Miracle-dz/UniFAR-FTUs huggingface dataset:
Alterations of Voltage-Dependent Calcium Channel Currents in Basilar Artery Smooth Muscle Cells at Early Stage of Subarachnoid Hemorrhage in a Rabbit Model

Objective To investigate the changes in the currents of voltage-dependent calcium channels (VDCCs) in smooth muscle cells of basilar artery in a rabbit model of subarachnoid hemorrhage (SAH). Methods New Zealand white rabbits were randomly divided into five groups: sham (C), normal (N), 24 hours (S1), 48 hours (S2) and 72 hours (S3) after SAH. Non-heparinized autologous arterial blood (1ml/kg) was injected into the cisterna magna to create SAH after intravenous anesthesia, and 1 ml/kg of saline was injected into cisterna magna in the sham group. Rabbits in group N received no injections. Basilar artery in S1, S2, S3 group were isolated at 24, 48, 72 hours after SAH. Basilar artery in group C was isolated at 72 hours after physiological saline injection. Basilar artery smooth muscle cells were isolated for all groups. Whole-cell patch-clamp technique was utilized to record cell membrane capacitance and VDCCs currents. The VDCCs antagonist nifedipine was added to the bath solution to block the Ca++ channels currents. Results There were no significant differences in the number of cells isolated, the cell size and membrane capacitance among all the five groups. VDCC currents in the S1–S3 groups had higher amplitudes than those in control and sham groups. The significant change of current amplitude was observed at 72 hours after SAH, which was higher than those of 24 and 48 hours. The VDCCs were shown to expression in human artery smooth muscle cells. Conclusions The changes of activation characteristics and voltage-current relationship at 72 hours after SAH might be an important event which leads to a series of molecular events in the microenvironment of the basilar artery smooth muscle cells. This may be the key time point for potential therapeutic intervention against subarachnoid hemorrhage.
Electropathological Substrate of Longstanding Persistent Atrial Fibrillation in Patients With Structural Heart Disease: Epicardial Breakthrough

Background— During persistent atrial fibrillation (AF), waves with a focal spread of activation are frequently observed. The origin of these waves and their relevance for the persistence of AF are unknown. Methods and Results— In 24 patients with longstanding persistent AF and structural heart disease, high-density mapping of the right and left atria was performed during cardiac surgery. In a reference group of 25 patients, AF was induced by rapid pacing. For data analysis, a mapping algorithm was developed that separated the fibrillatory process into its individual wavelets and identified waves with a focal origin. During persistent AF, the incidence of focal fibrillation waves in the right atrium was almost 4-fold higher than during acute AF (median, 0.46 versus 0.12 per cycle per 1 cm2 (25th to 75th percentile, 0.40 to 0.77 and 0.01 to 0.27; P<0.0001). They were widely distributed over both atria and were recorded at 46±18% of all electrodes. A large majority (90.5%) occurred as single events. Repetitive focal activity (>3) happened in only 0.8%. The coupling interval was not more than 11 ms shorter than the average AF cycle length (P=0.04), and they were not preceded by a long interval. Unipolar electrograms at the site of origin showed small but clear R waves. These data favor epicardial breakthrough rather than a cellular focal mechanism as the underlying mechanism. Often, conduction from a site of epicardial breakthrough was blocked in 1 or more directions. This generated separate multiple wave fronts propagating in different directions over the epicardium. Conclusions— Focal fibrillation waves are due to epicardial breakthrough of waves propagating in deeper layers of the atrial wall. In patients with longstanding AF, the frequency of epicardial breakthroughs was 4 times higher than during acute AF. Because they provide a constant source of independent fibrillation waves originating over the entire epicardial surface, they offer an adequate explanation for the high persistence of AF in patients with structural heart disease.
Chromosomal instability and human cancer

Genetic instability is a defining feature of human cancer. The main type of genetic instability, chromosomal instability (CIN), enhances the rate of gross chromosomal changes during cell division. CIN is brought about by mutations of CIN genes, i.e. genes that are involved in maintaining the genomic integrity of the cell. A major question in cancer genetics is whether genetic instability is a cause and hence a driving force of tumorigenesis. A mathematical framework for studying the somatic evolution of cancer sheds light onto the causal relations between CIN and human cancer.
Kinematics of elliptical galaxies with a diffuse dust component – II. Dust effects on kinematic modelling

Observations have demonstrated the presence of substantial amounts of interstellar dust in elliptical galaxies, most of which is believed to be distributed diffusely over the galaxy. Absorption by dust grains has a major impact on the transfer of stellar radiation, and affects the projection of each physical (and kinematic) quantity. In a previous paper, we have investigated the effects of a diffusely distributed dust component on the observed kinematics of spherical galaxies. In this paper we investigate the effect of not taking dust into account in dynamical modelling procedures. We use a set of semi-analytical dusty galaxy models to create synthetic line-of-sight velocity distribution (LOSVD) data sets, which we then model as if no dust were present. We find some considerable differences between the best-fitting models and the input models, and we find that these differences are dependent on the orbital structure of the input galaxy. For radial and isotropic models on the one hand, we find that the dynamical mass of the models decreases nearly linearly with optical depth, with an amount of 5 per cent per optical depth unit, whereas their orbital structure is hardly affected. For tangential models on the other hand, the dynamical mass decrease is smaller, but their orbital structure is affected: their distribution functions appear less tangentially anisotropic. For all models the mass-to-light ratio will be underestimated, by a factor of around 20 per cent per optical depth unit. We discuss these results in the light of the limited effects of dust extinction on the LOSVDs, as obtained in Paper I, and conclude that the determination of the dynamical mass and the kinematic structure of galaxies is not only determined by the observed kinematic quantities, but is also critically dependent on the potential and hence the observed light profile. We argue that dust, even in rather modest amounts, should therefore be taken into account in kinematic modelling procedures.
Deep belief nets for natural language call-routing

This paper considers application of Deep Belief Nets (DBNs) to natural language call routing. DBNs have been successfully applied to a number of tasks, including image, audio and speech classification, thanks to the recent discovery of an efficient learning technique. DBNs learn a multi-layer generative model from unlabeled data and the features discovered by this model are then used to initialize a feed-forward neural network which is fine-tuned with backpropagation. We compare a DBN-initialized neural network to three widely used text classification algorithms; Support Vector machines (SVM), Boosting and Maximum Entropy (MaxEnt). The DBN-based model gives a call-routing classification accuracy that is equal to the best of the other models even though it currently uses an impoverished representation of the input.
Strongly Improved Stability and Faster Convergence of Temporal Sequence Learning by Using Input Correlations Only

Currently all important, low-level, unsupervised network learning algorithms follow the paradigm of Hebb, where input and output activity are correlated to change the connection strength of a synapse. However, as a consequence, classical Hebbian learning always carries a potentially destabilizing autocorrelation term, which is due to the fact that every input is in a weighted form reflected in the neuron's output. This self-correlation can lead to positive feedback, where increasing weights will increase the output, and vice versa, which may result in divergence. This can be avoided by different strategies like weight normalization or weight saturation, which, however, can cause different problems. Consequently, in most cases, high learning rates cannot be used for Hebbian learning, leading to relatively slow convergence. Here we introduce a novel correlation-based learning rule that is related to our isotropic sequence order (ISO) learning rule (Porr & Wrgtter, 2003a), but replaces the derivative of the output in the learning rule with the derivative of the reflex input. Hence, the new rule uses input correlations only, effectively implementing strict heterosynaptic learning. This looks like a minor modification but leads to dramatically improved properties. Elimination of the output from the learning rule removes the unwanted, destabilizing autocorrelation term, allowing us to use high learning rates. As a consequence, we can mathematically show that the theoretical optimum of one-shot learning can be reached under ideal conditions with the new rule. This result is then tested against four different experimental setups, and we will show that in all of them, very few (and sometimes only one) learning experiences are needed to achieve the learning goal. As a consequence, the new learning rule is up to 100 times faster and in general more stable than ISO learning.
Glottal motion and its impact on airflow and aerosol deposition in upper airways during human breathing

During inhaled therapies several factors limits the amount of drug delivered to the lungs. E.g. the upper airways morphology and in particular the glottis, defined by the vocal-fold aperture, causes upper airways to narrow in a minimal cross section, which is determinant on aerosol depo­ sition by inertial impaction. This thesis aims to (i) investigate evolution of the glottal area during breathing, and (ii) predict the effects of a dynamic glottis and realistic airflow conditions on the aerosol deposition in upper airways using three-dimensional simulations.First, a clinical study was conducted on 20 healthy volunteers (10 males and 10 females) to explore the glottal motion during several specifie slow (below 20 cycles/min) and rapid breathing tasks (up to 90 cycles/min). The breathing was investigated simultaneously for the glottal area variations using laryngoscopie video recordings and for airflow rate using oral flowmeter.The experimental measurements showed that the glottal geometry observed during a breathing cycle can be extremely variable depending on the respiratory phase, tidal volume, and breathing frequency. Testing the dynamic behaviour of the glottis during breathing, two groups of subjects were identified: one with relatively constant glottal area and other with significant variations. In average, the variations for the latter group of subjects was observed for males at 26% comparing maximale and minimal glottal opening during inspiration and expiration respectively.The results of the clinical study together with anatomical morphological data served to create a madel with idealised geometry of upper airways. This madel represents the major geometrical characteristics of upper airways with special interest in the glottal region. Transport and deposition of aerosols was studied using 3D numerical cyclic simulations and parametrical analysis allowed to evaluate the influence of the cyclic flow, glottal dynamics, type of carrier gas (air or helium-oxygen mixture) and particle size on the deposition of aerosols in the upper airways.The numerical simulations demonstrated significant decrease of respiration work with He-02 and jet-like flow with recirculation zone in the oro-pharynx and downstream the glottal plane. The principal deposition mechanism is inertial impaction (for the particle diameters 1 - lOiJ.m) with most significant deposition region in the oro-pharynx. Important parameters for deposition are the particle size and the nature of carrier gas. For He-02 the deposition reaches two times smaller values than for air and the fraction of deposited particles increases significantly with diameter, reaching 80% of deposited efficiency for 10 iJ.m particles. Finally, the CFD results demonstrated negligible differences in aerosol transport and deposition between different glottal characteristics. Therefore, in normal breathing conditions the glottal motion can be neglected
Citalopram treatment of fluoxetine nonresponders.

BACKGROUND We assessed the tolerability and utility of switching fluoxetine nonresponders to citalopram the day that fluoxetine therapy was stopped. METHOD Fifty-eight outpatients with DSM-IV major depressive episode and prospectively confirmed nonresponse to fluoxetine (mean final dose = 31 mg/day) were switched directly to citalopram (20 mg/day). Of the 58 patients, 44 (76%) had never been successfully treated with antidepressant medication. During a 12-week open-label treatment period, citalopram could be titrated up to a maximum dose of 60 mg/day. Response was evaluated using the Clinical Global Impressions (CGI) scale, the 24-item Hamilton Rating Scale for Depression, and several other measures. RESULTS Eighty-one percent (N = 47) completed the trial, and citalopram (mean dose = 38.8 mg/day) was well tolerated. The intent-to-treat CGI response rate was 46% (26/57) at week 6 and 63% (36/57) at study endpoint; the completer response rate was 76% among the 47 patients who completed the 12-week trial. Improvement from baseline on all dependent measures was statistically significant after the first week of citalopram treatment. CONCLUSION Fluoxetine nonresponders can be quickly switched to citalopram, with good tolerability and reasonable chance of therapeutic benefit. Further work is necessary to assess the merits of this treatment strategy relative to other options.
Redefining the lipophilin family of proteolipid proteins

The past few years have seen a dramatic increase in our understanding, in molecular terms, of the involvement of the central nervous system proteolipid protein in myelinogenesis and X‐linked genetic diseases. In addition, we have expanded our knowledge of the proteins that have been recruited into the vertebrate myelin membrane over the past 400 million years with the molecular cloning of several cDNAs encoding proteins which are homologous to the proteolipid protein gene. In searching for a name to distinguish these proteins from other “proteolipid” proteins of nonneural origin I propose that we resurrect the term “lipophilins” which describes a small family of unusually hydrophobic integral membrane proteins exhibiting identical topologies and similar physical properties. Two subgroups are distinguishable among the lipophilins based on the patterns of expression during development and the presence or absence of a small motif that is exposed to the extracellular space. J. Neurosci. Res. 50:659–664, 1997. © 1997 Wiley‐Liss, Inc.
Anti-Allergic Activities of Smilax glabra Rhizome Extracts and Its Isolated Compounds.

BACKGROUND The rhizomes of Smilax glabra (SG) has long been used in Traditional Chinese and Thai herbal medicine to treat a variety of infectious diseases and immunological disorders. OBJECTIVE To investigate the in vitro anti-allergic activities of crude extracts andpure isolated flavonoid compounds from SG by determination of inhibitory effect on antigen-induced release of β-hexosaminidasefrom RBL-2H3 cells. MATERIAL AND METHOD The in vitro inhibitory effects ofcrude aqueous and organic extracts on β-hexosaminidase release in RBL-2H3 cells were evaluated as an in vitro indication ofpossible anti-allergic activity. Bioassay-guided fractionation of extracts was used to isolate flavonoid compounds from the ethanolic extracts. RESULTS The 95% and 50% ethanolic extracts of SG showed remarkably high anti-allergic activity, with IC50 values of 5.74 ± 2.44 and 23.54 ± 4.75 µg/ml, much higher activity than that for Ketotifen (IC50 58.90 µM). The water extract had negligible activity (IC50 > 100 µg/ml). The two isolated flavonols, Engeletin and Astilbin, showed weak anti-allergic activity, IC50 values 97.46 ± 2.04 and >100 µg/ml, respectively. CONCLUSION The 95% and 50% ethanolic extracts of SG showed strong anti-allergic activity, but two flavonol constituents did not show any significant anti-allergic activity. These findings suggest that a combination of effects of various phytochemicals in crude extracts used in traditional medicine, are responsible for the purported anti-allergic activity of SG herbal preparations. The plethora of constituents in crude extracts, as yet unidentified, are likely to be acting synergistically to account for the strong observed anti-allergic in vitro activity.
Histopathological spectrum of childhood idiopathic steroid-resistant nephrotic syndrome in Tunisia.

BACKGROUND In children, renal biopsy is routinely required in the management of idiopathic steroid-resistant nephrotic syndrome particularly prior to starting nephrotoxic immunosuppressive agents. AIM To investigate the correlations between the results of initial renal biopsy in Tunisian children with idiopathic steroid-resistant nephrotic syndrome and the subsequent response to cyclosporineprednisolone combination. METHODS We conducted a retrospective study of children with idiopathic steroid-resistant nephrotic syndrome over the period 2002- 2009. Data on clinico-biological features, histological diagnosis and response to cyclosporine-prednisolone were collected. RESULTS Thirty patients were enrolled, of whom 16 had focal segmental glomerulosclerosis, eight had minimal change disease and six had diffuse mesangial proliferation. Complete Remission was achieved in 15 patients (50%). Nine patients (30%) went into partial remission. Only six patients presented no response (20%). No statistically significant relationship between the different pathological types and the response to CsA-prednisone was found. CONCLUSION In our study, two important facts were noted: 1) the predominant histopathological subtype was the focal segmental glomerulosclerosis; 2) a high remission rate was achieved in our patients using a combined cyclosporine-prednisolone treatment regimen. This response is not dependent on the histological type.
Integral based source selection for uncooperative distributed information retrieval environments

In this paper, a new source selection algorithm for uncooperative distributed information retrieval environments is presented. The algorithm functions by modeling each information source as an integral, using the relevance score and the intra-collection position of its sampled documents in reference to a centralized sample index and selects the collections that cover the largest area in the rank-relevance space. Based on the above novel metric, the algorithm explicitly focuses on addressing the two goals of source selection; high recall which is important for source recommendation applications and high precision aiming to produce a high precision final merged list. For the latter goal in particular, the new approach steps away from the usual practice of DIR systems of explicitly declaring the number of collections that must be queried and instead receives as input only the number of retrieved documents in the final merged list, dynamically calculating the number of collections that are selected and the number of documents requested from each. The algorithm is tested in a wide range of testbeds in both recall and precision oriented settings and its effectiveness is found to be equal or better than other state-of-the-art algorithms.
Molecular Imaging of the Kinetics of Vascular Endothelial Growth Factor Gene Expression in Ischemic Myocardium

Background—Angiogenic gene therapy is a promising treatment paradigm for patients with ischemic heart disease. In this study, we used micro–positron emission tomography (microPET) to monitor the transgene expression, function, and effects in a whole-body system. Methods and Results—Adenovirus with cytomegalovirus promoter driving an angiogenic gene (vascular endothelial growth factor [VEGF]) linked to a PET reporter gene (herpes simplex virus type 1 mutant thymidine kinase; Ad-CMV-VEGF121-CMV-HSV1-sr39tk) was used to transfect rat embryonic cardiomyoblasts in vitro. Expression of both genes correlated strongly (r=0.98; P<0.001). Afterward, rats underwent ligation of the left anterior descending artery followed by injection of 1×1010 pfu of Ad-CMV-VEGF121-CMV-HSV1-sr39tk (study; n=35) or Ad-null (control; n=15) at the peri-infarct region. Noninvasive microPET imaging was used to assess the uptake of 9-(4-[18F]-fluoro-hydroxymethylbutyl)guanine ([18F]-FHBG) PET reporter probe by cells expressing the HSV1-sr39tk PET reporter gene. Cardiac transgene expression peaked at day 1 and declined over the next 2 weeks. Repeat adenoviral injections at day 60 yielded no detectable signal. The in vivo reporter gene expression (% injected dose/g of [18F]-FHBG) correlated well with ex vivo gamma counting (r=0.92), myocardial tissue HSV1-sr39TK enzyme activity (r=0.95), and myocardial tissue VEGF level (r=0.94; P<0.001 for all). The VEGF121 isoform induced significant increases in capillaries and small blood vessels. However, the level of neovasculature did not translate into significant improvements in functional parameters such as myocardial contractility by echocardiography, perfusion by nitrogen-13 ammonia imaging, and metabolism by [18F]-fluorodeoxyglucose imaging. Conclusions—Taken together, these findings establish the feasibility of molecular imaging for monitoring angiogenic gene expression with a PET reporter gene and probe noninvasively, quantitatively, and repetitively. The principles demonstrated here can be used to evaluate other therapeutic genes of interest in animal models before future clinical trials are initiated.
An experimental evaluation of peer-to-peer reliable multicast protocols

Tactical operations often involve the cooperation of multiple actors that need to communicate in a reliable and timely fashion. Numerous critical activities that are performed in this context, such as the dissemination of situational awareness data, or the dissemination of command and control information, present a point-to-multipoint pattern. Therefore, multicast protocols are a suitable approach to perform efficient data dissemination in this context. More specifically, some tactical information requires reliable point-to-multipoint delivery of information. In this paper, we experimentally evaluate four protocols (and corresponding implementations) that have been developed to support reliable multicast communications: NORM, JGroups, OpenPGM, and DisService. We report on two sets of experiments. The first set of experiments measure bandwidth utilization and average delivery time under different emulated network conditions. The second set of experiments performs a more in-depth comparison of the forward error correction approach implemented in NORM with DisService, which adopts an opportunistic approach for information dissemination.