bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compartmental endoscopic surgical anatomy of the medial intraconal orbital space
Authors: Bleier Benjamin S. , Healy David Y. , Chhabra Nipun , Freitag Suzanne 
Published: March 2014

BackgroundSurgical management of intraconal pathology represents the next frontier in endoscopic endonasal surgery. Despite this, the medial intraconal space remains a relatively unexplored region, secondary to its variable and technically demanding anatomy. The purpose of this study is to define the neurovascular structures in this region and introduce a compartmentalized approach to enhance surgical planning.MethodsThis study was an institutional review board (IRB)‐exempt endoscopic anatomic study in 10 cadaveric orbits. After dissection of the medial intraconal space, the pattern and trajectory of the oculomotor nerve and ophthalmic arterial arborizations were analyzed. The position of all vessels as well as the length of the oculomotor trunk and branches relative to the sphenoid face were calculated.ResultsA mean of 1.5 arterial branches were identified (n = 15; range, 1‐4) at a mean of 8.8 mm from the sphenoid face (range, 4‐15 mm). The majority of the arteries (n = 7) inserted adjacent to the midline of medial rectus. The oculomotor nerve inserted at the level of the sphenoid face and arborized with a large proximal trunk 5.5 ± 1.1 mm in length and multiple branches extending 13.2 ± 2.7 mm from the sphenoid face. The most anterior nerve and vascular pedicle were identified at 17.0 and 15.0 mm from the sphenoid face, respectively.ConclusionThe neurovascular supply to the medial rectus muscle describes a varied but predictable pattern. This data allows the compartmentalization of the medial intraconal space into 3 zones relative to the neurovascular supply. These zones inform the complexity of the dissection and provide a guideline for safe medial rectus retraction relative to the fixed landmark of the sphenoid face.
JC virus reactivation during prolonged natalizumab monotherapy for multiple sclerosis
Authors: Chalkias Spyridon , Dang Xin , Bord Evelyn , Stein Marion C. , Kinkel R. Philip , Sloane Jacob A. , Donnelly Maureen , Ionete Carolina , Houtchens Maria K. , Buckle Guy J. , Batson Stephanie , Koralnik Igor J. 
Published: March 2014

ObjectiveTo determine the prevalence of JC virus (JCV) reactivation and JCV‐specific cellular immune response during prolonged natalizumab treatment for multiple sclerosis (MS).MethodsWe enrolled 43 JCV‐seropositive MS patients, including 32 on natalizumab monotherapy >18 months, 6 on interferon β‐1a monotherapy >36 months, and 5 untreated controls. We performed quantitative real‐time polymerase chain reaction in cerebrospinal fluid (CSF), blood, and urine for JCV DNA, and we determined JCV‐specific T‐cell responses using enzyme‐linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) assays, ex vivo and after in vitro stimulation with JCV peptides.ResultsJCV DNA was detected in the CSF of 2 of 27 (7.4%) natalizumab‐treated MS patients who had no symptoms or magnetic resonance imaging–detected lesions consistent with progressive multifocal leukoencephalopathy. JCV DNA was detected in blood of 12 of 43 (27.9%) and in urine of 11 of 43 (25.6%) subjects without a difference between natalizumab‐treated patients and controls. JC viral load was higher in CD34+ cells and in monocytes compared to other subpopulations. ICS was more sensitive than ELISpot. JCV‐specific T‐cell responses, mediated by both CD4+ and CD8+ T lymphocytes, were detected more frequently after in vitro stimulation. JCV‐specific CD4+ T cells were detected ex vivo more frequently in MS patients with JCV DNA in CD34+ (p = 0.05) and B cells (p = 0.03).InterpretationAsymptomatic JCV reactivation may occur in CSF of natalizumab‐treated MS patients. JCV DNA load is higher in circulating CD34+ cells and monocytes compared to other mononuclear cells, and JCV in blood might trigger a JCV‐specific CD4+ T‐cell response. JCV‐specific cellular immune response is highly prevalent in all JCV‐seropositive MS patients, regardless of treatment. ANN NEUROL 2014;75:925–934
Quantitative study of cellular heterogeneity in doxorubicin uptake and its pharmacological effect on cancer cells
Authors: Deng Bin , Wang Zhi‐Ming , Zhou Zi‐Hao , Liu Yi‐Meng , Yang Xi‐Liang , Song Jian , Xiao Yu‐Xiu 
Published: March 2014

ABSTRACTCellular heterogeneity in doxorubicin (DOX) uptake and its relationship with pharmacological effect on cancer cells were quantitatively investigated for the first time. An in vitro experimental model was established by treating human leukemia K562 and breast cancer MCF‐7 cells with different schedules of DOX with or without surface P‐glycoprotein (P‐gp) inhibitor verapamil (VER). The cellular heterogeneity in DOX uptake was quantitatively examined by single‐cell analysis using capillary electrophoresis coupled with laser‐induced fluorescence detection. The corresponding cytotoxic effect was tested by cellular morphology, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium and flow cytometry assays. The expression of cellular membrane surface P‐gp was determined by flow cytometry. Results showed that the cellular heterogeneity exists in DOX uptake. The single‐high DOX schedule leads to lower uptake heterogeneity and higher mean drug uptake. The cellular heterogeneity in DOX uptake was found to be negatively correlated with drug cytotoxicity and surface P‐gp expression, with r = −0.7680 to ~ −0.9587. VER reduces the cellular variation in DOX uptake, suggesting that surface P‐gp may be one of the causes of the cellular heterogeneity in DOX uptake. This research demonstrates the importance of quantitative study of cellular heterogeneity in drug uptake and its potential application in drug schedule design, response prediction and therapy modulation. Copyright © 2014 John Wiley & Sons, Ltd.
Simultaneous reduction of MAD2 and BUBR1 expression induces mitotic spindle alterations associated with p53 dependent cell cycle arrest and death
Authors: Lentini Laura , Piscitello Desirèe , Veneziano Lorena , Di Leonardo Aldo 
Published: March 2014

AbstractMost human tumors are characterized by aneuploidy that is believed to be the consequence of chromosomal instability (CIN). The mechanism(s) leading to aneuploidy and the pathways that allow its tolerance are not completely understood. The Spindle Assembly Checkpoint (SAC) is a cellular surveillance mechanism working during mitosis, and alterations of genes that encode components of the SAC weakening the mitotic checkpoint, induce aneuploidy by chromosome mis‐segregation. We induced aneuploidy in near‐diploid tumor cells by simultaneous depletion of the SAC proteins MAD2 and BUBR1 by RNA interference in the attempt to gain further insight on the cellular responses to aneuploidy. Individual reduction of MAD2 and BUBR1 protein levels caused defective mitosis and aneuploidy, while co‐depletion of MAD2 and BUBR1 caused cell cycle arrest and cell death in addition to aneuploidy. The simultaneous reduction of the two SAC proteins induced high percentage of hyperdiploid cells and p53 stabilization suggesting that hyperdiploidy could activate a p53 controlled pathway. The results indicate that p53 is required to induce cell cycle arrest and cell death when the mitotic checkpoint is strongly perturbed, thereby preventing aneuploid cell propagation.
Human endometrial stem cells differentiation into functional hepatocyte‐like cells
Authors: Khademi Farzaneh , Soleimani Masoud , Verdi Javad , Tavangar Seyed Mohammad , Sadroddiny Esmaeil , Masumi Mohammad , Ai Jafar 
Published: March 2014

AbstractIn spite of certain clinical limitations, such as teratoma formation, the use of stem cells is considered as an appropriate source in cell therapy and tissue engineering. This study shows human endometrial stem cells (hEnSCs) has exceptional differentiation ability in hepatocyte formation. hEnSCs have high purification rate and immune‐tolerance, and can be used as an appropriate substitute for hepatocytes in liver disorders. Differentiation required hepatogenic medium. Quantitative reverse transcription‐polymerase chain reaction and immunofluorescent staining of hepatic genes and proteins including cytokeratin 18 (ck18), alpha‐fetoprotein (afp), and albumin (alb) were used to assess differentiation. Cells differentiated with a hepatocyte‐like morphology and expressed hepatic markers on 30 days of differentiation. The Periodic Acid‐Schiff (PAS) reaction showed storage of glycogen, and albumin and afp secretions were also detected. In vitro hEnSCs behave like hepatocyte after differentiation and may be a suitable source of cells in liver regeneration.
Kv7.2 regulates the function of peripheral sensory neurons
Authors: King Chih H. , Lancaster Eric , Salomon Daniela , Peles Elior , Scherer Steven S. 
Published: March 2014

ABSTRACTThe Kv7 (KCNQ) family of voltage‐gated K+ channels regulates cellular excitability. The functional role of Kv7.2 has been hampered by the lack of a viable Kcnq2‐null animal model. In this study, we generated homozygous Kcnq2‐null sensory neurons using the Cre‐Lox system; in these mice, Kv7.2 expression is absent in the peripheral sensory neurons, whereas the expression of other molecular components of nodes (including Kv7.3), paranodes, and juxtaparanodes is not altered. The conditional Kcnq2‐null animals exhibit normal motor performance but have increased thermal hyperalgesia and mechanical allodynia. Whole‐cell patch recording technique demonstrates that Kcnq2‐null sensory neurons have increased excitability and reduced spike frequency adaptation. Taken together, our results suggest that the loss of Kv7.2 activity increases the excitability of primary sensory neurons. J. Comp. Neurol. 522:3262–3280, 2014. © 2014 Wiley Periodicals, Inc.
A GEANT4 web‐based application to support Intra‐Operative Electron Radiotherapy using the European grid infrastructure
Authors: Casarino C. , Russo G. , Candiano G. C. , La Rocca G. , Barbera R. , Borasi G. , Guatelli S. , Messa C. , Passaro G. , Gilardi M.C. 
Published: March 2014

SummaryRadiotherapy techniques deliver ionizing radiations (X‐rays, photons, electrons, protons, etc.) inside cancerous tissues to kill the abnormal cells. Radiotherapy‐related activities such as the optimization of the therapeutic radiation dose to patients, workers' radioprotection, linear accelerator commissioning, quality assurance processes and technical innovations of linear accelerators are strongly based on the ability to predict the dose distribution. Monte Carlo based simulations are so far the most accurate tool for the calculation of dosimetric parameters, with the drawback of requiring extensive computing resources to achieve statistically meaningful results in a reasonable time frame. In the last years, advanced cancer treatment clinical and research communities have used e‐Infrastructures to support their activities. The present paper reports on the development of a computing facility for helping clinical researchers in using modern R&E networking and distributed computing and storage resources for a new radiotherapy technique: the Intra‐Operative Electron Radiotherapy. The web application developed addresses some technical and clinical needs as the design of linear accelerators' collimation systems and the optimization of the patient therapeutic dose distribution. Copyright © 2014 John Wiley & Sons, Ltd.
A single‐stage integrated bridgeless AC/DC converter for electrolytic capacitor‐less LED lighting applications
Authors: Ma Hongbo , Zheng Cong , Yu Wensong , Lai Jih‐Sheng (Jason) 
Published: March 2014

SummaryIn this paper, a single‐stage integrated bridgeless AC/DC converter is proposed. As compared to its counterpart that is composed of totem‐pole boost power factor correction (PFC) cascade fly‐back DC/DC converter, the studied circuit has less components number while overcoming the limits of the totem‐pole type. Thus, it is suitable to the low‐power LED lighting applications. Furthermore, when both PFC inductors Lb and magmatic inductance Lm of the transformer TR1 operate at discontinuous current mode, the bus voltage vCB can be used to decouple the ac input and constant dc output power. Thus, the approach of increasing bus voltage ripple is employed to eliminate electrolytic capacitors and obtain long operation lifetime. Additionally, it is able to be compatible with our studied twin‐bus configuration for increasing the overall efficiency. A 50‐W hardware prototype has been designed, fabricated, and tested in the laboratory to verify the proposed converter validity. Copyright © 2014 John Wiley & Sons, Ltd.
Effect of Anisotropic Ion Pressure on Solitary Waves in Magnetized Dusty Plasmas
Authors: Adnan M. , Mahmood S. , Qamar Anisa 
Published: March 2014

AbstractThe propagation of linear and nonlinear dust ion acoustic waves (DIAWs) are studied in a collisionless magnetized plasma which consists of warm ions having anisotropic thermal pressure, nonthermal (energetic) electrons and static dust particles of positive and negative charge polarity. The anisotropic ion pressure is defined using double adiabatic Chew‐Golberger‐Low (CGL) theory. In the linear regime, the propagation properties of the two possible modes are investigated via ion pressure anisotropy, dust particle polarity and nonthermality of electrons. Using reductive method Zakharov‐Kuznetsov (ZK) equation is derived for the propagation of two dimensional electrostatic dust ion acoustic solitary waves in dusty plasmas. It is found that both compressive and rarefactive solitons are formed in presence of nonthermal electrons using Cairn's distribution [R.A. Cairns, A.A. Mamun, R. Bingham, R.O. Dendy, R. Bostrom, C.M.C. Nairn and P.K. Shukla, Geophys.Res. Lett. 22, 2709 (1995)] in the system. The ion pressure anisotropy, nonthermality of electrons and charge polarity of the dust particles have significant effects on the amplitude and width of the dust ion acoustic solitary waves in such anisotropic nonthermal magnetized dusty plasmas. The numerical results are also presented for illustration. Our finding is applicable to space dusty plasma regimes having anisotropic ion pressure and nonthermal electrons. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
EEMHR: Energy‐efficient multilevel heterogeneous routing protocol for wireless sensor networks
Authors: Tanwar Sudeep , Kumar Neeraj , Niu Jian‐Wei 
Published: March 2014

SUMMARYWireless Sensor Networks (WSNs) are being used in wide areas of applications for data collection and processing. Energy management is one of the crucial issues that need special attention in WSNs. But most of the existing solutions for energy management are restricted in defining the number of levels for node heterogeneity for efficient energy management. Due to this restriction, a performance degradation has been observed in most of the applications in WSNs. Hence, keeping in the view of the aforementioned issue, in this paper, we proposed a new energy‐efficient multilevel heterogeneous routing (EEMHR) protocol for WSNs. Nodes are divided in to k levels of hierarchy in the proposed solution. A variable threshold defined by the ratio of number of alive nodes for current round to the total number of nodes is proposed for the selection of cluster heads. The performance of the proposed approach is evaluated by varying the various parameters of the network in comparison with other state‐of‐the‐art protocols such as stable election protocol (SEP) and multihop communication routing (MCR). Simulation results show that by varying the initial energy and node heterogeneity parameters, the network lifetime of EEMHR is improved by 17% in comparison with SEP and MCR. Moreover, EEMHR provides better stability and distribution of cluster heads in comparison with SEP and MCR. Copyright © 2014 John Wiley & Sons, Ltd.
De Novo Designed Copper α‐Helical Peptides: From Design to Function
Authors: Tegoni Matteo 
Published: March 2014

AbstractDe novo protein design is a fascinating and powerful approach to the design of metal sites in the interior of simplified protein scaffolds. A series of de novo designed copper peptides are herein described. They consist of peptide constructs that possess a secondary and tertiary structure, and that can be regarded as simplified proteins from which most of the structural complexity has been removed. Although relatively small, these copper peptides retain enough complexity to show features typical of proteins, such as enzyme‐like catalytic behavior or specific spectroscopic features. This review focuses on the de novo design of α‐helical constructs and in their use to devise different types of copper centers. Through the proper design of the peptide sequences, it has been possible to study the Cu‐triggered folding of peptide strands, which resulted in the isolation of enzyme regulators and biosensors for copper. Moreover, the use of Cys‐containing peptides allowed us to design sites structurally similar to the copper‐binding sites of biomolecules involved in copper trafficking and homeostasis. Finally, catalytic copper Type 2 sites capable of undergoing redox reactions and copper Type 1 and Type A centers with spectroscopic characteristics remarkably similar to those of natural proteins are discussed.
Self‐Assembled Cages from the Electroactive Bis(pyrrolo)tetrathiafulvalene (BPTTF) Building Block
Authors: Bivaud Sébastien , Goeb Sébastien , Balandier Jean‐Yves , Chas Marcos , Allain Magali , Sallé Marc 
Published: March 2014

AbstractA family of di‐ and tetratopic redox‐active ligands designed to generate discrete self‐assembled metallacages is described, including UV/Vis spectrometry and cyclic voltammetry studies, X‐ray diffraction on single crystals, and DFT calculations. A significant degree of conjugation between the π‐donating bis(pyrrolo)tetrathiafulvalene (BPTTF) and the electron‐withdrawing coordinating pyridyl units is observed. The tetrapyridyl ligand is able to self‐assemble in the presence of cis‐protected PtII complexes to produce the first examples of BPTTF‐based cages endowed with a cavity prone to guest encapsulation. These metallacages undergo an original chemical conversion upon being heated in DMSO to afford Pt–dithiolene complexes, one of which was characterized by XRD. This reaction could be extended to alternative BPTTF derivatives.
A computational approach predicting CYP450 metabolism and estrogenic activity of an endocrine disrupting compound (PCB-30)
Authors: Harris Jason B. , Eldridge Melanie L. , Sayler Gary , Menn Fu-Min , Layton Alice C. , Baudry Jerome 
Published: March 2014

Abstract

Endocrine disrupting chemicals influence growth and development through interactions with the hormone system, often through binding to hormone receptors such as the estrogen receptor. Computational methods can predict endocrine disrupting chemical activity of unmodified compounds, but approaches predicting activity following metabolism are lacking. The present study uses a well-known environmental contaminant, PCB-30 (2,4,6-trichlorobiphenyl), as a prototype endocrine disrupting chemical and integrates predictive (computational) and experimental methods to determine its metabolic transformation by cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6) into estrogenic byproducts. Computational predictions suggest that hydroxylation of PCB-30 occurs at the 3- or 4-phenol positions and leads to metabolites that bind more strongly than the parent molecule to the human estrogen receptor alpha (hER-α). Gas chromatography–mass spectrometry experiments confirmed that the primary metabolite for CYP3A4 and CYP2D6 is 4-hydroxy-PCB-30, and the secondary metabolite is 3-hydroxy-PCB-30. Cell-based bioassays (bioluminescent yeast expressing hER-α) confirmed that hydroxylated metabolites are more estrogenic than PCB-30. These experimental results support the applied model's ability to predict the metabolic and estrogenic fate of PCB-30, which could be used to identify other endocrine disrupting chemicals involved in similar pathways. Environ Toxicol Chem 2014;33:1615–1623. © 2014 SETAC
The power of neuroimaging biomarkers for screening frontotemporal dementia
Authors: McMillan Corey T. , Avants Brian B. , Cook Philip , Ungar Lyle , Trojanowski John Q. , Grossman Murray 
Published: March 2014

AbstractFrontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative disease that can result from either frontotemporal lobar degeneration (FTLD) or Alzheimer's disease (AD) pathology. It is critical to establish statistically powerful biomarkers that can achieve substantial cost‐savings and increase the feasibility of clinical trials. We assessed three broad categories of neuroimaging methods to screen underlying FTLD and AD pathology in a clinical FTD series: global measures (e.g., ventricular volume), anatomical volumes of interest (VOIs) (e.g., hippocampus) using a standard atlas, and data‐driven VOIs using Eigenanatomy. We evaluated clinical FTD patients (N = 93) with cerebrospinal fluid, gray matter (GM) magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI) to assess whether they had underlying FTLD or AD pathology. Linear regression was performed to identify the optimal VOIs for each method in a training dataset and then we evaluated classification sensitivity and specificity in an independent test cohort. Power was evaluated by calculating minimum sample sizes required in the test classification analyses for each model. The data‐driven VOI analysis using a multimodal combination of GM MRI and DTI achieved the greatest classification accuracy (89% sensitive and 89% specific) and required a lower minimum sample size (N = 26) relative to anatomical VOI and global measures. We conclude that a data‐driven VOI approach using Eigenanatomy provides more accurate classification, benefits from increased statistical power in unseen datasets, and therefore provides a robust method for screening underlying pathology in FTD patients for entry into clinical trials. Hum Brain Mapp 35:4827–4840, 2014. © 2014 Wiley Periodicals, Inc.
Insula and sensory insular cortex and somatosensory control in patients with insular stroke
Authors: Baier B. , zu Eulenburg P. , Geber C. , Rohde F. , Rolke R. , Maihöfner C. , Birklein F. , Dieterich M. 
Published: March 2014

AbstractBackgroundIn functional imaging studies, the insular cortex (IC) has been identified as an essential part of the processing of a whole spectrum of multimodal sensory input. However, there are no lesion studies including a sufficient number of patients, which would reinforce the functional imaging data obtained from healthy subjects. Such lesion studies should examine how damage to the IC affects sensory perception. We chose acute stroke patients with lesions affecting the IC in order to fill this gap.MethodsA comprehensive sensory profiling by applying a quantitative sensory testing protocol was performed and a voxel‐lesion behaviour mapping analysis in 24 patients with acute unilateral cortical damage was applied.ResultsOur data demonstrate that patients with lesions of the posterior IC have deficits in temperature perception, but did not show other sensory deficits such as hot or cold pain perception associated with specific lesion locations.ConclusionOur data allow the conclusion that the posterior IC may represent the major region responsible for encoding warm and cold perception in the brain. To what extent focal IC lesions may also impair pain processing or induce post‐stroke pain has to be addressed in future studies including more patients.