Fragment-Based Drug Discovery for RNA Targets

Rapid development within the fields of both fragment-based drug discovery (FBDD) and medicinal targeting of RNA provides possibilities for combining technologies and methods in novel ways. This review provides an overview of fragment-based screening (FBS) against RNA targets, including a discussion of the most recently used screening and hit validation methods such as NMR spectroscopy, X-ray crystallography, and virtual screening methods. A discussion of fragment library design based on research from small-molecule RNA binders provides an overview on both the currently limited guidelines within RNA-targeting fragment library design, and future possibilities. Finally, future perspectives are provided on screening and hit validation methods not yet used in combination with both fragment screening and RNA targets.     

Microwave hybrid fast sintering of red clay ceramics

This work aimed to examine the performance of the hybrid sintering of clay ceramic in a microwave furnace, compared to the sintering process in a conventional furnace. The raw materials were subjected to X-ray fluorescence, loss on ignition (LOI), X-ray diffraction, particle size distribution, real specific mass, and thermogravimetric analyses. The red clay ceramic mass was prepared, extruded, pre-sintered in a conventional furnace at 600°C/60 min, and sintered at temperatures between 700 °C and 1100 °C. The sintering conventional (resistive oven) was carried out for 60 min with a heating rate of 10°C/min. In the microwave furnace, the sintering times were 5, 10, and 15 min, with a heating rate of 50°C/min, with a sintering chamber coated with silicon carbide (susceptor). The sintered specimens were characterized according to linear shrinkage, water absorption, apparent porosity, apparent specific mass, X-ray diffraction, Raman spectroscopy analysis, spectroscopy analysis in the ultraviolet and visible regions, microhardness, and scanning electron microscopy. The results showed that microwave sintering promoted an increase in the microhardness and apparent specific mass, and reduction in water absorption and apparent porosity values, due to greater densification in the microstructure. The best results occurred for specimens sintered at 1100°C.     

Effect of different surface treatments on polypropylene composites reinforced with yerba mate fibers: Physical,mechanical, chemical,and morphological properties

This study presents the preparation of post-consumer polypropylene (r-PP) composites filled with 30 wt% yerba mate (YM) stick particles. To improve the fiber–matrix adhesion, three surface treatments were performed: alkaline treatment with sodium hydroxide (NaOH) and use of 3-aminopropyltriethoxysilane (APTS) and maleic anhydride graft polypropylene copolymer (PP-g-MA) as coupling agents. Mechanical properties including tensile, flexural, and impact resistance were determined, and chemical (Fourier transform infrared spectroscopy [FTIR]), physical (water absorption), and morphological analyses were performed. The main findings show that the treatments were efficient in improving the mechanical properties of the composites, with emphasis on the r-PP/YM30/APTS and r-PP/YM30/PP-g-MA composites, which proved to be superior in tensile, flexion and impact strength and absorption of water compared to the untreated composite. The morphological analysis showed a better interaction between the fiber and the polymeric matrix for the composites with YM/APTS and YM/PP-g-MA, which corroborates the results of tensile and flexural strength, as well as with the spectra of FTIR in which the chemical modification of the fibers is observed. However, the results show that these treatments are promising in obtaining composites with recycled matrix with better properties.     

Differences between Human and Mouse IgM Fc Receptor (FcµR)

Both non-immune “natural” and antigen-induced “immune” IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since the bona fide IgM Fc receptor (FcµR) was identified in humans by a functional cloning strategy in 2009, the roles of FcµR in these IgM effector functions have begun to be explored. In this short essay, we describe the differences between human and mouse FcµRs in terms of their identification processes, cellular distributions and ligand binding activities with emphasis on our recent findings from the mutational analysis of human FcµR. We have identified at least three sites of human FcµR, i.e., Asn66 in the CDR2, Lys79 to Arg83 in the DE loop and Asn109 in the CDR3, responsible for its constitutive IgM-ligand binding. Results of computational structural modeling analysis are consistent with these mutational data and a model of the ligand binding, Ig-like domain of human FcµR is proposed. Serendipitously, substitution of Glu41 and Met42 in the CDR1 of human FcµR with mouse equivalents Gln and Leu, either single or more prominently in combination, enhances both the receptor expression and IgM binding. These findings would help in the future development of preventive and therapeutic interventions targeting FcµR.     

Non-linear dissolution mechanisms of sodium calcium phosphate glasses as a function of pH in various aqueous media

Phosphate glasses for bioresorbable implants display dissolution rates that vary significantly with composition, however currently their mechanisms of dissolution are not well understood. Based on this systematic study we present new insights into these mechanisms. Two-stage dissolution was observed, with time dependence initially parabolic and later linear, and a two-stage model was developed to describe this behaviour. Dissolution was accelerated by lower Ca concentration in the glass, and lower pH in the dissolution medium. A new dissolution mechanism is proposed, involving an initial stage where diffusion-controlled formation of a conversion layer occurs. Once the conversion layer is stabilised, layer dissolution reactions become rate-limiting. Under this mechanism the transition time is sensitive to the nature of the conversion layer and solution conditions. These results reveal the dependence of P₂O₅–CaO–Na₂O glass dissolution on solution pH, and provide new insight into the dissolution mechanisms, particularly regarding the transition between the two dissolution stages.     

The association of anxiety and depressive symptoms with cognitive performance in community-dwelling older adults.

The authors examined the association of anxiety, depressive symptoms, and their co-occurrence on cognitive processes in 102 community-dwelling older adults. Participants completed anxiety and depression questionnaires as well as measures of episodic and semantic memory, word fluency, processing speed/shifting attention, and inhibition. Participants with only increased anxiety had poorer processing speed/shifting attention and inhibition, but depressive symptoms alone were not associated with any cognitive deficits. Although coexisting anxiety and depressive symptoms were associated with deficits in 3 cognitive domains, reductions in inhibition were solely attributed to anxiety. Findings suggest an excess cognitive load on inhibitory ability in normal older adults reporting mild anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Climate policy impacts on the competitiveness of energy-intensive manufacturing sectors

This study examines the impacts of energy price changes resulting from different carbon-pricing policies on the competitiveness of selected US energy-intensive industries. It further examines possible industry responses, and identifies and provides a preliminary evaluation of potential opportunities to mitigate these impacts. The industry sectors investigated – steel, aluminum, chemicals and paper – are among the largest industrial users of fossil fuels in the US economy. The results of this examination show that climate policies that put a price on carbon could have substantial impacts on the competitiveness of US energy-intensive manufacturing sectors over the next two decades, if climate regulations are applied only in the United States, and no action is taken to invest in advanced low- and no-carbon technologies. The extent of these impacts will vary across industries, depending on their energy intensities, the mix of energy sources they rely on and how energy is used in production activities (heat and power, feedstock). Of relevance is also the speed and rigor with which industries adopt new technologies and retire (or replace) old ones. Other factors affecting these impacts include an industry's vulnerability to foreign imports and its ability to pass through cost increases to its customers in the face of international market competition.     

A randomized trial of three diabetes registry implementation strategies in a community internal medicine practice

BACKGROUND: Disease registries are powerful tools with the potential to transform the way chronic diseases are managed. To date, however, little work has been done to determine how to optimize the implementation of a chronic disease registry in practice. METHODS: Twenty-nine physicians and their nurse teams in a large community internal medicine practice participated in this 6-month prospective randomized trial in 2000. Teams were assigned to one of three implementation strategies using information from a diabetes registry. Process and outcome measures for diabetes management were analyzed. Process measures included the percentage of patients completing glycosylated hemoglobin (Hgb) testing within 6 months and low-density lipoprotein (LDL) testing within 12 months. Outcome measures included the percentage of patients with a glycosylated Hgb > 9.3% (equivalent to a HgbA1c > 8.0%), the percentage of patients with an LDL cholesterol > 130 mg/dl, and the percentage of patients with controlled blood pressure, defined as < 130/85 millimeters of mercury. Mean change in LDL and glycosylated Hgb values was also measured. RESULTS: Teams randomized to an intervention strategy that included direct letters to patients showed significant improvement across a number of measures. The improvement was most apparent among patients without recent testing or with poorly controlled disease. The two interventions that did not include direct patient letters resulted in limited improvement. DISCUSSION: Disease registries can be used to improve outcomes in the management of diabetes and other chronic diseases. Better outcomes were seen in patients who received letters based on registry-generated data. This strategy should be included as part of a comprehensive chronic disease management plan. Further refinements in the use of registries should result in further incremental improvement.     

Threshold of stimulated Brillouin scattering by use of a solar pumped laser

What is to our knowledge the first stimulated Brillouin scattering experiment using a high-power low-gain solar pumped laser is presented. A threshold reflectivity of 0.23% was reached when a peak power of 20.7 kW was used at 7.6 GHz. A cw solar pumped laser was Q-switched with an acousto-optic modulator, and the bandwidth was narrowed with an intracavity etalon. A high polarization ratio (>99.4%) was achieved by use of an intracavity configuration. Higher reflectivity values were limited because of the lack of availability of optical switches.     

Perception and expectation gaps of information systems provider skills: the impact on user satisfaction

Abstract.  Past research indicates that expectations play a crucial role in the final satisfaction of users of information systems (IS). This includes expectations regarding the skill levels exhibited by the providers of the IS services and products. Typically, the expectations are examined as gaps from perceived performance or as gaps from realistic expectations. The interaction of these gaps has not been thoroughly explored in past research, although recent theories anticipate both gaps are crucial in meeting the desires of the users. A matched pair sample of IS users and IS providers is used to collect data on expected skill levels and perceived delivery of the skills demanded. Gaps, both between these two stakeholder groups regarding expectations and within the user group regarding perceived delivery, are found to impact user satisfaction in a two-way analysis. The results indicate that expectations should be managed to higher levels and commonly understood across the user and provider groups.