DNA minor groove binders-inspired by nature

The synthesis and biological activity of a variety of analogues to the naturally occurring anti-bacterial and anti-fungal Distamycin A were explored by a number of authors. These compounds were subject to a large array of assays. Some of these compounds showed high activity against a range of Gram-positive, Gram-negative bacteria as well as fungi. To explore the anti-parasitic activity of this class of compounds, specific modifications had to be made. A number of these compounds proved to be active against Trypanosoma brucei. The binding of a number of these compounds to short sequences of DNA were also examined using footprinting assays as well as NMR spectroscopy. Computer modelling was employed on selected compounds to understand the way these compounds bind to specific DNA sequences. A large number of variations were made to the standard structure of Distamycin. These changes involved the replacement of the pyrrole moieties as well as the head and tail groups with a number of heterocyclic compounds. Some of these MGBs were also investigated for their capability for the treatment of cancer and in particular lung cancer

Effect of zero tillage and different weeding methods on grain yield of durum wheat in semi-arid regions

Received: September 28th, 2020 ; Accepted: December 1st, 2020 ; Published: December 10th, 2020 ; Correspondence: [email protected] high grain yield of wheat is limited by the dominance of weeds, particularly wild oat. Therefore, to improve wheat yield under these conditions, a field experiment was carried out in Maru Agricultural Research Station, Jordan during 2015–2016 and 2016–2017 to investigate yield response of two wheat varieties (Triticum durum L.) to different tillage and weeding treatments. The experimental design used was a split-split arrangement in a randomized complete block design with three replicates. Two-tillage treatments (conventional vs. zero tillage) were applied to the main plot, two wheat varieties to sub-plot, and five weeding methods (hand weeding, broadleaf + narrow leaf herbicide, broadleaf herbicide, narrow leaf herbicide, and controls) as a sub-sub-plot. The variety ‘Umqais’ had higher plant height, biological, grain, and straw yield than the variety ‘Sham’. Hand weeding slightly increased grain yield compared with mixed herbicides (the 2,4-D plus Antelope Clodinatop- propagyl). Furthermore, mixed herbicides presented a higher grain yield than using either single herbicide. The interaction between tillage systems and weeding methods was significant in both years. The highest (P < 0.05) straw yield (5,990 kg ha-1 ) was obtained by hand weeding under conventional tillage in the first season while the highest grain yield (2,005 kg ha-1 ) was obtained by hand weeding under zero tillage in the second season. Under all weed control treatments, the variety ‘Umqais’ had higher biological, grain, and straw yields than the variety ‘Sham’ in the second season indicating that variety ‘Umqais’ performed better under dry conditions. Our results confirmed the superior of zero tillage for increasing the grain yield of the variety ‘Umqais’, and for increasing the biological and straw yields of the variety ‘Sham’ under semi-arid rainfed conditions of Jordan

Gallbladder cancer: 7-Year experience from Qatar

Thirty-five patients presented with GC during the study period, 10 females (28.6%) and 25 males (71.4%). Fourteen patients (40%) were diagnosed incidentally after laparoscopic cholecystectomy, 16 (48.6%) were diagnosed pathologically, and 4 (11.4%) were diagnosed radiologically. The median age at diagnosis was 54 years (31–78). 74.3% of the disease occurred in patients less than 60 years old. Metastatic disease was discovered in 25 patients (71.4%) versus no metastasis in 10 patients (28.6%). The most common sites for metastasis were the liver (42.9%), peritoneum (25.7%), and lymph nodes (25.7%). Curative central hepatic resection was done in 8 patients (22.9%). Pathology showed adenocarcinoma in 27 patients (77.1%), neuroendocrine tumor in 3 patients (8.6%) and high-grade dysplasia in 1 patient (2.9%). No histopathology was available for 4 patients (11.4%). Twenty-eight patients (80.0%) had regular follow up, with 22 (62.9%) still alive. Six patients (17.1%) died during follow up with survival after diagnosis ranging from 42 days to 6.8 years

Facile synthesis of Schiff and Mannich bases of isatin derivatives

We report herein on the synthesis of some isatin Schiff’s bases (1–11), which were prepared from the reaction of isatin and some aromatic amines. These in turn were converted to the corresponding Mannich bases (12-23) by reaction with a number of secondary amines and formaldehyde, taking advantage of the active –NH group in the isatin. The structures of these compounds were elucidated using standard spectroscopic and analytical methods

A detailed binding free energy study of 2 : 1 ligand–DNA complex formation by experiment and simulation

In 2004, we used NMR to solve the structure of the minor groove binder thiazotropsin A bound in a 2 : 1 complex to the DNA duplex, d(CGACTAGTCG)2. In this current work, we have combined theory and experiment to confirm the binding thermodynamics of this system. Molecular dynamics simulations that use polarizable or non-polarizable force fields with single and separate trajectory approaches have been used to explore complexation at the molecular level. We have shown that the binding process invokes large conformational changes in both the receptor and ligand, which is reflected by large adaptation energies. This is compensated for by the net binding free energy, which is enthalpy driven and entropically opposed. Such a conformational change upon binding directly impacts on how the process must be simulated in order to yield accurate results. Our MM-PBSA binding calculations from snapshots obtained from MD simulations of the polarizable force field using separate trajectories yield an absolute binding free energy (-15.4 kcal mol-1) very close to that determined by isothermal titration calorimetry (-10.2 kcal mol-1). Analysis of the major energy components reveals that favorable non-bonded van der Waals and electrostatic interactions contribute predominantly to the enthalpy term, whilst the unfavorable entropy appears to be driven by stabilization of the complex and the associated loss of conformational freedom. Our results have led to a deeper understanding of the nature of side-by-side minor groove ligand binding, which has significant implications for structure-based ligand development

Noise Effects on a Proposed Algorithm for Signal Reconstruction and Bandwidth Optimization

The development of wireless technology in recent years has increased the demand for channel resources within a limited spectrum. The system\u27s performance can be improved through bandwidth optimization, as the spectrum is a scarce resource. To reconstruct the signal, given incomplete knowledge about the original signal, signal reconstruction algorithms are needed. In this paper, we propose a new scheme for reducing the effect of adding additive white Gaussian noise (AWGN) using a noise reject filter (NRF) on a previously discussed algorithm for baseband signal transmission and reconstruction that can reconstruct most of the signal’s energy without any need to send most of the signal’s concentrated power like the conventional methods, thus achieving bandwidth optimization. The proposed scheme for noise reduction was tested for a pulse signal and stream of pulses with different rates (2, 4, 6, and 8 Mbps) and showed good reconstruction performance in terms of the normalized mean squared error (NMSE) and achieved an average enhancement of around 48%. The proposed schemes for signal reconstruction and noise reduction can be applied to different applications, such as ultra-wideband (UWB) communications, radio frequency identification (RFID) systems, mobile communication networks, and radar systems

Braille code classifications tool based on computer vision for visual impaired

Blind and visually impaired people (VIP) face many challenges in writing as they usually use traditional tools such as Slate and Stylus or expensive typewriters as Perkins Brailler, often causing accessibility and affordability issues. This article introduces a novel portable, cost-effective device that helps VIP how to write by utilizing a deep-learning model to detect a Braille cell. Using deep learning instead of electrical circuits can reduce costs and enable a mobile app to act as a virtual teacher for blind users. The app could suggest sentences for the user to write and check their work, providing an independent learning platform. This feature is difficult to implement when using electronic circuits. A portable device generates Braille character cells using light- emitting diode (LED) arrays instead of Braille holes. A smartphone camera captures the image, which is then processed by a deep learning model to detect the Braille and convert it to English text. This article provides a new dataset for custom-Braille character cells. Moreover, applying a transfer learning technique on the mobile network version 2 (MobileNetv2) model offers a basis for the development of a comprehensive mobile application. The accuracy based on the model reached 97%

Efficacy of tadalafil in Egyptian and Turkish men with erectile dysfunction

A randomised, double-blind, parallel, placebo-controlled, 12-week study was carried out to evaluate the efficacy and safety of 20-mg tadalafil taken ‘as needed’ in a population of men with erectile dysfunction (ED) from Egypt and Turkey. One hundred and thirty-two patients were randomised in this study. Tadalafil was superior to placebo on all three co-primary efficacy end points. The mean change from baseline for the erectile function domain of the International Index of Erectile Function was 9.3 ± 0.8 for the tadalafil group and 2.3 ± 1.6 for the placebo group. Tadalafil-treated patients reported a significantly greater improvement in the mean percentage of successful penetrations (tadalafil: 34.5 ± 4.1; placebo: −4.6 ± 8.1) and successful intercourse attempts (tadalafil: 52.2 ± 3.8; placebo: 16.8 ± 7.8) than placebo-treated patients as measured by the Sexual Encounter Profile. Tadalafil was generally well tolerated with 82% of adverse events being mild in severity. Tadalafil 20-mg taken ‘as needed’ significantly improved the erectile function in Egyptian and Turkish men with ED

Finite element based fatigue life prediction of cylinder head for two-stroke linear engine using stress-life approach

Abstract: This describes the finite element based fatigue life prediction of cylinder head for two-stroke linear engine subjected to variable amplitude loading applicable to electric power generation. A set of Al-alloys, cast iron and forged steel for cylinder head are considered in this study

In-cylinder heat transfer characteristics of hydrogen fueled engine: a steady state approach

Abstract: This study presents in-cylinder heat transfer characteristics of a single cylinder port injection Hydrogen fueled Internal Combustion Engine (H2ICE) using a steady state approach. Problem statement: The differences in characteristics between hydrogen and hydrocarbon fuels are led to the difference in the behavior of physical processes during engine cycle. One of these processes is the in-cylinder heat transfer. Approach: One dimensional gas dynamic model was used to describe the heat transfer characteristics of the engine. The engine speed was varied from 2000-5000 rpm, crank angle from -40° to +100°, while Air-Fuel Ratio (AFR) was changed from stoichiometric to lean limit. Results: The simulated results showed higher heat transfer rate but lower heat transfer to total fuel energy ratio with increasing the engine speed. The in-cylinder pressure and temperature were increased with decreasing AFR and increasing engine speed. The in-cylinder air flow rate was increased linearly with increasing engine speed as well as air fuel ratio. Conclusion/Recommendations: The results showed that the AFR has a vital effect on characteristics variation while the engine speed has minor effect. These results can be utilized for the study of combustion rocess, fuel consumption, emission production and engine performance