bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of thalamic hemorrhage with takotsubo cardiomyopathy
Authors: Inoue Teruhiro , Yanagawa Youichi , Omori Kazuhiko , Osaka Hiromichi , Oode Yasumasa , Sugita Manabu , Okamoto Ken 
Published: April 2014

CaseA 76‐year‐old woman was found unconscious by her family. She had suffered a fall and was soaked in kerosene. On arrival at our emergency department, she was unconscious, normotensive, with right hemiplegia and chemical burns. A computed tomographic scan of her head indicated left thalamic hemorrhage. An electrocardiogram showed ST elevation at the precardial leads. An echocardiogram revealed characteristic of takotsubo cardiomyopathy.OutcomeThe patient was intubated and treated conservatively. She was transferred to another hospital for rehabilitation after complete epithelization of the chemical burn. This is the second reported case of thalamic hemorrhage with takotsubo cardiomyopathy. The thalamic hemorrhage might have induced autonomic disturbances and caused the takotsubo cardiomyopathy in this case.ConclusionPhysicians should pay attention to the potential complication of takotsubo cardiomyopathy, which may affect cardiopulmonary function even when patients are being treated for intracerebral hemorrhage.
Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity
Authors: Breuer Johanna , Schwab Nicholas , Schneider‐Hohendorf Tilman , Marziniak Martin , Mohan Hema , Bhatia Urvashi , Gross Catharina C. , Clausen Björn E. , Weishaupt Carsten , Luger Thomas A. , Meuth Sven G. , Loser Karin , Wiendl Heinz 
Published: April 2014

ObjectiveEnvironmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated the mechanisms underlying the beneficial effects of immune regulatory processes induced in the skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity.MethodsEffects of UVB light were analyzed in a murine model of CNS autoimmunity (experimental autoimmune encephalomyelitis). Additionally, patients with relapsing–remitting MS were treated with narrowband UVB phototherapy. Immunomodulatory effects were examined in skin biopsies, serum samples, and immune cells of the peripheral blood.ResultsRegulatory T cells (Tregs), which are induced locally in the skin‐draining lymph nodes in response to UVB exposure, connect the cutaneous immune response to CNS immunity by migration to the sites of inflammation (blood, spleen, CNS). Here, they attenuate the inflammatory response and ameliorate disease symptoms. Treg‐inducing tolerogenic dendritic cells (DCs) were further necessary for induction of this systemic immune regulation by UVB radiation, because ablation of Langerhans cells abolished the UVB‐induced phenotype. MS patients treated with UVB phototherapy showed an increase in induced Tregs and tolerogenic DCs accompanied by the downregulation of the T‐cell effector cytokine interleukin 21. The treatment further induced elevated serum levels of vitamin D.InterpretationLocal UVB radiation of the skin influences systemic immune reactions and attenuates systemic autoimmunity via the induction of skin‐derived tolerogenic DCs and Tregs. Our data could have implications for the understanding or therapeutic modulation of environmental factors that influence immune tolerance. Ann Neurol 2014;75:739–758
Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome
Authors: Claassen Jan , Albers David , Schmidt J. Michael , De Marchis Gian Marco , Pugin Deborah , Falo Christina Maria , Mayer Stephan A. , Cremers Serge , Agarwal Sachin , Elkind Mitchell S. V. , Connolly E. Sander , Dukic Vanja , Hripcsak George , Badjatia Neeraj 
Published: April 2014

ObjectiveNonconvulsive seizures (NCSz) are frequent following acute brain injury and have been implicated as a cause of secondary brain injury, but mechanisms that cause NCSz are controversial. Proinflammatory states are common after many brain injuries, and inflammation‐mediated changes in blood–brain barrier permeability have been experimentally linked to seizures.MethodsIn this prospective observational study of aneurysmal subarachnoid hemorrhage (SAH) patients, we explored the link between the inflammatory response following SAH and in‐hospital NCSz studying clinical (systemic inflammatory response syndrome [SIRS]) and laboratory (tumor necrosis factor receptor 1 [TNF‐R1], high‐sensitivity C‐reactive protein [hsCRP]) markers of inflammation. Logistic regression, Cox proportional hazards regression, and mediation analyses were performed to investigate temporal and causal relationships.ResultsAmong 479 SAH patients, 53 (11%) had in‐hospital NCSz. Patients with in‐hospital NCSz had a more pronounced SIRS response (odds ratio [OR] = 1.9 per point increase in SIRS, 95% confidence interval [CI] = 1.3–2.9), inflammatory surges were more likely immediately preceding NCSz onset, and the negative impact of SIRS on functional outcome at 3 months was mediated in part through in‐hospital NCSz. In a subset with inflammatory serum biomarkers, we confirmed these findings linking higher serum TNF‐R1 and hsCRP to in‐hospital NCSz (OR = 1.2 per 20‐point hsCRP increase, 95% CI = 1.1–1.4; OR = 2.5 per 100‐point TNF‐R1 increase, 95% CI = 2.1–2.9). The association of inflammatory biomarkers with poor outcome was mediated in part through NCSz.InterpretationIn‐hospital NCSz were independently associated with a proinflammatory state following SAH as reflected in clinical symptoms and serum biomarkers of inflammation. Our findings suggest that inflammation following SAH is associated with poor outcome and that this effect is at least in part mediated through in‐hospital NCSz. Ann Neurol 2014;75:771–781
Elementary‐Siphon‐Based Control Policy for Flexible Manufacturing Systems with Partial Observability and Controllability of Transitions
Authors: Qin Meng , Li ZhiWu , Al‐Ahmari Abdulrahman M. 
Published: May 2014

AbstractElementary siphons have been extensively studied to solve deadlock problems in Petri nets. However, most of the existing approaches based on elementary siphons can deal with the Petri nets in which all the transitions are supposed to be controllable and observable. This paper develops an elementary‐siphon‐based deadlock control policy for flexible manufacturing systems with uncontrollable and unobservable transitions. For elementary siphons, their complementary sets are successively expanded by considering unobservability and uncontrollability of transitions. Monitors are designed for the expanded complementary sets. The proposed method permits that there are arcs from monitors to a set of special uncontrollable transitions. Moreover, we show that the dependent siphons are always marked in the controlled system that is derived from the proposed method when there exist uncontrollable and unobservable transitions.
Bemessungsdiagramme zur Ermittlung der Durchstanztragfähigkeit von Einzelfundamenten
Authors: Kueres Dominik , Siburg Carsten , Wieneke Katrin , Hegger Josef 
Published: May 2014

AbstractDie gesteigerte Komplexität, die sich infolge der iterativen Bestimmung des Durchstanzwiderstands nach DIN EN 1992‐1‐1+NA(D) bei gedrungenen Einzelfundamenten ergibt, verursacht sowohl bei Tragwerksplanern als auch bei Prüfingenieuren einen erheblichen Mehraufwand. Aufgrund fehlender Erfahrungswerte ist eine überschlägliche Bemessung kaum möglich und die Verwendung rechnergestützter Verfahren oft unvermeidbar.Mit dem Ziel, die Festlegung bzw. Kontrolle der Fundamentabmessungen in der Entwurfsphase wesentlich zu vereinfachen, wurden im Rahmen eines vom Deutschen Ausschuss für Stahlbeton e.V. geförderten Forschungsvorhabens Bemessungsdiagramme zur Bestimmung der Durchstanztragfähigkeit zentrisch und exzentrisch belasteter Einzelfundamente mit unterschiedlicher Stützen‐ und Fundamentgeometrie hergeleitet. Zur weiteren Vereinfachung wurden eine baupraktisch mindestens übliche Betondruckfestigkeit und ein Längsbewehrungsgrad festgelegt, um die aufnehmbare Stützenkraft direkt aus den Bemessungsdiagrammen ablesen zu können. In diesem Beitrag werden die Grundlagen der Berechnung sowie ausgewählte Diagramme als Ergebnis des Forschungsvorhabens präsentiert.Dimensioning Diagrams for Determining the Punching Shear Resistance of FootingsAccording to DIN EN 1992‐1‐1+NA(D), the punching shear resistance of compact footings has to be determined iteratively. This increased complexity results in significant additional effort for structural designers and inspecting structural engineers. Due to the lack of experienced data, an estimated structural design is hardly possible and computational methods often unavoidable.To simplify the determination of the footing's dimensions at design stage, dimensioning diagrams were derived to determine the punching shear resistance of centrically and eccentrically loaded compact footings with different column and footing dimensions. For further simplification a common concrete compressive strength and flexural reinforcement ratio were defined, thus the maximum column load can be determined directly from dimensioning diagrams. This article presents the results of this research project, which was funded by the German Commitee for Structural Concrete.
Mesenchymal stem cell based therapy for osteo‐diseases
Authors: Ghasroldasht Mohammad Mousaei , Irfan‐Maqsood Muhammad , Matin Maryam M. , Bidkhori Hamid Reza , Naderi‐Meshkin Hojjat , Moradi Ali , Bahrami Ahmad Reza 
Published: May 2014

AbstractStem cell therapy in recent years has gained much attention as the modern therapeutic approach to treat diseases. Mesenchymal stem cells (MSCs) are seen as the most reliable cells applied in therapy over other stem cells because of their versatility. Bone and cartilage diseases (osteo‐diseases) are the major target of therapy using MSCs. In this perspective, we have statistically analyzed the data available on clinical trials registry databases regarding the mesenchymal stem cell based therapy for a number of mentioned diseases and paid attention towards the osteodiseases. We report that MSC therapy for osteo‐diseases needs optimization in its standards to achieve acceptable results so that we can apply it in daily routine clinical practice.
Superbasic Alkyl‐Substituted Bisphosphazene Proton Sponges: Synthesis, Structural Features, Thermodynamic and Kinetic Basicity, Nucleophilicity and Coordination Chemistry
Authors: Kögel Julius F. , Xie Xiulan , Baal Eduard , Gesevičius Donatas , Oelkers Benjamin , Kovačević Borislav , Sundermeyer Jörg 
Published: May 2014

AbstractHerein we describe an easily accessible class of superbasic proton sponges based on the 1,8‐bisphosphazenylnaphthalene (PN) proton pincer motif and P‐alkyl substituents ranging from methyl (TMPN) ton‐butyl (TBPN), isopropyl (TiPrPN) and cyclopentyl (TcyPPN). These neutral bases with a pKBH+value (MeCN) of ∼30 were accessible via a Kirsanov condensation using commercially available 1,8‐diaminonaphthalene, and in case of TMPN and TBPN, simple one‐pot procedures starting from trisalkylphosphanes can be performed. Furthermore, the known pyrrolidinyl‐substituted superbase TPPN previously synthesized via a Staudinger reaction could also be prepared by the Kirsanov strategy allowing its preparation in a larger scale. The four alkyl‐substituted proton sponges were structurally characterized in their protonated form; molecular XRD structures were also obtained for unprotonated TiPrPN and TcyPPN. Moreover, we present a detailed description of spectroscopic features of chelating bisphosphazenes including TPPN and its hyperbasic homologue P2‐TPPN on which we reported recently. The four alkyl‐substituted superbases were investigated with respect to their basic features by computational means and by NMR titration experiments revealing unexpectedly high experimental pKBH+values in acetonitrile between 29.3 for TMPN and 30.9 for TBPN. Besides their thermodynamic basicity, we exemplarily studied the kinetic basicity of TMPN and TPPN by means of NMR‐spectroscopic methods. Furthermore, the competing nucleophilic versus basic properties were examined by reacting the proton sponges with ethyl iodide. Insight into the coordination chemistry of chelating superbases was provided by reacting TMPN with trimethylaluminum and trimethylgallium to give cationic complexes of Group XIII metal alkyls that were structurally characterized.
Synthesis of Purine and 7‐Deazapurine Nucleoside Analogues of 6‐N‐(4‐Nitrobenzyl)adenosine; Inhibition of Nucleoside Transport and Proliferation of Cancer Cells
Authors: Rayala Ramanjaneyulu , Theard Patricia , Ortiz Heysell , Yao Sylvia , Young James D. , Balzarini Jan , Robins Morris J. , Wnuk Stanislaw F. 
Published: April 2014

AbstractHuman equilibrative nucleoside transporter 1 (hENT1) is a prototypical nucleoside transporter protein ubiquitously expressed on the cell surface of almost all human tissue. Given the role of hENT1 in the transport of nucleoside drugs, an important class of therapeutics in the treatment of various cancers and viral infections, efforts have been made to better understand the mechanisms by which hENT1 modulates nucleoside transport. To that end, we report here the design and synthesis of novel tool compounds for the further study of hENT1. The 7‐deazapurine nucleoside antibiotic tubercidin was converted into its 4‐N‐benzyl and 4‐N‐(4‐nitrobenzyl) derivatives by alkylation at N3 followed by a Dimroth rearrangement to the 4‐N‐isomer or by fluoro‐diazotization followed by SNAr displacement of the 4‐fluoro group by a benzylamine. The 4‐N‐(4‐nitrobenzyl) derivatives of sangivamycin and toyocamycin antibiotics were prepared by the alkylation approach. Cross‐membrane transport of labeled uridine by hENT1 was inhibited to a weaker extent by the 4‐nitrobenzylated tubercidin and sangivamycin analogues than was observed with 6‐N‐(4‐nitrobenzyl)adenosine. Type‐specific inhibition of cancer cell proliferation was observed at micromolar concentrations with the 4‐N‐(4‐nitrobenzyl) derivatives of sangivamycin and toyocamycin, and also with 4‐N‐benzyltubercidin. Treatment of 2′,3′,5′‐O‐acetyladenosine with aryl isocyanates gave the 6‐ureido derivatives but none of them exhibited inhibitory activity against cancer cell proliferation or hENT1.
Induced neuronal reprogramming
Authors: Ang Cheen Euong , Wernig Marius 
Published: April 2014

ABSTRACTCellular differentiation processes during normal embryonic development are guided by extracellular soluble factors such as morphogen gradients and cell contact signals, eventually resulting in induction of specific combinations of lineage‐determining transcription factors. The young field of epigenetic reprogramming takes advantage of this knowledge and uses cell fate determination factors to convert one lineage into another such as the conversion of fibroblasts into pluripotent stem cells or neurons. These induced cell fate conversions open up new avenues for studying disease processes, generating cell material for therapeutic intervention such as drug screening and potentially also for cell‐based therapies. However, there are still limitations that have to be overcome to fulfill these promises, centering on reprogramming efficiencies, cell identity, and maturation. In this review, we discuss the discovery of induced neuronal reprogramming, ways to improve the conversion process, and finally how to define properly the identity of those converted neuronal cells. J. Comp. Neurol. 522:2877–2886, 2014. © 2014 Wiley Periodicals, Inc.
A novel cell migratory zone in the developing hippocampal formation
Authors: Sugiyama Taku , Osumi Noriko , Katsuyama Yu 
Published: April 2014

ABSTRACTThe hippocampal formation (HF) is a unique structure in the mammalian brain and is subdivided into the dentate gyrus, Ammon's horn, and subiculum by their functions and connectivity in the neuronal circuit. Because behaviors of the neural stem cells, neuronal progenitors, and the differentiating neurons are complex during hippocampal morphogenesis, the differentiation of these subdivisions has not been well understood. In this study, we investigated embryonic and postnatal expression of the proteins Prox1, Math2, and Ctip2, which clearly indicate principal cells of the dentate gyrus (Prox1 positive) and Ammon's horn (Math2 and Ctip2 positive). Expression patterns of Prox1 and Math2 were consistent with previously suggested localization of migratory pathways of the dentate granule cells and hippocampal pyramidal cells. Interestingly, we found intermingling of Prox1‐expressing cells and Math2‐expressing cells in a cell migratory stream, suggesting previously unknown behaviors of differentiating cells of the HF. J. Comp. Neurol. 522:3520–3538, 2014. © 2014 Wiley Periodicals, Inc.
Long‐term consequences of neonatal fluoxetine exposure in adult rats
Authors: Ko Meng‐Ching , Lee Lukas Jyuhn‐Hsiarn , Li Yang , Lee Li‐Jen 
Published: April 2014

ABSTRACTSerotonin (5‐HT) plays important roles during neural development. Administration of selective serotonin reuptake inhibitor (SSRI)‐type medication during gestation may influence the maturation of the fetal brain and subsequent brain functions. To mimic the condition of late‐gestation SSRI exposure, we administered fluoxetine (FLX) in neonatal rats during the first postnatal week, which roughly corresponds to the third trimester period of human gestation. FLX‐exposed adult male rats exhibited reduced locomotor activity and depression‐like behaviors. Furthermore, sensorimotor gating capacity was also impaired. Interestingly, increased social interaction was noticed in FLX‐exposed rats. When the levels of 5‐HT and tryptophan hydroxylase were examined, no significant changes were found in FLX rats compared to control (CON) rats. The behavioral phenotypes of FLX rats suggested malfunction of the limbic system. Dendritic architectures of neurons in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) were examined. Layer II/III mPFC pyramidal neurons in FLX rats had exuberant dendritic branches with elongated terminal segments compared to those in CON rats. In BLA pyramidal neurons, the dendritic profiles were comparable between the two groups. However, in FLX rats, the density of dendritic spines was reduced in both mPFC and BLA. Together, our results demonstrated the long‐lasting effects of early FLX treatment on emotional and social behaviors in adult rats in which impaired neuronal structure in the limbic system was also noticed. The risk of taking SSRI‐type antidepressants during pregnancy should be considered. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1038–1051, 2014
Rostral–caudal distribution of Emx1‐lineage stem/transit amplifying cells and lineage progression in embryonic cortex depend on hedgehog signaling
Authors: Lillien Laura 
Published: April 2014

ABSTRACTLineage progression of neural precursors to an EGF‐responsive state can be promoted by several extrinsic signals, including fibroblast growth factor 2 (FGF2) and Hedgehog (Hh). It has been suggested that EGF‐responsive precursors in the embryonic cerebral cortex originate in the ventral telencephalon in an FGF‐dependent manner and migrate dorsally. To determine whether cortical EGF‐responsive cells originate locally from dorsal precursors, we marked these precursors using Emx1‐cre and the cre reporter Z/EG and observed a local origin for EGF‐responsive cells. We also found a rostral–caudal difference in the abundance of self‐renewing, neurogenic Emx1‐lineage precursors, with more present rostrally. Deleting the Hh receptor smoothened in Emx‐1 lineage cells impaired their progression to an EGF‐responsive state. Moreover, loss of smoothened increased the proportion of neurogenic, self‐renewing Emx1‐lineage cells in caudal regions of cortex, eliminating their asymmetric distribution. Our results support the idea that Hh signaling promotes lineage progression of stem/transit amplifying cells, particularly in caudal regions of the embryonic cortex, leading to rostral–caudal differences in the abundance of neurogenic, self‐renewing precursors.© 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1096–1109, 2014
Transcriptome of Atoh7 retinal progenitor cells identifies new Atoh7‐dependent regulatory genes for retinal ganglion cell formation
Authors: Gao Zhiguang , Mao Chai‐An , Pan Ping , Mu Xiuqian , Klein William H. 
Published: May 2014

ABSTRACTThe bHLH transcription factor ATOH7 (Math5) is essential for establishing retinal ganglion cell (RGC) fate. However, Atoh7‐expressing retinal progenitor cells (RPCs) can give rise to all retinal cell types, suggesting that other factors are involved in specifying RGCs. The basis by which a subpopulation of Atoh7‐expressing RPCs commits to an RGC fate remains uncertain but is of critical importance to retinal development since RGCs are the earliest cell type to differentiate. To better understand the regulatory mechanisms leading to cell‐fate specification, a binary genetic system was generated to specifically label Atoh7‐expressing cells with green fluorescent protein (GFP). Fluorescence‐activated cell sorting (FACS)‐purified GFP+ and GFP− cells were profiled by RNA‐seq. Here, we identify 1497 transcripts that were differentially expressed between the two RPC populations. Pathway analysis revealed diminished growth factor signaling in Atoh7‐expressing RPCs, indicating that these cells had exited the cell cycle. In contrast, axon guidance signals were enriched, suggesting that axons of Atoh7‐expressing RPCs were already making synaptic connections. Notably, many genes enriched in Atoh7‐expressing RPCs encoded transcriptional regulators, and several were direct targets of ATOH7, including, and unexpectedly, Ebf3 and Eya2. We present evidence for a Pax6‐Atoh7‐Eya2 pathway that acts downstream of Atoh7 but upstream of differentiation factor Pou4f2. EYA2 is a protein phosphatase involved in protein–protein interactions and posttranslational regulation. These properties, along with Eya2 as an early target gene of ATOH7, suggest that EYA2 functions in RGC specification. Our results expand current knowledge of the regulatory networks operating in Atoh7‐expressing RPCs and offer new directions for exploring the earliest aspects of retinogenesis. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1123–1140, 2014
Generation of a Magoh conditional allele in mice
Authors: McMahon John J. , Shi Lei , Silver Debra L. 
Published: April 2014

SummaryMagoh encodes a core component of the exon junction complex (EJC), which binds mRNA and regulates mRNA metabolism. Magoh is highly expressed in proliferative tissues during development. EJC components have been implicated in several developmental disorders including TAR syndrome, Richieri–Costa–Pereira syndrome, and intellectual disability. Existing germline null Magoh mice are embryonic lethal as homozygotes and perinatal lethal as heterozygotes, precluding detailed analysis of embryonic and postnatal functions. Here, we report the generation of a new genetic tool to dissect temporal and tissue‐specific roles for Magoh in development and adult homeostasis. This Magoh conditional allele has two loxP sites flanking the second exon. Ubiquitous Cre‐mediated deletion of the floxed allele in a heterozygous mouse (Magohdel/+) causes 50% reduction of both Magoh mRNA and protein. Magohdel/+ mice exhibit both microcephaly and hypopigmentation, thus phenocopying germline haploinsufficient Magoh mice. Using Emx1‐Cre, we further show that conditional Magoh deletion in neural progenitors during embryonic development also causes microcephaly. We anticipate this novel conditional allele will be a valuable tool for assessing tissue‐specific roles for Magoh in mammalian development and postnatal processes. genesis 52:752–758, 2014. © 2014 Wiley Periodicals, Inc.