Mixed-Mode Interlaminar Fracture Toughness of Glass and Carbon Fibre Powder Epoxy Composites—For Design of Wind and Tidal Turbine Blades

Powder epoxy composites have several advantages for the processing of large composite structures, including low exotherm, viscosity and material cost, as well as the ability to carry out separate melting and curing operations. This work studies the mode I and mixed-mode toughness, as well as the in-plane mechanical properties of unidirectional stitched glass and carbon fibre reinforced powder epoxy composites. The interlaminar fracture toughness is studied in pure mode I by performing Double Cantilever Beam tests and at 25% mode II, 50% mode II and 75% mode II by performing Mixed Mode Bending testing according to the ASTM D5528-13 test standard. The tensile and compressive properties are comparable to that of standard epoxy composites but both the mode I and mixed-mode toughness are shown to be significantly higher than that of other epoxy composites, even when comparing to toughened epoxies. The mixed-mode critical strain energy release rate as a function of the delamination mode ratio is also provided. This paper highlights the potential for powder epoxy composites in the manufacturing of structures where there is a risk of delamination.     

Changing Blue Fluorescent Protein to Green Fluorescent Protein Using Chemical RNA Editing as a Novel Strategy in Genetic Restoration

Using the transition from cytosine of BFP (blue fluorescent protein) gene to uridine of GFP (green fluorescent protein) gene at position 199 as a model, we successfully controlled photochemical RNA editing to effect site‐directed deamination of cytidine (C) to uridine (U). Oligodeoxynucleotides (ODNs) containing 5′‐carboxyvinyl‐2′‐deoxyuridine (^CVU) were used for reversible photoligation, and single‐stranded 100‐nt BFP DNA and in vitro‐transcribed full‐length BFP mRNA were the targets. Photo‐cross‐linking with the responsive ODNs was performed using UV (366 nm) irradiation, which was followed by heat treatment, and the cross‐linked nucleotide was cleaved through photosplitting (UV, 312 nm). The products were analyzed using restriction fragment length polymorphism (RFLP) and fluorescence measurements. Western blotting and fluorescence‐analysis results revealed that in vitro‐translated proteins were synthesized from mRNAs after site‐directed RNA editing. We detected substantial amounts of the target‐base‐substituted fragment using RFLP and observed highly reproducible spectra of the transition‐GFP signal using fluorescence spectroscopy, which indicated protein stability. ODNc restored approximately 10% of the C‐to‐U transition. Thus, we successfully used non‐enzymatic site‐directed deamination for genetic restoration in vitro. In the near future, in vivo studies that include cultured cells and model animals will be conducted to treat genetic disorders.     

Structure‐Based Design and Synthesis of a Small Molecule that Exhibits Anti‐inflammatory Activity by Inhibition of MyD88‐mediated Signaling to Bacterial Toxin Exposure

Both Gram‐positive and Gram‐negative pathogens or pathogen‐derived components, such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate MyD88‐mediated pro‐inflammatory cellular immunity for host defense. However, dysregulated MyD88‐mediated signaling triggers exaggerated immune response that often leads to toxic shock and death. Previously, we reported a small molecule compound 1 mimicking BB‐loop structure of MyD88 was capable of inhibiting pro‐inflammatory response to SEB exposure in mice. In this study, we designed a dimeric structure compound 4210 covalently linked with compound 1 by a non‐polar cyclohexane linker which strongly inhibited the production of pro‐inflammatory cytokines in human primary cells to SEB (IC₅₀ 1–50 μm ) or LPS extracted from Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC₅₀ 10–200 μm ). Consistent with cytokine inhibition, in a ligand‐induced cell‐based reporter assay, compound 4210 inhibited Burkholderia mallei or LPS‐induced MyD88‐mediated NF‐kB‐dependent expression of reporter activity (IC₅₀ 10–30 μm ). Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited MyD88 dimer formation which is critical for pro‐inflammatory signaling. Importantly, a single administration of compound 4210 in mice showed complete protection from lethal toxin challenge. Collectively, these results demonstrated that compound 4210 inhibits toxin‐induced inflated pro‐inflammatory immune signaling, thus displays a potential bacterial toxin therapeutic.     

Monocarboxylate Transporter 1 Inhibitors as Potential Anticancer Agents

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Diversity of carbapenemases in clinical isolates: The emergence of blaVIM-5 in Bangladesh

Global emergence and dissemination of carbapenemases are clinically threatening, notably in countries with endemic bla_NDM. To analyze the extent of carbapenemases in Bangladesh, 71 isolates were collected from 7 different clinical sources: wound swab (n = 38), pus (n = 13), urine (n = 9), blood (n = 4), tracheal aspirate (n = 3), pleural fluid (n = 1) and vaginal swab (n = 3) from Dhaka Medical College Hospital, Bangladesh. Among the isolates, 25 were resistant to at least one of the three carbapenems (imipenem, meropenem and doripenem), including 15 being resistant to all. These resistant isolates were identified as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, P. hibiscicola, Proteus mirabilis, Providencia stuartii and Citrobacter sedlakii. Carbapenemase detection among these 25 isolates varied in individual phenotypic assays (83% in Modified Hodge Test, 50% in Combined Disk Test for Metallo-β-lactamase prediction) as compared with the genotypes observed (96% prevalence of various carbapenemases including bla_OXA-1,48, bla_NDM-1,5, bla_VIM-2,5). bla_OXA-48 was the most prevalent gene (84%) followed by bla_NDM (72%). Coexistence of multiple gene combination such as bla_NDM+bla_OXA-48+bla_OXA-1 was prevalent (48%). Harborage of bla_VIM-5 (n = 1) was characterized for the first time, while bla_NDM-5 (n = 5) was reported contemporarily with a recent study in Bangladesh. Presence of plasmids (64%) and integron class 1 (100%) signifies the transferable potential of resistant traits. The emergence of such new variants along with the presence of the mobile genetic elements demands strict surveillance and combating strategies.     

Subtypes A,C, G,and recombinant HIV type 1 are circulating in Bangladesh

We analyzed the genetic diversity of HIV-1 circulating in Bangladesh by direct sequencing and subsequent phylogenetic analysis of the V3 region of the env gene and p17 fragment of the gag gene from nine unrelated patients. The sequences from one sample grouped into subtype A, five samples grouped into subtype C, and one grouped into subtype G. In addition, two patients appeared to be infected with different recombinant viruses consisting of subtype A and unclassifiable viral sequences. Epidemiological analysis revealed heterosexual transmission in the majority of cases. Furthermore, most subjects had a history of traveling, either to India or to the Arabian Peninsula. This study shows that several HIV-1 subtypes are circulating in Bangladesh, and we conclude that there must have been several introductions of HIV-1 into the Bangladeshi population.     

Systolic blood pressure is the main etiology for poorly controlled hypertension

BACKGROUND: Isolated systolic hypertension is an important risk factor for cardiovascular events. The purpose of this study was to detect the prevalence of and to evaluate the effectiveness of currently available medications in the treatment of uncontrolled isolated systolic hypertension. METHODS: We randomly selected a total of 585 patients with hypertension from our database. The two most recent blood pressure (BP) readings and other data were obtained by chart review. RESULTS: Of 585 patients, 340 (58%) had controlled BP. Of 245 patients with uncontrolled hypertension, 77.1% had uncontrolled isolated systolic hypertension and the remaining 22.9% had uncontrolled diastolic hypertension. Patients with uncontrolled systolic hypertension were on average taking more antihypertensive medications than patients with controlled BP (2.10 +/- 0.09; P = .034). CONCLUSIONS: Systolic hypertension is the etiology of uncontrolled hypertension in the majority of patients. Currently available antihypertensive medications are less effective in controlling systolic hypertension.     

A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis

Objectives

Fibromyalgia is a condition which exhibits chronic widespread pain with neuropathic pain features and has a major impact on health-related quality of life. The pathophysiology remains unclear, however, there is increasing evidence for involvement of the peripheral nervous system with a high prevalence of small fiber pathology (SFP). The aim of this systematic literature review is to establish the prevalence of SFP in fibromyalgia.