bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene therapy for metabolic disorders: an overview with a focus on urea cycle disorders
Authors: Alexander Ian E. , Kok Cindy , Dane Allison P. , Cunningham Sharon C. 
Published: March 2012

AbstractMany metabolic diseases are compelling candidates for gene therapy, and are the subject of vigorous pre‐clinical research. Successful phenotype correction in mouse models is now commonplace and research effort is increasingly being directed towards addressing the translational challenges inherent in human clinical trials. This paper places current efforts to develop gene therapy approaches to metabolic disease in historical context and describes contemporary research in the authors’ laboratory on urea cycle defects, particularly ornithine transcarbamylase deficiency, in a manner that is illustrative of the general state of the field.
Lysine triggers apoptosis through a NADPH oxidase‐dependent mechanism in human renal tubular cells
Authors: Verzola Daniela , Famà Annamaria , Villaggio Barbara , Di Rocco Maia , Simonato Alchiede , D'Amato Elena , Gianiorio Fabio , Garibotto Giacomo 
Published: March 2012

AbstractProgressive chronic kidney disease (CKD) is common in lysinuric protein intolerance (LPI), a primary inherited aminoaciduria characterized by massive Lysine excretion in urine. However, by which mechanisms Lysine may cause kidney damage to tubule cells is still not understood. This study determined whether Lysine overloading of human proximal tubular cells (HK‐2) in culture enhances apoptotic cell loss and its associated mechanisms. Overloading HK‐2 with Lysine levels reproducing those observed in urine of patients affected by LPI (10 mM) increased apoptosis (+30%; p < 0.01 vs.C), as well as Bax and Apaf‐1 expressions (+30‐50% p < 0.05), while downregulated Bcl‐2 (‐40% p < 0.05). Apoptosis induced by high Lysine was no longer observed after addition of caspase‐9 and caspase‐3 inhibitors while caspase‐8 inhibitor had no protective effect. High Lysine induced elevations in ROS generation and NADPH oxidase subunits mRNAs (p22 phox +106±23%, p67 phox +108±22% and gp91 phox +75±4% p < 0.05‐0.01). In addition, the NADPH oxidase inhibitor DPI prevented both ROS production and apoptosis. Treating HK‐2 with antioxidants, such as Cysteine and its analog, N‐acetyl‐l‐cysteine (NAC), rescued the HK‐2 from apoptosis induced by Lysine. In summary, our data show that high Lysine in vitro increases the permissiveness of proximal tubule kidney cells to apoptosis by triggering a pathway involving NADPH oxidase signaling. This event may represent a key cellular effect in the increasing the susceptibility of human tubular cells to apoptosis when the tubules cope with a high Lysine load. This effect is instrumental to renal damage and disease progression in patients with LPI.
Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease
Authors: Yau Thomas , Wong Hilda , Chan Pierre , Yao T. J. , Pang R. , Cheung T. T. , Fan S. T. , Poon Ronnie T. 
Published: March 2012

Summary
Background The combination of bevacizumab (B) and erlotinib (E) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients. We aimed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment. Methods Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited. All patients received bevacizumab(B) at 10 mg/kg every 2 weeks with erlotinib(E) at 150 mg daily for a maximum of 6 cycles. Response assessments using both RECIST and modified RECIST criteria were performed after every 6 weeks. The primary endpoint was clinical benefit (CB) rate and a Simon two-stage design was employed. Results The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited. The median age was 47 years (range, 28–61) and all patients were in ECOG performance status 1. Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis. Among these 10 patients, none of the enrolled patients achieved response or stable disease. The median time-to-progression was 1.81 months (95 % confidence interval [C.I.], 1.08–1.74 months) and overall survival was 4.37 months (95 % C.I., 1.08–11.66 months). Rash (70 %), diarrhea (50 %) and malaise (40 %) were the most commonly encountered toxicities. Conclusion The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population. Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population.
Parsimonious Structural Equation Models for Repeated Measures Data, with Application to the Study of Consumer Preferences
Authors: Elrod Terry , Häubl Gerald , Tipps Steven W. 
Published: March 2012

AbstractRecent research reflects a growing awareness of the value of using structural equation models to analyze repeated measures data. However, such data, particularly in the presence of covariates, often lead to models that either fit the data poorly, are exceedingly general and hard to interpret, or are specified in a manner that is highly data dependent. This article introduces methods for developing parsimonious models for such data. The underlying technology uses reduced-rank representations of the variances, covariances and means of observed and latent variables. The value of this approach, which may be implemented using standard structural equation modeling software, is illustrated in an application study aimed at understanding heterogeneous consumer preferences. In this application, the parsimonious representations characterize systematic relationships among consumer demographics, attitudes and preferences that would otherwise be undetected. The result is a model that is parsimonious, illuminating, and fits the data well, while keeping data dependence to a minimum.
Posterior spinal fusion in patients with Ehlers–Danlos syndrome: A report of six cases
Authors: Rabenhorst Brien Michael , Garg Sumeet , Herring J. Anthony 
Published: March 2012

Purpose There is a paucity of literature describing posterior spinal fusion (PSF) in the Ehlers–Danlos syndrome (EDS) patient. The vast majority of these studies diagnosed EDS clinically. The purpose of this study is to discuss the management and complications of EDS patients with scoliosis treated with PSF at a single institution. Methods Clinical and radiographic data are presented describing six patients who had PSF for EDS. The diagnoses were confirmed by a geneticist. Results All of the patients in the current cohort underwent posterior fusion only, with no anterior approach. Neuromonitoring was also used in the majority. Half of our patients experienced complications. One patient had a hemoperitoneum that was initially treated nonoperatively but, unfortunately, they expired 1 month after discharge from abdominal bleeding. Another patient suffered neuropathic pain attributed to the type of implant used. A third underwent a total of seven procedures beginning at the age of 3 years in a different era of spinal surgery. The mean major curve, percentage correction, and estimated blood loss of the current cohort are similar to previous studies. Conclusion The fragility of the EDS patient population cannot be overlooked. Despite a conservative surgical approach, half of our patients experienced complications. The surgeon choosing to operate on EDS patients must do so with extreme caution.
Do corporate boards matter during the current financial crisis?
Authors: Francis Bill B. , Hasan Iftekhar , Wu Qiang 
Published: March 2012

AbstractThis study examines the impact of corporate boards on firm performance during the current financial crisis. Using buy‐and‐hold abnormal returns over the crisis to measure firm performance, we find that board independence, as traditionally defined, does not significantly affect firm performance. However, when we redefine independent directors as outside directors who are less connected with current CEOs, a measure we call strong independence, there is a positive and significant relationship between this measure and firm performance. Second, outside financial experts are important for firm performance. We find that the positive impact of outside financial experts on firm performance is more significant than that of strong independence. Overall, our results suggest that firm performance during a crisis is a function of firm‐level differences in corporate boards.
The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy
Authors: Lazarevic Bato , Hammarström Clara , Yang Jin , Ramberg Hakon , Diep Lien M. , Karlsen Steinar J. , Kucuk Omer , Saatcioglu Fahri , Taskèn Kristin A. , Svindland Aud 
Published: March 2012

Nutritionally relevant levels of genistein, the predominant isoflavone in soyabean associated with lower risk of prostate cancer (PCa), may modulate the expression of prostate tissue biomarkers associated with cancer prediction and progression. A phase 2 placebo-controlled, randomised, double-blind clinical trial was conducted in forty-seven Norwegian patients before prostatectomy. Intervention was 30 mg genistein or placebo capsules daily for 3–6 weeks. Luminal cells from malignant and benign glands were isolated with laser capture microdissection and the mRNA levels of androgen-related biomarkers (androgen receptor, NK3 homeobox 1, kallikrein-related peptide 4 (KLK4)) and cell cycle-related genes (p21Waf1/Cip1,p27Kip1,p53) were analysed with real-time semiquantitative PCR. Immunohistochemistry of androgen-, cell cycle-, proliferative- (Ki67 nuclear antigen), apoptotic- (B-cell CLL/lymphoma 2 (BCL-2) and BCL-2-associated X protein) and neuroendocrine differentiation-related biomarkers (neuron-specific enolase and cytoplasmic chromogranin A) was performed using tissue microarrays containing normal, Gleason grade 3 and grade 4 prostate tissues. There were no significant effects by genistein intervention on proliferation-, cell cycle-, apoptosis- or neuroendocrine biomarkers. Genistein intervention, however, significantly reduced the mRNA level of KLK4 in tumour cells (P = 0·033) and there was a non-significant reduction in androgen and cell cycle-related biomarkers, except for p27Kip1, whose expression in the nuclear compartment was increased. Genistein intervention modulated the expression of several biomarkers which may be related to PCa prediction and progression. The present study supports genistein as a chemopreventive agent in PCa. Further investigation is warranted in larger and longer-duration studies.
Influence of emotional distraction on working memory performance in borderline personality disorder
Authors: Krause-Utz A. , Oei N. Y. L. , Niedtfeld I. , Bohus M. , Spinhoven P. , Schmahl C. , Elzinga B. M. 
Published: March 2012

BackgroundEmotion dysregulation, characterized by heightened emotional arousal and increased emotional sensitivity, is a core feature of borderline personality disorder (BPD). Although current theories emphasize the disruptive potential of negative emotions on cognitive functioning in BPD, behavioral and neurobiological data on this relationship are still lacking.MethodUsing functional magnetic resonance imaging (fMRI), neural activity was investigated in 22 unmedicated BPD patients and 22 healthy participants (matched for age, education and intelligence) performing an adapted Sternberg working memory task, while being distracted by emotional (negatively arousing) and neutral pictures from the International Affective Picture System (IAPS).ResultsEmotional distraction was associated with significantly higher activation in the amygdala and decreased activation in the dorsolateral prefrontal cortex (DLPFC), extending findings of previous studies in healthy individuals. Patients with BPD showed significantly longer reaction times (RTs) along with significantly higher activation in the amygdala and insula during emotional distraction compared to healthy participants, suggesting that they were more distracted by emotional pictures during the working memory task. Moreover, in the group of BPD patients, a significant negative correlation was found between activation in limbic brain regions and self-reports of current dissociative states.ConclusionsOur findings suggest hyper-responsiveness to emotionally distracting pictures in BPD patients that negatively affects working memory performance. This stresses the importance of emotion dysregulation in the context of cognitive functioning. Moreover, our findings suggest that dissociative states have a dampening effect on neural reactivity during emotional challenge in BPD.
Alternative trajectory-tracking control approach for marine surface vessels with experimental verification
Authors: Fahimi Farbod , Van Kleeck Chris 
Published: March 2012

SUMMARYExperiments with a nonlinear trajectory-tracking controller for marine unmanned surface vessels are reported. The tracking controller is designed using a nonlinear robust model-based sliding mode approach. The marine vehicles can track arbitrary desired trajectories that are defined in Cartesian coordinate as continuous functions of time. The planar dynamic model used for the controller design consists of 3 degrees of freedom (DOFs) of surge, sway, and yaw. The vessel only has two actuators, so the vessel is underactuated. Therefore, only two outputs, which are functions of the 3-DOF, can be controlled. The Cartesian position of a control point on the vessel is defined as the output. The orientation dynamics is not directly controlled. It has been previously shown that the orientation dynamics, as the internal dynamics of this underactuated system, is stable. The result of field experiments show the effectiveness of tracking control laws in the presence of parameter uncertainty and disturbance. The experiments were performed in a large outdoor pond using a small test boat. This paper reports the first theoretical development and experimental verification of the proposed model-based nonlinear trajectory-tracking controller.
Influence of OPRM1 Asn40Asp variant (A118G) on [11C]carfentanil binding potential: preliminary findings in human subjects
Authors: Weerts Elise M. , McCaul Mary E. , Kuwabara Hiroto , Yang Xiaoju , Xu Xiaoqiang , Dannals Robert F. , Frost J. James , Wong Dean F. , Wand Gary S. 
Published: March 2012

AbstractThe Asn40Asp variant (A118G) of the µ opioid receptor (OPRM1) gene is thought to contribute to the development and treatment of alcohol dependence. Employing positron emission tomography (PET), we first examined whether the single nucleotide polymorphism (SNP) modifies binding potential (BPND) of the µ-selective ligand [11C]carfentanil in healthy control (Con) and 5-d abstinent alcohol-dependent (AD) subjects (unblocked basal scan). Second, we examined whether the allelic variants were associated with differences in OPRM1 occupancy by naltrexone (50 mg) in AD subjects. Con and AD carriers of the G allele (AG) had lower global BPND at the basal scan than subjects homozygous for the A allele (AA). In AD subjects, naltrexone occupancy was slightly higher in AG subjects (98.9%) compared to AA subjects (93.1%), but this was not significant. We are the first to demonstrate using PET in healthy normal and AD subjects that the A118G SNP alters OPRM1 availability.
Business Process Outsourcing and Legal Library Services: the Integreon Model – One Year On
Authors: Stanfield Kate 
Published: March 2012

AbstractWithin the legal library world “outsourcing” has become a hot topic, and not necessarily a welcome one. In the last 12 months there have been several law firms making the move to outsource their Information Services, so why is this happening and what are the options? Kate Stanfield, Vice President, Knowledge and Research at Integreon examines the issues. Her article is based on a presentation given at the BIALL Conference in June 2011.
On the onset of polar mesospheric cloud seasons as observed by SBUV
Authors: Benze Susanne , Randall Cora E. , Karlsson Bodil , Harvey V. Lynn , DeLand Matthew T. , Thomas Gary E. , Shettle Eric P. 
Published: March 2012

This paper describes an investigation using data from the Solar Backscatter Ultraviolet (SBUV) satellite instruments to explore and understand variations in the timing of the onset of Polar Mesospheric Cloud (PMC) seasons. Previous work has shown that for several recent southern hemisphere (SH) seasons, the PMC season onset was controlled by the timing of the shift from winter to summer zonal wind flow in the SH stratosphere. We extend the analysis of PMC season onset to 28 years of SBUV observations, including both hemispheres. A multiple linear regression analysis of SBUV data from 1984 to 2011 suggests that the SH PMC season onset is delayed by one day for every day that the zonal wind at 65°S and 50 hPa (∼20 km) remains in a winter‐like state. In addition, we find that the solar cycle plays a role: The SH season onset is delayed by about ten days at solar maximum compared to solar minimum. In the NH, the PMC season onset is delayed by ∼7 days at solar maximum compared to solar minimum; variations in the NH stratospheric wind, however, are not correlated with the NH onset date. On the other hand, inter‐hemispheric teleconnections are important in the NH; a one‐day shift in the NH season onset corresponds to a shift of ∼1.4 m/s in the SH stratospheric wind at 60.0°S and 20 hPa (∼26 km). Neither the NH nor the SH season onset date is correlated with the Quasi‐Biennial Oscillation, North Atlantic Oscillation, Arctic Oscillation, or El Niño Southern Oscillation.
Who is who in litter decomposition? Metaproteomics reveals major microbial players and their biogeochemical functions
Authors: Schneider Thomas , Keiblinger Katharina M , Schmid Emanuel , Sterflinger-Gleixner Katja , Ellersdorfer Günther , Roschitzki Bernd , Richter Andreas , Eberl Leo , Zechmeister-Boltenstern Sophie , Riedel Kathrin 
Published: March 2012

Abstract
Leaf-litter decomposition is a central process in carbon cycling; however, our knowledge about the microbial regulation of this process is still scarce. Metaproteomics allows us to link the abundance and activity of enzymes during nutrient cycling to their phylogenetic origin based on proteins, the ‘active building blocks’ in the system. Moreover, we employed metaproteomics to investigate the influence of environmental factors and nutrients on the decomposer structure and function during beech litter decomposition. Litter was collected at forest sites in Austria with different litter nutrient content. Proteins were analyzed by 1-D-SDS-PAGE followed by liquid-chromatography and tandem mass-spectrometry. Mass spectra were assigned to phylogenetic and functional groups by a newly developed bioinformatics workflow, assignments being validated by complementary approaches. We provide evidence that the litter nutrient content and the stoichiometry of C:N:P affect the decomposer community structure and activity. Fungi were found to be the main producers of extracellular hydrolytic enzymes, with no bacterial hydrolases being detected by our metaproteomics approach. Detailed investigation of microbial succession suggests that it is influenced by litter nutrient content. Microbial activity was stimulated at higher litter nutrient contents via a higher abundance and activity of extracellular enzymes.
Plant litter and soil type drive abundance, activity and community structure of alkB harbouring microbes in different soil compartments
Authors: Schulz Stephan , Giebler Julia , Chatzinotas Antonis , Wick Lukas Y , Fetzer Ingo , Welzl Gerhard , Harms Hauke , Schloter Michael 
Published: March 2012

Abstract
Alkanes are major constituents of plant-derived waxy materials. In this study, we investigated the abundance, community structure and activity of bacteria harbouring the alkane monooxygenase gene alkB, which catalyses a major step in the pathway of aerobic alkane degradation in the litter layer, the litter–soil interface and in bulk soil at three time points during the degradation of maize and pea plant litter (2, 8 and 30 weeks) to improve our understanding about drivers for microbial performance in different soil compartments. Soil cores of different soil textures (sandy and silty) were taken from an agricultural field and incubated at constant laboratory conditions. The abundance of alkB genes and transcripts (by qPCR) as well as the community structure (by terminal restriction fragment polymorphism fingerprinting) were measured in combination with the concentrations and composition of alkanes. The results obtained indicate a clear response pattern of all investigated biotic and abiotic parameters depending on the applied litter material, the type of soil used, the time point of sampling and the soil compartment studied. As expected the distribution of alkanes of different chain length formed a steep gradient from the litter layer to the bulk soil. Mainly in the two upper soil compartments community structure and abundance patterns of alkB were driven by the applied litter type and its degradation. Surprisingly, the differences between the compartments in one soil were more pronounced than the differences between similar compartments in the two soils studied. This indicates the necessity for analysing processes in different soil compartments to improve our mechanistic understanding of the dynamics of distinct functional groups of microbes.
Effect of oxygen minimum zone formation on communities of marine protists
Authors: Orsi William , Song Young C , Hallam Steven , Edgcomb Virginia 
Published: March 2012

Abstract
Changes in ocean temperature and circulation patterns compounded by human activities are leading to oxygen minimum zone (OMZ) expansion with concomitant alteration in nutrient and climate active trace gas cycling. Here, we report the response of microbial eukaryote populations to seasonal changes in water column oxygen-deficiency using Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island British Columbia, as a model ecosystem. We combine small subunit ribosomal RNA gene sequencing approaches with multivariate statistical methods to reveal shifts in operational taxonomic units during successive stages of seasonal stratification and renewal. A meta-analysis is used to identify common and unique patterns of community composition between Saanich Inlet and the anoxic/sulfidic Cariaco Basin (Venezuela) and Framvaren Fjord (Norway) to show shared and unique responses of microbial eukaryotes to oxygen and sulfide in these three environments. Our analyses also reveal temporal fluctuations in rare populations of microbial eukaryotes, particularly anaerobic ciliates, that may be of significant importance to the biogeochemical cycling of methane in OMZs.
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms
Authors: Caporaso J Gregory , Lauber Christian L , Walters William A , Berg-Lyons Donna , Huntley James , Fierer Noah , Owens Sarah M , Betley Jason , Fraser Louise , Bauer Markus , Gormley Niall , Gilbert Jack A , Smith Geoff , Knight Rob 
Published: March 2012

Abstract
DNA sequencing continues to decrease in cost with the Illumina HiSeq2000 generating up to 600 Gb of paired-end 100 base reads in a ten-day run. Here we present a protocol for community amplicon sequencing on the HiSeq2000 and MiSeq Illumina platforms, and apply that protocol to sequence 24 microbial communities from host-associated and free-living environments. A critical question as more sequencing platforms become available is whether biological conclusions derived on one platform are consistent with what would be derived on a different platform. We show that the protocol developed for these instruments successfully recaptures known biological results, and additionally that biological conclusions are consistent across sequencing platforms (the HiSeq2000 versus the MiSeq) and across the sequenced regions of amplicons.