in different stages of pregnancy or patients with different urothelial cancers. Using quantitative PCR, we conducted a global survey of the miRNA distribution in these fluids. RESULTS miRNAs were present in all fluids tested and showed distinct compositions in different fluid types. Several of the highly abundant miRNAs in these fluids were common among multiple fluid types, and some of the miRNAs were enriched in specific fluids. We also observed distinct miRNA patterns in the urine samples obtained from individuals with different physiopathological conditions. CONCLUSIONS MicroRNAs are ubiquitous in all the body fluid types tested. Fluid type-specific miRNAs may have functional roles associated with the surrounding tissues. In addition, the changes in miRNA spectra observed in the urine samples from patients with different urothelial conditions demonstrates the potential for using concentrations of specific miRNAs in body fluids as biomarkers for detecting and monitoring various physiopathological conditions.
Knowledge mobilisation in the Polish education system

Poland has made substantial progress in improving the quality of its education system in recent years. This paper aims to describe the situation of the Polish education system from a knowledge management perspective and, to some extent, through innovation policies in education. The many challenges, this paper argues, can be tackled only through more knowledge-intensive and evidence-based educational policies. This paper also develops the concept of ‘knowledge mobilisation’ as a more applicable tool, given the current situation in Poland, than ‘knowledge management’, and describes crucial parameters characterising it. Despite recent achievements of the Polish system of education in PISA tests, there remain substantial weaknesses such as, quality of teacher training, focus on past achievements and a reactive approach. Knowledge resources are not evenly distributed which means that too often appropriate knowledge is not available where needed. Based on analysis of current data and previous studies, this paper provides evidence in support of utilisation of ‘knowledge management’ and ‘knowledge mobilisation’ as effective remedies for the ailments of the Polish education system.
Calpain-1 Regulates Bax and Subsequent Smac-dependent Caspase-3 Activation in Neutrophil Apoptosis*

In the absence and in the resolution of inflammatory responses, neutrophils rapidly undergo spontaneous apoptosis. Here we report about a new apoptosis pathway in these cells that requires calpain-1 activation and is essential for the enzymatic activation of the critical effector caspase-3. Decreased levels of calpastatin, a highly specific intrinsic inhibitor of calpain, resulted in activation of calpain-1, but not calpain-2, in neutrophils undergoing apoptosis, a process that was blocked by a specific calpain-1 inhibitor or by intracellular delivery of a calpastatin peptide. Further support for the importance of the calpastatin-calpain system was obtained by analyzing neutrophils from patients with cystic fibrosis that exhibited delayed apoptosis, associated with markedly increased calpastatin and decreased calpain-1 protein levels compared with neutrophils from control individuals. Additional studies were designed to place calpain-1 into the hierarchy of biochemical events leading to neutrophil apoptosis. Pharmacological calpain inhibition during spontaneous and Fas receptor-induced neutrophil apoptosis prevented cleavage of Bax into an 18-kDa fragment unable to interact with Bcl-xL. Moreover, calpain blocking prevented the mitochondrial release of cytochrome c and Smac, which was indispensable for caspase-3 processing and enzymatic activation, both in the presence and absence of agonistic anti-Fas receptor antibodies. Taken together, calpastatin and calpain-1 represent critical proximal elements in a cascade of pro-apoptotic events leading to Bax, mitochondria, and caspase-3 activation, and their altered expression appears to influence the life span of neutrophils under pathologic conditions.
The morphological and biological effects of various antisera on avian infectious bronchitis virus.

Summary Biologically, homotypic and heterotypic antisera neutralized avian infectious bronchitis virus significantly more when unheated. Morphologically, using the electron microscope technique of negative staining, there was a clear distinction between the effects of homotypic and heterotypic antisera. Heated homotypic antiserum revealed antibody attached only to the projections of the virus, while with unheated homotypic serum heat labile components could be visualized but no basic change could be seen in particle morphology. Heterotypic serum contained antibodies directed both against the projections and the envelope of the virus. In addition, unheated heterotypic antiserum produced holes approximately 100 A in diameter in the virus membrane, suggesting that a form of virus lysis takes place. Rabbit antiserum prepared against uninfected chick-embryo fibroblasts was able to produce similar holes in the virus envelope and this led us to postulate that the envelope component of avian infectious bronchitis virus is closely related to normal chick host material.
Triadin Overexpression Stimulates Excitation-Contraction Coupling and Increases Predisposition to Cellular Arrhythmia in Cardiac Myocytes

Triadin 1 (TRD) is an integral membrane protein that associates with the ryanodine receptor (RyR2), calsequestrin (CASQ2) and junctin to form a macromolecular Ca signaling complex in the cardiac junctional sarcoplasmic reticulum (SR). To define the functional role of TRD, we examined the effects of adenoviral-mediated overexpression of the wild-type protein (TRDWT) or a TRD mutant lacking the putative CASQ2 interaction domain residues 200 to 224 (TRDDel.200–224) on intracellular Ca signaling in adult rat ventricular myocytes. Overexpression of TRDWT reduced the amplitude of ICa- induced Ca transients (at 0 mV) but voltage dependency of the Ca transients was markedly widened and flattened, such that even small ICa at low and high depolarizations triggered maximal Ca transients. The frequency of spontaneous Ca sparks was significantly increased in TRDWT myocytes, whereas the amplitude of individual sparks was reduced. Consistent with these changes in Ca release signals, SR Ca content was decreased in TRDWT myocytes. Periodic electrical stimulation of TRDWT myocytes resulted in irregular, spontaneous Ca transients and arrhythmic oscillations of the membrane potential. Expression of TRDDel.200–224 failed to produce any of the effects of the wild-type protein. The lipid bilayer technique was used to record the activity of single RyR2 channels using microsome samples obtained from control, TRDWT and TRDDel.200–224 myocytes. Elevation of TRDWT levels increased the open probability of RyR2 channels, whereas expression of the mutant protein did not affect RyR2 activity. We conclude that TRD enhances cardiac excitation-contraction coupling by directly stimulating the RyR2. Interaction of TRD with RyR2 may involve amino acids 200 to 224 in C-terminal domain of TRD.
Measurements of photo-oxidation products from the reaction of a series of alkyl-benzenes with hydroxyl radicals during EXACT using comprehensive gas chromatography

Abstract. Photo-oxidation products from the reaction of a series of alkyl-benzenes, (benzene, toluene, p -xylene and 1,3,5-trimethyl-benzene) with hydroxyl radicals in the presence of NO x have been investigated using comprehensive gas chromatography (GCxGC). A GCxGC system has been developed which utilises valve modulation and independent separations as a function of both volatility and polarity. A number of carbonyl-type compounds were identified during a series of reactions carried out at the European Photoreactor (EUPHORE), a large volume outdoor reaction chamber in Valencia, Spain. Experiments were carried as part of the EXACT project ( E ffects of the o X idation of A romatic C ompounds in the T roposphere). Two litre chamber air samples were cryo-focused, with a sampling frequency of 30 minutes, allowing the evolution of species to be followed over oxidation periods of 3-6 hours. To facilitate product identification, several carbonyl compounds, which were possible products of the photo-oxidation, were synthesised and used as reference standards. For toluene reactions, observed oxygenated intermediates found included the co-eluting pair a -angelicalactone/4-oxo-2-pentenal, maleic anhydride, citraconic anhydride, benzaldehyde and p -methyl benzoquinone. In the p -xylene experiment, the products identified were E/Z-hex-3-en-2,5-dione and citraconic anhydride. For 1,3,5-TMB reactions, the products identified were 3,5-dimethylbenzaldehyde, 3,5-dimethyl-3H-furan-2-one and 3-methyl-5-methylene-5H-furan-2-one. Preliminary quantification was carried out on identified compounds using liquid standards. Comparison of FTIR and GCxGC for the measurement of the parent aromatics generally showed good agreement. Comparison of the concentrations observed by GCxGC to concentration-time profiles simulated using the Master Chemical Mechanism, MCMv3, demonstrates that this mechanism significantly over-predicts the concentrations of many product compounds and highlights the uncertainties which exist in our understanding of the atmospheric oxidation of aromatics.
Response to letter from Bernardi

Sir, we would like to thank the authors of the correspondence on our recent article published in Brain (Hicks et al. , 2009) for their interest and the points they raise for discussion. We appreciate that our article might prompt debate, especially in reference to different interpretations of mitochondrial dysfunction (Angelin et al. , 2007). This is in the context of the more general controversy regarding the role of apoptosis within the field of muscular dystrophy as a whole and the difficulties in its identification and quantification. It was precisely our intention to focus this article on the specificity of the TMRM (tetramethyl rhodamine methyl ester) assay as a measure of permeability transition …
The genetics of moyamoya disease: recent insights into the pathogenesis of the disease.

tion. In fact Liu et al in a recent study have reported an odds ratio of 339 in Japanese populations with the p.R4810K polymorphism. An odds ratio of 190.8 has been reported for the p.R4859K polymorphism of the RNF213 gene. Other variant polymorphisms of the RNF213 gene seen in Caucasian populations with Moyamoya disease include p.P4608S and p.D4013N. Nearly 95% of families with Moyamoya disease demonstrate the p.R4859K polymorphism. Not surprisingly, animal studies have shown that RNF213 knockdown results in the formation of abnormal blood vessels with irregular walls. Similarly, recent data suggests that the p.R4810K polymorphism of the RNF213 gene has a strong influence on blood pressure especially systolic blood pressure. The above examples clearly illustrate the strong genetic basis of Moyamoya disease. Identification of these polymorphisms may help identify individuals at high risk of developing the disease.
Retroviral Gene Transfer Is Inhibited by Chondroitin Sulfate Proteoglycans/Glycosaminoglycans in Malignant Pleural Effusions*

Gene therapy may be an important adjuvant for treating cancer in the pleural space. The initial results of retroviral gene transfer to cancer cells in malignant pleural effusions revealed that transduction was markedly inhibited, and studies to characterize the inhibitory factor(s) were performed. The inhibition was contained within the soluble, rather than cellular, components of the effusions and was demonstrated with amphotropic, gibbon ape leukemia virus, and vesicular stomatitis virus-glycoprotein pseudotyped retroviral vectors. After excluding complement proteins, a series of studies identified chondroitin sulfates (CSs) as the inhibitory substances. First, treatment of the effusions with mammmalian hyaluronidase or chondroitinases, but not Streptomyces hyaluronidase, abolished the inhibitory activity. Second, addition of exogenous CS glycosaminoglycans mimicked the inhibition observed with pleural effusions. Third, immunoassays and biochemical analyses of malignant pleural effusion specimens revealed CS in relevant concentrations within pleural fluid. Fourth, proteoglycans/glycosaminoglycans isolated from the effusions inhibited retroviral gene transfer. Analyses of the mechanism of inhibition indicate that the chondroitin sulfates interact with vector in solution rather than at the target cell surface. These results suggest that drainage of the malignant pleural effusion, and perhaps enzymatic pretreatment of the pleural cavity, will be necessary for efficient retroviral vector mediated gene delivery to pleural metastases.
A novel asymmetrical FLC-based MPPT technique for photovoltaic generation system

In this paper, a novel asymmetrical fuzzy-logic-control (FLC) based maximum power point tracking (MPPT) algorithm for photovoltaic (PV) generation system (PGS) is proposed. The proposed method uses the power variation and voltage variation as the inputs, which significantly simplified the computation. Comparing with the conventional perturb and observe (P&O) method, the proposed asymmetrical FLC-based MPPT algorithm can improve the dynamic and steady state performance of the PGS simultaneously. Comparing with the proposed symmetrical FLC-based MPPT method, the transient time and the MPPT tracking accuracy are further improved by 38.1 % and 0.03 %, respectively.
Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions

Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelo-dysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu® for the reduction of transfusional iron overload in hematological disorders.
Choosing the safest acute therapy during chronic migraine prophylactic treatment: pharmacokinetic and pharmacodynamic considerations

ABSTRACT Introduction: Drugs used in the treatment of migraine have been reported to be highly associated with the occurrence of clinically significant drug-drug interactions (DDIs). Multiple drug therapy regimens are used for migraine treatment, particularly for chronic migraine. In fact, additional pharmacological agents are usually administered during an acute migraine attack in patients chronically treated with the prophylactic therapy. The variety of drugs available for migraine prophylactic and acute treatment, and consequently their pharmacological interactions, might complicate the choice of a safe combination therapy. Areas covered: This study discusses the prophylactic-acute DDIs from a pharmacokinetic and pharmacodynamic perspective, particularly interactions between antiepileptic drugs, tricyclic antidepressants, β-blockers, calcium channel blockers, triptans, nonsteroidal anti-inflammatory drugs and ergot derivatives. The available online tools have been used to evaluate the clinically significant DDIs. Expert opinion: The interactions between different drugs might be accurately predicted by the huge and detailed knowledge about the molecular pathways involved in pharmacodynamics and pharmacokinetics. Pharmacogenomic research has shed further light onto the mechanisms involved in the inter-individual variation in drug response and DDIs. Based on this knowledge, this paper will provide suggestions to improve the appropriateness of the drug choice in the prescription of preventative and acute migraine medications.
Anesthesia for Cesarean Delivery and Learning Disabilities in a Population-based Birth Cohort

Background:Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort. Methods:The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976–1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia). Results:Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia n = 193, and regional anesthesia n = 304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia before age 4 yr, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P = 0.017 for comparison of CD under regional anesthesia compared to vaginal delivery). Conclusion:Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.
A systematic discussion of fusion techniques for multi-modal affect recognition tasks

Recently, automatic emotion recognition has been established as a major research topic in the area of human computer interaction (HCI). Since humans express emotions through various channels, a user's emotional state can naturally be perceived by combining emotional cues derived from all available modalities. Yet most effort has been put into single-channel emotion recognition, while only a few studies with focus on the fusion of multiple channels have been published. Even though most of these studies apply rather simple fusion strategies -- such as the sum or product rule -- some of the reported results show promising improvements compared to the single channels. Such results encourage investigations if there is further potential for enhancement if more sophisticated methods are incorporated. Therefore we apply a wide variety of possible fusion techniques such as feature fusion, decision level combination rules, meta-classification or hybrid-fusion. We carry out a systematic comparison of a total of 16 fusion methods on different corpora and compare results using a novel visualization technique. We find that multi-modal fusion is in almost any case at least on par with single channel classification, though homogeneous results within corpora point to interchangeability between concrete fusion schemes.
CREB and CREB-binding proteins play an important role in the IE2 86-kilodalton protein-mediated transactivation of the human cytomegalovirus 2.2-kilobase RNA promoter

The human cytomegalovirus (HCMV) immediate-early region 2 86-kDa protein (IE2 86) is the major transactivator of the promoter for the 2.2-kb class of early RNAs (open reading frame UL 112-113). Previously, we reported that a DNA segment on this promoter between nucleotides (nt) -113 and -59 was critical for activation by IE2 86 in vivo and could be bound by IE2 86 in vitro (R. Schwartz, M. H. Sommer, A. Scully, and D. H. Spector, J. Virol. 68:5613-5622, 1994). With a set of site-specific mutations within nt -84 to -61, we have localized the essential cis-acting sequences to nt -72 to -61, which contain an ATF/CREB-binding site. The IE2 86-binding site between nt -113 and -85 is not essential for activation of the promoter by IE2 86 in transient-expression assays, but its presence can enhance the level of activation mediated through the sequences located between nt -84 and -59. Electrophoretic mobility shift assays with a segment containing nt -84 to -59 and nuclear extracts from human cells permissive for the HCMV infection revealed a complex band pattern. However, by supershift analysis with specific antibodies, we were able to identify CREB as the major ATF/CREB family member in the protein-DNA complexes. Further evidence that CREB is a target for IE2 86-mediated induction, is provided by the finding that IE2 86 activates the somatostatin promoter to high levels. Although the binding of IE2 86 to nonphosphorylated full-length CREB or deltaCREB is minimal, IE2 86 does form complexes with p300 and the CREB-binding protein (CBP), which in turn bind to CREB and can serve as adaptor proteins for CREB function. In addition, the in vivo functional relevance of the interaction between IE2 86 and CBP is indicated by the ability of IE2 86 to enhance transcriptional activation mediated by a GAL4-CBP fusion protein brought to a promoter by GAL4-binding sites.