Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric inhibition induces an open WPD-loop: a new avenue towards glioblastoma therapy

The mobility of loops around the catalytic site of a protein remains crucial to its activity. Dynamics of the WPD-loop is an essential determinant of the catalytic activity of tyrosine-protein phosphatase zeta, an implicated protein in glioblastoma cells. The WPD-loop assumes a closed conformation upon substrate binding in order to position its catalytic aspartate to participate in catalysis. Herein, we explore the impact of NAZ2329, a recently identified allosteric inhibitor of tyrosine-protein phosphatase zeta, on the atomic flexibility of the WPD-loop. The druglikeness of NAZ2329 was assessed using the SwissADME online tool. The enzymatic complex was then subjected to conformational simulations using the AMBER molecular dynamics software. Structural analysis revealed that NAZ2329 induced an open conformation of the crucial WPD-loop, consequently impeding enzyme activity even upon substrate binding. Based on the molecular interactions between NAZ2329 and tyrosine-protein phosphatase zeta, a pharmacophore model was generated to exhibit the important functional moieties of NAZ2329. These findings provide an insightful molecular and structural mechanism in targeting tyrosine-protein phosphatase zeta as a therapeutic intervention for glioblastoma. We believe that this optimized pharmacophoric model will aid in the design of improved anti-tyrosine phosphatase agents, thus allowing for increased patient adherence.
Effect of Acceleration on Wrap Faced Reinforced Soil Retaining Wall on Soft Clay by Performing Shaking Table Test

This research incorporates shaking table testing of scale wrap faced soil wall models to evaluate the seismic response of embankment. Currently the seismic designs of highway or railway embankment rely on little or no empirical data for calibrating numerical simulations. This research is working towards filling that empirical data gap. The specific purpose of the study was to evaluate the seismic response of constructed embankment model regarding the different input base accelerations with fixed frequency. A series of one-dimensional (1D) shaking table tests (0.05g, 0.1g, 0.15g and 0.2g), were performed on a 0.4 meters high wrap faced reinforced-soil wall model. Additionally, it was placed over 0.3 meters high soft clayey foundation. Predominantly, the influence of the base acceleration on the seismic response was studied in this paper. The physical models were subjected to harmonic sinusoidal input motions at a fixed frequency of 1 Hz, in order to assess the seismic behavior. The effects of parameters such as acceleration amplitudes and surcharge pressures on the seismic response of the model walls were considered. The relative density of the backfill material was kept fixed at 60%. The results of this study reveal that input accelerations and surcharge load had significant influence on the model wall, pore water pressure, and changes along the elevation. Acceleration response advances with the increase in base acceleration, so the difference being more perceptible at higher elevations. The pore water pressures were found to be high for high base shaking and low surcharge pressures at higher elevations. The results obtained from this study are helpful in understanding the relative performance of reinforced soil retaining wall under different test conditions resting on soft clay.
Tropical cyclone induced extreme wind, rainfall, and floods in the Mekong River Basin

Increasing magnitude and frequency of climate extremes under global warming are threatening the socioeconomic development in many parts of the world. The Mekong River Basin (MRB) is a good example for how climate extremes can affect society, as the transboundary MRB has experienced hydroclimate changes and fast socioeconomic development during the past decades. The MRB is a flood-prone area with high flood induced mortality, where heavy monsoon rainfall and tropical cyclones (TCs) landfall are the two main determinants of floods. This thesis focuses on the change in TCs and their associated impacts of extreme wind, rainfall, and floods on the MRB. Findings from this thesis provide an improved understanding of TCs and their impacts, which is useful to mitigate potential consequences of global warming in the MRB and other areas facing similar challenges. Employing reliable precipitation data, this thesis finds that TC induced rainfall plays a minor role in the annual mean precipitation in the MRB. But TCs are crucial to the occurrence of extreme rainfall events, particularly at the eastern lower basin. TC induced floods amount to about 24.6% of all flood occurrence in the lower riparian countries. TC induced floods cause higher impacts on human mortality and displacement rates than the average of floods induced by all possible causes do. Moreover, future projection shows increases in the future TC intensity under the Representative Concentration Pathway (RCP) 8.5 scenario. Overall, this thesis reveals that climate extremes, such as TC associated rainfall and floods, can substantially affect society, in terms of the high TC induced extreme rainfall and great human mortality and displacement rates caused by TC induced floods. The projected future intensified TCs indicate increasing TC risks.
Bacterial outer membrane vesicles provide an alternative pathway for trafficking of type III secreted effectors into epithelial cells

Outer membrane vesicles (OMVs) are proteo-liposomes universally shed by Gram-negative bacteria. Their secretion is significantly enhanced by the transition into the intra-host milieu and OMVs have been shown to play critical roles during pathogenesis. Enterohemorrhagic Escherichia coli O157 (EHEC), causes diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications including hemolytic uremic syndrome, have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severity in vivo. Here, we show that type III secreted substrates including translocators and effectors are incorporated into OMVs independent of type III secretion activity. EHEC strains with non-functional type III secretion systems shed more OMVs and vesicles enter host cells with accelerated kinetics compared to vesicles shed from wild type EHEC. The T3SS effector translocated intimin receptor (Tir) is trafficked from OMVs into host cells and localizes to the membrane. However, its clustering on the host membrane and co-localization with bacterial pedestals is intimin-dependent. We further show that OMV-delivered Tir can cross-complement an effector-deficient EHEC strain, demonstrating that OMV-associated effectors reach the host cell in a biologically intact form. Finally, we observe that the non-LEE encoded E3 ubiquitin ligase effector NleL is also trafficked to host cells via OMVs, where it ubiquitinylates its target kinase JNK. Together, these data demonstrate that trafficking of OMV-associated effectors is a novel and T3SS-independent pathway for the delivery of active effectors to host cells.
Impact of Socio-Economic Factors on Students’ Achievement in English Language in the Senior High Schools in West Akim Municipality of Ghana

The main focus of the study is to investigate the influence of students’ socio-economic background, parental involvement and teacher’s attitude on their achievement in English in the senior high schools in West Akim Municipality. The study also investigated the cumulative effect of the three factors on students’ achievement in the English language. Three research questions guided the study. Ex-post factor research design was adopted for the study. A total of 100 students were selected by means of simple random sampling technique while four schools in the municipal were selected via stratified sampling technique. Questionnaire was the major instrument data collection. Quantitative paradigm was employed for data analysis which involved the use of descriptive (percentages and frequencies) and inferential statistics of which tables were used to highlight the objectives of the study. Based on the investigative study conducted, it was discovered that Findings of the study revealed that socioeconomic background, parental involvement and teachers’ attitude are very important factors in determining students’ achievement in core subjects such as the English language. Additionally, findings reveal that teachers’ attitude is one most important factor instrumental to students’ achievement in the English language. This means students’ academic issues are not the only factors predictive of students’ achievement in the English language.
Evaluation of sternal morphology according to age and sex in multidedector computerized tomography

Objectives: The sternum is located in the middle of the anterior wall of the thoracic cage. It consists of three parts; manubrium, body (corpus) and xiphoid process. Since it is an easy bone to scan, it can be used for age and sex determination in forensic medicine. The aim of the study was to investigate the characteristics of the sternum according to age and gender. Methods: This study was performed retrospectively on 700 CT images. 3D volume rendering images of sternum were created from the axial CT images at a 1 mm slice thickness. Results: There were significant differences in sternum measurements according to age and sex. The xiphoid process was identified under three different types. Ossification between the manubrium and sternum body showed significant differences according to age and sex. Conclusion: Data collected from a single bone is important for age and sex prediction especially in forensic medicine. These data taken from a large series may also contribute to evaluation of variations in sternal morphology.
Vitamin D Deficiency and Clinically Detected Scoliosis among Male Adolescents at High-Altitude Area in Southwestern Saudi Arabia

BACKGROUND AND OBJECTIVES: Reports suggest that Vitamin D deficiency (VDD) is common and is a general health challenge worldwide and at high altitude in particular. AIM: The objectives were to explore Vitamin D status, to examine the association of VDD and clinically detected scoliosis, and to find a cutoff point of Vitamin D level predicting clinical scoliosis in Abha City (high-altitude area). METHODS: A nested case–control design was conducted among a screened population of 417 male adolescents from intermediate and secondary schools in Abha City, Southwest Saudi Arabia. From the surveyed adolescents, 62 cases with clinically detected scoliosis and 205 age-matched controls without scoliosis were selected. For both groups, serum level of 25-hydroxyvitamin D was assessed by standardized technique. RESULTS: More than two-thirds (68.5%) of male adolescents suffered from VDD (<25 nmol/L). The risk of clinical scoliosis was significantly higher among adolescents with VDD compared to those without deficiency (grade adjusted odds ratio = 6.88, 95% CI: 2.63–17.99). Receiver operating characteristic curve analysis showed acceptable discriminative ability of serum Vitamin D (area under the curve = 0.702) to predict scoliosis at a threshold value of ≤20.2 nmol/L. CONCLUSIONS: Overall levels of Vitamin D in the study adolescents suggest a high prevalence of VDD at high-altitude area in Southwest Saudi Arabia. There is evidence for a positive association between VDD and clinically detected scoliosis. A threshold cutoff value of 20.2 nmol/L has been identified to predict clinically detected scoliosis. The role of possible preventive effect of Vitamin D supplementation should be considered by school health authorities.
Australian Labradoodle Dystrophinopathy: A Novel Canine Model for the Study of Duchenne Muscular Dystrophy Cardiomyopathy

ii Acknowledgments . iv List of Tables . vii List of Figures . viii List of Abbreviations . ix Chapter 1: Literature Review . 1 DMD Epidemiology . 2 DMD Clinical Findings . 3 Therapeutic Strategies . 11 Dystrophin and the Dystrophin Associated Protein Complex . 13 DMD Animal Models . 21 Labradoodle History . 26 Transcriptomics . 27 Chapter 2: Characterization of Australian Labradoodle Dystrophinopathy . 31 Chapter 3: Cardiac transcriptome analysis identifies differentially expressed genes in Australian Labradoodle dystrophinopathy . 43 Chapter 4: Conclusions . 82 References . 86
A Study of Fetal Apgar score in Pregnancy beyond 40 Weeks

Postdated pregnancy or in other words the pregnancy which has crossed the EDD is one of the many reasons that causes a great amount of stress to the parents and also the pediatricians. Prolongation of pregnancies complicates pregnancies and carries increased risk to mother and fetus. Emerging evidence demonstrates that the incidence of complications increases after 40 weeks of gestation. The present study conducted to find out the fetal outcome of such prolonged pregnancy. Methods: A prospective study conducted in Department of Pediatrics Kanachur Institute of Medical Sciences, Deralakatte, Mangalore, Karnataka. Data collected from pregnant women completed 40 week of gestational age admitted in hospital were collected. Aim of study is to know the fetal complications. Result: In our study out of 30 pregnant women were selected. Conclusion: Post term pregnancies require early detection, effective and proper planning management.
Pulmonary trunk to ascending aorta ratio and reference values for diameters of pulmonary arteries and main bronchi in healthy adults

Objectives: The ratio of the diameter of pulmonary trunk (PT) to the diameter of the ascending aorta (AA) is used to evaluate cardiopulmonary diseases. Different values have been reported for the normal value of PT:AA ratio (to be less than 0.9, 1 or 1.4). In this study, we aimed to investigate the diameters of the PT, right (RPA) and left pulmonary artery (LPA), AA, right (RMB) and left main bronchus LMB) using multidetector computed tomography (MDCT) and to determine reference values for PT:AA according to age and sex in normal healthy adults. Methods: Thoracic CT images of 200 individuals, (103 males, 97 females; age 18–89 years), without cardiopulmonary pathology and surgery, were retrospectively evaluated using MDCT. Diameters of PT, RPA, LPA, AA were measured at the level of the pulmonary artery bifurcationand PT:AA ratio was calculated. Results: The mean diameters of PT, AA, RPA, LPA, RMB, LMB were found as 2.7±0.51 cm, 3.25±0.63 cm, 1.98±0.46 cm, 1.81±0.43 cm, 1.73±0.35 cm, and 1.66±0.55 cm, respectively. The mean value of PT:AA ratio was 0.84±0.18 cm in males and 0.86±0.13 cm in females. Conclusion: Determining the normal values of related measurements will contribute to diagnosis and treatment of cardiopulmonary diseases.
Solitary bee larvae prioritize carbohydrate over protein in parentally provided pollen

Most organisms must regulate their nutritional intake in an environment full of complex food choices. While this process is well understood for self-sufficient organisms, dependent offspring, such as bee larvae, in practice have limited food choices because food is provided by parents. Nutrient balancing may therefore be achieved by offspring, by parents on offspring’s behalf, or by both, whether cooperatively or in conflict. We used the Geometric Framework to investigate the capacity of dependent larval mason bees (Osmia bicornis) to regulate their intake of protein and carbohydrate. Female Osmia seal eggs individually inside cells they have provisioned with pollen, and have no contact with developing offspring, allowing offspring choices to be studied in isolation. Herbivorous insect larvae are typically expected to balance protein and carbohydrate to maximise growth and reproduction. Contrary to prediction, carbohydrate and not protein mediated both growth and survival to pupation. Accordingly, larvae prioritised maintaining a constant intake of carbohydrate and self-selected a relatively carbohydrate biased diet compared to other hymenopterans, while tolerating wide excesses and deficiencies of protein, rendering them potentially vulnerable to dietary change or manipulation. Reasons for prioritising carbohydrate may include (1) the relative abundance of protein in their normal pollen diet, (2) the relative paucity of nectar in parental provisions making carbohydrate a scarce resource, or (3) the requirement for diapause for all O. bicornis larvae. Larvae were intolerant of moderate dietary dilution, likely reflecting an evolutionary history of nutrient-dense food. Our results demonstrate that dependent offspring can remain active participants in balancing their own nutrients even when sedentary, and, moreover, even in mass provisioning systems where parents and offspring have no physical contact. Research should now focus on whether and how evolutionary interests of parent and dependent offspring coincide or conflict with respect to food composition, and the implications for species’ resilience to changing environments.
Mapping invasive plants with citizen science. A case study from Trieste (NE Italy)

Abstract A citizen science initiative was launched in the province of Trieste, aimed at mapping the distribution of Ailanthus altissima, Ambrosia artemisiifolia and Senecio inaequidens. The reliability of citizen data was tested against control data obtained by trained personnel with a stratified random sampling. In spite of the lack of a strict sampling strategy, citizen data were highly correlated with control data. This was mainly due to: 1) the easy identification of the species and 2) the instructions given to citizens for selecting their observation areas and for avoiding duplicate records. The three species tend to be most frequent in disturbed areas; Ailanthus is highly concentrated in the urban area, Senecio is widely distributed but avoids the city centre, with the highest frequency in the industrial area and along the railways, Ambrosia has a similar pattern, but is most frequent in areas with calcareous substrata. The interpretation of the distribution patterns in terms of land use and ecological factors proved to be quite easy when the three species are considered together (higher frequency in disturbed areas), less so when they are considered separately, most probably because of historical and sociological factors, such as incomplete migration into the survey area, and “gentrification effects”.
Versatility of Amantadine and Rimantadine for Detection of Cancer

for Detection of Cancer Bram Ramjiawan1,2, Andrew W Maksymiuk3,4, Paramjit S Tappia1*, Rashid Ahmed Bux5, Parveen S Akhtar6, Donald Miller2 and Daniel S Sitar2,4 1Asper Clinical Research Institute & Office of Clinical Research, Canada 2Department of Pharmacology & Therapeutics, Rady Faculty of Health Sciences, Canada 3Cancer Care Manitoba, Canada 4Department of Internal Medicine, Canada 5BioMark Diagnostics Inc., Canada 6Department of Medical Oncology, Bangladesh Crimson Publishers Wings to the Research Opinion
Enhanced nitrous oxide production in denitrifying Dechloromonas aromatica strain RCB under salt and alkaline stress conditions

Salinity and pH are important environmental parameters with direct and indirect impacts on the viability and metabolic activities of microorganisms. In this study, the effects of salt and alkaline stresses on the kinetic balance between nitrous oxide (N2O) production and consumption in the denitrification pathway of Dechloromonas aromatica strain RCB were examined. N2O accumulated transiently only in insignificant amounts at low salinity (≤0.5% NaCl) and circumneutral pH (7.0 and 7.5). Incubation at 0.7% salinity resulted in substantially longer lag phase and slower growth rate, along with the increase in the amounts of transiently accumulated N2O (15.8±2.8 μmoles N2O-N/vessel). Incubation at pH 8.0 severely inhibited growth and resulted in permanent accumulation of 29.9±1.3 μmoles N2O-N/vessel from reduction of 151±20 μmoles NO3-. The transcription analyses observed decreased nosZ/(nirS1+nirS2) ratios coinciding with N2O accumulation. The N2O consumption rates of resting D. aromatica cells subjected to the salt and alkaline stress conditions were significantly lower than the rates of N2O production from NO2- reduction at N2O / NO2- concentration of 0.1 mM, but not at a higher concentration (1.0 mM). These results indicate that alteration in N2O consumption kinetics was another cause of enhanced N2O production observed under the stress conditions. The findings in this study suggest that canonical denitrifiers may become a significant N2O source when faced with abrupt environmental changes. Importance Denitrification is one of the two most significant biological sources of N2O. In a complete denitrification pathway, N2O generated from stepwise reduction of NO3- via NO2- and NO is simultaneously reduced to N2. Thus, N2O evolution is often kept minimal in cultivation of canonical denitrifiers at their optimal growth conditions. This study discovered that this orchestration of the reactions in the denitrification cascade is disrupted in Dechloromonas aromatica, an environmentally abundant complete denitrifier, as a stress response to elevated salinity and pH impairing cell viability and growth. This disruption in the kinetic balance resulted in >100-fold increase in the amounts of N2O transiently or permanently produced during the course of denitrification. As rapid fluctuations of salinity and pH are often observed in both natural ecosystems and engineered systems, N2O emissions from the canonical denitrifiers responding to environmental stresses may be a significant, but previously unrecognized, source of N2O.
Interactions microalgues-bactéries en système expérimental bispécifique : effets sur la croissance de Dunaliella sp.

L’utilisation de cultures mixtes algues-bacteries a ete suggeree pour ameliorer les performances des cultures industrielles de microalgues. La presente etude s’attache a etudier l’impact de bacteries selectionnees sur la croissance de la microalgue Dunaliella sp. A cette fin, 97 souches de bacteries ont ete isolees a partir de cultures de microalgues marines. La diversite des souches fait apparaitre des representants des α -et γ-proteobacteries, Cytophaga-Flavobacterium-Bacteroides et gram-positives. Une approche en deux phases a ensuite ete mise en oeuvre pour selectionner des bacteries favorisant la croissance de Dunaliella sp. , a l’aide d’un dispositif original de crible a haut debit. Bien qu’une majorite de bacteries induise une reduction des performances de Dunaliella sp. , certaines conduisent a des ameliorations sensibles. En batch limite par l’azote, la bacterie Alteromonas sp. Possede un effet promoteur sur la biomasse algale et le rendement d’azote. L’hypothese d’une remineralisation par la bacterie, de l’azote organique relargue par Dunaliella sp. Est emise pour expliquer ces meilleurs rendements. Au contraire, en culture continue, le comportement observe laisse supposer une competition de la bacterie pour l’azote limitant. L’apparente contradiction entre les experiences peut etre associee aux variations d’equilibre entre les deux populations et les nutriments disponibles. Ces resultats revelent le potentiel des cultures mixtes pour ameliorer les productions de Dunaliella sp. Ils soulignent egalement la complexite des phenomenes sous-jacents et la necessite de travaux complementaires avant d’envisager un transfert vers les productions industrielles.