Miracle-dz/UniFAR-FTUs huggingface dataset:
Species diversification and phylogenetically constrained symbiont switching generated high modularity in the lichen genus Peltigera

Ecological interactions range from purely specialized to extremely generalized in nature. Recent research has showed very high levels of specialization in the cyanolichens involving Peltigera (mycobionts) and their Nostoc photosynthetic partners (cyanobionts). Yet, little is known about the mechanisms contributing to the establishment and maintenance of such high specialization levels. Here, we characterized interactions between Peltigera and Nostoc partners at a global scale, using more than one thousand thalli. We used tools from network theory, community phylogenetics and biogeographical history reconstruction to evaluate how these symbiotic interactions may have evolved. After splitting the interaction matrix into modules of preferentially interacting partners, we evaluated how module membership might have evolved along the mycobionts’ phylogeny. We also teased apart the contributions of geographical overlap vs phylogeny in driving interaction establishment between Peltigera and Nostoc taxa. Module affiliation rarely evolves through the splitting of large ancestral modules. Instead, new modules appear to emerge independently, which is often associated with a fungal speciation event. We also found strong phylogenetic signal in these interactions, which suggests that partner switching is constrained by conserved traits. Therefore, it seems that a high rate of fungal diversification following a switch to a new cyanobiont can lead to the formation of large modules, with cyanobionts associating with multiple closely retated Peltigera species. Finally, when restricting our analyses to Peltigera sister species, the latter differed more through partner acquisition/loss than replacement (i.e., switching). This pattern vanishes as we look at sister species that have diverged longer ago. This suggests that fungal speciation may be accompanied by a stepwise process of (a) novel partner acquisition and (b) loss of the ancestral partner. This could explain the maintenance of high specialization levels in this symbiotic system where the transmission of the cyanobiont to the next generation is assumed to be predominantly horizontal. Synthesis. Overall, our study suggests that oscillation between generalization and ancestral partner loss may maintain high specialization within the lichen genus Peltigera, and that partner selection is not only driven by partners’ geographical overlap, but also by their phylogenetically conserved traits.
Design and performance of a trickling air biofilter for chlorobenzene and o-dichlorobenzene vapors

From contaminated industrial sludge, two stable multistrain microbial enrichments (consortia) that were capable of rapidly utilizing chlorobenzene and o-dichlorobenzene, respectively, were obtained. These consortia were characterized as to their species composition, tolerance range, and activity maxima in order to establish and maintain the required operational parameters during their use in biofilters for the removal of chlorobenzene contaminants from air. The consortia were immobilized on a porous perlite support packed into filter columns. Metered airstreams containing the contaminant vapors were partially humidified and passed through these columns. The vapor concentrations prior to and after biofiltration were measured by gas chromatography. Liquid was circulated concurrently with the air, and the device was operated in the trickling air biofilter mode. The experimental arrangement allowed the independent variation of liquid flow, airflow, and solvent vapor concentrations. Bench-scale trickling air biofilters removed monochlorobenzene, o-dichlorobenzene, and their mixtures at rates of up to 300 g of solvent vapor h(-1) m(-3) filter volume. High liquid recirculation rates and automated pH control were critical for stable filtration performance. When the accumulating NaCl was periodically diluted, the trickling air biofilters continued to remove chlorobenzenes for several months with no loss of activity. The demonstrated high performance and stability of the described trickling air biofilters favor their use in industrial-scale air pollution control.
Matched follow-up study of 5-8 year old ICSI-singletons: comparison of their neuromotor development to IVF and naturally conceived singletons.

BACKGROUND Intracytoplasmic sperm injection (ICSI) is an invasive technique of artificial reproduction. We investigated the effect of ICSI on neuromotor development in 5-8 year old singletons. METHODS We did a follow-up of ICSI-singletons born between 1996 and 1999 after treatment in the Leiden University Medical Center and compared them with matched controls born after in vitro fertilization (IVF) and natural conception (NC). Children underwent a thorough neurological examination that focused on minor neurological dysfunction (MND). RESULTS There were no differences in outcome between ICSI (n = 81) and IVF-children (n = 81), all born at term: MND prevalence 66.3% versus 61.3%, prevalence ratio (PR) 1.08 [0.83; 1.29]. MND prevalence among all ICSI-children (n = 87) was higher than among NC-controls (n = 85) (66.3% versus 50.6%, PR 1.31 [1.02; 1.55]). After adjustment for maternal age and parity, the PR remained elevated but was no longer statistically significant (adjusted PR 1.22 [0.86; 1.52]). When comparing only term ICSI and NC-children (n = 81; n = 85), the PR adjusted for maternal age and parity was 1.20 [0.83; 1.51]. CONCLUSIONS Neuromotor outcome of 5-8 year old singletons born at term after ICSI or IVF was similar; ICSI-children (both the total group and term children only) deviated slightly from NC-controls. Part of this effect was explained by a difference in parity, but not prematurity.
Low loss and high dielectric constant poly(methyl methacrylate)/BaTiO3 nanocomposites prepared by in situ atom transfer radical polymerization

Poly(methyl methacrylate) (PMMA) nanocomposites containing BaTiO3 were prepared by in situ atom transfer radical polymerization (ATRP). The nanocomposites show significantly increased dielectric constant when compared with the pure PMMA, whereas the dielectric loss of the nanocomposite is kept at the same low level as that of the pure PMMA. For example, at 1000 Hz, the dielectric constant increases from 6.9 for the nanocomposite containing 15 vol% BaTiO3 to 15 for the nanocomposite with 32 vol% BaTiO3, while the dielectric loss is almost independent on the BaTiO3 content and has a low value of 0.045. 1H NMR spectra confirmed the chemical structure of PMMA shell on the surface of BaTiO3 nanoparticles. Scanning electron microscopy (SEM) revealed that the BaTiO3 nanoparticles are well dispersed in the nanocomposites.
Elastin, a Novel Extracellular Matrix Protein Adhering to Mycobacterial Antigen 85 Complex*

Background: Ag85A, Ag85B, and Ag85C are elastin/tropoelastin-binding proteins from mycobacteria. Results: The Ag85 complex-binding motif on tropoelastin is AAAKAA(K/Q)(Y/F). Conclusion: Mycobacterial Ag85 proteins interact with elastin and tropoelastin. Significance: This is the first evidence that Ag85 proteins bind to elastin and tropoelastin. The interaction of Ag85 antigen with elastin may contribute to the pathogenesis of this disease. The antigen 85 complex (Ag85) consists of three predominantly secreted proteins (Ag85A, Ag85B, and Ag85C), which play a key role in the mycobacterial pathogenesis and also possess enzymatic mycolyltransferase activity involved in cell wall synthesis. Ag85 is not only considered to be a virulence factor because its expression is essential for intracellular survival within macrophages, but also because it contributes to adherence, invasion, and dissemination of mycobacteria in host cells. In this study, we report that the extracellular matrix components, elastin and its precursor (tropoelastin) derived from human aorta, lung, and skin, serve as binding partners of Ag85 from Mycobacterium tuberculosis. The binding affinity of M. tuberculosis Ag85 to human tropoelastin was characterized (KD = 0.13 ± 0.006 μm), and a novel Ag85-binding motif, AAAKAA(K/Q)(Y/F), on multiple tropoelastin modules was identified. In addition, the negatively charged Glu-258 of Ag85 was demonstrated to participate in an electrostatic interaction with human tropoelastin. Moreover, binding of Ag85 on elastin siRNA-transfected Caco-2 cells was significantly reduced (34.3%), implying that elastin acts as an important ligand contributing to mycobacterial invasion.
Uncertainty-Aware Sensor Network Deployment

In this paper, we address the issue of handling uncertainty and information fusion for an efficient WSN deployment. We present a flexible framework for collaborative target detection within the transferable belief model. Using the developed framework, we propose an uncertainty-aware deployment algorithm that is able to determine the minimum number of sensors and their locations such that full area coverage is achieved. The issues of connectivity, obstacles, preferential coverage, challenging environments and sensor reliability are also discussed. Experimental results are provided to demonstrate the ability of our approach to achieve an efficient sensor deployment by exploiting a collaborative target detection scheme.
Isolation and characterization of a novel transcript embedded within HIRA, a gene deleted in DiGeorge syndrome.

We have isolated a few cDNAs from different human tissues, transcribed from the first intron of HIRA, a gene deleted in the DiGeorge syndrome. These cDNAs are produced by an intronic gene (22k48) which is transcribed by the HIRA opposite strand and is itself arranged in exons and subjected to alternative splicing. The longest continuum cDNA sequence we obtained is 3.6 kb long and contains 3 different exons and 2 introns. 22k48 cDNA is composed of several tandemly arranged repeated elements (Alu, LINEs, CAn) surrounding a unique sequence. In situ hybridization showed the presence of 22k48 RNA in the cytoplasm of CNS and PNS neurons. 22k48 RNA is able to bind cytoplasmic proteins in the range of 45 to 60 kDa. 22k48 is a new member of the small group of genes that are transcribed but not translated, and its haploinsufficiency could contribute to the pathogenesis of the DiGeorge syndrome.
MIMO Eigen Beamforming for HSUPA of TD SCDMA

As the evolution of the 3G standards, multiple input and multiple output (MIMO) has been adopted to enhance the performance of 3G systems for the potential of beamforming, spatial multiplexing or spatial diversity. So far, no MIMO scheme has been adopted for time division-synchronous code division multiple access (TD-SCDMA). In this paper, 2times8 MIMO eigen beamforming is proposed to improve the performance of TD-SCDMA. As size limited, the antennas at the UE or Node B are correlated, only one eigen mode of the spatial correlation matrix is found to be useful, and only the beamforming gain and spatial diversity gain can be obtained efficiently. The simulation results of high speed uplink packet access (HSUPA) in the fixed reference channel show that, compared to single input and multiple output (SIMO) 1times8, 3 dB performance gain can be obtained by MIMO 2times8 eigen beamforming; while compared to that of single input and single output (SISO), the performance gain is 8-3 dB
Molecular mechanisms of drug resistance in acute myeloid leukaemia

Resistance to chemotherapy in acute myeloid leukaemia is a major obstacle to a successful outcome for many patients. Often, there is resistance against a broad range of drugs due to multiple, simultaneously active processes. These mechanisms include effects on drug influx and efflux, drug activation/inactivation, DNA repair mechanisms, altered response of end targets, an altered haematopoietic microenvironment and dysfunctional apoptotic pathways. This article reviews the factors that determine leukaemic cell chemosensitivity and discusses the potential for rationally guided therapy.
ATPase activity of the sulfonylurea receptor: a catalytic function for the KATP channel complex

ATP‐sensitive K+ (KATP) channels are unique metabolic sensors formed by association of Kir6.2, an inwardly rectifying K+ channel, and the sulfonylurea receptor SUR, an ATP binding cassette protein. We identified an ATPase activity in immunoprecipitates of cardiac KATP channels and in purified fusion proteins containing nucleotide binding domains NBD1 and NBD2 of the cardiac SUR2A isoform. NBD2 hydrolyzed ATP with a twofold higher rate compared to NBD1. The ATPase required Mg2+ and was insensitive to ouabain, oligomycin, thapsigargin, or levamisole. K1348A and D1469N mutations in NBD2 reduced ATPase activity and produced channels with increased sensitivity to ATP. KATP channel openers, which bind to SUR, promoted ATPase activity in purified sarcolemma. At higher concentrations, openers reduced ATPase activity, possibly through stabilization of MgADP at the channel site. K1348A and D1469N mutations attenuated the effect of openers on KATP channel activity. Opener‐induced channel activation was also inhibited by the creatine kinase/creatine phosphate system that removes ADP from the channel complex. Thus, the KATP channel complex functions not only as a K+ conductance, but also as an enzyme regulating nucleotide‐dependent channel gating through an intrinsic ATPase activity of the SUR subunit. Modulation of the channel ATPase activity and/or scavenging the product of the ATPase reaction provide novel means to regulate cellular functions associated with KATP channel opening. —Bienengraeber, M. , Alekseev, A. E. , Abraham, M. R. , Carrasco, A. J., Moreau, C. , Vivaudou, M. , Dzeja, P. P., Terzic, A. ATPase activity of the sulfonylurea receptor: a catalytic function for the KATP channel complex. FASEB J. 14, 1943–1952 (2000)
Lipoprotein-associated coagulation inhibitor.

: TF mediated initiation of coagulation appears to play a critical role in normal hemostasis and probably pathologic thrombosis as well. Although teleological considerations would seem to suggest that a specific regulator of this process should exist, and although the presence in plasma of such an inhibitor was documented many years ago, it was not until the past five years that the inhibitor was characterized and its mechanism of action defined. LACI produces factor Xa-dependent feedback initiation of the VIIa/TF catalytic complex. The mechanism of this feedback inhibition is novel. First, LACI, a multi-headed protease inhibitor, binds factor Xa, a product of VIIa/TF catalysis, at one of its inhibitory domains. The Xa-LACI complex, possibly acting as a pseudosubstrate, then is able to bind to VIIa/TF in an appropriate conformation such that a second inhibitory domain of LACI is positioned to interact with factor VIIa in the VIIa/TF complex. Whether such a unique means of eliciting feedback inhibition in a protease cascade is repeated in nature is unknown. The existence of LACI appears to help explain the clinical need for both "extrinsic" and "intrinsic" coagulation pathways. In addition, data to the present are consistent with the notion that, in normal hemostasis at least, TF is responsible for an initial burst of factor Xa generation which provides sufficient thrombin to induce the aggregation of platelets and the activation of the critical coagulation cofactors factor V and factor VIII. Ultimate and persistent hemostasis, however, appears to require the continued production of additional factor Xa through the action of factor IXa and factor VIII. The fact that patients with factor XI deficiency suffers a variable but usually mild bleeding diathesis suggests that under certain conditions the initial burst of factor IXa formed through the action of VIIa/TF is insufficient and supplemental factor IXa generated by factor XIa is needed for normal hemostasis. The mechanism by which this factor XIa is generated in vivo, however, has not been determined. We stress that the predicted in vivo role of LACI is simply that--a prediction based on its known in vitro properties. Documentation of its physiologic importance remains to be provided and is an area of active research. Further, although significant progress has been made over the past few years in the characterization of LACI, many questions remain unanswered. For example: What is the mechanism for LACI's association with lipoproteins in plasma? What function, if any, does the third Kunitz-type protease inhibitor domain in LACI serve? (ABSTRACT TRUNCATED AT 400 WORDS)
Individual and Bivalent Vaccines Based on Alphavirus Replicons Protect Guinea Pigs against Infection with Lassa and Ebola Viruses

ABSTRACT Lassa and Ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. Although lethal human disease outbreaks have been confined so far to sub-Saharan Africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into North America and Europe. In the present study, we developed experimental individual vaccines for Lassa virus and bivalent vaccines for Lassa and Ebola viruses that are based on an RNA replicon vector derived from an attenuated strain of Venezuelan equine encephalitis virus. The Lassa and Ebola virus genes were expressed from recombinant replicon RNAs that also encoded the replicase function and were capable of efficient intracellular self-amplification. For vaccinations, the recombinant replicons were incorporated into virus-like replicon particles. Guinea pigs vaccinated with particles expressing Lassa virus nucleoprotein or glycoprotein genes were protected from lethal challenge with Lassa virus. Vaccination with particles expressing Ebola virus glycoprotein gene also protected the animals from lethal challenge with Ebola virus. In order to evaluate a single vaccine protecting against both Lassa and Ebola viruses, we developed dual-expression particles that expressed glycoprotein genes of both Ebola and Lassa viruses. Vaccination of guinea pigs with either dual-expression particles or with a mixture of particles expressing Ebola and Lassa virus glycoprotein genes protected the animals against challenges with Ebola and Lassa viruses. The results showed that immune responses can be induced against multiple vaccine antigens coexpressed from an alphavirus replicon and suggested the possibility of engineering multivalent vaccines based upon alphavirus vectors for arenaviruses, filoviruses, and possibly other emerging pathogens.
Advances in the Treatment of Childhood Acute Lymphoblastic Leukemia

In recent decades, survival rates for childhood acute lymphoblastic leukemia have improved remarkably, as demonstrated by risk-stratified, prospective multicenter studies. Treatment protocols have evolved and become better matched to both prognostic factors and treatment responses. Recently, new molecular prognostic factors have been discovered in leukemia genomic studies. New tumor subtypes with independent gene expression profiles have also been characterized. Furthermore, therapies targeted to specific candidate mutations are being identified to broaden therapeutic options for patients with poor prognoses. Many new drugs are in clinical trials and immunotherapy is attracting significant interest for the treatment of recurrent or refractory disease in childhood acute lymphoblastic leukemia. pISSN 2233-5250 / eISSN 2233-4580 https://doi.org/10.15264/cpho.2019. 26.1. 12 Clin Pediatr Hematol Oncol 2019;26:12∼26
Development of the Neuromuscular Junction

The neuromuscular junction (NMJ) is the peripheral cholinergic synapse between a motor neuron and skeletal muscle fiber (Fig. 1). It is the only synapse, in both invertebrates and vertebrates, whose structure and function are sufficiently well understood that the mechanisms governing its development can be analyzed. Although some information learned about the NMJ has allowed for improved understanding of the more difficult to study central nervous system synapses, the primary result of NMJ research is that more is known about the structure, biochemistry, and physiology of it than of any other synapse. Because the clinical practice of anesthesia routinely impacts on NMJ function, it is self-evident that a full understanding of the normal function and physiology of this synapse is highly desirable. This chapter aims to make clear the relevance of understanding the development of the NMJ to clinical practice. Particular effort will be made to highlighting recent advances in this field that are likely to have a significant impact on the clinical practice of anesthesia.
IAMIN: An Infrastructure-aware Middleware for the Reconfiguration of Unstructured Peer-to-Peer Overlay Networks

Peer to peer networks have become one of the most popular networking methods because of their flexibility and many use cases such as file sharing and distributed computations. Unstructured overlay peer to peer networks are one of key components of peer to peer systems that are considerable because of their low cost in network construction and maintenance. One of the main challenges in unstructured peer to peer overlay networks is the topology mismatch between overlay network and the underlying physical infrastructure. The root of this challenge is lack of awareness about peers in the network infrastructure during connection to and disconnection from overlay network, in addition to the neighbor selection mechanism in the overlay network. Different types of awareness of network infrastructure includes awareness of the location of internet service providers. Also awareness of proximity, geographical location and resources of peers. In this article we present a middleware which configures overlay network by using public measurements and the estimated delay among peers in order to have the most conformity with the topology of physical infrastructure. To evaluate the performance, our middleware is implemented on the top of Gnutella which is an unstructured overlay peer-to-peer network. Our simulations show that our middleware enhances the conformity of overlay network to the topology of physical network infrastructure. In addition, it improved the average throughput and the average delay.
Anti-Hepatitis B Virus Activity in Vitro of Combinations of Tenofovir with Nucleoside/nucleotide Analogues

Background: Long-term management of some chronic hepatitis B patients might require combination therapy using drugs with distinct resistance profiles to sustain viral suppression and to reduce the resistance-associated failure. Tenofovir disoproxil fumarate (TDF), approved for hepatitis B virus (HBV) and HIV-1 treatment, is active against wild-type HBV and HBV containing YMDD mutations, which confer resistance to emtricitabine (FTC), lamivudine (3TC) and telbivudine (LdT) and contribute to entecavir (ETV) resistance. We therefore evaluated the in vitro anti-HBV activity of tenofovir (TFV), the active parent drug of TDF, combined with FTC, 3TC, ETV, LdT and adefovir (AFV). Methods: The anti-HBV activities of the compounds were tested using the AD38 cell line that expresses wild-type HBV from a tetracycline-controllable promoter. Intracellular HBV DNA levels were quantified using real-time PCR assay and cytotoxicities were assessed with XTT assays. The antiviral data of the drug combinations were evaluated using MacSynergy analyses on the basis of the Bliss independence model as well as isobologram analyses on the basis of the Loewe additivity theory. Results: All drug combinations tested, FTC+TFV, 3TC+TFV, ETV+TFV, LdT+TFV and AFV+TFV, showed additive antiviral interactions as analysed by MacSynergy. Isobologram analyses revealed that these combination pairs were additive, with the exception of FTC+TFV, which demonstrated slight synergistic activity. No cytotoxic or antagonistic effects were observed with any of the combinations tested. Conclusions: The combination of TFV with FTC, 3TC, ETV, LdT or AFV had additive to slightly synergistic anti-HBV effects in vitro. These results support the use of TDF as a component in combination regimens with currently available anti-HBV nucleoside analogues.