Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.     

The Structures of Gd(III) Chelates Conjugated at the Periphery of 3-(1’-Hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer

3-(1’-Hexyloxyethyl)-3-devinyl-pyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll-a derivative currently undergoing human clinical trials, was conjugated at various peripheral positions (position-17 or 20) of HPPH with either Gd(III)-aminobenzyl-DTPA (Gd(III) DTPA) or Gd(III)-aminoethylamido-DOTA (Gd(III) DOTA). The corresponding conjugates were evaluated for in vitro PDT efficacy, T₁, T₂ relaxivities, in vivo fluorescence, and MR imaging under similar treatment parameters. Among these analogs, the water-soluble Gd(III)-aminoethylamido-DOTA linked at position-17 of HPPH, i. e., HPPH-17-Gd(III) DOTA, demonstrated strong potential for tumor imaging by both MR and fluorescence, while maintaining the PDT efficacy in BALB/c mice bearing Colon-26 tumors (7/10 mice were tumor free on day 60). In contrast to Gd(III) DTPA (Magnevist) and Gd(III) DOTA (Dotarem), the HPPH-Gd(III) DOTA retains in the tumor for a long period of time (24 to 48 h) and provides an option of fluorescence-guided cancer therapy. Thus, a single agent can be used for cancer-imaging and therapy. However, further detailed pharmacokinetic, pharmacodynamic, and toxicological studies of the conjugate are required before initiating Phase I human clinical trials.     

The impact of alphabet size on pattern complexity of maxmin-$$\omega$$ω cellular automata

Natural Computing - We present an analysis of an additive cellular automaton (CA) under asynchronous dynamics. The asynchronous scheme is maxmin-$$\omega$$, a deterministic system, introduced in...     

Analysis and assessment of a nanoparticle seeded small scale absorption refrigeration system driven by a low‐grade waste heat source

The thermoeconomic behaviour of a nanoparticle seeded single effect LiBr‐H₂O absorption refrigeration system (ARS) is investigated for a small scale application. In the proposed method, alumina nanoparticles with volume concentrations of 3%, 5%, and 7% are dispersed into an aqua lithium bromide solution. The multiobjective heat transfer search algorithm is employed to examine the design trade‐off between the coefficient of performance (COP) and total annualized cost (TAC). To analyze the overall performance of the system, the influence of five design parameters, namely the temperatures of the generator, absorber, evaporator, condenser and heat exchanger pipe diameter, are studied. It is found that with an increase in the COP, the TAC of the system is initially raised marginally, and after that, raised rigorously with further increment. The comparative results indicate that the COP and TAC of the nanofluid based ARS system are increased by about 7% and decreased by about 3.2%, respectively, corresponding to the Pareto points of the base ARS system. A lower break‐even point of about 2.6 years is achieved for the ARS system containing nanoparticles compared to the base ARS system. Overall, the ARS system containing 5% nanoparticles is the best solution from a thermodynamic and economic point of view.     

Effect of MQL and nanofluid on the machinability aspects of hardened alloy steel

Abstract

The current research comprises of various machinability aspects of 4340 hardened alloy steel which are scrutinized with in context of improvements in main cutting force, tool flank wear, crater wear, surface roughness, micro-hardness, machined surface morphology, chip morphology, chip reduction coefficient and apparent coefficient of friction under three different cutting fluid applications i.e. compressed air, water soluble coolant and nanofluid (using eco-friendly radiator coolant as the base fluid and Al₂O₃ as the nanoparticle) using uncoated cermet cutting inserts and a comparative assessment was performed to select which fluid performed better in terms of various machining attributes among three cutting fluids. The minimum quantity lubrication technique (MQL) was used in which a smaller volume of coolant sprinkled at high pressure. This method is found as the most effective alternative to minimize health risks and machining costs, which is quite high in other setups. The test specimen was machined at three different cutting speeds i.e. 100, 120 and 140?m/min along with two machining parameters i.e. feed and depth of cut were kept constant respectively at 0.2?mm/rev and 0.4?mm. Outcomes made a conclusion that Al₂O₃ enriched ecofriendly nanocoolant outperformed both compressed air and water soluble coolant in terms of every machinability aspects.     

Analytical Modeling of Surface Potential and Drain Current of Hetero-Dielectric DG TFET and Its Analog and Radio-Frequency Performance Evaluation

Semiconductors - In the present paper, analytical modeling of surface potential and drain current for hetero-dielectric double gate tunnel FET (HDG-TFET) has been done. The two dimensional (2D)...     

Effect of swirl and number of swirler vanes on combustion characteristics of methane inverse diffusion flame

Journal of Mechanical Science and Technology - An experimental study is performed to explore the effect of swirl and number of swirler vanes on combustion characteristics of methane inverse...     

A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability

Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1′-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the ¹²⁴I isotope). The PET imaging ability and ex vivo biodistribution of [¹²⁴I] 4 were compared with the well-studied methyl [3-(¹²⁴1′-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [¹²⁴I] 2 ) and [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [¹²⁴I] 4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [¹⁸F]FDG and [¹²⁴I] 2 in 2 % ethanol formulation, [¹²⁴I] 4 , at the same radioactive dose (25 μCi per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2 , which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [¹²⁴I] 4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types—brain, renal carcinomas, pancreas—in which [¹⁸F]FDG shows limitations.     

Preparation and physicochemical study of jute and glass composites of epoxy resin of (2E, 6E)-bis(4-hydroxybenzylidene)cyclohexanone

Polymer Bulletin - Jute and glass composites of epoxy resin of (2E, 6E)-bis(4-hydroxybenzylidene)cyclohexanone (EBHBC) were prepared by compressing molding technique using three different hardeners...