Miracle-dz/UniFAR-FTUs huggingface dataset:
Re-engineering of Human Urokinase Provides a System for Structure-based Drug Design at High Resolution and Reveals a Novel Structural Subsite*

Inhibition of urokinase has been shown to slow tumor growth and metastasis. To utilize structure-based drug design, human urokinase was re-engineered to provide a more optimal crystal form. The redesigned protein consists of residues Ile16-Lys243 (in the chymotrypsin numbering system; for the urokinase numbering system it is Ile159-Lys404) and two point mutations, C122A and N145Q (C279A and N302Q). The protein yields crystals that diffract to ultra-high resolution at a synchrotron source. The native structure has been refined to 1.5 Å resolution. This new crystal form contains an accessible active site that facilitates compound soaking, which was used to determine the co-crystal structures of urokinase in complex with the small molecule inhibitors amiloride, 4-iodo-benzo(b)thiophene-2-carboxamidine and phenylguanidine at 2.0–2.2 Å resolution. All three inhibitors bind at the primary binding pocket of urokinase. The structures of amiloride and 4-iodo-benzo(b)thiophene-2-carboxamidine also reveal that each of their halogen atoms are bound at a novel structural subsite adjacent to the primary binding pocket. This site consists of residues Gly218, Ser146, and Cys191–Cys220 and the side chain of Lys143. This pocket could be utilized in future drug design efforts. Crystal structures of these three inhibitors in complex with urokinase reveal strategies for the design of more potent nonpeptidic urokinase inhibitors.
Errors During Resuscitation: The Impact of Perceived Authority on Delivery of Care.

OBJECTIVE The aim of this study was to determine the influence of perceived authority on pediatric resuscitation teams' response to an incorrect order given by a medical superior. METHODS As part of a larger multicenter prospective interventional study, interprofessional pediatric resuscitation teams (n = 48) participated in a video-recorded simulated resuscitation scenario with an infant in unstable, refractory supraventricular tachycardia. A confederate actor playing a senior physician entered the scenario partway through and ordered the incorrect dose and delivery method of the antiarrhythmic, procainamide. Video recordings were analyzed with a modified Advocacy Inquiry Scale, assessing the teams' ability to challenge the incorrect order, and a novel confederate hierarchical demeanor rating. The association between Advocacy Inquiry score and hierarchical demeanor rating, and whether or not the confederate's incorrect order was followed were determined. RESULTS Fifty percent (n = 24) of resuscitation teams followed the confederate's incorrect order. The teams' ability to challenge the incorrect order (P < 0.0001) and confederate hierarchical demeanor rating (P < 0.05) were significantly associated with whether or not the incorrect order was followed. Significant differences between rates of following the incorrect order at different study sites were observed (P < 0.05). CONCLUSIONS The reluctance of resuscitation teams to appropriately challenge the incorrect order resulted in a high rate of inappropriate medication administration. The rate of teams following the incorrect order was significantly associated with poor challenging of the incorrect order and the hierarchical demeanor of the perceived authority figure. Institution-based factors may impact this rate of incorrect medication administration.
Hydrodynamical backflow in X-shaped radio galaxy PKS 2014−55

We present MeerKAT 1.28 GHz total-intensity, polarization, and spectral-index images covering the giant (projected length $l \approx 1.57$~Mpc) X-shaped radio source PKS~2014$-$55 with an unprecedented combination of brightness sensitivity and angular resolution. They show the clear "double boomerang" morphology of hydrodynamical backflows from the straight main jets deflected by the large and oblique hot-gas halo of the host galaxy PGC~064440. The magnetic field orientation in PKS~2014$-$55 follows the flow lines from the jets through the secondary wings. The radio source is embedded in faint ($T_\mathrm{b} \approx 0.5 \mathrm{\,K}$) cocoons having the uniform brightness temperature and sharp outer edges characteristic of subsonic expansion into the ambient intra-group medium. The position angle of the much smaller ($l \sim 25$~kpc) restarted central source is within $5^\circ$ of the main jets, ruling out models that invoke jet re-orientation or two independent jets. Compression and turbulence in the backflows probably produce the irregular and low polarization bright region behind the apex of each boomerang as well as several features in the flow with bright heads and dark tails.
Panoramic image construction using feature based registration methods

This paper presents the method to stitch multiple photographic images having overlapped fields of view to construct a panorama. Panoramic image provides wide view and covers the various aspect of scene under consideration. Keypoints from captured images have been extracted using Scale Invariant Feature Transform (SIFT) and Speeded-Up Robust Features (SURF). These input images vary in factors like illumination, viewpoint, rotation, scale, blurriness and noise (i.e. Gaussian and salt and pepper). Image registration geometrically aligns the images taken at different times which vary in their illumination. The heterogeneity in image illumination effects the feature extraction and ruins entire stitching process by leaving a visible seam at the junction of degraded images. This anomaly is overcome in preprocessing by making the intensity levels consistent in HSI color domain and also with the histogram equalization. Another widely practiced way for seam removal is to blend both images at the time of image stitching. Keypoints given by feature extraction method contain mismatches or outliers which are further removed from data using Random Sample Consensus (RANSAC). Homographic matrix has been estimated and used to implement affine and projective transformation model. Detailed discussion on the results is given at the end by comparing the techniques side by side. Potential applications for panoramas are medical imaging, high resolution photography and painting reproduction, real estate virtual tours, cinema etc.
Medicinal Chemistry Research Synthesis of 2-phenyl-1h-imidazo[4,5-b]pyridine as Type 2 Diabetes Inhibitors and Molecular Docking Studies

A series of imidazo[4,5-b]pyridines (3–32) was synthesized and evaluated for their ability to inhibit Baker's yeast α-glucosidase enzyme. The IC 50 values for all compounds were in the range of 13.5–93.7 µM with compound 15, a 2,4-dihydroxy-substituted analog, displayed the most potent activity potential. Structure–activity relationship strongly suggested the presence of hydroxyl group at aromatic side chain as the main contributing factor towards the inhibitory potential. Findings also suggested that compounds having hydroxyl groups at ortho and para positions are able to inhibit α-glucosidase enzyme efficiently. This experimental observation was further supported by docking studies carried out on human intestinal maltase-glucoamylase enzyme (PDB ID: 3TOP). The –NH– group of imidazo-pyridine of compound 15 formed H-bond with Asp1526, while both hydroxyls of catechol formed H-bond with Asp1279. Imidazo-pyridine ring was well stabilized by π–π stacking with Phe1560, and other hydrophobic inter
Stability criterion of droop-controlled parallel inverters based on terminal-characteristics of individual inverters

Droop-controlled parallel inverters are widely adopted in micro-grids due to its high reliability and low cost. However, the interaction among the inverters will cause whole system to be unstable even though each individual inverter can operate stably in stand-alone mode. A lot of work has been done for analyzing the stability of parallel inverters with droop control through state-space approach originally used in conventional electrical power system. For this existing approach it is necessary to have the knowledge of inside parameters of each individual inverter in advance, while in practical applications it is not so convenient to obtain the internal structure and parameters. To overcome this problem, this paper proposes a stability analysis approach for the droop-controlled parallel inverters based on the terminal-characteristics of individual inverters. At beginning, the terminal-characteristics of individual inverter with droop control are defined in system synchronous reference frame (SRF), which can be represented by the transfer function between output current and output voltage, and the transfer function between output current and fundamental angular frequency. Then the terminal-characteristics of the whole parallel system are derived out with the ones of each individual inverter. Furthermore, a stability criterion is proposed for the parallel inverters based on the terminal-characteristics of each individual inverter according to the Generalized Nyquist Criterion. Finally, the proposed terminal-characteristics and stable criterion for droop-controlled parallel inverters are verified in frequency domain.
Metastatic Renal Cell Carcinoma

3D spheroids are built by heterogeneous cell types in different proliferative and metabolic states and are enriched in cancer stem cells. The main aim of the study was to investigate the usefulness of a novel metastatic renal cell carcinoma (RCC) 3D spheroid culture for in vitro cancer stem cell physiology research and drug toxicity screening. RCC cell lines, Caki-1 (skin metastasis derived) and ACHN (pleural effusion derived), were efficiently cultured in growth-factor/serum deprived, defined, StemXvivo and Nutristem medium on laminin-coated or poly-D-lysine-coated plates. In optimal 3D culture conditions, ACHN cells (StemXVivo/poly-D-lysine) formed small spheroids with remaining adherent cells of an epithelial phenotype, while Caki-1 cells (StemXVivo/laminin) formed large dark spheroids with significantly reduced cell viability in the center. In the 3D structures, expression levels of genes encoding stem transcription factors (OCT4, SOX2, NES) and RCC stem cell markers (CD105, CD133) were deregulated in comparison to these expression levels in traditional 2D culture. Sunitinib, epirubicin and doxycycline were more toxic to cells cultured in monolayers than for cells in 3D spheroids. High numbers of cells arrested in the G0/G1 phase of the cell cycle were found in spheroids under sunitinib treatment. We showed that metastatic RCC 3D spheroids supported with ECM are a useful model to determine the cancer cell growth characteristics that are not found in adherent 2D cultures. Due to the more complex architecture, spheroids may mimic in vivo micrometastases and may be more appropriate to investigate novel drug candidate responses, including the direct effects of tyrosine kinase inhibitor activity against RCC cells.
Reduced viscous damping in high frequency Piezoelectric Resonant Nanochannels for sensing in fluids

This work reports on the demonstration of a new class of high frequency piezoelectric aluminum nitride resonant sensors, dubbed Piezoelectric Resonant Nanochannels (PRNs), for operation in liquid environment with reduced viscous damping. A novel process consisting of 7 lithographic steps was developed to fabricate the PRNs of this work. The new resonant devices operating at high frequencies (278 and 458 MHz) show an unchanged value of the electromechanical coupling, kt2 (about 0.7 and 0.8 %), whether the channel is filled with air or a liquid. A quality factor in fluid, Qƒ, as high as 464 and 340 is recorded when the 278 MHz PRN is filled with DI-water and 25% glycerol solution, respectively.
Anti-Hyperglycemic Activity of an Aqueous Extract from Flower Buds of Cleistocalyx operculatus (Roxb.) Merr and Perry

A screening of 5 plants used for making drinks in Vietnam revealed a Cleistocalyx operculatus (Roxb.) Merr and Perry flower bud extract to have the highest inhibitory activity against the α-glucosidase enzyme. The anti-hyperglycemic effects of an aqueous extract from flower buds of Cleistocalyx operculatus (CO), a commonly used material for drink preparation in Vietnam, were therefore investigated in vitro and in vivo. In vitro, the CO extract inhibited the rat-intestinal maltase and sucrase activities, with IC50 values of 0.70 and 0.47 mg/ml, respectively. These values are lower than those for a guava leaf extract (GE; IC50 0.97 and 1.28 mg/ml, respectively). Postprandial blood glucose testing of normal mice and STZ-induced diabetic rats by maltose loading (2 g/kg body weight (bw)) showed that the blood glucose reduction with CO (500 mg/kg bw) was slightly less than that with acarbose (25 mg/kg bw) but was more potent than that with GE (500 mg/kg bw). In an 8-week experiment, the blood glucose level of STZ diabetic rats treated with 500 mg of CO/kg bw/day was markedly decreased in comparison with that of non-treated diabetic rats. Consequently, CO is considered to be a promising material for preventing and treating diabetes.
Provincial screening rates for chronic diseases of lifestyle, cancers and HIV in a health-insured population.

BACKGROUND Screening for asymptomatic diseases can reduce the burden of morbidity and mortality in all population groups. There is widespread geographical variation in the quality of care. Few data are available on national screening rates in South Africa and how these vary across the provinces. OBJECTIVE To examine screening rates for chronic diseases of lifestyle (CDL), HIV and cancer in a privately insured population for a single insurer across all nine provinces in South Africa, and to determine whether or not there are any differences between the provinces. METHOD Screening rates were calculated as the proportion of eligible members who had received screening tests during 2011 in each province. Mean screening rates were compared between Gauteng and the other eight provinces. RESULTS Nationwide screening rates were 20.5% for CDL, 8.2% for HIV and 31.9% for cancer. Despite similar insurance coverage, screening rates ranged from 0.3% to 0.95% lower in other provinces compared with Gauteng. Of all the provinces, Gauteng had the highestannual screening rates for CDL, breast cancer, prostate cancer and HIV (p < 0.001), while the Western Cape had the highest rate for cervical cancer (p < 0.001). CONCLUSION There is much variation in preventive care utilisation across the provinces within this health-insured population. Provinces with more abundant healthcare resources have higher screening rates. Further research is required to understand the reasons for the variation, given equal payment access.
Education and occupation as proxies for reserve in aMCI converters and AD

Background: Previous reports have shown that higher education is associated with more severe brain pathology in patients with Alzheimer disease (AD), suggesting that these individuals have a functional reserve provided by education, which masks the clinical expression of a higher degree of neurodegeneration. It is unknown if a similar reserve mechanism exists in patients with amnestic mild cognitive impairment (aMCI). The aim of this study was to assess the impact of education and occupation on brain glucose metabolism (rCMRglc) measured with FDG-PET in aMCI and in a very large sample of subjects with probable AD (pAD). Methods: A total of 242 patients with pAD, 72 with aMCI, and 144 healthy controls participated in the study. At follow-up, 21 subjects with aMCI progressed to AD. A regression analysis was conducted (SPM2), with education and occupation as independent variables, and rCMRglc as dependent variable, adjusting for demographic data, global cognitive status, and neuropsychological scores. Results: The analysis showed a significant association between higher education/occupation and lower rCMRglc in posterior temporoparietal cortex and precuneus in pAD and aMCI converters, and no correlation in aMCI nonconverters and healthy controls. This means that, when submitted to FDG-PET for diagnostic evaluation, pAD and aMCI converters with higher education/occupation had, for comparable cognitive impairment, a more severe rCMRglc reduction than the ones with lower education/occupation. Conclusions: This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer disease (AD) pathology. The results in aMCI converters suggest that functional reserve is already at play in the predementia phase of AD.
Isolation, Growth, and Metabolism of an Obligately Anaerobic, Selenate-Respiring Bacterium, Strain SES-3

A gram-negative, strictly anaerobic, motile vibrio was isolated from a selenate-respiring enrichment culture. The isolate, designated strain SES-3, grew by coupling the oxidation of lactate to acetate plus CO2 with the concomitant reduction of selenate to selenite or of nitrate to ammonium. No growth was observed on sulfate or selenite, but cell suspensions readily reduced selenite to elemental selenium (Se0). Hence, SES-3 can carry out a complete reduction of selenate to Se0. Washed cell suspensions of selenate-grown cells did not reduce nitrate, and nitrate-grown cells did not reduce selenate, indicating that these reductions are achieved by separate inducible enzyme systems. However, both nitrate-grown and selenate-grown cells have a constitutive ability to reduce selenite or nitrite. The oxidation of [14C]lactate to 14CO2 coupled to the reduction of selenate or nitrate by cell suspensions was inhibited by CCCP (carbonyl cyanide m-chlorophenylhydrazone), cyanide, and azide. High concentrations of selenite (5 mM) were readily reduced to Se0 by selenate-grown cells, but selenite appeared to block the synthesis of pyruvate dehydrogenase. Tracer experiments with [75Se]selenite indicated that cell suspensions could achieve a rapid and quantitative reduction of selenite to Se0. This reduction was totally inhibited by sulfite, partially inhibited by selenate or nitrite, but unaffected by sulfate or nitrate. Cell suspensions could reduce thiosulfate, but not sulfite, to sulfide. These results suggest that reduction of selenite to Se0 may proceed, in part, by some of the components of a dissimilatory system for sulfur oxyanions.
Migration, Entrepreneurship and Development: A Critical Review

We provide an assessment of the state of scholarly and policy debates on migrant entrepreneurs in development. They are often described as super-entrepreneurs who contribute to development through (i) being more entrepreneurial than natives; (ii) providing remittances that fund start-ups in their countries of origin and (iii) returning entrepreneurial skills to their home countries when they re-migrate. We evaluate these three views and conclude that the empirical evidence to support the notion of the migrant as a super-entrepreneur is weak. We further argue that the evidence is less ambiguous on the general development contribution of migration over and above its contribution through entrepreneurship. The implication is that removal of discriminatory barriers against migrants and against migrant entrepreneurs in labour, consumer and financial markets will promote development in both sending and receiving countries, not least through reducing the shares of migrants that are reluctant entrepreneurs.
Antioxidant treatment and outcome of cortinarius orellanus poisoning: a case series

Abstract Objectives: To study the frequency, severity, and long-term outcome of renal injury in Cortinarius orellanus poisoning, to evaluate the association between the ingested amount of C. orellanus and outcome, and to evaluate the effect of N-acetylcysteine and corticosteroid treatment on outcome. Methods: Case series of eight patients. Diagnosis and severity of acute kidney injury (AKI) and chronic kidney disease (CKD) were classified according to current AKI and CKD definitions. N-acetylcysteine and corticosteroids were administered to six patients, former according to the standard for paracetamol poisoning. Main findings: All patients developed AKI, six in the most severe stage and four required renal replacement therapy (RRT). After 12 months, seven patients presented with CKD, of whom three required chronic RRT and further two were in advanced CKD. AKI and CKD severity highly correlated with the consumed amounts of Cortinarius orellanus (r = 0.98, p < 0.001 and r = 0.78, p = 0.02, respectively) but not with N-acetylcysteine and corticosteroid treatment. Conclusions: AKI and CKD by current definitions and classifications are frequent and severe after Cortinarius orellanus poisoning. The ingested amount of Cortinarius orellanus correlates with the severity of both AKI and CKD. N-acetylcysteine and corticosteroid treatment do not seem to have a beneficial effect on either AKI or CKD.
Analysis of the meiotic role of the mitochondrial ribosomal proteins Mrps17 and Mrpl37 in Saccharomyces cerevisiae

Sporulation in the yeast Saccharomyces cerevisiae is a complex and tightly regulated pathway that involves the induction of a large number of genes. We have identified MRPS17 in a cDNA library enriched for sporulation‐specific genes. Homology searches show that the first one‐third of Mrps17 has strong sequence similarity to bacterial S17 proteins, suggesting that Mrps17 is a potential mitochondrial ribosomal protein. This is further supported by the fact that mrps17Δ cells are respiratory‐deficient and that a Mrps17–GFP fusion localizes to the mitochondria. We have confirmed by Northern blot analysis that both MRPS17 and MRPL37 are strongly induced during the middle stages of sporulation and that this induction is dependent on the presence of a middle sporulation element (MSE) in the promoters of these genes. Interestingly, we found that Mrps17 and Mrpl37, but not other mitochondrial ribosomal proteins, accumulate during the middle stages of sporulation. These results suggest that Mrps17 and Mrpl37 may have additional meiosis‐specific roles. Copyright © 2004 John Wiley & Sons, Ltd.
Preoperative Craniofacial Dysmorphology in Isolated Sagittal Synostosis: A Comprehensive Anthropometric Evaluation

Although clinical descriptions of altered calvarial shape in isolated sagittal synostosis abound in the literature, systematic quantitative assessment of the total morphologic pattern of preoperative craniofacial dysmorphology remains limited in this population. To address this deficit, a retrospective study was undertaken of 256 preoperative patients younger than 6 years with isolated sagittal synostosis who were seen at the Dallas Craniofacial Center. Patients were examined using a battery of 23 anthropometric measurements of the head and face, from which 10 proportion indices were calculated. The measurements and proportions for each patient were compared with sex- and age-matched norms and converted to standard (Z) scores. The pooled data for each variable were analyzed using 1-sample t-tests. The patients were then separated into 2 age groups-younger than 6 months (n = 162) and 6 months or older (n = 94)-and compared via 2-sample t-tests to examine age-related differences. To further elucidate craniofacial growth patterns, standardized anthropometric measures were then correlated against age. Results indicated that the head was enlarged and elongated with compensatory transverse growth of the anterior cranial vault and reduction in the height of vertex. The face was enlarged, especially along the sagittal axis. The head and face were significantly larger relative to age in children younger than 6 months and show a general decrease in size relative to age in all dimensions except cranial length. The data indicate a complex pattern of dysmorphology, which involves the entire craniofacial complex, not just the cranial vault.