Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P)*

The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process.
Making the torch lighter: Areinforced active sampling framework for image classification

In this paper, we aim to construct a more reasonable and effective active sampling model, named as reinforcement uncertainty sampling with bag-of-visual-words (RUSB). Compared with traditional active sampling strategy based on uncertainty, both certainty metric and sample post-processing are introduced for better performance. The certainty metric is measured by the bag-of-visual-words (BoVW) classification model in order to entirely evaluate samples, and the post-processing module is driven by the Q-learning method to construct a compact and efficient training set for the BoVW module. The performance of BoVW is used to initialize and determine the status of the post-processing module during the process of iteration. Meanwhile, the weight of the measurement is associated with each iteration instead of being set manually. Experimental results on real world datasets show the effectiveness of the proposed framework.
Improved Syntheses of the mGlu5 Antagonists MMPEP and MTEP Using Sonogashira Cross-Coupling

The Sonogashira cross-coupling, a key step in the syntheses of the mGlu5 antagonists MMPEP and MTEP, provided an improved three-step method for the preparation of MMPEP in 62% overall yield. Using Spartan molecular modeling kit an explanation for the failure to employ analogues method in the synthesis of MTEP was sought. The DFT calculations indicated that meaningful isolated yields were obtained when the HOMO energy of the aryl halide was lower than the HOMO energy of the respective alkyne.
The gastric caecum of larval Aedes aegypti: stimulation of epithelial ion transport by 5-hydroxytryptamine and cAMP

ABSTRACT We report measurements of ion transport across the gastric caecum of larvae of Aedes aegypti, a vector of yellow fever that inhabits a variety of aquatic habitats ranging from freshwater to brackish water. We provide the first measurements of the effect of 5-hydroxytryptamine (5-HT) on transepithelial potential (TEP), luminal ion concentrations and electrochemical potentials, as well as basolateral membrane potential and H+, Na+ and K+ fluxes. TEP, basolateral membrane potential, and H+, K+ and Na+ fluxes across the gastric caeca declined within 3–6 min after isolation of the entire midgut from the larva. 5-HT restored both the TEP and active accumulation of H+, K+ and Na+ in the lumen. Additionally, 5-HT restored H+, K+ and Na+ fluxes across the distal caecum of freshwater larvae, and restored H+ fluxes across the distal caecum of brackish water larvae. There was no effect of 5-HT on ion fluxes across the proximal caecum. We have also shown that 5-HT restores the basolateral membrane potential in cells of the distal, but not proximal, caecum. Effects of 5-HT on TEP and basolateral membrane potential were mimicked by application of cAMP but not by a phorbol ester. We provide a working model which proposes that 5-HT and cAMP stimulate the vacuolar H+-ATPase of the distal caecum. Our results provide evidence that the gastric caecum is functionally distinct from the adjacent anterior midgut and we discuss possible roles of the gastric caecum in osmoregulation. We also describe similarities in the arrangement of ion transporters in the caecum with those of the Malpighian tubules. Summary: Transport of H+, Na+ and K+ across the gastric caecum of larval mosquitoes is stimulated by serotonin acting through the intracellular messenger cAMP.
Identification and characterization of homeobox (Hox) genes and conservation of the single Hox cluster (324.6 kb) in the water flea Daphnia magna

We report the complete sequence analysis of the entire complement of eight typical homeobox (Hox) genes (Lab, Pb, Dfd, Scr, Antp, Ubx, Abd-A, and Abd-B) and two other genes (Hox3 and Ftz) in a 324.6-kb region in the water flea Daphnia magna. In the cluster of D. magna Hox genes, we found one long interspersed nuclear element (LINE)/R2-NeSL between Ubx and Abd-A that was not present in Daphnia pulex Hox genes. In basal expression of Hox genes at different developmental stages, biothorax complex genes (Ubx, Abd-A, and Abd-B) and some antennapedia complex genes (Lab, Scr, Antp) were moderately expressed, but the Hox3 gene was barely expressed. Three homeobox genes (Antp, Ubx, Abd-A) were highly expressed at 6-7 days after release from the brood chamber and/or in the adult stage. The structural array and transcribed orientation of Dm-Hox genes were identical to those of the sister species D. pulex (∼340 kb), indicating that the Hox gene structure in daphnids is highly conserved. However, Dm- and Dp-Hox3, -deformed (Dfd), and -fushi tarazu (Ftz) genes varied from orthologous genes in pancrustacean species.
Wind Turbine Fault Detection Using a Denoising Autoencoder With Temporal Information

Data-driven approaches have gained increasing interests in the fault detection of wind turbines (WTs) due to the difficulty in system modeling and the availability of sensor data. However, the nonlinearity of WTs, uncertainty of disturbances and measurement noise, and temporal dependence in time-series data still pose grand challenges to effective fault detection. To this end, this paper proposes a new fault detector based on a recently developed unsupervised learning method, denoising autoencoder (DAE), which offers the learning of robust nonlinear representations from data against noise and input fluctuation. A DAE is used to build a robust multivariate reconstruction model on raw time-series data from multiple sensors, and then, the reconstruction error of the DAE trained with normal data is analyzed for fault detection. In addition, we apply the sliding-window technique to consider temporal information inherent in time-series data by including the current and past information within a small time window. A key advantage of the proposed approach is the ability to capture the nonlinear correlations among multiple sensor variables and the temporal dependence of each sensor variable simultaneously, which significantly enhanced the fault detection performance. Simulated data from a generic WT benchmark and field supervisory control and data acquisition data from a real wind farm are used to evaluate the proposed approach. The results of two case studies demonstrate the effectiveness and advantages of our proposed approach.
Democratic Changes and Economic Growth

Today it must be admitted that there is no significant connection between the level of development of democratic institutes and the value of economic growth. This conclusion invariably stems from the vast amount of theoretical and empirical studies that have been conducted over the last 50 years. Why have developed democracies become economic leaders? Why is the US economy growing faster than the economy in Angola, but slower than the economy in Botswana? There are still no answers to these seemingly simple questions. In this paper the author attempts to theoretically justify and empirically confirm the link between the democratic changes in countries and their economic growth. This link becomes apparent if we assume that the amount of transaction costs of exchange depends on the level of political and economic freedom. In turn, transaction costs have a significant influence on the effective functioning of the economy. A decrease in costs of exchange speeds up economic growth and an increase in costs slows down growth. This kind of approach enables us to explain the economic successes of democracies, the lagging behind of many countries in Asia and Africa, the historical reasons for the beginning of the industrial revolution in Europe, the speeding up of economic growth in the 18 th -19 th centuries, the rapid development of production in China and many other occurrences.
Effects of decreasing metabolizable protein and rumen-undegradable protein on milk production and composition and blood metabolites of Holstein dairy cows in early lactation.

This study was conducted to evaluate the effects of decreasing dietary protein and rumen-undegradable protein (RUP) on production performance, nitrogen retention, and nutrient digestibility in high-producing Holstein cows in early lactation. Twelve multiparous Holstein lactating cows (2 lactations; 50 ± 7 d in milk; 47 kg/d of milk production) were used in a Latin square design with 4 treatments and 3 replicates (cows). Treatments 1 to 4 consisted of diets containing 18, 17.2, 16.4, and 15.6% crude protein (CP), respectively, with the 18% CP diet considered the control group. Rumen-degradable protein levels were constant across the treatments (approximately 10.9% on a dry matter basis), whereas RUP was gradually decreased. All diets were calculated to supply a postruminal Lys:Met ratio of about 3:1. Dietary CP had no significant effects on milk production or milk composition. In fact, 16.4% dietary CP compared with 18% dietary CP led to higher milk production; however, this effect was not significant. Feed intake was higher for 16.4% CP than for 18% CP (25.7 vs. 24.3 kg/d). Control cows had greater CP and RUP intakes, which resulted in higher concentrations of plasma urea nitrogen and milk urea nitrogen; cows receiving 16.4 and 15.6% CP, respectively, exhibited lower concentrations of milk urea nitrogen (15.2 and 15.1 vs. 17.3 mg/dL). The control diet had a significant effect on predicted urinary N. Higher CP digestibility was recorded for 18% CP compared with the other diets. Decreasing CP and RUP to 15.6 and 4.6% of dietary dry matter, respectively, had no negative effects on milk production or composition when the amounts of Lys and Met and the Lys:Met ratio were balanced. Furthermore, decreasing CP and RUP to 16.4 and 5.4%, respectively, increased dry matter intake.
Robust and Efficient Joint Alignment of Multiple Musical Performances

The goal of music alignment is to map each temporal position in one version of a piece of music to the corresponding positions in other versions of the same piece. Despite considerable improvements in recent years, state-of-the-art methods still often fail to identify a correct alignment if versions differ substantially with respect to acoustic conditions or musical interpretation. To increase the robustness for these cases, we exploit in this work the availability of multiple versions of the piece to be aligned. By processing these jointly, we can supply the alignment process with additional examples of how a section might be interpreted or which acoustic conditions may arise. This way, we can use alignment information between two versions transitively to stabilize the alignment with a third version. Extending our previous work [1], we present two such joint alignment methods, progressive alignment and probabilistic profile, and discuss their fundamental differences and similarities on an algorithmic level. Our systematic experiments using 376 recordings of 9 pieces demonstrate that both methods can indeed improve the alignment accuracy and robustness over comparable pairwise methods. Further, we provide an in-depth analysis of the behavior of both joint alignment methods, studying the influence of parameters such as the number of performances available, comparing their computational costs, and investigating further strategies to increase both.
Finite element simulations of excitonic solar cells and organic light emitting diodes

This work describes the simulation of excitonic solar cells and organic light emitting diodes using the Finite Element Method. Although solar cells and light emitting diodes have different functions, the former is the time reversal of the latter. This equivalence enables these seemingly disparate functional devices to be simulated analogously. Solar cells based on organic polymers as well as dye-sensitised titanium dioxide are considered and remarkably, these can also be described using a common physical basis, termed the excitonic solar cell. This description accounts for the fact the generation profile of charge carriers in excitonic solar cells is different to that in conventional solar cells such as those made from silicon p-n junctions. Part I investigates two related timescales relevant to the dye-sensitised solar cell and compares a simple analytical model to the numerical simulations under fast extraction conditions. The transport time is shown to be well described numerically, however, the photovoltage rise time was not successfully obtained and the grounds for this discrepancy are investigated. Part II surveys devices based on organic materials. Firstly, a parametric study of solar cells with a complex inter-digitated structure are considered and are consistently shown to be limited by low charge transport efficiencies and space charge effects at high illumination intensity. In addition, the open circuit voltage in these devices is described by specified deviations from the built-in voltage. Secondly, experimental current-voltage characteristics of organic light emitting diodes (OLEDs) made from organic dendrimers are simulated. Distinct regions of the dendrimer molecule control different material properties, thus making them ideal candidates for future device applications where different attributes can be separately optimised. The simulations show that the Mott-Schottky model describing the charge injection barrier height from a metallic electrode is not adhered to in devices which are prepared and tested under ambient conditions.
Swell-shrink behaviour of lime precipitation treated soil

Previous investigation showed that sequential mixing of calcium chloride and sodium hydroxide solutions with an expansive soil resulted in lime precipitation in the soil mass, which controlled the swelling potentials and increased the unconfined compressive strength of treated specimens through strong modification and pozzolanic reactions. However, expansive soils in the field are subjected to cyclic wetting and drying due to environmental conditions, which affects the swell–shrink behaviour. Therefore, the present investigation examines the efficacy of the lime precipitation technique in controlling the swell–shrink potentials and strength characteristics of expansive soils subjected to cyclic wetting and drying. Expansive soil is mixed sequentially with different concentrations of calcium chloride and sodium hydroxide solutions to yield a range of lime precipitation contents, and cured for different time periods. The cured specimens were subjected to cyclic wetting and drying in modified odeometer cells.
Total and Segmental Body Composition Examination in Collegiate Football Players Using Multifrequency Bioelectrical Impedance Analysis and Dual X-ray Absorptiometry

Abstract Raymond, CJ, Dengel, DR, and Bosch, TA. Total and segmental body composition examination in collegiate football players using multifrequency bioelectrical impedance analysis and dual X-ray absorptiometry. J Strength Cond Res 32(3): 772–782, 2018—The current study examined the influence of player position on the agreement between multifrequency bioelectrical impedance analysis (MfBIA) and dual X-ray absorptiometry (DXA) when assessing total and segmental percent body fat (BF%), fat mass (FM), and fat-free mass (FFM) in National Collegiate Athletic Association Division I collegiate football athletes. Forty-four male collegiate athletes (age = 19 ± 1 year; height = 1.9 ± 1.0 m; and body mass = 106.4 ± 18.8 kg) participated. Player positions included: offensive linemen (OL; n = 7), tight ends (TE; n = 4), wide receivers (WR; n = 9), defensive linemen (DL; n = 6), defensive backs (DB; n = 8), linebackers (LB; n = 6), and running backs (RB; n = 4). Total and segmental body composition measured using MfBIA were compared with values obtained using DXA. Compared with DXA, MfBIA underestimated BF% (3.0 ± 3.8%), total FM (2.5 ± 4.3 kg), arm FM (0.4 ± 0.8 kg), arm FFM (1.4 ± 0.9 kg), leg FM (2.8 ± 2.0 kg), and leg FFM (5.4 ± 2.4 kg) (all p < 0.001; arm FM p = 0.002) and overestimated total FFM (−2.4 ± 4.5 kg) (p < 0.001). Limits of agreement (LOAs) were: ±7.39% (BF%), ±8.50 kg (total FM), ±1.50 kg (arm FM), ±1.83 kg (arm FFM), ±3.83 kg (leg FM), ±4.62 kg (leg FFM), and ±8.83 kg (total FFM). No significant differences were observed between devices for trunk FM (−0.3 ± 3.0 kg; p = 0.565) and trunk FFM (0.4 ± 2.4 kg; p = 0.278), with LOAs of ±5.92 and ±4.69 kg, respectively. Player position significantly affected all between-device mean body composition measurement differences (adjusted p ⩽ 0.05), with OL demonstrating the greatest effect on each variable. Therefore, MfBIA does not seem accurate in examining between-player body composition in college football players.
Estrogenic and anti‐estrogenic activity of butylparaben, butylated hydroxyanisole, butylated hydroxytoluene and propyl gallate and their binary mixtures on two estrogen responsive cell lines (T47D‐Kbluc, MCF‐7)

The estrogenic and anti‐estrogenic effects of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) were evaluated for individual compounds as well as for binary mixtures, using an estrogen‐dependent reporter gene assay in T47D‐Kbluc breast cancer cells and an estrogen‐dependent proliferation assay in MCF‐7 breast cancer cells. In terms of estrogenicity the potency of the selected compounds increased from BHA < PG < BuPB in the luciferase assay (with BHT showing no significant estrogenic activity), while in the proliferation assay the following order was observed: BHT < BHA < BuPB (with PG showing no significant estrogenic activity). Non‐monotonic dose–response curves were obtained for BuPB (in both assays) and PG (in the luciferase assay), respectively. In the presence of estradiol, a significant anti‐estrogenic activity was observed in both cell lines for PG, BuPB and BHA, while BHT showed weak anti‐estrogenic activity only in T47D‐Kbluc cells. The evaluation of binary mixtures confirmed the endocrine disruptive potential of the compounds, their individual potency being correlated with that of the mixtures. All mixtures were able to reduce the estradiol‐induced luminescence or cell proliferation, an effect that was accurately predicted by the dose addition mathematical model, suggesting the same (or at least partially overlapping) modes of action for the tested compounds. The results of the present study emphasize the importance of a cumulative risk assessment of endocrine disruptors.
Nurses’ care practices at the end of life in intensive care units in Bahrain

Background: The process of dying in intensive care units is complex as the technological environment shapes clinical decisions. Decisions at the end of life require the involvement of patient, families and healthcare professionals. The degree of involvement can vary depending on the professional and social culture of the unit. Nurses have an important role to play in caring for dying patients and their families; however, their knowledge is not always sought. Objectives: This study explored nurses’ care practices at the end of life, with the objective of describing and identifying end of life care practices that nurses contribute to, with an emphasis on culture, religious experiences and professional identity. Research Design and context: Grounded theory was used. In all, 10 nurses from intensive care unit in two large hospitals in Bahrain were participated. Ethical Considerations: Approval to carry out the research was given by the Research Ethics Committee of the host institution, and the two hospitals. Findings: A core category, Death Avoidance Talk, was emerged. This was supported by two major categories: (1) order-oriented care and (2) signalling death and care shifting. Discussion: Death talk was avoided by the nurses, doctors and family members. When a decision was made by the medical team that a patient was not to be resuscitated, the nurses took this as a sign that death was imminent. This led to a process of signalling death to family and of shifting care to family members. Conclusion: Despite the avoidance of death talk and nurses’ lack of professional autonomy, they created awareness that death was imminent to family members and ensured that end of life care was given in a culturally sensitive manner and aligned to Islamic values.
Pregnane X-receptor promotes stem cell-mediated colon cancer relapse

Colorectal cancer lethality usually results from post-treatment relapse in the majority of stage II-IV patients, due to the enhanced resistance of Cancer Stem Cells (CSCs). Here, we show that the nuclear receptor Pregnane X Receptor (PXR, NR1I2), behaves as a key driver of CSC-mediated tumor recurrence. First, PXR is specifically expressed in CSCs, where it drives the expression of genes involved in self-renewal and chemoresistance. Clinically, high levels of PXR correlate with poor recurrence-free survival in a cohort of >200 stage II/III colorectal cancer patients treated with chemotherapy, for whom finding biomarkers of treatment outcome is an urgent clinical need. shRNA silencing of PXR increased the chemo-sensitivity of human colon CSCs, reduced their self-renewal and tumor-initiating potential, and drastically delayed tumor recurrence in mice following chemotherapy. This study uncovers PXR as a key factor for CSC self-renewal and chemoresistance and targeting PXR thus represents a promising strategy to minimize colorectal cancer relapse by selectively sensitizing CSCs to chemotherapy.
Impact Behaviour of PtIr-Based Coatings with Different Interlayers for Glass Lens Moulding

Over the last decades demands for optical systems and complex optical products made of glass increased steadily. Precision glass moulding has a great potential for the bulk production of complex lenses with high precision and low costs. To prevent sticking or reactions between hot glass and moulding, and to reduce abrasive wear of the die a protective coating is deposited on the tool. In this research two coating systems suitable for this application are compared by analysing their behaviour under an impact load. The PVD (Physical Vapor Deposition) coating PtIr with two different bond coatings Ni or Cr is analysed. During impact test number of impacts and loads are varied. Compared to industrially used coating system PtIr with a Ni interlayer the adhesion can be improved by using a Cr interlayer. The PtIr-based coating with Cr as bond coating shows an excellent endurance even at very high loads causing Hertzian stresses in the range of 10 14 GPa. An impact load of 600 N which corresponds to a contact pressure of app. 13.2 GPa generates almost no damage after 200,000 impacts.