Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Atlas of the Cardiac Fiber Architecture: Study on a Healthy Population

Cardiac fibers, as well as their local arrangement in laminar sheets, have a complex spatial variation of their orientation that has an important role in mechanical and electrical cardiac functions. In this paper, a statistical atlas of this cardiac fiber architecture is built for the first time using human datasets. This atlas provides an average description of the human cardiac fiber architecture along with its variability within the population. In this study, the population is composed of ten healthy human hearts whose cardiac fiber architecture is imaged ex vivo with DT-MRI acquisitions. The atlas construction is based on a computational framework that minimizes user interactions and combines most recent advances in image analysis: graph cuts for segmentation, symmetric log-domain diffeomorphic demons for registration, and log-Euclidean metric for diffusion tensor processing and statistical analysis. Results show that the helix angle of the average fiber orientation is highly correlated to the transmural depth and ranges from -41° on the epicardium to +66° on the endocardium. Moreover, we find that the fiber orientation dispersion across the population (13°) is lower than for the laminar sheets (31°). This study, based on human hearts, extends previous studies on other mammals with concurring conclusions and provides a description of the cardiac fiber architecture more specific to human and better suited for clinical applications. Indeed, this statistical atlas can help to improve the computational models used for radio-frequency ablation, cardiac resynchronization therapy, surgical ventricular restoration, or diagnosis and followups of heart diseases due to fiber architecture anomalies.
Mechanisms of copper- and iron-dependent oxidative modification of human low density lipoprotein.

Oxidative modification of low density lipoprotein (LDL) has been suggested as a causal step in atherosclerosis, and both redox-active transition metal ions and superoxide (O2.-) have been implicated in this process. In order to determine the mechanisms of metal ion-dependent oxidation of LDL in the presence of O2. -, LDL was exposed to hypoxanthine (HX) and purified xanthine oxidase (XO) without and with added CuCl2 or Fe(3+)-citrate. Production of O2. - and hydrogen peroxide (H2O2) at pH 7.4 by the HX/XO system in the absence of metal ions was not sufficient to oxidize LDL. Preincubation of LDL with Cu2+ or Fe(3+)-citrate with subsequent removal of metal ions not tightly bound to the lipoprotein did not enable the HX/XO system to oxidize LDL. However, incubation of LDL with HX/XO and Cu2+ resulted in extensive modification of LDL. Exposure of LDL to Cu2+ alone also led to extensive modification, although the LDL was initially free of detectable amounts of lipid hydroperoxides (LOOH), i.e., < 0.005 molecules of LOOH per LDL particle. Although HX/XO and Cu2+ did not produce detectable amounts of O2. - or aqueous hydroxyl radicals (HO.), oxidation of LDL under these conditions was partially inhibited by superoxide dismutase, and completely inhibited by the HO. scavenger thiourea. In contrast to Cu(2+)-mediated oxidation of LDL, oxidation mediated by Fe(3+)-citrate was strictly dependent upon O2. -, as it was abolished by omission of the HX/XO system or by addition of superoxide dismutase to this system. (ABSTRACT TRUNCATED AT 250 WORDS)
Clinical-Grade Generation of Active NK Cells from Cord Blood Hematopoietic Progenitor Cells for Immunotherapy Using a Closed-System Culture Process

Natural killer (NK) cell-based adoptive immunotherapy is a promising treatment approach for many cancers. However, development of protocols that provide large numbers of functional NK cells produced under GMP conditions are required to facilitate clinical studies. In this study, we translated our cytokine-based culture protocol for ex vivo expansion of NK cells from umbilical cord blood (UCB) hematopoietic stem cells into a fully closed, large-scale, cell culture bioprocess. We optimized enrichment of CD34+ cells from cryopreserved UCB units using the CliniMACS system followed by efficient expansion for 14 days in gas-permeable cell culture bags. Thereafter, expanded CD34+ UCB cells could be reproducibly amplified and differentiated into CD56+CD3− NK cell products using bioreactors with a mean expansion of more than 2,000 fold and a purity of >90%. Moreover, expansion in the bioreactor yielded a clinically relevant dose of NK cells (mean: 2×109 NK cells), which display high expression of activating NK receptors and cytolytic activity against K562. Finally, we established a versatile closed washing procedure resulting in optimal reduction of medium, serum and cytokines used in the cell culture process without changes in phenotype and cytotoxic activity. These results demonstrate that large numbers of UCB stem cell-derived NK cell products for adoptive immunotherapy can be produced in closed, large-scale bioreactors for the use in clinical trials.
Acute Disseminated Encephalomyelitis in Children: Discordant Neurologic and Neuroimaging Abnormalities and Response to Plasmapheresis

Objectives. To describe our experience with acute disseminated encephalomyelitis (ADEM), focusing on (1) the relationship between clinical course and MRI findings and (2) the response to plasmapheresis in a subgroup of patients. Methods. A retrospective record review was conducted of 13 children who were admitted as inpatients with the diagnosis of ADEM during the period 1998–2003. Results. Diagnosis was established by clinical signs and symptoms, cerebrospinal fluid changes and multifocal involvement of deep gray and white matter based on MRI. Initial therapy was high-dose methylprednisolone and intravenous immunoglobulin in 12 patients. One child improved spontaneously. Six of 12 children did not improve with corticosteroid treatment. All 6 had an acute progressive course neurologically, and 5 of them also showed a delay in the onset of neuroimaging changes, eventually developing lesions in the deep gray matter and brainstem. This latter group received 5 sessions of plasmapheresis and recovered over the course of several months with varying degrees of residual neurologic deficits. Conclusions. Presentation of ADEM with delayed development of MRI lesions in deep gray matter and brainstem may herald a prolonged clinical course and lack of response to glucocorticoid therapy. Plasmapheresis might be an effective therapeutic intervention in these patients. The role of plasmapheresis versus corticosteroids and intravenous immunoglobulin as a primary treatment of ADEM needs to be investigated further.
Macula densa Na 1 / H 1 exchange activities mediated by apical NHE 2 and basolateral NHE 4 isoforms

JÁNOS PETI-PETERDI,1 RÉGINE CHAMBREY,2 ZSUZSANNA BEBOK,3 DANIEL BIEMESDERFER,4 PATRICIA L. ST. JOHN,5 DALE R. ABRAHAMSON,5 DAVID G. WARNOCK,1,3 AND P. DARWIN BELL1,3 Departments of 1Medicine, Division of Nephrology and Nephrology Research and Training Center, and 3Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294; 2Institut National de la Santé et de la Recherche Médicale 356, Université Pierre et Marie Curie, Paris 75270, France; 4Department of Internal Medicine and of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510; and 5Department of Anatomy and Cell Biology, University of Kansas Medical Center, School of Medicine, Kansas City, Kansas 66160
An in vitro evaluation of the efficacy of a novel iontophoresis fluoride tray on remineralization

Objectives: The aim of this study is to determine the effects on remineralization of a novel iontophoresis device called ‘Fluorinex’, conventional (acidulated phosphat fluoride) APF gel treatment, and conventional ionthophoresis device comparatively by laser fluorescence measurements. Study Design: Artificial incipient carious lesions were created on immature, 60 intact premolar and molar teeth with no defects. The specimens were randomly allocated to four groups. In the first group 1.23% APF gel was applied to specimens by conventional method for 4 minutes and in the second group 2% (sodium fluoride) NaF solution applied by conventional iontophoresis device for 4 minutes. In Fluorinex group specimens were pretreated with (copper chloride) CuCl2 for 1 minute and then treated for 4 minutes with 1.23% APF gel in a Fluoritray. Control group was placed in distilled water for 4 minutes. After these applications all specimens were included to a pH cycling. DIAGNOdent pen measurement were obtained in three different time intervals; after incipient carious lesions, after fluoride treatments and after pH cycling. Specimens were studied by SEM(scanning electron microscopy) after artificial caries lesions and fluoride treatments. Results: Alterations on DIAGNOdent pen measurements before and after treatment, the Fluorinex group was statistically different from conventional APF gel (p=0.011), conventional NaF iontophoresis (p<0.001) and control group (p<0.001). As the DIAGNOdent pen measurements before treatment and after pH cycling were compared, differences were statistically significant in Fluorinex and conventional APF gel groups (p<0.001). Conclusions: The results of this in vitro study has shown that fluoride application by Fluorinex was superior to the conventional APF gel application and NaF iontophoresis on incipient carious lesions. Key words:Fluoride, iontophoresis, remineralization.
Carbon-enhanced Photocatalysts for Visible Light Induced Detoxification and Disinfection

Photocatalysis is an advanced oxidation process for the purification and remediation of contaminated waters and wastewaters, and is advantageous over conventional treatment technologies due to its ability to degrade emerging and recalcitrant pollutants. In addition, photocatalytic disinfection is less chemical-intensive than other methods such as chlorination, and can inactivate even highly resistant microorganisms with good efficacy. Process sustainability and cost-effectiveness may be improved by utilizing solar irradiation as the source of necessary photons for photocatalyst excitation. However, solar-induced activity of the traditionally-used titania is poor due to its inefficient visible light absorption, and recombination of photo-excited species is problematic. Additionally, mass transfer limitations and difficulties separating the catalyst from the post-treatment slurry hinder conversions and efficiencies obtainable in practice. In this research, various strategies were explored to address these issues using novel visible light active photocatalysts. Two classes of carbon-enhanced photocatalytic materials were studied: activated carbon adsorbent photocatalyst composites, and carbon-doped TiO2. Adsorbent photocatalyst composites based on activated carbon and plasmonic silver/silver chloride structures were synthesized, characterized, and experimentally investigated for their photocatalytic activity towards the degradation of model organic pollutants (methyl orange dye, phenol) and the inactivation of a model microorganism (Escherichia coli K-12) under visible light. The adsorptive behaviour of the composites towards methyl orange dye was also studied and described according to appropriate models. Photocatalytic bacterial inactivation induced by the prepared composites was investigated, and the inactivation mechanisms and roles of incorporated antimicrobial silver on disinfection were probed and discussed. These composites were extended towards magnetic removal strategies for post-use separation through the incorporation of magnetic nanoparticles to prepare Ag/AgCl-magnetic activated carbon composites, and the effect of nanoparticles addition on the properties and photoactivities of the resulting materials was explored. Another silver/silver halide adsorbent photocatalyst composite based on activated carbon and Ag/AgBr exhibiting visible light absorption due to both localized surface plasmon resonance and optical band gap absorption was synthesized and its photocatalytic activity towards organics degradation and microbial
A Novel in Vivo Role for Osteoprotegerin Ligand in Activation of Monocyte Effector Function and Inflammatory Response*

Osteoprotegerin Ligand (OPGL) is a member of the tumor necrosis factor ligand superfamily and has been shown to be involved in interactions between T cells and dendritic cells. Its role in monocyte effector function, however, has not been defined. In the present study a role for OPGL in activating monocytes/macrophages has been characterized. OPGL was found to up-regulate receptor activator of NF-κB (RANK) receptor expression on monocytes, regulate their effector function by inducing cytokine and chemokine secretion, activate antigen presentation through up-regulation of co-stimulatory molecule expression, and promote survival. This activation is mediated through the MAPK pathway as evidenced by activation of p38 and p42/44 MAPK and up-regulation of BCL-XL protein levels. A physiological role for OPGL in monocyte activation and effector function was tested in a model of lipopolysaccharide-induced endotoxic shock. Administration of receptor activator of NF-κB (RANK)-Fc to block OPGL activity in vivo was able to protect mice from death induced by sepsis, indicating a hitherto undescribed role for OPGL in monocyte function and in mediating inflammatory response. This was further tested in an animal model of inflammation-mediated arthritis. Treatment with RANK-Fc significantly ameliorated disease development and attenuated bone destruction. Thus, our study strongly suggests that administration of receptor fusion proteins to specifically block OPGL activity in vivo may result in blocking development of monocyte/macrophage-mediated diseases.
Combining Donor Characteristics with Immunohistological Data Improves the Prediction of Islet Isolation Success

Variability of pancreatic donors may significantly impact the success of islet isolation. The aim of this study was to evaluate donor factors associated with isolation failure and to investigate whether immunohistology could contribute to organ selection. Donor characteristics were evaluated for both successful (n = 61) and failed (n = 98) islet isolations. Samples of donor pancreatic tissue (n = 78) were taken for immunohistochemical examination. Islet isolations with 250000 islet equivalents were considered successful. We confirmed that BMI of less than 25 kg/m2 (P < 0.001), cold ischemia time more than 8 hours (P < 0.01), hospitalization longer than 96 hours (P < 0.05), higher catecholamine doses (P < 0.05), and edematous pancreases (P < 0.01) all unfavorably affected isolation outcome. Subsequent immunohistochemical examination of donor pancreases confirmed significant differences in insulin-positive areas (P < 0.001). ROC analyses then established that the insulin-positive area in the pancreas could be used to predict the likely success of islet isolation (P < 0.001). At the optimal cutoff point (>1.02%), sensitivity and specificity were 89% and 76%, respectively. To conclude, while the insulin-positive area, determined preislet isolation, as a single variable, is sufficient to predict isolation outcome and helps to improve the success of this procedure, its combination with the established donor scoring system might further improve organ selection.
An Efficient Algorithm for Easy-First Non-Directional Dependency Parsing

We present a novel deterministic dependency parsing algorithm that attempts to create the easiest arcs in the dependency structure first in a non-directional manner. Traditional deterministic parsing algorithms are based on a shift-reduce framework: they traverse the sentence from left-to-right and, at each step, perform one of a possible set of actions, until a complete tree is built. A drawback of this approach is that it is extremely local: while decisions can be based on complex structures on the left, they can look only at a few words to the right. In contrast, our algorithm builds a dependency tree by iteratively selecting the best pair of neighbours to connect at each parsing step. This allows incorporation of features from already built structures both to the left and to the right of the attachment point. The parser learns both the attachment preferences and the order in which they should be performed. The result is a deterministic, best-first, O(nlogn) parser, which is significantly more accurate than best-first transition based parsers, and nears the performance of globally optimized parsing models.
Role of Specificity Protein 1, Hepatocyte Nuclear Factor 1α, and Pregnane X Receptor in the Basal and Rifampicin-Induced Transcriptional Regulation of Porcine Cytochrome P450 3A46

Cytochrome P450 (CYP) 3A46, one of human CYP3A4 homologs, functions as a key enzyme in the metabolism of xenobiotics in pigs. However, the regulatory mechanism for the transcriptional activation of CYP3A46 in porcine liver remains unknown. In this study, we confirmed that CYP3A46 is constitutively expressed in porcine primary hepatocytes, and its expression was significantly induced by rifampicin (RIF) instead of dexamethasone. We further found that a proximal GC box and a distal hepatocyte nuclear factor 1 (HNF1) binding site within the 5′-flanking region of CYP3A46 are the important cis-regulatory elements involved in regulating the constitutive expression of CYP3A46, via recruiting specificity protein 1 (Sp1) and HNF1α, respectively. Furthermore, we revealed that HNF1α and pregnane X receptor (PXR) activate the RIF-mediated transcription of CYP3A46 by binding to the distal HNF1 binding site and the proximal direct repeats of AGGTCA separated by 4 bases motif, respectively. Meanwhile, HNF1α is also involved in regulating RIF-induced expression of CYP3A4 through a novel distal HNF1 binding site identified in the xenobiotic-responsive enhancer module. In summary, our data demonstrate that several transcription factors, including Sp1, HNF1α, and PXR, function in the basal and RIF-mediated transcriptional regulation of CYP3A46 by binding to their related cis-regulatory elements in the proximal promoter and distal enhancer.
Energy-Efficient Crowdsensing of Human Mobility and Signal Levels in Cellular Networks

The paper presents a practical application of the crowdsensing idea to measure human mobility and signal coverage in cellular networks. Currently, virtually everyone is carrying a mobile phone, which may be used as a sensor to gather research data by measuring, e.g., human mobility and radio signal levels. However, many users are unwilling to participate in crowdsensing experiments. This work begins with the analysis of the barriers for engaging people in crowdsensing. A survey showed that people who agree to participate in crowdsensing expect a minimum impact on their battery lifetime and phone usage habits. To address these requirements, this paper proposes an application for measuring the location and signal strength data based on energy-efficient GPS tracking, which allows one to perform the measurements of human mobility and radio signal levels with minimum energy utilization and without any engagement of the user. The method described combines measurements from the accelerometer with effective management of the GPS to monitor the user mobility with the decrease in battery lifetime by approximately 20%. To show the applicability of the proposed platform, the sample results of signal level distribution and coverage maps gathered for an LTE network and representing human mobility are shown.
Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine

The (S)- and (R)-enantiomers of acyclic purine nucleoside phosphonate analogs (i.e., 3-hydroxy-2-phosphonomethoxypropyl [HPMP] derivatives, 3-fluoro-2-phosphonomethoxypropyl [FPMP] derivatives, and 2-phosphonomethoxypropyl [PMP] derivatives of adenine [A], 2-aminopurine, 2,6-diaminopurine [DAP], and guanine [G]) have been synthesized and evaluated for antiviral activity. As a rule, the HPMP derivatives proved effective against DNA viruses but not RNA viruses or retroviruses. In particular, (S)-HPMPA, (S)-HPMPDAP, and (R)- and (S)-HPMPG were exquisitely inhibitory to herpes simplex virus type 1 (50% effective concentrations, 0.63, 0.22, 0.10, and 0.66 microM, respectively). The FPMP and PMP derivatives showed marked inhibitory activities against retroviruses but not DNA viruses. The (S)-enantiomer of FPMPA and the (R)-enantiomer of PMPA were approximately 30- to 100-fold more effective against human immunodeficiency virus and Moloney murine sarcoma virus (MSV) than their enantiomeric counterparts. In contrast, both (S)- and (R)-enantiomers of the DAP and G derivatives proved equally effective against retroviruses, except for (R)-PMPDAP, which was 15- to 40-fold more inhibitory than (S)-PMPDAP. (R)-PMPDAP emerged as the most potent and selective inhibitor of MSV-induced transformation of murine C3H/3T3 cells and human immunodeficiency virus-induced cytopathicity in MT-4 and CEM cells (50% effective concentration, approximately 0.1 to 0.6 microM). When administered intraperitoneally at a single dose as low as 2 mg/kg, (R)-PMPDAP efficiently decreased MSV-induced tumor formation in newborn NMRI mice and significantly increased the survival time of MSV-infected mice. In addition, upon oral administration to MSV-infected mice, (R)-PMPDAP showed marked antiretroviral efficacy.
Induction of cytosolic phospholipase A2 and prostaglandin H2 synthase‐2 by ipopolysaccharide in human polymorphonuclear leukocytes

Abstract: Polymorphonuclear leukocytes (PMNs) produce arachidonic acid (AA) metabolites including thromboxane A2 (TXA2). These cells are the first line of defense against bacterial invasion, which often causes endotoxin shock. TXA2 which plays an important role in the pathogenesis of endotoxin shock is synthesized by three consecutive enzyme activation, cytosolic phospholipase A2 (cPLA2), prostaglandin H2 synthase (PHS type 1 and type 2) and TXA2 synthase. Among them, cPLA2‐ and PHS‐2 activity is known to be transcriptionally and/or post‐transcriptionally up‐regulated by various bioactive substances including lipopolysaccharide (LPS), a bacterial endotoxin, in many cell types. We investigated the action of LPS on TXA2 synthesis in human PMNs. A23187‐stimulated production of thromboxane B2 (TXB2, a stable metabolite of TXA2), assayed by specific radioimmunoassay (RIA), was significantly increased from 566.7±44.1 pg/106 cells to 966.7±44.1 pg/106 cells (p <0.05) after 6 h‐exposure to LPS at the concentration of 100 ng/ml. Messenger RNA for PHS‐2, PHS‐1, TXA2 synthase and cPLA2, which was assessed by reverse transcription‐polymerase chain reaction (RT‐PCR), was expressed in PMNs without LPS stimulation. Although PHS‐2 was putatively an inducible enzyme, abundance of mRNA for PHS‐2 in PMNs without LPS stimulation was detectable. Messenger RNA abundance for PHS‐2 and cPLA2, but not for PHS‐1 and TXA2 synthase, was enhanced by LPS‐treatment, indicating that the increased production of TXB2 was attributable to the up‐regulation of cPLA2 and PHS‐2. We conclude that (1) PHS‐2 plays a more important role than PHS‐1 in the production of TXA2 in human PMNs and (2) TXA2 synthesis in human PMNs is transcriptionally up‐regulated by new induction of cPLA2 as well as PHS‐2, when the cells encounter endotoxin producing bacteria.