bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of Crustal Thickness and Poisson's Ratio in the Coastal Area of South China
Authors: Hai‐Bo HUANG , Xing‐Wei GUO , Shao‐Hong XIA , Xue‐Lin QIU
Published: February 2015

The crustal thickness (H) and Poisson's ratio (ν) are two important parameters for understanding the plate motion and the structure in the earth. We collected teleseismic receiver functions of earthquakes, which occurred from 2001 to 2008, from 75 permanent seismic stations of Guangdong and Fujian networks. In total, 74 estimations of H and ν were obtained by making use of the H‐κ method. Combining characteristics of the fault distribution, seismicity and topography, several conclusions were achieved below: (1) Crustal thickness ranges from 26 to 32 km, reducing from land to sea and from north to south. Poisson's ratio is 0.23∼0.28, increasing from the inland to sea. Variations of H and ν have positive and negative correlations with surface topography, respectively. (2) Fault activity corresponds to the block‐like and band‐shaped distributions of H and ν. Transitional variation zones of H and ν spread in accordance with the seismicity. Earthquake clusters and mantle upwelling are generally corresponding to the rapid increase of ν. (3) Crustal rocks in this area mainly consist of intermediate and acidic mineral. Crustal thicknesses are positively and negatively related to Poisson's ratio under actions of extensional tectonics offshore and thrusting structure in folded regions, respectively, revealing the diverse evolution models in different eras and districts.
Study of Crust and Lithosphere Velocity Structure Character of Chinese North‐South Tectonic Belt and Its Adjacent Regions
Authors: Wei‐Wei JIANG , Di‐Di JIANG , Yi XU , Tian‐Yao HAO , Wei‐Jian HU , Jing‐Feng YU
Published: February 2015

In this paper, we based on gravity data and used the inversion method of Parker‐Oldenburg to calculate the crustal thickness in Chinese North‐South tectonic belt and its adjacent regions, while we also used the inversion method of seismic tomography to research the three‐dimensional velocity structure of the crust and mantle in the study area. According to the results of calculation we discussed the crust and lithosphere structures of the study area. We tried to reveal the deformation characteristics of crust and lithosphere of Chinese North‐South tectonic belt and its adjacent regions, and then discussed the deep causes of the crust‐mantle tectonic evolution in the Tibetan Plateau active zone, the upper mantle rheological property in the study area and its dynamics significance. The studies show that the crustal thickness of the North‐South tectonic belt changes rapidly, the west area has a thickening crust, the east area of Ordos Basin and Sichuan Basin has a stable crust, while further eastward the crust is thinning. The boundary between thinning and thickening lithosphere is limited in the Da Hinggan Ling Mountains‐Taihang Mountains‐Qinling Mountains‐Daba Mountains‐Wuling Mountains area. It is also the deep tectonic boundary of eastern continental margin zone and central Yangtze‐Ordos Craton regions. Not only are the shallow geological structures different on its two sides, but the physical property state and the thermal activities in the deep upper mantle are also distinctly different, which indicates that, in the study area, the structure of lithosphere and asthenosphere, and the distribution of deep material are laterally heterogeneous. Deep tectonic boundary of the central region and Tibetan Plateau is located at about 100°E–102°E longitude.
Pretransplant Coagulopathy and In‐hospital Outcomes Among Heart Transplant Recipients: A Propensity‐Matched Nationwide Inpatient Sample Study
Authors: Mujib Marjan , Khanna Neel , Mazumder Nabila K. , Aronow Wilbert S. , Kolte Dhaval , Khera Sahil , Palaniswamy Chandrasekar , Jain Diwakar , Lanier Gregg M. , Sule Sachin , Ahmed Ali , Levy Wayne C. , Prabhu Sumanth D. , Cooper Howard A. , Panza Julio A. , Gass Alan L. , Fonarow Gregg C.
Published: February 2015

Background

The prevalence and contemporary trends of pre–heart transplantation (HT) coagulopathy and associated clinical outcomes have not been studied from a national database.

Hypothesis

Pre‐HT coagulopathy is associated with increased in‐hospital mortality.

Methods

Among 2454 adult HT recipients from the 2003 to 2010 Nationwide Inpatient Sample databases, 707 (29%) had pre‐HT coagulopathy (defined as a comorbidity variable, based on International Classification of Diseases, Ninthe Revision, Clinical Modification and Diagnosis Related Group codes). We used propensity scores for coagulopathy to assemble a matched cohort of 664 pairs of patients with and without coagulopathy balanced in 54 baseline characteristics.

Results

The prevalence of pre‐HT coagulopathy increased from 17% in 2003 to 44% in 2010 (P for trend <0.001). In‐hospital mortality occurred in 8.6% and 4.7% of matched HT recipients with and without coagulopathy, respectively (hazard ratio: 1.81; 95% confidence interval [CI]: 1.17‐2.80; P = 0.008). Coagulopathy was not significantly associated with post‐HT graft complications (odds ratio [OR]: 1.20; 95% CI: 0.95‐1.52; P = 0.131) but was associated with increased blood transfusions (OR: 1.92; 95% CI, 1.54–2.41; P < 0.001). Coagulopathy and no‐coagulopathy groups had no difference in median length of stay (22 days in each group, P = 0.746), but median total hospital charges were higher among patients with coagulopathy compared to those without (US$425 643 vs US$389 656; P = 0.008).

Conclusions

In this national study of HT recipients, pretransplant coagulopathy was common, increased over time, and was not significantly associated with post‐HT graft complications or increased hospital stay. However, it was associated with increased bleeding risk, in‐hospital mortality, and total hospital charges. These findings may have implications for the selection of patients for HT.
Design and Synthesis of a MAO‐B‐Selectively Activated Prodrug Based on MPTP: A Mitochondria‐Targeting Chemotherapeutic Agent for Treatment of Human Malignant Gliomas
Authors: Sharpe Martyn A. , Han Junyan , Baskin Alexandra M. , Baskin David S.
Published: February 2015

Malignant gliomas, including glioblastomas, are extremely difficult to treat. The median survival for glioblastoma patients with optimal therapeutic intervention is 15 months. We developed a novel MAO‐B‐selectively activated prodrug, N,N‐bis(2‐chloroethyl)‐2‐(1‐methyl‐1,2,3,6‐tetrahydropyridin‐4‐yl)propanamide (MP‐MUS), for the treatment of gliomas based on 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). The design of neutral MP‐MUS involved the use of a seeker molecule capable of binding to mitochondrial MAO‐B, which is up‐regulated ≥fourfold in glioma cells. Once the binding occurs, MP‐MUS is converted into a positively charged moiety, P+‐MUS, which accumulates inside mitochondria at a theoretical maximal value of 1000:1 gradient. The LD50 of MP‐MUS against glioma cells is 75 μM, which is two‐ to threefold more potent than temozolomide, a primary drug for gliomas. Importantly, MP‐MUS was found to be selectively toxic toward glioma cells. In the concentration range of 150–180 μM MP‐MUS killed 90–95 % of glioma cells, but stimulated the growth of normal human astrocytes. Moreover, maturation of MP‐MUS is highly dependent on MAO‐B, and inhibition of MAO‐B activity with selegiline protected human glioma cells from apoptosis.
Screening and In Vitro Testing of Antifolate Inhibitors of Human Cytosolic Serine Hydroxymethyltransferase
Authors: Paiardini Alessandro , Fiascarelli Alessio , Rinaldo Serena , Daidone Frederick , Giardina Giorgio , Koes David R. , Parroni Alessia , Montini Giulia , Marani Marina , Paone Alessio , McDermott Lee A. , Contestabile Roberto , Cutruzzolà Francesca
Published: February 2015

Metabolic reprogramming of tumor cells toward serine catabolism is now recognized as a hallmark of cancer. Serine hydroxymethyltransferase (SHMT), the enzyme providing one‐carbon units by converting serine and tetrahydrofolate (H4PteGlu) to glycine and 5,10‐CH2‐H4PteGlu, therefore represents a target of interest in developing new chemotherapeutic drugs. In this study, 13 folate analogues under clinical evaluation or in therapeutic use were in silico screened against SHMT, ultimately identifying four antifolate agents worthy of closer evaluation. The interaction mode of SHMT with these four antifolate drugs (lometrexol, nolatrexed, raltitrexed, and methotrexate) was assessed. The mechanism of SHMT inhibition by the selected antifolate agents was investigated in vitro using the human cytosolic isozyme. The results of this study showed that lometrexol competitively inhibits SHMT with inhibition constant (Ki) values in the low micromolar. The binding mode of lometrexol to SHMT was further investigated by molecular docking. These results thus provide insights into the mechanism of action of antifolate drugs and constitute the basis for the rational design of novel and more potent inhibitors of SHMT.
Patient beliefs that chemotherapy may be curative and care received at the end of life among patients with metastatic lung and colorectal cancer
Authors: Mack Jennifer W. , Walling Anne , Dy Sydney , Antonio Anna Liza M. , Adams John , Keating Nancy L. , Tisnado Diana
Published: February 2015

BACKGROUND

Many patients with incurable cancer inaccurately believe that chemotherapy may cure them. Little is known about how such beliefs affect choices for care at the end of life. This study assessed whether patients with advanced cancer who believed that chemotherapy might offer a cure were more likely to receive chemotherapy in the last month of life and less likely to enroll in hospice care before death.

METHODS

This study examined patients diagnosed with stage IV lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance consortium, a population‐ and health system–based prospective cohort study. Among 722 patients who completed a baseline survey and died during the study period, logistic regression was used to assess the association of understanding goals of chemotherapy with chemotherapy use in the last month of life and hospice enrollment before death; adjustments were made for patient and tumor characteristics.

RESULTS

One‐third of the patients (33%) recognized that chemotherapy was “not at all” likely to cure their cancer. After adjustments, such patients were no less likely than other patients to receive end‐of‐life chemotherapy (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.84‐2.09), but they were more likely than other patients to enroll in hospice (OR, 1.97; 95% CI, 1.37‐2.82).

CONCLUSIONS

An understanding of the purpose of chemotherapy for incurable cancer is a critical aspect of informed consent. Still, advanced cancer patients who were well informed about chemotherapy's goals received late‐life chemotherapy at rates similar to those for other patients. An understanding of the incurable nature of cancer, however, is associated with increased hospice enrollment before death, and this suggests important care outcomes beyond chemotherapy use. Cancer 2015;121:1891–1897. © 2015 American Cancer Society.
Residential racial segregation and mortality among black, white, and Hispanic urban breast cancer patients in Texas, 1995 to 2009
Authors: Pruitt Sandi L. , Lee Simon J. Craddock , Tiro Jasmin A. , Xuan Lei , Ruiz John M. , Inrig Stephen
Published: February 2015

BACKGROUND

The authors investigated whether residential segregation (the degree to which racial/ethnic groups live separately from one another in a geographic area) 1) was associated with mortality among urban women with breast cancer, 2) explained racial/ethnic disparities in mortality, and 3) whether its association with mortality varied by race/ethnicity.

METHODS

Using Texas Cancer Registry data, all‐cause mortality and breast‐cancer mortality were examined among 109,749 urban black, Hispanic, and white women aged ≥50 years who were diagnosed with breast cancer from 1995 to 2009. Racial (black) segregation and ethnic (Hispanic) segregation of patient's neighborhoods were measured and were compared with the larger metropolitan statistical area using the location quotient measure. Shared frailty Cox proportional hazard models were used to nest patients within residential neighborhoods (census tract) and were controlled for race/ethnicity, age, diagnosis year, tumor stage, grade, histology, neighborhood poverty, and county‐level mammography availability.

RESULTS

Greater black segregation and Hispanic segregation were adversely associated with cause‐specific mortality and all‐cause mortality. For example, in adjusted models, Hispanic segregation was associated with cause‐specific mortality (adjusted hazard ratio, 1.24; 95% confidence interval, 1.05‐1.46). Compared with whites, blacks had higher mortality for both outcomes, whereas Hispanics demonstrated equivalent (cause‐specific) or lower (all‐cause) mortality. Segregation did not explain racial/ethnic disparities in mortality. Within each race/ethnicity strata, segregation was either adversely associated with mortality or was not significant.

CONCLUSIONS

Among urban women with breast cancer in Texas, segregation has an independent, adverse association with mortality, and the effect of segregation varies by patient race/ethnicity. The novel application of a small‐area measure of relative racial segregation should be examined in other cancer types with documented racial/ethnic disparities across varied geographic areas. Cancer 2015;121:1845–1855. © 2015 American Cancer Society.
Population pharmacokinetic/pharmacodynamic assessment of pharmacological effect of a selective estrogen receptor β agonist on total testosterone in healthy men
Authors: Hu Leijun , Jin Yan , Li Ying Grace , Borel Anthony
Published: February 2015

Background

LY500307 is a highly selective estrogen receptor β (ERβ) agonist, which loses its selectivity at high dose and leads to undesirable suppression of total testosterone (TT) concentration. The objective of the present analysis was to define the LY500307 dose with minimal effect on TT

Methods

LY500307 and TT concentrations were obtained from a single ascending‐dose study in a total of 30 healthy male subjects. LY500307 (in the range of 0.5 to 500 mg) or placebo was administered orally as a single dose on 2 occasions with a 3‐week washout period. A population pharmacokinetics/pharmacodynamics (PK/PD) model that integrated Fourier series in an indirect response model was developed to describe the circadian rhythm of TT and the exposure‐response relationship of LY500307 on TT.

Results

The maximum TT suppression (Emax) was approximately 28.6%. The potency (EC50) of LY500307 on TT suppression was approximately 1.69 ng/mL with a 95%CI of 0.871 to 4.44 ng/mL. This model could provide inferences on LY500307 dose levels that would result in various magnitudes of TT suppression.

Conclusions

Population PK/PD modeling is a highly sensitive tool to detect exposure‐response relationships on top of the complicated and highly variable circadian rhythm of TT.
Methods for Improving the Lifetime Performance of Organic Photovoltaics with Low‐Costing Encapsulation
Authors: Giannouli Myrsini , Drakonakis Vasileios M. , Savva Achilleas , Eleftheriou Polyvios , Florides Georgios , Choulis Stelios A.
Published: February 2015

Recent years have seen considerable advances in organic photovoltaics (OPVs), most notably a significant increase in their efficiency, from around 4 % to over 10 %. The stability of these devices, however, continues to remain an issue that needs to be resolved to enable their commercialization. This review discusses the main degradation processes of OPVs and recent methods that help to increase device stability and lifetime. One of the most effective steps that can be taken to increase the lifetime of OPVs is their encapsulation, which protects them from atmospheric degradation. Efficient encapsulation is essential for long‐term device performance, but it is equally important for the commercialization of OPVs to strike a balance between achieving the maximum device protection possible and using low‐cost processing for their encapsulation. Various encapsulation techniques are discussed herein, with emphasis on their cost effectiveness and their overall suitability for commercial applications.
Change of Surface Structure upon Foam Film Formation
Authors: Ridings Christiaan , Andersson Gunther G.
Published: February 2015

The charge distribution and coverage with surfactant molecules at foam film surfaces plays an important role in determining foam film structure and stability. This work uses the concentration depth profiling technique neutral impact collision ion scattering spectroscopy to experimentally observe the charge distribution in a foam film for the first time. The charge distribution at the surface of a foam film and the surface of the corresponding bulk liquid were measured for a cationic surfactant solution and the surface excess as well as the electric potential were determined. Describing the internal pressure of foam films by using the electrochemical potential is introduced as a new concept. The foam film can be seen to have a more negative surface charge compared to the bulk liquid surface due to re‐arranging of the surfactant molecules. It is discussed how the change in surface excess and electric potential change the electrochemical potential and the stability of the foam film.
Preparation of Iron‐Containing Schiff Base and Ionic Liquid Based Bifunctional Periodic Mesoporous Organosilica and Its Application in the Synthesis of 3,4‐Dihydropyrimidinones
Authors: Elhamifar Dawood , Nazari Elham
Published: February 2015

A novel iron‐containing Schiff base and ionic liquid based bifunctional periodic mesoporous organosilica (Fe@SBIL‐BPMO) was prepared, characterized, and its catalytic application was developed. The SBIL‐BPMO was first prepared by the grafting of 3‐aminopropyltrimethoxysilane on an ionic‐liquid‐based PMO followed by treatment with 2‐hydroxybenzaldehyde in toluene at reflux. This material was then reacted with Fe(NO3)3⋅9 H2O to afford the Fe@BPMO‐SBIL nanocatalyst. The catalyst was characterized by thermogravimetric analysis, nitrogen sorption experiments, diffuse reflectance FTIR spectroscopy, low‐angle powder XRD, and TEM. The Fe@SBIL‐BPMO catalyst was successfully applied in the one‐pot synthesis of 3,4‐dihydropyrimidinone/thione derivatives under solvent‐free reactions. The stability, reactivity, and reusability of the catalyst under the reaction conditions have also been investigated.
ALCHEMIST: Bringing genomic discovery and targeted therapies to early‐stage lung cancer
Authors: Gerber DE , Oxnard GR , Govindan R
Published: February 2015

The identification of druggable molecular alterations represents one of the greatest advances in cancer treatment. Such progress is particularly evident for lung cancer, which now has numerous molecularly defined subsets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. However, understanding of the significance of these genomic alterations is largely limited to incurable, metastatic lung cancer. ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) is a National Cancer Institute–sponsored initiative to address these questions in earlier‐stage disease.
Cannabis legalization with strict regulation, the overall superior policy option for public health
Authors: Rehm J , Fischer B
Published: February 2015

Cannabis is the most prevalently used drug globally, with many jurisdictions considering varying reform options to current policies to deal with this substance and associated harm. Three policy options are available: prohibition, decriminalization, and legalization, with prohibition currently the dominant model globally. This contribution gives reasons why legalization with strict regulation should be considered superior to other options with respect to public health in high income countries in North America.
Small and Medium Enterprises and Corporate Social Responsibility Practice: A Swedish Perspective
Authors: Lee Ki‐Hoon , Herold David M. , Yu Ae‐Li
Published: February 2015

The purpose of this paper is to investigate the characteristics of corporate social responsibility (CSR) practice in Swedish small and medium‐sized enterprises (SMEs). A case study approach is used to investigate the CSR perception, motivation, and activities of two Swedish SMEs. This paper indicates that two Swedish SMEs studied adopt a profit‐seeking rather than a profit‐sacrificing CSR approach. Furthermore, the paper argues that the perception, the motivation, and part of the CSR activities are well incorporated in the decision to engage in CSR. However, the Swedish SMEs in our case studies are often limited in communicating their CSR activities due to a lack of resources and management skills. This communication gap between intended and actual communication drives the overall CSR impact on business performance from marginal to non‐existent. As a result, looking at the overall business impact, a meant‐to‐be profit‐seeking strategy is actually turned into a profit‐sacrificing activity. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Quantitative Investigation of Free Radicals in Bio‐Oil and their Potential Role in Condensed‐Phase Polymerization
Authors: Kim Kwang Ho , Bai Xianglan , Cady Sarah , Gable Preston , Brown Robert C.
Published: February 2015

We report on the quantitative analysis of free radicals in bio‐oils produced from pyrolysis of cellulose, organosolv lignin, and corn stover by EPR spectroscopy. Also, we investigated their potential role in condensed‐phase polymerization. Bio‐oils produced from lignin and cellulose show clear evidence of homolytic cleavage reactions during pyrolysis that produce free radicals. The concentration of free radicals in lignin bio‐oil was 7.5×1020 spin g−1, which was 375 and 138 times higher than free‐radical concentrations in bio‐oil from cellulose and corn stover. Pyrolytic lignin had the highest concentration in free radicals, which could be a combination of carbon‐centered (benzyl radicals) and oxygen‐centered (phenoxy radicals) organic species because they are delocalized in a π system. Free‐radical concentrations did not change during accelerated aging tests despite increases in molecular weight of bio‐oils, suggesting that free radicals in condensed bio‐oils are stable.
Ultra‐low voltage fractional‐order circuits using current mirrors
Authors: Tsirimokou Georgia , Psychalinos Costas
Published: February 2015

Fractional‐order blocks, including differentiators, lossy and lossless integrators as well as filters of order 1 + a (0 < a < 1), are presented in this paper. The proposed topologies offer the benefit of ultra low‐voltage operation; in addition, reduced circuit complexity is achieved compared to the corresponding companding schemes, which have been already introduced in the literature. The ultra‐low voltage operation is performed through the employment of metal oxide semiconductor transistors biased in the subthreshold region. The reduction of circuit complexity is achieved through the utilization of current mirrors as active elements for realizing the required building blocks. The performance of the proposed fractional‐order circuits has been evaluated through the Analog Design Environment of the Cadence software and the design kit provided by the Taiwan Semiconductor Manufacturing Company (TSMC) 180 nm complementary metal oxide semiconductor process. Copyright © 2015 John Wiley & Sons, Ltd.
What, if anything, are topological maps for?
Authors: Wilson Stuart P. , Bednar James A.
Published: February 2015

What, if anything, is the functional significance of spatial patterning in cortical feature maps? We ask this question of four major theories of cortical map formation: self‐organizing maps, wiring optimization, place coding, and reaction‐diffusion. We argue that (i) self‐organizing maps yield spatial patterning only as a by‐product of efficient mechanisms for developing environmentally appropriate distributions of feature preferences, (ii) wiring optimization assumes rather than explains a map‐like organization, (iii) place‐coding mechanisms can at best explain only a subset of maps in functional terms, and (iv) reaction‐diffusion models suggest two factors in the evolution of maps, the first based on efficient development of feature distributions, and the second based on generating feature‐specific long‐range recurrent cortical circuitry. None of these explanations for the existence of topological maps requires spatial patterning in maps to be useful. Thus despite these useful frameworks for understanding how maps form and how they are wired, the possibility that patterns are merely epiphenomena in the evolution of mammalian neocortex cannot be rejected. The article is intended as a nontechnical introduction to the assumptions and predictions of these four important classes of models, along with other possible functional explanations for maps. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 667–681, 2015
Development of the zebrafish mesonephros
Authors: Diep Cuong Q. , Peng Zhenzhen , Ukah Tobechukwu K. , Kelly Paul M. , Daigle Renee V. , Davidson Alan J.
Published: February 2015

The vertebrate kidney plays an essential role in removing metabolic waste and balancing water and salt. This is carried out by nephrons, which comprise a blood filter attached to an epithelial tubule with proximal and distal segments. In zebrafish, two nephrons are first formed as part of the embryonic kidney (pronephros) and hundreds are formed later to make up the adult kidney (mesonephros). Previous studies have focused on the development of the pronephros while considerably less is known about how the mesonephros is formed. Here, we characterize mesonephros development in zebrafish and examine the nephrons that form during larval metamorphosis. These nephrons, arising from proliferating progenitor cells that express the renal transcription factor genes wt1b, pax2a, and lhx1a, form on top of the pronephric tubules and develop a segmentation pattern similar to pronephric nephrons. We find that the pronephros acts as a scaffold for the mesonephros, where new nephrons fuse with the distal segments of the pronephric tubules to form the final branching network that characterizes the adult zebrafish kidney. genesis 53:257–269, 2015. © 2015 Wiley Periodicals, Inc.
Ecohydrological controls on water distribution and productivity of moss communities in western boreal peatlands, Canada
Authors: Goetz Jonathan D. , Price Jonathan S.
Published: February 2015

Different peatland mosses have varying strategies for water storage and capillary rise mechanisms depending on their particular hydrophysical properties and preferred water sources. To understand these strategies, the retention and redistribution of water from various sources in Sphagnum, feather and Tomenthypnum moss communities were addressed through investigation of the sensitivity of moss moisture dynamics to environmental variables, field surveys and a drought stress experiment. Feather mosses preferred habitats well above the water table, and their relatively low volumetric water content (θ) increased only with precipitation events. The relatively high residual θ (0·22) of Sphagnum capitula helped the moss type maintain conditions suitable for photosynthesis over a range of water table conditions. Tomenthypnum mosses occurred over a broader range of water table positions than Sphagnum or feather mosses because of their ability to use both capillary rise and atmospheric water for growth. While Tomenthypnum had relatively low near‐surface θ (~0·10), evaporative losses were sustained by both small nocturnal additions by condensation of vapour and upward capillary rise. An intermediate layer of partially decomposed mosses supported contact with the underlying peat and helped transport sufficient water to the Tomenthypnum moss surface. However, Tomenthypnum θ and productivity changes were more sensitive to rainfall additions as the uppermost portion of moss shoots can easily desiccate under typical evaporative demand. As a result, nocturnal sources of atmospheric water from dew (~0·15 mm per night) and distillation (~0·10 mm per night) provided temporary relief from desiccation for potentially important early morning photosynthesis and helped drive evaporation and capillary rise. Copyright © 2015 John Wiley & Sons, Ltd.
Galectin‐3 and histological, molecular and biochemical aspects of myocardial fibrosis in heart failure of hypertensive origin
Authors: López Begoña , González Arantxa , Querejeta Ramón , Zubillaga Elena , Larman Mariano , Díez Javier
Published: February 2015

Aims

The aim of this study was to investigate whether galectin‐3 (Gal‐3) is associated with myocardial histological and molecular parameters related to fibrosis and with the circulating biomarkers of the extracellular generation of mature fibril‐forming collagen types I (C‐terminal propeptide of procollagen type I, PICP) and III (N‐terminal propeptide of procollagen type III, PIIINP) in two independent studies of hypertensive patients with heart failure (HF).

Methods and results

Endomyocardial biopsies and blood samples from 39 HF patients (invasive study), and blood samples from 220 HF patients (non‐invasive study) were analysed. Necropsies (n = 7) and blood samples (n = 20) from healthy subjects were used as controls. In the invasive study myocardial mRNA and protein expression of Gal‐3 and collagen types I and III, plasma Gal‐3 and serum PICP and PIIINP were all significantly increased in patients compared with controls. Neither myocardial nor plasma Gal‐3 were correlated with myocardial collagen and circulating biomarkers; whereas PICP was correlated with myocardial total (r = 0.819, P < 0.001) and collagen type I (r = 0.744, P < 0.001) deposition, PIIINP was not. In the non‐invasive study both plasma Gal‐3 and serum PICP were increased (P < 0.001) in patients compared with controls. No correlation was found between Gal‐3 and PICP in HF patients.

Conclusions

These findings show that although an excess of cardiac and systemic Gal‐3 is present in patients with HF of hypertensive origin, this molecule is not associated with histological, molecular and biochemical parameters related to myocardial fibrosis in these patients.
miR‐148a promotes plasma cell differentiation and targets the germinal center transcription factors Mitf and Bach2
Authors: Porstner Martina , Winkelmann Rebecca , Daum Patrick , Schmid Julia , Pracht Katharina , Côrte‐Real Joana , Schreiber Sandra , Haftmann Claudia , Brandl Andreas , Mashreghi Mir‐Farzin , Gelse Kolja , Hauke Manuela , Wirries Ina , Zwick Markus , Roth Edith , Radbruch Andreas , Wittmann Jürgen , Jäck Hans‐Martin
Published: February 2015

B cells undergo affinity maturation and class switch recombination of their immunoglobulin receptors during a germinal center (GC) reaction, before they differentiate into long‐lived antibody‐secreting plasma cells (PCs). Transcription factors such as Bach2 and Mitf are essential during this process, as they delay premature differentiation of GC B cells by repressing Blimp‐1 and IRF4, two transcription factors required for terminal PC differentiation. Therefore, Bach2 and Mitf expression must be attenuated in activated B cells to allow terminal PC differentiation, but the precise mechanism remains enigmatic. Here, we provide evidence that miR‐148a, a small noncoding microRNA, fosters PC differentiation and survival. Next‐generation sequencing revealed that miR‐148a is the most abundant microRNA in primary human and murine PCs, and its expression is upregulated in activated murine B cells and coincides with Blimp‐1 synthesis. miR‐148a targets Bach2, Mitf and proapoptotic factors such as PTEN and Bim. When prematurely expressed, miR‐148a promotes the differentiation and survival of plasmablasts and reduces frequencies of IgG1+ cells in primary B‐cell cultures. In summary, we propose that miR‐148a is a new player in the regulatory network controlling terminal PC differentiation and could, therefore, be a therapeutic target for interfering with PC differentiation and survival.
Conditional depletion of mast cells has no impact on the severity of experimental epidermolysis bullosa acquisita
Authors: Kasprick Anika , Yu Xinhua , Scholten Julia , Hartmann Karin , Pas Hendri H. , Zillikens Detlef , Ludwig Ralf J. , Petersen Frank
Published: February 2015

The role of mast cells (MCs) in autoimmunity is the matter of an intensive scientific debate. Based on observations in different MC‐deficient mouse strains, MCs are considered as fundamental players in autoimmune diseases. However, most recent data suggest that the outcome of such diseases is strongly affected by the individual mouse strain used. By the use of two c‐Kit mutant MC‐deficient mouse strains and one c‐Kit‐independent strain, we here investigated the role of MCs in a systemic Ab transfer model of epidermolysis bullosa acquisita, a subepidermal autoimmune blistering skin disease characterized by autoantibodies against type VII collagen. While C57BL/6J‐KitW‐sh/W‐sh mice developed an unexpected increased blistering phenotype, no significant differences to WT controls were seen in WBB6F1‐KitW/W‐v or the novel Mcpt5‐Cre iDTR animals. Interestingly, in a local Ab transfer model, which induces a localized disease, we showed that application of high concentrations of anti‐COL7 (where COL7 is type VII collagen) Abs induced MC activation and MC‐dependent edema formation that did, however, not contribute to blister induction. Our results indicate that in the autoimmune disorder epidermolysis bullosa acquisita MCs do not contribute to the immune‐mediated tissue injury. Modern c‐Kit mutant‐independent MC‐deficient mouse strains will help to further redefine the role of MCs in autoimmunity.
Estrogen‐inducible sFRP5 inhibits early B‐lymphopoiesis in vivo, but not during pregnancy
Authors: Yokota Takafumi , Oritani Kenji , Sudo Takao , Ishibashi Tomohiko , Doi Yukiko , Habuchi Yoko , Ichii Michiko , Fukushima Kentaro , Okuzaki Daisuke , Tomizuka Kazuma , Yamawaki Kengo , Kakitani Makoto , Shimono Akihiko , Morii Eiichi , Kincade Paul W. , Kanakura Yuzuru
Published: February 2015

Mammals have evolved to protect their offspring during early fetal development. Elaborated mechanisms induce tolerance in the maternal immune system for the fetus. Female hormones, mainly estrogen, play a role in suppressing maternal lymphopoiesis. However, the molecular mechanisms involved in the maternal immune tolerance are largely unknown. Here, we show that estrogen‐induced soluble Frizzled‐related proteins (sFRPs), and particularly sFRP5, suppress B‐lymphopoiesis in vivo in transgenic mice. Mice overexpressing sFRP5 had fewer B‐lymphocytes in the peripheral blood and spleen. High levels of sFRP5 inhibited early B‐cell differentiation in the bone marrow (BM), resulting in the accumulation of cells with a common lymphoid progenitor (CLP) phenotype. Conversely, sFRP5 deficiency reduced the number of hematopoietic stem cells (HSCs) and primitive lymphoid progenitors in the BM, particularly when estrogen was administered. Furthermore, a significant reduction in CLPs and B‐lineage‐committed progenitors was observed in the BM of sfrp5‐null pregnant females. We concluded that, although high sFRP5 expression inhibits B‐lymphopoiesis in vivo, physiologically, it contributes to the preservation of very primitive lymphopoietic progenitors, including HSCs, under high estrogen levels. Thus, sFRP5 regulates early lympho‐hematopoiesis in the maternal BM, but the maternal–fetal immune tolerance still involves other molecular mechanisms that remain to be uncovered.
Blocking of LFA‐1 enhances expansion of Th17 cells induced by human CD14+CD16++ nonclassical monocytes
Authors: Traunecker Emmanuel , Gardner Rui , Fonseca João Eurico , Polido‐Pereira Joaquim , Seitz Michael , Villiger Peter M. , Iezzi Giandomenica , Padovan Elisabetta
Published: February 2015

Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14++CD16− (cMo) and intermediate CD14++CD16+ (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14+CD16++ Mo (nMo) on T‐cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL‐17+ T‐cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4+ T cells in the absence of TLR‐2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL‐17‐producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA‐1/ICAM‐1 interaction resulted in a significant increase in the percentage of IL‐17+ T cells expanded in nMo/T‐cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T‐cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T‐cell responses and suggest that nMo could become a critical therapeutic target against IL‐17‐mediated inflammatory diseases.
Synthesis of CpM(CO)3–DAB and –PAMAM Dendrimer Conjugates and Preliminary Evaluation of Their Biological Activity
Authors: Hu Wanning , Hoyer Jan , Neundorf Ines , Govender Preshendren , Smith Gregory S. , Schatzschneider Ulrich
Published: February 2015

Dendrimers of different generations and core structures [diaminobutane poly(propylenimine) (DAB) G1, G2, G3; poly(amidoamine) (PAMAM) G1] were chosen as carriers for bioactive organometallic half‐sandwich complexes of the type CpM(CO)3 (Cp = cyclopentadienyl, M = Mn or Re) to study the influence of these parameters on their biological activity against cancer cells. Structure–activity relationships were determined by variation of the metal center as well as the type, molecular weight, and number of terminal functional groups of the dendrimer conjugates. All conjugates were characterized by IR and NMR spectroscopy as well as HPLC. Their biological activity was determined on MCF‐7 human breast cancer cells by the resazurin assay. Interestingly, the most‐active compounds were the first‐generation dendrimer conjugates. The Mn and Re series showed nearly the same activities. Thus, the cytotoxicity of the dendrimer conjugates does not seem to directly correlate with the type or number of terminal functional groups. Rather, it points to a mechanism of action that is different from that previously observed for peptide conjugates with similar CpM(CO)3 functional groups.
Generation of Defect‐Modulated Metal–Organic Frameworks by Fragmented‐Linker Co‐Assembly of CPO‐27(M) Frameworks
Authors: El‐Gamel Nadia E. A.
Published: February 2015

The generation of defect‐modulated metal–organic frameworks (MOFs) by the successful stepwise doping of 2‐hydroxyterephthalate (BDC‐OH) into frameworks of the CPO‐27‐M type is discussed. The influence of MgII, CoII, and NiII ions on the product formation has been investigated by powder XRD (PXRD), IR spectroscopy, and thermal analysis. To establish the successful incorporation of the fragmented linker molecule, 1H NMR spectra were recorded after the digestion of the MOFs in DCl/[D6]dimethyl sulfoxide. After the incorporation of BDC‐OH, microporous structures were generated with reasonable porosity. The morphologies of the reaction products were checked by SEM measurements, and no significant changes to the morphologies were observed after the fragmented‐linker doping.
Spring‐Loaded Iron(II) Complexes as Magnetogenic Probes Reporting on a Chemical Analyte in Water
Authors: Gondrand Corentin , Touti Fayçal , Godart Estelle , Berezhanskyy Yevgen , Jeanneau Erwann , Maurin Philippe , Hasserodt Jens
Published: February 2015

A paramagnetic quality may be established in an aqueous sample if it contains a molecular probe that responds to the addition of a chemical analyte by turning from a diamagnetic state into a paramagnetic one (off–on). We explore here a stable, low‐spin, binary iron(II) complex that stores so much potential energy that its transformation by the target analyte leads to its fragmentation into a high‐spin complex despite the imposing strength of the chelate effect. The underlying ligand is a mixed aminal, the components of which can be freely varied to optimize response kinetics with the initial probe stability preserved. With decreasing leaving‐group character of the azole component, the probe stability improves, and the response kinetics diminish. An optimal arrangement can be found with a pyrazole paired with an electron‐deficient aromatic carbaldehyde component (nitro substitution). The drastic electronic reversion associated with the reduction of the nitro group to an amino group is the principal reason for the observation of an initially stable probe that suffers swift fragmentation when reacted with a reductive analyte.
On the Iron(V) Reactivity of an Aggressive Tail‐Fluorinated Tetraamido Macrocyclic Ligand (TAML) Activator
Authors: Ren Qizhi , Guo Yisong , Mills Matthew R. , Ryabov Alexander D. , Collins Terrence J.
Published: February 2015

The electronic properties of iron tetraamido macrocyclic ligand (TAML) activators of peroxides can be finely and coarsely tuned by varying the substituents on the “head” and “tail” macrocyclic components, respectively. By examining the reactivity of the TAML oxidoiron(V) complex with head‐NO2 and tail‐F substituents, one is able to compare the impact of significantly reduced macrocyclic tetraamide donor capacity on fundamental processes such as hydrogen‐atom abstraction, oxygen‐atom transfer, and electron transfer by using prior studies with more electron‐rich TAML systems. Herein, we demonstrate that the oxidoiron(V) form 3c can be generated by treatment of [Fe{4‐NO2C6H3‐1,2‐(N2COCMe2N3CO)2CF2(Fe–N2)(Fe–N3)}(OH2)]– (1c) with m‐chloroperoxybenzoic acid (mCPBA) in MeCN at –40 °C. The oxidation proceeds through the intermediacy of the μ‐oxo[iron(IV)]2 dimer. The overall rate of the FeIII→FeV conversion by mCPBA is slightly faster for 1c than that of its less electron‐rich precursor [Fe{C6H4‐1,2‐(N1COCMe2N2CO)2CMe2(Fe–N1)(Fe–N2)}(OH2)]– (1a). Nevertheless, the oxidative reactivity of 3c toward thioanisole and the hydrocarbons ethylbenzene and cyclohexane exceeds that of 3a by 4.3, 2.1, and 2.6 times, respectively. The reactivity of 3c is significantly greater towards ethylbenzene than that of the oxidoiron(V) species 3b derived from [Fe{C6H4‐1,2‐(N1COCMe2N2CO)2NMe(Fe–N1)(Fe–N2)}(OH2)]– (1b).
Cycloaddition Reactions of Alkyl Cyclopropenecarboxylates Generated in situ with Nitrones: Construction of Substituted Pyrroles and 1,2‐Oxazinanes
Authors: Hu Junhao , Zhang Min , Gong Yuefa
Published: February 2015

A highly regioselective [3+2] cycloaddition reaction of nitrones 1 with alkyl 2‐aroylcyclopropenecarboxylates generated in situ from alkyl 2‐aroyl‐1‐chlorocyclopropanecarboxylates 2 under basic conditions is described. The reaction proceeded readily to afford ring‐fused isoxazolidines 3 in moderate‐to‐high yields. The strained ring‐fused cycloaddition products were selectively transformed into the corresponding polysubstituted pyrroles, for example, pyrrolizine derivatives, through N–O bond cleavage or 1,2‐oxazinane derivatives through ring‐opening by treatment with HCl·pyridine in alcoholic solvents.
Synthesis, Properties, and Redox Behavior of Tris(1‐azulenyltetracyanobutadiene) and Tris[1‐azulenylbis(tetracyanobutadiene)] Chromophores Connected to a 1,3,5‐Tri(1‐azulenyl)benzene Core
Authors: Shoji Taku , Maruyama Akifumi , Shimomura Erika , Nagai Daichi , Ito Shunji , Okujima Tetsuo , Toyota Kozo
Published: February 2015

Tris(1‐azulenylacetylene) and tris(1‐azulenylethynylarylacetylene) chromophores connected to a 1,3,5‐tri(1‐azulenyl)benzene core have been prepared by the Pd‐catalyzed alkynylations of 1‐ethynylazulene with tris(3‐iodo‐1‐azulenyl)benzene or iodoarene derivatives substituted with a 1‐azulenylethynyl group with tris(3‐ethynyl‐1‐azulenyl)benzene under Sonogashira–Hagihara cross‐coupling conditions. These compounds reacted with tetracyanoethylene in formal [2+2] cycloaddition–retroelectrocyclization reactions to afford the corresponding tris(1‐azulenyltetracyanobutadiene) and tris[1‐azulenylbis(tetracyanobutadiene)] chromophores in excellent yields. The redox behavior of the tetracyanobutadiene (TCBD) derivatives was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed their multistep electrochemical reduction properties. Moreover, significant color changes were observed by visible spectroscopy under the electrochemical reduction conditions.
Stabilization of a Natural β‐Hairpin by a Twist‐Compatible β‐Turn Mimetic
Authors: Körling Matthias , Geyer Armin
Published: February 2015

Dissecting proteins into their secondary structure elements (subdomains) should yield discrete peptide epitopes. However, β‐hairpins detached from their natural protein environment usually lose their well‐defined shape and, consequently, molecular recognition processes, such as antibody binding or protein interactions, are affected significantly. Thus, the isolated central β‐hairpin (residues 12–24) of Foldon, the protein domain of this study, relaxes into a multitude of rotamers, although it still fulfills all necessary requirements to fold into a highly twisted shape. Here, two stabilization strategies from either end of the antiparallel strands of the discrete hairpin are opposed to each other, which reconstitute its shape in solution. The local side chain to backbone cyclization by the twist‐compatible bicyclic β‐turn mimetic Hot=Tap is identified to be superior to macrocyclic disulfide cyclization, which provokes local structural distortions.
Chiral (Cyclopentadienone)iron Complexes for the Catalytic Asymmetric Hydrogenation of Ketones
Authors: Gajewski Piotr , Renom‐Carrasco Marc , Facchini Sofia Vailati , Pignataro Luca , Lefort Laurent , de Vries Johannes G. , Ferraccioli Raffaella , Forni Alessandra , Piarulli Umberto , Gennari Cesare
Published: February 2015

Three chiral (cyclopentadienone)iron complexes derived from (R)‐BINOL (CK1–3) were synthesized and their structures unambiguously confirmed by X‐ray analysis (CK3). Under suitable conditions for the in situ conversion into the corresponding (hydroxycyclopentadienyl)iron hydrides (Me3NO, H2), the new chiral complexes were tested in the catalytic asymmetric hydrogenation of ketones, showing moderate to good enantioselectivity. In particular, the complex bearing methoxy substituents at the 3,3′‐positions of the binaphthyl moiety (CK2) proved remarkably more enantioselective than the unsubstituted one (CK1) and reached the highest level of enantioselectivity (up to 77 % ee) ever obtained with chiral (cyclopentadienone)iron complexes.
Death awareness and body–self dualism: A why and how of afterlife belief
Authors: Heflick Nathan A. , Goldenberg Jamie L. , Hart Joshua , Kamp Siri‐Maria
Published: February 2015

Belief in life after death offers potential comfort in the face of inevitable death. However, afterlife belief likely requires not only an awareness of death but also body–self dualism—the perception that the self (e.g., the mind) is distinct from the physical, undeniably mortal, body. In turn, we hypothesized that mortality salience (MS) should heighten afterlife belief only when dualism is facilitated. Study 1 found that MS increased belief for people high, relative to low, in trait mind–body dualism. In Study 2, MS only increased belief when people first wrote about their thoughts and personality, which a pilot study confirmed facilitated dualistic belief, relative to thinking about the physical self. Study 3 used the brain–computer interface technology to induce a dualistic experience: MS increased belief when participants accurately “typed” without the use of their external body (i.e., no hands). Together, these findings support the position that mortality awareness and body–self dualism constitute a “why” and “how” of afterlife belief. Copyright © 2015 John Wiley & Sons, Ltd.