bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approximating peak responses in seismically isolated buildings using generalized modal analysis
Authors: Becker Tracy C. , Mahin Stephen A. 
Published: April 2013

SUMMARYAlthough the ability to simulate accurately the detailed behavior of nonlinear isolation bearings and the effects of this nonlinearity on dynamic response of the isolated building is desirable, such detailed analyses are not feasible during initial design stages when bearing properties are being selected. However, it would be very beneficial to be able to estimate accurately key engineering demand parameters at the early stages of design to understand the dynamic response characteristics of the isolated structure and to balance and optimize the bearing and structural characteristics to achieve the performance goals set for the building. Unfortunately, classical modal response spectrum analysis methods do not provide accurate results for problems with large, nonclassical damping, as is characteristic of isolated buildings. To find a method capable of predicting peak building responses even with large nonclassical damping, generalized modal response spectrum analysis is implemented. The responses of several buildings having different heights and isolated by linear viscous as well as triple friction pendulum and single friction pendulum isolation systems are investigated. Generalized modal response spectrum analysis methods were found to give significantly better predictions for all systems compared with classical methods. The behavior of buildings isolated with single friction pendulum systems exhibiting sudden changes in stiffness could not be well predicted by either general or classical modal response spectrum analysis when effective damping was increased. Copyright © 2013 John Wiley & Sons, Ltd.
A Dynamic Factor Approach to Mortality Modeling
Authors: French Declan , O'Hare Colin 
Published: April 2013

ABSTRACTLongevity risk has become one of the major risks facing the insurance and pensions markets globally. The trade in longevity risk is underpinned by accurate forecasting of mortality rates. Using techniques from macroeconomic forecasting we propose a dynamic factor model of mortality that fits and forecasts age‐specific mortality rates parsimoniously. We compare the forecasting quality of this model against the Lee–Carter model and its variants. Our results show the dynamic factor model generally provides superior forecasts when applied to international mortality data. We also show that existing multifactorial models have superior fit but their forecasting performance worsens as more factors are added. The dynamic factor approach used here can potentially be further improved upon by applying an appropriate stopping rule for the number of static and dynamic factors. Copyright © 2013 John Wiley & Sons, Ltd.
The effect of P2X7 receptor activation on nuclear factor‐kappa B phosphorylation induced by status epilepticus in the rat hippocampus
Authors: Kim Ji‐Eun , Kim Duk‐Soo , Jin Ryu Hea , Il Kim Won , Kim Min‐Ju , Won Kim Dae , Young Choi Soo , Kang Tea‐Cheon 
Published: April 2013

AbstractNuclear factor‐kappa B (NFκB) signal is essential for neuronal survival and its activation may protect neuron against various stimuli. Since purinergic signals activate NFκB through the P2X7 receptor, we investigated the distinct pattern of NF‐κB phosphorylation in neurons by P2X7 receptor activation following status epilepticus (SE) in an effort to understand the role of P2X7 receptor in epileptogenic insult. In non‐SE animals, 2′(3′)‐O‐(4‐benzoyl)benzoyl adenosine 5′‐triphosphate (BzATP, a P2X7R agonist) treatment increased only p52‐Ser869 NF‐κB phosphorylation in neuron. Following SE, p52‐Ser865, p52‐Ser869, p65‐Ser276, p65‐Ser311, p65‐Ser468, and p65‐Ser529 NF‐κB phosphorylation was significantly decreased in CA1 and CA3 neurons. However, BzATP treatment prevented reductions in p65‐Ser276, p65‐Ser311, p65‐Ser529, and p52‐Ser869 NF‐κB phosphorylations in CA1 and/or CA3 neurons induced by SE. Furthermore, BzATP treatment reduced SE‐induced p65‐Ser311, p65‐Ser468, p65‐Ser536, and p52‐Ser869 NF‐κB phosphorylations in astrocytes. These findings indicate that P2X7 functions may be involved in the regulation of SE‐induced reactive astrocytes and neuronal degeneration via NF‐κB phosphorylations in response to pilocarpine‐induced SE in the rat hippocampus. © 2013 Wiley Periodicals, Inc.
Association of the dopamine β‐hydroxylase 19 bp insertion/deletion polymorphism with positive symptoms but not tardive dyskinesia in schizophrenia
Authors: Zhou Na , Yu Qiong , Li Xiaokun , Yu Yaqin , Kou Changgui , Li Wenjun , Xu Hongqin , Luo Xingguang , Zuo Lingjun , Kosten Thomas R. , Zhang Xiang Yang 
Published: April 2013

ObjectiveOveractivity of dopaminergic neurotransmission is a putative mechanism of tardive dyskinesia (TD). Dopamine beta‐hydroxylase (DBH) is a key enzyme in the conversion of dopamine to norepinephrine, and plasma DBH activity is altered in TD patients. This study examined whether the functional DBH 5'‐Ins/Del polymorphism was associated with TD severity in Chinese patients with schizophrenia.MethodsWe compared the rate of this polymorphism in patients with (n = 312) and without TD (n = 435), and healthy controls (n = 625). The severity of TD was assessed using the Abnormal Involuntary Movement Scale (AIMS) and psychopathology using the Positive and Negative Syndrome Scale (PANSS).ResultsThere were no significant differences in the distribution of the allele and genotype frequencies between the patients and controls, or between the patients with and without TD. Also, there was no significant difference in the AIMS total score between the three genotype groups. However, the PANSS positive symptom subscore was significantly higher in patients with Del/Del genotype (13.2 ± 5.2) than those with Ins/Del (11.2 ± 4.9) and Ins/Ins (11.1 ± 3.1) genotypes (both p < 0.05).ConclusionThese results suggest that although the DBH 5'‐Ins/Del polymorphism was not associated with susceptibility to TD in patients with schizophrenia, it might be related to positive symptoms of schizophrenia. Copyright © 2013 John Wiley & Sons, Ltd.
Identification of endogenous reference genes for RT‐qPCR analysis of plasma microRNAs levels in rats with acetaminophen‐induced hepatotoxicity
Authors: Wang Yan , Tang Naping , Hui Taotao , Wang Shuyan , Zeng Xiancheng , Li Hua , Ma Jing 
Published: April 2013

ABSTRACTCirculating microRNA (miRNA) expression profiles have been reported to be promising biomarkers for drug‐induced liver injury in preclinical and clinical practice. Proper normalization is critical for accurate miRNAs expression analysis. Herein, using SYBR green quantitative real‐time PCR (RT‐qPCR), we evaluated the expression stability of six candidate reference genes including two commonly used small RNAs (U6, 5S) and four miRNAs (let‐7a, miR‐92a, miR‐103 and miR‐16) in plasma of rats with acetaminophen‐induced hepatotoxicity. Data were analysed using geNorm, Normfinder, BestKeeper and comparative delta‐Ct statistical models, and the results consistently show that miR‐103 is the most stably expressed reference gene. Whereas the commonly used housekeeping genes 5S or U6 are all not suitable normalizers, because 5S exhibits extensive variability in expression and U6 has a low expression level across the plasma samples. Then the effect of reference genes on normalization of plasma miR‐122 was assessed; when normalized to the most stable reference gene there were significant differences between the acetaminophen‐treated group and the vehicle group. However, when the data were normalized to a less stably expressed gene, miR‐16, a biased result was obtained. Therefore, we recommend that miR‐103 as suitable reference gene for plasma miRNAs analysis for acetaminophen‐induced liver injury. Data presented in this paper are crucial to successful biomarker discovery and validation for the diagnosis of the early stage of acetaminophen hepatotoxicity. Copyright © 2013 John Wiley & Sons, Ltd.
Genomic biomarkers for cardiotoxicity in rats as a sensitive tool in preclinical studies
Authors: Nishimura Yoko , Morikawa Yuji , Kondo Chiaki , Tonomura Yutaka , Fukushima Ryou , Torii Mikinori , Uehara Takeki 
Published: April 2013

ABSTRACTThe development of safer drugs is a high priority for pharmaceutical companies. Among the various toxicities caused by drugs, cardiotoxicity is an important issue because of its lethality. In addition, cardiovascular toxicity leads to the attrition of many drug candidates in both preclinical and clinical phases. Although histopathological and blood chemistry examinations are the current gold standards for detecting cardiotoxicity in preclinical studies, the large number of withdrawals from clinical studies owing to safety problems indicate that a more sensitive tool is required. We recently identified 32 genes that were candidate genomic biomarkers for cardiotoxicity in rats. Based on their functions, the present study focused on 8 of these 32 genes (Spp1, Fhl1, Timp1, Serpine1, Bcat1, Lmcd1, Rnd1 and Tgfb2). Diagnostic accuracy for the genes was determined by a receiver‐operating characteristic (ROC) analysis using more cardiotoxic and non‐cardiotoxic compounds. In addition, an optimized support vector machine (SVM) model that was composed of Spp1 and Timp1 was newly constructed. This new multi‐gene model exhibited a much higher diagnostic accuracy than that observed for plasma cardiac troponin I (cTnI), which is one of the most useful plasma biomarkers for cardiotoxicity detection. Furthermore, we determined that this multi‐gene model could predict potential cardiotoxicity in rats in the absence of any cardiac histopathological lesions or elevations of plasma cTnI. Overall, this multi‐gene model exhibited advantages over classic tools commonly used for cardiotoxicity evaluations in rats. Our current results suggest that application of the model could potentially lead to the production of safer drugs. Copyright © 2013 John Wiley & Sons, Ltd.
Student award winner in the Ph.D. category for the 2013 society for biomaterials annual meeting and exposition, april 10–13, 2013, Boston, Massachusetts
Authors: Tzeng Stephany Y. , Higgins Luke J. , Pomper Martin G. , Green Jordan J. 
Published: April 2013

AbstractLiver cancer is a leading cause of cancer death. Most patients are treated by arterial injection of chemoembolizing agents, providing a convenient avenue for local treatment by novel therapies, including gene therapy. Poly(beta‐amino ester)s (PBAEs) were synthesized and used to form nanoparticles for non‐viral transfection of buffalo rat hepatoma (MCA‐RH7777) and hepatocyte (BRL‐3A) lines with eGFP and luciferase DNA. Hepatoma cells were transfected with up to (98 ± 0.4)% efficacy with no measurable cytotoxicity. Hepatocytes were transfected with as high as (73 ± 0.4)% efficacy with (10 ± 4)% non‐specific cytotoxicity. In contrast, positive controls (branched polyethylenimine, Lipofectamine™ 2000, and X‐tremeGENE® DNA HP) caused 30–90% toxicity in BRL‐3A cells at doses required for >50% transfection. Of the 21 optimized PBAE‐DNA formulations tested, 12 showed significant specificity for hepatoma cells over hepatocytes in monoculture (p < 0.05 for both percentage transfected and eGFP expression intensity). Top polymers from eGFP studies also delivered luciferase DNA with 220 ± 30‐fold and 470 ± 30‐fold greater specificity for hepatoma cells than hepatocytes. Transfections of co‐cultures of hepatoma and hepatocytes with eGFP DNA also showed high specificity (1.9 ± 0.1‐ to 5.8± 1.4‐fold more transfected hepatoma cells than hepatocytes, measured by percentage transfected and flow cytometry). By eGFP intensity, up to 530 ±60‐fold higher average expression per cell was measured in hepatoma cells. One top formulation caused (95 ± 0.2)% transfection in hepatoma cells and (27 ± 0.2)% in hepatocytes [(96 ± 9)% relative hepatocyte viability]. PBAE‐based nanoparticles are a viable strategy for liver cancer treatment, delivering genes to nearly 100% of cancer cells while maintaining high biomaterial‐mediated specificity to prevent toxic side‐effects on healthy hepatocytes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Weighted registration of 123I‐FP‐CIT SPECT images improves accuracy of binding potential estimates in pathologically low striatal uptake
Authors: Ciarmiello Andrea , Giovacchini Giampiero , Guidotti Claudio , Meniconi Martina , Lazzeri Patrizia , Carabelli Elena , Mansi Luigi , Mariani Giuliano , Volterrani Duccio , Del Sette Massimo 
Published: April 2013

AbstractTo test whether the use of a striatum weighted image may improve registration accuracy and diagnostic outcome in patients with parkinsonian syndromes (PS), weighted images were generated by increasing signal intensity of striatal voxels and used as intermediate dataset for co‐registering the brain image onto template. Experimental validation was performed using an anthropomorphic striatal phantom. 123I‐FP‐CIT SPECT binding ratios were manually determined in 67 PS subjects and compared to those obtained using unsupervised standard (UWR) and weighted registered (WR) approach. Normalized cost function was used to evaluate the accuracy of phantom and subjects registered images to the template. Reproducibility between unsupervised and manual ratios was assessed by using intra‐class correlation coefficient (ICC) and Bland and Altman analysis. Correlation coefficient was used to assess the dependence of semi‐quantitative ratios on clinical findings. Weighted method improves accuracy of brain registration onto template as determined by cost function in phantom (0.86 ± 0.06 vs. 0.98 ± 0.02; Student's t‐test, P = 0.04) and in subject scans (0.69 ± 0.06 vs. 0.53 ± 0.06; Student's t‐test, P < 0.0001). Agreement between manual and unsupervised derived binding ratios as measured by ICC was significantly higher on WR as compared to UWR images (0.91 vs. 0.76). Motor UPDRS score was significantly correlated with manual and unsupervised derived binding potential. In phantom, as well as in subjects studies, correlations were more significant using the WR method (BPm: R2 = 0.36, P = 0.0001; BPwr: R2 = 0.368, P = 0.0001; BPuwr: R2 = 0.300, P = 0.0008). Weighted registration improves accuracy of binding potential estimates and may be a promising approach to enhance the diagnostic outcome of SPECT imaging, correlation with disease severity, and for monitoring disease progression in Parkinsonian syndromes. J. Cell. Physiol. 228: 2086–2094, 2013. © 2013 Wiley Periodicals, Inc.
Effect of different parameters used for in vitro gene electrotransfer on gene expression efficiency, cell viability and visualization of plasmid DNA at the membrane level
Authors: Haberl Saša , Kandušer Maša , Flisar Karel , Hodžić Duša , Bregar Vladimir Boštjan , Miklavčič Damijan , Escoffre Jean‐Michel , Rols Marie‐Pierre , Pavlin Mojca 
Published: April 2013

AbstractBackgroundGene electrotransfer is a nonviral method used for DNA delivery into cells. Several steps are involved. One of them is the interaction of DNA with the cell membrane, which is crucial before DNA can enter the cell. We analysed the level of DNA–membrane interaction in relation to electrotransfer efficiency and the importance of the electrophoretic accumulation of DNA at the cell membrane. Systematic comparison of long‐duration, short‐duration and combinations of electropermeabilizing short (high‐voltage; HV) and electrophoretic long (low‐voltage; LV) pulses were performed. The effect of Mg2+ ion concentrations on electrotransfer and their effect on DNase activity were explored.MethodsTo visualize the DNA–membrane interaction, TOTO‐1 labeled DNA was used. Transfection efficiency was assessed with plasmid DNA coding for green fluorescent protein.ResultsHigher relative electrotransfer efficiency was obtained by using longer pulses, whereas shorter pulses preserved cell viability. Short‐duration pulses enabled higher (24%) overall transfection yield compared to long‐duration pulses (12%), although a higher DNA–membrane interaction was observed. No significant difference in transfection was obtained between different HV‐LV pulsing protocols, although the highest DNA–membrane interaction was observed with HV + LV pulses. The formation of the DNA–membrane complex depended on the Mg2+ concentration, whereas DNase inhibitor did not affect gene expression.ConclusionsGene electrotransfer is a complex phenomenon, where many factors mutually affect the process and the DNA–membrane interaction only comprises the first step. We showed that longer electric pulses are optimal for higher transfection efficiency but reduce viability, whereas shorter pulses enable moderate transfection efficiency and preserve viability. Thus, each application needs a careful choice of pulsing protocol. Copyright © 2013 John Wiley & Sons, Ltd.
Development of a handoff evaluation tool for shift‐to‐shift physician handoffs: The handoff CEX
Authors: Horwitz Leora I. , Rand David , Staisiunas Paul , Van Ness Peter H. , Araujo Katy L. B. , Banerjee Stacy S. , Farnan Jeanne M. , Arora Vineet M. 
Published: April 2013

BACKGROUNDIncreasing frequency of shift‐to‐shift handoffs coupled with regulatory requirements to evaluate handoff quality make a handoff evaluation tool necessary.OBJECTIVETo develop a handoff evaluation tool.DESIGNTool development.SETTINGTwo academic medical centers.SUBJECTSNurse practitioners, medicine housestaff, and hospitalist attendings.INTERVENTIONConcurrent peer and external evaluations of shift‐to‐shift handoffs.MEASUREMENTSThe Handoff CEX (clinical evaluation exercise) consists of 6 subdomains and 1 overall assessment, each scored from 1 to 9, where 1 to 3 is unsatisfactory and 7 to 9 is superior. We assessed range of scores, performance among subgroups, internal consistency, and agreement among types of raters.RESULTSWe conducted 675 evaluations of 97 unique individuals during 149 handoff sessions. Scores ranged from unsatisfactory to superior in each domain. The highest rated domain for handoff providers was professionalism (median: 8; interquartile range [IQR]: 7–9); the lowest was content (median: 7; IQR: 6–8). Scores at the 2 institutions were similar, and scores did not differ significantly by training level. Spearman correlation coefficients among the CEX subdomains for provider scores ranged from 0.71 to 0.86, except for setting (0.39–0.40). Third‐party external evaluators consistently gave lower marks for the same handoff than peer evaluators did. Weighted kappa scores for provider evaluations comparing external evaluators to peers ranged from 0.28 (95% confidence interval [CI]: 0.01, 0.56) for setting to 0.59 (95% CI: 0.38, 0.80) for organization.CONCLUSIONSThis handoff evaluation tool was easily used by trainees and attendings, had high internal consistency, and performed similarly across institutions. Because peers consistently provided higher scores than external evaluators, this tool may be most appropriate for external evaluation. Journal of Hospital Medicine 2013;8:191–200. © 2013 Society of Hospital Medicine
Brain iron MRI: A biomarker for amyotrophic lateral sclerosis
Authors: Ignjatović Aleksandar , Stević Zorica , Lavrnić Slobodan , Daković Marko , Bačić Goran 
Published: April 2013

PurposeTo evaluate the usefulness of MRI detection of hypointensity areas (iron deposits) in the brain using a dedicated MRI technique in patients with ALS in establishing this sign as a potential surrogate biomarker that correlates with the severity of disease.Materials and MethodsForty‐six ALS patients and 26 age‐matched controls were examined by MRI. The ALS Functional Rating Scale (ALSFRS) score was determined before the first MRI examination. The sub‐set of 25 ALS patients was re‐examined around 6 months after the first MRI examination. The MRI examination consisted of routine T1W, T2W, and FLAIR sequences with the addition of a thin slice heavily T2* weighted sequence to accentuate magnetic susceptibility artifacts.ResultsT2*W sequence is superior to any other MRI sequence in detecting hypointensities in the brain of ALS patients. Hypointensities were found only in the precentral gyruses gray matter (PGGM) and were detected in 42 patients. The extent of hypointensities was measured and scored (0–3) and correlated with ALSFRS (r = −0.545). Twenty‐five patients were re‐examined 6 months later, and the majority of them showed the shift toward higher MRI scores. No control subjects had hypointensities in PGGM.ConclusionThe detection of hypointensities in PGGM appears to be a very promising surrogate MRI biomarker for ALS due to its simplicity, high sensitivity and specificity, suitability for longitudinal studies, and relationship with the pathogenesis of the disease. J. Magn. Reson. Imaging 2013;38:1472–1479. © 2013 Wiley Periodicals, Inc.
Cardiac diffusion‐weighted MR imaging in recent, subacute, and chronic myocardial infarction: A pilot study
Authors: Laissy Jean‐Pierre , Gaxotte Virginia , Ironde‐Laissy Elisabeth , Klein Isabelle , Ribet Aurélie , Bendriss Ahmed , Chillon Sylvie , Schouman‐Claeys Elisabeth , Steg P. Gabriel , Serfaty Jean‐Michel 
Published: April 2013

PurposeTo investigate the clinical feasibility of diffusion‐weighted imaging (DWI) to detect recent myocardial infarction (MI) and to differentiate it from subacute and chronic MI, with late‐gadolinium enhancement (LGE) sequence as reference. Furthermore, to measure variation of the myocardial apparent diffusion coefficient (ADC) according to the age of MI.Materials and MethodsSeventy‐four MI patients were separated in 3 groups. Group A included 34 recent (< 8 days) MI patients; group B, 22 subacute (9–90 days) MI patients; group C, 18 chronic (> 90 days) MI patients; a fourth group (group D) included 24 controls. DWI and LGE images were acquired on a 1.5T system. DWI and LGE matched images were assessed visually by two blinded observers for hyperintense areas in corresponding segments.ResultsQualitative assessment of DWI compared with LGE images yielded a sensitivity of 97% and a specificity of 61%/14% to differentiate recent from chronic/subacute MI, respectively. The absolute ADCs (recent 0.00632 ± 0.00037 mm2/s, subacute 0.00639 ± 0.00035 mm2/s, chronic 0.00743 ± 0.00056 mm2/s, remote or normal 0.00895 ± 0.00019 mm2/s) and relative ADCs were significantly different between groups (P < 0.001) except between recent and subacute MIs.ConclusionDWI is a sensitive technique to diagnose recent MI. DWI MR sequences could help differentiate recent from chronic MI. From these preliminary results, one should expect DWI to be used in the triage of emergency patients with atypical chest pain, to clarify if an MI is present or not in just a few minutes. J. Magn. Reson. Imaging 2013;38:1377–1387. © 2013 Wiley Periodicals, Inc.
Wie das Krokodil zu Zähnen kam
Authors: Groß Michael 
Published: April 2013

AbstractDa Zähne vielfältige, genetisch determinierte Formen bilden und sich post mortem gut erhalten, eignen sie sich ideal, um Entwicklung und Evolution zu untersuchen. Diese Forschung ist noch lange nicht abgeschlossen und könnte eines Tages die Zahnmedizin revolutionieren.