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This article analyzes an intermodal transportation network for international container cargoes in Korea. The actual transportation situation in Korea is formulated by a linear programming model. The model is validated first by comparing the model output with actual performance, and then the model is extended by incorporating various externalities arising from inland transport modes such as air pollution, congestion, accidents, noise pollution, and wear and tear. Moreover, the model is extended for assessing the effects of complying with carbon taxation and emission trading schemes, which loom large in international shipping communities. Test results of the models using the data obtained from reliable sources are presented and policy directions are discussed from an environmental perspective. [ABSTRACT FROM AUTHOR]

This paper considers a multimodal transportation problem, which is the problem of determining the transportation flow, i.e. volume of container cargoes, and the transportation mode in each trade route, for the objective of minimizing the sum of shipping and inland transportation costs. The problem takes account of two restrictions: maximum cargo volumes capacitated at each seaport and maximum number of vehicles available at each transportation mode. To solve optimally the problem, this paper employs a mixed integer programming, which is an operations research technique. A case study is performed on the container cargo data in Korea and we draw several implications to improve efficiency in the transportation of international trade cargoes in Korea. [ABSTRACT FROM AUTHOR]

Chemical genetics is a powerful method which utilizes small molecule regulators to reveal the molecular basis of diverse biological processes. However, the current chemical genetic approach sometimes meets a serious bottleneck during the process of target identification. One faces difficulty in conjugating the active compound to an affinity matrix without losing or reducing its activity that leads to laborious structure–activity relationship (SAR) studies. To facilitate this process, we have developed a tagged triazine library containing a built-in linker that provides a straightforward transition from phenotypic screening to target identification. A strategy for constructinig a tagged library and applications with a streamlined target identification and subsequent mechanistic study are discussed in this Account. [ABSTRACT FROM AUTHOR]

The article offers information about chemical genetics, a branch of chemistry that deals with studies on a gene's role by altering the activity of cognate protein, using small molecule inhibitors analogously to the genetic knockout. Chemical genetics is divided into two approaches: the phenotype to genotype which requires no specific gene target from the onset and the forward chemical genetics which substitutes random mutagenesis with a collection of unbiased compounds as protein function regulator.

Two novel heparin sensors, Heparin Orange and Heparin Blue, were developed by a diversity oriented fluorescence library approach (DOFLA) from a benzimidazolium library; the discovered compounds showed remarkable properties and have the potential to be applied to monitoring heparin levels in clinical plasma samples for point-of-care detection. [ABSTRACT FROM AUTHOR]

The article describes the synthesis of a combinatorial benzimidazolium dye library and the discovery of the first turn-on fluorescent GTP sensor. A novel solid-phase synthesis pathway for the benzimidazolium library is developed. Various lengths of the linker were tested and optimized for best loading of the benzimidazolium compound into the resin. Various excitation/emission wavelengths were observed due to the structural diversity.

Examines the synthesis and biological characterization of the ceramide library. Role of fatty acids and metabolites on cellular transduction; Regulation of hormones; Use of representative scheme for natural ceramide.

Due to weakening demand since the 2008 global recession, ports have had to reconsider how to compete differently to attract new business and new investors. Extant literature mainly focuses on either customer competitiveness or investor competitiveness. This study develops a new model of port competitiveness that simultaneously considers the effect of port strategy on customers and investors. This model is referred to as the "balanced theory of port competitiveness." An analytical hierarchy process model builds on 10 factors that customers and investors consider important, and it is tested on 12 global seaports. The results show that port managers should consider the effect of their decisions among the factors because failure to do so can improve one factor of competitiveness while harming another. This study tests a theory that explains the behaviour of port managers and provides them with a practical guide to evaluate the effect of their decisions on customers and investors. [ABSTRACT FROM AUTHOR]

When encapsulated by human serum albumin (HSA), certain derivatives of the green fluorescent protein (GFP) chromophore recover their fluorescence due to inhibition of torsional motion. These derivatives show remarkable sensitivity and selectivity as well as favorable spectroscopic properties toward HSA, thus providing selective probes for this and similar proteins and demonstrating the use of GFP chro-mophores as topological fluorophores. [ABSTRACT FROM AUTHOR]

A chemosensor array comprising 45 off-the-shelf colorimetric dyes, dubbed the Singapore Tongue (SGT), that is capable of discriminating different brands of bottled water and waters of different geographical attribute is described. Twelve kinds of bottled waters were tested by the SGT, and changes of absorbance spectra were analyzed by unsupervised classification methods to validate the SGT system for water analysis. All 12 bottled waters were discriminated at 1 × concentration, and SGT could distinguish the identity of samples of the waters diluted up to 100 times, except distilled waters. Following the study of 63 tap waters in different mass rapid transit stations in Singapore, two distinct clusters were observed from a principal component analysis plot, which correspond to the origin of the tap water. The successful discrimination and identification of in this study demonstrates the practical application of the SGT as a simple tool for water analysis. [ABSTRACT FROM AUTHOR]

The diversity-oriented fluorescence library approach (DOFLA) has emerged and found applications in various fields to meet the acute demands for novel fluorescence sensors. The power of this approach has been demonstrated with the impressive discoveries of novel sensors for polymers such as DNA and heparin or for small molecules such as GTP and glutathione ( J. Am. Chem. Soc.2003, 125, 1130− 1131; J. Am. Chem. Soc.2006, 128, 10380− 10381; J. Am. Chem. Soc.2007, 129, 4510− 4511; Chem. Commun.[Online early access]. DOI: 10.1039/b717058k. Published online Dec 11, 2008. http://www.rsc.org/publishing/journals/CC/article.asp?doi=b717058k). Herein we report the application of this approach on quinaldinium fluorescent dye library synthesis on solid support and novel chymotrypsin sensor discovery. The new sensors are not only selective to chymotrypsin over other proteins but also only to the active conformation of chymotrypsin. [ABSTRACT FROM AUTHOR]

A fluorescent dye library approach for the development of a bioanalyte sensor was sought. The screening of a rosamine dye library against diverse macromolecules led to the discovery of a highly sensitive human serum albumin binder, G13, with ∼36-fold fluorescence intensity change. G13showed a highly selective response to HSA over other macromolecules including albumins from other species. The potential use of G13for the detection of HSA in biofluids is described. [ABSTRACT FROM AUTHOR]

Countries throughout the world, and especially within Asia, are investing heavily in container port infrastructure in the hopes of capturing a larger share of global shipping activity for their economies. Many existing ports are emphasizing developing the capacity to serve as a hub port, building deepwater berths with large terminals to facilitate transfer of containers from feeder ships to mother ships for intercontinental transport. We develop a game-theoretic best response framework for understanding how competitor ports will respond to development at a focus port, and whether the focus port will be able to capture or defend market share by building additional capacity. We apply this model to investment and competition currently occurring between the ports of Busan and Shanghai. [ABSTRACT FROM AUTHOR]

Transition-metal ions (Cu2+ and Zn2+) play critical roles in the Aβ plaque formation. However, precise roles of the metal ions in the Aβ amyloidogenesis have been controversial. In this study, the molecular mechanism of the metal-induced Aβ oligomerization was investigated with extensive metal ion titration NMR experiments. Upon additions of the metal ions, the N-terminal region (1-16) of the Aβ (1-40) peptide was selectively perturbed. In particular, polar residues 4-8 and 13-15 were more strongly affected by the metal ions, suggesting that those regions may be the major binding sites of the metal ions. The NMR signal changes of the N-terminal region were dependent on the peptide concentrations (higher peptide concentrations resulted in stronger signal changes), suggesting that the metal ions facilitate the intermolecular contact between the Aβ peptides. The Aβ (1-40) peptides (>30 μM) were eventually oligomerized even at low temperature (3 °C), where the Aβ peptides are stable as monomeric forms without the metal ions. The real-time oligomerization process was monitored by ¹H/15N HSQC NMR experiments, which provided the first residue-specific structural transition information. Hydrophobic residues 12-21 initially underwent conformational changes due to the intermolecular interactions. After the initial structural rearrangements, the C-terminal residues (32-40) readjusted their conformations presumably for effective oligomerization. Similar structural changes of the metal-free Aβ (1-40) peptides were also observed in the presence of the preformed oligomers, suggesting that the conformational transitions may be the general molecular mechanism of the Aβ (1-40) amyloidogenesis. [ABSTRACT FROM AUTHOR]

Discusses the efforts of Korea to develop its marine tourism resources. Role of marine tourism in the growth of nature-based travel industry; Reasons for the low domestic use of marine tourism resources in Korea; History of the tourism industry in the country; Obstacles to the development of marine tourism industry.

By a systematic ionic effect study in colorimetric dye arrays, we effectively suppressed the anion effect using the proper buffer condition and configured a universal cation sensor system. This result cast a warning for careful validation for other anion sensing systems in aqueous solution. [ABSTRACT FROM AUTHOR]

Summary: Inorganic polyphosphates (polyPs) are linear polymers of orthophosphate units linked by phosphoanhydride bonds. Polyphosphates represent important stores of phosphate and energy, and are abundant in many pro‐ and eukaryotic organisms. In plants, the existence of polyPs has been established using microscopy and biochemical extraction methods that are now known to produce artifacts. Here we use a polyP‐specific dye and a polyP‐binding domain to detect polyPs in plant and algal cells. To develop the staining protocol, we induced polyP granules in Nicotiana benthamiana and Arabidopsis cells by heterologous expression of Escherichia coli polyphosphate kinase 1 (PPK1). Over‐expression of PPK1 but not of a catalytically impaired version of the enzyme leads to severe growth phenotypes, suggesting that ATP‐dependent synthesis and accumulation of polyPs in the plant cytosol is toxic. We next crossed stable PPK1‐expressing Arabidopsis lines with plants expressing the polyP‐binding domain of E. coli exopolyphosphatase (PPX1c), which co‐localized with PPK1‐generated polyP granules. These granules were stained by the polyP‐specific dye JC‐D7 and appeared as electron‐dense structures in transmission electron microscopy sections. Using the polyP staining protocol derived from these experiments, we screened for polyP stores in different organs and tissues of both mono‐ and dicotyledonous plants. While we could not detect polyP granules in higher plants, we could visualize the polyP‐rich acidocalcisomes in the green alga Chlamydomonas reinhardtii. Significance Statement: A chemical dye and an inorganic polyphosphate‐binding domain are shown to specifically label inorganic polyphosphate granules in transgenic Arabidopsis lines and Chlamydomonas acidocalcisomes. Using these tools we show that, in contrast to many prokaryotic and eukaryotic organisms, higher plants do not seem to contain large stores of inorganic polyphosphate. [ABSTRACT FROM AUTHOR]

We describe the use of the fluorescent reporter compound CDr10b to label mid-intestinal structures in zebrafish larvae after simple immersion. CDr10b is deposited into the gut where it initially fills the lumen and is excreted. Using laser-mediated injury of the intestine, we show that CDr10b provides a useful readout of the integrity and repair of the epithelial cell barrier. In addition, CDr10b specifically labels the absorptive mid-intestine segment that is analogous to the mammalian small intestine. By perturbing retinoic acid signaling, which regulates the size of the mid-intestine segment, we show that CDr10b is a valuable tool to rapidly assess developmental malformations of the intestine in live animals. [ABSTRACT FROM AUTHOR]

Peroxynitrite (ONOO-) is a kind of reactive oxygen species (ROS) with super activity of oxidization and nitration, and overproduction of ONOO- is associated with pathogenesis of many diseases. Thus, accurate detection of ONOO- with high sensitivity and selectivity is imperative for elucidating its functions in health or disease states. Herein we for the first time present a new two-photon ratiometric fluorescent ONOO- probe (MITO-CC) based on FRET mechanism by combining rational design strategy and dye-screening approach. MITO-CC, with fast response rate (within 20 s), excellent sensitivity (detection limit = 11.30 nM) and outstanding selectivity toward ONOO-, was successfully applied to ratiometric detection of endogenous ONOO- produced by HepG2/RAW264.7 cells and further employed for imaging oxidative stress in an inflamed mouse model. Therefore, probe MITO-CC could be a potential biological tool to explore the roles of ONOO- under different physiological and pathological settings. [ABSTRACT FROM AUTHOR]

Intracellular viscosity is a fundamental physical parameter that indicates the functioning of cells. In this work, we developed a simple boron-dipyrromethene (BODIPY)-based probe, BTV, for cellular mitochondria viscosity imaging by coupling a simple BODIPY rotor with a mitochondria-targeting unit. The BTV exhibited a significant fluorescence intensity enhancement of more than 100-fold as the solvent viscosity increased. Also, the probe showed a direct linear relationship between the fluorescence lifetime and the media viscosity, which makes it possible to trace the change of the medium viscosity. Furthermore, it was demonstrated that BTV could achieve practical applicability in the monitoring of mitochondrial viscosity changes in live cells through fluorescence lifetime imaging microscopy (FLIM). [ABSTRACT FROM AUTHOR]

The article describes the first combinatorial synthesis of a rosamine library and its use as a fluorescent probe for monitoring the cellular concentration of glutathione. Solid-phase chemistry was incorporated to generate the final product rosamine. Initially, three different 3-amino-6-nitro-9H-xanthone derivatives were synthesized. The library compounds were screened for fluorescence intensity change toward a variety of biorelevant analytes.

Hydrogen sulfi de (H2S) has been recognized as one of most important gaseous signaling molecules mediated by a variety of physiological and pathological processes. Yet, its functions remain largely elusive due to the lack of potent monitoring methods. Hereby this issue is addressed with a powerful new platform--dye-assembled upconversion nanoparticles (UCNPs). A series of chromophores with different absorption bands and fast responses towards H2S is combined with UCNPs and results in a library of H2S sensors with responsive emission signals ranging from the visible to the near-infrared (NIR) region. These nanoprobes demonstrate highly selective and rapid responses to H2S in vitro and in cells. Furthermore, H2S levels in blood can be detected using the developed nanoprobes. Hence the reported H2S sensing platform can serve as a powerful diagnostic tool to research H2S functions and to investigate H2S-related diseases. [ABSTRACT FROM AUTHOR]

Bacterial biofilms are responsible for a wide range of persistent infections. In the clinic, diagnosis of biofilm-associated infections relies heavily on culturing methods, which fail to detect nonculturable bacteria. Identification of novel fluorescent probes for biofilm imaging will greatly facilitate diagnosis of pathogenic bacterial infection. Herein, we report a novel fluorescent probe, CDy11 (compound of designation yellow 11), which targets amyloid in the Pseudomonas aeruginosa biofilm matrix through a diversity oriented fluorescent library approach (DOFLA). CDy11 was further demonstrated for in vivo imaging of P. aeruginosa in implant and corneal infection mice models. [ABSTRACT FROM AUTHOR]

In this work, we report that high-density, vertically grown silicon nanowires (vg-SiNWs) direct a new in vitro developmental pathway of primary hippocampal neurons. Neurons on vg-SiNWs formed a single, extremely elongated major neurite earlier than minor neurites, which led to accelerated polarization. Additionally, the development of lamellipodia, which generally occurs on 2D culture coverslips, was absent on vg-SiNWs. The results indicate that surface topography is an important factor that influences neuronal development and also provide implications for the role of topography in neuronal development in vivo. [ABSTRACT FROM AUTHOR]

Aggregation of amyloid β-peptide (Aβ) is implicated in the pathology of Alzheimer's disease (AD), with the soluble, Aβ oligomeric species thought to be the critical pathological species. Identification and characterization of intermediate species formed during the aggregation process is crucial to the understanding of the mechanisms by which oligomeric species mediate neuronal toxicity and following disease progression. Probing these species proved to be extremely challenging, as evident by the lack of reliable sensors, due to their heterogeneous and transient nature. We describe here an oligomer-specific fluorescent chemical probe, BoDipy-Oligomer (BD-Oligo), developed through the use of the diversity-oriented fluorescent library approach (DOFLA) and high-content, imaging-based screening. This probe enables dynamic oligomer monitoring during fibrillogenesis in vitro and shows in vivo Aβ oligomers staining possibility in the AD mice model. [ABSTRACT FROM AUTHOR]

Hypochlorous acid (HOCI), as a highly potent oxidant, is well-known as a key "killer" for pathogens in the innate immune system. Recently, mounting evidence indicates that intracellular HOCI plays additional important roles in regulating inflammation and cellular apoptosis. However, the organelle (s) involved in the distribution of HOCI remain unknown, causing difficulty to fully exploit its biological functions in cellular signaling pathways and various diseases. One of the main reasons lies in the lack of effective chemical tools to directly detect HOCI at subcellular levels due to low concentration, strong oxidization, and short lifetime of HOCI. Herein, the first two-photon fluorescent HOCI probe (TP-HOCl 1) and its mitochondria- (MITO-TP) and lysosome- (LYSO-TP) targetable derivatives for imaging mitochondrial and lysosomal HOCI were reported. These probes exhibit fast response (within seconds), good selectivity, and high sensitivity (<20 nM) toward HOCI. In live cell experiments, both probes MITO-TP and LYSO-TP were successfully applied to detect intracellular HOCI in corresponding organelles. In particular, the two-photon imaging of MITO-TP and LYSO-TP in murine model shows that higher amount of HOCI can be detected in both lysosome and mitochondria of macrophage cells during inflammation condition. Thus, these probes could not only help clarify the distribution of subcellular HOCI, but also serve as excellent tools to exploit and elucidate functions of HOCI at subcellular levels. [ABSTRACT FROM AUTHOR]

Two-photon (TP) microscopy has an advantage for live tissue imaging which allows a deeper tissue penetration up to 1 mm comparing to one-photon (OP) microscopy. While there are several OP fluorescence probes in use for pancreatic islet imaging, TP imaging of selective cells in live islet still remains a challenge. Herein, we report the discovery of first TP live pancreatic islet imaging probe; TP-α (Two Photon-alpha) which can selectively stain glucagon secreting alpha cells. Through fluorescent image based screening using three pancreatic cell lines, we discovered TP-α from a TP fluorescent dye library TPG (TP-Green). In vitro fluorescence test showed that TP-α have direct interaction and appear glucagon with a significant fluorescence increase, but not with insulin or other hormones/analytes. Finally, TP-α was successfully applied for 3D imaging of live islets by staining alpha cell directly. The newly developed TP-α can be a practical tool to evaluate and identify live alpha cells in terms of localization, distribution and availability in the intact islets. [ABSTRACT FROM AUTHOR]

Development of highly sensitive and selective sensing systems of divalent zinc ion (Zn2+) in organisms has been a growing interest in the past decades owing to its pivotal role in cellular metabolism, apoptosis, and neurotransmission. Herein, we report the rational design and synthesis of a Zn2+ fluorescent-based probe by assembling lanthanide-doped upconversion nanoparticles (UCNPs) with chromophores. Specifically, upconversion luminescence (UCL) can be effectively quenched by the chromophores on the surface of nanoparticles via a fluorescence resonant energy transfer (FRET) process and subsequently recovered upon the addition of Zn2+, thus allowing for quantitative monitoring of Zn2+. Importantly, the sensing system enables detection of Zn2+ in real biological samples. We demonstrate that this chromophore-UCNP nanosystem is capable of implementing an efficient in vitro and in vivo detection of Zn2+ in mouse brain slice with Alzheimer's disease and zebrafish, respectively. [ABSTRACT FROM AUTHOR]

We report the development of a small fluorescent molecule, BDNCA3-D2, herein referred to as PT-Yellow. Soaking zebrafish embryos in PT-Yellow or intraperitoneal injection into adults results in non-toxic in vivo fluorescent labeling of the renal proximal tubules, the major site of blood filtrate reabsorption and a common target of injury in acute kidney injury. We demonstrate the applicability of this new compound as a rapid and simple readout for zebrafish kidney filtration and proximal tubule reabsorption function. [ABSTRACT FROM AUTHOR]

Screening of bead-based peptide libraries against fluorescent dyelabeled target proteins was found to be significantly influenced by the dye characteristics. Commercially available red fluorescent dyes with net negative charges adversely showed strong interactions with library beads. The introduction of zwitterionic dyes significantly reduced the unwanted interactions, which sheds light upon using the right fluorescent probe for acquisition of reliable results in various fluorescence-assisted applications. [ABSTRACT FROM AUTHOR]

The dynamics of cellular heat production and propagation remains elusive at a subcellular level. Here we report the first small molecule fluorescent thermometer selectively targeting the endoplasmic reticulum (ER thermo yellow), with the highest sensitivity reported so far (3.9%/°C). Unlike nanoparticle thermometers, ER thermo yellow stains the target organelle evenly without the commonly encountered problem of aggregation, and successfully demonstrates the ability to monitor intracellular temperature gradients generated by external heat sources in various cell types. We further confirm the ability of ER thermo yellow to monitor heat production by intracellular Ca2+ changes in HeLa cells. Our thermometer anchored at nearly-zero distance from the ER, i.e. the heat source, allowed the detection of the heat as it readily dissipated, and revealed the dynamics of heat production in real time at a subcellular level. [ABSTRACT FROM AUTHOR]

The first fluorescent sensor for milk fat was developed. It exhibited a magnificent, yet selective turn-on feature towards fat molecules in a complicated milk matrix by a disaggregation-induced emission mechanism. Further construction of a handy fluorescence milk fat detector provided a convenient rapid tool to measure the fat amount quantitatively. This discovery may help enhance the milk quality control process. [ABSTRACT FROM AUTHOR]

Herein, a small-molecule fluorescent sensor array for rapid identification of seven heavy metal ions was designed and synthesized, with its sensing mechanism mimicking that of a tongue. The photoinduced electron transfer and intramolecular charge transfer mechanism result in combinatorial interactions between sensor array and heavy metal ions, which lead to diversified fluorescence wavelength shifts and emission intensity changes. Upon principle component analysis (PCA), this result renders clear identification of each heavy metal ion on a 3D spatial dispersion graph. Further exploration provides a concentration-dependent pattern, allowing both qualitative and quantitative measurements of heavy metal ions. On the basis of this information, a "safe-zone" concept was proposed, which provides rapid exclusion of versatile hazardous species from clean water samples based on toxicity characteristic leaching procedure standards. This type of small-molecule fluorescent sensor array could open a new avenue for multiple heavy metal ion detection and simplified water quality analysis. [ABSTRACT FROM AUTHOR]

''Aggregation-caused signal change'' is a well-established mechanism by now and has been widely used as the basis for optical probe and sensor development. Compared to aggregation, its reverse process, disaggregation, has received much less attention and is not properly discussed in the literature so far. With the less established paradigm or mechanism, although some of the reported sensors and probes seem to work through disaggregation phenomena, the proper interpretation of the results and applying the concept to novel probe development is seriously hampered. The process from aggregation to disaggregation generally causes a recovery or enhancement of fluorescence signals, and thus provides an interesting new path to design ''turn-on'' probes. This tutorial review will provide the balanced comparison between aggregation and disaggregation mechanism, and focuses on the less explored advantages of ''disaggregation'' as a novel sensing mechanism and its recent applications in probe development. [ABSTRACT FROM AUTHOR]

The development of a fluorescent probe capable of detecting and distinguishing the wide diversity of G-quadruplex structures is particularly challenging. Herein, we report a novel BODIPY-based fluorescent sensor (GQR) that shows unprecedented selectivity to parallel-stranded G-quadruplexes with exposed ends and four medium grooves. Mechanistic studies suggest that GQR associates with G-quadruplex grooves close to the end of the tetrad core, which may explain the dye's specificity to only a subset of parallel structures. This specific recognition favours the disaggregation of GQR in aqueous solutions thereby recovering the inherent fluorescence of the dye. Due to its unique features, GQR represents a valuable tool for basic biological research and the rapid discovery of novel, specific ligands that target similar structural features of G-quadruplexes [ABSTRACT FROM AUTHOR]

Successful identification of nodal metastases in patients with cancer is crucial to prescribe suitable treatment regimens that can improve recurrence-free survival. Although some new imaging technologies for nodal staging have been developed, such as nanoparticle-enhanced MRI and quantum-dot--based fluorescence imaging, sound technologies for intraoperative differentiation of metastatic and inflamed lymph nodes remain lacking. In this study, we illustrate the feasibility of using a macrophage-specific fluorescent probe (MFP) to visualize sentinel lymph nodes during surgery, highlighting abnormalities related to inflammation and tumor infiltration with signal enhancement and reduction methods using this technology. MFP was identified by high-throughput screening of fluorescent small-molecule libraries synthesized with a diversity-oriented approach. It selectively visualized monocyte and macrophage cell populations in vitro, by live-cell imaging and flow cytometry, as well as in vivo, for imaging-guided surgery. Collectively, this study provides preclinical proof of concept for an intraoperative imaging platform to accurately assess lymph node status, eliminating the need for invasive nodal dissections that can contribute to complications of cancer therapy. [ABSTRACT FROM AUTHOR]

A focused fluorescent probe library for metal cations was developed by combining metal chelators and picolinium/quinolinium moieties as combinatorial blocks connected through a styryl group. Furthermore, metal complexes derived from metal chelators having high binding affinities for metal cations were used to construct a focused probe library for phosphorylated biomolecules. More than 250 fluorescent probes were screened for identifying an ultraselective probe for dTTP. [ABSTRACT FROM AUTHOR]

Elucidating how molecules bind to HSA is fundamental for predicting drug incompatibilities. Through combinatorial screening, we identified a novel fluorescent dye (BD140) with turn-on fluorescence emission and specific binding at HSA drug site 2. We further combined it with dansylamide to develop a fluorescent dye cocktail for high-throughput mapping of the interaction between therapeutics at HSA drug-binding sites. [ABSTRACT FROM AUTHOR]

Novel structures of an near-infrared (NIR) tetraarylazadipyrromethene (aza-BODIPY) series have been prepared. We designed the core structure containing two amido groups at the para-position of the aromatic rings. The amido group was incorporated to secure insensitivity to pH and to ensure a bathochromic shift to the NIR region. Forty members of aza-BODIPY compounds were synthesized by substitution of the acetyl group with commercial amines on the alpha bromide. The physicochemical properties and photostability were investigated and the fluorescence emission maxima (745~755 nm) were found to be in the near infrared (NIR) range of fluorescence. [ABSTRACT FROM AUTHOR]

Phosphopeptides play a crucial role in many biological processes and constitute some of the most powerful biomarkers in disease detection. However they are often present in very low concentration, which makes their detection highly challenging. Here, we demonstrate the use of a solution-dispersible graphene-titania platform for the selective extraction of phosphopeptides from peptide mixtures. This is followed by direct analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The efficient charge and energy exchange between graphene and TiO2 during laser irradiation in SELDI-TOF MS promotes the soft ionization of analytes and affords a detection limit in the attomole range, which is 102-105 more sensitive than conventional platforms. The graphene-titania platform can also be used for detecting phosphopeptides in cancer cells (HeLa cells), where it shows high specificity (94%). An expanded library of 967 unique phosphopeptides is detected using significantly reduced loading of extraction matrixes compared to conventional TiO2 bead-based assays. [ABSTRACT FROM AUTHOR]

The article discusses the combinatorial strategies in the development of fluorescent probe. It states that the combinatorial approaches which were first exploited in drug discovery to gain structurally related drug candidates have boosted the optimization and generation of fluorescent probe. It says that the combinatorial strategies have widened the scope of fluorescent probes to targets which were not accessible including cell differentiation stages, cell phenotypes, and macrostructures.

Herein we report the solid-phase synthesis of a. combinatorial aryl, alkyl-triazine library and its application to biofuet production. The combination of Grignard reactions and solid supported .Suzuki coupling reactions afforded unique 120 triazine compounds with high purities and minimum purification steps. Through an unbiased phenotypic screening for improved biofuel generation m oleaginous yeast, we found one diaryl triazine derivative (E4) which increased the biolipid production up to 86%. [ABSTRACT FROM AUTHOR]

Fluorescent small molecules have become indispensable tools for biomedical research along with the rapidly developing optical imaging technology. We report here a neural stem cell specific borondipyrromethane (BODIPY) derivative compound of designation red 3 (CDr3), developed through a high throughput/content screening of in-house generated diversity oriented fluorescence library in stem cells at different developmental stages. This novel compound specifically detects living neural stem cells of both human and mouse origin. Furthermore, we identified its binding target by proteomic analysis as fatty acid binding protein 7 (FABP7), also known as brain lipid binding protein) which is highly expressed in neural stem cells and localized in the cytoplasm. CDr3 will be a valuable chemical tool in the study and applications of neural stem cells. [ABSTRACT FROM AUTHOR]

Small peptide tags such as c-myc, HA, or FLAG tag have facilitated efficient Western- blotting of proteins of interest especially when speciic antibodies for the proteins are not available. However, the conventional Western-blotting requires the multi-steps process taking at least several hours up to two days. With examples of various applications, here we show a convenient and time-saving method for protein detection which employs a fluorescent chemical BDED and its binding peptide RC-tag. And we propose "Estern staining", as a standard term for protein detection method using fluorescent chemicals and their binding small peptide tags. Eastern staining may substitutes for the time-consuming "immuno-staining" in many versatile applications. [ABSTRACT FROM AUTHOR]

Background: The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, Plasmodium falciparum. Methods: A high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown in vitro in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope. Results: Image analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasite's phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts. Conclusion: Collectively, our results show that high-content live cell-imaging (HCLCI) can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials. [ABSTRACT FROM AUTHOR]

We report a novel design, based on a combination of lanthanide-doped upconversion nanoparticles and manganese dioxide nanosheets, for rapid, selective detection of glutathione in aqueous solutions and living cells. In this approach, manganese dioxide (MnO2) nanosheets formed on the surface of nanoparticles serve as an efficient quencher for upconverted luminescence. The luminescence can be turned on by introducing glutathione that reduces MnO2 into Mn2+. The ability to monitor the glutathione concentration intracellularly may enable rational design of a convenient platform for targeted drug and gene delivery. [ABSTRACT FROM AUTHOR]

Prion diseases currently have no effective therapy. These illnesses affect both animal and human populations, and are characterized by the conformational change of a normal self protein PrPC (C for cellular) to a pathological and infectious conformer, PrPSc (Sc for scrapie). We used a well characterized tissue culture model of prion infection, where mouse neuroblastoma cells (N2a) were infected with 22L PrPSc, to screen compounds for anti-prion activity. In a prior study we designed a library of styryl based, potential imaging compounds which were selected for high affinity binding to Alzheimer's disease &bgr;-amyloid plaques and good blood-brain barrier permeability. In the current study we screened this library for activity in the N2a/22L tissue culture system. We also tested the anti-prion activity of two clinically used drugs, trimipramine and fluphenazine, in the N2a/22L system. These were selected based on their structural similarity to quinacrine, which was previously reported to have anti-prion activity. All the compounds were also screened for toxicity in tissue culture and their ability to disaggregate amyloid fibrils composed of PrP and &bgr;-amyloid synthetic peptides in vitro. Two of the imaging agents, 23I and 59, were found to be both effective at inhibiting prion infection in N2a/22L tissue culture and to be non-toxic. These two compounds, as well as trimipramine and fluphenazine were evaluated in vivo using wild-type CD-1 mice infected peripherally with 139A PrPSc. All four agents significantly prolonged the asymptomatic incubation period of prion infection (p<0.0001 log-rank test), as well as significantly reducing the degree of spongiform change, astrocytosis and PrPSc levels in the brains of treated mice. These four compounds can be considered, with further development, as candidates for prion therapy. [ABSTRACT FROM AUTHOR]

Structural variants of α-galactosylceramide (αGC) that activate invariant natural killer T cells (iNKT cells) are being developed as potential immunomodulatory agents for a variety of applications. Identification of specific forms of these glycolipids that bias responses to favor production of proinflammatory vs anti-inflammatory cytokines is central to current efforts, but this goal has been hampered by the lack of in vitro screening assays that reliably predict the in vivo biological activity of these compounds. Here we describe a fluorescence-based assay to identify functionally distinct αGC analogues. Our assay is based on recent findings showing that presentation of glycolipid antigens by CD1d molecules localized to plasma membrane detergent-resistant microdomains (lipid rafts) is correlated with induction of interferon-&#x03B3 secretion and Th1-biased cytokine responses. Using an assay that measures lipid raft residency of CD1d molecules loaded with αGC, we screened a library of ∼200 synthetic αGC analogues and identified 19 agonists with potential Th1-biasing activity. Analysis of a subset of these novel candidate Th1 type agonists in vivo in mice confirmed their ability to induce systemic cytokine responses consistent with a Th1 type bias. These results demonstrate the predictive value of this novel in vitro assay for assessing the in vivo functionality of glycolipid agonists and provide the basis for a relatively simple high-throughput assay for identification and functional classification of iNKT cell activating glycolipids. [ABSTRACT FROM AUTHOR]

Investigation of the genetic functions in complex biological systems is a challenging step in recent year. Hence, several valuable and interesting research projects have been developed with novel ideas to find out the unknown functions of genes or proteins. To validate the applicability of their novel ideas, various approaches are built up. To date, the most promising and commonly used approach for discovering the target proteins from biological system using small molecule is well known a forward chemical genetics which is considered to be more convenient than the classical genetics. Although, the forward chemical genetics consists of the three basic components, the target identification is the most challenging step to chemical biology researchers. Hence, the diverse target identification methods have been developed and adopted to disclose the small molecule bound protein. Herein, in this review, we briefly described the first two parts chemical toolbox and screening, and then the target identifications in forward chemical genetics are thoroughly described along with the illustrative real example case study. In the tabular form, the different biological active small molecules which are the successful examples of target identifications are accounted in this research review. [ABSTRACT FROM AUTHOR]