Synthesis, molecular modelling and CYP24A1 inhibitory activity of novel of (E)-N-(2-(1H-imidazol-1-yl)-2-(phenylethyl)-3/4-styrylbenzamides

CYP24A1 (25-hydroxyvitamin D-24-hydroxylase) is a useful enzyme target for a range of medical conditions including cancer, cardiovascular and autoimmune disease, which show elevated CYP24A1 levels and corresponding reduction of calcitriol (the biologically active form of vitamin D). A series of (E)-N-(2-(1H-imidazol-1-yl)-2-(phenylethyl)-3/4-styrylbenzamides have been synthesised using an efficient synthetic route and shown to be potent inhibitors of CYP24A1 (IC50 0.11–0.35 μM) compared with the standard ketoconazole. Molecular modelling using our CYP24A1 homology model showed the inhibitors to fill the hydrophobic binding site, forming key transition metal interaction between the imidazole nitrogen and the haem Fe3+ and multiple interactions with the active site amino acid residues

Adiabatic Formation of Rydberg Crystals with Chirped Laser Pulses

Ultracold atomic gases have been used extensively in recent years to realize textbook examples of condensed matter phenomena. Recently, phase transitions to ordered structures have been predicted for gases of highly excited, 'frozen' Rydberg atoms. Such Rydberg crystals are a model for dilute metallic solids with tunable lattice parameters, and provide access to a wide variety of fundamental phenomena. We investigate theoretically how such structures can be created in four distinct cold atomic systems, by using tailored laser-excitation in the presence of strong Rydberg-Rydberg interactions. We study in detail the experimental requirements and limitations for these systems, and characterize the basic properties of small crystalline Rydberg structures in one, two and three dimensions.Comment: 23 pages, 10 figures, MPIPKS-ITAMP Tandem Workshop, Cold Rydberg Gases and Ultracold Plasmas (CRYP10), Sept. 6-17, 201

Breast cancer management and outcome according to surgeon's affiliation: a population-based comparison adjusted for patient's selection bias

Background Studies have reported that breast cancer (BC) units could increase the quality of care but none has evaluated the efficacy of alternative options such as private BC networks, which is our study objective. Patients and methods We included all 1404 BC patients operated in the public unit or the private network and recorded at the Geneva Cancer Registry between 2000 and 2005. We compared quality indicators of care between the public BC unit and the private BC network by logistic regression and evaluated the effect of surgeon's affiliation on BC-specific mortality by the Cox model adjusting for the propensity score. Results Both the groups had high care quality scores. For invasive cancer, histological assessment before surgery and axillary lymph node dissection when indicated were less frequent in the public sector (adjusted odds ratio (OR): 0.4, 95% confidence interval (CI) 0.3-0.7, and OR: 0.4, 95% CI 0.2-0.8, respectively), while radiation therapy after breast-conserving surgery was more frequent (OR: 2.5, 95% CI 1.4-4.8). Surgeon affiliation had no substantial effect on BC-specific mortality (adjusted hazard ratio (HR): 0.8, 95% CI 0.5-1.4). Conclusions This study suggests that private BC networks could be an alternative to public BC units with both structures presenting high quality indicators of BC care and similar BC-specific mortalit

Imaging Mass Spectrometry: Hype or Hope?

Imaging mass spectrometry is currently receiving a significant amount of attention in the mass spectrometric community. It offers the potential of direct examination of biomolecular patterns from cells and tissue. This makes it a seemingly ideal tool for biomedical diagnostics and molecular histology. It is able to generate beautiful molecular images from a large variety of surfaces, ranging from cancer tissue sections to polished cross sections from old-master paintings. What are the parameters that define and control the implications, challenges, opportunities, and (im)possibilities associated with the application of imaging MS to biomedical tissue studies. Is this just another technological hype or does it really offer the hope to gain new insights in molecular processes in living tissue? In this critical insight this question is addressed through the discussion of a number of aspects of MS imaging technology and sample preparation that strongly determine the outcome of imaging MS experiments

Multivariate analyses for biomarkers hunting and validation through on-tissue bottom-up or in-source decay in MALDI-MSI: application to prostate cancer.

peer reviewe

Left ventricular pseudo-aneurysm: Do not make the same mistake

The differentiation between left ventricular pseudo-aneurysm and true aneurysm is sometimes difficult and there are some pitfalls in the process of making the right diagnosis. Correct diagnosis has considerable effect on the outcome and management of the patients. We report the case of 59-year-old man who referred to the emergency department with complaints of lower extremity edema and dyspnea on exertion. In his past medical history, he had been diagnosed with post-myocardial infarction and apical true aneurysm four months before his arrival at the emergency ward. The patient was under strict medical follow-up for his condition. Echocardiography was conducted in the emergency ward, and it revealed a huge apical pseudo-aneurysm, which had been miss-diagnosed in the past echocardiographic examination. We herein seek to address this issue and underscore the pitfalls in making the correct and necessary distinction between these two not so uncommon entities

Analysis of the binding sites of vitamin D 1α-hydroxylase (CYP27B1) and vitamin D 24-hydroxylase (CYP24A1) for the design of selective CYP24A1 inhibitors: homology modelling, molecular dynamics simulations and identification of key binding requirements

A homology model of human CYP27B1 was built using MOE and was further optimised by molecular dynamics simulations of the hCYP27B1 homology model and a hCYP27B1-SDZ-88357 complex. Docking results from the hCYP27B1-SDZ-88357 complex showed amino acids Arg107, Asn387 and Asp320 have an important role in binding interaction, with Asp320 part of the important acid-alcohol pair situated in the I-helix with the conserved sequence (A/G) GX (E/D) (T/S), which assumes an essential role in the binding of an oxygen molecule for catalysis. Additional docking experiments with selective hCYP27B1 or hCYP24A1 inhibitors using both the hCYP27B1 model and a triple mutant hCYP24A1 model provided further support for the importance of H-bonding interactions with the three identified active site amino acids. To confirm the role of Arg107, Asn387 and Asp320 in the active site of hCYP27B1 compounds were designed that would form H-bonding interactions, as determined from docking experiments with the hCYP27B1 model. Subsequent synthesis and CYP24A1 and CYP27B1 enzyme assays of the designed compounds 1a and 1b showed a ∼5-fold selectivity for CYP27B1 confirming the importance of Asp320 in particular and also Asn387 and Arg107 as important amino acids for CYP27B1 inhibitory activity

Experimental and mathematical survey of sound absorption performance of date palm fibers

The present study examines the acoustic behavior sample composites made of date palm natural fibers and polyvinyl alcohol. It also provides the comparison between the sound absorption coefficients obtained from the experimental tests and the ones predicted by the mathematical models. An impedance tube system was used to measure the normal sound absorption coefficient of the samples. Using the differential equation algorithm, the predicted sound absorption coefficient for the Johnson-Champoux-Allard model was also calculated. The sound absorption properties of samples increased significantly by increasing the frequency, and increasing the thickness of materials with constant density. Comparison of the data from the experimental tests and mathematical model showed that increasing the thickness of samples will make the predicted and tested values of acoustic absorption coefficient significantly comparable. Date palm fibers have a good potential for dissipating the energy of sound waves particularly when an air gap is introduced behind the sample and can be used as a new source for the fabrication of natural fiber reinforced composites. © 2019 The Author(s

Employment of the Master of Arts in Mathematics Education Graduates of a University in Northern Philippines

This study aimed to trace the 2015 to 2019 MAME graduates in the College of Teacher Education for Graduate Studies of the University of Northern Philippines in terms of their personal profile, their work-related profile before and after taking their master’s degree, reasons of taking up the program, competency level before and after taking the program, appraisal of the most useful courses offered in the program, evaluation on the contribution of the program to their personal and professional growth and assessment on the features of the program and suggestions of how to improve the program. The researcher utilized mixed method of research. The subjects were the MAME graduates, and a questionnaire and open-ended questions were sent to them thru various online flat forms. Based on the findings of the study, the following conclusions are derived: pursuing graduate studies chooses no sex, civil status or age as long as there is a will to improve one's self; students have math- related educational background and finished the program within the prescribed number of years; having master’s degree could contribute greatly in landing a permanent teaching job in public schools; professional and personal growth and development is the strongest drive to pursue advance education; the program offers subjects that are useful which enhanced the teaching competencies of the graduates and consequently contribute to the holistic development of the graduates; and that there are areas needing improvement in the MAME program

Determination of Discharge Coefficient for both Semicircular and Triangular Labyrinth Weirs

A Labyrinth weir is a type of nonlinear weir folded in plan-view, with the ability to pass a large flow at low heads due to an increase in the effective length of the weir crest for a given channel width. The discharge coefficients (Cd) were experimentally determined for both semicircular and triangular labyrinth weirs of varying sidewall angles (α) under free-flow conditions using eight physical models. Dimensional analyses are conducted using the Buckingham π theorem to find the dependent and non-dependent variables. A nonlinear empirical equation was developed using (Statistical Package for the Social Sciences 22) software. The findings show that the discharge coefficient decreases with the increase of headwater to (Ht /P) for both types of labyrinth weir with different plan forms. It is found that the efficiency of the semicircular and triangular labyrinth is higher than linear weir for (Ht /P ≤ 0.45) and decreases with increasing the value of (Ht /P) due to interference of flow between the layers in downstream. The obtained results revealed that the discharge coefficient (Cd) values obtained empirically using multivariable power regression and 5th degree polynomial equations considerably agree with the experimental data, for both of the semicircular and triangular labyrinth weirs. Furthermore, the correlation coefficient R2was (0.9951) and (0.9637) using 5th degree polynomial equation, and their values were (0.9643) and (0.9274) using multivariable power regression equation for both semicircular and triangular labyrinth weir models, respectively. The results in the present study compared quite well with the predicted results of the proposed equations obtained by other investigators