bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth and functional harvesting of human mesenchymal stromal cells cultured on a microcarrier‐based system
Authors: Caruso Sâmia R. , Orellana Maristela D. , Mizukami Amanda , Fernandes Taisa R. , Fontes Aparecida M. , Suazo Claudio A. T. , Oliveira Viviane C. , Covas Dimas T. , Swiech Kamilla
Published: February 2014

Human mesenchymal stromal cells (hMSCs) cells are attractive for applications in tissue engineering and cell therapy. Because of the low availability of hMSCs in tissues and the high doses of hMSCs necessary for infusion, scalable and cost‐effective technologies forin vitrocell expansion are needed to produce MSCs while maintaining their functional, immunophenotypic and cytogenetic characteristics. Microcarrier‐based culture systems are a good alternative to traditional systems for hMSC expansion. The aim of the present study was to develop a scalable bioprocess for the expansion of human bone marrow mesenchymal stromal cells (hBM‐MSCs) on microcarriers to optimize growth and functional harvesting. In general, the results obtained demonstrated the feasibility of expanding hBM‐MSCs using microcarrier technology. The maximum cell concentration (n= 5) was ∼4.82 ± 1.18 × 105cell mL−1at day 7, representing a 3.9‐fold increase relative to the amount of inoculated cells. At the end of culture, 87.2% of the cells could be harvested (viability = 95%). Cell metabolism analysis revealed that there was no depletion of important nutrients such as glucose and glutamine during culture, and neither lactate nor ammonia byproducts were formed at inhibitory concentrations. The cells that were recovered after the expansion retained their immunophenotypic and functional characteristics. These results represent an important step toward the implementation of a GMP‐compliant large‐scale production system for hMSCs for cellular therapy. © 2014 American Institute of Chemical EngineersBiotechnol. Prog., 30:889–895, 2014
Patterns of chemotherapy‐associated toxicity and supportive care in US oncology practice: a nationwide prospective cohort study
Authors: Culakova Eva , Thota Ramya , Poniewierski Marek S. , Kuderer Nicole M. , Wogu Adane F. , Dale David C. , Crawford Jeffrey , Lyman Gary H.
Published: February 2014

Neutropenic complications remain an important dose‐limiting toxicity of cancer chemotherapy‐associated with considerable morbidity, mortality, and cost. Risk of the initial neutropenic event is greatest during the first cycle. The purpose of this study was to better understand timing of neutropenic events in relation to delivered chemotherapy dose intensity and utilization of supportive care during cancer treatment. A prospective cohort study of adult patients with solid tumors or lymphoma initiating chemotherapy was conducted at 115 randomly selected US practice sites between 2002 and 2006. Chemotherapy‐associated toxicities were captured in up to four treatment cycles including severe neutropenia, febrile neutropenia, and infection. Documented interventions included colony‐stimulating factor (CSF), antibiotics use, and reductions in chemotherapy relative dose intensity (RDI). A total of 3638 patients with breast (39.7%), lung (23.7%), colorectal (13.6%), ovarian (8.3%) cancers, or lymphoma (14.7%) were eligible for this analysis. The majority of neutropenic and infection events occurred in the first cycle. A significant inverse relationship was observed between reductions in neutropenic and infectious events and increased utilization of measures to reduce these complications in subsequent cycles. More than 60% of patients with stage IV solid tumors underwent reductions in RDI. Patients with lymphoma and stage I–III solid tumors had less dose reductions while receiving more prophylactic CSFs. Approximately, 15% of patients received prophylactic antibiotics. While the risk of neutropenic complications remains greatest during the initial cycle of chemotherapy, subsequently instituted clinical measures in efforts to reduce the risk of these events vary with cancer type and stage.
Primary cerebral and cerebellar astrocytes display differential sensitivity to extracellular sodium with significant effects on apoptosis
Authors: Takeda Tomohiko , Makinodan Manabu , Fukami Shin‐ichi , Toritsuka Michihiro , Ikawa Daisuke , Yamashita Yasunori , Kishimoto Toshifumi
Published: February 2014

Central pontine myelinolysis is one of the idiopathic or iatrogenic brain dysfunction, and the most common cause is excessively rapid correction of chronic hyponatraemia. While myelin disruption is the main pathology, as the diagnostic name indicates, a previous study has reported that astrocyte death precedes the destruction of the myelin sheath after the rapid correction of chronic low Na+ levels, and interestingly, certain brain regions (cerebral cortex, hippocampus, etc.) are specifically damaged but not cerebellum. Here, using primary astrocyte cultures derived from rat cerebral cortex and cerebellum, we examined how extracellular Na+ alterations affect astrocyte death and whether the response is different between the two populations of astrocytes. Twice the amount of extracellular [Na+] and voltage‐gated Na+ channel opening induced substantial apoptosis in both populations of astrocytes, while, in contrast, one half [Na+] prevented apoptosis in cerebellar astrocytes, in which the Na+–Ca2+ exchanger, NCX2, was highly expressed but not in cerebral astrocytes. Strikingly, the rapid correction of chronic one half [Na+] exposure significantly increased apoptosis in cerebellar astrocytes but not in cerebral astrocytes. These results indicate that extracellular [Na+] affects astrocyte apoptosis, and the response to alterations in [Na+] is dependent on the brain region from which the astrocyte is derived. Copyright © 2014 John Wiley & Sons, Ltd.
First in human percutaneous implantation of a balloon expandable transcatheter heart valve in a severely stenosed native mitral valve
Authors: Guerrero Mayra , Greenbaum Adam , O'Neill William
Published: February 2014

Transcatheter implantation of a balloon expandable valve in calcified severely stenosed native mitral valves has recently been described. The two cases reported so far utilized the surgical transapical approach generally used for transapical transcatheter aortic valve replacement. A percutaneous approach has not been published. We report the first successful percutaneous implantation of a balloon expandable transcatheter valve in the native mitral valve without a surgical incision. © 2014 Wiley Periodicals, Inc.
Implantation and preliminary follow‐up of the Bard Valeo stent in pulmonary artery stenosis
Authors: Kudumula Vikram , Noonan Patrick , Taliotis Demetris , Duke Christopher
Published: February 2014

Objectives

To evaluate the performance of the Bard Valeo stent in pulmonary artery stenoses.

Background

The premounted Valeo stent requires only 6–7 French access and can be post‐dilated to 20 mm on bench testing. Although it appears ideal for implantation in pulmonary artery stenoses in children, it has been unclear whether it has sufficient radial strength to prevent vessel recoil and stent collapse.

Methods

Twelve stents were implanted in 10 patients aged 1.2–19.9 years (weight 9.9–54 kg). Implant results were assessed retrospectively.

Results

All implants were successful with no complications. The stent tracked easily and was readily visible on fluoroscopy. The median (range) diameter of the pulmonary artery stenosis increased from 4.9 (1.8–7.4) mm to 9 (6–10.6) mm (P ≤ 0.01), the median peak to peak systolic pressure gradient across the pulmonary artery stenosis decreased from 16 (11–66) mmHg to 6 (0–10) mmHg (P ≤ 0.01), and the right ventricle to systemic blood pressure ratio fell from 0.72 (0.54–1.1) to 0.54 (0.28–0.69) (P ≤ 0.01). Median stent recoil was 5.5 (0–21)%. Jailed side branches remained patent. Nine stents were assessed fluoroscopically on 11.5 (0–30) month follow‐up. There were no stent fractures. 6 stents were not distorted, 2 had minor distortion, and 1 stent, implanted in a highly resistant lesion, had moderate distortion.

Conclusions

The Valeo stent is low profile, conformable, and easy to deliver, even in small children. It has adequate radial strength to stent pulmonary artery stenoses with minimal recoil. It maintains its geometry on medium term follow up in compliant lesions. Resistant stenoses may distort the stent. © 2014 Wiley Periodicals, Inc.
Di‐tert‐butyl Peroxide Promoted Direct CH Arylation of Unactivated Arenes with Aryl Halides
Authors: Zhu Yi‐Wei , Yi Wen‐Bin , Qian Jin‐Long , Cai Chun
Published: February 2014

Di‐tert‐butyl peroxide can smoothly promote the coupling of aryl halides with benzene derivatives without the aid of transition‐metal catalysts through a chain homolytic aromatic substitution mechanism in the presence of potassium tert‐butoxide.
Comprehensive kinetic model for the dissolution, reaction, and crystallization processes involved in the synthesis of aspirin
Authors: Joiner David E. , Billeter Julien , McNally Mary Ellen P. , Hoffman Ron M. , Gemperline Paul J.
Published: February 2014

Kinetic modeling of batch reactions monitored by in situ spectroscopy has been shown to be a helpful method for developing a complete understanding of reaction systems. Much work has been carried out to demonstrate the ability to model dissolution, reaction, and crystallization processes separately; however, little has been performed in terms of combining all of these into one comprehensive kinetic model. This paper demonstrates the integration of models of dissolution, temperature‐dependent solubility, and unseeded crystallization driven by cooling into a comprehensive kinetic model describing the evolution of a slurry reaction monitored by in situ attenuated total reflectance ultraviolet–visible spectroscopy. The model estimates changes in the volume of the dissolved fraction of the slurry by use of the partial molar volume of the dissolved species that change during the course of reagent addition, dissolution, reaction, and crystallization. The comprehensive model accurately estimates concentration profiles of dissolved and undissolved components of the slurry and, thereby, the degree of undersaturation and supersaturation necessary for estimation of the rates of dissolution and crystallization. Results were validated across two subsequent batches via offline high‐performance liquid chromatography measurements. Copyright © 2014 John Wiley & Sons, Ltd.
Synthesis, Characterizations, Magnetism and Thermal Degradation of a 2‐Fold Interpenetrated 3D Cobalt‐Organic Framework
Authors: Yang Linyan , Xin Liangliang , Gu Wen , Liao Shengyun , Du Peiyao , Tian Jinlei , Zhang Yanping , Lv Rui , Wei Xiaohua , Liu Xin , Liao Daizheng
Published: February 2014

A new coordination polymer, [Co2(L)2(4,4′‐bipy)]n·3nH2O (1) based on 5‐(3‐methyl‐5‐phenyl‐4H‐1,2,4‐triazol‐4‐yl)isophthalic acid (H2L) and 4,4′‐bipyridine (4,4′‐bipy) has been hydrothermally synthesized and characterized by single‐crystal X‐ray diffraction, XRPD, IR, and elemental analysis. Temperature‐dependent magnetic susceptibility and thermal degradation for 1 were also studied. The asymmetric unit of compound 1 consists of two crystallographically independent Co(II) ion, two L2− ligand, one 4,4′‐bipy ligand, and three lattice water molecules. The 2D triangle networks were linked by the bridging 4,4′‐bipy ligand to give rise to a 2‐fold interpenetrated 3D architecture. The simplest cyclic motif of the 2D networks is a triangle ring consisting of three Co(II) cations and three L2− ligands. So we can define Co(II) ions as 4‐connected nodes and the L2− ligands as 3‐connected nodes. Thus, the 3D structure can be described as a 2‐fold parallel interpenetrated ins InS 3,4‐conn topology.
Photo‐Induced Water Oxidation Based on a Mononuclear Cobalt(II) Complex
Authors: Wang Hongyan , Lu Yongbin , Mijangos Edgar , Thapper Anders
Published: February 2014

Photo‐induced water oxidation based on first row transition metal complexes has drawn much attention recently as a part of the efforts to design systems for solar fuel production. Here, the classic tetradentate ligand TPA (tris(2‐pyridylmethyl)amine) is used together with cobalt(II) in CH3CN to form a mononuclear cobalt complex [Co(TPA)Cl]Cl. Single crystal X‐ray diffraction shows that [Co(TPA)Cl]Cl is composed of discrete cationic units with a penta‐coordinate cobalt center, along with chloride counter ions. In borate buffer, the Co complex acts as a water oxidation catalyst, as shown by the presence of a catalytic wave in electrochemistry. Under visible light irradiation, in the presence of photosensitizer and electron acceptor, the Co complex catalyzes O2 evolution with a turnover frequency (TOF) of 1.0 mol(O2)·mol(Co)−1·s−1 and a turnover number (TON) of 55 mol(O2)·mol(Co)−1 in pH 8 borate buffer.
A 40 M–1000 MHz 77.2‐dB spurious free dynamic range CMOS RF variable gain amplifier for digital TV tuner ICs
Authors: Kwon Kuduck
Published: February 2014

In this paper, a 40 M–1000 MHz 77.2‐dB spurious free dynamic range (SFDR) CMOS RF variable gain amplifier (VGA) has been presented for digital TV tuner applications. The proposed RFVGA adopts a wideband operational‐amplifier‐based VGA and a wideband buffer with differential multiple gated transistor linearization method for wideband operation and high linearity. The SFDR of the proposed RFVGA is also analyzed in detail. Fabricated in a 0.13‐µm CMOS process, the RFVGA provides 31‐dB gain range with 1‐dB gain step, a minimum noise figure of 7.5 dB at a maximum gain of 27 dB, and maximum in‐band output‐referred third‐order intercept point of 27.7 dBm, while drawing an average current of 27.8 mA with a supply voltage of 3.3 V. The chip core area is 0.54 mm × 0.4 mm. Copyright © 2014 John Wiley & Sons, Ltd.
Cooperative Relay‐Aware Spectrum leasing based on Nash bargaining solution in cognitive radio networks
Authors: Ma Kai , Yang Jie , Hu Guoqiang , Guan Xinping
Published: February 2014

This paper proposes a spectrum leasing strategy based on cooperative relaying for cognitive radio networks. The basic idea is to make the primary user lease a fraction of the licensed spectrum to the secondary user, which acts as a relay for the primary user in return. We formulate the spectrum leasing problem as a Nash bargaining game to avoid the ineffective solution obtained by Stackelberg game. The cooperative condition and the optimal time allocation can be obtained by solving the game. Numerical results demonstrate that both the primary user and the secondary user can obtain larger profits from the spectrum leasing based on Nash bargaining solution. Copyright © 2014 John Wiley & Sons, Ltd.
Optimal epidemic broadcasting for vehicular ad hoc networks
Authors: Tian Daxin , Zhou Jianshan , Wang Yunpeng , Xia Haiying , Yi Zhenguo , Liu He
Published: February 2014

Dynamic nature of vehicular ad hoc networks (VANETs) creates great challenges for message dissemination. To satisfy the high reliability and low delivery latency requirements for safety applications in VANETs, a dynamic epidemic broadcasting model is presented in this paper. On the basis of the ordinary differential equations, the proposed optimal control scheme is analyzed to understand the epidemic broadcasting properties, which include the message delivery probability, the expected delivery latency, and the number of copies. The correctness of the theoretical analyses is confirmed by simulations, and the experiment results prove the efficiency of the optimal epidemic broadcasting model. Copyright © 2014 John Wiley & Sons, Ltd.
Sea urchin neural development and the metazoan paradigm of neurogenesis
Authors: Burke Robert D. , Moller Daniel J. , Krupke Oliver A. , Taylor Valerie J.
Published: February 2014

Urchin embryos continue to prove useful as a means of studying embryonic signaling and gene regulatory networks, which together control early development. Recent progress in understanding the molecular mechanisms underlying the patterning of ectoderm has renewed interest in urchin neurogenesis. We have employed an emerging model of neurogenesis that appears to be broadly shared by metazoans as a framework for this review. We use the model to provide context and summarize what is known about neurogenesis in urchin embryos. We review morphological features of the differentiation phase of neurogenesis and summarize current understanding of neural specification and regulation of proneural networks. Delta‐Notch signaling is a common feature of metazoan neurogenesis that produces committed progenitors and it appears to be a critical phase of neurogenesis in urchin embryos. Descriptions of the differentiation phase of neurogenesis indicate a stereotypic sequence of neural differentiation and patterns of axonal growth. Features of neural differentiation are consistent with localized signals guiding growth cones with trophic, adhesive, and tropic cues. Urchins are a facile, postgenomic model with the potential of revealing many shared and derived features of deuterostome neurogenesis. genesis 52:208–221. © 2014 Wiley Periodicals, Inc.
A bird distribution model for ring recovery data: where do theEuropean robins go?
Authors: Korner‐Nievergelt Fränzi , Liechti Felix , Thorup Kasper
Published: February 2014

For the study of migratory connectivity, birds have been individually marked by metal rings for more than 100 years. The resulting ring recovery data have been compiled in numerous bird migration atlases. However, estimation of what proportion of a particular population is migrating to which region is confounded by spatial heterogeneity in ring recovery probability. We present a product multinomial model that enables quantifying the continent‐wide distribution of different bird populations during different seasons based on ring recovery data while accounting for spatial heterogeneity of ring recovery probability. We applied the model to an example data set of theEuropean robinErithacus rubecula. We assumed that ring recovery probability was equal between different groups of birds and that survival probability was constant. Simulated data indicate that violation of the assumption of constant survival did not affect our estimated bird distribution parameters but biased the estimates for recovery probability. Posterior predictive model checking indicated a good general model fit but also revealed lack of fit for a few groups of birds. This lack of fit may be due to between‐group differences in the spatial distribution on smaller scales within regions. We found that 48% of the Scandinavian robins, but only 31% of the central European robins, wintered in northern Africa. The remaining parts of both populations wintered in southern and central Europe. Therefore, a substantial part of the Scandinavian population appears to leap over individuals from the central European population during migration. The model is applied to summary tables of numbers of ringed and recovered birds. This allows us to handle very large data sets as, for example, those presented in bird migration atlases.
Disturbance by large herbivores alters the relative importance of the ecological processes that influence the assembly pattern in heterogeneous meta‐communities
Authors: Ohashi Haruka , Hoshino Yoshinobu
Published: February 2014

Disturbance caused by large herbivores can affect the relative importance of ecological processes in determining community assembly and may cause a systematic loss of biodiversity across scales. To examine changes in the community assembly pattern caused by an overabundance of large herbivores in Japan, we analyzed community composition data from before and after the overabundance occurred. The community assembly pattern becomes more random after the deer overabundance. In addition, result of variation partitioning revealed decrease in importance of environmental processes and increase in importance of spatial processes. However, response of turnover rate, niche breadth, and niche overlap was heterogeneous, according to scale of each environmental gradient. Our results emphasize the importance of conserving habitat specialists that represent the local environment (habitat type and topography) at various altitudinal ranges to maintain biodiversity at regional scales under the increasing pressure of large herbivores.
Relationships between invertebrate communities and both hydrological regime and other environmental factors across New Zealand's rivers
Authors: Booker D. J. , Snelder T. H. , Greenwood M. J. , Crow S. K.
Published: February 2014

Robust relationships between biological characteristics and hydrological indices are required to provide a quantitative basis for environmental flows. Data from 1075 river sites distributed across New Zealand were used to investigate relationships between invertebrate communities and flow regimes, whilst also including the influence of additional environmental factors. Variance decomposition analysis was used to investigate the proportion of variance explained by hydrological, geomorphological, land cover, and catchment characteristics for the community matrix and each of three biotic indices representing taxon richness, Macroinvertebrate Community Index, and percentage of species in the Ephemeroptera, Plecoptera, and Trichoptera orders. Results showed that hydrological regime contributes a unique component to the explainable variation in the community, but this contribution is overestimated if other explanatory factors are not considered. A gradient forest model comprised of 93 random forest models, each predicting the probability of occurrence of a taxon, indicated the importance of high flows and also other dimensions of hydrological variation for predicting invertebrate taxa and biotic indices. Although many freshwater invertebrates in New Zealand are well adapted to a range of flow conditions through resistance traits and/or rapid colonization, this study suggests that several aspects of the flow regime influence invertebrate communities. These results suggest that environmental flows may be designed to sustain or even optimize specific ecological attributes or taxa, but changes along several dimensions of hydrological variability are likely to disadvantage other taxa and change invertebrate community composition. Copyright © 2014 John Wiley & Sons, Ltd.
Lnk prevents inflammatory CD8+ T‐cell proliferation and contributes to intestinal homeostasis
Authors: Katayama Hiroko , Mori Taizo , Seki Yoichi , Anraku Masaki , Iseki Masanori , Ikutani Masashi , Iwasaki Yukiko , Yoshida Nobuaki , Takatsu Kiyoshi , Takaki Satoshi
Published: February 2014

The intracellular adaptor Lnk (also known as SH2B3) regulates cytokine signals that control lymphohematopoiesis, and Lnk−/− mice have expanded B‐cell, megakaryocyte, and hematopoietic stem‐cell populations. Moreover, mutations in the LNK gene are found in patients with myeloproliferative disease, whereas LNK polymorphisms have recently been associated with inflammatory and autoimmune diseases, including celiac disease. Here, we describe a previously unrecognized function of Lnk in the control of inflammatory CD8+ T‐cell proliferation and in intestinal homeostasis. Mature T cells from newly generated Lnk–Venus reporter mice had low but substantial expression of Lnk, whereas Lnk expression was downregulated during homeostatic T‐cell proliferation under lymphopenic conditions. The numbers of CD44hiIFN‐γ+CD8+ effector or memory T cells were found to be increased in Lnk−/− mice, which also exhibited shortening of villi in the small intestine. Lnk−/− CD8+ T cells survived longer in response to stimulation with IL‐15 and proliferated even in nonlymphopenic hosts. Transfer of Lnk−/− CD8+ T cells together with WT CD4+ T cells into Rag2‐deficient mice recapitulated a sign of villous abnormality. Our results reveal a link between Lnk and immune cell‐mediated intestinal tissue destruction.
Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell‐autonomous activation of vitamin D in dendritic cells
Authors: Kundu Rhiannon , Chain Benjamin M. , Coussens Anna K. , Khoo Bernard , Noursadeghi Mahdad
Published: February 2014

The active vitamin D metabolite 1α,25‐dihydroxyvitamin D (1,25[OH]2D) potently inhibits DC priming of T‐cell activation, suggesting that it mediates a homeostatic role in this context. Therefore, careful regulation of 1,25[OH]2D levels is necessary to avoid inappropriate inhibition of T‐cell activation. Cell‐autonomous control of vitamin D activity can be modulated by the action of the vitamin D‐activating and ‐inactivating hydroxylases, CYP27B1, and CYP24A1, respectively. We show that in comparison to macrophages, human monocyte‐derived DCs exhibit significantly less activation of 25‐dihydroxyvitamin D to 1,25[OH]2D, and that DCs predominantly express a truncated CYP27B1 transcript that may contribute to the deficiency in activation of vitamin D. Furthermore, in response to stimulation with 1,25[OH]2D, upregulation of the inactivating enzyme CYP24A1 curtailed the functional effects of vitamin D in DCs, but not macrophages. Production of 1,25[OH]2D by macrophages was adequate to induce expression of vitamin D‐responsive genes by DCs, inhibit DC maturation in response to innate immune stimulation and DC‐dependent T‐cell responses. Our data suggest that in comparison to macrophages, differential regulation of hydroxylases limits autocrine vitamin D activity in DCs, and that paracrine activation of vitamin D exerts a more potent mechanism for homeostatic control of DC function.
Beef tallow as an alternative to fish oil in diets for gilthead sea bream (Sparus aurata) juveniles: Effects on fish performance, tissue fatty acid composition, health and flesh nutritional value
Authors: Pérez José A. , Rodríguez Covadonga , Bolaños Ana , Cejas Juana R. , Lorenzo Antonio
Published: February 2014

Gilthead sea bream juveniles of 135 g average body weight were fed for 120 days a fish oil‐based commercial diet (CTRL) or one of two experimental isonitrogenous and isolipidic low fat (LF) fish meal‐based diets differing only by the lipid source, in order to evaluate the efficacy of beef tallow (BT) as an ingredient in aquafeeds. Both experimental feeds were formulated with 60 g/kg of BT; the LFBTFO diet also contained 35 g/kg of fish oil (FO) whereas a blend of BT and vegetable oils (VO) completely replaced FO in the LFBTVO diet. No differences in growth and feed efficiency were found between fish fed the LFBTFO diet and the CTRL group whereas fish fed the diet devoid of FO (LFBTVO) presented the poorest growth indicators and the lowest feed and protein efficiencies. The use of LF feeds contributed to maintain the hepatosomatic index and the proportion of triacylglycerols (TAG) in muscle and brain in spite of the dietary replacement of FO. Flesh from fish fed the LFBTFO diet supplied the same absolute amount of EPA + DHA than that of fish fed the CTRL diet, whereas a reduction of approximately 45% was registered when fish were deprived of FO.

Practical applications: High proportions of BT can effectively be used as a valuable alternative to partially substitute FO in diets for gilthead sea bream juveniles without significantly affecting fish performance and health while promoting a limited impact on its health benefits for human consumption. The decline in the inclusion of marine ingredients in aquafeeds could actively contribute to the sustainability and profitability of the marine aquaculture industry.
δ‐Peptides from RuAAC‐Derived 1,5‐Disubstituted Triazole Units
Authors: Johansson Johan R. , Hermansson Elin , Nordén Bengt , Kann Nina , Beke‐Somfai Tamás
Published: February 2014

Non‐natural peptides with structures and functions similar to natural peptides have emerged lately in biomedical as well as nanotechnological contexts. They are interesting for pharmaceutical applications since they can adopt structures with new targeting potentials and because they are generally not prone to degradation by proteases. We report here a new set of peptidomimetics derived from δ‐peptides, consisting of n units of a 1,5‐disubstituted 1,2,3‐triazole amino acid (5Tzl). The monomer was prepared using ruthenium‐catalyzed azide–alkyne cycloaddition (RuAAC) chemistry using [RuCl2Cp*]x as the catalyst, allowing for simpler purification and resulting in excellent yields. This achiral monomer was used to prepare peptide oligomers that are water soluble independent of peptide chain length. Conformational analysis and structural investigations of the oligomers were performed by 2D NOESY NMR experiments, and by quantum chemical calculations using the ωB97X‐D functional. These data indicate that several conformations may co‐exist with slight energetic differences. Together with their increased hydrophilicity, this feature of homo‐5Tzl may prove essential for mimicking natural peptides composed of α‐amino acids, where the various secondary structures are achieved by side chain effects and not by the rigidity of the peptide backbone. The improved synthetic method allows for facile variation of the 5Tzl amino acid side chains, further increasing the versatility of these compounds.
Proteomic analysis indicates that overexpression and nuclear translocation of lactoylglutathione lyase (GLO1) is associated with tumor progression in murine fibrosarcoma
Authors: Wang Yufeng , Kuramitsu Yasuhiro , Tokuda Kazuhiro , Okada Futoshi , Baron Byron , Akada Junko , Kitagawa Takao , Nakamura Kazuyuki
Published: February 2014

Lactoylglutathione lyase (GLO1), a ubiquitously expressed methylglyoxal (MG) detoxification enzyme, is implicated in the progression of various human malignant diseases. However, the role of GLO1 in the development or progression of murine fibrosarcoma is still unclear. We performed proteomic analysis to identify differences in the intracellular proteins of the regressive tumor cell line QR‐32 and the inflammatory cell‐promoting progressive tumor cell line QRsP‐11 of murine fibrosarcoma by 2DE combined with MS. Seven upregulated proteins were identified in QRsP‐11 compared to QR‐32 cells, namely, GLO1, annexin A1, adenylate kinase isoenzyme 1, transcription factor BTF3, myosin light polypeptide 6, low molecular weight phosphotyrosine protein phosphatase and nucleoside diphosphate kinase B. Heat shock protein beta‐1 (HspB1), a methylglyoxal‐adducted protein, is concomitantly over‐expressed in QRsP‐11 as compared to QR‐32 cells. We also found out that GLO1 is translocated into the nucleus to a higher extent in QRsP‐11 compared to QR‐32 cells, which can be reversed by using a MEK inhibitor (U0126). Moreover, U0126 and GLO1 siRNA can inhibit cell proliferation and migration in QRsP‐11 cells. Our data suggest that overexpression and nuclear translocation of GLO1 might be associated with tumor progression in murine fibrosarcoma.
Functional polymorphisms in apoptosis pathway genes and survival in patients with gastric cancer
Authors: Gu Dongying , Du Mulong , Tang Cuiju , Chu Haiyan , Xu Zhi , Huo Xinyin , Gong Weida , Tang Yongfei , Zhou Jianwei , Tong Na , Xu Yong , Zhang Zhengdong , Wang Meilin , Chen Jinfei
Published: February 2014

The FAS, FAS ligand (FASL), and CASP8 are key regulators for apoptosis and their deregulations play an important role in carcinogenesis. However, the effects of promoter polymorphisms of the FAS, and FASL, and CASP8 genes on the survival of gastric cancer are unknown. In this study, we investigated the association of four polymorphisms (FAS −1377G > A, −670A > G, FASL −844C > T, and CASP8 −652 6N ins > del) with the clinical outcome of 940 gastric cancer patients in a Chinese population. The correlation between genotype and survival outcomes was assessed by the Kaplan–Meier method, Cox proportional hazards models and the log‐rank test. Our results revealed that individuals with CASP8 −652 6N ins/del + del/del genotypes had a decreased risk of death compared with those with ins/ins genotype (log‐rank P = 0.005; hazard ratio = 0.75, 95% confidence interval = 0.62–0.92). The protective effect of the del allele was further confirmed in subgroups of patients with tumor size ≤5 cm (0.66, 0.50–0.86) and T2 depth invasion (0.59, 0.37–0.94), but no significant association was observed in the subgroups of lymph node metastasis (0.67, 0.47–0.97), and distance metastasis (0.73, 0.60–0.90). Our findings suggest that, if validated in different independent populations, the CASP8 −652 6N ins > del polymorphism may serve as a promising genetic marker for gastric cancer prognosis. Environ. Mol. Mutagen. 55:421–427, 2014. © 2014 Wiley Periodicals, Inc.
Experimental testing of a rocking timber shear wall with slip‐friction connectors
Authors: Loo Wei Y. , Kun Chern , Quenneville Pierre , Chouw Nawawi
Published: February 2014

Allowing a structure to uplift and rock during an earthquake is one way in which activated forces can be capped and damage to the structure avoided or minimised. Slip‐friction connectors (also known as slotted‐bolt connectors) were originally developed for use in steel construction, but for this research have been adapted for use as hold‐downs in an experimental 2.4 m × 2.4 m rigid timber shear wall. A novel approach is used to achieve the desired sliding threshold in the connectors, and the wall uplifts when this threshold is reached. From a series of quasi‐static cyclic tests, it is shown that slip‐friction connectors can impart ductile and elasto‐plastic characteristics to what would otherwise be essentially brittle structures. Because forces on the wall were capped by the slip‐friction connectors to levels well below the design level, no damage to the wall was observed. Self‐centring potential was also found to be excellent. The slip‐friction connectors themselves are of a unique design and have proven to be robust and durable, adequately performing their duty even after almost 14 m of cumulative travel under high contact pressures. To resist base shear without unduly affecting rocking behaviour, a new type of shear‐key is proposed and implemented, and a procedure developed to quantify its influence on overall wall behaviour. Copyright © 2014 John Wiley & Sons, Ltd.
Robust classification for the joint velocity‐intermittency structure of turbulent flow over fixed and mobile bedforms
Authors: Keylock Christopher J. , Singh Arvind , Venditti Jeremy G. , Foufoula‐Georgiou Efi
Published: February 2014

Two datasets of turbulence velocities collected over different bedform types under contrasting experimental conditions show similarity in terms of velocity‐intermittency characteristics and suggest a universality to the velocity‐intermittency structure for flow over bedforms. One dataset was obtained by sampling flow over static bedforms in different locations, and the other was based on a static position but mobile bedforms. A flow classification based on the velocity‐intermittency behaviour is shown to reveal some differences from that based on an analysis of Reynolds stresses, boundary layer correlation and turbulent kinetic energy. This may be attributed to the intermittency variable, which captures the local effect of individual turbulent flow structures. Locations in the wake region or the outer layer of the flow are both shown to have a velocity‐intermittency behaviour that departs from that for idealized wakes or outer layer flow because of the superposition of localized flow structures generated by bedforms. The combined effect of this yields a velocity‐intermittency structure unique to bedform flow.

The use of a time series of a single velocity component highlights the potential power of our approach for field, numerical and laboratory studies. The further validation of the velocity‐intermittency method for non‐idealized flows undertaken here suggests that this technique can be used for flow classification purposes in geomorphology, hydraulics, meteorology and environmental fluid mechanics. © 2014 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd.
Pro‐glacial soil variability and geomorphic activity – the case of three Swiss valleys
Authors: Temme Arnaud J. A. M. , Lange Kas
Published: February 2014

Soils in pro‐glacial areas are often approached from a chronosequence viewpoint. In the chronosequence approach, the objective is to derive rates of soil formation from differences in properties between soils of different age. For this reason, in chronosequence studies, soils are sampled in locations that are assumed geomorphically stable and that have different age. As a result, these studies do not necessarily yield a complete view of soil variability in pro‐glacial areas, and may miss important relations between geomorphology and soil development. In this contribution, we present new soil observations from three closely related pro‐glacial areas in Switzerland. These observations were intended to get closer to a complete view of soil variability, and to assess impacts from factors other than time on soil development. About 40 soils were visited in each pro‐glacial valley in a combined design‐convenience sampling scheme and described in the field. Linear modelling was used to assess effects of time and topographic factors on soil properties. The time since glacial retreat turned out to rarely explain more than half of the variation in soil properties, and a linear model combining effects of time and topographic variables explained typically about half of the variation in each pro‐glacial valley. Models differed and were not transferable between valleys. Apparently, time and the present‐day shape of the landscape combined are insufficient information to accurately predict soil properties. Field evidence points to the importance of the geomorphic history and regime of the valleys as a reason for this. Copyright © 2014 John Wiley & Sons, Ltd.
Estimating Genome‐Wide Significance for Whole‐Genome Sequencing Studies
Authors: Xu ChangJiang , Tachmazidou Ioanna , Walter Klaudia , Ciampi Antonio , Zeggini Eleftheria , Greenwood Celia M. T. ,   the UK10K Consortium
Published: February 2014

Although a standard genome‐wide significance level has been accepted for the testing of association between common genetic variants and disease, the era of whole‐genome sequencing (WGS) requires a new threshold. The allele frequency spectrum of sequence‐identified variants is very different from common variants, and the identified rare genetic variation is usually jointly analyzed in a series of genomic windows or regions. In nearby or overlapping windows, these test statistics will be correlated, and the degree of correlation is likely to depend on the choice of window size, overlap, and the test statistic. Furthermore, multiple analyses may be performed using different windows or test statistics. Here we propose an empirical approach for estimating genome‐wide significance thresholds for data arising from WGS studies, and we demonstrate that the empirical threshold can be efficiently estimated by extrapolating from calculations performed on a small genomic region. Because analysis of WGS may need to be repeated with different choices of test statistics or windows, this prediction approach makes it computationally feasible to estimate genome‐wide significance thresholds for different analysis choices. Based on UK10K whole‐genome sequence data, we derive genome‐wide significance thresholds ranging between 2.5 × 10−8 and 8 × 10−8 for our analytic choices in window‐based testing, and thresholds of 0.6 × 10−8–1.5 × 10−8 for a combined analytic strategy of testing common variants using single‐SNP tests together with rare variants analyzed with our sliding‐window test strategy.
The relationship between task‐related and subsequent memory effects
Authors: de Chastelaine Marianne , Rugg Michael D.
Published: February 2014

The primary aim of this fMRI study was to assess the proposal that negative subsequent memory effects—greater activity for later forgotten relative to later remembered study items—are localized to regions demonstrating task‐negative effects, and hence to potential components of the default mode network. Additionally, we assessed whether positive subsequent memory effects overlapped with regions demonstrating task‐positive effects. Eighteen participants were scanned while they made easy or difficult relational judgments on visually presented word pairs. Easy and hard task blocks were interleaved with fixation‐only rest periods. In the later unscanned test phase, associative recognition judgments were required on intact word pairs (studied pairs), rearranged pairs (pairs formed from words presented on different study trials) and new pairs. Subsequent memory effects were identified by contrasting the activity elicited by study pairs that went on to be correctly endorsed as intact versus incorrectly endorsed as rearranged. Task effects were identified by contrasting all study items and rest blocks. Both task‐negative and task‐positive effects were evident in widespread cortical regions and negative and positive subsequent memory effects were generally confined to task‐negative and task‐positive regions respectively. However, subsequent memory effects could be identified in only a fraction of task‐sensitive voxels and, unlike task effects, were insensitive to the difficulty manipulation. The findings for the negative subsequent memory effects are consistent with recent proposals that the default mode network is functionally heterogeneous, and suggest that these effects are not accurately characterized as reflections of the modulation of the network as a whole. Hum Brain Mapp 35:3687–3700, 2014. © 2013 Wiley Periodicals, Inc.
Frontostriatal activity and connectivity increase during proactive inhibition across adolescence and early adulthood
Authors: Vink Matthijs , Zandbelt Bram B. , Gladwin Thomas , Hillegers Manon , Hoogendam Janna Marie , van den Wildenberg Wery P.M. , Du Plessis Stefan , Kahn René S.
Published: February 2014

During adolescence, functional and structural changes in the brain facilitate the transition from childhood to adulthood. Because the cortex and the striatum mature at different rates, temporary imbalances in the frontostriatal network occur. Here, we investigate the development of the subcortical and cortical components of the frontostriatal network from early adolescence to early adulthood in 60 subjects in a cross‐sectional design, using functional MRI and a stop‐signal task measuring two forms of inhibitory control: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping). During development, reactive inhibition improved: older subjects were faster in reactive inhibition. In the brain, this was paralleled by an increase in motor cortex suppression. The level of proactive inhibition increased, with older subjects slowing down responding more than younger subjects when anticipating a stop‐signal. Activation increased in the right striatum, right ventral and dorsal inferior frontal gyrus, and supplementary motor area. Moreover, functional connectivity during proactive inhibition increased between striatum and frontal regions with age. In conclusion, we demonstrate that developmental improvements in proactive inhibition are paralleled by increases in activation and functional connectivity of the frontostriatal network. These data serve as a stepping stone to investigate abnormal development of the frontostriatal network in disorders such as schizophrenia and attention‐deficit hyperactivity disorder. Hum Brain Mapp 35:4415–4427, 2014. © 2014 Wiley Periodicals, Inc.
Role of reflux‐induced epithelial–mesenchymal transition in periprosthetic leakage after prosthetic voice rehabilitation
Authors: Lorenz Kai J. , Kraft Klaus , Graf Franziska , Pröpper Christian , Steinestel Konrad
Published: February 2014

Background

Gastroesophageal reflux (GER) contributes to periprosthetic leakage after prosthetic voice rehabilitation. However, underlying mechanisms are unclear, and markers predicting anti‐reflux therapy response are missing.

Methods

We assessed epithelial–mesenchymal transition in 148 consecutive biopsies from 44 patients with/without fistula enlargement under dual‐probe pH monitoring before and after proton‐pump inhibitor (PPI) therapy applying immunohistochemistry. Results were correlated with reflux intensity and clinical and histologic findings.

Results

Epithelial–mesenchymal transition correlated with GER in all samples, and patients with fistula enlargement showed higher epithelial–mesenchymal transition scores. Contrary to patients without enlargement, epithelial–mesenchymal transition scores did not regress during therapy in this group. Furthermore, pretherapeutic epithelial–mesenchymal transition scores were lower in therapy responders than in nonresponders without reaching significance (p = .07).

Conclusion

We demonstrate that epithelial–mesenchymal transition correlates with severity of GER and presence of periprosthetic fistula enlargement in patients who underwent prosthetic voice rehabilitation, but epithelial–mesenchymal transition seems to be reversible upon PPI treatment in early stages only. © 2014 Wiley Periodicals, Inc. Head Neck 37: 530–536, 2015
Rapid awakening protocol in complex head and neck reconstruction
Authors: Clemens Mark W. , Hanson Summer E. , Rao Samir , Truong Angela , Liu Jun , Yu Peirong
Published: February 2014

Background

Patients undergoing complex head and neck free flap reconstructions are commonly maintained on mechanical ventilation in an intensive care unit (ICU). This study reviews indications and outcomes of such patients undergoing a rapid awakening protocol (RAP).

Methods

We retrospectively reviewed consecutive patients who underwent head and neck microvascular reconstructions by a single surgeon between 2001 and 2013.

Results

Seventy‐five patients underwent RAP and 605 received mechanical ventilation. Overall complications were significantly higher in mechanical ventilation patients than in the RAP cohort (61% vs 31%, respectively; p < .001). Univariate analysis demonstrates mechanical ventilation, age, and aerodigestive tract involvement are significant risk factors for a complication and longer hospital stay. Multivariate logistic regression model demonstrates RAP patients had significantly less risk of a complication (odds ratio [OR] = 0.32; 95% [CI] = 0.19–0.54; p < .001).

Conclusion

The recovery of select patients with early extubation/spontaneous breathing is superior to maintenance on mechanical ventilation. © 2014 Wiley Periodicals, Inc. Head Neck 37: 464–470, 2015
Oral cavity anaerobic pathogens in biofilm formation on voice prostheses
Authors: Bertl Kristina , Zijnge Vincent , Zatorska Beata , Leonhard Matthias , Schneider–Stickler Berit , Harmsen Hermie J. M.
Published: February 2014

Background

A polymerase chain reaction (PCR)‐based method has been used to identify oral anaerobic pathogens in biofilms on voice prostheses. The purpose of the present study was to determine the location of those pathogens inside the biofilms.

Methods

Biofilms of 15 voice prostheses were sampled and used to identify the oral pathogens. Fluorescence in situ hybridization was applied on smears made on glass slides and on sections of intact biofilms visualized by confocal laser scanning microscopy (CLSM).

Results

Fusobacterium nucleatum (F. nucleatum) was the most frequently detected pathogen and the only tested species detected in microcolonies. The other microbes (Parvimonas micra [P. micra], Porphyromonas gingivalis [P. gingivalis], Tannerella forsythia [T. forsythia], and Treponema denticola [T. denticola]) were not detected or only detected as single cells. CLSM analysis showed that F. nucleatum resided on the biofilm surface.

Conclusion

Although detectable, oral anaerobic pathogens seem to be no more than passers‐by that adhere without further observed proliferation and apparently play no striking role in biofilm formation on voice prostheses. © 2014 Wiley Periodicals, Inc. Head Neck 37: 524–529, 2015