bluuebunny/crossref_metadata_2025 huggingface dataset:
Dehydration among lactating mothers in the Amazon: A neglected problem
Authors: Rosinger Asher
Published: December 2014

Objectives

The purpose of this study was to compare hydration status between lactating and non‐lactating women in the hot‐humid Amazon.

Methods

Fifty‐four women (15–81 years) from two villages at different distances to the market provided urine samples, anthropometric measurements, and health recalls. Urine samples were analyzed for urine specific gravity (USG). Bivariate and multiple linear and logistic regressions tested differences in USG and dehydration (USG > 1.020) between women of different lactating status.

Results

Lactating women (1.024 g/ml; 78% dehydrated) had significantly higher USG levels (β = 0.004; P = 0.011) than non‐lactating women (1.020 g/ml; 50% dehydrated) and were significantly more likely to be dehydrated adjusting for covariates (OR: 4.05; 95% CI 1.1–14.7).

Conclusions

Women living in hot‐humid rural environments with minimal access to clean water are at greater risk of dehydration when breastfeeding. Future research should examine lactating women longitudinally and assess whether chronic dehydration affects breast milk composition. Am. J. Hum. Biol. 27:576–578, 2015. © 2014 Wiley Periodicals, Inc.
Silver‐Catalyzed Arylation of (Hetero)arenes by Oxidative Decarboxylation of Aromatic Carboxylic Acids
Authors: Kan Jian , Huang Shijun , Lin Jin , Zhang Min , Su Weiping
Published: December 2014

A long‐standing challenge in Minisci reactions is achieving the arylation of heteroarenes by oxidative decarboxylation of aromatic carboxylic acids. To address this challenge, the silver‐catalyzed intermolecular Minisci reaction of aromatic carboxylic acids was developed. With an inexpensive silver salt as a catalyst, this new reaction enables a variety of aromatic carboxylic acids to undergo decarboxylative coupling with electron‐deficient arenes or heteroarenes regardless of the position of the substituents on the aromatic carboxylic acid, thus eliminating the need for ortho‐substituted aromatic carboxylic acids, which were a limitation of previously reported methods.
Crystalline Stereocomplexed Polycarbonates: Hydrogen‐Bond‐Driven Interlocked Orderly Assembly of the Opposite Enantiomers
Authors: Liu Ye , Ren Wei‐Min , Wang Meng , Liu Chuang , Lu Xiao‐Bing
Published: December 2014

Four novel crystalline stereocomplexed polymers are formed by mixing isotactic (R)‐ and (S)‐polycarbonates in 1:1 mass ratio. They show the enhanced thermal stability and new crystalline behavior, significantly distinct from the component enantiomer. Two stereocomplexed CO2‐based polycarbonates from meso‐3,4‐epoxytetrahydrofuran and 4,4‐dimethyl‐3,5,8‐trioxabicyclo[5.1.0]octane have high melting temperatures of up to 300 °C, about 30 °C higher than the individual enantiomers. Isotactic (R)‐ or (S)‐poly(cyclopentene carbonate) and poly(cis‐2,3‐butene carbonate) are typical amorphous polymeric materials, however, upon mixing both enantiomers together, a strong interlocked interaction between polymer chains of opposite configuration occurs, affording the crystalline stereocomplexes with melting temperatures of about 200 °C and 180 °C, respectively. A DFT study suggests that the driving force forming the stereocomplex is the hydrogen‐bonding between carbonate units of the opposite enantiomers.
CLONING, EXPRESSION, AND CHARACTERIZATION OF PROPHENOLOXIDASE FROMAntheraea pernyi
Authors: Lu Wang Xia , Yue Du , Hai Zhang Jing , Daihua Wen , Yi Zhao Ming , Fu Wu Chun , Rong Zhang
Published: December 2014

Prophenoloxidase (PPO) is an essential enzyme in insect innate immunity because of its role in humoral defense. In this study, we have cloned a full‐length cDNA ofAntheraea pernyiprophenoloxidase (ApPPO) with an open‐reading frame encoding 683 amino acids, and the deduced amino acid sequence of ApPPO exhibited a high similarity with those of lepidoptera. The expression of ApPPO was inducible so that the mRNA level was significantly upregulated in the microbial challenged tissues, including fat body, hemocytes, and midgut. To better investigate the enzymatic and immunological properties of ApPPO, recombinant ApPPO (rApPPO) was produced inEscherichia coli. Several functional verification experiments were performed after studying the enzymatic properties. It was found that rApPPO could be stimulated by the microbial challenged larvae hemolymph and then killed bacteria in the radial diffusion assay. Furthermore, rApPPO also induced the transcription of cecropins after injected into the larvae 24 h later.
Gradiometer and Ground‐penetrating Radar Survey of Two Reducción Settlements in the Zaña Valley, Peru
Authors: Vanvalkenburgh Parker , Walker Chester P. , Sturm Jennie O.
Published: December 2014

In this study, we utilize ground‐penetrating radar and gradiometer survey to map buried architecture and investigate the political dimensions of the built environment at two Spanish colonial period archaeological sites in Peru's north coast region, Carrizales (C123) and Mocupe Viejo (74). Based on historical sources, we argue that both sites were founded during the Toledan reducción movement – a large‐scale attempt by Peru's viceregal government to forcibly resettle indigenous populations into planned towns in the 1570s ce. Coupled with excavations, geophysical survey has revealed diversity in how these planned towns were constructed. At Carrizales, domestic architectural features revealed through gradiometer survey and confirmed through excavations suggest that the town's layout broadly conformed to the prescriptions of reducción plans, centring on a large plaza and following a rectilinear layout. Ground‐penetrating radar results at the site were limited by high soil salinity. In contrast, at Mocupe Viejo, ground‐penetrating radar, gradiometer survey, and excavations have recovered no evidence of a gridded street plan, and demonstrate that the church was located in an idiosyncratic position. Together, these results suggest that the resettlement process was contested and that plans were modified to serve more proximate political, ecclesiastical, and practical concerns, illustrating the limited reach of colonial state power in the sixteenth century. Copyright © 2014 John Wiley & Sons, Ltd.
Sex differences in bladder cancer pathology and survival: analysis of a population‐based cancer registry
Authors: Zaitsu Masayoshi , Toyokawa Satoshi , Tonooka Akiko , Nakamura Fumiaki , Takeuchi Takumi , Homma Yukio , Kobayashi Yasuki
Published: December 2014

Sex differences in bladder cancer pathology and epidemiology have been the focus of recent research. We investigated the epidemiological characteristics and compared bladder cancer pathology and survival between men and women in Japan. A total of 13,184 patients with primary bladder cancer diagnosed from 1954 to 2010 were identified in a large‐scale cancer registry database in Kanagawa Prefecture. Using this database, we compared the odds ratios (ORs) for nonurothelial carcinoma (non‐UC) using a multiple logistic regression model adjusted for age and diagnosis periods. We also compared hazard ratios (HRs) for overall death and cancer‐specific death using a Cox proportional hazards model adjusted for non‐UC, age, and diagnosis period. The proportion of non‐UC was significantly higher in female compared with male patients (OR = 2.14, 95% confidence interval [CI]: 1.81–2.52). Furthermore, survival was significantly poorer in female patients than in male patients after adjusting for UC or non‐UC (HR for overall death = 1.15, 95% CI: 1.06–1.23; HR for cancer‐specific death = 1.39, 95% CI: 1.28–1.52). Sex differences exist in the epidemiological characteristics of bladder cancer in Japan, with female patients having less favorable pathology and poorer survival compared with male patients.
Nucleos(t)ide analogues associated with a reduced risk of hepatocellular carcinoma in hepatitis B patients: A population‐based cohort study
Authors: Wang Jack P. , Kao Feng‐Yu , Wu Chen‐Yi , Hung Yi‐Ping , Chao Yee , Chou Yiing‐Jenq , Li Chung‐Pin
Published: December 2014

BACKGROUND

Hepatocellular carcinoma (HCC) is a major complication of hepatitis B virus (HBV) infection. This study investigated the association between nucleos(t)ide analogue (NA) use and the risk of HCC and mortality in HBV carriers on the basis of the Taiwan National Health Insurance Database.

METHODS

In all, 1544 HBV carriers taking NAs (treated cohort) who were identified between October 1, 2003 and December 31, 2011 were examined for their risk of HCC and mortality; 1544 patients not receiving NA treatment (untreated cohort) were selected via propensity score matching as the comparison group. The risks of first tumor occurrence and mortality were compared.

RESULTS

The treated cohort had a significantly lower HCC occurrence rate (6.0%; 95% confidence interval [CI], 4.4%‐7.9%) in comparison with the untreated cohort (8.5%; 95% CI, 6.6%‐10.6%; P = .0025). The overall mortality rates for the treated and untreated cohorts were 6.9% (95% CI, 5.3%‐8.7%) and 9.4% (95% CI, 7.7%‐11.3%), respectively (P = .0003). After adjustments for competing confounders, Cox regression analyses showed that NA use significantly reduced the risk of HCC (hazard ratio [HR], 0.64; 95% CI, 0.45‐0.93; P = .017) and overall mortality (HR, 0.58; 95% CI, 0.43‐0.79; P < .001). There was a dose‐response relationship between NA use and the risk of HCC in the treated cohort. With respect to no NA use, the adjusted HRs were 0.93 (95% CI, 0.58‐1.48), 0.67 (95% CI, 0.42‐1.06), and 0.35 (95% CI, 0.17‐0.70) for 90 to 365, 366 to 730, and >730 cumulative defined daily doses of NAs, respectively.

CONCLUSIONS

NA use reduced the risk of HCC and overall mortality in HBV carriers. Cancer 2015;121:1446–1455. © 2014 American Cancer Society.
Assessment of EGFR and KRAS mutation status from FNAs and core‐needle biopsies of non‐small cell lung cancer
Authors: Lozano Maria D. , Labiano Tania , Echeveste Jose , Gurpide Alfonso , Martín‐Algarra Salvador , Zhang Guili , Sharma Abha , Palma John F.
Published: December 2014

BACKGROUND

Molecular testing to determine gene mutation status is now the recommended standard of care for patients with advanced or metastatic Non‐small cell lung cancer (NSCLC). Because the majority of patients with NSCLC present with metastatic disease, minimally invasive procedures are necessary for diagnosis, staging, and molecular analysis. However, the resulting samples have perceived limitations in the oncology community, and most commercially available tests have not been validated for these sample types. The current study was undertaken to assess the feasibility of determining epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status in fine‐needle aspirates (FNAs) and core‐needle biopsies (CNBs) after staining with Papanicolaou or hematoxylin and eosin, respectively.

METHODS

Gene mutation status was determined in 140 NSCLC tumor samples with proprietary tests for EGFR and KRAS mutations (cobas tests) followed by Sanger sequencing of exons 18 through 21 of the EGFR gene and exon 2 of the KRAS gene. The results were analyzed based on FNA (n = 91) or CNB (n = 49) sampling.

RESULTS

The cobas tests yielded valid results in the majority of FNA and CNB samples for both EGFR (97.9%) and KRAS (93.6%). Moreover, valid results were obtained for 90% of samples that had DNA concentrations below the values recommended by the manufacturer. For samples with valid results from both cobas testing and Sanger sequencing, 95.7% and 93% agreement were observed for EGFR status and KRAS status, respectively.

CONCLUSIONS

Gene mutation testing can be successfully performed on cytology and CNB samples, expanding the potential of personalized cancer treatment to patients who have limited tissue samples. Cancer (Cancer Cytopathol) 2015;123:230–236. © 2014 The Authors. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Old and new immunophenotypic markers in multiple myeloma for discrimination of responding and relapsing patients: The importance of “normal” residual plasma cell analysis
Authors: Pojero Fanny , Casuccio Alessandra , Parrino Maria Francesca , Cardinale Giovanni , Colonna Romano Giuseppina , Caruso Calogero , Gervasi Francesco
Published: December 2014

Background

Multiple myeloma is an incurable disease characterized by proliferation of clonal malignant plasma cells (CPCs), which can be immunophenotypically distinguished from polyclonal plasma cells (PPCs) by multiparameter flow cytometry (MFC). The utility of PPCs analysis in detecting prognostic and predictive information is still a matter of debate. Methods: we tested the ability of 11 MFC markers in detecting differences in the immunophenotype of CPCs and PPCs among patients in various disease stages; we verified if these markers could be associated with disease stage/response to therapy despite the role of clinical parameters. Results: significant changes in the expression of markers occurred both in CPCs and PPCs. CD58 on PPCs of responding patients was downregulated compared with PPC of relapsing group. Fraction of CD200 expressing PCs was lower in control subjects than in PPCs from MGUS and myeloma groups. CD11a levels of expression on both CPCs and PPCs showed an upregulation in newly diagnosed and relapsing patients versus PCs of controls; CD20 was less expressed on control PCs than on MGUS CPCs and PPCs. CD49d revealed to be advantageous in discrimination of PPCs from CPCs. In our multiple regression model, CD19 and CD49d on CPCs, and CD45, CD58 and CD56 on PPCs maintained their association with groups of patients independently of other prognostic variables. Conclusions: we provide a feasible start point to put in order ranges of expression on PPCs in healthy and myeloma subjects; we propose a new approach based on PPC analysis to monitor the stages of the disease. © 2014 International Clinical Cytometry Society © 2014 International Clinical Cytometry Society
Lower‐limb amputation following foot ulcers in patients with diabetes: classification systems, external validation and comparative analysis
Authors: Monteiro‐Soares Matilde , Martins‐Mendes Daniela , Vaz‐Carneiro António , Dinis‐Ribeiro Mário
Published: December 2014

Background

This study aimed to validate and compare the existing systems developed to stratify subjects with diabetic foot ulcers by risk of consequent lower extremity amputation.

Methods

We conducted a prospective cohort study on a consecutive series of patients (mean age of 68 years; 64% male) with active ulcer who were attending our Hospital Diabetic Foot Clinic (n = 293) from January 2010 to March 2013. At baseline, we collected information on the participants' characteristics and the relevant variables. Afterwards, we assessed the predictive value of each variable and each system's prognostic accuracy for amputation occurrence.

Results

During a median follow‐up of 91 days (interquartile range of 98), ulcers healed in 62% of the subjects. Major amputation occurred in 7% and minor occurred in 17%. Previous ulcer or amputation, ulcer area, and gangrene were associated with amputation occurrence. Nephropathy, pulses number, ulcer aetiology, depth, and number were associated with risk of amputation. Systems typically presented sensitivity values ≥80% and negative likelihood ratios ≤0.5 for the highest risk group; area under the receiver operating characteristic curve ranged from 0.56 to 0.83 and positive likelihood ratios from 1.0 to 5.9. If one chose only major amputation as an outcome, positive predictive values were lower, and negative predictive values tended to be higher.

Conclusions

System stages, grades, scores, and/or prognostics were generally associated with amputation, presenting overall substantial accuracy values. Nevertheless, great improvement is possible. A multicentre study validating and refining the existing systems is needed to improve clinical decision‐making in this area. Copyright © 2014 John Wiley & Sons, Ltd.
Specific labeling of climbing fibers shows early synaptic interactions with immature Purkinje cells in the prenatal cerebellum
Authors: Kita Yoshiaki , Tanaka Kazuto , Murakami Fujio
Published: December 2014

During development, growing axons must locate target cells to form synapses. This is not easy, since target cells are also growing and even actively migrating. In some brain regions, such axons have been reported to wait for the timing when target cells become mature, without invading their target region. However, in the cerebellum climbing fibers (CFs), major afferent axons, arrive near their target neurons, Purkinje cells, when the neurons are still actively migrating. We, therefore, examined whether synaptic contacts are established at such early stages. To specifically label CFs, we introduced by in utero electroporation a mixture of genes encoding for Ptf1a‐enhancer‐driven Cre recombinase and Cre‐dependent fluorescent protein into the mouse hindbrain at embryonic day (E) 10.5 and observed them during development. The earliest stages at which labeled CFs were observed in the cerebellar primordium were E15.5–E16.5. These fibers were fasciculated in the dorsal region and entered the cerebellar primordium. Some fibers defasciculated and reached the caudal region. At E17.5 and E18.5, fasciculated fibers were also found in the mantle region, and some grew toward the surface of the primordium to penetrate a mass of Purkinje cells. Interestingly, as early as E16.5, labeled fibers were found to run in close apposition to Purkinje cell dendrites and to express a presynaptic marker. These observations suggest that CFs form synapses with Purkinje cells as soon as the fibers enter the cerebellum. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 927–934, 2015
Developmental Dyslexia and Phonological Processing in European Portuguese Orthography
Authors: Moura Octávio , Moreno Joana , Pereira Marcelino , Simões Mário R.
Published: December 2014

This study analysed the performance of phonological processing, the diagnostic accuracy and the influence on reading in children who were native speakers of an orthography of intermediate depth. Portuguese children with developmental dyslexia (DD; N = 24; aged 10–12 years), chronological age (CA)‐matched controls (N = 24; aged 10–12 years) and reading level (RL)‐matched controls (N = 24; aged 7–9 years) were tested on measures of phonological processing (phonological awareness, naming speed and verbal short‐term memory) and reading. The results indicated that the children with DD performed significantly poorer in all measures compared with the CA and RL. Phonological awareness and naming speed showed a high accuracy (receiver operating characteristics curve analysis) for discriminating the children with DD from the CA and RL, whereas the presence of abnormally low scores in phonological awareness and naming speed was more frequent in the DD group than in the controls and the normative population. Hierarchical linear regression analyses revealed that phonological awareness was the most important predictor of all reading accuracy measures, whereas naming speed was particularly related to text reading fluency. Copyright © 2014 John Wiley & Sons, Ltd.
Evaluating nurse plants for restoring native woody species to degraded subtropical woodlands
Authors: Yelenik Stephanie G. , DiManno Nicole , D'Antonio Carla M.
Published: December 2014

Harsh habitats dominated by invasive species are difficult to restore. Invasive grasses in arid environments slow succession toward more desired composition, yet grass removal exacerbates high light and temperature, making the use of “nurse plants” an appealing strategy. In this study of degraded subtropical woodlands dominated by alien grasses in Hawai'i, we evaluated whether individuals of two native (Dodonaea viscosa, Leptocophylla tameiameia) and one non‐native (Morella faya) woody species (1) act as natural nodes of recruitment for native woody species and (2) can be used to enhance survivorship of outplanted native woody species. To address these questions, we quantified the presence and persistence of seedlings naturally recruiting beneath adult nurse shrubs and compared survival and growth of experimentally outplanted seedlings of seven native woody species under the nurse species compared to intact and cleared alien‐grass plots. We found that the two native nurse shrubs recruit their own offspring, but do not act as establishment nodes for other species. Morella faya recruited even fewer seedlings than native shrubs. Thus, outplanting will be necessary to increase abundance and diversity of native woody species. Outplant survival was the highest under shrubs compared to away from them with few differences between nurse species. The worst habitat for native seedling survival and growth was within the unmanaged invasive grass matrix. Although the two native nurse species did not differentially affect outplant survival, D. viscosa is the most widespread and easily propagated and is thus more likely to be useful as an initial nurse species. The outplanted species showed variable responses to nurse habitats that we attribute to resource requirements resulting from their typical successional stage and nitrogen fixation capability.
Structure of trophic and mutualistic networks across broad environmental gradients
Authors: Welti Ellen A. R. , Joern Anthony
Published: December 2014

This study aims to understand how inherent ecological network structures of nestedness and modularity vary over large geographic scales with implications for community stability. Bipartite networks from previous research from 68 locations globally were analyzed. Using a meta‐analysis approach, we examine relationships between the structure of 22 trophic and 46 mutualistic bipartite networks in response to extensive gradients of temperature and precipitation. Network structures varied significantly across temperature gradients. Trophic networks showed decreasing modularity with increasing variation in temperature within years. Nestedness of mutualistic networks decreased with increasing temperature variability between years. Mean annual precipitation and variability of precipitation were not found to have significant influence on the structure of either trophic or mutualistic networks. By examining changes in ecological networks across large‐scale abiotic gradients, this study identifies temperature variability as a potential environmental mediator of community stability. Understanding these relationships contributes to our ability to predict responses of biodiversity to climate change at the community level.
Buchwald–Hartwig Reactions of Monohaloflavones
Authors: Kónya Krisztina , Pajtás Dávid , Kiss‐Szikszai Attila , Patonay Tamás
Published: December 2014

The article describes the amination of different monobromo‐ or monochloroflavones with primary and secondary alkylamines and aniline derivatives by Buchwald–Hartwig reaction. The influence of the phosphine ligands used is described. The use of amino acid derivatives as a nitrogen source is also demonstrated. This latter reaction allows the synthesis of unique flavone–amino‐acid conjugates.
An experimental investigation on char pattern and depth at postflashover compartments using medium‐density fibreboard (MDF)
Authors: Li Kai‐Yuan , Wang Jinhui , Ji Jie
Published: December 2014

To determine the fire origins for postflashover compartments, the char pattern and depth are investigated. A set of experiments was carried out using large‐scale compartments made of medium‐density fibreboard. A liquefied petroleum gas burner was used as the ignition source to mimic the fire origin. The burner was set at different locations in different experiments. It is found that time to flashover, intermittent flame of gas burner and ventilation condition have effects on the char patterns. The ‘ventilation patterns’ are likely to confuse the fire investigators; therefore, it needs to be identified from the ‘flame patterns’. In general, the ventilation patterns at the floor would initiate directly from the compartment opening. CFD simulations is used to reflect the ventilation conditions during fires thus assisting the identification of ventilation patterns. For those cases with less distinguishable char patterns, the profiles of total leftover material thickness and char depth were used to determine the fire origin. The char layer and total thickness in the flame regions were found to be respectively deeper and thinner than the rest parts of the compartment. The ventilation condition also affects the char depth profile; therefore, it cannot be ignored from analysis. At the end, a strategy of fire origin determination is proposed. Copyright © 2014 John Wiley & Sons, Ltd.
Double‐layered emulsions as beverage clouding agents
Authors: Zhang Jian , Peppard Terry L. , Reineccius Gary A.
Published: December 2014

There is a constant interest in finding alternatives to gum arabic in flavour and beverage industries. The ability to prepare beverage‐cloud emulsions using a layer‐by‐layer deposition technique was developed with extremely low usage levels of proteins and polysaccharides. Sodium caseinate (S) and β‐lactoglobulin (L) were selected to stabilize the primary emulsions. Polysaccharides of sodium alginate (A), ι‐carrageenan (C), gum arabic (G) and pectin (P) were evaluated as secondary layers. Polysaccharide concentration was optimized based on droplet size and ζ‐potential. The performance of double‐layered emulsions in beverage‐cloud applications was evaluated. Polysaccharide concentration and pH were found critical to the formation of stable multilayered emulsions. Protein and polysaccharide type also impacted droplet size and ζ‐potential of multilayered emulsions. β‐Lactoglobulin was found to be better than sodium caseinate in forming protein–polysaccharide interfacial complexes, as demonstrated by smaller mean droplet diameters (MDD) of L–A, L–P and L–C than those of S–A, S–P and S–C. It was also found that the polysaccharide concentration has to be above a critical value (0.2–0.5 wt% depending on the type of polysaccharides) to prevent multilayered emulsions from bridging flocculation. Data showed that double‐layered emulsions of L–A, L–C and L–G formed by electrostatic deposition could provide the same performance as traditional emulsifiers of gum arabic (G) and modified starch (M). After four weeks of storage at room temperature, beverage clouds stabilized with G, M, L–A, L–C and L–G showed MDDs of 0.68, 0.67, 0.90, 0.82 and 0.65 µm, respectively, and turbidity losses of 18, 28, 22, 19 and 25%, respectively. Copyright © 2014 John Wiley & Sons, Ltd.
Tailored Selection of Study Individuals to be Sequenced in Order to Improve the Accuracy of Genotype Imputation
Authors: Peil Barbara , Kabisch Maria , Fischer Christine , Hamann Ute , Bermejo Justo Lorenzo
Published: December 2014

The addition of sequence data from own‐study individuals to genotypes from external data repositories, for example, the HapMap, has been shown to improve the accuracy of imputed genotypes. Early approaches for reference panel selection favored individuals who best reflect recombination patterns in the study population. By contrast, a maximization of genetic diversity in the reference panel has been recently proposed. We investigate here a novel strategy to select individuals for sequencing that relies on the characterization of the ancestral kernel of the study population. The simulated study scenarios consisted of several combinations of subpopulations from HapMap. HapMap individuals who did not belong to the study population constituted an external reference panel which was complemented with the sequences of study individuals selected according to different strategies. In addition to a random choice, individuals with the largest statistical depth according to the first genetic principal components were selected. In all simulated scenarios the integration of sequences from own‐study individuals increased imputation accuracy. The selection of individuals based on the statistical depth resulted in the highest imputation accuracy for European and Asian study scenarios, whereas random selection performed best for an African‐study scenario. Present findings indicate that there is no universal ‘best strategy’ to select individuals for sequencing. We propose to use the methodology described in the manuscript to assess the advantage of focusing on the ancestral kernel under own study characteristics (study size, genetic diversity, availability and properties of external reference panels, frequency of imputed variants…).
Endoscopic transnasal approaches to pterygopalatine fossa tumors
Authors: Battaglia Paolo , Turri–Zanoni Mario , Lepera Davide , Sica Eleonora , Karligkiotis Apostolos , Dallan Iacopo , Castelnuovo Paolo
Published: December 2014

Background

The pterygopalatine fossa (PPF) is a difficult area to access, as it has been traditionally treated by external approaches. The development of endoscopic transnasal approaches enables surgeons to reach this region through a minimally invasive route, reducing the associated morbidity.

Methods

We conducted a retrospective review of patients with benign and malignant tumors arising in or extending to the PPF, treated from 2000 to 2013 at a single institute, using endoscopic transnasal transmaxillary approaches.

Results

Thirty‐seven consecutive patients with benign (27 cases) and malignant (10 cases) tumors were treated with curative intent. Radical resection was achieved in 36 of 37 patients. No major complications were observed. No local recurrences were observed, with a median follow‐up of 38.5 months for malignancies and 60 months for benign tumors.

Conclusion

The endoscopic transnasal approaches are safe and feasible techniques for the radical resection of selected tumors involving the PPF and should be tailored according to the biology and extension of the lesion. © 2015 Wiley Periodicals, Inc. Head Neck 38: E214–E220, 2016
CXCR4 inhibition in tumor microenvironment facilitates anti‐programmed death receptor‐1 immunotherapy in sorafenib‐treated hepatocellular carcinoma in mice
Authors: Chen Yunching , Ramjiawan Rakesh R. , Reiberger Thomas , Ng Mei R. , Hato Tai , Huang Yuhui , Ochiai Hiroki , Kitahara Shuji , Unan Elizabeth C. , Reddy Tejaswini P. , Fan Christopher , Huang Peigen , Bardeesy Nabeel , Zhu Andrew X. , Jain Rakesh K. , Duda Dan G.
Published: December 2014

Sorafenib, a broad tyrosine kinase inhibitor, is the only approved systemic therapy for advanced hepatocellular carcinoma (HCC) but provides limited survival benefits. Recently, immunotherapy has emerged as a promising treatment strategy, but its role remains unclear in HCCs, which are associated with decreased cytotoxic CD8+ T‐lymphocyte infiltration in both murine and human tumors. Moreover, in mouse models after sorafenib treatment intratumoral hypoxia is increased and may fuel evasive resistance. Using orthotopic HCC models, we now show that increased hypoxia after sorafenib treatment promotes immunosuppression, characterized by increased intratumoral expression of the immune checkpoint inhibitor programmed death ligand‐1 and accumulation of T‐regulatory cells and M2‐type macrophages. We also show that the recruitment of immunosuppressive cells is mediated in part by hypoxia‐induced up‐regulation of stromal cell–derived 1 alpha. Inhibition of the stromal cell–derived 1 alpha receptor (C‐X‐C receptor type 4 or CXCR4) using AMD3100 prevented the polarization toward an immunosuppressive microenvironment after sorafenib treatment, inhibited tumor growth, reduced lung metastasis, and improved survival. However, the combination of AMD3100 and sorafenib did not significantly change cytotoxic CD8+ T‐lymphocyte infiltration into HCC tumors and did not modify their activation status. In separate experiments, antibody blockade of the programmed death ligand‐1 receptor programmed death receptor‐1 (PD‐1) showed antitumor effects in treatment‐naive tumors in orthotopic (grafted and genetically engineered) models of HCC. However, anti‐PD‐1 antibody treatment had additional antitumor activity only when combined with sorafenib and AMD3100 and not when combined with sorafenib alone. Conclusion: Anti‐PD‐1 treatment can boost antitumor immune responses in HCC models; when used in combination with sorafenib, anti‐PD‐1 immunotherapy shows efficacy only with concomitant targeting of the hypoxic and immunosuppressive microenvironment with agents such as CXCR4 inhibitors. (Hepatology 2015;61:1591–1602)
Post‐training, intrahippocampal HDAC inhibition differentially impacts neural circuits underlying spatial memory in adult and aged mice
Authors: Dagnas Malorie , Micheau Jacques , Decorte Laurence , Beracochea Daniel , Mons Nicole
Published: December 2014

Converging evidence indicates that pharmacologically elevating histone acetylation using post‐training, systemic or intrahippocampal, administration of histone deacetylase inhibitor (HDACi) can enhance memory consolidation processes in young rodents but it is not yet clear, whether such treatment is sufficient to prevent memory impairments associated with aging. To address this question, we used a 1‐day massed spatial learning task in the water maze to investigate the effects of immediate post‐training injection of the HDACi trichostatin A (TSA) into the dorsal hippocampus on long‐term memory consolidation in 3–4 and 18–20 month‐old mice. We show that TSA improved the 24 h‐memory retention for the hidden platform location in young‐adults, but failed to rescue memory impairments in older mice. The results further indicate that Young‐TSA mice sacrificed 1 h after training had a robust increase in histone H4 acetylation in the dorsal hippocampal CA1 region (dCA1) and the dorsomedial part of the striatum (DMS), a structure important for spatial information processing. Importantly, TSA infusion in aged mice completely rescued altered H4 acetylation in the dCA1 but failed to alleviate age‐associated decreased H4 acetylation in the DMS. Moreover, intrahippocampal TSA infusion produced concomitant decreases (in adults) or increases (in older mice) of acetylated histone levels in the ventral hippocampus (vCA1 and vCA3) and the lateral amygdala, two structures critically involved in stress and emotional responses. These data suggest that the failure of post‐training, intrahippocampal TSA injection to reverse age‐associated memory impairments may be related to an inability to recruit appropriate circuit‐specific epigenetic patterns during early consolidation processes. © 2014 Wiley Periodicals, Inc.
Permissive expansion and homing of adoptively transferred T cells in tumor‐bearing hosts
Authors: Perez C. , Jukica A. , Listopad J.J. , Anders K. , Kühl A.A. , Loddenkemper C. , Blankenstein T. , Charo J.
Published: December 2014

Activated T cells expressing endogenous or transduced TCRs are two cell types currently used in clinical adoptive T‐cell therapy. The ability of these cells to recognize their antigen, expand and traffic to the tumor site are the initial steps necessary for successful therapy. In this study, we used in vivo bioluminescent imaging (BLI) of Renilla luciferase (RLuc) expressing T cells to evaluate the ability of adoptively transferred T cells to survive, expand and home to tumor site in vivo. Using this method, termed RT‐Rack (Rluc T cell tracking), we followed T‐cell response against tumors in vivo. Expansion and homing of adoptively transferred T cells were antigen dependent, but independent of the host immune status. Moreover, we successfully detected T‐cell response to small and large tumors, including autochthonous liver tumors. The adoptively transferred T cells were not ignorant or excluded in a partially tolerant host, which expressed low level of the target in the periphery. Using T cell receptor (TCR)‐engineered T cells, we showed the ability of these cells to respond in tumor‐bearing hosts by expanding and homing to the tumor site. In all these models, the host immune status, the nature of the tumor or of the antigen, the tumor size and the presence of the targeted antigen in the periphery did not prevent the adoptively transferred T cells from responding by expanding and homing to the tumor. However, T cells had higher expression of the inhibitory receptor PD1 and reduced functional activity when a self‐antigen was targeted.
MicroRNA‐139‐5p Suppresses 3T3‐L1 Preadipocyte Differentiation Through Notch and IRS1/PI3K/Akt Insulin Signaling Pathways
Authors: Mi Lin , Chen Yaosheng , Zheng Xueli , Li Youlei , Zhang Qiangling , Mo Delin , Yang Gongshe
Published: December 2014

MicroRNAs (miRNAs) participate in the regulation of adipogenesis. Identification of the full repertoire of miRNAs expressed in adipose tissue is likely to significantly improve our understanding of adipose tissue growth and development. Here, miR‐139–5p was identified as an inhibitor of 3T3‐L1 adipocyte differentiation with significantly down‐regulating the expression levels of adipogenic marker genes PPAR γ (P < 0.01), aP2 (P < 0.01) and FAS (P < 0.01). Importantly, flow cytometry and EdU incorporation assay indicated that this inhibition was partly due to the dysfunction of clonal expansion. Furthermore, we firstly demonstrated that miR‐139–5p blocked adipogenesis via directly targeted the 3' untranslated regions (UTRs) of Notch1 and IRS1 mRNAs, a key member of Notch signaling and IRS1/PI3K/Akt insulin signaling, respectively. In addition, the overexpression of Notch1 or IRS1 partially restored the suppressive effects miR‐139–5p on differentiation of 3T3‐L1 cells. To our knowledge, this was the first report that miR‐139–5p functioned negatively by targeting Notch1 and IRS1 during 3T3‐L1 adipogenesis, regulating the transition from clonal expansion to terminal differentiation. J. Cell. Biochem. 116: 1195–1204, 2015. © 2014 Wiley Periodicals, Inc.
Heparan Sulfate D‐Glucosaminyl 3‐O‐Sulfotransferase‐3B1 (HS3ST3B1) Promotes Angiogenesis and Proliferation by Induction of VEGF in Acute Myeloid Leukemia Cells
Authors: Zhang Lei , Song Kai , Zhou Ling , Xie Zhishen , Zhou Ping , Zhao Yiming , Han Yue , Xu Xiaojun , Li Ping
Published: December 2014

Heparan sulfate (HS) are complex polysaccharides that reside on the plasma membrane of almost all mammalian cells, and play an important role in physiological and pathological conditions. Heparan sulfate D‐glucosamine 3‐O‐sulfotransferase 3B1 (HS3ST3B1) participates in the last biosynthetic steps of HS and transfers sulfate to the 3‐O‐position of glucosamine residues to yield mature sugar chains. To date very few biological processes or proteins have been described that are modulated by HS3ST3B1. In this study, we observed that HS3ST3B1 positively contributed to acute myeloid leukemia (AML) progression in vitro and in vivo, and these activities were associated with an induction of the proangiogenic factor VEGF expression and shedding. Moreover, the effects of HS3ST3B1 on VEGF release can be attenuated after treatment of heparanase inhibitor suramin, which prevented VEGF secretion and subsequently blocked VEGF‐induced activation of ERK and AKT, suggesting that 3‐O‐sulfation of HS by HS3ST3B1 facilitated VEGF shedding; the effects of HS3ST3B1 on activation of ERK and AKT can also be blocked by VEGFR inhibitor axitinib, suggestive of a relationship between 3‐O‐sulfation of HS and VEGF‐activated signaling pathways. Taken together, our findings support that VEGF is an important functional target of HS3ST3B1 and provide a new mechanism of HS3ST3B1 in AML. J. Cell. Biochem. 116: 1101–1112, 2015. © 2014 Wiley Periodicals, Inc.
Resveratrol Potentiates Vitamin D and Nuclear Receptor Signaling
Authors: Dampf Stone Angelika , Batie Shane F. , Sabir Marya S. , Jacobs Elizabeth T. , Lee Jamie H. , Whitfield G. Kerr , Haussler Mark R. , Jurutka Peter W.
Published: December 2014

The 1,25‐dihydroxyvitamin D3 (1,25D) hormone is derived from vitamin D generated in skin or obtained from the diet, and binds to and activates the vitamin D receptor (VDR) in target tissues including kidney, colon/small intestine, and bone/muscle. We tested resveratrol for its ability to modulate VDR signaling, using vitamin D responsive element (VDRE) and mammalian 2‐hybrid (M2H) transcriptional system technology. Via VDRE‐based assays in kidney, colon and myoblast cells, VDR‐mediated transcription was activated by resveratrol, and a cooperative effect on transactivation was observed with resveratrol plus 1,25D. The M2H assay revealed a modest, resveratrol‐induced dimerization of VDR with its retinoid X receptor (RXR) heteropartner. Cells treated with both resveratrol and 1,25D displayed synergistic stimulation of VDR–RXR heterodimerization, while resveratrol antagonized rexinoid‐mediated RXR‐RXR homodimerization. Increased transactivation in response to resveratrol was also observed with a subset of other nuclear receptors and their respective cognate responsive elements. Evaluation of wild‐type versus a ligand‐binding domain mutant VDR revealed that hormone‐responsiveness to 1,25D was severely depressed, while the response to resveratrol was only moderately attenuated. Moreover, radiolabeled 1,25D‐displacement assays demonstrated an increase in VDR‐bound 1,25D in the presence of resveratrol. Thus, resveratrol may affect VDR and other nuclear receptors indirectly, likely via the ability of resveratrol to: (1) potentiate 1,25D binding to VDR; (2) activate RXR; and/or (3) stimulate SIRT1, an enzyme known to deacetylate nuclear receptors. The results of this study elucidate a possible pathway for crosstalk between two nutritionally derived lipids, vitamin D and resveratrol, both of which converge on VDR signaling. J. Cell. Biochem. 116: 1130–1143, 2015. © 2014 Wiley Periodicals, Inc.
An Enumeration of Certain Projective Ternary Two‐Weight Codes
Authors: Martis Michael , Bamberg John , Morris Sylvia
Published: December 2014

We detail the enumeration of all two‐intersection sets of the five‐dimensional projective space over the field of order 3 that are invariant under an element of order 7, which include the examples of Hill (1973) and Gulliver (1996). Up to projective equivalence, there are 6,635 such two‐intersection sets.
Being in the Right Place at the Right Time: An Organizational Contingency Perspective of the Fortune 1000
Authors: Guo Chiquan , Wang Yong J.
Published: December 2014

Large corporations enjoy many benefits, such as name recognition, prestige, and stature. In several respects, Fortune 1000 companies, the largest entities in the United States according to data complied by Fortune magazine, are deemed the pinnacles of success. Countless commercial organizations strive to win a spot on the list, while companies that are already on it jockey to improve their rankings. An investigation of the factors associated with the size of the 2011 Fortune 1000 firms, measured in both relative and absolute terms, shows that company age, headquarters location, and industry type are related to firm size. The findings also show that there is no shortcut to organizational success. Business leaders must take careful steps to ensure that their organizations adapt to the environmental changes they inevitably will encounter on the way to world‐class status. ©2015 Wiley Periodicals, Inc.
Modelling of membranes in the material point method with applications
Authors: Hamad Fursan , Stolle Dieter , Vermeer Pieter
Published: December 2014

The objective of this paper is to formulate and validate an accurate MPM approach for the numerical simulation of the large displacement of membranes containing soil. In the proposed approach, the membrane is discretised by a surface mesh that allows accurate simulation of membrane stresses. The membrane is free to move through a three‐dimensional grid for a continuum consisting of tetrahedral elements. The approach is applied to model a geocontainer being released from a split barge, taking into account the frictional contact between the geotextile and the barge. No‐slip contact is assumed between the geotextile and the soil inside. The effect of geocontainer interaction is investigated by dropping a second container. Copyright © 2014 John Wiley & Sons, Ltd.
Numerical solution of one‐dimensional Burgers' equation
Authors: Li FuXiang , Fei ZhaoFu , Han Jing , Wei Jia
Published: December 2014

In this article, an iterative method for the approximate solution of a class of Burgers' equation is obtained in reproducing kernel space . It is proved the approximation converges uniformly to the exact solution u(x, t) for any initial function under trivial conditions, the derivatives of are also convergent to the derivatives of u(x, t), and the approximate solution is the best approximation under the system © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 1251–1264, 2015
A compact C0 discontinuous Galerkin method for Kirchhoff plates
Authors: An Rong , Huang Xuehai
Published: December 2014

A compact C0 discontinuous Galerkin (CCDG) method is developed for solving the Kirchhoff plate bending problems. Based on the CDG (LCDG) method for Kirchhoff plate bending problems, the CCDG method is obtained by canceling the term of global lifting operator and enhancing the term of local lifting operator. The resulted CCDG method possesses the compact stencil, that is only the degrees of freedom belonging to neighboring elements are connected. The advantages of CCDG method are: (1) CCDG method just requires C0 finite element spaces; (2) the stiffness matrix is sparser than CDG (LCDG) method; and (3) it does not contain any parameter which can not be quantified a priori compared to C0 interior penalty (IP) method. The optimal order error estimates in certain broken energy norm and H1‐norm for the CCDG method are derived under minimal regularity assumptions on the exact solution with the help of some local lower bound estimates of a posteriori error analysis. Some numerical results are included to verify the theoretical convergence orders. © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 1265–1287, 2015
The information and decision support needs of older women (>75 yrs) facing treatment choices for breast cancer: a qualitative study
Authors: Burton Maria , Collins Karen Anna , Lifford Kate Joanna , Brain Kate , Wyld Lynda , Caldon L. , Gath Jacqui , Revell Deirdre , Reed Malcolm William
Published: December 2014

Objective

Primary Endocrine Therapy (PET) is a good alternative to surgery for breast cancer in older frailer women. Overall survival rates are equivalent although rates of local control are inferior. There is little research regarding the decision support needs of older patients faced with this choice. This qualitative study aimed to explore these among older breast cancer patients offered a choice of treatment, as the basis to develop an appropriate decision support tool.

Methods

Semi‐structured interviews were undertaken with older women (>75 years) with breast cancer who had been offered a choice of PET or surgery at diagnosis. Women's involvement in their treatment decision and support for the process were explored and analysed using framework analysis.

Results

Thirty‐three interviews were undertaken (median age 82, range 75–95 years, 22 PET, 11 surgery). Most women, regardless of treatment choice, wanted tailored information about the different treatment options, their impact on independence, the practicalities of treatment and the risk of recurrence and spread. Surgery was the treatment of choice in women wanting optimal disease control; those choosing PET felt that they were ‘too old’ for surgery and wanted minimal disruption.

Conclusions

Older women described making active treatment decisions. However, some knowledge was inaccurate. Women wanted information and decision support from their clinicians along with a specific tailored information booklet to support this process. Copyright © 2014 John Wiley & Sons, Ltd.