Miracle-dz/UniFAR-FTUs huggingface dataset:
Flavone-resistant Leishmania donovani Overexpresses LdMRP2 Transporter in the Parasite and Activates Host MRP2 on Macrophages to Circumvent the Flavone-mediated Cell Death*

Background: Leishmania donovani adopts several defense mechanisms to become resistant to antileishmanial agents. Results: Laboratory-grown flavone (baicalein)-resistant parasites exhibit efflux of drug by LdABCC2 transporter. Inside the host macrophage, this parasite up-regulates host MRP2 transporter by an Nrf2-dependent pathway. Conclusion: Resistant Leishmania parasite exploits ABC transporter in the parasite and inside the host. Significance: The mechanism of drug resistance in clinical isolates can be probed. In parasites, ATP-binding cassette (ABC) transporters represent an important family of proteins related to drug resistance and other biological activities. Resistance of leishmanial parasites to therapeutic drugs continues to escalate in developing countries, and in many instances, it is due to overexpressed ABC efflux pumps. Progressively adapted baicalein (BLN)-resistant parasites (pB25R) show overexpression of a novel ABC transporter, which was classified as ABCC2 or Leishmania donovani multidrug resistance protein 2 (LdMRP2). The protein is primarily localized in the flagellar pocket region and in internal vesicles. Overexpressed LdABCC2 confers substantial BLN resistance to the parasites by rapid drug efflux. The BLN-resistant promastigotes when transformed into amastigotes in macrophage cells cannot be cured by treatment of macrophages with BLN. Amastigote resistance is concomitant with the overexpression of macrophage MRP2 transporter. Reporter analysis and site-directed mutagenesis assays demonstrated that antioxidant response element 1 is activated upon infection. The expression of this phase II detoxifying gene is regulated by NFE2-related factor 2 (Nrf2)-mediated antioxidant response element activation. In view of the fact that the signaling pathway of phosphoinositol 3-kinase controls microfilament rearrangement and translocation of actin-associated proteins, the current study correlates with the intricate pathway of phosphoinositol 3-kinase-mediated nuclear translocation of Nrf2, which activates MRP2 expression in macrophages upon infection by the parasites. In contrast, phalloidin, an agent that prevents depolymerization of actin filaments, inhibits Nrf2 translocation and Mrp2 gene activation by pB25R infection. Taken together, these results provide insight into the mechanisms by which resistant clinical isolates of L. donovani induce intracellular events relevant to drug resistance.
The Cellular Lesion of Humoral Rejection: Predominant Recruitment of Monocytes to Peritubular and Glomerular Capillaries

Accumulation of inflammatory cells within capillaries is a common morphologic feature of humoral renal allograft rejection and is most easily appreciated if it occurs in glomeruli. The aim of our study was to determine the amount and composition of immune cells within glomeruli and peritubular capillaries (PTC) in cellular and humoral allograft rejection.
Noninvasive Bioluminescence Imaging of α-Synuclein Oligomerization in Mouse Brain Using Split Firefly Luciferase Reporters

Alpha-synuclein (αSYN) aggregation plays a pivotal role in the pathogenesis of Parkinson's disease and other synucleinopathies. In this multistep process, oligomerization of αSYN monomers is the first step in the formation of fibrils and intracytoplasmic inclusions. Although αSYN oligomers are generally considered to be the culprit of these diseases, the methodology currently available to follow-up oligomerization in cells and in brain is inadequate. We developed a split firefly luciferase complementation system to visualize oligomerization of viral vector-encoded αSYN fusion proteins. αSYN oligomerization resulted in successful luciferase complementation in cell culture and in mouse brain. Oligomerization of αSYN was monitored noninvasively with bioluminescence imaging in the mouse striatum and substantia nigra up to 8 months after injection. Moreover, the visualized αSYN oligomers retained their toxic and aggregation properties in both model systems. Next, the effect of two small molecules, FK506 and (-)-epigallocatechin-3-gallate (EGCG), known to inhibit αSYN fibril formation, was investigated. FK506 inhibited the observed αSYN oligomerization both in cell culture and in mouse brain. In conclusion, the split firefly luciferase-αSYN complementation assay will increase our insight in the role of αSYN oligomers in synucleinopathies and opens new opportunities to evaluate potential αSYN-based neuroprotective therapies.
Parental Presence during Induction of Anesthesia: Physiological Effects on Parents

Background The authors conducted a randomized controlled trial to determine whether parental presence during induction of anesthesia (PPIA) is associated with parental physiologic and behavioral manifestations of stress. Methods Children and their parents (N = 80) were randomly assigned to one of three groups: (1) PPIA; (2) PPIA plus 0.5 mg/kg oral midazolam; and (3) control (no PPIA or midazolam). The effect of the group assignment on parental heart rate (HR), parental blood pressure, and parental skin conductance level (SCL) were assessed. Both parental HR and parental SCL were monitored continually. Anxiety of the parent and child was also assessed. Results Parental HR increased from baseline until the induction of anesthesia (P = 0.001). A group-by-time effect (P = 0.005) was also found. That is, throughout the induction period there were several time points at which parents in the two PPIA groups had a significantly higher HR than did parents in the control group (P < 0.05). Similarly, SCL was found to increase in all parents from baseline until induction of anesthesia (P = 0.001). Significant group differences in SCL changes over time were found as well (P = 0.009). State anxiety and blood pressure following induction of anesthesia did not differ significantly between groups (P = nonsignificant). Examination of parental Holter data revealed no rhythm abnormalities and no electrocardiogram changes indicating ischemia. Conclusions The authors found that PPIA is associated with increased parental HR and SCL. However, no increased incidence of electrocardiogram abnormalities were found in parents present during induction of anesthesia.
Packaging of Genomic and Amplicon DNA by the Herpes Simplex Virus Type 1 UL25-Null Mutant KUL25NS

ABSTRACT The herpes simplex virus type 1 (HSV-1) mutant KUL25NS, containing a null mutation within the UL25 gene, was isolated and characterized by McNab and coworkers (A. R. McNab, P. Desai, S. Person, L. L. Roof, D. R. Thomsen, W. W. Newcomb, J. C. Brown, and F. L. Homa, J. Virol. 72:1060–1070, 1998). This mutant was able to cleave the concatemeric products of viral DNA replication into monomeric units, but in contrast to wild-type (wt) HSV-1, they were degraded by DNase treatment, indicating that they were not stably packaged into virus capsids. I have examined the packaging of the KUL25NS genome and an HSV-1 amplicon in cells infected with the mutant virus. In contrast to the previous results, a low level of KUL25NS DNA was resistant to DNase digestion, indicating that it was retained in capsids. The proportion of this packaged DNA present as full-length genomes was much lower than in cells infected by wt HSV-1, and there was a significant overrepresentation of the long terminus and underrepresentation of the short terminus. KUL25NS was less impaired in stably packaging amplicon DNA than in packaging its own genome, and the packaged molecules contained approximately equimolar amounts of the two terminal fragments. Below about 100 kbp, the packaged amplicon molecules exhibited an abundance and size distribution similar to those generated using wt HSV-1 as a helper, but the mutant was relatively impaired in packaging longer amplicon molecules. Both packaged genomic and amplicon DNAs were retained in the nuclei of KUL25NS-infected cells. These results suggest that the UL25 protein may play an important role during the later stages of the head-filling process, prior to release of capsids into the cytoplasm.
SMAD‐proteins as a molecular switch from hypertrophy to apoptosis induction in adult ventricular cardiomyocytes

Heart failure development goes along with a transition from hypertrophic growth to apoptosis induction. In adult cardiomyocytes SMAD proteins are only activated under apoptotic, but not under hypertrophic conditions and are increased at the transition to heart failure. Therefore, SMADs could be candidates that turn the balance from hypertrophic growth to apoptosis resulting in heart failure development. To test this hypothesis we infected isolated rat ventricular cardiomyocytes with adenovirus encoding SMAD4 (AdSMAD4) and investigated the impact of SMAD4 overexpression on the development of apoptosis and hypertrophy under stimulation with phenylephrine (PE). Infection of cardiomyocytes with AdSMAD4 significantly enhanced SMAD‐binding activity while apoptosis after 24 and 36 h infection did not rise. But when SMAD4 overexpressing cardiomyocytes were incubated with PE (10 µM), the number of apoptotic cells increased (Ctrl: 94.97 ± 6.91%; PE: 102.48 ± 4.78% vs. AdSMAD4 + PE: 118.64 ± 3.28%). Furthermore expression of caspase 3 as well as bax/bcl2 ratio increased in SMAD4 overexpressing, PE‐stimulated cardiomyocytes. In addition, the effects of SMAD4 overexpression on PE‐induced hypertrophic growth were analyzed. Protein synthesis 36 h after AdSMAD4 infection was comparable to control cells, whereas the increase in protein synthesis stimulated by phyenylephrine was significantly reduced in SMAD4 overexpressing cells (134.28 ± 10.02% vs. 100.57 ± 8.86%). SMAD4 triggers the transition from hypertrophy to apoptosis in ventricular cardiomyocytes. Since SMADs are increased under several pathophysiological conditions in the heart, it can be assumed that it triggers apoptosis induction and therefore contributes to negative remodeling and heart failure progression. J. Cell. Physiol. 220: 515–523, 2009. © 2009 Wiley‐Liss, Inc.
Therapist immediacy: The association with working alliance, real relationship, session quality, and time in psychotherapy

Abstract Objective: This longitudinal analysis examined the relationship between amount of therapist immediacy in sessions and client post-session ratings of working alliance (WAI), real relationship (RRI), and session quality (SES). Method: Using hierarchal linear modeling (HLM), we disaggregated the variables into within-client (differences between sessions in immediacy) and between-clients (differences between clients in immediacy) components, in order to test associations over time in treatment. Three hundred and sixty four sessions were nested within 16 clients and 9 therapists. Results: When therapists used more immediacy in a session, clients gave higher SES ratings for that session, compared to their sessions with less immediacy (within-client effect). For WAI, it appeared to matter when immediacy was used in treatment. The interaction effect between time in treatment and within-client immediacy revealed that early in treatment, more immediacy in a session was related to lower WAI for that session, whereas later in treatment, more immediacy in a session was related to higher WAI for that session. Another interaction effect was found between time in treatment and between-clients immediacy. Clients with less immediacy in treatment, gave higher SES scores for early sessions, than clients with more immediacy in treatment. Conclusions: Immediacy has an overall positive effect on session quality, but the time in which it is used in treatment and client characteristics should be taken into account both in practice and research.
Evaluation of a Performance-Based Expert Elicitation: WHO Global Attribution of Foodborne Diseases

For many societally important science-based decisions, data are inadequate, unreliable or non-existent, and expert advice is sought. In such cases, procedures for eliciting structured expert judgments (SEJ) are increasingly used. This raises questions regarding validity and reproducibility. This paper presents new findings from a large-scale international SEJ study intended to estimate the global burden of foodborne disease on behalf of WHO. The study involved 72 experts distributed over 134 expert panels, with panels comprising thirteen experts on average. Elicitations were conducted in five languages. Performance-based weighted solutions for target questions of interest were formed for each panel. These weights were based on individual expert’s statistical accuracy and informativeness, determined using between ten and fifteen calibration variables from the experts' field with known values. Equal weights combinations were also calculated. The main conclusions on expert performance are: (1) SEJ does provide a science-based method for attribution of the global burden of foodborne diseases; (2) equal weighting of experts per panel increased statistical accuracy to acceptable levels, but at the cost of informativeness; (3) performance-based weighting increased informativeness, while retaining accuracy; (4) due to study constraints individual experts’ accuracies were generally lower than in other SEJ studies, and (5) there was a negative correlation between experts' informativeness and statistical accuracy which attenuated as accuracy improved, revealing that the least accurate experts drive the negative correlation. It is shown, however, that performance-based weighting has the ability to yield statistically accurate and informative combinations of experts' judgments, thereby offsetting this contrary influence. The present findings suggest that application of SEJ on a large scale is feasible, and motivate the development of enhanced training and tools for remote elicitation of multiple, internationally-dispersed panels.
Cervical vertebrae maturation index estimates on cone beam CT: 3D reconstructions vs sagittal sections.

OBJECTIVES The aim of this study was to evaluate the performance of CBCT three-dimensional (3D) reconstructions and sagittal sections for estimates of cervical vertebrae maturation index (CVMI). METHODS The sample consisted of 72 CBCT examinations from patients aged 8-16 years (45 females and 27 males) selected from the archives of two private clinics. Two calibrated observers (kappa scores: ≥0.901) interpreted the CBCT settings twice. Intra- and interobserver agreement for both imaging exhibition modes was analyzed by kappa statistics, which was also used to analyze the agreement between 3D reconstructions and sagittal sections. Correlations between cervical vertebrae maturation estimates and chronological age, as well as between the assessments by 3D reconstructions and sagittal sections, were analyzed using gamma Goodman-Kruskal coefficients (α = 0.05). RESULTS The kappa scores evidenced almost perfect agreement between the first and second assessments of the cervical vertebrae by 3D reconstructions (0.933-0.983) and sagittal sections (0.983-1.000). Similarly, the agreement between 3D reconstructions and sagittal sections was almost perfect (kappa index: 0.983). In most divergent cases, the difference between 3D reconstructions and sagittal sections was one stage of CVMI. Strongly positive correlations (>0.8, p < 0.001) were found not only between chronological age and CVMI but also between the estimates by 3D reconstructions and sagittal sections (p < 0.001). CONCLUSIONS Although CBCT imaging must not be used exclusively for this purpose, it may be suitable for skeletal maturity assessments.
Instrumented Posterolateral Lumbar Fusion: Results and Comparison With Anterior Interbody Fusion

Study Design. Prospective case series. Objectives. To assess the results of instrumented posterolateral lumbar fusion, using recognized outcome assessment techniques, to evaluate the correlation between technical and clinical results and the effects of assessment techniques, and to compare the outcome with that of anterior lumbar fusion. Summary of Background Data. Assessments of lumbar spinal fusion results have frequently been published in forms that render direct comparison difficult and thus have not provided optimal assistance in the selection of a preferred method of treatment. Methods. One hundred and thirty‐five patients with intractable back pain underwent instrumented posterolateral lumbar spinal fusion performed by a single surgeon. Review of results was undertaken by independent observers, using a recognized outcome assessment measure. Results. A solid bony fusion was obtained in 82% of patients. The method of outcome assessment profoundly affected the results; whereas 65% of patients rated themselves significantly improved by the procedure, only 19% achieved a good or excellent result on the Low Back Outcome Score. Patients undergoing a second procedure did not do well, and "salvage" surgery is not recommended. Compensation status was a significant prognostic factor. Psychological distress at review had a profound effect on the disability score and on patient satisfaction ratings. Overall, the results were inferior to those in a similar series treated by anterior lumbar fusion. Conclusion. It is recommended that in future studies a recognized outcome score be used and that the analysis specifically include compensation status and psychological distress.
Automatic Reconstruction of Building Objects From Multiaspect Meter-Resolution SAR Images

Reconstruction of 3-D objects from multiaspect high- resolution synthetic aperture radar (SAR) images is of great importance for SAR technology applications. In this paper, simple building objects are modeled as cuboids, and an approach for automatic reconstruction of 3-D building objects from multiaspect SAR images in meter resolution is developed. The edge detector of constant false alarm rate and a Hough transform technique for parallel line segment pairs are first employed to extract the parallelogram-like image of the building walls in SAR images. A set of probability density functions is presented to describe the object images and their multiaspect coherence. The maximum-likelihood estimation of an object is then derived from its multiaspect object images. A hybrid priority criterion is defined to evaluate the reliability of the reconstruction result. An automatic reconstruction algorithm is further developed to match object images of different aspects and, finally, to reconstruct the building objects. Besides, an iterative method is proposed for the coregistration of multiaspect building images. Four-aspect simulated images of a virtual scene and four-aspect Pi-SAR images over the campus of Tohoku University, Japan, are investigated. Reconstruction of building objects from their multiaspect images shows the fidelity of the whole process chain and the feasibility of 3-D objects automatic reconstruction from multiaspect SAR images. At last, a practical application that is based on spaceborne meter-resolution SAR is proposed.
Plant defense in the absence of jasmonic acid: The role of cyclopentenones

The Arabidopsis opr3 mutant is defective in the isoform of 12-oxo-phytodienoate (OPDA) reductase required for jasmonic acid (JA) biosynthesis. Oxylipin signatures of wounded opr3 leaves revealed the absence of detectable 3R,7S-JA as well as altered levels of its cyclopentenone precursors OPDA and dinor OPDA. In contrast to JA-insensitive coi1 plants and to the fad3 fad7 fad8 mutant lacking the fatty acid precursors of JA synthesis, opr3 plants exhibited strong resistance to the dipteran Bradysia impatiens and the fungus Alternaria brassicicola. Analysis of transcript profiles in opr3 showed the wound induction of genes previously known to be JA-dependent, suggesting that cyclopentenones could fulfill some JA roles in vivo. Treating opr3 plants with exogenous OPDA powerfully up-regulated several genes and disclosed two distinct downstream signal pathways, one through COI1, the other via an electrophile effect of the cyclopentenones. We conclude that the jasmonate family cyclopentenone OPDA (most likely together with dinor OPDA) regulates gene expression in concert with JA to fine-tune the expression of defense genes. More generally, resistance to insect and fungal attack can be observed in the absence of JA.
Fixed-Ratio Compression of an RGBW Image and Its Hardware Implementation

In the latest large-screen TVs, an RGBW color domain is widely used to enhance the brightness of liquid crystal display (LCD) panels. As the correlations among RGBW color components are different from those among conventional RGB components, a compression algorithm developed for an RGB image may not be efficient for RGBW compression. For high-fidelity RGBW image coding, a novel prediction-based coding algorithm is proposed in this paper. The proposed algorithm is composed of two prediction steps that take advantage of spatial correlation and inter-color correlations, respectively. For residual coding, this paper proposes a fixed-ratio coding method based on Golomb-Rice coding. The proposed encoder is composed of two sub-coders: pre-coder and post-coder. The pre-coder estimates the length of the bitstream for various quantization levels. Based on that estimation, the appropriate quantization level is selected. The post-coder generates the final bitstream. Experimental results show that the average peak signal-to-noise ratio (PSNR) of the proposed algorithm is 51.16 dB. The throughput of the proposed encoder and decoder hardwares is 26.7 Gb/s, and their respective gate counts are 56.1 K and 39.6 K.
Fingermark Evidence Evaluation Based on Automated Fingerprint Identification System Matching Scores: The Effect of Different Types of Conditioning on Likelihood Ratios

In recent studies, the evidential value of the similarity of minutiae configurations of fingermarks and fingerprints, for example expressed by automated fingerprint identification systems (AFIS), is determined by likelihood ratios (LRs). The paper explores whether there is an effect on LRs if conditioning takes place on specified fingers, fingerprints, or fingermarks under competing hypotheses: In addition, an approach is explored where conditioning is asymmetric. Comparisons between fingerprints and simulated fingermarks with eight minutiae are performed to produce similarity score distributions for each type of conditioning, given a fixed AFIS matching algorithm. Both similarity scores and LRs are significantly different if the conditioning changes. Given a common‐source scenario, “LRs” resulting from asymmetric conditioning are on average higher. The difference may reach a factor of 2000. As conditioning on a suspect's finger(print) is labor‐intensive and requires a cooperating suspect, it is recommended to just condition on the number of minutiae in the fingermark.