bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of alkaloids in onion nectar by micellar electrokinetic chromatography
Authors: Carolina Soto Verónica , Jofré Viviana Patricia , Galmarini Claudio Romulo , Silva María Fernanda
Published: March 2016

Nectar is the most important floral reward offered by plants to insects. Minor components such as alkaloid compounds in nectar affect bee foraging, with great influence in seed production. CE is an advantageous tool for the analysis of unexplored samples such as onion nectar due to the limited amounts of samples. Considering the importance of these compounds, a simultaneous determination of nicotine, theophylline, theobromine, caffeine, harmaline, piperine in onion nectar by MEKC‐UV is herein reported. The extraction of alkaloid compounds in nectar was performed by SPE using a homemade miniaturized column (C18). Effects of several important factors affecting extraction efficiency as well as electrophoretic performance were investigated to acquire optimum conditions. Under the proposed conditions, the analytes can be separated within 15 min in a 50 cm effective length capillary (75 μm id) at a separation voltage of 20 kV in 20 mmol/L sodium tretraborate, 100 mmol/L SDS. The amount of sample requirement was reduced up to 2000 times, when compared to traditional methods, reaching limits of detection as low as 0.0153 ng/L. For the first time, this study demonstrates that there are marked qualitative and quantitative differences in nectar alkaloids between open pollinated and male sterile lines (MSLs) and also within MSLs.
Understand how legislative updates affect student‐veterans
Authors: Sutton Halley
Published: March 2016

ANAHEIM, CALIF. — Stay on top of these legislative updates regarding student‐veterans to make sure that your campus is serving student‐veterans effectively while avoiding potentially costly fines or audits. In a session at the recent Pacific Association of Collegiate Registrars and Admissions Officers annual conference, Chryssa Jones, veterans services coordinator for the University of California, Riverside and public relations chair for the National Association of Veterans' Program Administrators, shared recent updates to legislation affecting student‐veterans on college and university campuses.
Time to change? Consider what your institution needs to do to thrive
Authors: Dennis Marguerite J.
Published: March 2016

If you are an enrollment manager, you may have your president or provost looking over your shoulder asking about THE NUMBERS! The May 1 deposit due date is not far off and your school is, in your opinion, too dependent on tuition‐paying domestic and international students.
Understand your community's needs to serve your students
Authors: Sutton Halley
Published: March 2016

Anna Behar‐Russell's background as a program developer for California State University‐Long Beach came in handy when she made the transition to marketing for the university. As a program designer, she worked to develop a certificate program on campus, among other programming, an experience that led her to discover what kind of training needs were not being met in the community. It was an experience that helped shape her philosophy as director of marketing, communications and outreach for the College of Continuing and Professional Education at CSULB.
Experimental and numerical simulation studies on diesel pool fire
Authors: Sahu Deepak , Kumar Shashi , Jain Shorab , Gupta Akhilesh
Published: March 2016

Experimental studies are performed under different ventilation conditions to investigate the effect of ventilation on compartment fires. A compartment of size 4 m × 4 m × 4 m having a door of size 2 m × 1 m is used for experiments. The experiments are conducted with full door open and half door open conditions. Diesel, used as a fuel source, is placed in a pan of 40 cm diameter and 15 cm height, which is kept in the center of the compartment. During experiments a constant 12 cm height of the fuel is maintained above the pan bottom. The maximum heat release rate is found to be 100 kW and 115 kW in full door open and half door open experiments respectively. It is observed that the size of door opening affected the heat release rate, burning rate and thermal environment inside the compartment after the growth period of 800 s. The numerical simulation is also performed for full door open experiment using CFD code, Fire Dynamics Simulator (FDS, version 6.0.1) developed by NIST. Simulation is accomplished with the refinement of mesh size near the fire source; results from FDS closely match with the experimental results. Copyright © 2016 John Wiley & Sons, Ltd.
Development of ZMYM2‐FGFR1 driven AML in human CD34+ cells in immunocompromised mice
Authors: Ren Mingqiang , Qin Haiyan , Wu Qing , Savage Natasha M. , George Tracy I. , Cowell John K.
Published: March 2016

Acute myelogenous leukemia (AML) has an overall poor survival rate and shows considerable molecular heterogeneity in its etiology. In the WHO classification there are >50 cytogenetic subgroups of AML, many showing highly specific chromosome translocations that lead to constitutive activation of individual kinases. In a rare stem cell leukemia/lymphoma syndrome, translocations involving 8p11 lead to constitutive activation of the fibroblast growth factor receptor 1 (FGFR1) kinase. This disorder shows myeloproliferative disease with almost invariable progresses to AML and conventional therapeutic strategies are largely unsuccessful. Because of the rare nature of this syndrome, models that faithfully recapitulate the human disease are needed to evaluate therapeutic strategies. The t(8;13)(p11;q12) chromosome translocation is most common rearrangement seen in this syndrome and creates a ZMYM2‐FGFR1 chimeric kinase. To understand more about the molecular etiology of AML induced by this particular rearrangement, we have created a model human CD34+ cells transplanted into immunocompromized mice which develop myeloproliferative disease that progresses to AML with a long (>12 months) latency period. As in humans, these mice show hepatospenomegaly, hypercellular bone marrow and a CD45 + CD34 + CD13+ immunophenotype. Molecular studies demonstrate upregulation of genes such as KLF4 and FLT3 that promote stemness, and overexpression of MYC, which is associated with suppression of myeloid cell differentiation. This murine model, therefore, provides an opportunity to develop therapeutic strategies against the most common subtype within these FGFR1 driven neoplasms and study the molecular etiology in more depth.
Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study
Authors: Thomsen Louise T. , Dehlendorff Christian , Junge Jette , Waldstrøm Marianne , Schledermann Doris , Frederiksen Kirsten , Kjaer Susanne K.
Published: March 2016

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC‐US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30–65 years with ASC‐US during 2005–2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV‐Proofer (n = 3,226) or for high‐risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n = 9,405) or Linear Array HPV‐Genotyping test (LA) (n = 1,533). Women with ≥1 subsequent examination in the register (n = 13,729) were followed for up to 9.5 years for high‐grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow‐up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8–89.6%] versus 59.3% [95% CI: 58.1–60.4%]) and higher positive predictive value (PPV) (38.2% [95% CI: 33.8%–43.1%] versus 19.5% [95% CI: 17.8–20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3–74.5%] versus 97.0% [95% CI: 95.5–98.4%]), and women testing mRNA negative had higher 3‐year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2–4.2%] versus 0.5% [95% CI: 0.3–0.7%]). Patterns were similar after 18 months and 5 years'; follow‐up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC‐US triage due to its low sensitivity and the substantial risk for precancer following a negative test.
Idiopathic Acquired Osteosclerosis in a Middle-Aged Woman With Systemic Lupus Erythematosus
Authors: Guañabens Núria , Mumm Steven , Gifre Laia , Ruiz-Gaspà Silvia , Demertzis Jennifer L , Stolina Marina , Novack Deborah V , Whyte Michael P
Published: March 2016

Widely distributed osteosclerosis is an unusual radiographic finding with multiple causes. A 42-year-old premenopausal Spanish woman gradually acquired dense bone diffusely affecting her axial skeleton and focally affecting her proximal long bones. Systemic lupus erythematosus (SLE) diagnosed in adolescence had been well controlled. She had not fractured or received antiresorptive therapy, and she was hepatitis C virus antibody negative. Family members had low bone mass. Lumbar spine bone mineral density (BMD) measured by dual-photon absorptiometry (DPA) at age 17 years, while receiving glucocorticoids, was 79% the average value of age-matched controls. From ages 30 to 37 years, dual-energy X-ray absorptiometry (DXA) BMD Z-scores steadily increased in her lumbar spine from +3.8 to +7.9, and in her femoral neck from –1.4 to –0.7. Serum calcium and phosphorus levels were consistently normal, 25-hydroxyvitamin D (25OHD) <20 ng/mL, and parathyroid hormone (PTH) sometimes slightly increased. Her reduced estimated glomerular filtration rate (eGFR) was 38 to 55 mL/min. Hypocalciuria likely reflected positive mineral balance. During increasing BMD, turnover markers (serum bone-specific alkaline phosphatase [ALP], procollagen type 1 N propeptide [P1NP], osteocalcin [OCN], and carboxy-terminal cross-linking telopeptide of type 1 collagen [CTx], and urinary amino-terminal cross-linking telopeptide of type 1 collagen [NTx and CTx]) were 1.6- to 2.8-fold above the reference limits. Those of bone formation seemed increased more than those of resorption. FGF-23 was slightly elevated, perhaps from kidney disease. Serum osteoprotegerin (OPG) and TGFβ1 levels were normal, but sclerostin (SOST) and receptor activator of nuclear factor kappa-B ligand (RANKL) were elevated. Serum multiplex biomarker profiling confirmed a high level of SOST and RANKL, whereas Dickkopf-1 (DKK-1) seemed low. Matrix metalloproteinases-3 (MMP-3) and -7 (MMP-7) were elevated. Iliac crest biopsy revealed tetracycline labels, no distinction between thick trabeculae and cortical bone, absence of peritrabecular fibrosis, few osteoclasts, and no mastocytosis. Then, for the past 3 years, BMD Z-scores steadily decreased. Skeletal fluorosis, mastocytosis, myelofibrosis, hepatitis C-associated osteosclerosis, multiple myeloma, and aberrant phosphate homeostasis did not explain her osteosclerosis. Mutation analysis of the LRP5, LRP4, SOST, and osteopetrosis genes was negative. Microarray showed no notable copy number variation. Perhaps her osteosclerosis reflected an interval of autoimmune-mediated resistance to SOST and/or RANKL. © 2016 American Society for Bone and Mineral Research.
The Effect of Age on the Pharmacokinetics of Udenafil in Healthy Subjects
Authors: Choi Hyang‐Ki , Jung Jin Ah , Shon Jihong , Bahng Mi Young , Cho Doo‐Yeoun , Yeo Chang Woo , Kim Eun‐Young , Shin Jae‐Gook
Published: March 2016

Udenafil, a cyclic guanosine monophosphate–specific phosphodiesterase type 5 inhibitor, has been developed to treat erectile dysfunction. We evaluated the effect of age on the pharmacokinetics and tolerability of udenafil. A single‐center, open‐label, parallel‐group phase 1 study was conducted in healthy adult subjects who took a single oral dose of udenafil (100 mg). The pharmacokinetics and tolerability of udenafil were compared between 12 healthy young men (21–27 years) and 12 healthy elderly men (65–78 years). Serial blood and urine samples were collected for up to 60 and 48 hours after dosing. The plasma concentrations of udenafil and its major metabolite, DA‐8164, were analyzed using a validated liquid chromatography‐tandem mass spectrometry method. The mean Cmax of udenafil tended to be slightly less (214.0 vs 292.8 μg/L) in the elderly compared with the young (GMR, 68.9; 95% CI, 48.9–97.1); however, the AUC did not differ between the groups (1858.8 vs 2100.6 μg·h/L; GMR, 84.6; 95% CI, 66.1–108.4). The mean t1/2 was prolonged by approximately 5 hours in the elderly (P < .05). The clearance and metabolic AUC ratio did not differ between the elderly and young. In terms of tolerability, all adverse events were mild, and all subjects recovered without additional therapy. The systemic exposure of elderly subjects to udenafil appears to be comparable to or slightly less than that of young healthy subjects. Based on our pharmacokinetic comparisons, udenafil dose adjustment is unlikely to be required in the elderly population.
Improving Leadership Skills in Physicians: A 6‐Month Retrospective Study
Authors: Fernandez Claudia S. P. , Noble Cheryl C. , Jensen Elizabeth T. , Chapin Janet
Published: March 2016

The complex medical environment of today calls for physicians to have an array of leadership skills in addition to a thorough knowledge of their specific practice areas. The American College of Obstetrics and Gynecologists (ACOG) Robert C. Cefalo National Leadership Institute is a 3.5‐day intensive leadership development course targeted to physician leaders. A group of 37 physicians completed the ACOG National Leadership Institute in spring of 2013. At course completion and 6‐month postcourse, participants were asked to complete a retrospective pre‐ and posttest of perceived skill levels in 10 targeted competency areas. Course completion and 6‐month postcourse scores indicated statistically significant improvements in scores on all 10 competency areas, which was supported by a Wilcoxon signed‐rank test of median score difference. Qualitative data gathered at the 6‐month postcourse survey provide examples of how participants had applied their skills. The data presented in the current study suggested that intensive, “short‐burst,” experiential leadership training is an effective approach for leadership skills development in physicians.
Transformational Instructor‐Leadership in Higher Education Teaching: A Meta‐Analytic Review and Research Agenda
Authors: Balwant Paul T.
Published: March 2016

Researchers have shown that transformational leadership is applicable to higher education teaching, that is, transformational instructor‐leadership. However, such research is fractionated across diverse fields. To address the fractionated literature, the purpose of the current study was to conduct a meta‐analytic review of transformational instructor‐leadership and to analyze research in which such leadership has been empirically associated with student outcomes. For the meta‐analysis, the Hunter–Schmidt approach was adopted, and thus, correlations were corrected for attenuation due to measurement error. The findings indicated that transformational instructor‐leadership was positively associated with students’ motivation, satisfaction, perceptions of instructor credibility, academic performance, affective learning, and cognitive learning. Moderator analyses revealed that culture, course delivery, instrument, and gender were all significant moderators of the relationship between transformational instructor‐leadership and specific student outcomes. The findings also showed that there were significant differences between the transformational leadership dimensions, thus supporting the notion that each dimension is conceptually distinct. The present meta‐analysis drew from varied disciplines in contributing the first integrative review on transformational instructor‐leadership. Future research needs to extend the literature with regard to context sensitivity, common method variance, causal conclusions, mechanisms, outcome measures, and control variables. Practically, higher education institutions should consider training transformational instructor‐leaders.
Quantification of renal steatosis in type II diabetes mellitus using dixon‐based MRI
Authors: Yokoo Takeshi , Clark Haley R. , Pedrosa Ivan , Yuan Qing , Dimitrov Ivan , Zhang Yue , Lingvay Ildiko , Beg Muhammad S. , Bobulescu I. Alexandru
Published: March 2016

Purpose

To evaluate renal lipid content in subjects with and without type II diabetes mellitus (DM2) using Dixon‐based magnetic resonance imaging (MRI).

Materials and Methods

This retrospective study was approved by the Institutional Review Board and compliant with the Health Insurance Portability and Accountability Act. Sixty‐nine adults with or without DM2 (n = 29, n = 40) underwent 3T MRI of the abdomen using 3D multiecho Dixon gradient‐echo acquisition and proton‐density fat fraction (FF) reconstruction. FF values were recorded within segmented regions of interest in the kidneys and liver. The FF measurement error was estimated from the within‐subject difference between the right and left kidneys using Bland–Altman analysis. Correlation between renal FF, hepatic FF, and body mass index (BMI) was evaluated. The association between renal FF and DM2 was evaluated by Wilcoxon rank sum test as well as by multivariate regression to correct for potential confounding effects of age, sex, BMI, creatinine, and hepatic FF. P < 0.05 was considered statistically significant.

Results

Per‐subject 95% limits of agreement of the renal FF measurement were [–3.26%, +3.22%]. BMI was significantly correlated with renal FF (r = 0.266, P = 0.027) and with liver FF (r = 0.344, P = 0.006). Correlation between renal and hepatic FF did not reach statistical significance (r = 0.215, P = 0.090). Median renal FF (±interquartile range) was 2.18% (±2.52%) in the DM2 cohort, significantly higher than 0.80% (±2.63%) in the non‐DM2 cohort (P < 0.001). After correcting for potential confounders, the relationship between DM2 and renal FF remained statistically significant (P = 0.005).

Conclusion

Renal lipid content can be measured noninvasively using Dixon‐based MRI and may be increased in subjects with DM2 compared to those without DM2. J. Magn. Reson. Imaging 2016;44:1312–1319.
High prevalence of clinically unsuspected dengue disease among children in Ribeirao Preto city, Brazil
Authors: Poloni Telma Regina , Dornas Fabio Pio , dos Santos Nilton Nascimento , Soares Adriana Moreira , Amarilla Alberto Anastacio , Alfonso Helda Liz , Trigueiro Sabrina , Lavrador Marco Aurélio Sicchiroli , Yamamoto Aparecida Yulie , Aquino Victor Hugo
Published: March 2016

The aim of this study was to analyze the characteristics of Dengue virus (DENV)‐infected children and the accuracy of dengue diagnosis based on clinical presentations. The inclusion criteria were children ≥1‐year‐old presenting febrile illness with 1–7 days of onset. Children (n = 110) aged 2–15 years were included in this study. DENV infection was confirmed with virological tests using serum, salvia, and/or urine samples. The attending pediatricians classified 56/110 (50.91%) of the children as suspected dengue cases. The DENV infection was confirmed by specific laboratory tests in 52/56 (92.9%) of the suspected dengue cases but also in 44/54 (81.5%) of the unsuspected dengue cases; total of 96/110 (87.27%) confirmed dengue cases. The clinical diagnosis gave an overall sensitivity of 54.2% (52/96) and a specificity of 71.4% (10/14). The positive predictive value of the clinical diagnosis was 92.8% and negative predictive value was 18.5%. After the third day of onset of symptoms, the DENV genome detection rate was similar in serum and saliva samples, suggesting that saliva samples represent an alternative to blood samples for early dengue diagnosis. Vaccination against Yellow fever virus did not influence the antibody response against DENV‐1, DENV‐2, and DENV‐3, which circulated during the study period. Although the signs and symptoms were compatible with dengue, the attending pediatricians did not suspect the disease in several children. Therefore, the inclusion of virological tests for early diagnosis in the protocols for dengue surveillance would help in the implementation of prompt treatment of patients and epidemic containment strategies. J. Med. Virol. 88:1711–1719, 2016. © 2016 Wiley Periodicals, Inc.
Investigation of the chemical enhancement contribution to SERS using a Kretschmann arrangement
Authors: Mohaghegh Faezeh , Mazaheri Tehrani Alireza , Materny Arnulf
Published: March 2016

Using a Kretschmann configuration‐based setup, surface‐enhanced Raman scattering (SERS) experiments have been performed on a monolayer of Nile blue. The experiment has been optimized to achieve reproducible conditions. Laser excitation resulted in a fast decay of the Raman line intensities ending at a stable signal level. We have analyzed this intensity variation mode specifically. The Raman deactivation rate was found to be different for different vibrational modes where high‐wavenumber vibrations showed slower decay than the group of low‐wavenumber modes. SERS spectra were obtained excluding the contribution of this deactivation process for different angles of incidence of the exciting laser beam. The variation of the surface plasmon excitation in the thin silver film coated onto the prism surface of the Kretschmann configuration resulted in drastically different relative enhancements of the different Raman modes pointing to a major contribution of the chemical enhancement mechanism in the single‐layer SERS experiment. The enhancement was found to be mode‐specific. High‐wavenumber modes showed a stronger enhancement than the low‐wavenumber group. Copyright © 2016 John Wiley & Sons, Ltd.
Field‐based experimental water footprint study of sunflower growth in a semi‐arid region of China
Authors: Qin Lijie , Jin Yinghua , Duan Peili , He Hongshi
Published: March 2016

BACKGROUND

Field‐scale changes in the water footprint during crop growth play an important role in formulating sustainable water utilisation strategies. This study aimed to explore field‐scale variation in the water footprint of growing sunflowers in the western Jilin Province, China, during a 3‐year field experiment. The goals of this study were to (1) determine the components of the ‘blue’ and ‘green’ water footprints for sunflowers sown with water, and (2) analyse variations in water footprints and soil water balance under different combinations of temperature and precipitation. Specific actions could be adopted to maintain sustainable agricultural water utilisation in the semi‐arid region based on this study.

RESULTS

The green, blue, and grey water footprints accounted for 93.7–94.7%, 0.4–0.5%, and 4.9–5.8%, respectively, of the water footprint of growing sunflowers. The green water footprint for effective precipitation during the growing season accounted for 58.8% in a normal drought year but 48.2% in an extreme drought year. When the effective precipitation during the growing season could not meet the green water use, a moisture deficit arose. This increase in the moisture deficit can have a significant impact on soil water balance.

CONCLUSION

Green water was the primary water source for sunflower growth in the study area, where a scarcity of irrigation water during sunflower growth damaged the soil water balance, particularly in years with continuous drought. The combination of temperature and precipitation effected the growing environment, leading to differences in yield and water footprint. The field experiments in this area may benefit from further water footprint studies at the global, national and regional scale. © 2016 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Evaluation of alternative sorbents for dispersive solid‐phase extraction clean‐up in the QuEChERS method for the determination of pesticide residues in rice by liquid chromatography with tandem mass spectrometry
Authors: Cabrera Liziara da C. , Caldas Sergiane S. , Prestes Osmar D. , Primel Ednei G. , Zanella Renato
Published: March 2016

Many compounds are used for pest control during the production and storage of rice, making it necessary to employ multiclass methods for pesticide residues determination. For this purpose, QuEChERS‐based methods are very efficient, fast and accurate, and improvements in the clean‐up step are important, especially for complex matrices, like cereals. In this work, different sorbents such as chitosan, florisil®, alumina, diatomaceous earth, graphitized carbon black, besides the commonly used primary secondary amine and octadecylsilane, were evaluated for dispersive solid‐phase extraction clean‐up in acetate‐buffered QuEChERS method for the determination of residues of 20 representative pesticides and one metabolite in rice by liquid chromatography coupled to tandem mass spectrometry. The sorbent C18 presented the best results, however, chitosan showed similar results, and the best performance among the unconventional sorbents evaluated. The method limit of quantification, attending accuracy (70–120% recovery) and precision (RSD ≤20%) criteria, ranged from 5 to 20 μg/kg. Results showed that chitosan is an effective alternative to reduce analysis costs, maintaining the method reliability and accuracy.
CRISPR1 analysis of naturalized surface water and fecal Escherichia coli suggests common origin
Authors: Tymensen Lisa D.
Published: March 2016

Clustered regularly interspaced short palindromic repeats (CRISPRs) are part of an acquired bacterial immune system that functions as a barrier to exogenous genetic elements. Since naturalized Escherichia coli are likely to encounter different genetic elements in aquatic environments compared to enteric strains, we hypothesized that such differences would be reflected within the hypervariable CRISPR alleles of these two populations. Comparison of CRISPR1 alleles from naturalized and fecal phylogroup B1 E. coli strains revealed that the alleles could be categorized into four major distinct groups (designated G6–G9), and all four allele groups were found among naturalized strains and fecal strains. The distribution of CRIPSR G6 and G8 alleles was similar among strains of both ecotypes, while naturalized strains tended to have CRISPR G7 alleles rather than G9 alleles. Since CRISPR G7 alleles were not specific to naturalized strains, they, however, would not be useful as a marker for identifying naturalized strains. Notably, CRISPR alleles from naturalized and fecal strains also had similar spacer repertoires. This indicates a shared history of encounter with mobile genetic elements and suggests that the two populations were derived from common ancestors.
Antiplatelet activity of chrysin via inhibiting platelet αIIbβ3‐mediated signaling pathway
Authors: Liu Gang , Xie Wen , He Ao‐Di , Da Xing‐Wen , Liang Ming‐Lu , Yao Guang‐qiang , Xiang Ji‐Zhou , Gao Cun‐ji , Ming Zhang‐Yin
Published: March 2016

Scope

Propolis is thought to help prevent thrombotic and related cardiovascular diseases in humans. Chrysin, a bioflavonoids compound found in high levels in propolis and in honey, has been reported to possess antiplatelet activity. However, the mechanism by which it inhibits platelet function is unclear.

Methods and results

The effects of chrysin on agonist‐activated platelet‐aggregation, granule‐secretion, and integrin αIIbβ3 activation were examined. Its effects on the phosphorylation of Akt, GSK3β, MAPKs, and several proteins of the glycoprotein VI (GPVI) signaling pathway were also studied on collaged‐activated platelets. In addition, human platelet spreading on immobilized fibrinogen was also tested. We found that chrysin dose dependently inhibited platelet aggregation and granule secretion induced by collagen, as well as platelet aggregation induced by ADP, thrombin, and U46619. Chrysin also markedly reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen. Biochemical analysis revealed that chrysin inhibited collagen‐induced activation of Syk, PLCγ2, PKC, as well as the phosphorylation of Akt and ERK1/2. Additionally, chrysin attenuated phosphorylation of molecules such as FcγRIIa, FAK, Akt, and GSK3β in platelet spreading on immobilized fibrinogen.

Conclusions

Our findings indicate that chrysin suppresses not only integrin αIIbβ3‐mediated “inside‐out” signaling, but also the “outside‐in” signal transmission. This implies that chrysin may represent a potential candidate for an antiplatelet agent.
Combined high‐fat‐resveratrol diet and RIP140 knockout mice reveal a novel relationship between elevated bone mitochondrial content and compromised bone microarchitecture, bone mineral mass, and bone strength in the tibia
Authors: Miotto Paula M. , Frendo‐Cumbo Scott , Sacco Sandra M. , Wright David C. , Ward Wendy E. , Holloway Graham P.
Published: March 2016

Scope

While resveratrol (RSV) is associated with the prevention of high‐fat (HF) diet‐induced insulin resistance, the effects on bone health combined with an HF‐diet is unknown. Therefore, we determined the effect of RSV on bone microarchitecture in the presence of an HF‐diet, while also elucidating molecular adaptations within bone that could contribute to bone health status.

Methods and results

Male C57BL6 mice were provided control (10% fat) or HF‐diet (60% fat) in the presence or absence of RSV for 12 weeks. While RSV prevented HF diet‐induced glucose intolerance, HF‐RSV compromised tibial microarchitecture, mineral mass, and strength. The compromised outcomes following HF‐RSV corresponded with higher markers of osteoclast‐activation and bone‐resorption (decreased OPG/RANKL ratio; increased cathepsin K), as well as higher markers of tibial mitochondrial content. A molecular model of elevated mitochondrial content (RIP140 knock out (KO) mice) was utilized to determine proof‐of‐principle that increasing mitochondrial content coincides with decrements in bone health. RIP140 KO mice displayed higher markers of mitochondrial content, and similar to HF‐RSV, had compromised bone microarchitecture, lower BMD/strength, and higher markers of osteoclast‐activation/bone‐resorption.

Conclusion

These data show that in the presence of an HF‐diet, RSV negatively alters bone health, a process associated with increased mitochondrial content and markers of bone resorption.
Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention
Authors: Matualatupauw Juri C. , Radonjic Marijana , van de Rest Ondine , de Groot Lisette C. P. G. M. , Geleijnse Johanna M. , Müller Michael , Afman Lydia A.
Published: March 2016

Scope

People who carry the apolipoprotein E4 (APOE4) single nucleotide polymorphism have an increased risk of cardiovascular disease (CVD). Fish‐oil supplementation may help in the prevention of CVD, though interindividual differences in the response to n‐3 PUFAs have been observed. We aimed to assess the impact of APOE genotype on peripheral blood mononuclear cell whole genome gene expression at baseline and following a fish‐oil intervention.

Methods and results

Participants received 6 months of fish‐oil supplementation containing 1800 mg of eicosapentaenoic acid and docosahexaenoic acid per day. APOE genotype and peripheral blood mononuclear cell whole genome gene expression before and after supplementation were measured. We characterized the differences in gene expression profiles in carriers of APOE4 (N = 8) compared to noncarriers (N = 15). At baseline, 1320 genes were differentially expressed and the fish‐oil supplementation differentially regulated 866 genes between APOE4 carriers and noncarriers. Gene set enrichment analysis showed that carriers had a higher gene expression of cholesterol biosynthesis and IFN signaling pathways. Fish‐oil supplementation reduced expression of IFN‐related genes in carriers only.

Conclusion

The increased expression of IFN signaling and cholesterol biosynthesis pathways might explain part of the association between APOE4 and CVD. Fish‐oil supplementation may particularly benefit APOE4 carriers by decreasing expression of IFN‐related genes.
Induction of cell cycle arrest and apoptosis with downregulation of Hsp90 client proteins and histone modification by 4β‐hydroxywithanolide E isolated fromPhysalis peruviana
Authors: Park Eun‐Jung , Sang‐Ngern Mayuramas , Chang Leng Chee , Pezzuto John M.
Published: March 2016

Scope

Physalis peruviana(Solanaceae) is used for culinary and medicinal purposes. We currently report withanolides, isolated fromP. peruviana, inhibit the growth of colon cancer monolayer and spheroid cultures. A detailed mechanistic evaluation was performed with 4β‐hydroxywithanolide E (4HWE).

Methods and results

Treatment of HT‐29 cells with low concentrations of 4HWE inhibited growth while enhancing levels of p21Waf1/Cip1and reducing levels of several cell cycle‐related proteins. Apoptosis was induced at higher concentrations. In addition, 4HWE treatment downregulated the levels of Hsp90 client proteins. Nuclear sirtuin 1 (SIRT1) was increased and histone H3 acetylated at lysine 9 was decreased. An additional consequence of SIRT1 elevation in the nucleus may be inhibition of c‐Jun activity. The expression of 21 genes was altered, including downregulation ofPTGS2, and this correlated with reduced protein levels of cyclooxygenase‐2 (COX‐2). Overall, efficacious induction of G0/G1 cell cycle arrest at low concentrations, and induction of apoptosis at higher concentrations are interesting 4HWE‐mediated phenomena that are accompanied by a complex array of molecular events.

Conclusion

Considering the worldwide prevalence of colon cancer, and the unique mode of action mediated by 4HWE, it is reasonable to investigate additional mechanistic details and the potential utility of this compound.
Soy isoflavones and glucose metabolism in menopausal women: A systematic review and meta‐analysis of randomized controlled trials
Authors: Fang Ke , Dong Hui , Wang Dingkun , Gong Jing , Huang Wenya , Lu Fuer
Published: March 2016

Scope

The aim of this meta‐analysis was to investigate whether soy isoflavones, a type of phytoestrogen, would affect glucose homeostasis in menopausal women.

Methods and results

Studies concerning about the relationship between soy isoflavone treatment and glucose metabolism were searched on MEDLINE and WEB OF SCIENCE (updated through April 2015) and EMBASE (1990–April 2015). Seventeen randomized controlled trials (RCTs) with a total number of 1529 menopausal women were identified for meta‐analysis. Soy isoflavones were found to show great significance for the improvement of glucose metabolism, though marked heterogeneity was found between studies. The overall results showed that the average difference in fasting blood glucose values between women assigned to soy isoflavones and women in placebo groups was −0.22 mmol/L (95% CI: −0.38 to −0.07 mmol/L) under a random‐effects model. In addition, the effect of soy isoflavones on insulin was also significant: −0.43 μIU/mL (95% CI: −0.71 to −0.14 μIU/mL), as was the effect on homeostasis model assessment insulin resistance (HOMA‐IR): −0.52 (95% CI: −0.76 to −0.28).

Conclusion

Although the results displayed a significant tendency in favor of soy isoflavones, it appears that genistein alone played an important role in improving glucose metabolism due to its low heterogeneity.
Glutamine promotes intestinal SIgA secretion through intestinal microbiota and IL‐13
Authors: Wu Miaomiao , Xiao Hao , Liu Gang , Chen Shuai , Tan Bie , Ren Wenkai , Bazer Fuller W. , Wu Guoyao , Yin Yulong
Published: March 2016

Scope

Glutamine supplementation enhances secretory IgA (SIgA) production in the intestine, but the mechanism is largely unknown. We examined this issue using a mouse model.

Methods and Results

In mouse model, glutamine supplementation increased both SIgA abundance in intestinal luminal contents and IgA+ plasma cell numbers in the mouse ileum, and decreased bacterial loads in mouse mesenteric lymph nodes. Glutamine supplementation increased mouse ileal expression of cytokines associated with T cell‐dependent and T cell‐independent pathways of SIgA induction, including IL‐5, IL‐6, IL‐13, transforming growth factor (TGF‐β), a proliferation‐inducing ligand (APRIL), B cell‐activating factor (BAFF), vasoactive intestinal peptide (VIP) receptor, and retinal dehydrogenases. Injecting an IL‐13 antibody during glutamine supplementation reduced J‐chain expression in the mouse ileum. Glutamine supplementation increased bacterial invasion into the mouse ileal wall, while disrupting the mouse intestinal microbiota abrogated the influence of glutamine supplementation on SIgA secretion.

Conclusion

Glutamine supplementation appears to enhance SIgA secretion in the mouse intestine through the intestinal microbiota and subsequently through T cell‐dependent and T cell‐independent pathways.
Performance Standards and Employee Effort: Evidence From Teacher Absences
Authors: Gershenson Seth
Published: March 2016

The 2001 No Child Left Behind Act (NCLB) increased accountability pressure in U.S. public schools by threatening to impose sanctions on Title‐1 schools that failed to make adequate yearly progress (AYP) in consecutive years. Difference‐in‐difference estimates of the effect of failing AYP in the first year of NCLB on teacher effort in the subsequent year suggest that on average, teacher absences in North Carolina fell by about 10 percent. The probability of being frequently absent similarly decreased. These reductions in teacher absences were driven by within‐teacher increases in effort and by teachers in the bottom half of the effectiveness distribution. On average, only a modest amount of the achievement gains attributable to the increased accountability pressure are explained by the corresponding decline in teacher absences.
High dielectric and actuated properties of silicone dielectric elastomers filled with magnesium‐doped calcium copper titanate particles
Authors: Duan Lei , Wang Gen Lin , Zhang Yi Yang , Zhang Ya Nan , Wei Yuan Yuan , Wang Zhi Feng , Zhang Ming
Published: March 2016

In this paper, magnesium‐doped calcium copper titanate (M‐CCTO) submicron particles, which had high dielectric constant by a broadband dielectric analyzer, were successfully designed and prepared by the coprecipitation method. Then, the silicone elastomer filled with M‐CCTO particles had high dielectric constant, low dielectric loss, and actuated strain which was greatly improved in low electric field. Compared with CCTO/commercial polydimethyl siloxane (PDMS) composites, M‐CCTO/PDMS composites with 2 wt% content exhibited higher actuated strain, which increased 41.6% in a low electric field of 10 V/μm. It is found that the Mg doping enhanced the change in actuated strain approximately to 2 times in pure silicone elastomer, as well. Our work provided a simple, low‐cost and effective method to prepare high performance dielectric elastomers (DEs), which facilitated the wide application of DEs composites, especially in the biological and medical fields such as biosensors, artificial muscles, and prosthetics. POLYM. COMPOS., 39:691–697, 2018. © 2016 Society of Plastics Engineers
Application of cancer‐associated glycoforms and glycan‐binding probes to an in vitro diagnostic multivariate index assay for precise diagnoses of cancer
Authors: Kang Jeong Gu , Ko Jeong‐Heon , Kim Yong‐Sam
Published: March 2016

Personalized medicine has emerged as a widely accepted trend in medicine for the efficacious and safe treatment of various diseases. It covers every medical treatment tailored according to various properties of individuals. Cancer‐associated glycosylation mirrors cancer states more precisely, and this “sweet side of cancer” is thus intended to spur the development of an advanced in vitro diagnostic system. The changes of glyco‐codes are often subtle and thus not easy to trace, thereby making it difficult to discriminate changes from various compounding factors. Special glycan‐binding probes, often lectins, can be paired with aglycosylated antibodies to enable quantitative and qualitative measurements of glycoforms. With the in vitro diagnosis multivariate index assay (IVDMIA) considered to be capable of yielding patient‐specific results, the combinatorial use of multiple glycoproteins may be a good modality to ensure disease‐specific, personalized diagnoses.
The nocebo effect of drugs
Authors: Planès Sara , Villier Céline , Mallaret Michel
Published: March 2016

While the placebo effect has been studied for a long time, much less is known about its negative counterpart, named the nocebo effect. However, it may be of particular importance because of its impact on the treatment outcomes and public health. We conducted a review on the nocebo effect using PubMed and other databases up to July 2014. The nocebo effect refers by definition to the induction or the worsening of symptoms induced by sham or active therapies. Examples are numerous and concerns both clinical trials and daily practice. The underlying mechanisms are, on one hand, psychological (conditioning and negative expectations) and, on the other hand, neurobiological (role of cholecystokinin, endogenous opioids and dopamine). Nocebo effects can modulate the outcome of a given therapy in a negative way, as do placebo effects in a positive way. The verbal and nonverbal communications of physicians contain numerous unintentional negative suggestions that may trigger a nocebo response. This raises the important issue of how physicians can at the same time obtain informed consent and minimize nocebo‐related risks. Every physician has to deal with this apparent contradiction between primum non nocere and to deliver truthful information about risks. Meticulous identification of patients at risk, information techniques such as positive framing, contextualized informed consent, and even noninformation, is valuable.
An efficient solid‐phase synthesis of peptidyl‐N‐acetylguanidines for use in native chemical ligation
Authors: Okamoto Ryo , Isoe Madoka , Izumi Masayuki , Kajihara Yasuhiro
Published: March 2016

In the modern protocols of chemical protein syntheses, peptide‐α‐thioesters have been used as key components for the assembly of full‐length polypeptides through chemoselective peptide coupling reactions. A variety of thioester precursors have been developed for the synthesis of the peptide‐α‐thioesters by Fmoc solid phase peptide synthesis (Fmoc‐SPPS). Recently our group found a peptidyl‐N‐acetylguanidine as a new peptide‐α‐thioester precursor. This peptide derivative can be converted into a corresponding peptide‐α‐thioester only by treatment with an excess amount of a thiol in aqueous buffers at around neutral pH. This unique property allowed us to envision the practical use of the peptidyl‐N‐acetylguanidines for the chemical syntheses of proteins; however, an efficient synthetic method has been lacking. Herein, we report an efficient solid‐phase synthesis of peptidyl‐N‐acetylguanidines. This new synthetic method employing selective activation and cleavage of a peptide bond successfully provided peptidyl‐N‐acetylguanidines from the on‐resin protected peptides prepared by standard Fmoc‐SPPS. We also evaluated the reactivity of a peptidyl‐N‐acetylguanidine in native chemical ligation through the synthesis of glucose‐dependent insulinotropic polypeptide analogue. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Low leakage stoichiometric SrTiO3 dielectric for advanced metal–insulator–metal capacitors
Authors: Popovici Mihaela , Kaczer Ben , Afanas'ev Valeri V. , Sereni Gabriele , Larcher Luca , Redolfi Augusto , Elshocht Sven Van , Jurczak Malgorzata
Published: March 2016

Metal–insulator–metal capacitors (MIMCAP) with stoichiometric SrTiO3 dielectric were deposited stacking two strontium titanate (STO) layers, followed by intermixing the grain determining Sr‐rich STO seed layer, with the Ti‐rich STO top layer. The resulted stoichiometric SrTiO3 would have a structure with less defects as demonstrated by internal photoemission experiments. Consequently, the leakage current density is lower compared to Sr‐rich STO which allow further equivalent oxide thickness downscaling.

Schematic of MIMCAP with stoichiometric STO dielectric formed from bottom Sr‐rich STO and top Ti‐rich STO after intermixing during crystallization anneal.

magnified image

Schematic of MIMCAP with stoichiometric STO dielectric formed from bottom Sr‐rich STO and top Ti‐rich STO after intermixing during crystallization anneal.

(© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Statistical Modelling of Wear and Damage Trajectories of Railway Wheelsets
Authors: Andrade Antonio Ramos , Stow Julian
Published: March 2016

This paper discusses the use of linear mixed models and generalized linear mixed models to predict the wear and damage trajectories of railway wheelsets for a fleet of modern multiple unit trains. The wear trajectory is described by the evolution of the wheel flange thickness, the flange height and the tread diameter, whereas the damage trajectory is assessed through the probabilities of various types of wheel tread damage such as rolling contact fatigue, wheel flats and cavities occurring. Different model specifications are compared based on an information criterion. Copyright © 2016 John Wiley & Sons, Ltd.
Firm‐specific human capital investments as a signal of general value: Revisiting assumptions about human capital and how it is managed
Authors: Morris Shad S. , Alvarez Sharon A. , Barney Jay B. , Molloy Janice C.
Published: March 2016

Research summary: Prior scholarship has assumed that firm‐specific and general human capital can be analyzed separately. This article argues that, in some settings, this is not the case because prior firm‐specific human capital investments can be a market signal of an individual's willingness and ability to make such investments in the future. As such, the willingness and ability to make firm‐specific investments is a type of general human capital that links firm‐specific and general human capital in important ways. The article develops theory about these investments, market signals, and value appropriation. Then, the article examines implications for human resource management and several important questions in the field of strategic management, including theories of the firm and microfoundations of competitive advantage.

Managerial summary: While managers don't often use the terms firm‐specific and general skills, they certainly recognize that investments employees make in their skill sets are more or less relevant to a specific firm. For instance, investing in specific relationships within a firm or learning a firm's proprietary software would be considered firm‐specific investments. While such skills may seem relevant only to the particular firm in which they were invested, these investments may also send valuable signals to competing firms that such employees are willing and able to make similar investments elsewhere. Hence, managers should be interested in determining if a potential hire has made prior firm‐specific investments to help them know whether that person might be likely to make such investments in his or her future place of employment. Copyright © 2016 John Wiley & Sons, Ltd.