bluuebunny/crossref_metadata_2025 huggingface dataset:
Lithiated Primary Amine—A New Material for Hydrogen Storage
Authors: Chen Juner , Wu Hui , Wu Guotao , Xiong Zhitao , Wang Ruiming , Fan Hongjun , Zhou Wei , Liu Bin , Chua Yongshen , Ju Xiaohua , Chen Ping
Published: April 2014

A facile method for synthesizing crystalline lithiated amines by ball milling primary amines with LiH was developed. The lithiated amines exhibit an unprecedented endothermic dehydrogenation feature in the temperature range of 150–250 °C, which shows potential as a new type of hydrogen storage material. Structural analysis and mechanistic studies on lithiated ethylenediamine (Li2EDA) indicates that Li may mediate the dehydrogenation through an α,β‐LiH elimination mechanism, creating a more energy favorable pathway for the selective H2 release.
Cyanoborohydride‐Based Ionic Liquids as Green Aerospace Bipropellant Fuels
Authors: Zhang Qinghua , Yin Ping , Zhang Jiaheng , Shreeve Jean'ne M.
Published: April 2014

In propellant systems, the most common bipropellants are composed of two chemicals, a fuel (or reducer) and an oxidizer. Currently, the choices for propellant fuels rely mainly on hydrazine and its methylated derivatives, even though they are extremely toxic, highly volatile, sensitive to adiabatic compression (risk of detonation), and, therefore, difficult to handle. With this background, the search for alternative green propellant fuels has been an urgent goal of space science. In this study, a new family of cyanoborohydride‐based ionic liquids (ILs) with properties and performances comparable to hydrazine derivatives were designed and synthesized. These new ILs as bipropellant fuels, have some unique advantages including negligible vapor pressure, ultra‐short ignition delay (ID) time, and reduced synthetic and storage costs, thereby showing great application potential as environmentally friendly fuels in bipropellant formulations.
Lanthanide Tris(β‐diketonates) as Useful Probes for Chirality Determination of Biological Amino Alcohols in Vibrational Circular Dichroism: Ligand to Ligand Chirality Transfer in Lanthanide Coordination Sphere
Authors: Miyake Hiroyuki , Terada Keiko , Tsukube Hiroshi
Published: April 2014

A series of lanthanide tris(β‐diketonates) functioned as useful chirality probes in the vibrational circular dichroism (VCD) characterization of biological amino alcohols. Various chiral amino alcohols induced intense VCD signals upon ternary complexation with racemic lanthanide tris(β‐diketonates). The VCD signals observed around 1500 cm−1 (β‐diketonate IR absorption region) correlated well with the stereochemistry and enantiomeric purity of the targeted amino alcohol, while the corresponding monoalcohol, monoamine, and diol substrates induced very weak VCD signals. The high‐coordination number and dynamic property of the lanthanide complex offer an effective chirality VCD probing of biological substrates. Chirality 26:293–299, 2014. © 2014 Wiley Periodicals, Inc.
Design, Synthesis, and Activity Evaluation of GK/PPARγ Dual‐Target‐Directed Ligands as Hypoglycemic Agents
Authors: Lu Jianxun , Lei Lei , Huan Yi , Li Yongqiang , Zhang Lijing , Shen Zhufang , Hu Wenxiang , Feng Zhiqiang
Published: April 2014

Based on the multi‐target strategy to treat type 2 diabetes mellitus (T2DM), glucokinase/peroxisome proliferator‐activated receptor γ (GK/PPARγ) dual‐target molecules were constructed by the rational combination of pharmacophores from known GK activators and PPARγ agonists. A series of dual‐target agents were designed and synthesized, and their capacities to induce GK and PPARγ transcriptional activity were evaluated. Three of these compounds showed particularly high potency toward GK, moderate activity toward PPARγ, and their structure–activity relationships were preliminarily analyzed. The putative binding modes of one of the most promising compounds were also explored by molecular docking simulations with GK and PPARγ.
Spatial mapping of translational diffusion coefficients using diffusion tensor imaging: A mathematical description
Authors: Shetty Anil N. , Chiang Sharon , Maletic‐Savatic Mirjana , Kasprian Gregor , Vannucci Marina , Lee Wesley
Published: April 2014

In this article, we discuss the theoretical background for diffusion weighted imaging and diffusion tensor imaging. Molecular diffusion is a random process involving thermal Brownian motion. In biological tissues, the underlying microstructures restrict the diffusion of water molecules, making diffusion directionally dependent. Water diffusion in tissue is mathematically characterized by the diffusion tensor, the elements of which contain information about the magnitude and direction of diffusion and is a function of the coordinate system. Thus, it is possible to generate contrast in tissue based primarily on diffusion effects. Expressing diffusion in terms of the measured diffusion coefficient (eigenvalue) in any one direction can lead to errors. Nowhere is this more evident than in white matter, due to the preferential orientation of myelin fibers. The directional dependency is removed by diagonalization of the diffusion tensor, which then yields a set of three eigenvalues and eigenvectors, representing the magnitude and direction of the three orthogonal axes of the diffusion ellipsoid, respectively. For example, the eigenvalue corresponding to the eigenvector along the long axis of the fiber corresponds qualitatively to diffusion with least restriction. Determination of the principal values of the diffusion tensor and various anisotropic indices provides structural information. We review the use of diffusion measurements using the modified Stejskal–Tanner diffusion equation. The anisotropy is analyzed by decomposing the diffusion tensor based on symmetrical properties describing the geometry of diffusion tensor. We further describe diffusion tensor properties in visualizing fiber tract organization of the human brain. © 2014 Wiley Periodicals, Inc. Concepts Magn Reson Part A 43A: 1–27, 2014.
BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high‐risk pancreatic cancer screening and pancreatic cancer cohorts
Authors: Lucas Aimee L. , Frado Laura E. , Hwang Caroline , Kumar Sheila , Khanna Lauren G. , Levinson Elana J. , Chabot John A. , Chung Wendy K. , Frucht Harold
Published: April 2014

BACKGROUND

Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) is due to a genetic predisposition, including the breast and ovarian cancer syndrome germline mutations BRCA1 and BRCA2. Knowledge of specific genetic mutations predisposing to PDAC may enable risk stratification, early detection, and the development of effective screening and surveillance programs. In the current study, the authors attempted to determine the diagnostic yield of testing for BRCA1/2 germline mutations in a PDAC screening cohort and a PDAC cohort referred for genetic testing.

METHODS

Patients in a high‐risk PDAC prevention and genetics program or those with a personal history of PDAC who were referred for genetic evaluation underwent testing for BRCA1/2 germline mutations. Clinical BRCA1/2 genetic testing included testing for the 3 Ashkenazi Jewish founder mutations or BRCA1/2 comprehensive testing.

RESULTS

A total of 37 patients without PDAC underwent BRCA1/2 testing at the study institution. Genetic testing identified 7 patients who were BRCA1/2 carriers for a yield of 18.9%. Six patients carried Ashkenazi Jewish founder mutations (3 with BRCA1 and 3 with BRCA2), and 1 patient was found to have a BRCA2 mutation on comprehensive testing. Thirty‐two patients with PDAC underwent BRCA1/2 genetic testing. Five patients had Ashkenazi Jewish founder mutations (2 with BRCA1 and 3 with BRCA2), and 2 patients were found to have BRCA2 mutations on comprehensive testing. The diagnostic yield was 7 of 32 patients (21.9%).

CONCLUSIONS

BRCA1/2 testing is useful in PDAC risk stratification and alters risk assignment and screening recommendations for mutation‐positive patients and their families. Clinical BRCA1/2 testing should be considered in patients of Ashkenazi Jewish descent with a personal history or family history of PDAC, even in the absence of a family history of breast and ovarian cancer. Cancer 2014;120:1960–1967. © 2014 American Cancer Society.
Independent oncogenic and therapeutic significance of phosphatase PRL‐3 in FLT3‐ITD–negative acute myeloid leukemia
Authors: Qu Shuang , Liu Bin , Guo Xiaoling , Shi Hongshun , Zhou Meifeng , Li Li , Yang Shulan , Tong Xiuzhen , Wang Haihe
Published: April 2014

BACKGROUND

Internal tandem duplication of FMS‐like tyrosine kinase (FLT3‐ITD) is well known to be involved in acute myeloid leukemia (AML) progression, but FLT3‐ITD–negative AML cases account for 70% to 80% of AML, and the mechanisms underlying their pathology remain unclear. This study identifies protein tyrosine phophatase PRL‐3 as a key mediator of FLT3‐ITD–negative AML.

METHODS

A total of 112 FLT3‐ITD–negative AML patients were sampled between 2010 and 2013, and the occurrence of PRL‐3 hyperexpression in FLT3‐ITD–negative AML was evaluated by multivariate probit regression analysis. Overexpression or depletion of endogenous PRL‐3 expression with the specific small interfering RNAs was performed to investigate the role of PRL‐3 in AML progression. Xenograft models were also used to confirm the oncogenic role of PRL‐3.

RESULTS

Compared to healthy donors, PRL‐3 is upregulated more than 3‐fold in 40.2% of FLT3‐ITD–negative AML patients. PRL‐3 expression level is adversely correlated to the overall survival of the AML patients, and the AML relapses accompany with re‐upregulation of PRL‐3. Mechanistically, aberrant PRL‐3 expression promoted cell cycle progression and enhanced the antiapoptotic machinery of AML cells to drug cytotoxicity through downregulation of p21 and upregulation of Cyclin D1 and CDK2 and activation of STAT5 and AKT. Depletion of endogenous PRL‐3 sensitizes AML cells to therapeutic drugs, concomitant with apoptosis by upregulation of cleaved PARP (poly ADP ribose polymerase) and apoptosis‐related caspases. Xenograft assays further confirmed PRL‐3's oncogenic role in leukemogenesis.

CONCLUSIONS

Our results demonstrated that PRL‐3 is a novel independent crucial player in both FLT3‐ITD–positive and FLT3‐ITD–negative AML and could be a potential therapeutic target. Cancer 2014;120:2130–2141. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib
Authors: Joensuu Heikki , Eriksson Mikael , Hall Kirsten Sundby , Hartmann Jörg T. , Pink Daniel , Schütte Jochen , Ramadori Giuliano , Hohenberger Peter , Duyster Justus , Al‐Batran Salah‐Eddin , Schlemmer Marcus , Bauer Sebastian , Wardelmann Eva , Sarlomo‐Rikala Maarit , Nilsson Bengt , Sihto Harri , Ballman Karla V. , Leinonen Mika , DeMatteo Ronald P. , Reichardt Peter
Published: April 2014

BACKGROUND

Little is known about the factors that predict for gastrointestinal stromal tumor (GIST) recurrence in patients treated with adjuvant imatinib.

METHODS

Risk factors for GIST recurrence were identified, and 2 risk stratification scores were developed using the database of the Scandinavian Sarcoma Group (SSG) XVIII trial, where 358 patients with high‐risk GIST with no overt metastases were randomly assigned to adjuvant imatinib 400 mg/day either for 12 or 36 months after surgery. The findings were validated in the imatinib arm of the American College of Surgeons Oncology Group Z9001 trial, where 359 patients with GIST were randomized to receive imatinib and 354 were to receive placebo for 12 months.

RESULTS

Five factors (high tumor mitotic count, nongastric location, large size, rupture, and adjuvant imatinib for 12 months) were independently associated with unfavorable recurrence‐free survival (RFS) in a multivariable analysis in the SSGXVIII cohort. A risk score based on these 5 factors had a concordance index with GIST recurrence of 78.9%. When a simpler score consisting of the 2 strongest predictive factors (mitotic count and tumor site) was devised, the groups with the lowest, intermediate high, and the highest risk had 5‐year RFS of 76.7%, 47.5%, and 8.4%, respectively. Both scores were strongly associated with RFS in the validation cohort (P < .001 for each comparison).

CONCLUSIONS

The scores generated were effective in stratifying the risk of GIST recurrence in patient populations treated with adjuvant imatinib. Patients with nongastric GIST with a high mitotic count are at a particularly high risk for recurrence. Cancer 2014;120:2325–2333 © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Colorectal cancer screening in high‐risk groups is increasing, although current smokers fall behind
Authors: Oluyemi Aminat O. , Welch Amy R. , Yoo Lisa J. , Lehman Erik B. , McGarrity Thomas J. , Chuang Cynthia H.
Published: April 2014

BACKGROUND

There is limited information about colorectal cancer (CRC) screening trends in high‐risk groups, including the black, obese, diabetic, and smoking populations. For this study, the authors evaluated national CRC screening trends in these high‐risk groups to provide insights into whether screening resources are being appropriately used.

METHODS

This was a nationally representative, population‐based study using the Behavioral Risk Factor Surveillance System from the Centers for Disease Control. Data analysis was performed using bivariate analyses with weighted logistic regression.

RESULTS

In the general population, CRC screening increased significantly from 59% to 65% during the years 2006 to 2010. The screening prevalence in non‐Hispanic blacks was 58% in 2006 and 65% in 2010. Among obese individuals, the prevalence of up‐to‐date CRC screening increased significantly from 59% in 2006 to 66% in 2010. Screening prevalence in individuals with diabetes was 63% in 2006 and 69% in 2010. The CRC screening prevalence in current smokers was 45% in 2006 and 50% in 2010. The odds of CRC screening in the non‐Hispanic black population, the obese population, and the diabetic population were higher than in non‐Hispanic whites, normal weight individuals, and the population without diabetes, respectively. Current smokers had significantly lower odds of CRC screening than never‐smokers in the years studied (2006: odds ratio [OR], 0.71; 95% confidence interval [CI], 0.66‐0.76; 2008: OR, 0.67; 95% CI, 0.63‐0.71; 2010: OR, 0.69; 95% CI, 0.66‐0.73).

CONCLUSIONS

The prevalence of CRC screening in high‐risk groups is trending upward. Despite this, current smokers have significantly lower odds of CRC screening compared with the general population. Cancer 2014;120:2106–2113. © 2014 American Cancer Society.
Acute renal failure associated with the new BRAF inhibitor vemurafenib: A case series of 8 patients
Authors: Launay‐Vacher Vincent , Zimner‐Rapuch Sarah , Poulalhon Nicolas , Fraisse Thibault , Garrigue Valérie , Gosselin Morgane , Amet Sabine , Janus Nicolas , Deray Gilbert
Published: April 2014

BACKGROUND

Vemurafenib is a BRAF inhibitor that has become the cornerstone of metastatic or inoperable melanoma therapy since its approval in 2011 in the United States and 2012 in Europe. This targeted therapy has shown impressive results in terms of increased progression‐free and overall survival as compared to dacarbazine. The safety profile did not include any renal manifestations at that time.

METHODS

This report is the first case series of 8 patients who experienced significant to severe renal insufficiency under vemurafenib treatment.

RESULTS

This case series shows that vemurafenib may induce potentially severe acute renal failure, including renal sequelae and persistent kidney disease in some cases.

CONCLUSIONS

Further studies are needed to investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function should be closely monitored in treated patients for early detection of any renal dysfunction occurrence. Cancer 2014;120:2158–2163. © 2014 American Cancer Society.
State of the science in cervical cancer: Where we are today and where we need to go
Authors: Dizon Don S. , Mackay Helen J. , Thomas Gillian M. , Werner Theresa L. , Kohn Elise C. , Hess Dina , Rose Peter G. , Covens Allan L.
Published: April 2014

Invasive cervical cancer remains an important global cause of death, despite the declining prevalence within the United States. Definitive therapies, including surgical resection of early‐stage disease and chemoradiation for locally advanced disease, can be curative. For women who experience local or distant recurrences, the prognosis remains poor and better treatments are required. On July 18, 2013, The Gynecologic Oncology Group sponsored a State of the Science in Cervical Cancer Symposium with experts, researchers, clinicians, and interested stakeholders. This article summarize the progress that has been made, questions that require further investigation, and contemporary genomic findings and innovative treatments that may help inform the next generation of clinical trials for patients with cervical cancer. Cancer 2014;120:2282–2288. © 2014 American Cancer Society.
Costs and benefits of an organized fecal immunochemical test‐based colorectal cancer screening program in the United States
Authors: Guy Gery P. , Richardson Lisa C. , Pignone Michael P. , Plescia Marcus
Published: April 2014

BACKGROUND

Despite clear recommendations and evidence linking colorectal cancer screening to lower incidence and mortality, > 40% of adults are not up to date with screening. Existing domestic and international models of organized cancer screening programs have been effective in increasing screening rates. Implementing an organized, evidence‐based, national screening program may be an effective approach to increasing screening rates.

METHODS

In the current study, the authors estimated the initial investment required and the cost per person screened of a nationwide fecal immunochemical test (FIT)‐based colorectal cancer screening program among adults aged 50 years to 75 years.

RESULTS

The initial additional investment required was estimated at $277.9 to $318.2 million annually, with an estimated 8.7 to 9.4 million individuals screened at a cost of $32 to $39 per person screened. The program was estimated to prevent 2900 to 3100 deaths annually.

CONCLUSIONS

The results of the current study indicate that implementing a national screening program would make a substantial public health impact at a moderate cost per person screened. Results from this analysis may provide useful information for understanding the public health benefit of an organized screening delivery system and the potential resources required to implement a nationwide colorectal cancer screening program, and help guide decisions about program planning, design, and implementation. Cancer 2014;120:2308–2315. © 2014 American Cancer Society.
BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer
Authors: Yaeger Rona , Cercek Andrea , Chou Joanne F. , Sylvester Brooke E. , Kemeny Nancy E. , Hechtman Jaclyn F. , Ladanyi Marc , Rosen Neal , Weiser Martin R. , Capanu Marinela , Solit David B. , D'Angelica Michael I. , Vakiani Efsevia , Saltz Leonard B.
Published: April 2014

BACKGROUND

BRAFmutations occur in 5% to 11% of patients with metastatic colorectal cancer (mCRC) and have been associated with poor prognosis. The current study was undertaken to determine the clinicopathologic characteristics,PIK3CA(phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, catalytic subunit alpha) mutation frequency, and outcomes after metastasectomy in patients withBRAF‐mutant mCRC.

METHODS

Data from 1941 consecutive patients with mCRC who underwentKRAS/BRAFmutation testing between 2009 and 2012 at a single institution were identified to identifyBRAF‐mutant mCRC cases (92 cases).BRAFwild‐type mCRC cases from 2011 (423 cases) served as a control group.

RESULTS

BRAF‐mutated mCRC was found to be significantly associated with older age at diagnosis, female sex, right‐sided location, poorly differentiated morphology, and mucinous histology compared with wild‐type cases.BRAF‐mutant cases more frequently progressed from stage III disease (32% vs 17%;P = .003) and among those patients with stage III disease, T4 disease was more common (48% vs 27%;P = .05).PIK3CAwas found to be co‐mutated in 5% ofBRAF‐mutant tumors versus 17% ofKRAS‐mutant tumors (P < .01) and 4% ofBRAF/KRASwild‐type cases. Patients withBRAF‐mutated mCRC presented more frequently with peritoneal involvement (26% vs 14%;P < 0.01) and less frequently with liver‐limited metastases (41% vs 63%;P < .01). Patients withBRAF‐mutated mCRC were less likely to undergo metastasectomy (41% vs 26% at 2 years from diagnosis of metastatic disease;P < .01) and were found to have lower overall survival (P < .01) after metastasectomy.

CONCLUSIONS

BRAF‐mutant mCRC is associated with worse clinical outcome. Patients withBRAF‐mutant tumors more commonly develop peritoneal metastases, less frequently present with disease limited to the liver, and have shorter survival after metastasectomy compared with patients withBRAFwild‐type tumors.Cancer2014;120:2316–2324.©2014 American Cancer Society.
Two‐Electron Carbon Dioxide Reduction Catalyzed by Rhenium(I) Bis(imino)acenaphthene Carbonyl Complexes
Authors: Portenkirchner Engelbert , Kianfar Elham , Sariciftci Niyazi Serdar , Knör Günther
Published: April 2014

Rhenium(I) carbonyl complexes carrying substituted bis(arylimino)acenaphthene ligands (BIAN‐R) have been tested as potential catalysts for the two‐electron reduction of carbon dioxide. Cyclic voltammetric studies as well as controlled potential electrolysis experiments were performed using CO2‐saturated solutions of the complexes in acetonitrile and acetonitrile–water mixtures. Faradaic efficiencies of more than 30 % have been determined for the electrocatalytic production of CO. The effects of ligand substitution patterns and water content of the reaction medium on the catalytic performance of the new catalysts are discussed.
Chemically Stable Perovskites as Cathode Materials for Solid Oxide Fuel Cells: La‐Doped Ba0.5Sr0.5Co0.8Fe0.2O3−δ
Authors: Kim Junyoung , Choi Sihyuk , Jun Areum , Jeong Hu Young , Shin Jeeyoung , Kim Guntae
Published: April 2014

Ba0.5Sr0.5Co0.8Fe0.2O3−δ (BSCF) has won tremendous attention as a cathode material for intermediate‐temperature solid‐oxide fuel cells (IT‐SOFC) on the basis of its fast oxygen‐ion transport properties. Nevertheless, wide application of BSCF is impeded by its phase instabilities at intermediate temperature. Here we report on a chemically stable SOFC cathode material, La0.5Ba0.25Sr0.25Co0.8Fe0.2O3−δ (LBSCF), prepared by strategic approaches using the Goldschmidt tolerance factor. The tolerance factors of LBSCF and BSCF indicate that the structure of the former has a smaller deformation of cubic symmetry than that of the latter. The electrical property and electrochemical performance of LBSCF are improved compared with those of BSCF. LBSCF also shows excellent chemical stability under air, a CO2‐containg atmosphere, and low oxygen partial pressure while BSCF decomposed under the same conditions. Together with this excellent stability, LBSCF shows a power density of 0.81 W cm−2 after 100 h, whereas 25 % degradation for BSCF is observed after 100 h.
Inducing bias modulates sensitivity to nonverbal cues of others' pain
Authors: Pronina I. , Rule N.O.
Published: April 2014

Background

There is ample research to support the existence of bias in the perception of others' pain. Both studies involving health‐care professionals and student surrogate samples have found that, firstly, pain is under‐perceived when using nonverbal cues to gauge another's suffering and, secondly, that personal characteristics of both the viewer and the target (such as gender) can bias pain perception, affecting the allocation of help. However, the extant research shows conflicts about the direction of the bias that target gender exerts on pain perception. Our study aims to address these challenges by examining whether under‐perception of pain can be attenuated or exacerbated with gender primes and how target gender affects nonverbal pain perception, in particular.

Methods

University students (N = 120) were primed with either masculine, neutral, or feminine concepts followed by photos of male and female targets displaying various levels of pain and asked to quantify the photographed targets' distress.

Results

Participants perceived lower target distress when this task was preceded by a masculine gender prime, as compared to a neutral or feminine gender prime. Pain was underestimated for all targets; however, this underestimation was significantly more pronounced for female targets.

Conclusions

These results suggest that gender cues may influence the perception of observed pain and, as a result, clinical decision making. They also support the conjecture that nonverbal pain cues may be under‐perceived in women.
Angiotensin (1–7) prevents angiotensin II‐induced nociceptive behaviour via inhibition of p38 MAPK phosphorylation mediated through spinal Mas receptors in mice
Authors: Nemoto W. , Ogata Y. , Nakagawasai O. , Yaoita F. , Tadano T. , Tan‐No K.
Published: April 2014

Background

We have recently demonstrated that intrathecal (i.t.) administration of angiotensin II (Ang II) induces nociceptive behaviour in mice accompanied by a phosphorylation of p38 mitogen‐activated protein kinase (MAPK) mediated through Ang II type 1 (AT1) receptors. The N‐terminal fragment of Ang II, Ang (1–7), plays a pivotal role in counterbalancing many of the well‐established actions induced by Ang II. However, the role of Ang (1–7) in spinal nociceptive transmission remains unclear. Therefore, we examined whether i.t. administration of Ang (1–7) can inhibit the Ang II‐induced nociceptive behaviour in mice.

Methods

In the behavioural experiments, the accumulated response time of nociceptive behaviour consisting of scratching, biting and licking in conscious mice was determined during a 25‐min period starting after i.t. injection. The distribution and localization of AT1 or Mas receptors were analysed using a MapAnalyzer and confocal microscope, respectively. Phosphorylation of p38 MAPK in the dorsal spinal cord was measured by Western blotting.

Results

The nociceptive behaviour induced by Ang II was dose‐dependently inhibited by the co‐administration of Ang (1–7). The inhibitory effect of Ang (1–7) was reversed by the co‐administration of A779, a Mas receptor antagonist. Western blot analysis showed that the increase in spinal p38 MAPK phosphorylation following the i.t. administration of Ang II was also inhibited by Ang (1–7), and the Ang (1–7) induced‐inhibition was prevented by A779.

Conclusions

Our data show that the i.t. administration of Ang (1–7) attenuates an Ang II‐induced nociceptive behaviour and is accompanied by the inhibition of p38 MAPK phosphorylation mediated through Mas receptors.
A Pencil Graphite Electrode In Situ Modified by Monovalent Copper: a Promising Tool for the Determination of Methylxanthines
Authors: Navratil Rudolf , Jelen Frantisek , Ugur Kayran Yasin , Trnkova Libuse
Published: April 2014

A pencil graphite electrode (PeGE) exhibits a promising tool for the electrochemical analysis of xanthine (Xan) and its N‐methyl derivatives (1‐, 3‐, 7‐ and 9‐mXan). The changes in their level in blood, serum, urine, as products of purine catabolism, can indicate the development of some diseases. Sensitivity‐enhanced voltammetric detection of mXans was achieved by forming of complex with Cu(I) and application of elimination procedure. The Cu(I)‐mXan complex was identified by means of titration of electrochemically produced cuprous ions by mXan. Our approach enables separation of overlapped mXan oxidation signals. Based on the obtained results, we found that the effect of methyl group position on the xanthine skeleton was significant and it was also discussed.
Hydrophilic interaction electrokinetic chromatography using bio‐based nanofillers
Authors: Kawai Takayuki , Watanabe Masato , Uetani Kojiro , Fukushima Yudai , Sueyoshi Kenji , Kubo Takuya , Kitagawa Fumihiko , Yano Hiroyuki , Otsuka Koji
Published: April 2014

Hydrophilic interaction (HI)‐based separation like HILIC is effective for analyzing hydrophilic biological samples such as carbohydrates, peptides, and metabolites. To overcome the drawbacks of conventional HILIC such as large consumption of organic solvents and easy deterioration of the separation column, we developed HI electrokinetic chromatography (EKC) by employing bio‐based nanomaterials as the hydrophilic pseudostationary phase. By mechanical/chemical treatments, cellulose, chitin, and chitosan were processed to 10‐nm wide nanofibers/nanowhiskers (NFs/NWs), which are longer/shorter than 1000/200 nm, respectively. In HI‐EKC of oligosaccharides using 0.001% uncharged cellulose NFs, strong interaction was observed for the large‐size oligosaccharides with the retention factors (k) of up to 1.56, indicating a HILIC‐mode interaction. In HI‐EKC with 0.1% positively charged chitosan NFs, benzenedisulfonic acid, benzenesulfonic acid (BS), and p‐hydroxy BS (HBS) had k values of 0.036, 0.018, and 0.018, respectively, suggesting that the ion‐exchange interaction mainly occurred via sulfonate groups. Finally, HI‐EKC was demonstrated using 0.05% chitin or chitosan NWs. In both cases using chitin and chitosan NWs, HBS showed much stronger interaction with k > 0.192 compared with BS with k < 0.070. It indicated structural difference between NFs and NWs affected the HI behavior in terms of both the ion‐exchange and HILIC modes.
Single‐use wave‐mixed versus stirred bioreactors for insect‐cell/BEVS‐based protein expression at benchtop scale
Authors: Imseng Nicole , Steiger Nina , Frasson David , Sievers Martin , Tappe Alexander , Greller Gerhard , Eibl Dieter , Eibl Regine
Published: April 2014

Spodoptera frugiperda‐9 (Sf‐9) cells used in conjunction with the baculovirus expression vector system (BEVS) represent a promising platform for the rapid development and manufacture of protein complexes and virus‐like particle (VLP) products. Several studies have described the superiority of single‐use wave‐mixed bioreactors although reusable stirred and, more recently, single‐use stirred bioreactors have also been successfully applied. Due to their bioengineering characteristics (more homogeneous energy dissipation, reduced foam formation), wave‐mixed systems are often preferred. However, a direct comparison of the influence of single‐use wave‐mixed and single‐use stirred bioreactors on cell growth and protein expression in Sf‐9/BEVS‐based production processes was still lacking. We investigated Sf‐9 cell growth and expression of a recombinant secreted alkaline phosphatase (rSEAP) in the wave‐mixed BIOSTAT® RM as well as the stirred UniVessel® SU and a serum‐free culture medium. Irrespective of the bioreactor system, comparable growth, substrate, and metabolite courses as well as peak cell densities (>1.2 × 107 cells mL−1) were observed in Sf‐9 cell expansions performed in batch mode. Additionally, identical rSEAP quality and maximum rSEAP activities were found in biphasic productions in both bioreactor systems. Concluding, comparability of single‐use wave‐mixed and stirred bioreactors for insect cell culture processes was demonstrated for the first time.
Effect of methanogenic effluent recycling on continuous H2 production from food waste
Authors: Redondas Vanesa , Moran Antonio , Martínez Judith E. , Fierro Julio , Gomez Xiomar
Published: April 2014

The production of hydrogen from food wastes was studied in a two‐stage (dark fermentation‐digestion) process under mesophilic conditions. The effect of a recycling stream, from the methanogenic phase to the fermentation phase, over H2 production and alkali consumption was evaluated in a semicontinuous fermentation process. The cases of no‐recycling, direct recycling, and membrane permeate recycling of methanogenic supernatant (using an ultrafiltration and nanofiltration membrane) were evaluated.

Adding a recycling stream from a methanogenic reactor to the hydrogen‐producing reactor significantly reduced the need of external alkali addition for pH control, up to 52%. The performance of the hydrogen‐producing reactors receiving the recycling stream was similar in all cases tested, with values of specific hydrogen production of about 30 mL g−1 VSadded. This value was also similar to that one obtained from the no‐recycling configuration. The use of a membrane pretreatment stage proved to be not necessary. Operating conditions established in the fermentation stage were enough to avoid any detrimental effect associated to methanogenic microflora predominance. © 2014 American Institute of Chemical Engineers Environ Prog, 34: 227–233, 2015
Pain in care home residents with dementia: an exploration of frequency, prescribing and relatives' perspectives
Authors: Barry Heather E. , Parsons Carole , Passmore A. Peter , Hughes Carmel M.
Published: April 2014

Objectives

This study aims to determine pain frequency amongst care home residents with dementia, to investigate variables associated with pain, to explore analgesic use among residents and to seek residents' relatives' views on provision of care and management of pain by the care home.

Methods

Structured face‐to‐face interviews were conducted with residents, nursing staff and relatives from nine dementia care homes in Northern Ireland, between May 2010 and March 2012. Demographic information was collected from participants, neuropsychiatric tests were used to assess residents' cognitive functioning, medication use was determined from care home records and residents' pain was assessed using a verbal descriptor scale. Relatives' views were sought on care provision and management of pain.

Results

Forty‐two residents, 16 nurses/care assistants and 35 relatives participated; the participation rate of residents was low (27.6%). Most residents were suffering moderate–severe dementia, and some residents (26.2%) were unable to provide a self‐report of pain. A significantly higher proportion of relatives (57.1%) deemed residents to be experiencing pain at the time of the interview, compared with residents (23.8%, p = 0.005) and nurses/care assistants (42.9%, p = 0.035). Most residents (88.1%) were prescribed with analgesia; non‐opioid analgesics were most commonly prescribed. High proportions of residents were prescribed with psychoactive medications. Antipsychotic drug use was associated with presence of pain (p = 0.046).

Conclusions

This study has reinforced the challenge of assessing and managing pain in this resident population and highlighted issues to be addressed by long‐term care providers and clinicians. Participation of people with dementia, and their families, in healthcare research needs to be improved. Copyright © 2014 John Wiley & Sons, Ltd.
Linking cognition and frailty in middle and old age: metabolic syndrome matters
Authors: Lin Feng , Roiland Rachel , Chen Ding‐Geng (Din) , Qiu Christina
Published: April 2014

Objectives

This study examined whether metabolic syndrome (MetS) would moderate the association of cognition with frailty in middle and old age.

Methods

A cross‐sectional design was used. Six hundred and ninety participants (age ≥ 50 years) from an on‐going national survey were included in the study. Confirmatory factor analysis was applied to determine latent variables of executive function (EF), episodic memory (EM), and MetS based on relevant measurements. Frailty was defined using a modified form of Fried's criteria.

Results

Applying structural equation modeling, having MetS significantly increased the likelihood of being frail. Better performance on EM tasks, but not EF, was significantly associated with lower likelihood of MetS. Worse performance on EF, but not EM, significantly increased the likelihood of being frail. There was a significant interacting effect between MetS and EF, but not EM, on frailty. Further contrast analysis indicated that having MetS strengthened the negative association between EF and frailty.

Conclusion

Metabolic syndrome moderates the relationship between EF and frailty. A prospecitve study is needed to validate such relationships before developing interventions targeting the prevention or treatment of EF and frailty in individuals with MetS. Copyright © 2014 John Wiley & Sons, Ltd.
Topological methods reveal high and low functioning neuro‐phenotypes within fragile X syndrome
Authors: Romano David , Nicolau Monica , Quintin Eve‐Marie , Mazaika Paul K. , Lightbody Amy A. , Cody Hazlett Heather , Piven Joseph , Carlsson Gunnar , Reiss Allan L.
Published: April 2014

Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common known inherited cause of developmental disability as well as the most common single‐gene risk factor for autism. Our goal was to examine variation in brain structure in FXS with topological data analysis (TDA), and to assess how such variation is associated with measures of IQ and autism‐related behaviors. To this end, we analyzed imaging and behavioral data from young boys (n = 52; aged 1.57–4.15 years) diagnosed with FXS. Application of topological methods to structural MRI data revealed two large subgroups within the study population. Comparison of these subgroups showed significant between‐subgroup neuroanatomical differences similar to those previously reported to distinguish children with FXS from typically developing controls (e.g., enlarged caudate). In addition to neuroanatomy, the groups showed significant differences in IQ and autism severity scores. These results suggest that despite arising from a single gene mutation, FXS may encompass two biologically, and clinically separable phenotypes. In addition, these findings underscore the potential of TDA as a powerful tool in the search for biological phenotypes of neuropsychiatric disorders. Hum Brain Mapp 35:4904–4915, 2014. © 2014 Wiley Periodicals, Inc.
A single‐dose, randomized, double‐blind, double dummy, placebo and positive‐controlled, five‐way cross‐over study to assess the pharmacodynamic effects of lorediplon in a phase advance model of insomnia in healthy Caucasian adult male subjects
Authors: Horoszok Lucy , Baleeiro Thais , D'Aniello Fabiana , Gropper Savion , Santos Benjamin , Guglietta Antonio , Roth Thomas
Published: April 2014

Objective

A 5‐h phase advance model of insomnia was used to evaluate the efficacy of lorediplon, a new non‐benzodiazepine hypnotic.

Methods

Thirty‐five male, healthy subjects were included in a five‐way randomized cross‐over study. During each of the periods, sleep was recorded, and residual effects were measured. All subjects received lorediplon 1, 5, and 10 mg, placebo, and zolpidem 10 mg (i.e., active control).

Results

Polysomnographic evaluation revealed that lorediplon (5 and 10 mg) significantly decreased wake after sleep onset (WASO) and increased total sleep time. Analysis by quarters of the night showed a progressive increasing effectiveness of lorediplon 10 mg across the first three quarters. Lorediplon increased non‐rapid eye movement slow wave sleep and stage N2 sleep in the second and third quarters. The magnitude of these effects was dose related, with minimal effects seen with 1 mg. No residual effects were observed 13 h post dose.

Conclusions

Lorediplon demonstrated a dose‐dependent improvement in sleep, whereas zolpidem showed a more sustained WASO effect. No next‐day hangover effects were observed. These sleep effects are also consistent with the pharmacokinetic profile of lorediplon. These results warrant clinical trials in patients with insomnia. Copyright © 2014 John Wiley & Sons, Ltd.
Event‐related Potentials Elicited to Performance Feedback in High‐Shy and Low‐Shy Adolescents
Authors: Lackner Christine L. , Santesso Diane L. , Dywan Jane , Wade Terrance J. , Segalowitz Sidney J.
Published: April 2014

Shyness has been associated with hyper‐responsivity to both social feedback and monetary reward. Electrophysiological paradigms investigating sensitivity to social feedback frequently use emotional face stimuli as their main measure. However, some behavioural evidence suggests that shy individuals show aberrant responses to non‐social rewards as well. Here, we investigate the neurophysiological correlates of adolescent shyness in a group of 12–14 year olds as they performed a simple reaction time task with embedded rewards and losses. High‐shy adolescents had more positive late P2/early N2 responses to cues signalling the potential to win or lose money than did low‐shy adolescents. Regardless of feedback type (e.g. win or loss), high‐shy adolescents showed more positive frontal P2 and late FRN amplitudes than did low‐shy adolescents. This suggests that high‐shy adolescents are hyper‐attentive to both environmental cues about forthcoming behavioural requirements and feedback from the environment about their behaviour. P2 results were not attributable to anxiety levels, whereas the FRN effect did not remain once anxiety was controlled for. Anxiety has sometimes been associated with amplitudes of similar ERP components and is often correlated with shyness. Copyright © 2014 John Wiley & Sons, Ltd.
Dual‐polarization Raman spectral imaging to extract overlapping molecular fingerprints of living cells
Authors: Chiu Liang‐da , Palonpon Almar F. , Smith Nicholas I. , Kawata Satoshi , Sodeoka Mikiko , Fujita Katsumasa
Published: April 2014

Raman spectral imaging is gaining more and more attention in biological studies because of its label‐free characteristic. However, the discrimination of overlapping chemical contrasts has been a major challenge. In this study, we introduce an optical method to simultaneously obtain two orthogonally polarized Raman images from a single scan of the sample. We demonstrate how this technique can improve the quality and quantity of the hyperspectral Raman dataset and how the technique is expected to further extend the horizons of Raman spectral imaging in biological studies by providing more detailed chemical information.

The dual‐polarization Raman images of a HeLa cell.

magnified image

The dual‐polarization Raman images of a HeLa cell.
Lithium‐end‐capped polylactide thin films influence osteoblast progenitor cell differentiation and mineralization
Authors: Gomillion Cheryl T. , Lakhman Rubinder Kaur , Kasi Rajeswari M. , Weiss R. A. , Kuhn Liisa T. , Goldberg A. Jon
Published: April 2014

End‐capping by covalently binding functional groups to the ends of polymer chains offers potential advantages for tissue engineering scaffolds, but the ability of such polymers to influence cell behavior has not been studied. As a demonstration, polylactide (PLA) was end‐capped with lithium carboxylate ionic groups (hPLA13kLi) and evaluated. Thin films of the hPLA13kLi and PLA homopolymer were prepared with and without surface texturing. Murine osteoblast progenitor cells from collagen 1α1 transgenic reporter mice were used to assess cell attachment, proliferation, differentiation, and mineralization. Measurement of green fluorescent protein expressed by these cells and xylenol orange staining for mineral allowed quantitative analysis. The hPLA13kLi was biologically active, increasing initial cell attachment and enhancing differentiation, while reducing proliferation and strongly suppressing mineralization, relative to PLA. These effects of bound lithium ions (Li+) had not been previously reported, and were generally consistent with the literature on soluble additions of lithium. The surface texturing generated here did not influence cell behavior. These results demonstrate that end‐capping could be a useful approach in scaffold design, where a wide range of biologically active groups could be employed, while likely retaining the desirable characteristics associated with the unaltered homopolymer backbone. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 500–510, 2015.
Optimization of the activation and nucleation steps in the precipitation of a calcium phosphate primer layer on electrospun poly(ɛ‐caprolactone)
Authors: Luickx Nathalie , Van den Vreken Natasja , D'Oosterlinck Willem , Van der Schueren Lien , Declercq Heidi , De Clerck Karen , Cornelissen Maria , Verbeeck Ronald
Published: April 2014

The present study aimed to optimize the procedure for coating electrospun poly(ε‐caprolactone) (PCL) fibers with a calcium phosphate (CP) layer in order to improve their potential as bone tissue engineering scaffold. In particular, attention was paid to the reproducibility of the procedure, the morphology of the coating, and the preservation of the porous structure of the scaffold. Ethanol dipping followed by an ultrasonic assisted hydrolysis of the fiber surface with sodium hydroxide solution efficiently activated the surface. The resulting reactive groups served as nucleation points for CP precipitation, induced by alternate dipping of the samples in calcium and phosphate rich solutions. By controlling the deposition, a reproducible thin layer of CP was grown onto the fiber surface. The deposited CP was identified as calcium‐deficient apatite (CDHAp). Analysis of the cell viability, adhesion, and proliferation of MC3T3‐E1 cells on untreated and CDHAp coated PCL scaffolds showed that the CDHAp coating enhanced the cell response, as the number of attached cells was higher in comparison to the untreated PCL and cells on the CDHAp coated samples showed similar morphologies as the ones found in the positive control. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 511–524, 2015.
The cell‐engineered construct of cartilage on the basis of biopolymer hydrogel matrix and human adipose tissue‐derived mesenchymal stromal cells (in vitro study)
Authors: Surguchenko Valentina A. , Ponomareva Anna S. , Kirsanova Ljudmila A. , Skaleckij Nikolaj N. , Sevastianov Viktor I.
Published: April 2014

The study results ofin vitroformation of tissue‐engineered cartilage construct on the basis of cell‐engineered construct composed of biopolymer hydrogel matrix and human adipose tissue‐derived mesenchymal stromal cells (hADSCs) are presented. It was revealed that hADSCs in biopolymer hydrogel matrixSphero®GEL under chondrogenic conditions generate three‐dimensional structures and produce cartilaginous extracellular matrix components: collagen type II and glycosaminoglycans. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 463–470, 2015.
MiR‐124 Inhibits Myogenic Differentiation of Mesenchymal Stem Cells Via Targeting Dlx5
Authors: Qadir Abdul S. , Woo Kyung Mi , Ryoo Hyun‐Mo , Yi TacGhee , Song Sun U. , Baek Jeong‐Hwa
Published: April 2014

MicroRNAs (miRNAs), including miR‐1, miR‐133, and miR‐206, play a crucial role in muscle development by regulating muscle cell proliferation and differentiation. The aim of the present study was to define the effect of miR‐124 on myogenic differentiation of mesenchymal stem cells (MSCs). The expression level of miR‐124 in skeletal muscles was much lower than those in primary cultured bone marrow‐derived MSCs and the bone, fat and brain tissues obtained from C57BL/6 mice. Myogenic stimuli significantly decreased the expression levels of miR‐124 in mouse bone marrow‐derived MSCs and C2C12 cells. Forced expression of miR‐124 suppressed the expression of myogenic marker genes such as Myf5, Myod1, myogenin and myosin heavy chain and multinucleated myotube formation. Blockade of endogenous miR‐124 with a hairpin inhibitor enhanced myogenic marker gene expression and myotube formation. During myogenic differentiation of MSCs and C2C12 cells, the levels of Dlx5, a known target of miR‐124, were inversely regulated with those of miR‐124. Furthermore, overexpression of Dlx5 increased myogenic differentiation, whereas knockdown of Dlx5 using siRNA inhibited myogenesis in C2C12 cells. These results suggest that miR‐124 is a negative regulator of myogenic differentiation of MSCs and that upregulation of Dlx5 accompanied with downregulation of miR‐124 by myogenic stimuli is necessary for the proper progression of myogenic differentiation. J. Cell. Biochem. 115: 1572–1581, 2014. © 2014 Wiley Periodicals, Inc.