Designed spiro-bicyclic analogues targeting the ribosomal decoding center

The bacterial ribosome represents the confirmed biological target for many known antibiotics that interfere with bacterial protein synthesis. Aminoglycosides represent a lead paradigm in RNA molecular recognition and constitute ideal starting points for the design and synthesis of novel RNA binders. Previous rational design approaches of RNA-targeting small molecules have been mainly concentrated on direct functionalization of aminoglycosidic substructures. Herein, we successfully designed and synthesized rigid spirocyclic scaffolds locked in a predicted ribosome-bound "bioactive" conformation. These analogues are able to mimic many of the interactions of the natural products for the A-site, as proven by their obtained binding affinities. The development of an optimized approach for their synthesis and their potential to inhibit protein production in vitro are presented. Our results could be further utilized for the development of analogues with improved antibiotic profiles.     

Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling

Diabetes mellitus is a debilitating disease, plaguing a significant number of people around the globe. Attempts to develop new drugs on well-defined atoxic metalloforms, which are capable of influencing fundamental cellular processes overcoming insulin resistance, has triggered an upsurge in molecular research linked to zinc metallodrugs. To that end, meticulous efforts were launched toward the design and synthesis of materials with insulin mimetic potential. Henceforth, trigonelline and N-(2-hydroxyethyl)-iminodiacetic acid (HeidaH₂) were selected as organic substrates seeking binding to zinc (Zn(II)), with new crystalline compounds characterized by elemental analysis, FT-IR, X-rays, thermogravimetry (TGA), luminescence, NMR, and ESI-MS spectrometry. Physicochemical characterization was followed by in vitro biochemical experiments, in which three out of the five zinc compounds emerged as atoxic, exhibiting bio-activity profiles reflecting enhanced adipogenic potential. Concurrently, well-defined qualitative–quantitative experiments provided links to genetic loci responsible for the observed effects, thereby unraveling their key involvement in signaling pathways in adipocyte tissue and insulin mimetic behavior. The collective results (a) signify the quintessential role of molecular studies in unearthing unknown facets of pathophysiological events in diabetes mellitus II, (b) reflect the close associations of properly configured molecular zincoforms to well-defined biological profiles, and (c) set the stage for further physicochemical-based development of efficient zinc antidiabetic metallodrugs.     

Effect of chromium(VI) on bacterial kinetics of heterotrophic biomass of activated sludge

The effect of hexavalent chromium, Cr(VI), on the maximum specific growth rate, mu(m) and biomass yield, Y(H), of heterotrophic biomass was studied in batch tests conducted under high (= 10) and low (= 1.5) substrate-to-biomass ratios (S0/X0). The effects of sludge age and biomass acclimatization to Cr(VI) on the bacterial kinetics were also studied. The mu(m) values were determined by measuring oxygen uptake rate (OUR) and volatile suspended solids (VSS) increase. Cr(VI) concentrations equal or greater than 10 mg l(-1) inhibited the growth of unacclimatized activated sludge and caused a significant decrease in mu(m) and Y(H) values. The acclimatization of biomass and the selection of a high operating sludge age reduced the inhibitory effect of Cr(VI). At a sludge age of 20 days, Cr(VI) concentrations of <10 mg l(-1) stimulated bacterial growth as evidenced by an increase in both the mu(m) and Y(H) values. Determining mu(m) values by OUR and VSS methods, revealed that the presence of Cr(VI) in unacclimatized biomass caused an inhibitory effect mostly on substrate oxidation, while in acclimatized biomass, anabolic pathways were inhibited more.     

A Linear Model for the Continuous Network Design Problem

Abstract:   This article is concerned with the continuous network design problem on traffic networks, assuming system optimum traffic flow conditions and time-dependent demand. A linear programming formulation is introduced based on a dynamic traffic assignment (DTA) model that propagates traffic according to the cell transmission model. The introduced approach is limited to continuous link improvements and does not provide for new link additions. The main contribution of the article is to provide an analytical formulation for network design that accounts for DTA conditions that can be used for further analysis and extensions. The model is tested on a single destination example network, resembling a freeway corridor, for various congestion levels, loading patterns and budget sizes, to demonstrate the simplicity and effectiveness of the approach.     

Differential mobility analyser transfer functions in scanning mode

A novel method is described for the calculation of the differential mobility analyser (DMA) transfer function in scanning mode, which is based on the derivation of an analytical solution for the non-diffusive particle trajectories inside the DMA, under exponentially varying electrical field and fully developed laminar flow. The scanning mode transfer functions can substantially improve the measurement accuracy of fast scanning mobility particle sizers (SMPS) as shown by Collins, Cocker, Flagan, and Seinfeld [(2004). The scanning DMA transfer function. Aerosol Science and Technology, 38, 833–850]. Compared to the Monte Carlo simulations described by Collins et al., the method developed here is much more accurate and sufficiently fast to be employed in advanced DMA inversion algorithms.     

A new technological approach proposed for distillate production using immobilized cells

A new technological approach to distillate production using immobilized cells was investigated. The effect of temperature on the main volatile by-products in distillates was determined. Wines produced by delignified cellulose-, gluten- and kissiris-supported biocatalysis were used as starting materials. The produced distillates were analyzed for ethanol, methanol, acetaldehyde, ethyl acetate, propanol-1, isobutanol and amyl alcohol content. The results showed that distillates from delignified cellulosic material (DCM) at 16 degrees C contained smaller amounts of amyl alcohols, 57% of that produced by gluten and 32% of that produced by kissiris. The ethyl acetate content of distillates from DCM improved the aroma of distillates. These results agree with those of sensory evaluation. Subsequently, the scale-up for low-temperature distillate production at 16 degrees C using DCM was further investigated. A new version of an industrial multi-stage fixed bed tower (MFBT) bioreactor with a capacity of 11,000 l proved to be suitable for continuous fermentation by DCM-supported biocatalysis. Economic analysis showed a reduction in the cost of almost 30% for distillate production and 78% for wine production.     

Examination of freshness degradation of sourdough bread made with kefir through monitoring the aroma volatile composition during storage

The aroma volatile compositions of sourdough breads containing kefir grains were monitored by SPME GC–MS analysis during a 5-day storage. Breads were made with (A) 20% w/w and (B) 10% w/w (on flour basis) kefir sourdough, and were compared with breads made with 20% w/w commercial sourdough (C) and sourdough prepared in the laboratory (D) without addition of starter culture. A dramatic decrease of volatiles was observed during storage for all samples, but the kefir sourdough breads (A and B) exhibited more complex profiles of volatiles with lower loss rates during storage. Differences in the percentages of esters on total volatiles were also observed (6.2%, 5.0%, 2.8% and 2% in the case of breads A, B, C, and D, respectively). The customer oriented sensory evaluation revealed significant differences among the tested samples, with best results scored in the case of bread A in all days of storage, agreeing with the analytical data.     

Effect of freeze–dried kefir culture on proteolysis in feta-type and whey-cheeses

The effect of freeze–dried kefir culture on the proteolysis of feta-type and whey-cheese was investigated. All nitrogen fractions increased during ripening. Although no significant differences were observed in total nitrogen (TN), the levels of water-soluble nitrogen (WSN), pH 4.4-soluble nitrogen (SN), 12% trichloroacetic acid-soluble nitrogen (TCA-SN) and phosphotungstic acid-soluble nitrogen (PTA-SN) were significantly higher in cheeses produced by freeze–dried kefir culture during the later stages of ripening. Content of total free amino acids (FAA) was significantly affected by freeze–dried kefir starter culture and it was continuously increased in kefir-cheese while, in rennet-cheese it was increased up to 30 days of ripening and then slightly decreased. On the other hand, FAA content continuously decreased in kefir-whey-cheese whereas it increased in whey-cheese. The cheese samples produced by freeze–dried kefir as starter culture were characterised as high-quality products during the preliminary sensory evaluation and they were accepted by the panel. Overall, the use of freeze–dried kefir suggested acceleration of cheese ripening and resulted in improved sensory characteristics.