bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable Groundwater Management: A Comparative Study of Local Policy Changes and Ecosystem Services in South Africa and Germany
Authors: Knüppe Kathrin , Pahl‐Wostl Claudia , Vinke‐de Kruijf Joanne
Published: July 2015

Groundwater‐dependent ecosystem services provide benefits to human well‐being and play a key role in regulating ecosystem processes and functions. Improving groundwater management is of fundamental importance to reduce ecological trade‐offs and to avoid long‐term negative consequences for societies. In this context, local groundwater policies as well as multi‐level governance processes play a key role. This article provides an improved understanding of how local policies change in response to social–ecological drivers and how these changes contribute to the sustainable provision of groundwater‐dependent ecosystem services. Within this context, we analyze recent changes in local groundwater policies in the Sandveld region (South Africa) and the Spreewald region (Germany) from a multi‐level governance perspective. In both cases a combination of drivers – in particular ecological degradation experienced at the local level and socio‐political transformation – led to changes of local groundwater policies. A positive impact of these changes is expected, but not yet visible. The studied policies consider the complexity of groundwater functions and the different users depending on them. However, they do not explicitly mention ecosystem services and ignore important ecological processes and functions. Therefore, we conclude that groundwater management could become more sustainable by taking ecosystem services and stakeholder interests more explicitly into account in local policy processes. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Elevated growth differentiation factor 15 levels predict outcome in patients undergoing transcatheter aortic valve implantation
Authors: Krau Nora‐Christina , Lünstedt Nina‐Sophie , Freitag‐Wolf Sandra , Brehm Doreen , Petzina Rainer , Lutter Georg , Bramlage Peter , Dempfle Astrid , Frey Norbert , Frank Derk
Published: July 2015

Aims

Transcatheter aortic valve implantation (TAVI) has emerged as a treatment of aortic stenosis in patients at high surgical risk. However, risk stratification in this elderly population is challenging, as patients at extreme risk might not benefit from TAVI. While several clinical criteria have been proposed for estimating the outcome, prediction of individual risk remains difficult. Therefore, our aim was to assess the prognostic value of the biomarker growth differentiation factor 15 (GDF15).

Methods and results

Over a 2.9‐year period, we prospectively enrolled 217 patients undergoing TAVI. Clinical parameters, risk scores, and biomarkers (NT‐proBNP and GDF15) were measured at baseline. The primary endpoint was survival time; prognostic factors were analysed by Cox regression analysis. Mean age of study participants was 81.8 ± 6.0 years. Median Logistic EuroSCORE was 20.1 (Q1–Q3 13.6–32.6). Thirty‐day mortality was 6.9%; 30.4% of the patients died during follow‐up [median 349 days (Q1–Q3 106–660)]. Median pre‐procedural GDF15 values were 2256 pg/mL (1585–3082). High GDF15 levels were associated with numerous factors that could contribute to poor outcome. Analyses comparing the upper quartile with the lower three quartiles for biomarker levels revealed a hazard ratio (HR) of increased GDF15 for adverse outcome of 2.4 [95% confidence interval (CI) 1.5–3.9, P < 0.001]. Of note, in multiple analyses, elevated GDF15 levels were superior to NT‐proBNP for predicting negative outcome (adjusted HR of GDF15 1.97, 95% CI 1.2–3.3; P = 0.009).

Conclusion

Elevated GDF15 levels were superior to NT‐proBNP for TAVI risk stratification and provided additional prognostic information. Thus, patient selection for TAVI may benefit from measurement of GDF15.
Trimetallic PEPPSI‐Type Palladium N‐Heterocyclic Carbene Complexes – Improved Catalyst Lifetime in the Mizoroki–Heck Coupling Reaction
Authors: Martínez‐Olid Francisco , Andrés Román , Flores Juan C. , Gómez‐Sal Pilar
Published: July 2015

A series of mono‐ and dendritic trimetallic PEPPSI‐type (pyridine‐enhanced precatalyst preparation stabilization and initiation) complexes bearing N‐heterocyclic carbene (NHC) ligands containing a protected amine in the form of an ethylphthalimido group have been synthesized. These discrete prototypes of complexes covalently bound to suitable supports have been studied in the Mizoroki–Heck coupling of aryl iodides under mild conditions, including sets of experiments to assess the lifetime of the active species. The palladated dendrons are more efficient and robust catalysts than their monometallic counterparts.
Metal‐Free Oxidative C–H Amidation of N,N′‐Diarylureas with PhI(OAc)2: Synthesis of Benzimidazol‐2‐one Derivatives
Authors: Yu Jipan , Gao Chang , Song Zhixuan , Yang Haijun , Fu Hua
Published: July 2015

Benzimidazol‐2‐ones have various biological functions and are usually prepared by reactions of substituted benzene‐1,2‐diamines with carbonyl‐containing compounds or intramolecular N‐arylations using substrates with carbon‐halogen bonds. However, the starting materials of these protocols are often not readily available. Herein, a simple and practical metal‐free oxidative C–H amidation of N,N′‐diarylureas has been developed that takes place at room temperature. This protocol uses readily available N,N′‐diarylureas as the starting materials and inexpensive PhI(OAc)2 as the oxidant without the need of a catalyst, ligand, or the exclusion of air. The present method has a wide functional group tolerance and affords a new and practical strategy for the synthesis of N‐heterocycles.
Corrosion Behavior of Biocompatible Stainless Steels in Physiological Medium for Non‐invasive Diagnosis of Small Fiber Neuropathies Applications
Authors: Calmet Amandine , Amar Abdelilah , Griveau Sophie , Lair Virginie , Sutter Eliane , Recio Francisco Javier , Brunswick Philippe , Bedioui Fethi , Cassir Michel
Published: July 2015

A non‐invasive device based on measurements of electrochemical skin conductance can detect small fiber neuropathy, a sweat gland dysfunction implicated in several diseases. The measurement is related to sweat composition and notably to chloride concentration. To optimize the electrode material, in vitro experiments are performed in mimetic sweat solutions. This work reports on the resistance to pitting corrosion of biocompatible stainless steels (AISI 304L, AISI 430, AISI 430T, D2205) in sweat mimicking electrolyte at pH 7 with variable chloride concentration, to determine the most sensitive material to sweat composition. AISI 430 is promising due to its high sensitivity to chloride concentration variations.
Physicochemical Properties and Slurry Ability of Lignite Upgraded by a Solvent‐Extraction Approach
Authors: Sun Ye , Wang Xingjun , Dai Zhenghua , Yu Guangsuo , Wang Fuchen
Published: July 2015

Supercritical carbon dioxide (scCO2)/coal tar/N‐methyl‐2‐pyrrolidinone (NMP) mixed solvent was used to upgrade lignite by extraction in a semicontinuous supercritical extraction device. The upgraded lignite has potential applications in coal–water slurry (CWS) gasification. The effects of the process conditions (operating temperature, pressure, solvent ratio, and particle size) on the physical and chemical properties of the upgraded lignite were studied. The Brunauer–Emmett–Teller specific surface area and the Barrett–Joyner–Halenda absorption pore volume of the upgraded coal increased to approximately twice those of the raw lignite. The BJH adsorption average pore diameter of the upgraded coal was smaller than that of raw lignite. The heavy constituents in coal tar were absorbed into the coal pore structure, and the low‐molecular‐weight compounds in lignite and coal tar could be extracted. The results showed that upgraded lignite with a better slurry ability was achieved by extraction with the scCO2/coal tar/NMP mixed solvent. The upgraded CWS concentration increased by 6–10 %. The flowability of the upgraded CWS improved slightly. After upgrade through the scCO2/tar/NMP process, the pseudoplastic‐fluid trend of the upgraded CWS improved, and the lignite gasification reactivity improved.
New Careers in Nursing Scholar Alumni: Options in the Early Career Years
Authors: Millett Catherine M. , Stickler Leslie M. , Wang Haijiang
Published: July 2015

The New Careers in Nursing (NCIN) Alumni Survey was designed to advance knowledge in the field of nursing education by looking at post‐degree experiences of NCIN scholarship recipients, such as employment and graduate degree attainment. The NCIN Alumni Study also focused on the reflections of NCIN scholars who have graduated and moved into the field, on their satisfaction with various aspects of NCIN and their academic programs, and on how these programmatic aspects have influenced their postdegree experiences.
Buccal adhesive nanofibers containing human growth hormone for oral mucositis
Authors: Choi Ji Suk , Han Suk‐Hee , Hyun Changbaig , Yoo Hyuk Sang
Published: July 2015

Due to a lack of proper drug carriers to deliver treatments for mucositis, many cancer patients suffer from oral mucositis caused by chemotherapy and radiotherapy. We prepared a double‐layered electrospun nanofibrous sheets composed of Eudragit and chitosan to accelerate the healing rate of oral mucous ulcer. Human growth hormone (hGH) and Eudragit in a mixture of dimethylacetamide and ethanol were co‐electrospun to nanofibrous sheets. The electrospun fibrous mat was subsequently layered with chitosan by a dip‐coating method. Chitosan‐layered sheets showed attenuated mass erosion while uncoated sheets were instantly melted at the physiological condition. The released hGH was trapped on the chitosan layer by the ionic interaction between positively charged chitosan and negatively charged hGH, and a large number of entrapped proteins remained on the SIS membrane due to the muco‐adhesive properties of chitosan. hGH‐incorporated sheets significantly increased proliferation of human dermal fibroblasts. In vivo study employing oral ulcers in dogs, the ulcers dressed with chitosan‐layered sheets showed enhanced wound recovery and the chitosan layers on the sheet greatly assisted prolonged recovery. Therefore, chitosan‐layered Eudragit nanofibrous sheets can be potentially applied to developing muco‐adhesive wound dressing materials with pH‐dependent drug release by adjusting the thickness of chitosan sheath on the sheets. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1396–1406, 2016.
In vitro and in vivo evaluation of a shape memory polymer foam‐over‐wire embolization device delivered in saccular aneurysm models
Authors: Boyle Anthony J. , Landsman Todd L. , Wierzbicki Mark A. , Nash Landon D. , Hwang Wonjun , Miller Matthew W. , Tuzun Egemen , Hasan Sayyeda M. , Maitland Duncan J.
Published: July 2015

Current endovascular therapies for intracranial saccular aneurysms result in high recurrence rates due to poor tissue healing, coil compaction, and aneurysm growth. We propose treatment of saccular aneurysms using shape memory polymer (SMP) foam to improve clinical outcomes. SMP foam‐over‐wire (FOW) embolization devices were delivered to in vitro and in vivo porcine saccular aneurysm models to evaluate device efficacy, aneurysm occlusion, and acute clotting. FOW devices demonstrated effective delivery and stable implantation in vitro. In vivo porcine aneurysms were successfully occluded using FOW devices with theoretical volume occlusion values greater than 72% and rapid, stable thrombus formation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1407–1415, 2016.
An enhanced Monte Carlo outlier detection method
Authors: Zhang Liangxiao , Li Peiwu , Mao Jin , Ma Fei , Ding Xiaoxia , Zhang Qi
Published: July 2015

Outlier detection is crucial in building a highly predictive model. In this study, we proposed an enhanced Monte Carlo outlier detection method by establishing cross‐prediction models based on determinate normal samples and analyzing the distribution of prediction errors individually for dubious samples. One simulated and three real datasets were used to illustrate and validate the performance of our method, and the results indicated that this method outperformed Monte Carlo outlier detection in outlier diagnosis. After these outliers were removed, the value of validation by Kovats retention indices and the root mean square error of prediction decreased from 3.195 to 1.655, and the average cross‐validation prediction error decreased from 2.0341 to 1.2780. This method helps establish a good model by eliminating outliers. © 2015 Wiley Periodicals, Inc.
Interaction of water with a benzimidazole derivative: fluorescence and colorimetric recognition of trace level water involving intra‐molecular charge transfer process
Authors: Nandi Sandip , Mandal Sandip , Matalobos Jesus Sanmartin , Sahana Animesh , Das Debasis
Published: July 2015

Benzimidazole‐derived ICT‐based probe, DFPBEN is developed for trace level determination of water. In presence of water, the naked eye color of DFPBEN changes from red to yellow, while it turns to green from red under UV light. Upon addition of water, DFPBEN shows a ratiometric absorbance change in methanol. Copyright © 2015 John Wiley & Sons, Ltd.
Relationship between MRI T1rho value and histological findings of intact and radially incised menisci in microminipigs
Authors: Nakagawa Yusuke , Sekiya Ichiro , Kondo Shimpei , Tabuchi Takashi , Ichinose Shizuko , Koga Hideyuki , Tsuji Kunikazu , Muneta Takeshi
Published: July 2015

Purpose

To examine whether the T1rho value reflects histological changes in menisci we analyzed the relationship between T1rho value and histological findings in intact and radially incised menisci of pigs.

Materials and Methods

Seven microminipigs were used for this experiment. A radial incision was created and repaired in the medial meniscus, which was evaluated 4 weeks after surgery. Sagittal T1rho mapping images were taken by 3.0T magnetic resonance imaging (MRI). The region of interest was set by dividing the meniscus into six zones (from zone 1 to zone 6). For histological evaluation of intact menisci, characteristics of each zone were determined. In incised menisci, a histological score was used to evaluate pathological change.

Results

In intact lateral menisci, the zone where histological findings indicated fibrocartilage showed a lower T1rho value (34.2 ± 2.3 msec) than hyaline‐like cartilage (38.2 ± 2.5 msec) or fibrous tissue (37.2 ± 2.0 msec). In incised medial menisci, T1rho values increased (about 50–90 msec) in the zone where histological findings indicated that synovial ingrowth, scar tissue formation, and degenerative changes had occurred. There were correlations between T1rho values and histological scores in all zones (r = 0.62–0.92, P = 0.001–0.026).

Conclusion

Zonal variations of the T1rho value were observed in intact menisci due to varying structure in each zone. T1rho values were correlated with histological changes such as collagen fiber organization and safranin‐o stainability in incised menisci. This study supports T1rho mapping as useful for evaluating ultrastructural composition in menisci. J. Magn. Reson. Imaging 2016;43:434–445.
Longitudinal study of the substantia nigra in Parkinson disease: A high‐field 1H‐MR spectroscopy imaging study
Authors: Seraji‐Bozorgzad Navid , Bao Fen , George Edwin , Krstevska Shana , Gorden Veronica , Chorostecki Jessica , Santiago Carla , Zak Imad , Caon Christina , Khan Omar
Published: July 2015

Introduction

The value of biomarkers in early diagnosis and development of therapeutics in Parkinson's disease (PD) is well established.

Methods

We used proton magnetic resonance spectroscopy in a prospective, longitudinal study of 23 patients with early PD, naïve to dopaminergic therapy, and six age‐matched healthy controls to examine the temporal changes in metabolic profile of substantia nigra over a period of 3 months.

Results

N‐acetyl aspartate to creatine ratio at month 3 was compared with baseline values in the PD and control groups, as well as the side‐to‐side difference of the ratio at baseline. By month 3, n‐acetyl aspartate to creatine ratio had decreased by 4.4% in patients with PD (P = 0.024), without a concomitant change in healthy controls. The side‐to‐side asymmetry was significantly higher in the PD group (16.7%) vs. healthy controls (1.6%, P = 0.0024).

Conclusion

Estimation of change in the n‐acetyl aspartate to creatine ratio appears to be a fast, quantifiable, and reliable marker of dopaminergic neuronal viability in PD. © 2015 International Parkinson and Movement Disorder Society
A Rebuttal to Comments on ‘Sacrifice of the Social Outsider’
Authors: Kieffer C. L.
Published: July 2015

A recent publication by the author documented two probable cases of Klippel–Feil Syndrome at the site of Midnight Terror Cave in the Cayo District of Belize. Radiographic images recently taken of the multiple congenital fused vertebrae from these two individuals raised discussion regarding the initial assessment of Klippel–Feil Syndrome. This commentary further discusses the topic by dealing with researcher assumptions of the syndrome and indicates radiographic data do not provide enough evidence to change the initial assessment. Copyright © 2015 John Wiley & Sons, Ltd.
Nitrogen Radical and Plasma Diagnostics in Dual Frequency Hybrid Plasmas to Investigate N2/SiH4 PECVD Process
Authors: Sahu Bibhuti Bhusan , Han Jeon Geon , Shin Kyung Sik , Hori Masaru
Published: July 2015

The present work addresses a systematic approach for measuring the atomic nitrogen radicals using vacuum ultraviolet absorption spectroscopy (VUVAS) in the N2‐SiH4 PECVD processes using alternate plasma concepts. Measurements using VUVAS and RF compensated Langmuir probe reveal that there is significant enhancement in the radical and plasma density when the discharge is operated using the dual frequency hybrid source using the combination of a low and a very high‐frequency source. The behavior of low frequency and dual frequency capacitively coupled plasma (CCP) discharges is experimentally investigated. This study also presents a detailed analysis and effectiveness of the dual frequency hybrid plasmas for the practical applications.
Combining large number of weak biomarkers based on AUC
Authors: Yan Li , Tian Lili , Liu Song
Published: July 2015

Combining multiple biomarkers to improve diagnosis and/or prognosis accuracy is a common practice in clinical medicine. Both parametric and non‐parametric methods have been developed for finding the optimal linear combination of biomarkers to maximize the area under the receiver operating characteristic curve (AUC), primarily focusing on the setting with a small number of well‐defined biomarkers. This problem becomes more challenging when the number of observations is not order of magnitude greater than the number of variables, especially when the involved biomarkers are relatively weak. Such settings are not uncommon in certain applied fields. The first aim of this paper is to empirically evaluate the performance of existing linear combination methods under such settings. The second aim is to propose a new combination method, namely, the pairwise approach, to maximizeAUC. Our simulation studies demonstrated that the performance of several existing methods can become unsatisfactory as the number of markers becomes large, while the newly proposed pairwise method performs reasonably well. Furthermore, we apply all the combination methods to real datasets used for the development and validation of MammaPrint. The implication of our study for the design of optimal linear combination methods is discussed. Copyright © 2015 John Wiley & Sons, Ltd.
The perilous leap between exploration and exploitation
Authors: Swift Tim
Published: July 2015

Research summary: R&D‐based exploration and exploitation are necessary in order for firms to have sustainable competitive advantage. Yet, transitioning between these orthogonal types of R&D is considered profound organizational change. Building on recent research showing that compact, significant changes in R&D expenditure is an antecedent to the transition between explorative and exploitative R&D, I show that this leap between exploration and exploitation is quite hazardous. The magnitude of changes in R&D expenditure, whether increases or decreases, is positively associated with organizational failure. Firms maintaining higher levels of absorptive capacity are more capable of surviving the leap from R&D‐based exploitation to exploration, and firms that do not use reductions in R&D expenditure to manipulate short‐term earnings performance are more likely to survive the leap from exploration to exploitation.

Managerial summary: In order to survive and thrive, innovative companies must be able to exploit their existing competencies, and to explore for new ones once those current competencies decline in value. However, transiting from one form of innovation to the other is difficult because the skills required to explore are fundamentally opposed to those required to exploit. In this article, I describe how difficult this leap between exploration and exploitation can be. I show that the move between R&D‐based exploration and exploitation is related to organizational failure. In addition, firms that are superior learners are more likely to survive the leap from exploitation to exploration, and firms that are not cutting R&D expenditure to manipulate earnings are more likely to survive the leap from exploration to exploitation. Copyright © 2015 John Wiley & Sons, Ltd.
Concise Review: Patient-Derived Stem Cell Research for Monogenic Disorders
Authors: Qin Yiren , Gao Wei-Qiang
Published: July 2015

Monogenic disorders (MGDs) are caused by a single gene mutation and have a serious impact on human health. At present, there are no effective therapeutic methods for MGDs. Stem cell techniques provide insights into potential treatments for MGDs. With the development of patient-derived stem cells, we can begin to progressively understand the molecular mechanism of MGDs and identify new drugs for MGD treatment. Using powerful genome editing tools, such as zinc finger nucleases, transcriptional activator-like effector nucleases, and the clustered regulatory interspaced short palindromic repeat/Cas9 system, MGD-associated gene mutations can be corrected in MGD stem cells in vitro and then transplanted into MGD animal models to assess their safety and therapeutic effects. Despite the continued challenges surrounding potential pluripotent stem cell tumorigenicity and concerns regarding the genetic modification of stem cells, the extensive clinical application of MGD patient-specific stem cells will be pursued through further advances in basic research in the MGD field. In this review, we will summarize the latest progress in research into the use of patient-derived stem cells for the potential treatment of MGDs and provide predictions regarding the direction of future investigations.
In Vitro T-Cell Generation From Adult, Embryonic, and Induced Pluripotent Stem Cells: Many Roads to One Destination
Authors: Smith Michelle J. , Webber Beau R. , Mohtashami Mahmood , Stefanski Heather E. , Zún˜iga-Pflücker Juan Carlos , Blazar Bruce R.
Published: July 2015

T lymphocytes are critical mediators of the adaptive immune system and have the capacity to serve as therapeutic agents in the areas of transplant and cancer immunotherapy. While T cells can be isolated and expanded from patients, T cells derived in vitro from both hematopoietic stem/progenitor cells (HSPCs) and human pluripotent stem cells (hPSCs) offer great potential advantages in generating a self-renewing source of T cells that can be readily genetically modified. T-cell differentiation in vivo is a complex process requiring tightly regulated signals; providing the correct signals in vitro to induce T-cell lineage commitment followed by their development into mature, functional, single positive T cells, is similarly complex. In this review, we discuss current methods for the in vitro derivation of T cells from murine and human HSPCs and hPSCs that use feeder-cell and feeder-cell-free systems. Furthermore, we explore their potential for adoption for use in T-cell-based therapies. Stem Cells  2015;33:3174–3180
Autocrine Action of Thrombospondin-2 Determines the Chondrogenic Differentiation Potential and Suppresses Hypertrophic Maturation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells
Authors: Jeong Sang Young , Ha Jueun , Lee Miyoung , Jin Hye Jin , Kim Dong Hyun , Choi Soo Jin , Oh Wonil , Yang Yoon Sun , Kim Jae-Sung , Kim Byung-Gyu , Chang Jeong Ho , Cho Dong-Hyung , Jeon Hong Bae
Published: July 2015

Previous studies have shown that mesenchymal stem cell (MSC)-based therapies have varying efficacies for the treatment of various diseases, including cartilage defects. In this study, we demonstrated that the chondrogenic differentiation potential of human umbilical cord blood-derived MSCs (hUCB-MSCs) obtained from different individual donors varies, and we investigated the molecular basis for this variation. Microarray gene expression analysis identified thrombospondin-2 (TSP2) as a candidate gene underlying the interindividual variation in the chondrogenic differentiation potential of hUCB-MSCs. To assess the association between TSP-2 and the differentiation potential, we evaluated chondrogenic differentiation of hUCB-MSCs treated with TSP2 siRNA. In addition, we studied the effect of supplementing exogenous recombinant TSP-2 on TSP2 siRNA-treated hUCB-MSCs. We found that TSP-2 autocrinally promoted chondrogenic differentiation of hUCB-MSCs via the Notch signaling pathway, which was confirmed in MSCs from other sources such as bone marrow and adipose tissue. Interestingly, we observed that TSP-2 attenuated hypertrophy, which inevitably occurs during chondrogenic differentiation of hUCB-MSCs. Our findings indicated that the variable chondrogenic differentiation potential of MSCs obtained from different donors is influenced by the TSP-2 level in the differentiating cells. Thus, the TSP-2 level can be used as a marker to select MSCs with superior chondrogenic differentiation potential for use in cartilage regeneration therapy. Stem Cells  2015;33:3291–3303
Negative Regulation of miR-375 by Interleukin-10 Enhances Bone Marrow-Derived Progenitor Cell-Mediated Myocardial Repair and Function After Myocardial Infarction
Authors: Garikipati Venkata Naga Srikanth , Krishnamurthy Prasanna , Verma Suresh Kumar , Khan Mohsin , Abramova Tatiana , Mackie Alexander R. , Qin Gangjian , Benedict Cynthia , Nickoloff Emily , Johnson Jennifer , Gao Ehre , Losordo Douglas W. , Houser Steven R. , Koch Walter J. , Kishore Raj
Published: July 2015

Poor survival and function of transplanted cells in ischemic and inflamed myocardium likely compromises the functional benefit of stem cell-based therapies. We have earlier reported that co-administration of interleukin (IL)−10 and BMPAC enhances cell survival and improves left ventricular (LV) functions after acute myocardial infarction (MI) in mice. We hypothesized that IL-10 regulates microRNA-375 (miR-375) signaling in BMPACs to enhance their survival and function in ischemic myocardium after MI and attenuates left ventricular dysfunction after MI. miR-375 expression is significantly upregulated in BMPACs upon exposure to inflammatory/hypoxic stimulus and also after MI. IL-10 knockout mice display significantly elevated miR-375 levels. We report that ex vivo miR-375 knockdown in BMPAC before transplantation in the ischemic myocardium after MI significantly improve the survival and retention of transplanted BMPACs and also BMPAC-mediated post-infarct repair, neovascularization, and LV functions. Our in vitro studies revealed that knockdown of miR-375-enhanced BMPAC proliferation and tube formation and inhibited apoptosis; over expression of miR-375 in BMPAC had opposite effects. Mechanistically, miR-375 negatively regulated 3-phosphoinositide-dependent protein kinase-1 (PDK-1) expression and PDK-1-mediated activation of PI3kinase/AKT signaling. Interestingly, BMPAC isolated from IL-10-deficient mice showed elevated basal levels of miR-375 and exhibited functional deficiencies, which were partly rescued by miR-375 knockdown, enhancing BMPAC function in vitro and in vivo. Taken together, our studies suggest that miR-375 is negatively associated with BMPAC function and survival and IL-10-mediated repression of miR-375 enhances BMPAC survival and function. Stem Cells  2015;33:3519–3529
Transcriptome Dynamics of Developing Photoreceptors in Three-Dimensional Retina Cultures Recapitulates Temporal Sequence of Human Cone and Rod Differentiation Revealing Cell Surface Markers and Gene Networks
Authors: Kaewkhaw Rossukon , Kaya Koray Dogan , Brooks Matthew , Homma Kohei , Zou Jizhong , Chaitankar Vijender , Rao Mahendra , Swaroop Anand
Published: July 2015

The derivation of three-dimensional (3D) stratified neural retina from pluripotent stem cells has permitted investigations of human photoreceptors. We have generated a H9 human embryonic stem cell subclone that carries a green fluorescent protein (GFP) reporter under the control of the promoter of cone-rod homeobox (CRX), an established marker of postmitotic photoreceptor precursors. The CRXp-GFP reporter replicates endogenous CRX expression in vitro when the H9 subclone is induced to form self-organizing 3D retina-like tissue. At day 37, CRX+ photoreceptors appear in the basal or middle part of neural retina and migrate to apical side by day 67. Temporal and spatial patterns of retinal cell type markers recapitulate the predicted sequence of development. Cone gene expression is concomitant with CRX, whereas rod differentiation factor neural retina leucine zipper protein (NRL) is first observed at day 67. At day 90, robust expression of NRL and its target nuclear receptor NR2E3 is evident in many CRX+ cells, while minimal S-opsin and no rhodopsin or L/M-opsin is present. The transcriptome profile, by RNA-seq, of developing human photoreceptors is remarkably concordant with mRNA and immunohistochemistry data available for human fetal retina although many targets of CRX, including phototransduction genes, exhibit a significant delay in expression. We report on temporal changes in gene signatures, including expression of cell surface markers and transcription factors; these expression changes should assist in isolation of photoreceptors at distinct stages of differentiation and in delineating coexpression networks. Our studies establish the first global expression database of developing human photoreceptors, providing a reference map for functional studies in retinal cultures. Stem Cells  2015;33:3504–3518
Azide Chemistry – An Inorganic Perspective, Part II[‡][3+2]‐Cycloaddition Reactions of Metal Azides and Related Systems
Authors: Fehlhammer Wolf Peter , Beck Wolfgang
Published: July 2015

In whatever state of bonding – whether covalent to an organic residue or a heteroatom, or polar to ionic in contact with a metal – the azide moiety N3is characterized by its high potential of reactivity which essentially manifests itself in two basic processes: the elimination of dinitrogen and the entry into 1, 3‐dipolar cycloadditions with suitable dipolarophiles, the latter of which clearly predominates the chemistry of azide, also that of its metal compounds. In a preceding review entitled“Part I – Metal Azides: Overview, General Trends and Recent Developments”which was meant to lay the foundations for the present paper, these and other reactions have already been touched upon. The present review – Part II – now focusses in great detail on the formation of five‐membered heterocycles – tetrazol(at)es, triazol(at)es, triazolin(at)es, thiatriazol(at)es, etc. as well as various consecutive products – from azide and nitriles, isocyanides, alkynes, alkenes and heteroallenes (CS2, RN=C=S) in the ligand sphere of the metal. Generally, these [3+2]‐cycloadditions are found to proceed under much milder conditions in comparison with the strictly organic case whose triumphant progress since the 1960s is intimately bound up with the name of Huisgen. Mechanistic considerations on the matter are presented. A secondary aspect still occupying quite a part of the discussion is concerned with the role of metals in [3+2]‐cycloadditions particularly of the highly topical “click”‐type, e.g. (CuAAC), (RuAAC). Likewise, a short chapter deals with the question of pentazol(at)e (N5–) which according to numerous theoretical studies could well be stabilized and isolated in combination with metals, e.g., in the form of azametallocenes. A last chapter is devoted to a cursory survey of related systems, in particular fulminato complexes, metallonitrile ylides and metallonitrile imines, in which the metal acts as a substituent on the 1, 3‐dipole (metallo‐1, 3‐dipole). Other systems with a metal substituent on the dipolarophile (metallo‐dipolarophile), or, with metal itself in the three‐ (two‐) atom arrangement constituting the dipole (dipolarophile) [metalla‐1, 3‐dipole, metalla‐dipolarophile] are only quoted by way of example.
Hořava-Lifshitz gravity from dynamical Newton-Cartan geometry
Authors: Hartong Jelle , Obers Niels A.
Published: July 2015

Abstract

Recently it has been established that torsional Newton-Cartan (TNC) geometry is the appropriate geometrical framework to which non-relativistic field theories couple. We show that when these geometries are made dynamical they give rise to Hořava-Lifshitz (HL) gravity. Projectable HL gravity corresponds to dynamical Newton-Cartan (NC) geometry without torsion and non-projectable HL gravity corresponds to dynamical NC geometry with twistless torsion (hypersurface orthogonal foliation). We build a precise dictionary relating all fields (including the scalar khronon), their transformations and other properties in both HL gravity and dynamical TNC geometry. We use TNC invariance to construct the effective action for dynamical twistless torsional Newton-Cartan geometries in 2+1 dimensions for dynamical exponent 1 < z ≤ 2 and demonstrate that this exactly agrees with the most general forms of the HL actions constructed in the literature. Further, we identify the origin of the U(1) symmetry observed by Hořava and Melby-Thompson as coming from the Bargmann extension of the local Galilean algebra that acts on the tangent space to TNC geometries. We argue that TNC geometry, which is manifestly diffeomorphism covariant, is a natural geometrical framework underlying HL gravity and discuss some of its implications.
Blackfolds, plane waves and minimal surfaces
Authors: Armas Jay , Blau Matthias
Published: July 2015

Abstract

Minimal surfaces in Euclidean space provide examples of possible non-compact horizon geometries and topologies in asymptotically flat space-time. On the other hand, the existence of limiting surfaces in the space-time provides a simple mechanism for making these configurations compact. Limiting surfaces appear naturally in a given space-time by making minimal surfaces rotate but they are also inherent to plane wave or de Sitter space-times in which case minimal surfaces can be static and compact. We use the blackfold approach in order to scan for possible black hole horizon geometries and topologies in asymptotically flat, plane wave and de Sitter space-times. In the process we uncover several new configurations, such as black helicoids and catenoids, some of which have an asymptotically flat counterpart. In particular, we find that the ultraspinning regime of singly-spinning Myers-Perry black holes, described in terms of the simplest minimal surface (the plane), can be obtained as a limit of a black helicoid, suggesting that these two families of black holes are connected. We also show that minimal surfaces embedded in spheres rather than Euclidean space can be used to construct static compact horizons in asymptotically de Sitter space-times.
Effective theories for Dark Matter interactions and the neutrino portal paradigm
Authors: Macías Vannia González , Wudka José
Published: July 2015

Abstract

In this article we discuss a general effective-theory description of a multicomponent dark sector with an unspecified non-trivial symmetry and its interactions with the Standard Model generated by the exchange of heavy mediators. We then categorize the relevant effective operators given the current experimental sensistivity where the underlying theory is weakly coupled and renormalizable, with neutral mediators: either scalars or fermions. An interesting scenario resulting from this categorization is the neutrino portal, where only fermion mediators are present, and where the dark sector consists of fermions and scalars such that the lightest dark particle is a fermion, this scenario is characterized by having naturally suppressed couplings of the DM to all SM particles except the neutrinos and has received little attention in the literature. We find that there is a wide region in parameter space allowed by the current experimental constraints (relic abundance, direct and indirect detection limits); the cleanest signature of this paradigm is the presence of monochromatic neutrino lines with energy equal to that of the DM mass, but experimental sensitivity would have to be improved significantly before this can be probed.
Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice
Authors: Gupta Sapna , Wang Liqun , Kruger Warren D.
Published: July 2015

Cystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other treatments such as methionine restriction and supplemental B‐vitamins. However, the effectiveness of betaine supplementation by itself in the treatment of CBS deficiency has not been well explored. Here, we have examined the effect of a betaine supplemented diet on the Tg‐I278T Cbs−/− mouse model of CBS deficiency and compared its effectiveness to our previously published data using a methionine restricted diet. Tg‐I278T Cbs−/− mice on betaine, from the time of weaning until for 240 days of age, had a 40 % decrease in mean tHcy level and a 137 % increase in serum methionine levels. Betaine‐treated Tg‐I278T Cbs−/− mice also exhibited increased levels of betaine‐dependent homocysteine methyl transferase (BHMT), increased levels of the lipogenic enzyme stearoyl‐coenzyme A desaturase (SCD‐1), and increased lipid droplet accumulation in the liver. Betaine supplementation largely reversed the hair loss phenotype in Tg‐I278T Cbs−/− animals, but was far less effective than methionine restriction in reversing the weight‐loss, fat‐loss, and osteoporosis phenotypes. Surprisingly, betaine supplementation had several negative effects in control Tg‐I278T Cbs+/− mice including decreased weight gain, lean mass, and bone mineral density. Our findings indicate that while betaine supplementation does have some beneficial effects, it is not as effective as methionine restriction for reversing the phenotypes associated with severe CBS deficiency in mice.
The Swedish Adoption Twin Study of Aging: An Update
Authors: Pedersen N.L. , McClearn G.E. , Plomin R. , Nesselroade J.R. , Berg S. , DeFaire U.
Published: July 2015

The Swedish Adoption/Twin Study of Aging (SATSA) is a longitudinal program of research in gerontological genetics which is currently in its fifth year. The base population is comprised of 351 pairs of twins reared apart and 407 matched control pairs of twins reared together who responded to a questionnaire (Q1) in 1984. Two additional stages of SATSA have recently been completed: a longitudinal follow-up questionnaire mailed out in 1987 (Q2) and extensive in-person testing (IPT1) which included a health examination and cognitive battery. A second wave of IPT was started in January 1989. A summary of some of the major findings from Q1 and a description of IPT1 are reported.
Genetics, ethics and archaeology
Authors: Evison Martin P.
Published: July 2015

A further contribution on the issues raised by modern genetics, and on their relationship to the material evidence offered by archaeological remains.
Polyphenol-rich juices reduce blood pressure measures in a randomised controlled trial in high normal and hypertensive volunteers
Authors: Tjelle Torunn Elisabeth , Holtung Linda , Bøhn Siv Kjølsrud , Aaby Kjersti , Thoresen Magne , Wiik Siv Åshild , Paur Ingvild , Karlsen Anette Solli , Retterstøl Kjetil , Iversen Per Ole , Blomhoff Rune
Published: July 2015

Intake of fruits and berries may lower blood pressure (BP), most probably due to the high content of polyphenols. In the present study, we tested whether consumption of two polyphenol-rich juices could lower BP. In a randomised, double-blinded, placebo-controlled trial of 12 weeks, 134 healthy individuals, aged 50–70 years, with high normal range BP (130/85–139/89 mmHg, seventy-two subjects) or stage 1-2 hypertension (140/90–179/109 mmHg, sixty-two subjects), were included. They consumed 500 ml/d of one of either (1) a commercially available polyphenol-rich juice based on red grapes, cherries, chokeberries and bilberries; (2) a juice similar to (1) but enriched with polyphenol-rich extracts from blackcurrant press-residue or (3) a placebo juice (polyphenol contents 245·5, 305·2 and 76 mg/100 g, respectively). Resting BP was measured three times, with a 1 min interval, at baseline and after 6 and 12 weeks of intervention. Systolic BP significantly reduced over time (6 and 12 weeks, respectively) in the pooled juice group compared with the placebo group in the first of the three measurements, both for the whole study group (6·9 and 3·4 mmHg; P= 0·01) and even more pronounced in the hypertensive subjects when analysed separately (7·3 and 6·8 mmHg; P= 0·04). The variation in the BP measurements was significantly reduced in the pooled juice group compared with the placebo group (1·4 and 1·7 mmHg; P= 0·03). In conclusion, the present findings suggest that polyphenol-rich berry juice may contribute to a BP- and BP variability lowering effect, being more pronounced in hypertensive than in normotensive subjects.
Cladistic analysis of the Early Cambrian olenelloid trilobites
Authors: Lieberman Bruce S.
Published: July 2015

A phylogenetic analysis was used to determine evolutionary relationships within the Early Cambrian superfamily Olenelloidea Walcott, 1890. Phylogenetic patterns within the suborder Olenellina Walcott, 1890, which contains the Olenelloidea and the Fallotaspidoidea Hupé, 1953, are also discussed. The Olenelloidea are monophyletic, and synapomorphies uniting them include the condition of the ocular lobes where they intersect the frontal lobe of the glabella, and the condition of the lateral margins of the glabellar lobes. In contrast, taxa formerly assigned to the Fallotaspidoidea are shown to represent a paraphyletic grade of several genera, some more closely related to the Olenelloidea, and some more closely related to the Redlichiina Richter, 1933. Seventy-nine exoskeletal characters were coded for 26 taxa within the Olenellina. These included 22 ingroup Olenelloidea and four outgroup taxa that have traditionally been assigned to the Fallotaspidoidea. When subjected to parsimony analysis these character data yielded a single most parsimonious cladogram that provides an hypothesis of relationship for the generic clades within the superfamily. Two new genera are recognized herein,FritzolenellusandLochmanolenellus.It has been argued that genetic flexibility was so great and trilobite morphology was so plastic in the Early Cambrian that suprageneric classification of Early Cambrian trilobites is precluded. Although levels of intraspecific variability may have been slightly higher in the Early Cambrian relative to the mid Paleozoic, based on the extent of polymorphic character codings, it was not so high as to obviate attempts at recovering phylogenetic structure in a major clade of Early Cambrian taxa. In addition, the consistency index recovered by this analysis is not unduly low for a phylogenetic database of this size. The phylogenetic analysis also has bearing on patterns of allometric heterochrony, which have often been held to be significant in Early Cambrian trilobites. The paedomorphic retention of advanced genal spines into the adult probably evolved at least four times. Three of the episodes can be best described as neoteny, the fourth, as progenesis. Finally, based on the phylogeny, it is likely that rates of speciation in trilobites may have been two to three times higher in the Early Cambrian than in the mid Paleozoic.
Oolitized fragments of filamentous calcimicrobes and the pseudofossil affinity of Nuia Maslov from the Upper Cambrian rocks of central Texas
Authors: Spincer Ben R.
Published: July 2015

The origin and affinity of the problematic Nuia Maslov is reappraised from exceptionally preserved specimens in Upper Cambrian (Sunwaptan) rocks of the Llano Uplift, central Texas. Nuia is suggested to be a radial calcitic ooid that has nucleated on fragments of reworked filamentous calcimicrobes rather than a separate microorganism as has been assumed previously. Nuia is found predominantly in intrareef grainstone accumulations, as well as in interreef grainstones, invariably accompanied by other bioclastic debris showing similar radial calcite ooid overgrowths.
The classification of athyridid brachiopods
Authors: Alvarez Fernando , Jia-Yu Rong , Boucot A. J.
Published: July 2015

Phylogenetic relationships among higher taxa of articulate brachiopods that developed a spiralium as mineralized support for the lophophore, and the resulting classifications, are not universally agreed upon due to the complex pattern of character evolution within the phylum. Our results, using phylogenetic methodology in conjunction with traditional methods, showed a more complete and easily testable picture of this evolution than either method used alone. A detailed working hypothesis of athyridide phylogeny and the supporting evidence on character distribution is given, and a new classification of the impunctate and punctate athyrids sensu lato is presented with diagnoses to subfamily. Agreement between the stratigraphical first appearance of athyridid subfamilies and their cladistic rank was quite good (except for the koninckinoids), suggesting that both outgroup and traditional paleontological methods indicate a similar direction of character polarity in the evolution of the group. The classification is proposed based on a mix of external and internal characters which persisted during unbroken lineages. New taxa are the families Parazygidae and Triathyrididae; the subfamilies Whitfieldellinae, Triathyridinae, Septathyridinae, Cleiothyridininae, Ochotathyridinae and Plectospirinae, and the generaBrimethyris, Carteridina, TetralobaandCooperispira.We studied the great morphological diversity among the athyridids. Their complete stratigraphical ranges help in building phyletic lineages.
Early Middle CambrianAlbertellaBiozone trilobites of the Pioche Shale, southeastern Nevada
Authors: Eddy Julie D. , McCollum Linda B.
Published: July 2015

Thirty-four species of trilobites belonging to 21 genera are recognized in theAlbertellaBiozone within the Grassy Spring Member (new name) of the Pioche Shale of southeastern Nevada. Genera includePagetia, Poliella, Kootenia, Olenoides, Albertella, Albertellina, Albertelloides, Delamarella, Mexicaspis, Paralbertella, Ptarmiganoides, Ursinella, Zacanthoides?,Amecephalites, Mexicella, Nyella, Onchocephalites?,Pachyaspis, Panacus, Plagiura, andVolocephalina.Two new corynexochid genera and species,Delamarella brevispinaspisandUrsinella major, are described. The existing corynexochid genusAlbertellais revised to include two new species,A. fritziandA. highlandensis.A new species,Albertelloides kitai, is described. Two new ptychopariid genera,AmecephalitesandPanacus, plus four new ptychopariid species,Amecephalites sundbergi, Mexicella granulata, Panacus palmeri, andVolocephalina variosa, are described andNyella immoderataPalmer is revised. In addition, theAlbertellaBiozone is divided into three new subbiozones, the lowerAlbertellina aspinosaSubbiozone, the middle unnamed subbiozone, and theAlbertella highlandensisSubbiozone.