Triplin: Functional Probing of Its Structure and the Dynamics of the Voltage-Gating Process

Gram-negative bacteria have a large variety of channel-forming proteins in their outer membrane, generally referred to as porins. Some display weak voltage dependence. A similar trimeric channel former, named Triplin, displays very steep voltage dependence, rivaling that responsible for the electrical excitability of mammals, and high inter-subunit cooperativity. We report detailed insights into the molecular basis for these very unusual properties explored at the single-molecule level. By using chemical modification to reduce the charge on the voltage sensors, they were shown to be positively charged structures. Trypsin cleavage of the sensor eliminates voltage gating by cleaving the sensor. From asymmetrical addition of these reagents, the positively charged voltage sensors translocate across the membrane and are, thus, responsible energetically for the steep voltage dependence. A mechanism underlying the cooperativity was also identified. Theoretical calculations indicate that the charge on the voltage sensor can explain the rectification of the current flowing through the open pores if it is located near the pore mouth in the open state. All results support the hypothesis that one of the three subunits is oriented in a direction opposite to that of the other two. These properties make Triplin perhaps the most complex pore-forming molecular machine described to date.     

Controlled fabrication of Pr(OH)3 nanowires for enhanced photocatalytic activities

In this report, praseodymium hydroxide Pr(OH)₃ nanowires with different aspect ratios (length to diameter ratios) were synthesized by a facile hydrothermal approach. The variations in alkali concentration during synthesis are found to form different aspect ratios of nanowires. The X-ray diffraction and Raman spectroscopy analysis demonstrate the absence of any impurity phases in as-prepared materials. Subsequently, photocatalytic activities of as-prepared nanowires were evaluated by the degradation of methyl orange (MO). Our findings reveal that the nanowires with larger aspect ratios have higher photocatalytic efficiency than the smaller aspect ratio samples. X-ray photospectroscopy investigations reveal that the samples with higher aspect ratio are found to exhibit more oxygen vacancies as compared to lower aspect ratio samples. The enhanced photocatalytic activities can be attributed to the presence of higher percentage of active crystal facet (100), higher concentration of defects densities and narrower band gap. Thus, Pr(OH)₃ nanowires can be considered as a potential candidate for the application of wastewater treatment and related technologies.     

Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.     

Effect of flexibility on the dynamic stability of a four-bar mechanism

Dynamic behavior of flexible components of mechanisms is prone to instabilities which create resonant speed barriers. By considering small deformations superimposed on the steady dynamic state, equations governing evolution of disturbances can be obtained. For the case of mechanisms driven by periodic inputs these equations reduce to a system of coupled Mathieu-Hill equations for the amplitudes of modes of vibrations. Application of the Floquet theory determines the critical conditions of speed, geometry and material properties causing dynamic instability.     

Effects of energy conversation measures the life cycle cost of Kuwaiti residential buildings

With increasing energy supply costs, considerable interest is now being shown in introducing energy conservation measures in the construction of residential houses. Kuwait, like any other country, is becoming increasingly aware of the value of conserving its natural fuel resources. For seven months of the year the temperatures in Kuwait are above comfort level; consequently 60% of its consumed energy is used for space cooling.The effects of energy conservation measures are evaluated for a typical two-storey residential building for two design alternatives. The analysis shows that adding insulation material to the walls and roof will reduce owning and operating costs by 173 Kuwaiti Dinars (K.D.)¹ annually for the houseowner, while the saving to the Government will be 1982 K.D. annually for each such housing unit.If additional measures are introduced, such as double glazing of windows, shading devices, use of air-to-air heat exchangers and tight construction to reduce infiltration, the owning and operating costs will be reduced by 870 K.D. annually for the houseowner and an annual saving of 4287 K.D. will be realized for the Government. These figures are based on a 10% discount rate.     

Model predictions and analysis of enhanced biological effectiveness at low dose rates

A severe challenge to all models purporting to describe the biological effects of ionizing radiation has arisen with the discovery of two phenomena: the anomalous trend with dose rate of the frequency of neoplastic transformation of mammalian cells and the apparent excessive damaging power of electron-capture radionuclides when incorporated into cell nuclei. A new model is proposed which predicts and enables interpretation of these phenomena. Radiation effectiveness is found to be expressible absolutely in terms of the net geometrical cross-sectional area of the radiosensitive sites, the duration of the irradiation, the mean free path for ionization, the influence of particles in the slowing-down spectrum pertaining in the medium and two collective time factors determining the mean repair rate and the mean lifetime of unidentified reactive chemical species.     

Liquid axial dispersion coefficient in a packed cooling tower

A dynamic method is used to predict the liquid axial dispersion coefficient in cooling towers. A KCl tracer was employed on the water inlet on the top of the tower. Input and response signals were measured. Cooling tower parameters were determined by predicting the response tracer signal and curve fitting technique in the time domain.     

HEED: a hybrid, energy-efficient, distributed clustering approach for ad hoc sensor networks

Topology control in a sensor network balances load on sensor nodes and increases network scalability and lifetime. Clustering sensor nodes is an effective topology control approach. We propose a novel distributed clustering approach for long-lived ad hoc sensor networks. Our proposed approach does not make any assumptions about the presence of infrastructure or about node capabilities, other than the availability of multiple power levels in sensor nodes. We present a protocol, HEED (Hybrid Energy-Efficient Distributed clustering), that periodically selects cluster heads according to a hybrid of the node residual energy and a secondary parameter, such as node proximity to its neighbors or node degree. HEED terminates in O(1) iterations, incurs low message overhead, and achieves fairly uniform cluster head distribution across the network. We prove that, with appropriate bounds on node density and intracluster and intercluster transmission ranges, HEED can asymptotically almost surely guarantee connectivity of clustered networks. Simulation results demonstrate that our proposed approach is effective in prolonging the network lifetime and supporting scalable data aggregation.     

Chemotherapy of Schistosomiasis present and past

The primary objective of chemotherapy is to cure individual patient by eradication of the infection. This eradication leads to cessation of egg deposition which is the main pathogenic agent for the patient and community. The present generation of antischistosomal drugs provides physicians and public health practitioners with flexible, well tolerated, convenient, highly efficient tools for control of schistosomal morbidity in human, in contrast old generation of antischistosomal drugs were not so.     

Overall heat transfer coefficient in the presence of the axial dispersion coefficient for a forced draught cooling tower

An overall heat transfer coefficient was calculated for a forced draught counterflow cooling tower by using the pulse response technique. The presence of an axial dispersion coefficient for both gas and liquid was considered. Results indicate that, on neglecting the axial mixing and assuming a plug flow, the overall heat transfer coefficient is overestimated and can lead to errors in design applications.