bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topiramate use during pregnancy and major congenital malformations in multiple populations
Authors: Tennis Patricia , Chan K. Arnold , Curkendall Suellen M. , Li De‐Kun , Mines Daniel , Peterson Craig , Andrews Elizabeth B. , Calingaert Brian , Chen Hong Y. , Deshpande Gaurav , Everage Nicholas , Holick Crystal N. , Meyer Nicole M. , Nkhoma Ella T. , Quinn Sherry , Rothman Kenneth J. , Esposito Daina B. 
Published: March 2015

BackgroundWe measured birth prevalence of major congenital malformations (MCMs) after topiramate use during pregnancy to screen for a possible signal of increased risk.MethodsUsing four healthcare databases, we identified three cohorts of pregnant women: cohort 1, used topiramate during the first trimester; cohort 2, used topiramate or another antiepileptic drug previously but not during pregnancy; and cohort 3, were pregnant and did not use topiramate but had indications for use individually matched to those of users. Cohort 1 was compared with cohorts 2 and 3. MCMs were a code for any major congenital malformation dated within 30 days of the delivery date on the mother's claims or within 365 days after infant birth date, excluding a genetic or syndromic basis, and with procedure or healthcare usage consistent with the MCM diagnosis code in the 365 days after infant birth.ResultsOf the 10 specific common MCMs evaluated, 1 (conotruncal heart defects) had a prevalence ratio greater than 1.5 for both primary comparisons, and 4 (ventricular septal defect, atrial septal defect, hypospadias, coarctation of the aorta) had a prevalence ratio greater than 1.5 for one of the two comparisons. Following screening of organ systems with elevated MCMs, the prevalence ratio was greater than 1.5 for patent ductus arteriosus in both comparisons and for obstructive genitourinary defects in one comparison.ConclusionTo evaluate a large number of MCMs across many pregnancies, we used crude methods for detecting potential signals. Therefore, these results should be seen as potential signals, not causal. Birth Defects Research (Part A) 103:269–275, 2015. © 2015 Wiley Periodicals, Inc.
A genome‐wide study of inherited deletions identified two regions associated with nonsyndromic isolated oral clefts
Authors: Younkin Samuel G. , Scharpf Robert B. , Schwender Holger , Parker Margaret M. , Scott Alan F. , Marazita Mary L. , Beaty Terri H. , Ruczinski Ingo 
Published: March 2015

BackgroundDNA copy number variants play an important part in the development of common birth defects such as oral clefts. Individual patients with multiple birth defects (including oral clefts) have been shown to carry small and large chromosomal deletions.MethodsWe investigated the role of polymorphic copy number deletions by comparing transmission rates of deletions from parents to offspring in case‐parent trios of European ancestry ascertained through a cleft proband with trios ascertained through a normal offspring. DNA copy numbers in trios were called using the joint hidden Markov model in the freely available PennCNV software. All statistical analyses were performed using Bioconductor tools in the open source environment R.ResultsWe identified a 67 kb region in the gene MGAM on chromosome 7q34, and a 206 kb region overlapping genes ADAM3A and ADAM5 on chromosome 8p11, where deletions are more frequently transmitted to cleft offspring than control offspring.ConclusionsThese genes or nearby regulatory elements may be involved in the etiology of oral clefts. Birth Defects Research (Part A) 103:276–283, 2015. © 2015 Wiley Periodicals, Inc.
A multiscale view of therapeutic protein aggregation: A colloid science perspective
Authors: Nicoud Lucrèce , Owczarz Marta , Arosio Paolo , Morbidelli Massimo 
Published: March 2015

AbstractThe formation of aggregates in protein‐based pharmaceuticals is a major issue that can compromise drug safety and drug efficacy. With a view to improving protein stability, considerable effort is put forth to unravel the fundamental mechanisms underlying the aggregation process. However, therapeutic protein aggregation is a complex multistep phenomenon that involves time and length scales spanning several orders of magnitude, and strategies addressing protein aggregation inhibition are currently still largely empirical in practice. Here, we review how key concepts developed in the frame of colloid science can be applied to gain knowledge on the kinetics and thermodynamics of therapeutic protein aggregation across different length scales. In particular, we discuss the use of coarse‐grained molecular interaction potentials to quantify protein colloidal stability. We then show how population balance equations simulations can provide insights into the mechanisms of aggregate formation at the mesoscale, and we highlight the strength of the concept of fractal scaling to quantify irregular aggregate morphologies. Finally, we correlate the macroscopic rheological properties of protein solutions with the occupied volume fraction and the aggregate structure. Overall, this work illustrates the power and limitations of colloidal approaches in the multiscale description of the aggregation of therapeutic proteins.
Postsynaptic gephyrin clustering controls the development of adult‐born granule cells in the olfactory bulb
Authors: Deprez Francine , Pallotto Marta , Vogt Fabia , Grabiec Marta , Virtanen Mari A. , Tyagarajan Shiva K. , Panzanelli Patrizia , Fritschy Jean‐Marc 
Published: March 2015

ABSTRACTIn adult rodent olfactory bulb, GABAergic signaling regulates migration, differentiation, and synaptic integration of newborn granule cells (GCs), migrating from the subventricular zone. Here we show that these effects depend on the formation of a postsynaptic scaffold organized by gephyrin—the main scaffolding protein of GABAergic synapses, which anchors receptors and signaling molecules to the postsynaptic density—and are regulated by the phosphorylation status of gephyrin. Using lentiviral vectors to selectively transfect adult‐born GCs, we observed that overexpression of the phospho‐deficient gephyrin mutant eGFP‐gephyrin(S270A), which facilitates the formation of supernumerary GABAergic synapses in vitro, favors dendritic branching and the formation of transient GABAergic synapses on spines, identified by the presence of α2‐GABAARs. In contrast, overexpression of the dominant‐negative eGFP‐gephyrin(L2B) (a chimera that is enzymatically active but clustering defective), curtailed dendritic growth, spine formation, and long‐term survival of GCs, pointing to the essential role of gephyrin cluster formation for its function. We could exclude any gephyrin overexpression artifacts, as GCs infected with eGFP‐gephyrin were comparable to those infected with eGFP alone. The opposite effects induced by the two gephyrin mutant constructs indicate that the gephyrin scaffold at GABAergic synapses orchestrates signaling cascades acting on the cytoskeleton to regulate neuronal growth and synapse formation. Specifically, gephyrin phosphorylation emerges as a novel mechanism regulating morphological differentiation and long‐term survival of adult‐born olfactory bulb neurons. J. Comp. Neurol. 523:1998–2016, 2015 © 2015 Wiley Periodicals, Inc.
An artificial DNA for self‐descripting and self‐building embedded real‐time systems
Authors: Brinkschulte Uwe 
Published: March 2015

SummaryEmbedded systems are growing more and more complex because of the increasing chip integration density, larger number of chips in distributed applications, and demanding application fields (e.g., in cars and in households). Bio‐inspired techniques like self‐organization are a key feature to handle this complexity. However, self‐organization needs a guideline for setting up and managing the system. In biology, the structure and organization of a system are coded in its DNA. In this paper, we present an approach to use an artificial DNA for that purpose. Because many embedded systems can be composed from a limited number of basic elements, the structure and parameters of such systems can be stored in a compact way, representing an artificial DNA deposited in each computation node. This leads to a self‐describing system. Based on the DNA, the self‐organization mechanisms can build the system autonomously, providing a self‐building system. System repair and optimization at runtime are also possible, leading to higher robustness, dependability, and flexibility. Copyright © 2015 John Wiley & Sons, Ltd.
Factor‐Optical‐Factor Exchanges Method: a new load balancing method for Extended Optical Transpose Interconnection System‐n‐Cube networks
Authors: Al‐Sadi Jehad A. 
Published: March 2015

SummaryThe Optical Transpose Interconnection System (OTIS) optoelectronic interconnection network architecture is a promising attraction in the new era of parallel computing topologies because of its attractive topological properties. Recently, many enhancements were presented on OTIS topologies including the Extended OTIS‐n‐Cube interconnection networks. Therefore, all performance improvement characteristics of such a promising architecture need to be investigated; one of which is load balancing technique. This paper focuses on developing an efficient algorithm for load balancing on the promising Extended OTIS‐n‐Cube interconnection networks. The proposed algorithm is called Factor‐Optical‐Factor Exchange Model. Furthermore, this paper presents theoretical and experimental study on the proposed algorithm in terms of various parameters including execution time, load balancing accuracy, number of communication steps, and speed. Results show superiority of the proposed algorithm over the well‐known Clustered Dimension Exchange Method (CDEM) algorithm in terms of execution time, number of communication steps, and speed, while maintaining the same level of accuracy. Copyright © 2015 John Wiley & Sons, Ltd.
Mechanochemical Ritter Reaction: A Rapid Approach to Functionalized Amides at Room Temperature
Authors: Dokli Irena , Gredičak Matija 
Published: March 2015

AbstractA fast and efficient mechanochemical Ritter reaction between alcohols and nitriles under mild conditions is demonstrated. The reaction proceeds rapidly at room temperature in a solvent‐free or low‐solvent environment by using a Brønsted acid catalyst. Its general application has been verified through a substrate screening comprising a wide range of functionalized nitriles as well as secondary and tertiary alcohols.
Uptake of perfluoroalkyl acids in the leaves of coniferous and deciduous broad-leaved trees
Authors: Zhang Huanhuan , Liu Wei , He Xin , Wang Yu , Zhang Qian 
Published: March 2015

Abstract

Analytical methods for determining perfluoroalkyl acids (PFAAs) in leaves were developed to quantify a suite of analytes in both coniferous and deciduous broad-leaved trees. Sodium hydroxide-methanol and solid-phase extraction was selected as the extracting and cleanup strategy for PFAA analysis. Ten perfluorocarboxylic acids (PFCAs) and 4 perfluorosulfonic acids (PFSAs) were monitored in 7 kinds of leaves grown in the urban areas of Dalian, China. The results show that coniferous tree leaves take up more PFAAs than broad-leaved tree leaves, with the highest amount of 150 ng/g in pine needles. Leaf PFCA levels were much higher than PFSAs level. Short carbon–chain PFCAs with 3 to 6 perfluorinated carbons account for approximately 40% to 80% of the total leaf PFAAs, where uptake decreased with increasing carbon chain length. Temporal observation of leaf PFAAs revealed no significant variation of concentrations in the leaves over a weekly interval and the absence of significant seasonal change in pine needles and sophora. The present study provides some evidence for the accumulation of PFAAs in leaves, which is valuable for understanding their environmental behavior and the development of alternative bioindicator. Environ Toxicol Chem 2015;34:1499–1504. © 2015 SETAC
A massive MIMO terminal concept based on small‐size multi‐mode antennas
Authors: Hoeher P. A. , Doose N. 
Published: March 2015

AbstractIn this tutorial, a novel variation of massive multiple‐input multiple‐output (MIMO) is proposed, dubbed multi‐mode massive MIMO. A key feature is an advanced antenna design suitable for small‐scale user terminals like smartphones. Unlike traditional antenna layouts employing a single‐antenna port per antenna element, multiple orthogonal modes shall be excited on a conductive body, like the printed circuit board. This antenna conception is motivated by the theory of characteristic modes for conductive bodies. Each mode can be assigned with an individual antenna port, and all antenna ports can be fed independently. In conjunction with suitable baseband processing, unique features, such as single‐mode beamforming, can be exploited. Most importantly, some bottlenecks of conventional massive MIMO in conjunction with single‐antenna terminals like single‐stream processing on the uplink and pilot contamination on the downlink can be improved. Performance results for a three‐port prototype multi‐mode antenna support the feasibility of the proposed concept. The terminal concept is suitable in context of the upcoming fifth mobile radio generation (5G) and for ultra‐fast (100 Gbps) wireless internet access among other applications. Copyright © 2015 John Wiley & Sons, Ltd.
Structure and Absolute Configuration of Aspergilumamide A, a Novel Lumazine Peptide from the Mangrove‐Derived Fungus Aspergillus sp.
Authors: Zheng Cai‐Juan , Wu Lu‐Yong , Li Xiao‐Bao , Song Xin‐Ming , Niu Zhi‐Gang , Song Xiao‐Ping , Chen Guang‐Ying , Wang Chang‐Yun 
Published: March 2015

AbstractA novel lumazine peptide, aspergilumamide A (1), as well as a known analog penilumamide (2), were isolated from the mycelia of a marine‐derived fungus Aspergillus sp. (33241), obtained from the mangrove Bruguiera sexangula var. rhynchopetala collected from the South China Sea. The structure of 1 was identified by comprehensive spectroscopic analysis, including 1D‐ and 2D‐NMR, ESI‐MS, and MS/MS experiments. The absolute configuration of 1 was determined by Marfey's method.
Formation of Dialkyl 2‐[3‐Alkoxy‐1‐(alkylimino)‐1‐chloro‐3‐oxopropan‐2‐ylidene]hydrazine‐1,1‐dicarboxylates of α‐(Alkoxycarbonyl)imidoyl Chlorides from PhosphineDiazo Ester Zwitterions and Nef‐Isocyanide Adducts
Authors: Yavari Issa , Hosseinpour Reza , Pashazadeh Ramin 
Published: March 2015

AbstractA novel transformation involving phosphinediazo ester zwitterions (generated from dialkyl azodicarboxylates with Ph3P) and α‐(alkoxycarbonyl)imidoyl chlorides (prepared from α‐addition of acyl chlorides to alkyl isocyanides) to afford dialkyl 2‐[3‐alkoxy‐1‐(alkylimino)‐1‐chloro‐3‐oxopropan‐2‐ylidene]hydrazine‐1,1‐dicarboxylates in moderate yields, is described.
Towards Stereoselective Synthesis of the C(31)–C(39) and C(20)–C(27) Fragments of Phorboxazole A
Authors: Raju Kammari Bal , Kumar Bejjanki Naveen , Kumar Bandari Sampath , Nagaiah Kommu 
Published: March 2015

AbstractThe stereoselective synthesis of the C(31)–C(39) and C(20)–C(27) fragments of phorboxazole A (1) was achieved from commercially available and inexpensive D‐mannitol. Crimmins aldol reaction and a decarboxylative Claisen‐type reaction are the key steps for the C(31)–C(39) fragment, and L‐proline‐catalyzed aldol reaction, Sharpless asymmetric epoxidation, and epoxide ring opening reaction with Gilman's reagent are the key steps for the C(20)–C(27) fragment of phorboxazole.
Oncogenic and Therapeutic Targeting of PTEN Loss in Bone Malignancies
Authors: Xi Yongming , Chen Yan 
Published: March 2015

ABSTRACTBeing a tumor suppressor, PTEN functions as a dual‐specificity protein and phospholipid phosphatase and regulates a variety of cellular processes and signal transduction pathways. Loss of PTEN function has been detected frequently in different forms of cancers, such as breast, prostate and lung cancer, gastric and colon cancer, skin cancer, as well as endometrial carcinoma. In this review, we provide a summary of PTEN and its role in bone malignancies including bone metastases, multiple myeloma, and osteosarcoma, etc. We highlight the importance of PTEN loss leading to activation of the oncogenic PI3K/Akt/mTOR pathway in tumorigenesis and progression, which can be attributed to both genetic and non‐genetic alterations involving gene mutation, loss of heterozygosity, promoter hypermethylation, and microRNA mediated negative regulation. We also discuss the emerging therapeutic applications targeting PTEN loss for the treatment of these bone malignant diseases. J. Cell. Biochem. 116: 1837–1847, 2015. © 2015 Wiley Periodicals, Inc.
Turning Bone Morphogenetic Protein 2 (BMP2) on and off in Mesenchymal Cells
Authors: Rogers Melissa B. , Shah Tapan A. , Shaikh Nadia N. 
Published: March 2015

AbstractThe concentration, location, and timing of bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) gene expression must be precisely regulated. Abnormal BMP2 levels cause congenital anomalies and diseases involving the mesenchymal cells that differentiate into muscle, fat, cartilage, and bone. The molecules and conditions that influence BMP2 synthesis are diverse. Understandably, complex mechanisms control Bmp2 gene expression. This review includes a compilation of agents and conditions that can induce Bmp2. The currently known trans‐regulatory factors and cis‐regulatory elements that modulate Bmp2 expression are summarized and discussed. Bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) is a classical morphogen; a molecule that acts at a distance and whose concentration influences cell behavior. In mesenchymal cells, the concentration of BMP2 influences myogenesis, adipogenesis, chondrogenesis, and osteogenesis. Because the amount, timing, and location of BMP2 synthesis influence the allocation of cells to muscle, fat, cartilage, and bone, the mechanisms that regulate the Bmp2 gene are crucial. Key early mesodermal events that require precise Bmp2 regulation include heart specification and morphogenesis. Originally named for its osteoinductive properties, healing fractures requires BMP2. The human Bmp2 gene also has been linked to osteoporosis and osteoarthritis. In addition, all forms of pathological calcification in the vasculature and in cardiac valves involve the pro‐osteogenic BMP2. The diverse tissues, mechanisms, and diseases influenced by BMP2 are too numerous to list here (see OMIM: 112261). However, in all BMP2‐influenced pathologies, changes in the behavior and differentiation of pluripotent mesenchymal cells are a recurring theme. Consequently, much effort has been devoted to identifying the molecules and conditions that influence BMP2 synthesis and the complex mechanisms that control Bmp2 gene expression. This review begins with an overview of the Bmp2 gene's chromosomal neighborhood and then summarizes and evaluates known regulatory mechanisms and inducers. J. Cell. Biochem. 116: 2127–2138, 2015. © 2015 Wiley Periodicals, Inc.
Two‐stage anaerobic digestion for reduced hydrogen sulphide production
Authors: Moestedt Jan , Nordell Erik , Hallin Sara , Schnürer Anna 
Published: March 2015

AbstractBACKGROUNDThis study evaluated a two‐stage process as an alternative to single‐stage anaerobic degradation, with the aim of separating sulphidogenesis and methanogenesis while treating a mixture of organic fraction municipal solid waste (OFMSW) and thin stillage. For full‐scale applications, no pH regulation was applied. The hydrolytic/acidogenic stage was evaluated with a hydraulic retention time (HRT) between 3 and 15 days, with and without recirculation of methanogenic stage reactor material.RESULTSHomoacetogenesis dominated in the hydrolytic/acidogenic stage. However, sulphate reduction was unsuccessful. Using a two‐stage approach with OFMSW at a HRT of 10 days in the first stage and 28 days in the second stage resulted in a 12% increase in specific methane production and a 6% increase in methane content. The two‐stage process with thin stillage was less effective, probably because of decreasing pH (<4) in the first stage.CONCLUSIONTwo‐stage operation resulted in a pH too low (~4) for successful sulphate reduction in the first stage. However the resulting pH and applied organic loading rate caused homoacetogenesis to dominate, producing acetate as a favourable energy carrier between the stages. © 2015 Society of Chemical Industry
An examination of the variation in maternal placentae across the genus Poeciliopsis (Poeciliidae)
Authors: Kwan Lucia , Fris Megan , Rodd F. Helen , Rowe Locke , Tuhela Laura , Panhuis Tami M. 
Published: March 2015

ABSTRACTPlacentae show considerable diversity in a number of nonmammalian, viviparous organisms, including amphibians, reptilian sauropsids, teleost fish, and chondrichthyes. However, the evolutionary processes driving the evolution of placenta are still debated. In teleost fishes, the genus Poeciliopsis (Poeciliidae) offers a rare opportunity for studying placental evolution: extensive placentation has evolved three independent times within the last 750,000 years and there is substantial interspecific variation in the degree of embryonic, maternal nutrient provisioning and development of the placenta. In poeciliids, the placenta is composed of a hypertrophied maternal follicular epithelium apposed to a highly vascularized embryonic pericardial sac. To better understand placental evolution, we have undertaken a comprehensive comparative study of the maternal follicle in eight closely related Poeciliopsis species that span the range in postfertilization, embryonic, maternal nutrient provisioning (from lecithotrophs, to moderate matrotrophs, to extensive matrotrophs). Using light and scanning electron microscopy, we found that the species that provide extensive postfertilization maternal nutrient provisioning (extensive matrotrophs) have thicker follicles and more extensive folding of the follicular epithelium compared to the lecithotrophs and moderate matrotrophs. Follicle sections and histology revealed that epithelial folds of the extensive matrotrophs are comprised primarily of cuboidal and columnar cells and are richly supplied with capillaries. Among the extensive matrotrophs, enhancements of follicle traits corresponded with increases in the level of maternal nutrient provisioning. Hypertrophied maternal follicles with richly vascularized folds can serve to increase the surface area and, thus, facilitate the transfer of substances between the mother and developing embryo. Finally, we found egg envelopes in the lecithotrophs and moderate matrotrophs, but not in the extensive matrotrophs. Morphological studies, like this one, can provide a better understanding of the natural variation in the structure and functioning of maternal and offspring traits associated with matrotrophy and, thus, insights into the processes driving placental evolution. J. Morphol. 276:707–720, 2015. © 2015 Wiley Periodicals, Inc.
Water‐soluble cationic polypyrrole based probe for fluorometric and voltammetric detection of base pair mismatched oligonucleotides
Authors: Guo Jiangna , Zhao Jie , Wang Bin , Yan Feng 
Published: March 2015

ABSTRACTWater‐soluble cationic polypyrrole, poly(N‐(4‐butyl‐(1‐methylimidazole)) pyrrole bromide) (PNBMIP‐Br), was synthesized and applied for base pair mismatched oligonucleotides detection. Interactions between PNBMIP‐Br and a series of oligonucleotides, including ss‐DNA and base pair mismatched ds‐DNA were studied by fluorometric spectra, circular dichroism spectra and voltammetric detection. The results showed that the electrostatic attraction and fluorescence resonance energy transfer of PNBMIP‐Br/DNA complexes resulted in an amplification and effective recognition of the fluorescence signals. The results of cyclic voltammograms indicate that voltammetric detection is an effective method to distinguish ss‐DNA and ds‐DNA. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1600–1605