Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutting Edge: Plasmodium falciparum Induces Trained Innate Immunity

Malarial infection in naive individuals induces a robust innate immune response. In the recently described model of innate immune memory, an initial stimulus primes the innate immune system to either hyperrespond (termed training) or hyporespond (tolerance) to subsequent immune challenge. Previous work in both mice and humans demonstrated that infection with malaria can both serve as a priming stimulus and promote tolerance to subsequent infection. In this study, we demonstrate that initial stimulation with Plasmodium falciparum–infected RBCs or the malaria crystal hemozoin induced human adherent PBMCs to hyperrespond to subsequent ligation of TLR2. This hyperresponsiveness correlated with increased H3K4me3 at important immunometabolic promoters, and these epigenetic modifications were also seen in Kenyan children naturally infected with malaria. However, the use of epigenetic and metabolic inhibitors indicated that the induction of trained immunity by malaria and its ligands may occur via a previously unrecognized mechanism(s).
Metal nanoparticles: The protective nanoshield against virus infection

Abstract Re-emergence of resistance in different pathogens including viruses are the major cause of human disease and death, which is posing a serious challenge to the medical, pharmaceutical and biotechnological sectors. Though many efforts have been made to develop drug and vaccines against re-emerging viruses, researchers are continuously engaged in the development of novel, cheap and broad-spectrum antiviral agents, not only to fight against viruses but also to act as a protective shield against pathogens attack. Current advancement in nanotechnology provides a novel platform for the development of potential and effective agents by modifying the materials at nanolevel with remarkable physicochemical properties, high surface area to volume ratio and increased reactivity. Among metal nanoparticles, silver nanoparticles have strong antibacterial, antifungal and antiviral potential to boost the host immunity against pathogen attack. Nevertheless, the interaction of silver nanoparticles with viruses is a largely unexplored field. The present review discusses antiviral activity of the metal nanoparticles, especially the mechanism of action of silver nanoparticles, against different viruses such HSV, HIV, HBV, MPV, RSV, etc. It is also focused on how silver nanoparticles can be used in therapeutics by considering their cytotoxic level, to avoid human and environmental risks.
Mapping the termini and intron of the spliced immediate-early transcript of equine herpesvirus 1

Equine herpesvirus 1 (EHV-1) has been shown to synthesize a 6.0-kilobase (kb) species of immediate-early (IE) mRNA in productively infected cells. This IE gene region maps within the outer portion (map units 0.79 to 0.83 and 0.96 to 1.00) of the two inverted repeat segments of the short genomic region, and elucidation of its DNA sequence has revealed multiple potential open reading frames (ORFs), including a major ORF of 4,461 nucleotides (F. J. Grundy, R. P. Baumann, and D. J. O'Callaghan, Virology 172:223-236, 1989). Analyses of IE polypeptides synthesized in EHV-1-infected cells (in vivo) and in vitro translation of hybrid-selected IE mRNA indicated that multiple species of IE proteins are encoded by this IE mRNA species. To address the nature of the 6.0-kb IE RNA species, Northern (RNA) blot hybridization, S1 nuclease mapping, and primer extension analyses have been employed. These data revealed that no major introns were detected within the body of the IE transcript. However, the IE mRNA was shown to be spliced at the 5' terminus, such that a 372-base intron containing two small ORFs (19 and 51 amino acids) was removed from the leader region of the transcript. This splicing event reduced the leader region from 625 to 253 bases. S1 and primer extension analyses of the 5' terminus of this transcript revealed that the transcription initiation site is located 24 to 26 bases downstream of the consensus TATAAA motif. The 3' transcription termination site was mapped by S1 nuclease analysis to approximately 10 to 20 bases downstream of the polyadenylation signal, AATAAA. The distance from the stop codon of the major ORF to the polyadenylation site is approximately 300 bases. Results from S1 nuclease experiments indicated that splicing does not occur at the 3' terminus. These studies indicated that the EHV-1 6.0-kb IE mRNA is spliced at the 5' terminus and that alternative splicing of this transcript may function in regulating translation of the IE mRNA species.
Advancing the Accuracy of Protein Fold Recognition by Utilizing Profiles From Hidden Markov Models

Protein fold recognition is an important step towards solving protein function and tertiary structure prediction problems. Among a wide range of approaches proposed to solve this problem, pattern recognition based techniques have achieved the best results. The most effective pattern recognition-based techniques for solving this problem have been based on extracting evolutionary-based features. Most studies have relied on the Position Specific Scoring Matrix (PSSM) to extract these features. However it is known that profile-profile sequence alignment techniques can identify more remote homologs than sequence-profile approaches like PSIBLAST. In this study we use a profile-profile sequence alignment technique, namely HHblits, to extract HMM profiles. We will show that unlike previous studies, using the HMM profile to extract evolutionary information can significantly enhance the protein fold prediction accuracy. We develop a new pattern recognition based system called HMMFold which extracts HMM based evolutionary information and captures remote homology information better than previous studies. Using HMMFold we achieve up to 93.8% and 86.0% prediction accuracies when the sequential similarity rates are less than 40% and 25%, respectively. These results are up to 10% better than previously reported results for this task. Our results show significant enhancement especially for benchmarks with sequential similarity as low as 25% which highlights the effectiveness of HMMFold to address this problem and its superiority over previously proposed approaches found in the literature. The HMMFold is available online at: http://sparks-lab.org/pmwiki/download/index.php? Download =HMMFold.tar. bz2.
Sites and Regulation of Auxin Biosynthesis in Arabidopsis Roots

Auxin has been shown to be important for many aspects of root development, including initiation and emergence of lateral roots, patterning of the root apical meristem, gravitropism, and root elongation. Auxin biosynthesis occurs in both aerial portions of the plant and in roots; thus, the auxin required for root development could come from either source, or both. To monitor putative internal sites of auxin synthesis in the root, a method for measuring indole-3-acetic acid (IAA) biosynthesis with tissue resolution was developed. We monitored IAA synthesis in 0.5- to 2-mm sections of Arabidopsis thaliana roots and were able to identify an important auxin source in the meristematic region of the primary root tip as well as in the tips of emerged lateral roots. Lower but significant synthesis capacity was observed in tissues upward from the tip, showing that the root contains multiple auxin sources. Root-localized IAA synthesis was diminished in a cyp79B2 cyp79B3 double knockout, suggesting an important role for Trp-dependent IAA synthesis pathways in the root. We present a model for how the primary root is supplied with auxin during early seedling development.
A Platform to View Huntingtin Exon 1 Aggregation Flux in the Cell Reveals Divergent Influences from Chaperones hsp40 and hsp70

Background: How misfolded proteins such as mutant huntingtin aggregate in the cell remains enigmatic. Results: We built a platform to view how aggregation proceeds and assessed the impact of quality control chaperones hsp40 and hsp70. Conclusion: hsp70 enhanced survival of cells with aggregates; hsp40 suppressed aggregation. Significance: We developed a new toolkit to illustrate the impact of protein aggregation on cell biology. Our capacity for tracking how misfolded proteins aggregate inside a cell and how different aggregation states impact cell biology remains enigmatic. To address this, we built a new toolkit that enabled the high throughput tracking of individual cells enriched with polyglutamine-expanded Htt exon 1 (Httex1) monomers, oligomers, and inclusions using biosensors of aggregation state and flow cytometry pulse shape analysis. Supplemented with gel filtration chromatography and fluorescence-adapted sedimentation velocity analysis of cell lysates, we collated a multidimensional view of Httex1 aggregation in cells with respect to time, polyglutamine length, expression levels, cell survival, and overexpression of protein quality control chaperones hsp40 (DNAJB1) and hsp70 (HSPA1A). Cell death rates trended higher for Neuro2a cells containing Httex1 in inclusions than with Httex1 dispersed through the cytosol at time points of expression over 2 days. hsp40 stabilized monomers and suppressed inclusion formation but did not otherwise change Httex1 toxicity. hsp70, however, had no major effect on aggregation of Httex1 but increased the survival rate of cells with inclusions. hsp40 and hsp70 also increased levels of a second bicistronic reporter of Httex1 expression, mKate2, and increased total numbers of cells in culture, suggesting these chaperones partly rectify Httex1-induced deficiencies in quality control and growth rates. Collectively, these data suggest that Httex1 overstretches the protein quality control resources and that the defects can be partly rescued by overexpression of hsp40 and hsp70. Importantly, these effects occurred in a pronounced manner for soluble Httex1, which points to Httex1 aggregation occurring subsequently to more acute impacts on the cell.
A comparison of the effects of tamsulosin and alfuzosin on neurally evoked increases in bladder neck and seminal vesicle pressure in rats

To assess the effects of the α1‐adrenoceptor antagonists alfuzosin and tamsulosin on the physiological events associated with ejaculation in the rat, because when these drugs are used for treating symptomatic benign prostatic hyperplasia in men they may affect ejaculation by impairing bladder neck closure and seminal vesicle contraction.
Increased insulin sensitivity is associated with reduced insulin and glucagon secretion and increased insulin clearance in man.

Insulin secretion is increased in insulin resistance. In this study, we examined whether high insulin sensitivity results in low insulin secretion. Twelve male master athletes [age 25.6 +/- 4.1 (mean +/- SD) yr] and seven male sedentary students (age 25.0 +/- 2.0 yr) underwent a hyperinsulinemic, euglycemic clamp and a glucose-dependent arginine stimulation test. Athletes had high insulin sensitivity [230 +/- 18 vs. 92 +/- 12 (nmol glucose/kg.min)/(pmol insulin/liter), P < 0.001] and low insulin response to arginine (at fasting glucose 135 +/- 22 vs. 394 +/- 60 pmol/liter, P < 0.001), which resulted in unaltered disposition index (32.8 +/- 3.8 vs. 33.5 +/- 3.3 micro mol glucose/kg.min, NS). Also, the C-peptide response to arginine was reduced (at fasting glucose 0.71 +/- 0.09 vs. 0.89 +/- 0.09 nmol/liter, P = 0.034). However, the C-peptide reduction was not as large as the insulin reduction yielding increased disposition index in athletes when calculated from C-peptide data (184 +/- 9 vs. 76 +/- 11 micro mol glucose/kg.min, P < 0.001). This difference is explained by increased insulin clearance among the athletes during the first 5 min after arginine (81.1% +/- 1.8% vs. 53.6% +/- 4.7%, P < 0.001). Also, the glucagon response to arginine was reduced in the athletes (58.8 +/- 6.7 vs. 90.1 +/- 9.9 ng/liter at fasting glucose, P = 0.009). We conclude that high insulin sensitivity results in low islet hormone secretion and increased insulin clearance.
Gelling behaviour of natural ester transformer liquid under thermal ageing

There have been increasing interests on natural esters as potential substitutes to conventional mineral oils in transformers, due to their less-flammable, non-toxic and environmentally friendly properties. The application has been successful in traction and distribution transformers with sealed type. But the susceptibility to oxidation and hence the suspected gelling behaviour prevent the application of natural esters in free-breathing transformers. This paper presents an experimental study of gelling/oxidation behaviour of thin films of a natural ester under thermal ageing. Ageing experiments were carried out with presence of air at different temperatures of 120 °C and 20 °C and durations up to 2 years. The gelling/oxidation behaviour of natural ester was evaluated in terms of changes in viscosity and acidity. Results showed that both viscosity and acidity can be used to assess gelling/oxidation behaviour of natural ester from initial liquid phase to eventually gelled form. In addition to temperature, the thickness of the thin film samples has a significant effect on the gelling speed, i.e. the thinner of the film, the faster of the gelling speed.
N-acetylgalactosamine on the putative insect receptor aminopeptidase N is recognised by a site on the domain III lectin-like fold of a Bacillus thuringiensis insecticidal toxin.

Binding of the insecticidal Bacillus thuringiensis Cry1Ac toxin to the putative receptor aminopeptidase N is specifically inhibited by N-acetylgalactosamine (GalNAc), suggesting that this toxin recognises GalNAc on the receptor. A possible structural basis for involvement of domain III of the toxin in carbohydrate-mediated receptor recognition was noted in the similarity between the domain III fold of the related toxin Cry3A and a carbohydrate-binding domain in the 1,4-beta-glucanase from Cellulomonas fimi. This possibility was investigated by making selected mutations in domain III of the Cry1Ac delta-endotoxin. Mutagenesis of residues Asn506, Gln509 or Tyr513 resulted in toxins with reduced binding and a slower rate of pore formation in Manduca sexta midgut membrane vesicles compared to the wild-type Cry1Ac. These mutants also showed reduced binding to the 120 kDa Cry1Ac putative receptor aminopeptidase N. Unlike the wild-type toxin, binding of the triple mutant N506D,Q509E,Y513A (Tmut) to M. sexta midgut membrane vesicles could not be inhibited by GalNAc. These data indicate that GalNAc binding is located on domain III of Cry1Ac and therefore support a lectin-like role for this domain. A preliminary analysis of the Cry1Ac crystal structure locates Asn506, Gln509 and Tyr513 in a region on and adjacent to beta-16 in domain III, which has a unique conformation compared to the other known Cry structures. These residues are in a favourable position to interact with either soluble or protein-bound carbohydrate.
Evaluation of Human Rights, Civics and Democracy Curriculum through Eisner s Evaluation Framework

Human Rights, Civics and Democracy Curriculum for 4th graders was began to be implemented in 2015-2016 academic year. In this study, we aim to evaluate this curriculum regarding the universality of human rights concept; the appropriateness of the curriculum with its educational goals, content, instructional material and methods in terms of students’ cognitive level and finally teacher competencies to teach this course. A qualitative intrinsic case study method was utilized. The data was collected through document analysis; eight-hours of classroom observation, and semi-structured interviews with seven elementary school teachers and six “experts”. Eisner’s Educational Connoisseurship and Criticism Model was used as an evaluation framework. Deductive content analysis was used to analyze the data and to illuminate specific details about the case under investigation. Results showed that attainments and content were consistent with the universality of human rights perspective; also, instruction and assessment methods were consistent with the philosophy (constructivism) of the curriculum. However, the course material, as regards to its aims, content and philosophy; and the practices applied inside the classroom were highly inconsistent with the goals of the curriculum.
Toward Implementing an MRI-Based PET Attenuation-Correction Method for Neurologic Studies on the MR-PET Brain Prototype

Several factors have to be considered for implementing an accurate attenuation-correction (AC) method in a combined MR-PET scanner. In this work, some of these challenges were investigated, and an AC method based entirely on the MRI data obtained with a single dedicated sequence was developed and used for neurologic studies performed with the MR-PET human brain scanner prototype. Methods: The focus was on the problem of bone–air segmentation, selection of the linear attenuation coefficient for bone, and positioning of the radiofrequency coil. The impact of these factors on PET data quantification was studied in simulations and experimental measurements performed on the combined MR-PET scanner. A novel dual-echo ultrashort echo time (DUTE) MRI sequence was proposed for head imaging. Simultaneous MR-PET data were acquired, and the PET images reconstructed using the proposed DUTE MRI–based AC method were compared with the PET images that had been reconstructed using a CT-based AC method. Results: Our data suggest that incorrectly accounting for the bone tissue attenuation can lead to large underestimations (>20%) of the radiotracer concentration in the cortex. Assigning a linear attenuation coefficient of 0.143 or 0.151 cm−1 to bone tissue appears to give the best trade-off between bias and variability in the resulting images. Not identifying the internal air cavities introduces large overestimations (>20%) in adjacent structures. On the basis of these results, the segmented CT AC method was established as the silver standard for the segmented MRI-based AC method. For an integrated MR-PET scanner, in particular, ignoring the radiofrequency coil attenuation can cause large underestimations (i.e., ≤50%) in the reconstructed images. Furthermore, the coil location in the PET field of view has to be accurately known. High-quality bone–air segmentation can be performed using the DUTE data. The PET images obtained using the DUTE MRI– and CT-based AC methods compare favorably in most of the brain structures. Conclusion: A DUTE MRI–based AC method considering all these factors was implemented. Preliminary results suggest that this method could potentially be as accurate as the segmented CT method and could be used for quantitative neurologic MR-PET studies.
Positive inotropic and lusitropic effects of HNO/NO− in failing hearts: Independence from β-adrenergic signaling

Nitroxyl anion (HNO/NO−), the one-electron reduced form of nitric oxide (NO), induces positive cardiac inotropy and selective venodilation in the normal in vivo circulation. Here we tested whether HNO/NO− augments systolic and diastolic function of failing hearts, and whether contrary to NO/nitrates such modulation enhances rather than blunts β-adrenergic stimulation and is accompanied by increased plasma calcitonin gene-related peptide (CGRP). HNO/NO− generated by Angelis' salt (AS) was infused (10 μg/kg per min, i.v.) to conscious dogs with cardiac failure induced by chronic tachycardia pacing. AS nearly doubled contractility, enhanced relaxation, and lowered cardiac preload and afterload (all P < 0.001) without altering plasma cGMP. This contrasted to modest systolic depression induced by an NO donor diethylamine(DEA)/NO or nitroglycerin (NTG). Cardiotropic changes from AS were similar in failing hearts as in controls despite depressed β-adrenergic and calcium signaling in the former. Inotropic effects of AS were additive to dobutamine, whereas DEA/NO blunted β-stimulation and NTG was neutral. Administration of propranolol to nonfailing hearts fully blocked isoproterenol stimulation but had minimal effect on AS inotropy and enhanced lusitropy. Arterial plasma CGRP rose 3-fold with AS but was unaltered by DEA/NO or NTG, supporting a proposed role of this peptide to HNO/NO− cardiotropic action. Thus, HNO/NO− has positive inotropic and lusitropic action, which unlike NO/nitrates is independent and additive to β-adrenergic stimulation and stimulates CGRP release. This suggests potential of HNO/NO− donors for the treatment of heart failure.
Design of a Distributed Oscillator in 130 nm SOI MOS Technology

In this paper, the design and the results of a silicon-on-insulator (SOI) CMOS distributed amplifier (DA) and oscillator are presented. The four stage cascode DA (CDA) is designed with a 130 nm SOI floating body n-MOSFET in each stage requiring a chip area of 0.75 mm2. A gain of 7 dB and a unity-gain bandwidth of 26 GHz are measured at 1.4 V supply voltage with a measured power consumption of 54 mW. The CDA circuit has been extended to design a cascode distributed oscillator (CDO) showing a 3 dBm carrier at 10 GHz oscillating frequency, for 2.5 V supply voltage
Defining an evaluation framework for digital cities implementation

Digital cities are nowadays an important topic, both for social and for economic studies. However, the main papers about digital cities regard the technical implementation of infrastructures and networks, or the shaping of urban spaces. Few attention is paid to the socio-economic value of digital cities and to the concrete benefits deriving from their implementation, together with costs and burdens linked with the governance and maintenance of technical and legal platforms. The goal of this paper is to define an evaluation framework to assess the quality and value of a digital city environment, including all the actors involved both in its building and in its regulation, in its use and in its economic exploitation. The evaluation framework should support the choices regarding the prioritization of programs and technical solutions, considering the socio-economic impacts of the digital city on all the project stakeholders. Moreover, the same framework should also be able to measure ex-post benefits really gained by all the stakeholder categories, and to support improvements of the platform and further implementations. The framework design is based on a theoretical investigation on international literature about this topic; its realization will involve companies, local governments, infrastructure providers, users.
Depth map compression via edge-based inpainting

This work presents a novel intra-frame coding scheme for depth maps that makes use of the characteristics of depth images: large smooth areas separated by sharp edges. The proposed method is block-based, thus can be easily integrated into H.264/AVC framework. By using the extracted edge information, each block is divided into several regions and each region is handled independently. Most regions are predicted via image inpainting based on the Laplace equation. The others that could not be inpainted are predicted by their mean values or a default value. Both the extracted edge information and the mean values are compressed under the rate-distortion (RD) optimization principle. Compared with H.264/AVC, the results show that the proposed scheme achieves both PSNR gain in depth maps and visual quality improvement in rendered views.