bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing products with set-based design: How to set up an idea portfolio and a team organization to establish design feasibility
Authors: Schulze Anja
Published: July 2016

Prior research has identified set-based design as a method that accounts for the high level of uncertainty that is associated with the design of innovative products or systems. Rather than precisely specifying a system architecture in the early design stages, set-based design builds on designing a system and its architecture in an evolutionary way. The literature on set-based design has studied how a system's design evolves by moving from a number of optional design ideas to the final system through gradually eliminating unfeasible design ideas and continually developing design ideas for which engineers increasingly establish feasibility. However, little is known about how firms set up the design process and the organization to successfully create new products with set-based design. Our research contributes to closing this gap. First, we study how firms determine the number (i.e., portfolio) of design ideas to pursue, an important step of the early design process. Second, we study how firms organize for set-based design by assigning teams to develop design ideas and eventually design a system's architecture. Our research uses an exploratory case study approach, investigating five cases in three different firms. First, we find that the early design process is characterized by the absence of formal idea evaluation and selection. Instead, firms start to pursue all initially created design ideas, evaluating and selecting them in an evolutionary manner as the design project progresses. Second, we identify two organizational approaches associated with set-based design: assign one team to pursue all ideas or assign one team per design idea.
Model-based reliability analysis
Authors: Lindén Julia , Sellgren Ulf , Söderberg Anders
Published: July 2016

The main function of a heavy truck is to transport goods, with ton-kilometers/year as an example of a major quantitative performance measure. Furthermore, the truck is directly operated by a driver, who has several additional functional requirements, of both ergonomic and communicative characters. Failure of these functions may be a subjective experience, differing between drivers, but the failures are still important. Today's just-in-time delivery systems rely on getting the goods on time, and this requires high availability. Availability is reduced not only by technical failures but also by subjectively experienced failures, because these also require repairs, or downtime. Product reliability is a systems property that cannot be attributed to a single component. It is in many cases related to interaction between components, or to interaction between humans and the technical system, in the case of subjectively experienced failures. Reliability assessments of systems with interactive functions require a system model that includes the interfaces between the technical system and human features that are carriers of interactive functions. This paper proposes a model of system architecture, for the purpose of reliability assessments, that integrates different and complementary representations, such as function–means diagrams and a design structure matrix. The novelty of the presented approach is that it treats and integrates the technical and the human subsystems through the human–technical system interfaces. The proposed systems reliability approach is described and verified with a component analysis case study of an extended truck cab and driver system.
Coffee consumption and mortality in three Eastern European countries: results from the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study
Authors: Grosso Giuseppe , Stepaniak Urszula , Micek Agnieszka , Stefler Denes , Bobak Martin , Pajak Andrzej
Published: July 2016

Objective

To test the association between coffee consumption and risk of all-cause, CVD and cancer death in a European cohort.

Design

Prospective cohort study. Cox proportional hazards models with adjustment for potential confounders to estimate multivariable hazard ratios (HR) and 95 % CI were used.

Setting

Czech Republic, Russia and Poland.

Subjects

A total of 28561 individuals followed for 6·1 years.

Results

A total of 2121 deaths (43·1 % CVD and 35·7 % cancer mortality) occurred during the follow-up. Consumption of 3–4 cups coffee/d was associated with lower mortality risk in men (HR=0·83; 95 % CI 0·71, 0·99) and women (HR=0·63; 95 % CI 0·47, 0·84), while further intake showed non-significant reduced risk estimates (HR=0·71; 95 % CI 0·49, 1·04 and HR=0·51; 95 % CI 0·24, 1·10 in men and women, respectively). Decreased risk of CVD mortality was also found in men (HR=0·71; 95 % CI 0·54, 0·93) for consumption of 3–4 cups coffee/d. Stratified analysis revealed that consumption of a similar amount of coffee was associated with decreased risk of all-cause (HR=0·61; 95 % CI 0·43, 0·87) and cancer mortality (HR=0·59; 95 % CI 0·35, 0·99) in non-smoking women and decreased risk of all-cause mortality for >4 cups coffee/d in men with no/moderate alcohol intake.

Conclusions

Coffee consumption was associated with decreased risk of mortality. The protective effect was even stronger when stratification by smoking status and alcohol intake was performed.
GPRC5A is a potential oncogene in pancreatic ductal adenocarcinoma cells that is upregulated by gemcitabine with help from HuR
Authors: Zhou H , Telonis A G , Jing Y , Xia N L , Biederman L , Jimbo M , Blanco F , Londin E , Brody J R , Rigoutsos I
Published: July 2016

GPRC5A is an orphan G-protein coupled receptor with an intriguing dual behavior, acting as an oncogene in some cancers and as a tumor suppressor in other cancers. In the pancreatic cancer context, very little is known about GPRC5A. By analyzing messenger RNA (mRNA) expression data from 675 human cancer cell lines and 10 609 samples from The Cancer Genome Atlas (TCGA) we found that GPRC5A’s abundance in pancreatic cancer is highest (cell lines) or second highest (TCGA) among all tissues and cancer types. Further analyses of an independent set of 252 pancreatic normal and cancer samples showed GPRC5A mRNA to be more than twofold upregulated in primary tumor samples compared with normal pancreas (P-value<10−5), and even further upregulated in pancreatic cancer metastases to various organs (P-value=0.0021). Immunostaining of 208 cores (103 samples) of a tissue microarray showed generally low expression of GPRC5A protein in normal pancreatic ductal cells; on the other hand, in primary and metastatic samples, GPRC5A protein levels were dramatically increased in pancreatic ductal cells. In vitro studies of multiple pancreatic cancer cell lines showed that an increase in GPRC5A protein levels promoted pancreatic cancer cell growth and migration. Unexpectedly, when we treated pancreatic cancer cell lines with gemcitabine (2′,2′-difluorodeoxycytidine), we observed an increase in GPRC5A protein abundance. On the other hand, when we knocked down GPRC5A we sensitized pancreatic cancer cells to gemcitabine. Through further experimentation we showed that the monotonic increase in GPRC5A protein levels that we observe for the first 18 h following gemcitabine treatment results from interactions between GPRC5A’s mRNA and the RNA-binding protein HuR, which is an established key mediator of gemcitabine’s efficacy in cancer cells. As we discovered, the interaction between GPRC5A and HuR is mediated by at least one HuR-binding site in GPRC5A’s mRNA. Our findings indicate that GPRC5A is part of a complex molecular axis that involves gemcitabine and HuR, and, possibly, other genes. Further work is warranted before it can be established unequivocally that GPRC5A is an oncogene in the pancreatic cancer context.
Double-edged-sword effect of IL-1β on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-κB, MAPK and BMP/Smad signaling pathways
Authors: Mao C-y , Wang Y-g , Zhang X , Zheng X-y , Tang T-t , Lu E-y
Published: July 2016

Microenvironmental conditions can interfere with the functional role and differentiation of mesenchymal stem cells (MSCs). Recent studies suggest that an inflammatory microenvironment can significantly impact the osteogenic potential of periodontal ligament stem cells (PDLSCs), but the precise effects and mechanisms involved remain unclear. Here, we show for the first time that interleukin-1β(IL-1β) has dual roles in the osteogenesis of PDLSCs at concentrations ranging from physiologically healthy levels to those found in chronic periodontitis. Low doses of IL-1βactivate the BMP/Smad signaling pathway to promote the osteogenesis of PDLSCs, but higher doses of IL-1βinhibit BMP/Smad signaling through the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, inhibiting osteogenesis. These results demonstrate that crosstalk between NF-κB, MAPK and BMP/Smad signaling mediates this dual effect of IL-1βon PDLSCs. We also show that the impaired osteogenesis of PDLSCs results in more inflammatory cytokines and chemokines being released, inducing the chemotaxis of macrophages, which further clarifies the role of PDLSCs in the pathogenesis of periodontitis.
Structural basis of transcobalamin recognition by human CD320 receptor
Authors: Alam Amer , Woo Jae-Sung , Schmitz Jennifer , Prinz Bernadette , Root Katharina , Chen Fan , Bloch Joël S. , Zenobi Renato , Locher Kaspar P.
Published: July 2016

Cellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin (TC) from the plasma by CD320, a ubiquitous cell surface receptor of the LDLR family. Here we present the crystal structure of human holo-TC in complex with the extracellular domain of CD320, visualizing the structural basis of the TC-CD320 interaction. The observed interaction chemistry can rationalize the high affinity of CD320 for TC and lack of haptocorrin binding. The in vitro affinity and complex stability of TC-CD320 were quantitated using a solid-phase binding assay and thermostability analysis. Stable complexes with TC were also observed for the disease-causing CD320ΔE88 mutant and for the isolated LDLR-A2 domain. We also determined the structure of the TC-CD320ΔE88 complex, which revealed only minor changes compared with the wild-type complex. Finally, we demonstrate significantly reduced in vitro affinity of TC for CD320 at low pH, recapitulating the proposed ligand release during the endocytic pathway.
SREBP1c-CRY1 signalling represses hepatic glucose production by promoting FOXO1 degradation during refeeding
Authors: Jang Hagoon , Lee Gha Young , Selby Christopher P. , Lee Gung , Jeon Yong Geun , Lee Jae Ho , Cheng Kenneth King Yip , Titchenell Paul , Birnbaum Morris J. , Xu Aimin , Sancar Aziz , Kim Jae Bum
Published: July 2016

SREBP1c is a key lipogenic transcription factor activated by insulin in the postprandial state. Although SREBP1c appears to be involved in suppression of hepatic gluconeogenesis, the molecular mechanism is not thoroughly understood. Here we show that CRY1 is activated by insulin-induced SREBP1c and decreases hepatic gluconeogenesis through FOXO1 degradation, at least, at specific circadian time points. SREBP1c−/− and CRY1−/− mice show higher blood glucose than wild-type (WT) mice in pyruvate tolerance tests, accompanied with enhanced expression of PEPCK and G6Pase genes. CRY1 promotes degradation of nuclear FOXO1 by promoting its binding to the ubiquitin E3 ligase MDM2. Although SREBP1c fails to upregulate CRY1 expression in db/db mice, overexpression of CRY1 attenuates hyperglycaemia through reduction of hepatic FOXO1 protein and gluconeogenic gene expression. These data suggest that insulin-activated SREBP1c downregulates gluconeogenesis through CRY1-mediated FOXO1 degradation and that dysregulation of hepatic SREBP1c-CRY1 signalling may contribute to hyperglycaemia in diabetic animals.
Direct TEM observations of growth mechanisms of two-dimensional MoS2 flakes
Authors: Fei Linfeng , Lei Shuijin , Zhang Wei-Bing , Lu Wei , Lin Ziyuan , Lam Chi Hang , Chai Yang , Wang Yu
Published: July 2016

A microscopic understanding of the growth mechanism of two-dimensional materials is of particular importance for controllable synthesis of functional nanostructures. Because of the lack of direct and insightful observations, how to control the orientation and the size of two-dimensional material grains is still under debate. Here we discern distinct formation stages for MoS2 flakes from the thermolysis of ammonium thiomolybdates using in situ transmission electron microscopy. In the initial stage (400 °C), vertically aligned MoS2 structures grow in a layer-by-layer mode. With the increasing temperature of up to 780 °C, the orientation of MoS2 structures becomes horizontal. When the growth temperature reaches 850 °C, the crystalline size of MoS2 increases by merging adjacent flakes. Our study shows direct observations of MoS2 growth as the temperature evolves, and sheds light on the controllable orientation and grain size of two-dimensional materials.
Global climate change driven by soot at the K-Pg boundary as the cause of the mass extinction
Authors: Kaiho Kunio , Oshima Naga , Adachi Kouji , Adachi Yukimasa , Mizukami Takuya , Fujibayashi Megumu , Saito Ryosuke
Published: July 2016

The mass extinction of life 66 million years ago at the Cretaceous/Paleogene boundary, marked by the extinctions of dinosaurs and shallow marine organisms, is important because it led to the macroevolution of mammals and appearance of humans. The current hypothesis for the extinction is that an asteroid impact in present-day Mexico formed condensed aerosols in the stratosphere, which caused the cessation of photosynthesis and global near-freezing conditions. Here, we show that the stratospheric aerosols did not induce darkness that resulted in milder cooling than previously thought. We propose a new hypothesis that latitude-dependent climate changes caused by massive stratospheric soot explain the known mortality and survival on land and in oceans at the Cretaceous/Paleogene boundary. The stratospheric soot was ejected from the oil-rich area by the asteroid impact and was spread globally. The soot aerosols caused sufficiently colder climates at mid–high latitudes and drought with milder cooling at low latitudes on land, in addition to causing limited cessation of photosynthesis in global oceans within a few months to two years after the impact, followed by surface-water cooling in global oceans in a few years. The rapid climate change induced terrestrial extinctions followed by marine extinctions over several years.
Carbon Storage Patterns of Caragana korshinskii in Areas of Reduced Environmental Moisture on the Loess Plateau, China
Authors: Gong Chunmei , Bai Juan , Wang Junhui , Zhou Yulu , Kang Tai , Wang Jiajia , Hu Congxia , Guo Hongbo , Chen Peilei , Xie Pei , Li Yuanfeng
Published: July 2016

Precipitation patterns are influenced by climate change and profoundly alter the carbon sequestration potential of ecosystems. Carbon uptake by shrubbery alone accounts for approximately one-third of the total carbon sink; however, whether such uptake is altered by reduced precipitation is unclear. In this study, five experimental sites characterised by gradual reductions in precipitation from south to north across the Loess Plateau were used to evaluate theCaragana korshinskii’s functional and physiological features, particularly its carbon fixation capacity, as well as the relationships among these features. We found the improved net CO2assimilation rates and inhibited transpiration at the north leaf were caused by lower canopy stomatal conductance, which enhanced the instantaneous water use efficiency and promoted plant biomass as well as carbon accumulation. Regional-scale precipitation reductions over a certain range triggered a distinct increase in the shrub’s organic carbon storage with an inevitable decrease in the soil’s organic carbon storage. Our results confirmC. korshinskiiis the optimal dominant species for the reconstruction of fragile dryland ecosystems. The patterns of organic carbon storage associated with this shrub occurred mostly in the soil at wetter sites, and in the branches and leaves at drier sites across the arid and semi-arid region.
Human Thanatomicrobiome Succession and Time Since Death
Authors: Javan Gulnaz T. , Finley Sheree J. , Can Ismail , Wilkinson Jeremy E. , Hanson J. Delton , Tarone Aaron M.
Published: July 2016

The thanatomicrobiome (thanatos, Greek for death) is a relatively new term and is the study of the microbes colonizing the internal organs and orifices after death. Recent scientific breakthroughs in an initial study of the thanatomicrobiome have revealed that a majority of the microbes within the human body are the obligate anaerobes,Clostridium spp., in the internal postmortem microbial communities. We hypothesized that time-dependent changes in the thanatomicrobiome within internal organs can estimate the time of death as a human body decays. Here we report a cross-sectional study of the sampling of 27 human corpses from criminal cases with postmortem intervals between 3.5–240 hours. The impetus for examining microbial communities in different internal organs is to address the paucity of empirical data on thanatomicrobiomic succession caused by the limited access to these organs prior to death and a dearth of knowledge regarding the movement of microbes within remains. Our sequencing results of 16S rRNA gene amplicons of 27 postmortem samples from cadavers demonstrated statistically significant time-, organ- and sex-dependent changes. These results suggest that comprehensive knowledge of the number and abundance of each organ’s signature microorganisms could be useful to forensic microbiologists as a new source of data for estimating postmortem interval.
Mediterranean circulation perturbations over the last five centuries: Relevance to past Eastern Mediterranean Transient-type events
Authors: Incarbona Alessandro , Martrat Belen , Mortyn P. Graham , Sprovieri Mario , Ziveri Patrizia , Gogou Alexandra , Jordà Gabriel , Xoplaki Elena , Luterbacher Juerg , Langone Leonardo , Marino Gianluca , Rodríguez-Sanz Laura , Triantaphyllou Maria , Di Stefano Enrico , Grimalt Joan O. , Tranchida Giorgio , Sprovieri Rodolfo , Mazzola Salvatore
Published: July 2016

The Eastern Mediterranean Transient (EMT) occurred in the Aegean Sea from 1988 to 1995 and is the most significant intermediate-to-deep Mediterranean overturning perturbation reported by instrumental records. The EMT was likely caused by accumulation of high salinity waters in the Levantine and enhanced heat loss in the Aegean Sea, coupled with surface water freshening in the Sicily Channel. It is still unknown whether similar transients occurred in the past and, if so, what their forcing processes were. In this study, sediments from the Sicily Channel document surface water freshening (SCFR) at 1910 ± 12, 1812 ± 18, 1725 ± 25 and 1580 ± 30 CE. A regional ocean hindcast links SCFR to enhanced deep-water production and in turn to strengthened Mediterranean thermohaline circulation. Independent evidence collected in the Aegean Sea supports this reconstruction, showing that enhanced bottom water ventilation in the Eastern Mediterranean was associated with each SCFR event. Comparison between the records and multi-decadal atmospheric circulation patterns and climatic external forcings indicates that Mediterranean circulation destabilisation occurs during positive North Atlantic Oscillation (NAO) and negative Atlantic Multidecadal Oscillation (AMO) phases, reduced solar activity and strong tropical volcanic eruptions. They may have recurrently produced favourable deep-water formation conditions, both increasing salinity and reducing temperature on multi-decadal time scales.
Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway
Authors: Belvedere Raffaella , Bizzarro Valentina , Forte Giovanni , Dal Piaz Fabrizio , Parente Luca , Petrella Antonello
Published: July 2016

Annexin A1 (ANXA1) is a Ca2+-binding protein over-expressed in pancreatic cancer (PC). We recently reported that extracellular ANXA1 mediates PC cell motility acting on Formyl Peptide Receptors (FPRs). Here, we describe other mechanisms by which intracellular ANXA1 could mediate PC progression. We obtained ANXA1 Knock-Out (KO) MIA PaCa-2 cells using the CRISPR/Cas9 genome editing technology. LC-MS/MS analysis showed altered expression of several proteins involved in cytoskeletal organization. As a result, ANXA1 KO MIA PaCa-2 partially lost their migratory and invasive capabilities with a mechanism that appeared independent of FPRs. The acquisition of a less aggressive phenotype has been further investigated in vivo. Wild type (WT), PGS (scrambled) and ANXA1 KO MIA PaCa-2 cells were engrafted orthotopically in SCID mice. No differences were found about PC primary mass, conversely liver metastatization appeared particularly reduced in ANXA1 KO MIA PaCa-2 engrafted mice. In summary, we show that intracellular ANXA1 is able to preserve the cytoskeleton integrity and to maintain a malignant phenotype in vitro. The protein has a relevant role in the metastatization process in vivo, as such it appears attractive and suitable as prognostic and therapeutic marker in PC progression.
ROCK1 reduces mitochondrial content and irisin production in muscle suppressing adipocyte browning and impairing insulin sensitivity
Authors: Zhou Xiaoshuang , Li Rongshan , Liu Xinyan , Wang Lihua , Hui Peng , Chan Lawrence , Saha Pradip K. , Hu Zhaoyong
Published: July 2016

Irisin reportedly promotes the conversion of preadipocytes into “brown-like” adipocytes within subcutaneous white adipose tissue (WAT) via a mechanism that stimulates UCP-1 expression. An increase in plasma irisin has been associated with improved obesity and insulin resistance in mice with type 2 diabetes. But whether a low level of irisin stimulates the development of obesity has not been determined. In studying mice with muscle-specific constitutive ROCK1 activation (mCaROCK1), we found that irisin production was down-regulated and the mice developed obesity and insulin resistance. Therefore, we studied the effects of irisin deficiency on energy metabolism in mCaROCK1 mice. Constitutively activation of ROCK1 in muscle suppressed irisin expression in muscle resulting in a low level of irisin in circulation. Irisin deficiency reduced heat production and decreased the expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) and subcutaneous WAT. Moreover, mCaROCK1 mice also displayed impaired glucose tolerance. Notably, irisin replenishment in mCaROCK1 mice partially reversed insulin resistance and obesity and these changes were associated with increased expression of UCP1 and Pref-1 in subcutaneous WAT. These results demonstrate that irisin mediates muscle-adipose tissue communication and regulates energy and glucose homeostasis. Irisin administration can correct obesity and insulin resistance in mice.
The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors
Authors: Dufort Sandrine , Le Duc Géraldine , Salomé Murielle , Bentivegna Valerie , Sancey Lucie , Bräuer-Krisch Elke , Requardt Herwig , Lux François , Coll Jean-Luc , Perriat Pascal , Roux Stéphane , Tillement Olivier
Published: July 2016

We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.
Analysis of the mouse gut microbiome using full-length 16S rRNA amplicon sequencing
Authors: Shin Jongoh , Lee Sooin , Go Min-Jeong , Lee Sang Yup , Kim Sun Chang , Lee Chul-Ho , Cho Byung-Kwan
Published: July 2016

Demands for faster and more accurate methods to analyze microbial communities from natural and clinical samples have been increasing in the medical and healthcare industry. Recent advances in next-generation sequencing technologies have facilitated the elucidation of the microbial community composition with higher accuracy and greater throughput than was previously achievable; however, the short sequencing reads often limit the microbial composition analysis at the species level due to the high similarity of 16S rRNA amplicon sequences. To overcome this limitation, we used the nanopore sequencing platform to sequence full-length 16S rRNA amplicon libraries prepared from the mouse gut microbiota. A comparison of the nanopore and short-read sequencing data showed that there were no significant differences in major taxonomic units (89%) except one phylotype and three taxonomic units. Moreover, both sequencing data were highly similar at all taxonomic resolutions except the species level. At the species level, nanopore sequencing allowed identification of more species than short-read sequencing, facilitating the accurate classification of the bacterial community composition. Therefore, this method of full-length 16S rRNA amplicon sequencing will be useful for rapid, accurate and efficient detection of microbial diversity in various biological and clinical samples.
Roles of OA1 octopamine receptor and Dop1 dopamine receptor in mediating appetitive and aversive reinforcement revealed by RNAi studies
Authors: Awata Hiroko , Wakuda Ryo , Ishimaru Yoshiyasu , Matsuoka Yuji , Terao Kanta , Katata Satomi , Matsumoto Yukihisa , Hamanaka Yoshitaka , Noji Sumihare , Mito Taro , Mizunami Makoto
Published: July 2016

Revealing reinforcing mechanisms in associative learning is important for elucidation of brain mechanisms of behavior. In mammals, dopamine neurons are thought to mediate both appetitive and aversive reinforcement signals. Studies using transgenic fruit-flies suggested that dopamine neurons mediate both appetitive and aversive reinforcements, through the Dop1 dopamine receptor, but our studies using octopamine and dopamine receptor antagonists and using Dop1 knockout crickets suggested that octopamine neurons mediate appetitive reinforcement and dopamine neurons mediate aversive reinforcement in associative learning in crickets. To fully resolve this issue, we examined the effects of silencing of expression of genes that code the OA1 octopamine receptor and Dop1 and Dop2 dopamine receptors by RNAi in crickets. OA1-silenced crickets exhibited impairment in appetitive learning with water but not in aversive learning with sodium chloride solution, while Dop1-silenced crickets exhibited impairment in aversive learning but not in appetitive learning. Dop2-silenced crickets showed normal scores in both appetitive learning and aversive learning. The results indicate that octopamine neurons mediate appetitive reinforcement via OA1 and that dopamine neurons mediate aversive reinforcement via Dop1 in crickets, providing decisive evidence that neurotransmitters and receptors that mediate appetitive reinforcement indeed differ among different species of insects.
Oncogenic KRAS triggers MAPK-dependent errors in mitosis and MYC-dependent sensitivity to anti-mitotic agents
Authors: Perera David , Venkitaraman Ashok R.
Published: July 2016

Oncogenic KRAS induces cell proliferation and transformation, but little is known about its effects on cell division. Functional genetic screens have recently revealed that cancer cell lines expressing oncogenic KRAS are sensitive to interference with mitosis, but neither the mechanism nor the uniformity of anti-mitotic drug sensitivity connected with mutant KRAS expression are yet clear. Here, we report that acute expression of oncogenic KRAS in HeLa cells induces mitotic delay and defects in chromosome segregation through mitogen-activated protein kinase (MAPK) pathway activation and de-regulated expression of several mitosis-related genes. These anomalies are accompanied by increased sensitivity to anti-mitotic agents, a phenotype dependent on the transcription factor MYC and its downstream target anti-apoptotic protein BCL-XL. Unexpectedly, we find no correlation between KRAS mutational status or MYC expression levels and anti-mitotic drug sensitivity when surveying a large database of anti-cancer drug responses. However, we report that the co-existence of KRAS mutations and high MYC expression predicts anti-mitotic drug sensitivity. Our findings reveal a novel function of oncogenic KRAS in regulating accurate mitotic progression and suggest new avenues to therapeutically target KRAS-mutant tumours and stratify patients in ongoing clinical trials of anti-mitotic drugs.
Highly Selective Enrichment of Glycopeptides Based on Zwitterionically Functionalized Soluble Nanopolymers
Authors: Cao Weiqian , Huang Jiangming , Jiang Biyun , Gao Xing , Yang Pengyuan
Published: July 2016

Efficient glycopeptides enrichment prior to mass spectrometry analysis is essential for glycoproteome study. ZIC-HILIC (zwitterionic hydrophilic interaction liquid chromatography) based glycopeptides enrichment approaches have been attracting more attention for several benefits like easy operating, high enrichment specificity and intact glycopeptide retained. In this study, Poly (amidoamine) dendrimer (PAMAM) was adopted for the synthesis of zwitterionically functionalized (ZICF) materials for glycopeptide enrichment. The multiple branched structure and good solubility of ZICF-PAMAM enables a sufficient interaction with glycopeptides. The ZICF-PAMAM combined with the FASP-mode enrichment strategy exhibits more superior performance compared with the existing methods. It has the minimum detectable concentration of femtomolar level and high recovery rate of over 90.01%, and can efficiently enrich glycopeptides from complex biological samples even for merely 0.1 μL human serum. The remarkable glycopeptides enrichment capacity of ZICF-PAMAM highlights the potential application in in-depth glycoproteome research, which may open up new opportunities for the development of glycoproteomics.
An efficient method for gene silencing in human primary plasmacytoid dendritic cells: silencing of the TLR7/IRF-7 pathway as a proof of concept
Authors: Smith Nikaïa , Vidalain Pierre-Olivier , Nisole Sébastien , Herbeuval Jean-Philippe
Published: July 2016

Plasmacytoid dendritic cells (pDC) are specialized immune cells that produce massive levels of type I interferon in response to pathogens. Unfortunately, pDC are fragile and extremely rare, rendering their functional study a tough challenge. However, because of their central role in numerous pathologies, there is a considerable need for an efficient and reproducible protocol for gene silencing in these cells. In this report, we tested six different methods for siRNA delivery into primary human pDC including viral-based, lipid-based, electroporation and poly-ethylenimine (PEI) technologies. We show that lipid-based reagent DOTAP was extremely efficient for siRNA delivery into pDC and did not induce cell death or pDC activation. We successfully silenced Toll-Like Receptor 7 (TLR7), CXCR4 and IFN regulatory factor 7 (IRF-7) gene expression in pDC as assessed by RT-qPCR or cytometry. Finally, we showed that TLR7 or IRF-7 silencing in pDC specifically suppressed IFN-α production upon stimulation, providing a functional validation of our transfection protocol.
Towards Cyclodextrin-Based Supramolecular Materials
Authors: Karim Anis Abdul , Loh Xian Jun
Published: July 2016

Inclusion complexation between cyclodextrins (CDs) and various guests has been extensively investigated in supramolecular chemistry. Besides CDs, there are several important macrocyclic host families, such as crown ethers and cucurbiturils. Until now, the contribution of these other families to macromolecular self-assembly has been small compared to CDs. This chapter will focus on CDs as hosts for interaction with guest monomers to form hydrogels. CD interactions with other monomers were made possible depending on proper molecular recognition. Macroscopic molecular recognition can be categorized by three types of interactions: main chain (polyrotaxane), side chain, and sequential complexes. Utilizing CD as host molecule, polymers such as polyethers, cationic polymers, polyamines, polyesters, π-conjugated polymers, polyolefins, polyamides, polyurethanes, and inorganic polymers could interact to form inclusion complexes. This chapter will attempt to discuss these studies. Depending on the functional groups attached to the polymeric component, supramolecular formation can be altered based on the stimuli response. Introducing polymer side chains or groups that respond selectively towards external stimuli could affect the hydrogel formation. This chapter also discusses the stimuli response of such systems.
Recent progress in solid-phase microextraction and its pharmaceutical and biomedical applications
Authors: Kataoka Hiroyuki , Ishizaki Atsushi , Saito Keita
Published: July 2016

Configurations of various devices for various SPME techniques.
Selection of two optional covalent bonds by electric stimuli: dual catalytic switching of redox-active copper
Authors: Kamamoto Yu , Nitta Yuya , Kubo Kazuyuki , Mizuta Tsutomu , Kume Shoko
Published: July 2016

Two types of redox functionality were selected for covalent binding on a carbon electrode, responding to an electric potential applied to a dual-active copper catalyst.
Extended conjugated microporous polymers for photocatalytic hydrogen evolution from water
Authors: Sprick Reiner Sebastian , Bonillo Baltasar , Sachs Michael , Clowes Rob , Durrant James R. , Adams Dave J. , Cooper Andrew I.
Published: July 2016

Conjugated microporous polymers (CMPs) have been used as photocatalysts for hydrogen production from water in the presence of a sacrificial electron donor.
Probing the chemical structure of monolayer covalent-organic frameworks grown via Schiff-base condensation reactions
Authors: Hu Ya , Goodeal Niall , Chen Ying , Ganose Alex M. , Palgrave Robert G. , Bronstein Hugo , Blunt Matthew O.
Published: July 2016

XPS and STM analysis shows that covalent links formed within a surface-supported Schiff-base 2D-COF consist of a mixture of imine and hemiaminal groups.
Fluorescent vinblastine probes for live cell imaging
Authors: Meimetis Labros G. , Giedt Randy J. , Mikula Hannes , Carlson Jonathan C. , Kohler Rainer H. , Pirovich David B. , Weissleder Ralph
Published: July 2016

We describe the synthesis of several fluorescent analogues of the clinically approved microtubule destabilizing agent vinblastine. The evaluated probes are the most potent described and provides the first example of uptake, distribution and live cell imaging of this well known antimitotic agent.
Ruthenium(0)-catalyzed hydroarylation of alkynes via ketone-directed C–H functionalization using in situ-generated ruthenium complexes
Authors: Hu Feng , Szostak Michal
Published: July 2016

Ketone-directed Ru(0)-catalyzed hydroarylation of alkynes enabled byin situgeneration of a Ru(0) catalyst from an air-stable, inexpensive and user-friendly Ru(ii) precatalyst is reported.
One-pot synthesis with in situ preconcentration of spherical monodispersed gold nanoparticles using thermoresponsive 3-(alkyldimethylammonio)-propyl sulfate zwitterionic surfactants
Authors: Takagai Yoshitaka , Miura Ryo , Endo Arata , Hinze Willie L.
Published: July 2016

Homogeneous solutions of thermoresponsive zwitterionic 3-(alkyldimethylammonio)-propyl sulfate surfactants at elevated temperatures were employed for the synthesis of gold nanoparticles (AuNPs) by the citrate reduction method.
Intramolecular cooperativity in frustrated Lewis pairs
Authors: Körte Leif A. , Blomeyer Sebastian , Heidemeyer Shari , Mix Andreas , Neumann Beate , Mitzel Norbert W.
Published: July 2016

The doubly Lewis-acid functionalised aniline PhN[(CH2)3B(C6F5)2]2 features two competing boron functions in fast exchange for binding to the central Lewis base. In contrast to the mono acid-functionalised PhMeN[(CH2)3B(C6F5)2], it is an active frustrated Lewis pair.
A TP-FRET-based two-photon fluorescent probe for ratiometric visualization of endogenous sulfur dioxide derivatives in mitochondria of living cells and tissues
Authors: Yang Xiaoguang , Zhou Yibo , Zhang Xiufang , Yang Sheng , Chen Yun , Guo Jingru , Li Xiaoxuan , Qing Zhihe , Yang Ronghua
Published: July 2016

A TP-FRET-based ratiometric two-photon fluorescent probe for endogenous SO2 derivative imaging in mitochondria has been developed for the first time.
Chelation competition induced polymerization (CCIP): construction of integrated hollow polydopamine nanocontainers with tailorable functionalities
Authors: Xiang Siyuan , Wang Dandan , Zhang Kai , Liu Wendong , Wu Ce , Meng Qingnan , Sun Hongchen , Yang Bai
Published: July 2016

A novel CCIP strategy is exploited to construct integrated hollow polydopamine nanocontainers, and Au NRs@PDA NCTs constructed through this method show excellent performance in cancer eradication.
Ultrafast electron injection into photo-excited organic molecules
Authors: Cvetko Dean , Fratesi Guido , Kladnik Gregor , Cossaro Albano , Brivio Gian Paolo , Venkataraman Latha , Morgante Alberto
Published: July 2016

State-of-the-art X-ray spectroscopy allows femtosecond gating of energy levels of photo-excited molecules on a metal substrate enabling ultrafast and bi-directional charge transfer across the interface with controllable dependence on the molecular adsorption geometry.
Solid state synthesis of Ru–MC with highly dispersed semi-embedded ruthenium nanoparticles in a porous carbon framework for benzoic acid hydrogenation
Authors: Jiang Zhengliang , Lan Guojun , Liu Xiaoyan , Tang Haodong , Li Ying
Published: July 2016

A dry grinding approach was reported for mesoporous Ru–carbon catalysts with semi-embedded Ru nanoparticles, which shows excellent performance in aromatic hydrogenation of benzoic acid to cyclohexane carboxylic acid.
A novel in situ synthesis of SiBCN-Zr composites prepared by a sol–gel process and spark plasma sintering
Authors: Miao Yang , Yang Zhihua , Liang Bin , Li Quan , Chen Qingqing , Jia Dechang , Cheng Yi-Bing , Zhou Yu
Published: July 2016

Microstructures of SiBCN-Zr composites with excellent properties.
Lanthanide-based metal–organic frameworks as luminescent probes
Authors: Xu Hang , Cao Chun-Shuai , Kang Xiao-Min , Zhao Bin
Published: July 2016

We discuss the construction of lanthanide-based metal–organic frameworks, their applications in possible detection mechanisms, and summarize some examples of Ln-MOFs as luminescent probes.
The origin and evolution of assessment criteria for persistent, bioaccumulative and toxic (PBT) chemicals and persistent organic pollutants (POPs)
Authors: Matthies Michael , Solomon Keith , Vighi Marco , Gilman Andy , Tarazona Jose V.
Published: July 2016

PBT and POP assessment criteria were developed from best science available from 1970 to 1990 and consensus-based policy discussions.
Potentiation of the bioavailability of blueberry phenolic compounds by co-ingested grape phenolic compounds in mice, revealed by targeted metabolomic profiling in plasma and feces
Authors: Dudonné Stéphanie , Dal-Pan Alexandre , Dubé Pascal , Varin Thibault V. , Calon Frédéric , Desjardins Yves
Published: July 2016

Acute or chronic (15 days) co-administration of blueberry and grape extracts in mice enhanced the absorption of blueberry phenolic compounds.
Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 1. High abundance proteins, acute phase proteins and peptidomics
Authors: Thomas Funmilola Clara , Mullen William , Tassi Riccardo , Ramírez-Torres Adela , Mudaliar Manikhandan , McNeilly Tom N. , Zadoks Ruth N. , Burchmore Richard , David Eckersall P.
Published: July 2016

Acute phase proteins and a group of 77 peptides in a biomarker panel increase in milk during bovine mastitis caused by aStreptococcus uberisinfection of mammary glands.
Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 3. Untargeted metabolomics
Authors: Thomas Funmilola Clara , Mudaliar Manikhandan , Tassi Riccardo , McNeilly Tom N. , Burchmore Richard , Burgess Karl , Herzyk Pawel , Zadoks Ruth N. , Eckersall P. David
Published: July 2016

Metabolomic investigation of milk from cows with bovine mastitis has revealed major changes in carbohydrates, lipids, amino acids, nucleotides and bile acids.
Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 2. Label-free relative quantitative proteomics
Authors: Mudaliar Manikhandan , Tassi Riccardo , Thomas Funmilola C. , McNeilly Tom N. , Weidt Stefan K. , McLaughlin Mark , Wilson David , Burchmore Richard , Herzyk Pawel , Eckersall P. David , Zadoks Ruth N.
Published: July 2016

Longitudinal proteomic analysis of bovine milk shows consistent changes over time across cows after intramammary challenge withStreptococcus uberis.
Simultaneous tunable structure and composition of PtAg alloyed nanocrystals as superior catalysts
Authors: Fang Caihong , Zhao Jun , Zhao Guili , Kuai Long , Geng Baoyou
Published: July 2016

Porous PtAg alloyed nanocrystals with tunable structure and composition were prepared. The alloys can be tuned from multipetals to multioctahedra with composition varying from Pt76Ag24 to Pt66Ag34. The PtAg exhibit superior catalytic performances toward the reduction of 4-nitrophenol and methanol oxidation reaction.
Temperature-controlled redox-neutral ruthenium(ii)-catalyzed regioselective allylation of benzamides with allylic acetates
Authors: Manikandan Rajendran , Jeganmohan Masilamani
Published: July 2016

Temperature controlled regioselective synthesis of ortho allyl and vinyl benzamides under redox-free conditions was reported. Detailed mechanistic investigation of the C–H bond activation and isomerization reactions was carried out.
Functional PEG building blocks via copolymerization of ethylene carbonate and tert-butyl glycidyl ether
Authors: Kapiti G. , Keul H. , Möller M.
Published: July 2016

Functional poly(ethylene glycol) building blocks were synthesized with ethylene carbonate as a new source for ethylene oxide repeating units.
Synergetic enhancement of antitumor efficacy with charge-reversal and reduction-sensitive polymer micelles
Authors: Li Shi-Xi , Liu Lei , Zhang Liu-Jie , Wu Bo , Wang Cai-Xia , Zhou Wei , Zhuo Ren-Xi , Huang Shi-Wen
Published: July 2016

An amphiphilic block copolymer PLA-SS-PAEMA/DMMA was used to encapsulate and deliver Doxorubicin for synergetic enhancement of antitumor efficacy by the combinational effect of charge-reversal on cellular uptake and reduction-sensitivity on intracellular DOX release.
Synthesis and characterization of kesterite Cu2ZnSnTe4via ball-milling of elemental powder precursors
Authors: Pareek Devendra , Balasubramaniam K. R. , Sharma Pratibha
Published: July 2016

Cu2ZnSnTe4 was synthesized using mechano-chemical route from its elemental precursors. A homologous series of kesterite light absorber material Cu2ZnSnX4 (X: S, Se, Te) can be used for realization of multi-junction solar cells.
Enhanced proton conductivity of proton exchange membranes by incorporating phosphorylated hollow titania spheres
Authors: Cao Li , Shen Xiaohui , Yang Xin , Zhang Bei , Li Zongyu , Gang Mingyue , Wang Chongbin , Wu Hong , Jiang Zhongyi
Published: July 2016

The synergistic enhancement in proton conductivity of hybrid membranes by improving the water retention capacity and introducing additional proton transfer sites is reported.
Flame synthesis of nitrogen doped carbon for the oxygen reduction reaction and non-enzymatic methyl parathion sensor
Authors: Karikalan Natarajan , Velmurugan Murugan , Chen Shen-Ming , Karuppiah Chelladurai , Al-Anazi K. M. , Ali M. Ajmal , Lou Bih-Show
Published: July 2016

We report nitrogen-doped carbon nanoparticles from a one-step flame synthesis by directly burning pyrrole at room temperature and in an air atmosphere.
Preparation of THPC-generated silver, platinum, and palladium nanoparticles and their use in the synthesis of Ag, Pt, Pd, and Pt/Ag nanoshells
Authors: Bryan William W. , Jamison Andrew C. , Chinwangso Pawilai , Rittikulsittichai Supparesk , Lee Tai-Chou , Lee T. Randall
Published: July 2016

Seed nanoparticles of Ag, Pt, and Pd (typically ≤4 nm in diameter) were synthesized using tetrakis(hydroxymethyl)phosphonium chloride (THPC) as reducing agent and utilized to prepare Ag, Pt, and Pd nanoshells, as well as hybrid Pt/Ag nanoshells, on silica cores.
PEG-SANM nanocomposite: a new catalytic application towards clean and highly efficient Biginelli-like reaction under solvent-free conditions
Authors: Dalil Heirati Seyedeh Zahra , Shirini Farhad , Shojaei Abdollah Fallah
Published: July 2016

The poly (ethylene glycol)-sulfonated sodium montmorillonite (PEG-SANM) nanocomposite with various ratios was prepared and used as a highly efficient and reusable solid acid nanocatalyst for synthesis of pyrimidinone derivatives under solvent-free conditions.
Dielectric constant measurements of thin films and liquids using terahertz metamaterials
Authors: Park S. J. , Yoon S. A. N. , Ahn Y. H.
Published: July 2016

In this paper, we demonstrate that terahertz (THz) metamaterials are powerful tools for determination of dielectric constants of polymer films and polar liquids.
Influence of synthesis conditions on the morphologies of ReBO3 microstructures and white light emission of YBO3:Eu3+ phosphors prepared by an oleic acid-assisted hydrothermal method
Authors: Liu Baobao , Xiao Xiuzhen , Yu Jun , Mao Dongsen , Lu Guanzhong
Published: July 2016

YBO3:5%Eu3+ phosphor prepared by the OA-assisted hydrothermal method displays the white color under excitation at 394 nm, and the light color of YBO3:Eu3+ can be varied with the Eu3+ dopant concentration or the excitation wavelength.
Osteometrics in burned human skeletal remains by neutron and optical vibrational spectroscopy
Authors: Marques M. P. M. , Gonçalves D. , Amarante A. I. C. , Makhoul C. I. , Parker S. F. , Batista de Carvalho L. A. E.
Published: July 2016

Vibrational spectroscopic techniques are applied to the osteometric study of burned human skeletal remains.
Tunable surface topography in fluoropolymers using photo-embossing
Authors: Kommeren S. , Sullivan T. , Bastiaansen C. W. M.
Published: July 2016

We describe and characterise a novel method of producing tuneable surface topography in fluorinated elastomers using a modified photo-embossing process.
Cl2/Ar based dry etching of GaCrN using inductively coupled plasma
Authors: Patil Tarkeshwar C.
Published: July 2016

Dry etching of GaCrN, a novel DMS spintronics material.
Coupling two enzymes into a tandem nanoreactor utilizing a hierarchically structured MOF
Authors: Lian Xizhen , Chen Ying-Pin , Liu Tian-Fu , Zhou Hong-Cai
Published: July 2016

A hierarchically structured MOF is utilized to couple two enzymes in a tandem manner. A stepwise encapsulation with a specific order is the only way to achieve this goal.
Enhanced electrochemical reduction of CO2to CO on Ag electrocatalysts with increased unoccupied density of states
Authors: Sun Kun , Wu Lina , Qin Wu , Zhou Jigang , Hu Yongfeng , Jiang Zhaohua , Shen Baozhong , Wang Zhijiang
Published: July 2016

Ag-based electrocatalysts with higher unoccupied DOS of d-character present a stronger selectivity, durability and activity to reduce CO2to CO.
Conjugated polymers for the optical control of the electrical activity of living cells
Authors: Vaquero Susana , Bossio Caterina , Bellani Sebastiano , Martino Nicola , Zucchetti Elena , Lanzani Guglielmo , Antognazza Maria Rosa
Published: July 2016

Different conjugated polymers are proposed as bio-optical interfaces. Selected polymers are capable to sustain thermal sterilization but provide different optical coupling with living cells.