Miracle-dz/UniFAR-FTUs huggingface dataset:
Amoeba/Amoebal Symbiont Genetic Transfers: Lessons from Giant Virus Neighbours

Free-living amoebae serve as hosts for a variety of amoebae-resisting microorganisms, including giant viruses and certain bacteria. The latter include symbiotic bacteria as well as bacteria exhibiting a pathogenic phenotype towards amoebae. Amoebae-resisting bacteria have been shown to be widespread in water and to use the amoebae as a reservoir, a replication niche, a protective armour as well as a training ground to select virulence traits allowing survival in the face of microbicidal effects of macrophages, the first line of defense against invading pathogens. More importantly, amoebae play a significant role as a melting pot for genetic exchanges. These ecological and evolutionary roles of amoebae might also be at play for giant viruses and knowledge derived from the study of amoebae-resisting bacteria is useful for the study and understanding of interactions between amoebae and giant viruses. This is especially important since some genes have spread in all domains of life and the exponential availability of eukaryotic genomes and metagenomic sequences will allow researchers to explore these genetic exchanges in a more comprehensive way, thus completely changing our perception of the evolutionary history of organisms. Thus, a large part of this review is dedicated to report current known gene exchanges between the different amoebae-resisting organisms and between amoebae and the internalized bacteria.
Convex Modeling and Optimization of a Vehicle Powertrain Equipped With a Generator–Turbine Throttle Unit

This paper investigates an internal combustion (gasoline) engine throttled by a generator-turbine unit. Apart from throttling, the purpose of this device is to complement the operation of a conventional car alternator and support its downsizing by introducing an additional source of energy for the electric auxiliaries. Its energy recovery potential is examined by employing a novel, convex approach to modeling and optimization of the resulting vehicle powertrain. For a given gear-shifting strategy, the proposed method allows the computation of optimal control trajectories, e.g., the optimal engine fuel, alternator, and turbine power, as well as of optimal design parameters, i.e., the optimal battery, alternator and turbogenerator size. The conducted numerical case study shows that a generator-turbine throttle unit has a potential to reduce the total operational (fuel) and component (battery, alternator, and turbogenerator) costs by typically 2%–6%, depending on factors such as the engine size and the choice of a driving cycle.
Molecular analysis of the role of streptococcal pyrogenic exotoxin A (SPEA) in invasive soft‐tissue infection resulting from Streptococcus pyogenes

Epidemiological studies strongly implicate the bacterial superantigen, streptococcal pyrogenic exotoxin A (SPEA), in the pathogenesis of necrotizing soft‐tissue infection and toxic shock syndrome resulting from Streptococcus pyogenes. SPEA can act as a superantigen and cellular toxin ex vivo, but its role during invasive streptococcal infection is unclear. We have disrupted the wild‐type spea gene in an M1 streptococcal isolate. Supernatants from toxin‐negative mutant bacteria demonstrated a 50% reduction in pro‐mitogenic activity in HLA DQ‐positive murine splenocyte culture, and up to 20% reduction in activity in human PBMC culture. Mutant and wild‐type bacteria were then compared in mouse models of bacteraemia and streptococcal muscle infection. Disruption of spea was not associated with attenuation of virulence in either model. Indeed, a paradoxical increase in mutant strain‐induced mortality was seen after intravenous infection. Intramuscular infection with the SPEA‐negative mutant led to increased bacteraemia at 24 h and a reduction in neutrophils at the site of primary muscle infection. Purified SPEA led to a dose‐dependent increase in peritoneal neutrophils 6 h after administration. SPEA is not a critical virulence factor in invasive soft‐tissue infection or bacteraemia caused by S. pyogenes, and it could have a protective role in murine immunity to pyogenic infection. The role of this toxin may be different in hosts with augmented superantigen responsiveness.
The periodontal pathogen Porphyromonas gingivalis harnesses the chemistry of the mu-oxo bishaem of iron protoporphyrin IX to protect against hydrogen peroxide.

The major haem component in the black pigment of Porphyromonas gingivalis is the mu-oxo bishaem of iron protoporphyrin IX and formation and cell-surface binding of this haem species is proposed as an extracellular buffer against reactive oxidants [Smalley, J.W. et al. (1998) Biochem. J. 331, 681-685]. P. gingivalis cells grown in the presence of the mu-oxo bishaem were protected against H(2)O(2) compared to control cells grown without it. When added to the growth medium, soluble mu-oxo bishaem inactivated H(2)O(2) and supported cell growth. Cells carrying a surface layer of mu-oxo bishaem were less susceptible to peroxidation by H(2)O(2). Cell-surface haems were slowly destroyed during reaction with H(2)O(2). Binding of mu-oxo bishaem by P. gingivalis may aid survival during neutrophil attack through inactivation of hydrogen peroxide.
The solar cycle as seen by low-ℓ p-mode frequencies: comparison with global and decomposed activity proxies

We present a detailed study of variations observed in low-angular degree solar p-mode frequencies during solar cycles 22 and 23, and their relation to global and spatially decomposed proxies of the surface activity. To do so, we have analysed 11 yr of unresolved (Sun-as-a-star) Doppler velocity observations of the solar disc made by the Birmingham Solar-Oscillations Network (BiSON). The sensitivity of these observations to different azimuthal orders, m, is such that for the degree range studied (0 less than or equal to l less than or equal to 2) extracted frequencies can be regarded as providing a measure of the response of the sectoral modes (with \m\ = l). After allowing for the dependence of the frequency shifts on mode frequency and inertia, we find the average = 0 shift is significantly weaker than that at = 2; the magnitude of the average = 1 shift lies in between the two. The comparative sizes of the shifts are observed to match those of the corresponding spherical harmonic (Legendre) components of both the Kitt Peak magnetogram (KPMI) and He I equivalent width activity indices, and reflect, therefore, the sensitivity of the observed mode components to the distribution of activity over the solar surface (i.e. a 'spatial' contribution to the shifts). When the falling and rising parts of the cycles are analysed independently, we uncover a significant difference in behaviour at l = 1. Possible reasons for this are discussed.
Cross-Modal Retrieval via Deep and Bidirectional Representation Learning

Cross-modal retrieval emphasizes understanding inter-modality semantic correlations, which is often achieved by designing a similarity function. Generally, one of the most important things considered by the similarity function is how to make the cross-modal similarity computable. In this paper, a deep and bidirectional representation learning model is proposed to address the issue of image-text cross-modal retrieval. Owing to the solid progress of deep learning in computer vision and natural language processing, it is reliable to extract semantic representations from both raw image and text data by using deep neural networks. Therefore, in the proposed model, two convolution-based networks are adopted to accomplish representation learning for images and texts. By passing the networks, images and texts are mapped to a common space, in which the cross-modal similarity is measured by cosine distance. Subsequently, a bidirectional network architecture is designed to capture the property of the cross-modal retrieval-the bidirectional search. Such architecture is characterized by simultaneously involving the matched and unmatched image-text pairs for training. Accordingly, a learning framework with maximum likelihood criterion is finally developed. The network parameters are optimized via backpropagation and stochastic gradient descent. A great deal of experiments are conducted to sufficiently evaluate the proposed method on three publicly released datasets: IAPRTC-12, Flickr30k, and Flickr8k. The overall results definitely show that the proposed architecture is effective and the learned representations have good semantics to achieve superior cross-modal retrieval performance.
Evolving therapeutic paradigms for multiple myeloma: back to the future

Abstract Multiple myeloma (MM) is an ancient disease, but until the alkylating agent melphalan was found to have anti-myeloma properties in the 1950s there was virtually no effective therapy. By the late 1960s, extended dosing with melphalan and prednisone tripled survival from diagnosis and became the standard of care for newly diagnosed MM. “Maintenance therapy” to prolong survival through sustained disease control following induction chemotherapy was sought by 1970, but early strategies were ineffective and toxic. Subsequent applications of high-dose therapy (HDT)/autologous stem cell transplant (ASCT) changed the treatment paradigm for MM from extended dosing to an intensive strategy designed to eradicate the malignant cells in a single course of treatment. Although HDT-ASCT resulted in prolonged duration of remission and improved survival, the vast majority of patients still relapsed. Interferon (IFN) and glucocorticoid maintenance therapies demonstrated marginal improvements in outcomes but significant adverse effects. Novel agents introduced over the last decade have prolonged survival when given for maintenance following HDT-ASCT, but have also challenged the HDT-ASCT paradigm by achieving comparable remission rates when used alone as extended frontline therapy. This article reviews the evolution of therapeutic strategies for MM and discusses future questions facing MM investigators.
Human leukocyte antigen B27 selects for rare escape mutations that significantly impair hepatitis C virus replication and require compensatory mutations

Human leukocyte antigen B27 is associated with spontaneous viral clearance in hepatitis C virus (HCV) infection. Viral escape within the immunodominant, HLA‐B27‐restricted, HCV‐specific, cluster of differentiation (CD)8+ T‐cell epitope, nonstructural protein (NS)5B2841‐2849 (ARMILMTHF), has been shown to be limited by viral fitness costs as well as broad T‐cell cross‐recognition, suggesting a potential mechanism of protection by HLA‐B27. Here, we studied the subdominant HLA‐B27‐restricted epitope, NS5B2936‐2944 (GRAAICGKY), to further define the mechanisms of protection by HLA‐B27. We identified a unique pattern of escape mutations within this epitope in a large cohort of HCV genotype 1a–infected patients. The predominant escape mutations represented conservative substitutions at the main HLA‐B27 anchor residue or a T‐cell receptor contact site, neither of which impaired viral replication capacity, as assessed in a subgenomic HCV replicon system. In contrast, however, in a subset of HLA‐B27+ subjects, rare escape mutations arose at the HLA‐B27 anchor residue, R2937, which nearly abolished viral replication. Notably, these rare mutations only occurred in conjunction with the selection of two equally rare, and structurally proximal, upstream mutations. Coexpression of these upstream mutations with the rare escape mutations dramatically restored viral replication capacity from <5% to ≥70% of wild‐type levels. Conclusion: The selection of rare CTL escape mutations in this HLA‐B27‐restricted epitope dramatically impairs viral replicative fitness, unless properly compensated. These data support a role for the targeting of highly constrained regions by HLA‐B27 in its ability to assert immune control of HCV and other highly variable pathogens. (HEPATOLOGY 2011;)
Plasma membrane vesicles of opposite sidedness from soybean hypocotyls by preparative free-flow electrophoresis.

Absolute orientations (sidedness) of plasma membrane vesicles obtained in highly purified fractions by preparative free-flow electrophoresis and by aqueous two-phase partition were determined based on ATPase latency and morphological criteria. Free-flow electrophoresis yielded two plasma membrane fractions. One, the least electronegative and designated fraction ;E,' was pure plasma membrane. The other, more electronegative and designated fraction ;C,' was heavily contaminated by various other cellular membranes. Plasma membrane vesicles from both fraction C and fraction E partitioned into the upper phase with aqueous two-phase partitioning. Purified plasma membrane obtained from microsomes by two-phase partition (upper phase) when subjected to free-flow electrophoresis also yielded two fractions, one fraction co-migrated with fraction C and another fraction co-migrated with fraction E. Both fractions exhibited an ATPase activity sensitive to vanadate and insensitive to nitrate and azide. ATPase activity was used as a structure-linked latency marker for the inner membrane surface. Concanavalin A binding (linked to peroxidase) was used as an imposed electron microscope marker for the outer membrane surface. Fraction E vesicles showed low ATPase latency (two-fold or less) and weak reactivity with concanavalin A peroxidase. In contrast, fraction C vesicles were characterized by much greater latencies upon detergent treatment (sevenfold) and a strong reaction with concanavalin A peroxidase. Two-phase partition as the initial procedure for plasma membrane isolation, yielded mixtures of vesicles of both inside out and right-side out orientation. Free-flow electrophoresis resolved the plasma membrane isolates into vesicles from fraction C which were right-side out (cytoplasmic side in), and vesicles from fraction E which were wrong-side out (cytoplasmic side out). Therefore, the two methods used in series, provided highly purified membrane preparations of apparently homogenous vesicles of opposite known absolute orientations.
Practitioner review: computerized assessment of neuropsychological function in children: clinical and research applications of the Cambridge Neuropsychological Testing Automated Battery (CANTAB).

BACKGROUND Computers have been used for a number of years in neuropsychological assessment to facilitate the scoring, interpretation, and administration of a variety of commonly used tests. There has been recent interest in applying computerized technology to pediatric neuropsychological assessment, which poses unique demands based on the need to interpret performance relative to the child's developmental level. FINDINGS However, pediatric neuropsychologists have tended to implement computers in the scoring, but not administration, of tests. This trend is changing based on the work of experimental neuropsychologists who frequently combine data obtained from test batteries with lesion or neuroimaging data allowing descriptions of brain-behavior relations to be made with increasing confidence. One such battery is the Cambridge Neuropsychological Testing Automated Battery (CANTAB), and current studies in which the CANTAB has been used to measure executive functions in children are reviewed. CONCLUSIONS Computerized batteries of this type can record aspects of performance that are difficult for psychometrists to achieve, and these may reflect activity in developing neural networks with more sensitivity than can be achieved with traditional tests. However, before computerized test administration becomes a routine part of pediatric neuropsychological assessment, several obstacles must be overcome. Despite these limitations, it is concluded that computerized assessment can improve the field by facilitating the collection of normative and clinical data.
New P&O MPPT algorithm for FPGA implementation

This paper proposes an FPGA implementation of a new Maximum Power Point Tracking (MPPT) technique for Photovoltaic (PV) applications. The main idea is to develop an improved Perturb and Observe (P&O) MPPT control for an easy FPGA implementation. This new algorithm consists of a constant perturbation with an offset control which will make easier the FPGA PV power data acquisition process. This strategy of control has, in first time, been validated by simulations. After, some experimental results are obtained using Boost converter and FPGA MPPT control in real conditions for battery charging.
Cell type-specific fusion cofactors determine human immunodeficiency virus type 1 tropism for T-cell lines versus primary macrophages

Work in this laboratory previously demonstrated that the tropism of different human immunodeficiency type 1 isolates for infection of human CD4+ continuous cell lines (e.g., T-cell lines and HeLa-CD4 transformants) versus primary macrophages is associated with parallel intrinsic fusogenic specificities of the corresponding envelope glycoproteins (Envs). For T-cell line-tropic isolates, it is well established that the target cell must also contain a human-specific fusion cofactor(s) whose identity is unknown. In this study, we tested the hypothesis that the Env fusion specificities underlying T-cell line versus macrophage tropism are determined by distinct cell type-specific fusion cofactors. We applied a recombinant vaccinia virus-based reporter gene assay for Env-CD4-mediated cell fusion; the LAV and Ba-L Envs served as prototypes for T-cell line-tropic and macrophage-tropic isolates, respectively. We examined CD4+ promyeloctic and monocytic cell lines that are infectible by T-cell line-tropic isolates and become susceptible to macrophage-tropic strains only after treatment with differentiating agents. We observed parallel changes in fusion specificity: untreated cells supported fusion by the LAV but not the Ba-L Env, whereas cells treated with differentiating agents acquired fusion competence for Ba-L. These results suggest that in untreated cells, the block to infection by macrophage-tropic isolates is at the level of membrane fusion; furthermore, the differential regulation of fusion permissiveness for the two classes of Envs is consistent with the existence of distinct fusion cofactors. To test this notion directly, we conducted experiments with transient cell hybrids formed between CD4-expressing nonhuman cells (murine NIH 3T3) and different human cell types. Hybrids formed with HeLa cells supported fusion by the LAV Env but not by the Ba-L Env, whereas hybrids formed with primary macrophages showed the opposite specificity; hybrids formed between HeLa cells and macrophages supported fusion by both Envs. These results suggest the existence of cell type-specific fusion cofactors selective for each type of Env, rather than fusion inhibitors for discordant Env-cell combinations. Finally, analyses based on recombinant protein expression and antibody blocking did not support the proposals by others that the CD44 or CD26 antigens are involved directly in the entry of macrophage-tropic isolates.
Physical Activity Benefits the Skeleton of Children Genetically Predisposed to Lower Bone Density in Adulthood

Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high‐, and low‐impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome‐wide association study (GWAS)‐implicated BMD variants. We used dual‐energy X‐ray absorptiometry to estimate femoral neck, total hip, and spine areal‐BMD and total body less head (TBLH) bone mineral content (BMC) Z‐scores. The BMD genetic score was negatively associated with each bone Z‐score (eg, TBLH‐BMC: estimate = –0.03, p = 1.3 × 10−6). Total PA was positively associated with bone Z‐scores; these associations were driven by time spent in high‐impact PA (eg, TBLH‐BMC: estimate = 0.05, p = 4.0 × 10−10) and were observed even for children with lower than average bone Z‐scores. We found no evidence of PA‐adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA‐genetic score–Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH‐BMC in males (p interaction = 7.1 × 10−5), where PA was associated with higher TBLH‐BMC Z‐score among the BMD‐lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10−9). In conclusion, the beneficial effect of PA on bone, especially high‐impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS‐implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.
Circulating histones for predicting prognosis after cardiac surgery: a prospective study.

OBJECTIVES The objective of this study was to assess the perioperative changes in circulating histones and their relationships with other biomarkers and clinical outcomes after cardiac surgery with cardiopulmonary bypass (CPB) in patients. METHODS Forty-eight patients with congenital cardiac diseases undergoing corrective procedure with CPB were prospectively enrolled in this study. Circulating histones, N-terminal pro-brain natriuretic peptide (NT-proBNP), procalcitonin (PCT) and C-reactive protein (CRP) were measured preoperatively (T0) and at 0 (T1), 24 (T2), 48 (T3) and 72 (T4) h postoperatively. The relationships between biomarkers and clinical outcomes were analysed. RESULTS Circulating histones, NT-proBNP, PCT and CRP increased significantly postoperatively, with histones reaching the peak value earliest at T1. Circulating histone levels were higher in patients with adverse events. Receiver operating characteristic curve analysis showed that peak histone levels had a better predictive value for adverse events postoperatively. Peak histone levels correlated with the peak level of NT-proBNP (r = 0.563, P < 0.01), PCT (r = 0.551, P < 0.01), CRP (r = 0.606, P < 0.01) and clinical parameters such as ventilation time (r = 0.601, P < 0.01) and intensive care unit time (r = 0.623, P < 0.01). CONCLUSIONS Circulating histones reached peak levels faster than NT-proBNP, PCT and CRP. Furthermore, peak histone levels correlated with biomarkers and postoperative clinical outcomes. Circulating histones may be used as a prognostic indicator for patients after cardiac surgery with CPB. CLINICAL TRIALS ClinicalTrials.gov (ID: NCT02325765).
Fungal Malignant Otitis Externa: Pitfalls, Diagnosis, and Treatment

Hypothesis Oral voriconazole is a viable alternative modality treatment to traditionally used intravenous vancomycin in the treatment of malignant otitis externa (MOE). Background The incidence of MOE is on the rise, more so in Saudi Arabia where diabetes mellitus is endemic. Although Pseudomonas aeruginosa is the most common offending organism, we are observing an increasing number of fungal MOE, in particular, Aspergillus species. The clinical findings in these patients can be quite different from those of the classic gram-negative bacteria. Methods Chart review of patients with a diagnosis of MOE who underwent oral voriconazole treatment. Results Three cases of Aspergillus MOE are reported in detail, pointing the pitfalls in clinical findings, diagnosis, and management of this entity. Conclusion Oral voriconazole proved to be an excellent alternative modality treatment in this population of patients with MOE.