Determination of Phenolic Compounds in Various Propolis Samples Collected from an African and an Asian Region and Their Impact on Antioxidant and Antibacterial Activities

The biological activities of propolis samples are the result of many bioactive compounds present in the propolis. The aim of the present study was to determine the various chemical compounds of some selected propolis samples collected from Palestine and Morocco by the High-Performance Liquid Chromatography–Photodiode Array Detection (HPLC-PDA) method, as well as the antioxidant and antibacterial activities of this bee product. The chemical analysis of propolis samples by HPLC-PDA shows the cinnamic acid content in the Palestinian sample is higher compared to that in Moroccan propolis. The results of antioxidant activity demonstrated an important free radical scavenging activity (2,2-Diphenyl-1-picrylhydrazyl (DPPH); 2,2′-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and reducing power assays) with EC₅₀ values ranging between 0.02 ± 0.001 and 0.14 ± 0.01 mg/mL. Additionally, all tested propolis samples possessed a moderate antibacterial activity against bacterial strains. Notably, Minimum Inhibitory Concentrations (MICs) values ranged from 0.31 to 2.50 mg/mL for Gram-negative bacterial strains and from 0.09 to 0.125 mg/mL for Gram-positive bacterial strains. The S2 sample from Morocco and the S4 sample from Palestine had the highest content of polyphenol level. Thus, the strong antioxidant and antibacterial properties were apparently due to the high total phenolic and flavone/flavonol contents in the samples. As a conclusion, the activities of propolis samples collected from both countries are similar, while the cinnamic acid in the Palestinian samples was more than that of the Moroccan samples.     

Waiting Time Distribution for the Emergence of Superpatterns

Consider a sequence \(\{X_{n}\}_{n=1}^{\infty }\) of i.i.d. uniform random variables taking values in the alphabet set {1, 2,…, d}. A k-superpattern is a realization of \(\{X_{n}\}_{n=1}^{t}\) that contains, as an embedded subsequence, each of the non-order-isomorphic subpatterns of length k. We focus on the (non-trivial) case of d = k = 3 and study the waiting time distribution of \(\tau =\inf \{t\ge 1:\{X_{n}\}_{n=1}^{t}\ \text {is\ a\ superpattern}\}\). Our restricted set-up leads to proofs that are very combinatorial in nature, since we are essentially conducting a string analysis.     

Enantiomeric deoxycholic acid: total synthesis, characterization, and preliminary toxicity toward colon cancer cell lines

Deoxycholic acid (DCA) is an endogenous secondary bile acid implicated in numerous pathological conditions including colon cancer formation and progression and cholestatic liver disease. DCA involvement in these disease processes results partly from its ability to modulate signaling cascades within the cell, presumably through both direct receptor activation and general detergent mediated membrane changes. To further explore DCA induced changes in cell signaling, we completed a total synthesis of enantiomeric deoxycholic acid (ent-DCA) from achiral 2-methyl-1,3-cyclopentanedione. Using a modified method of the synthesis of ent-testosterone that proceeds through the (R)-(-)-Hajos-Parrish ketone, we have completed the successful synthesis of ent-DCA in 25 steps with a yield of 0.3% with all stereochemical assignments of the product confirmed by X-ray crystallography. Our studies toward this synthesis also uncovered the methodology for the development of a novel A,B-cis steroidal skeleton system containing a C3-C9 single bond as well as conditions to selectively ketalize the typically less reactive 12-carbonyl in poly-keto A,B-cis androgens. The critical micelle concentration (cmc) of ent-DCA, determined by a dye solubilization method, was identical to the cmc of natural DCA. Toxicity studies toward HT-29 and HCT-116 human colon cancer cell lines demonstrated that ent-DCA had similar effects on proliferation, yet showed a markedly decreased ability to induce apoptosis as compared to natural DCA.     

Transition‐Metal‐Catalyzed Direct Arylation of (Hetero)Arenes by C?H Bond Cleavage

The area of transition‐metal‐catalyzed direct arylation through cleavage of C? H bonds has undergone rapid development in recent years, and is becoming an increasingly viable alternative to traditional cross‐coupling reactions with organometallic reagents. In particular, palladium and ruthenium catalysts have been described that enable the direct arylation of (hetero)arenes with challenging coupling partners—including electrophilic aryl chlorides and tosylates as well as simple arenes in cross‐dehydrogenative arylations. Furthermore, less expensive copper, iron, and nickel complexes were recently shown to be effective for economically attractive direct arylations.     

Exploiting noninnocent (E,E)-dibenzylideneacetone (dba) effects in palladium(0)-mediated cross-coupling reactions: modulation of the electronic properties of dba affects catalyst activity and stability in ligand and ligand-free reaction systems

The reactivity of palladium(0) complexes, [Pd(0) (2)(dba-n,n'-Z)(3)] (n,n'-Z=4,4'-F; 4,4'-CF(3); 4,4'-H; 4,4'-MeO) and [Pd(0)(dba-n,n'-Z)(2)] (n,n'-Z=4,4'-CF(3); 4,4'-H; 3,3',5,5'-OMe), used as precursor catalysts with suitable donor ligands (e.g. phosphines, N-heterocyclic carbenes), has been correlated in several palladium(0)-mediated cross-coupling processes. Increasing the electron density on the aryl moiety of the dba-n,n'-Z ligand increases the overall catalytic activity in the majority of these processes. This effect primarily derives from destabilization of the L(n)Pd(0)-eta(2)-dba interaction (in dpi-pi* synergic bonding, n=1 or 2), which ultimately increases the global concentration of catalytically active L(n)Pd(0) available for reaction with aryl halide in the first committed step in the general catalytic cycle(s) (oxidative addition). Decreasing electron density on the aryl moiety of the dba-n,n'-Z ligand stabilizes the Pd(0)-eta(2)-dba interaction, reducing catalytic activity. The specific type of dba-n,n'-Z ligand appears to also play a stabilizing role in the catalytic cycle, preventing Pd agglomeration, and increasing catalyst longevity. A subtle balance therefore exists between the L(n)Pd(0) concentration (and the associated catalytic activity) and catalyst longevity. Changing the type of dba-n,n'-Z ligand controls the concentration of L(n)Pd(0) and the rate of the oxidative addition step, and not other intimate steps within the catalytic cycle(s), for example, transmetallation (or carbopalladation) and reductive elimination. The role of dba-n,n'-Z ligands in Heck arylation is more convoluted and dependent on the alkene substrate employed, although trends have emerged. Changes in the structure of dba-n,n'-Z had a minimal affect on Buchwald-Hartwig aryl amination processes. A secondary Michael reaction of dba-n,n'-Z with amine and/or base effectively lessens its interference in the catalytic cycle.     

Development of a gradient elution preparative high performance liquid chromatography method for the recovery of the antibiotic ertapenem from crystallization process streams

A gradient elution preparative chromatography method was developed for the recovery of the antibiotic ertapenem from crystallization mother-liquor streams. The preparative HPLC method that was developed on the lab-scale employs an analytical size column of conventional dimensions (25 cm x 0.46 cm) packed with Kromasil C8 stationary phase. Gradient elution was used with aqueous acetic acid and acetonitrile as mobile phases. A target of processing approximately 30 mg of ertapenem per half an hour at a flow rate of 1.5 mL/min with high yield and adequate rejection of all major impurities was achieved. This corresponds to a productivity of approximately 0.6 kg ertapenem as free acid per kilogram of stationary phase per day (kkd). The scalability of the method was demonstrated by using a 5 cm i.d. column configuration to generate 10 g of purified ertapenem. This work complements a previous study improving on the productivity and throughput of the method by employing gradient elution and the use of crystallization to remove some key impurities that are chromatographically difficult to resolve [A. Vailaya, P. Sajonz, O. Sudah, V. Capodanno, R. Helmy, F.D. Antia, J. Chromatogr. A 1079 (2005) 80].     

An integrated region-, boundary-, shape-based active contour for multiple object overlap resolution in histological imagery

Active contours and active shape models (ASM) have been widely employed in image segmentation. A major limitation of active contours, however, is in their 1) inability to resolve boundaries of intersecting objects and to 2) handle occlusion. Multiple overlapping objects are typically segmented out as a single object. On the other hand, ASMs are limited by point correspondence issues since object landmarks need to be identified across multiple objects for initial object alignment. ASMs are also are constrained in that they can usually only segment a single object in an image. In this paper, we present a novel synergistic boundary and region-based active contour model that incorporates shape priors in a level set formulation with automated initialization based on watershed. We demonstrate an application of these synergistic active contour models using multiple level sets to segment nuclear and glandular structures on digitized histopathology images of breast and prostate biopsy specimens. Unlike previous related approaches, our model is able to resolve object overlap and separate occluded boundaries of multiple objects simultaneously. The energy functional of the active contour is comprised of three terms. The first term is the prior shape term, modeled on the object of interest, thereby constraining the deformation achievable by the active contour. The second term, a boundary-based term detects object boundaries from image gradients. The third term drives the shape prior and the contour towards the object boundary based on region statistics. The results of qualitative and quantitative evaluation on 100 prostate and 14 breast cancer histology images for the task of detecting and segmenting nuclei and lymphocytes reveals that the model easily outperforms two state of the art segmentation schemes (geodesic active contour and Rousson shape-based model) and on average is able to resolve up to 91% of overlapping/occluded structures in the images.     

Multifeature landmark-free active appearance models: application to prostate MRI segmentation

Active shape models (ASMs) and active appearance models (AAMs) are popular approaches for medical image segmentation that use shape information to drive the segmentation process. Both approaches rely on image derived landmarks (specified either manually or automatically) to define the object's shape, which require accurate triangulation and alignment. An alternative approach to modeling shape is the levelset representation, defined as a set of signed distances to the object's surface. In addition, using multiple image derived attributes (IDAs) such as gradient information has previously shown to offer improved segmentation results when applied to ASMs, yet little work has been done exploring IDAs in the context of AAMs. In this work, we present a novel AAM methodology that utilizes the levelset implementation to overcome the issues relating to specifying landmarks, and locates the object of interest in a new image using a registration based scheme. Additionally, the framework allows for incorporation of multiple IDAs. Our multifeature landmark-free AAM (MFLAAM) utilizes an efficient, intuitive, and accurate algorithm for identifying those IDAs that will offer the most accurate segmentations. In this paper, we evaluate our MFLAAM scheme for the problem of prostate segmentation from T2-w MRI volumes. On a cohort of 108 studies, the levelset MFLAAM yielded a mean Dice accuracy of 88% ± 5%, and a mean surface error of 1.5 mm ±.8 mm with a segmentation time of 150/s per volume. In comparison, a state of the art AAM yielded mean Dice and surface error values of 86% ± 9% and 1.6 mm ± 1.0 mm, respectively. The differences with respect to our levelset-based MFLAAM model are statistically significant . In addition, our results were in most cases superior to several recent state of the art prostate MRI segmentation methods.     

Miniaturized Salinity Gradient Energy Harvesting Devices

Harvesting salinity gradient energy, also known as “osmotic energy” or “blue energy”, generated from the free energy mixing of seawater and fresh river water provides a renewable and sustainable alternative for circumventing the recent upsurge in global energy consumption. The osmotic pressure resulting from mixing water streams with different salinities can be converted into electrical energy driven by a potential difference or ionic gradients. Reversed-electrodialysis (RED) has become more prominent among the conventional membrane-based separation methodologies due to its higher energy efficiency and lesser susceptibility to membrane fouling than pressure-retarded osmosis (PRO). However, the ion-exchange membranes used for RED systems often encounter limitations while adapting to a real-world system due to their limited pore sizes and internal resistance. The worldwide demand for clean energy production has reinvigorated the interest in salinity gradient energy conversion. In addition to the large energy conversion devices, the miniaturized devices used for powering a portable or wearable micro-device have attracted much attention. This review provides insights into developing miniaturized salinity gradient energy harvesting devices and recent advances in the membranes designed for optimized osmotic power extraction. Furthermore, we present various applications utilizing the salinity gradient energy conversion.