Miracle-dz/UniFAR-FTUs huggingface dataset:
The Proteasomal Rpn11 Metalloprotease Suppresses Tombusvirus RNA Recombination and Promotes Viral Replication via Facilitating Assembly of the Viral Replicase Complex

ABSTRACT RNA viruses co-opt a large number of cellular proteins that affect virus replication and, in some cases, viral genetic recombination. RNA recombination helps viruses in an evolutionary arms race with the host's antiviral responses and adaptation of viruses to new hosts. Tombusviruses and a yeast model host are used to identify cellular factors affecting RNA virus replication and RNA recombination. In this study, we have examined the role of the conserved Rpn11p metalloprotease subunit of the proteasome, which couples deubiquitination and degradation of proteasome substrates, in tombusvirus replication and recombination in Saccharomyces cerevisiae and plants. Depletion or mutations of Rpn11p lead to the rapid formation of viral RNA recombinants in combination with reduced levels of viral RNA replication in yeast or in vitro based on cell extracts. Rpn11p interacts with the viral replication proteins and is recruited to the viral replicase complex (VRC). Analysis of the multifunctional Rpn11p has revealed that the primary role of Rpn11p is to act as a “matchmaker” that brings the viral p92pol replication protein and the DDX3-like Ded1p/RH20 DEAD box helicases into VRCs. Overexpression of Ded1p can complement the defect observed in rpn11 mutant yeast by reducing TBSV recombination. This suggests that Rpn11p can suppress tombusvirus recombination via facilitating the recruitment of the cellular Ded1p helicase, which is a strong suppressor of viral recombination, into VRCs. Overall, this work demonstrates that the co-opted Rpn11p, which is involved in the assembly of the functional proteasome, also functions in the proper assembly of the tombusvirus VRCs. IMPORTANCE RNA viruses evolve rapidly due to genetic changes based on mutations and RNA recombination. Viral genetic recombination helps viruses in an evolutionary arms race with the host's antiviral responses and facilitates adaptation of viruses to new hosts. Cellular factors affect viral RNA recombination, although the role of the host in virus evolution is still understudied. In this study, we used a plant RNA virus, tombusvirus, to examine the role of a cellular proteasomal protein, called Rpn11, in tombusvirus recombination in a yeast model host, in plants, and in vitro. We found that the cellular Rpn11 is subverted for tombusvirus replication and Rpn11 has a proteasome-independent function in facilitating viral replication. When the Rpn11 level is knocked down or a mutated Rpn11 is expressed, then tombusvirus RNA goes through rapid viral recombination and evolution. Taken together, the results show that the co-opted cellular Rpn11 is a critical host factor for tombusviruses by regulating viral replication and genetic recombination.
Influence of TMSO calibration standards uncertainties on VNA S-parameter measurements

For the widespread, 12-term TMSO calibration of four-sampler vector network analyzers (VNAs), the sensitivity coefficients of the S-parameters of two ports are determined as functions of the deviations of the reflection coefficients of the one-port calibration standards and of an imperfect through connection. The expressions obtained, which have been experimentally verified, are suitable for the establishment of the uncertainty budget.
Characterization and genomic analysis of two Staphylococcus aureus bacteriophages isolated from poultry/livestock farms

Staphylococcus aureus is one of the most important pathogens, causing various diseases in humans and animals. As methicillin-resistant S. aureus (MRSA) has become increasingly prevalent, controlling this pathogen with standard antibiotic treatment has become challenging. Bacteriophages (phages) have attracted interest as alternative antibacterial agents to control MRSA. In this study, we isolated six S. aureus phages from soils of poultry/livestock farms. Based on the results of host range determination with 150 S. aureus strains and restriction enzyme treatment of phage DNA, two phages, designated SP5 and SP6, were selected for further characterization and genome sequencing. Both SP5 and SP6 were classified as members of the family Siphoviridae. The genome of SP5 comprises 43 305 bp and contains 63 ORFs, while the SP6 genome comprises 42 902 bp and contains 61 ORFs. Although they have different host spectra, the phage genomes exhibit high nucleotide similarity to each other. Adsorption assay results suggested that the host range determinants of the two phages are involved in both adsorption and infection. Comparative genomic analyses of the two phages provided evidence that the lysogenic/lytic control module and tail proteins may be important for host specificity.
Abnormally Increased Secretion in Olfactory Neuronal Precursors from a Case of Schizophrenia Is Modulated by Melatonin: A Pilot Study

The alterations that underlie the pathophysiology of schizophrenia (SCZ) include the dysregulation of structural and functional properties of neurons. Among these, the secretion of neurotransmitters and hormones, which plays a key role for neuronal communication and development, is altered. Neuronal precursors from the human olfactory epithelium have been recently characterized as a reliable model for studying the etiopathogenesis of neuropsychiatric diseases. Our previous work has shown that melatonin enhances the development of morphological and functional features of cloned olfactory neuronal precursors (ONPs) from a healthy subject. In this work we found that primary cultures of ONPs obtained from a schizophrenic patient display an increased potassium-evoked secretion, when compared with ONPs from an age- and gender-matched healthy control subject (HCS). Secretion was evaluated by FM1-43 fluorescence cumulative changes in response to depolarization. Interestingly, a 12 h-melatonin treatment modulated the abnormally increased secretion in SCZ ONPs and brought it to levels similar to those found in the HCS ONPs. Our results suggest that the actin cytoskeleton might be a target for melatonin effects, since it induces the thickening of actin microfilament bundles. Further research will address the mechanisms by which melatonin modulates neurochemical secretion from ONPs.
Tension Stiffening and Cracking of Hybrid Fiber-Reinforced Concrete

An experimental program has been carried out to study the effect of hybrid fibers on the tension stiffening and cracking characteristics of high-performance concrete (HPC). A total of 24 axially reinforced concrete tension members were cast and tested under uniaxial tension. The main variables considered were the volume fraction of: 1) crimped steel fibers (0.5 and 1.0%); and 2) polypropylene fibers (0.1, 0.15, and 0.2%). Load-deformation response was recorded and analyzed. Crack width and crack spacing were also measured at all stages of loading. Test results indicate that the addition of fibers in hybrid form significantly improves the tension stiffening effect and resistance to cracking. The combination of 1% steel fiber and 0.1% polypropylene fiber showed better performance than the other combinations considered in this study. A method is proposed to predict the crack width of hybrid fiber-reinforced, high-performance concrete tension members, and the computed values compared satisfactorily with the test results.
C IRCSIM -Tutor: An Intelligent Tutoring System Using Natural Language Dialogue*

C IRCSIM -Tutor version 2, a dialogue-based intelligent tutoring system (ITS), is nearly five years old. It conducts a conversation with a student to help the student learn to solve a class of problems in cardio-vascular physiology dealing with the regulation of blood pressure. It uses natural language for both input and output, and can handle a variety of syntactic constructions and lexical items, including sentence fragments and misspelled words
Framework selection can influence pharmacokinetics of a humanized therapeutic antibody through differences in molecule charge

Pharmacokinetic (PK) testing of a humanized (κI, VH3 framework) and affinity matured anti-hepatitis C virus E2-glycoprotein (HCV-E2) antibody (hu5B3.κ1VH3.v3) in rats revealed unexpected fast clearance (34.9 mL/day/kg). This antibody binds to the rat recycling receptor FcRn as expected for a human IgG1 antibody and does not display non-specific binding to baculovirus particles in an assay that is correlated with fast clearance in cynomolgus monkey. The antigen is not expressed in rat so target-dependent clearance does not contribute to PK. Removal of the affinity maturation changes (hu5B3.κ1VH3.v1) did not restore normal clearance. The antibody was re-humanized on a κ4, VH1 framework and the non-affinity matured version (hu5B3.κ4VH1.v1) was shown to have normal clearance (8.5 mL/day/kg). Since the change in framework results in a lower pI, primarily due to more negative charge on the κ4 template, the effect of additional charge variation on antibody PK was tested by incorporating substitutions obtained through phage display affinity maturation of hu5B3. κ1VH3. v1. A variant having a pI of 8.61 gave very fast clearance (140 mL/day/kg) whereas a molecule with pI of 6.10 gave slow clearance (5.8 mL/kg/day). Both antibodies exhibited comparable binding to rat FcRn, but biodistribution experiments showed that the high pI variant was catabolized in liver and spleen. These results suggest antibody charge can have an effect on PK through alterations in antibody catabolism independent of FcRn-mediated recycling. Furthermore, introduction of affinity maturation changes into the lower pI framework yielded a candidate with PK and virus neutralization properties suitable for clinical development.
Micromagnetic analysis and development of high sensitivity spin-valve magnetic sensors

In this paper we present a micromagnetic analysis and development of low-field magnetic sensors based on the planar Hall effect (PHE) in Permalloy (Ni80Fe20) thin films and spin-valve structures. We used these sensors for field measurements, biomolecules detection in lab-on-a-chip applications and angle positioning devices. Both field and angular PHE measurements were performed. Some distortions and hysteretic effects were observed at low magnetic fields for the angular dependence of the PHE voltage. Micromagnetic simulations were performed to explain the field and the angular dependence of the PHE voltage. We used dc biasing fields to improve the response of the PHE sensor and we compare these results with our micromagnetic simulations.
RClassify: Classifying Race Conditions in Web Applications via Deterministic Replay

Race conditions are common in web applicationsbut are difficult to diagnose and repair. Although there existtools for detecting races in web applications, they all report alarge number of false positives. That is, the races they report areeither bogus, meaning they can never occur in practice, or benign, meaning they do not lead to erroneous behaviors. Since manuallydiagnosing them is tedious and error prone, reporting theserace warnings to developers would be counter-productive. Wepropose a platform-agnostic, deterministic replay-based methodfor identifying not only the real but also the truly harmful raceconditions. It relies on executing each pair of racing events in twodifferent orders and assessing their impact on the program state:we say a race is harmful only if (1) both of the two executions arefeasible and (2) they lead to different program states. We haveevaluated our evidence-based classification method on a large setof real websites from Fortune-500 companies and demonstratedthat it significantly outperforms all state-of-the-art techniques.
Virological and immunological responses to efavirenz or boosted lopinavir as first-line therapy for patients with HIV

Background Efavirenz and lopinavir boosted with ritonavir are both recommended as first-line therapies for patients with HIV when combined with two nucleoside reverse transcriptase inhibitors. It is uncertain which therapy is more effective for patients starting therapy with an advanced infection. Methods We estimated the relative effect of these two therapies on rates of virological and immunological failure within the Swiss HIV Cohort Study and considered whether estimates depended on the CD4+ T-cell count when starting therapy. We defined virological failure as either an incomplete virological response or viral rebound after viral suppression and immunological failure as failure to achieve an expected CD4+ T-cell increase calculated from EuroSIDA statistics. Results Patients starting efavirenz (n=660) and lopinavir (n=541) were followed for a median of 4.5 and 3.1 years, respectively. Virological failure was less likely for patients on efavirenz, with the adjusted hazard ratio (95% confidence interval) of 0.63 (0.50–0.78) then multiplied by a factor of 1.00 (0.90–1.12) for each 100 cells/mm3 decrease in CD4+ T-cell count below the mean when starting therapy. Immunological failure was also less likely for patients on efavirenz, with the adjusted hazard ratio of 0.68 (0.51–0.91) then multiplied by a factor of 1.29 (1.14–1.46) for each 100 cells/ mm3 decrease in CD4+ T-cell count below the mean when starting therapy. Conclusions Virological failure is less likely with efavirenz regardless of the CD4+ T-cell count when starting therapy. Immunological failure is also less likely with efavirenz; however, this advantage disappears if patients start therapy with a low CD4+ T-cell count.
Preferentialness Design of a Composite Impeller with Ultra-Low Unit Speed Centrifugal Pump

According to main factors which affect the design of a composite impeller with ultra-low Unit speed centrifugal pump—the leaf number of the composite impeller’s short blade design, the relative position of the blade’s radial inlet, the bias degree of the blade’s circumferential direction, the deflection angle and so on. The paper applies Orthogonal method and establishes 16 design schemes. The preferentialness design of Composite Impeller’s short blade with ultra-low unit speed centrifugal pump was gained by numerical simulation. Contrast to the method of permutation and combination, this kind of method can decrease the designer’s workload greatly. As the results show, the composite impeller’s inner stress field and velocity field distribute reasonably, H - Q curve method is smoother, curve directs to large discharge and the work performance becomes well by applying orthogonal method.
A multi-method exploration: The use of mobile spiritual applications amongst older adults

Gathering user requirements for older adults can be a complex and difficult process, in terms of working with them should be applied differently compared to general users. The age-related ability changes are sensitive to be discussed and sometimes, the unwillingness might occur in this requirements gathering stage. It is important to underscore the importance and significance of this research in the light of proper requirements gathering techniques in working with older adults and this situation supported by the growing trend of older users' role in technology development included for mobile phone applications. Although many of the existing mobile applications are widely used and covers many aspects of daily routines included for spiritual-oriented mobile applications, there is still lacking of the mobile applications that have been used are well suited to older adult users. The study found that older adults were able to learn and use mobile spiritual apps. However, the methods of requirements gathering should be applied in an appropriate way, since religious and spirituality experiences are sensitive to be discussed in the public. This paper reports on a multi-method research effort that employed cultural probe workshop, written daily activity diaries, interviews, and participant observations to explore about mobile spiritual application use amongst older adults in Malaysia. The results are presented by reflecting on the authors' experience which highlight some suggestions on how cultural probe workshop and diary study activities may support the process of gathering user requirements for mobile spiritual applications amongst older adults.
[Mount Reventino greenstone: assessment of tremolite fibre dispersion in the workplace].

BACKGROUND Mount Reventino, a massif located in the Calabria Region of Italy, has several ophiolite outcrops of greenstone. These deposits are an important economical resource in the surrounding area. Some rock layers contain tremolite, a type of asbestos fibre. OBJECTIVES The aim of this paper was to analyze the chemical and physical structure of the outcrops of Mount Reventino, and to assess and reduce the risk to workers associated with exposure to airborne fibres. METHODS Personal and environmental samples were collected and analysed by Scanning Electron Microscopy equipped with energy-dispersive X-ray analysis. RESULTS The analysis of samples showed a difference in mineralogical features not only between the quarries under study, but also between the two opposite sides of the mountain. Exploitation of the quarries produces a fibre dispersion that is higher than the natural emission. Occupational exposure to asbestos fibres during greenstone transformation was confirmed by by the results of analysis of the collected samples. CONCLUSIONS This study made it possible to identify working activities with highest exposure to asbestos and establish the correct procedures to abate fibre dispersion, in order to reduce the correlated risk. Environmental samples collected in the urban area surrounding the quarries showed that the asbestos fibre concentrations were very low, however, further studies are needed in order to confirm these findings.
Quad-core media processor SoC with implicative dynamic parallel programming model

The advancement of process technology enables the integration of multiple cores featuring the parallel processing with low operating energy and efficient resource utilization in embedded media processors. We propose mobile media processor SoC integrating RISC core and quad-core data processing engines with shared array of memory modules. The implicative dynamic parallel programming model dynamically distributes the programmer-specified parallelizable functions into multiple cores. The experimental result with parallelized audio processing algorithm on FPGA platform shows the effectiveness of the proposed processor SoC.
On the Capacity of Generalized Fading/Shadowing Channels

In this paper the Shannon capacity of generalized-gamma (GG) fading channels is studied, under different adaptive transmission techniques. The GG is a generic distribution, which is considered to be appropriate for modeling fading/shadowing phenomena. Hence, assuming single (i.e., no diversity), as well as, dual-branch selection diversity receivers, novel expressions for the capacity under three adaptive transmission policies, namely optimal power and rate adaptation (OPRA), channel inversion with fixed rate (CIFR) and truncated CIFR (TIFR), are obtained. The derived expressions are in closed form and generalize previously presented results. The proposed analysis is accompanied by numerical results, clearly demonstrating the usefulness of the theoretical approach.
3D reconstruction of rib cage geometry from biplanar radiographs using a statistical parametric model approach

Rib cage 3D reconstruction is an important prerequisite for thoracic spine modelling, particularly for studies of the deformed thorax in adolescent idiopathic scoliosis. This study proposes a new method for rib cage 3D reconstruction from biplanar radiographs, using a statistical parametric model approach. Simplified parametric models were defined at the hierarchical levels of rib cage surface, rib midline and rib surface, and applied on a database of 86 trunks. The resulting parameter database served to train statistical models which were used to quickly provide a first estimate of the reconstruction from identifications on both radiographs. This solution was then refined by manual adjustments in order to improve the matching between model and image. Accuracy was assessed by comparison with 29 rib cages from CT scans in terms of geometrical parameter differences and in terms of line-to-line error distance between the rib midlines. Intra and inter-observer reproducibility was determined for 20 scoliotic patients. The first estimate (mean reconstruction time of 2 min 30 s) was sufficient to extract the main rib cage global parameters with a 95% confidence interval lower than 7%, 8%, 2% and 4° for rib cage volume, antero-posterior and lateral maximal diameters and maximal rib hump, respectively. The mean error distance was 5.4 mm (max 35 mm) down to 3.6 mm (max 24 mm) after the manual adjustment step (3 min 30 s). The proposed method will improve developments of rib cage finite element modelling and evaluation of clinical outcomes.
Terminations of Pregnancy for Exposure to Oral Retinoids in South Australia, 1985–1993

Summary: The oral retinoids, isotretinoin and etretinate, are highly teratogenic drugs which have been available in Australia since 1985 because of their unique effectiveness in severe cystic acne, psoriasis and other keratinization disorders. Only dermatologists can prescribe them, but in spite of strict guidelines by the manufacturers and the College of Dermatologists, exposed pregnancies have occurred. We attempted to determine the circumstances of exposure to these drugs for the 18 pregnancies terminated in South Australia in 1985–1993, using questionnaires to medical practitioners who notified the terminations under legislation. The main reason for their occurrence was the lack of compliance with the use of effective contraception by the women. In South Australia, some prescriptions of oral retinoids by unauthorized doctors have been dispensed during this period. Using statistics on prescriptions dispensed, an estimate was made of 1 termination of pregnancy for 319 courses of treatment for women with isotretinoin. Extension of guidelines for prescription and more detailed counselling in relation to the use of contraception are recommended. It is also suggested that doctors intending to recommend terminations obtain consent to discuss exposure with the dermatologists concerned, who may not be aware of the exposed pregnancy.