Miracle-dz/UniFAR-FTUs huggingface dataset:
Proline mechanisms of stress survival.

SIGNIFICANCE The imino acid proline is utilized by different organisms to offset cellular imbalances caused by environmental stress. The wide use in nature of proline as a stress adaptor molecule indicates that proline has a fundamental biological role in stress response. Understanding the mechanisms by which proline enhances abiotic/biotic stress response will facilitate agricultural crop research and improve human health. RECENT ADVANCES It is now recognized that proline metabolism propels cellular signaling processes that promote cellular apoptosis or survival. Studies have shown that proline metabolism influences signaling pathways by increasing reactive oxygen species (ROS) formation in the mitochondria via the electron transport chain. Enhanced ROS production due to proline metabolism has been implicated in the hypersensitive response in plants, lifespan extension in worms, and apoptosis, tumor suppression, and cell survival in animals. CRITICAL ISSUES The ability of proline to influence disparate cellular outcomes may be governed by ROS levels generated in the mitochondria. Defining the threshold at which proline metabolic enzyme expression switches from inducing survival pathways to cellular apoptosis would provide molecular insights into cellular redox regulation by proline. Are ROS the only mediators of proline metabolic signaling or are other factors involved? FUTURE DIRECTIONS New evidence suggests that proline biosynthesis enzymes interact with redox proteins such as thioredoxin. An important future pursuit will be to identify other interacting partners of proline metabolic enzymes to uncover novel regulatory and signaling networks of cellular stress response.
Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

It is well-established that neurons in the adult mammalian central nervous system (CNS) are terminally differentiated and, if injured, will be unable to regenerate their connections. In contrast to mammals, zebrafish and other teleosts display a robust neuroregenerative response. Following optic nerve crush (ONX), retinal ganglion cells (RGC) regrow their axons to synapse with topographically correct targets in the optic tectum, such that vision is restored in ~21 days. What accounts for these differences between teleostean and mammalian responses to neural injury is not fully understood. A time course analysis of global gene expression patterns in the zebrafish eye after ONX can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration. To define different phases of regeneration after ONX, alpha tubulin 1 (tuba1) and growth-associated protein 43 (gap43), markers previously shown to correspond to morphophological events, were measured by real time quantitative PCR (qPCR). Microarray analysis was then performed at defined intervals (6 hours, 1, 4, 12, and 21 days) post-ONX and compared to SHAM. Results show that optic nerve damage induces multiple, phase-related transcriptional programs, with the maximum number of genes changed and highest fold-change occurring at 4 days. Several functional groups affected by optic nerve regeneration, including cell adhesion, apoptosis, cell cycle, energy metabolism, ion channel activity, and calcium signaling, were identified. Utilizing the whole eye allowed us to identify signaling contributions from the vitreous, immune and glial cells as well as the neural cells of the retina. Comparisons between our dataset and transcriptional profiles from other models of regeneration in zebrafish retina, heart and fin revealed a subset of commonly regulated transcripts, indicating shared mechanisms in different regenerating tissues. Knowledge of gene expression patterns in all components of the eye in a model of successful regeneration provides an entry point for functional analyses, and will help in devising hypotheses for testing normal and toxic regulatory factors.
Origin and Evolution of GALA-LRR, a New Member of the CC-LRR Subfamily: From Plants to Bacteria?

The phytopathogenic bacterium Ralstonia solanacearum encodes type III effectors, called GALA proteins, which contain F-box and LRR domains. The GALA LRRs do not perfectly fit any of the previously described LRR subfamilies. By applying protein sequence analysis and structural prediction, we clarify this ambiguous case of LRR classification and assign GALA-LRRs to CC-LRR subfamily. We demonstrate that side-by-side packing of LRRs in the 3D structures may control the limits of repeat variability within the LRR subfamilies during evolution. The LRR packing can be used as a criterion, complementing the repeat sequences, to classify newly identified LRR domains. Our phylogenetic analysis of F-box domains proposes the lateral gene transfer of bacterial GALA proteins from host plants. We also present an evolutionary scenario which can explain the transformation of the original plant LRRs into slightly different bacterial LRRs. The examination of the selective evolutionary pressure acting on GALA proteins suggests that the convex side of their horse-shoe shaped LRR domains is more prone to positive selection than the concave side, and we therefore hypothesize that the convex surface might be the site of protein binding relevant to the adaptor function of the F-box GALA proteins. This conclusion provides a strong background for further functional studies aimed at determining the role of these type III effectors in the virulence of R. solanacearum.
Analysis and Design of Rib Support ( ADRS ) A Rib Support Design Methodology for Australian Collieries

The outcome of the project is a design methodology and software tool called, Analysis and Design of Rib Support (ADRS). ADRS is an empirical technique, which recognises that several geotechnical and design factors affect ribline performance and in addition that operational and safety issues essentially dictate the level of performance required. Therefore, the design recommendations associated with ADRS are specific to the Australian coal industry; however the procedure(s) for data collection and analysis could be applied to other countries' 'underground coal industries.
Identification of the genetic defect in the original Wagner syndrome family.

PURPOSE The aim of the present study was to determine the genetic defect in Wagner syndrome, a rare disorder belonging to the group of hereditary vitreoretinal degenerations. This disease has been genetically mapped to chromosome 5q14.3. METHODS Molecular analysis was performed in the progeny of the original pedigree described by Wagner in 1938. We searched for pathogenic mutations and their effects in two candidate genes, CSPG2 and EDIL3, which locate to the critical chromosomal interval. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was used to investigate potential splice defects of CSPG2 transcripts. RESULTS While no alterations were detected in the exons of EDIL3, several changes were identified in the CSPG2 gene. Only one of the novel changes, a heterozygous G to A substitution of the first nucleotide in intron 8, cosegregates with the disease phenotype. This change disrupts the highly conserved splice donor sequence. In blood cells of an index patient, we found CSPG2 transcripts with normally spliced exon 8/9 junction but also two additional CSPG2 transcripts, which were not detected in the control. One lacks the entire exon 8, while the other is missing only the last 21 bp of exon 8. CONCLUSIONS CSPG2 encodes versican, a large proteoglycan, which is an extracellular matrix component of the human vitreous and participates in the formation of the vitreous gel. The splice site mutation described here may lead to a complete lack of exon 8 in CSPG2 transcripts, which shortens the predicted protein by 1754 amino acids and leads to severe reduction of glycosaminoglycan attachment sites.
Mobility, proprioception, strength and FMS as predictors of injury in professional footballers

Background The premise of this study was to investigate if anthropometric variables such as mobility, proprioception, strength and modified Functional Movement Screen (mFMS) could be used as primary indicators of injury risk in an English Championship division football team. This study focused on moderate injuries occurring in the lower extremities, during the 2014/2015 competitive season. Methods To differentiate between minor, moderate and severe injuries, this study classified moderate injuries as an injury with an average injury severity of 2–28 days. This study is composed of 4 individual investigations. Each variable was assessed against 2 groups: injured (n=6) and non-injured (n=10). The 2 groups were compiled from the first team, with the criteria that each participant of this study required: full preseason assessment and injury history for the time period, 1 July 2014 to 19 March 2015. A Mann-Whitney U test (0.05% significance) was applied to statistically analyse if each variable showed any variation across the 2 groups. Effect size was estimated with Cliff's d. Results Strength asymmetry displayed significant difference (p=0.007), mobility, proprioception and mFMS did not (p=0.263, p=0.792 and p=0.181, respectively). Mean scores for mobility, proprioception, strength asymmetry and mFMS for injured versus non-injured players (effect size) were: 40.00 vs 38.00 (0.37), 10.33 vs 10.20 (0.10), 61.13 vs 30.40 (0.80) and 7.33 vs 8.90 (−0.4), respectively. Conclusions This study found no relationship between mobility/proprioception and injury risk; however, strength asymmetry was statistically significant in predicting injury and mFMS exhibited enough positive difference for recommendation of further investigation.
Long QT Syndrome:

Point of View. Long QT syndrome type 1 (LQFI) causes torsades de pointes arrhythmia, ventricular fibrillation, and sudden death. It usually is inherited as an autosomal dominant trait (Romano‐Ward syndrome). The primary defect in LQTI is a mutation in KVLQT1, a gene that encodes the pore‐forming α‐subunit of a K+ channel. KvLQT1 α‐subunits coassemble with minK β‐subunits to form channels that conduct the slow delayed rectifier K+ current (IKs) in the heart. Recessive mutations in KVLQT1 cause Jervell and Lange‐Nielsen syndrome, which is characterized by more severe arrhythmias and congenital neural deafness. Heterologous expression studies demonstrated that mutations in KVLQT1reduce IKs by causing loss of channel function, altered channel gating, and/or a dominant‐negative effect. It remains to be proven that an understanding of the molecular basis of LQT1 will lead to more effective therapy.
A study on metamodeling techniques, ensembles, and multi-surrogates in evolutionary computation

Surrogate-Assisted Memetic Algorithm (SAMA) is a hybrid evolutionary algorithm, particularly a memetic algorithm that employs surrogate models in the optimization search. Since most of the objective function evaluations in SAMA are approximated, the search performance of SAMA is likely to be affected by the characteristics of the models used. In this paper, we study the search performance of using different meta modeling techniques, ensembles, and multi-surrogates in SAMA. In particular, we consider the SAMA-TRF, a SAMA model management framework that incorporates a trust region scheme for interleaving use of exact objective function with computationally cheap local meta models during local searches. Four different metamodels, namely Gaussian Process (GP), Radial Basis Function (RBF), Polynomial Regression (PR), and Extreme Learning Machine (ELM) neural network are used in the study. Empirical results obtained show that while some metamodeling techniques perform best on particular benchmark problems, ensemble of metamodels and multisurrogates yield robust and improved solution quality on the benchmark problems in general, for the same computational budget.
A Model of Fault Tolerance Applied to Train Operations at a Classic Railway Junction

The operation of a rail network is safeguarded through the use of train control and protection systems, traditionally in the forms of ‘block signalling’ and ‘interlocking’ (e.g. Bonett, 2005; Profilids, 2006; Pachl, 2009). Current rules of railway operations employed in the UK can be regarded as being overly conservative. While the safety of passengers is a clearly an overriding paramount consideration, overly conservative rules may represent a drawback in that they reduce capacity. At present, with high and growing demand there is a clear need to increase railway capacity. Whilst construction of new lines or significant augmentation of existing ones offer ways of providing increased capacity, there is a long gestation period and it is extremely expensive at a time of tight governmental budgetary constraints.
THE PHYSICS OF PROTONEUTRON STAR WINDS: IMPLICATIONS FOR R-PROCESS NUCLEOSYNTHESIS

We solve the general-relativistic steady-state eigenvalu e problem of neutrino-driven protoneutron star winds, which immediately follow core-collapse supernova explosi on . We provide velocity, density, temperature, and composition profiles and explore the systematics and struct u es generic to such a wind for a variety of protoneutron star characteristics. Furthermore, we derive the entr opy, dynamical timescale, and neutron-to-seed ratio in the general relativistic framework essential in assessing thi s site as a candidate for r-process nucleosynthesis. Generally, we find that for a given mass outflow rate ( Ṁ), the dynamical timescale of the wind is significantly short er than previously thought. We argue against the existence or viability of a high entropy (& 300 per kB per baryon), long dynamical timescaler-process epoch. In support of this conclusion, we model the p rotoneutron star cooling phase, calculate nucleosynthetic yields in our steady-state profiles , and estimate the integrated mass loss. We find that transonic winds enter a high entropy phase only with very low Ṁ (. 1×10−9 M⊙ s−1) and extremely long dynamical timescale ( τρ & 0.2 seconds). Our results support the possible existence of an earlyr-process epoch at modest entropy (∼ 150) and very short dynamical timescale, consistent in our c alculations with a very massive or very compact protoneutron star that contracts rapidly after the preceding supernova. We explore possible modifications to our models, which might yield significant r-process nucleosynthesis generically. Finally, we speculate on the effect of fallback and shocks on b th the wind physics and nucleosynthesis. We find that a termination or reverse shock in the wind, but exter ior to the wind sonic point, may have important nucleosynthetic consequences. Subject headings: Winds, neutrinos, supernovae, neutron stars, nucleosynth esis
MODIFICATIONS ON EQUIVALENT LATERAL FORCE METHOD

It is important that deformation demands be predicted when evaluating the seismic performance of structures. In this paper, a statistical process is outlined to estimate the seismic demands of roof and story for MDOF structures. Roof drift demand is related to the maximum story drift demand through a simplified process that provides quick and reasonable estimates of seismic demands. An attempt has been made to adjust and extend the concept of response modification factor by introducing a modifying factor RT. This factor accounts for the inelastic response in the dynamic analysis of MDOF structures. The analysis involves MDOF shear and frame buildings with various dynamic characteristics. Nonlinear and corresponding linear time history analyses were performed for severe earthquake ground motions. The data were used to derive empirical formulae for the maximum story and roof displacements. The results of the study can provide a simple and practical way to determine the nonlinear dynamic response of MDOF structures. An approximate approach is presented to calculate the maximum inelastic deformations in a structure with a given strength distribution. The relationships proposed in this paper could be useful in the conceptual design phase, estimating deformation demands for performance assessment, and improving the basic understanding of seismic behavior.
Immaturity of the Oculomotor Saccade and Vergence Interaction in Dyslexic Children: Evidence from a Reading and Visual Search Study

Studies comparing binocular eye movements during reading and visual search in dyslexic children are, at our knowledge, inexistent. In the present study we examined ocular motor characteristics in dyslexic children versus two groups of non dyslexic children with chronological/reading age-matched. Binocular eye movements were recorded by an infrared system (mobileEBT®, e(ye)BRAIN) in twelve dyslexic children (mean age 11 years old) and a group of chronological age-matched (N = 9) and reading age-matched (N = 10) non dyslexic children. Two visual tasks were used: text reading and visual search. Independently of the task, the ocular motor behavior in dyslexic children is similar to those reported in reading age-matched non dyslexic children: many and longer fixations as well as poor quality of binocular coordination during and after the saccades. In contrast, chronological age-matched non dyslexic children showed a small number of fixations and short duration of fixations in reading task with respect to visual search task; furthermore their saccades were well yoked in both tasks. The atypical eye movement's patterns observed in dyslexic children suggest a deficiency in the visual attentional processing as well as an immaturity of the ocular motor saccade and vergence systems interaction.
SUBANESTHETIC DOSE OF ISOFLURANE PROTECTS AGAINST ZYMOSAN-INDUCED GENERALIZED INFLAMMATION AND ITS ASSOCIATED ACUTE LUNG INJURY IN MICE

Multiple organ dysfunction syndrome (MODS) is one of the leading causes of death in the intensive care unit. Organ failure especially lung injury is highly associated with the mortality for MODS patients. Volatile anesthetic isoflurane (ISO) is one of the most widely used anesthetic agents, and ISO anesthesia has been reported to improve the survival rate and organ function in sepsis/MODS models. However, the application of anesthetic dose ISO in critically ill patients is limited. Compared with i.v. anesthetic pentobarbital treatment, we showed that twice inhalation of ISO at subanesthetic dose (0.7%, 0.5 minimum alveolar concentration) alleviated lung injury at 24 h after zymosan (ZY) injection and increased the 7-day survival rate from 10% to 45% in mice. We also showed that ISO exerted its protection by significantly improving the activities of superoxide dismutase and catalase in lung and serum when compared with those in pentobarbital-treated mice. The catalase inhibitor 3-amino-1, 2, 4-triazole partially abolished the protective effect of ISO in ZY-challenged mice. We conclude that subanesthetic dose ISO protects against ZY-induced generalized inflammation and its associated lung injury via enhancing the activities of antioxidant enzymes in mice, which may provide a new strategy for the treatment of critically ill patients.ABBREVIATIONS-8-iso-PGF2&agr;-8-iso-prostaglandin F2&agr;; ALI-acute lung injury; AT-3-amino-1,2,4-triazole; BALF-bronchoalveolar lavage fluid; CAT-catalase; CLP-cecal ligation and puncture; ELISA-enzyme-linked immunosorbent assay; ICU-intensive care unit; ISO-isoflurane; LSD-least significant difference; MAC-minimum alveolar concentration; MODS-multiple organ dysfunction syndrome; MPO-myeloperoxidase; NS-normal saline; PT-pentobarbital; SIRS-systemic inflammatory response syndrome; SOD-superoxide dismutase; W/D-wet/dry; ZY-zymosan
New clinical grading scales and objective measurement for conjunctival injection.

PURPOSE To establish a new clinical grading scale and objective measurement method to evaluate conjunctival injection. METHODS Photographs of conjunctival injection with variable ocular diseases in 429 eyes were reviewed. Seventy-three images with concordance by three ophthalmologists were classified into a 4-step and 10-step subjective grading scale, and used as standard photographs. Each image was quantified in four ways: the relative magnitude of the redness component of each red-green-blue (RGB) pixel; two different algorithms based on the occupied area by blood vessels (K-means clustering with LAB color model and contrast-limited adaptive histogram equalization [CLAHE] algorithm); and the presence of blood vessel edges, based on the Canny edge-detection algorithm. Area under the receiver operating characteristic curves (AUCs) were calculated to summarize diagnostic accuracies of the four algorithms. RESULTS The RGB color model, K-means clustering with LAB color model, and CLAHE algorithm showed good correlation with the clinical 10-step grading scale (R = 0.741, 0.784, 0.919, respectively) and with the clinical 4-step grading scale (R = 0.645, 0.702, 0.838, respectively). The CLAHE method showed the largest AUC, best distinction power (P < 0.001, ANOVA, Bonferroni multiple comparison test), and high reproducibility (R = 0.996). CONCLUSIONS CLAHE algorithm showed the best correlation with the 10-step and 4-step subjective clinical grading scales together with high distinction power and reproducibility. CLAHE algorithm can be a useful for method for assessment of conjunctival injection.
Soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy

Pathophysiological cardiac hypertrophy is one of the most common causes of heart failure. Epoxyeicosatrienoic acids, hydrolyzed and degraded by soluble epoxide hydrolase (sEH), can function as endothelium-derived hyperpolarizing factors to induce dilation of coronary arteries and thus are cardioprotective. In this study, we investigated the role of sEH in two rodent models of angiotensin II (Ang II)-induced cardiac hypertrophy. The protein level of sEH was elevated in the heart of both spontaneously hypertensive rats and Ang II-infused Wistar rats. Blocking the Ang II type 1 receptor with losartan could abolish this induction. Administration of a potent sEH inhibitor (sEHI) prevented the pathogenesis of the Ang II-induced hypertrophy, as demonstrated by decreased left-ventricular hypertrophy assessed by echocardiography, reduced cardiomyocyte size, and attenuated expression of hypertrophy markers, including atrial natriuretic factor and β-myosin heavy chain. Because sEH elevation was not observed in exercise- or norepinephrine-induced hypertrophy, the sEH induction was closely associated with Ang II-induced hypertrophy. In vitro, Ang II upregulated sEH and hypertrophy markers in neonatal cardiomyocytes isolated from rat and mouse. Expression of these marker genes was elevated with adenovirus-mediated sEH overexpression but decreased with sEHI treatment. These results were supported by studies in neonatal cardiomyocytes from sEH−/− mice. Our results suggest that sEH is specifically upregulated by Ang II, which directly mediates Ang II-induced cardiac hypertrophy. Thus, pharmacological inhibition of sEH would be a useful approach to prevent and treat Ang II-induced cardiac hypertrophy.