bluuebunny/crossref_metadata_2025 huggingface dataset:
Point rainfall statistics for ecohydrological analyses derived from satellite integrated rainfall measurements
Authors: del Jesus Manuel , Rinaldo Andrea , Rodríguez‐Iturbe Ignacio
Published: April 2015

Satellite rainfall measurements, nowadays commonly available, provide valuable information about the spatial structure of rainfall. In areas with low‐density rain gage networks, or where these networks are nonexistent, satellite rainfall measurements can also provide useful estimates to be used as virtual rain gages. However, satellite and rain gage measurements are statistically different in nature and cannot be directly compared to one another. In the present paper, we develop a methodology to downscale satellite rainfall measurements to generate rain‐gage‐equivalent statistics. We apply the methodology to four locations along a strong rainfall gradient in the Kalahari transect, southern Africa, to validate the methodology. We show that the method allows the estimation of point rainfall statistics where only satellite measurements exist. Point rainfall statistics are key descriptors for ecohydrologic studies linking the response of vegetation to rainfall dynamics.
Deformation Field Analysis in Equal Channel Angular Extrusion of Metals Using Asymmetric Flow Function
Authors: Hasani Arman , Toth Laszlo S.
Published: April 2015

The trajectory and the corresponding plastic deformation of a material element during equal channel angular extrusion (ECAE) are analyzed with the help of a flow line function applicable for any ECAE die angle. The function contains the following three parameters: the parameter n that describes the sharpness of the line and the α and m parameters that account for the asymmetry of the flow line. The approach permits to determine the velocity field, the strain rate field, and, in general, the shape of the plastic deformation zone in ECAE experiments even for flow lines that are asymmetric with respect to the ECAE geometry. The flow line function was applied to flow lines observed in 90° and 120° ECAE of commercially pure aluminum as well as for 135° ECAE of pure copper to describe the characteristics of the deformation field and the evolution of the crystallographic texture.
Perceptions of presidential candidates' personalities in twitter
Authors: Bhattacharya Sanmitra , Yang Chao , Srinivasan Padmini , Boynton Bob
Published: April 2015

Political sentiment analysis using social media, especially Twitter, has attracted wide interest in recent years. In such research, opinions about politicians are typically divided into positive, negative, or neutral. In our research, the goal is to mine political opinion from social media at a higher resolution by assessing statements of opinion related to the personality traits of politicians; this is an angle that has not yet been considered in social media research. A second goal is to contribute a novel retrieval‐based approach for tracking public perception of personality using Gough and Heilbrun's Adjective Check List (ACL) of 110 terms describing key traits. This is in contrast to the typical lexical and machine‐learning approaches used in sentiment analysis. High‐precision search templates developed from the ACL were run on an 18‐month span of Twitter posts mentioning Obama and Romney and these retrieved more than half a million tweets. For example, the results indicated that Romney was perceived as more of an achiever and Obama was perceived as somewhat more friendly. The traits were also aggregated into 14 broad personality dimensions. For example, Obama rated far higher than Romney on the Moderation dimension and lower on the Machiavellianism dimension. The temporal variability of such perceptions was explored.
What is the function of mitochondrial networks? A theoretical assessment of hypotheses and proposal for future research
Authors: Hoitzing Hanne , Johnston Iain G. , Jones Nick S.
Published: April 2015

Mitochondria can change their shape from discrete isolated organelles to a large continuous reticulum. The cellular advantages underlying these fused networks are still incompletely understood. In this paper, we describe and compare hypotheses regarding the function of mitochondrial networks. We use mathematical and physical tools both to investigate existing hypotheses and to generate new ones, and we suggest experimental and modelling strategies. Among the novel insights we underline from this work are the possibilities that (i) selective mitophagy is not required for quality control because selective fusion is sufficient; (ii) increased connectivity may have non‐linear effects on the diffusion rate of proteins; and (iii) fused networks can act to dampen biochemical fluctuations. We hope to convey to the reader that quantitative approaches can drive advances in the understanding of the physiological advantage of these morphological changes.
Evaluating nonindigenous species management in a Bayesian networks derived relative risk framework for Padilla Bay, WA, USA
Authors: Herring Carlie E , Stinson Jonah , Landis Wayne G
Published: April 2015

Many coastal regions are encountering issues with the spread of nonindigenous species (NIS). In this study, we conducted a regional risk assessment using a Bayesian network relative risk model (BN-RRM) to analyze multiple vectors of NIS introductions to Padilla Bay, Washington, a National Estuarine Research Reserve. We had 3 objectives in this study. The 1st objective was to determine whether the BN-RRM could be used to calculate risk from NIS introductions for Padilla Bay. Our 2nd objective was to determine which regions and endpoints were at greatest risk from NIS introductions. Our 3rd objective was to incorporate a management option into the model and predict endpoint risk if it were to be implemented. Eradication can occur at different stages of NIS invasions, such as the elimination of these species before being introduced to the habitat or removal of the species after settlement. We incorporated the ballast water treatment management scenario into the model, observed the risk to the endpoints, and compared this risk with the initial risk estimates. The model results indicated that the southern portion of the bay was at greatest risk because of NIS. Changes in community composition, Dungeness crab, and eelgrass were the endpoints most at risk from NIS introductions. The currents node, which controls the exposure of NIS to the bay from the surrounding marine environment, was the parameter that had the greatest influence on risk. The ballast water management scenario displayed an approximate 1% reduction in risk in this Padilla Bay case study. The models we developed provide an adaptable template for decision makers interested in managing NIS in other coastal regions and large bodies of water. Integr Environ Assess Manag 2015;X:000–000. ©2015 SETAC

Key Points

We approached the issue of nonindigenous species (NIS) from a landscape-scale ecological risk assessment, analyzing multiple vectors of introduction and their associated spectrum of NIS, and created a model that enables us to quantitatively calculate risk from NIS introductions to coastal endpoints. The most important variable in the estimation of risk was the Currents node, which described both an important vector for the rate introduction of propagules from transportation and as a connection to existing patches of NIS in the region We incorporated a ballast water treatment management scenario into the Bayesian network model, which predicted little change in risk from the initial risk calculations. The BN-RRM approach described in this paper can be used as a template for other coastal communities interested in calculating and managing risk from NIS.
Prospective study of Helicobacter pylori antigens and gastric noncardia cancer risk in the nutrition intervention trial cohort
Authors: Murphy Gwen , Freedman Neal D. , Michel Angelika , Fan Jin‐Hu , Taylor Philip R. , Pawlita Michael , Qiao You‐Lin , Zhang Han , Yu Kai , Abnet Christian C. , Dawsey Sanford M.
Published: April 2015

Helicobacter pylori (H. pylori) infection is the strongest known risk factor for gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of noncardia gastric cancer in Linxian, China. We included 448 GNCA cases and 1242 controls from two time points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to ≥4 of the 15 included antigens. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk factors. In addition, we undertook a meta‐analysis combining H. pylori multiplex serology data from both time points. H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both time points in a meta‐analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA. We identified six individual antigens that confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen that may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA.
Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway
Authors: Wu Xiafei , Zhang Feng , Xiong Xin , Lu Chunfeng , Lian Naqi , Lu Yin , Zheng Shizhong
Published: April 2015

Hepatic fibrosis is concomitant with liver inflammation, which has been highlighted as significant treatment of chronic liver disease. We previously demonstrated that tetramethylpyrazine (TMP), the effective component of Ligusticum chuanxiong Hort, can inhibit the activation of HSCs and consequential anti‐hepatic fibrosis. In this study, our work demonstrated that TMP improved liver histological architecture, decreased hepatic enzyme levels and attenuated collagen deposition in the rat fibrotic liver. In addition, TMP significantly protected the liver from CCl4‐caused injury and fibrogenesis by suppressing inflammation with reducing levels of inflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), NLRP3, nuclear factor‐kappa B (NF‐κB) and interleukin‐1β (IL‐1β). Experiments in vitro showed that TMP inhibited inflammatory cytokine expression in HSCs associated with disrupting platelet‐derived growth factor‐b receptor (PDGF‐βR)/NLRP3/caspase1 pathway. These data collectively indicate that TMP can attenuate liver inflammation in liver fibrosis and possibly by targeting HSCs via PDGF‐βR/NLRP3/caspase1 pathway. It provides novel mechanistic insights into TMP as a potential therapeutic remedy for hepatic fibrosis. © 2015 IUBMB Life, 67(4):312–321, 2015
Winter habitat use of greater sage‐grouse relative to activity levels at natural gas well pads
Authors: Holloran Matthew J. , Fedy Bradley C. , Dahlke John
Published: April 2015

Energy development in western North America has been shown to negatively influence greater sage‐grouse (Centrocercus urophasianus) populations. No effective methods of reducing on‐site impacts of energy development to greater sage‐grouse are known. We investigated greater sage‐grouse use of wintering habitats relative to distances to infrastructure, densities of infrastructure, and activity levels associated with infrastructure of a natural gas field over 5 years in southwestern Wyoming. We compared year‐long drilling locations, locations of conventional well pads, locations of well pads with off‐site condensate and produced water gathering systems (LGS), and plowed main haul roads to the number of and time associated with greater sage‐grouse visits to continually monitored, distinct patches of habitat. Liquid gathering systems reduced human activity levels at producing well pads approximately 53%. We used data loggers to monitor distinct patches of habitat throughout the 2005–2006 to 2009–2010 winters and used the number of times and the amount of time individuals from a sample of greater sage‐grouse (n = 236) were detected at data logger stations to model frequency and time of occurrence as functions of anthropogenic and habitat variables. Greater sage‐grouse avoided suitable winter habitats in areas with high well pad densities regardless of differences in activity levels associated with well pads. Our results further suggested that greater sage‐grouse avoidance of conventional well pads was stronger than LGS well pads. We found relatively consistent positive relationships between distance to infrastructure with high levels of human activity and average hours greater sage‐grouse spent in an area. Greater sage‐grouse avoidance of natural gas field infrastructure during the winter may be explained mechanistically as movements of individuals from areas close to high levels of activity—movements that may occur at the time human activity is experienced—followed by a lack of movement back into these areas. Minimizing the densities of well pads may reduce on‐site impacts of energy development on wintering greater sage‐grouse. Our study, additionally, indicated that reducing anthropogenic activity levels associated with energy developments may reduce the temporal scale of indirect greater sage‐grouse winter habitat loss. © 2015 The Wildlife Society.
Living Anionic Polymerization of Benzofulvene in Hydrocarbon Solvent
Authors: Kosaka Yuki , Goseki Raita , Kawauchi Susumu , Ishizone Takashi
Published: April 2015

Anionic polymerization of benzofulvene (BF) quantitatively proceeded with sec‐BuLi in benzene at 0∼55 °C. The resulting poly(BF) s possessed predicted molecular weights based on the molar ratios between monomer and initiator and narrow molecular weight distributions (Mw/Mn < 1.1). The result of postpolymerization demonstrated that the propagating chain end anion of poly(BF) was stable in benzene at 0 °C for at least 1 h. Anionic sequential copolymerization of isoprene and BF was also performed in benzene to afford a well‐defined polyisoprene‐b‐poly(BF) in quantitative yield. The 13C NMR analysis revealed that the poly(BF) obtained with sec‐BuLi in benzene at 0 °C possessed 76% of the 1,4‐structure and 24% of the 1,2‐structure.
Development and validation of a clinical scale for rating the severity of Blepharospasm
Authors: Defazio Giovanni , Hallett Mark , Jinnah Hyder A. , Stebbins Glenn T. , Gigante Angelo F. , Ferrazzano Gina , Conte Antonella , Fabbrini Giovanni , Berardelli Alfredo
Published: April 2015

Existing scales for rating the severity of blepharospasm (BSP) are limited by a number of potential drawbacks. We therefore developed and validated a novel scale for rating the severity of BSP. The development of the scale started with careful examination of the clinical spectrum of the condition by a panel of experts who selected phenomenological aspects thought to be relevant to disease severity. Thereafter, selected items were first checked for reliability, then reliable items were combined to generate the scale, and clinimetric properties of the scale were evaluated. Finally, the confidence with which the scale could be used by people without high levels of movement disorders skill was assessed. The new scale, based on objective criteria, yielded moderate to almost perfect reliability, acceptable internal consistency, satisfactory scaling assumptions, lack of floor and ceiling effects, partial correlations with a prior severity scale and with a quality of life scale, and good sensitivity to change. Despite a few limitations, the foregoing features make the novel scale more suitable than existing scales to assess the severity of BSP in natural history and pathophysiologic studies as well as in clinical trials. © 2015 International Parkinson and Movement Disorder Society
Selecting a prospective test for early detection of diabetic polyneuropathy
Authors: Ruhdorfer Anja S. , Azaryan Mihran , Kraus Joerg , Grinzinger Susanne , Hitzl Wolfgang , Ebmer Johannes , Dellon A. Lee , Hölzl Bertram
Published: April 2015

Microneurolysis of entrapped peripheral nerve has the best chance of success when compression has not created significant axonal loss. The purpose of this study is to learn the best way to identify potential surgical candidates at the earliest time for intervention, by examining patients in a clinical setting using objective, electrodiagnostic nerve conduction studies (NCS), and subjective touch threshold studies, Semmes‐Weinstein monofilaments (SWM) and Pressure‐Specified Sensory Device™ (PSSD). Fifty‐five patients with diabetic polyneuropathy over the age of 30 years were included. Neuropathy symptom score was the gold standard for statistical calculation, with a prevalence of 70%. In the symptomatic population, prevalence was 64% for NCS (n = 25), 59% for SWM (n = 43), and 88% for PSSD (n = 51). In the asymptomatic population, prevalence was 70% for NCS, 27% for SWM, and 92% for PSSD. It is concluded that the PSSD is the most sensitive device of those tested for identifying peripheral neuropathy in an at risk population of patients. © 2015 Wiley Periodicals, Inc. Microsurgery 35:512–517, 2015.
Matters of fiber size and myonuclear domain: Does size matter more than age?
Authors: Karlsen Anders , Couppé Christian , Andersen Jesper L. , Mikkelsen Ulla R. , Nielsen Rie H. , Magnusson S. Peter , Kjaer Michael , Mackey Abigail L.
Published: April 2015

Introduction: The relationship between fiber size and myonuclear content is poorly understood. Methods: Biopsy cross‐sections from young and old trained and untrained healthy individuals were analyzed for fiber area and myonuclei, and 2 fiber‐size‐dependent cluster analyses were performed. Results: When comparing fibers of similar size, no effect of training or age was found for myonuclear domain. There was a linear relationship between fiber area and myonuclei per fiber (r = 0.99; P < 0.001) and a non‐linear relationship between fiber area and domain (r = 0.97–0.99; P < 0.0001), with a markedly smaller domain in fibers <3,000 µm2. A higher proportion of type II fibers <3,000 µm2 was observed in the old subjects. Conclusions: These findings suggest that age‐related reductions in myonuclear domain size could be explained by the greater proportion of small fibers. The data also highlight the usefulness of determining fiber‐size‐based clusters for gaining mechanistic insight into the relationship between skeletal muscle fiber size and myonuclear content. Muscle Nerve 52: 1040–1046, 2015
Spinal muscular atrophy functional composite score: A functional measure in spinal muscular atrophy
Authors: Montes Jacqueline , Glanzman Allan M. , Mazzone Elena S. , Martens William B. , Dunaway Sally , Pasternak Amy , Riley Susan O , Quigley Janet , Pandya Shree , De Vivo Darryl C , Kaufmann Petra , Chiriboga Claudia A. , Finkel Richard S. , Tennekoon Gihan I. , Darras Basil T. , Pane Marika , Mercuri Eugenio , Mcdermott Michael P. ,   for the Pediatric Neuromuscular Clinical Research Network, Muscle Study Group, SMA Europe
Published: April 2015

Introduction: With clinical trials underway, our objective was to construct a composite score of global function that could discriminate among people with spinal muscular atrophy (SMA). Methods: Data were collected from 126 participants with SMA types 2 and 3. Scores from the Hammersmith Functional Motor Scale—Expanded and Upper Limb Module were expressed as a percentage of the maximum score and 6‐minute walk test as percent of predicted normal distance. A principal component analysis was performed on the correlation matrix for the 3 percentage scores. Results: The first principal component yielded a composite score with approximately equal weighting of the 3 components and accounted for 82% of the total variability. The SMA functional composite score, an unweighted average of the 3 individual percentage scores, correlated almost perfectly with the first principal component. Conclusions: This combination of measures broadens the spectrum of ability that can be quantified in type 2 and 3 SMA patients. Muscle Nerve 52: 942–947, 2015
High‐performance thin film composite membranes with well‐defined poly(dimethylsiloxane)‐b‐poly(ethylene glycol) copolymer additives for CO2 separation
Authors: Scofield Joel M. P. , Gurr Paul A. , Kim Jinguk , Fu Qiang , Halim Andri , Kentish Sandra E. , Qiao Greg G.
Published: April 2015

A series of well‐defined diblock copolymers (BCPs) consisting of poly(ethylene glycol) (PEG) and poly(dimethylsiloxane) (PDMS) were synthesized and blended with commercially available PEBAX® 2533 to form the active layer of thin‐film composite (TFC) membranes, via spin‐coating. BCPs with a PEG component ranging from 1 to 10 kDa and a PDMS component ranging from 1 to 10 kDa were synthesized by a facile condensation reaction of hydroxyl terminated PEG and carboxylic acid functionalized PDMS. The BCP/PEBAX® 2533 blends up to 50 wt % on cross‐linked PDMS gutter layers were tested at 35 °C and 350 kPa. TFC membranes containing BCPs of 1 kDa PEG and 1–5 kDa PDMS produced optimal results with CO2 permeances of approximately 1000 GPU which is an increase up to 250% of the permeance of pure PEBAX® 2533 composite membranes, while maintaining a CO2/N2 selectivity of 21. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1500–1511
Optically active helical polymers with pendent thiourea groups: Chiral organocatalyst for asymmetric michael addition reaction
Authors: Zhang Haiyang , Yang Wantai , Deng Jianping
Published: April 2015

This article reports a novel category of helical substituted polyacetylenes bearing pendant thiourea groups and showing remarkable asymmetric catalysis ability. Thiourea‐based monomer and another chiral monomer underwent copolymerization, affording copolymers with considerable optical activity. The copolymers were used as chiral organocatalyst to homogeneously catalyze the asymmetric Michael addition of diethyl malonate to trans‐β‐nitrostyrene. During catalysis, a synergetic effect occurred between the pendant thiourea moieties and the helical structures in the polymer backbones. The enantioselectivity of the reaction was governed by the thiourea moieties. Meanwhile, the concaves along the helices provided specific domains where the substrates and catalytic groups were packed together, leading to a remarkable enhancement of product yield and enantioselectivity. Product with high yield (85%) and satisfactory ee (up to 72%) can be obtained. The present helical polymers open up new opportunities for developing macromolecules as mimetic enzymes catalyzing asymmetric reactions. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1816–1823
Structural Characterization of γ‐Terpinene Thin Films Using Mass Spectroscopy and X‐Ray Photoelectron Spectroscopy
Authors: Ahmad Jakaria , Bazaka Kateryna , Whittle Jason D. , Michelmore Andrew , Jacob Mohan V.
Published: April 2015

Understanding the polymerization mechanism of a precursor is indispensable to enhance the requisite material properties. In situ mass spectroscopy and X‐ray photoelectron spectroscopy is used in this study to understand the RF plasma polymerization of γ‐terpinene. High‐resolution mass spectra positive ion mass spectrometry data of the plasma phase demonstrates the presence of oligomeric species of the type [M+H]+ and [2M+H]+, where M represents a unit of the starting material. In addition, there is abundant fragmented species, with most dominant being [M+] (136 m/z), C10H13+ (133 m/z), C9H11+ (119 m/z), and C7H9+ (93 m/z). The results reported in this manuscript enables to comprehend the relationship between the degree of incorporation of oxygen and the rate of deposition with the input RF power.
Structural analysis of the polo‐box domain of human Polo‐like kinase 2
Authors: Kim Ju Hee , Ku Bonsu , Lee Kyung S. , Kim Seung Jun
Published: April 2015

Polo‐like kinases (Plks) are the key regulators of cell cycle progression, the members of which share a kinase domain and a polo‐box domain (PBD) that serves as a protein‐binding module. While Plk1 is a promising target for antitumor therapy, Plk2 is regarded as a tumor suppressor even though the two Plks commonly recognize the S‐pS/T‐P motif through their PBD. Herein, we report the crystal structure of the PBD of Plk2 at 2.7 Å. Despite the overall structural similarity with that of Plk1 reflecting their high sequence homology, the crystal structure also contains its own features including the highly ordered loop connecting two subdomains and the absence of 310‐helices in the N‐terminal region unlike the PBD of Plk1. Based on the three‐dimensional structure, we furthermore could model its interaction with two types of phosphopeptides, one of which was previously screened as the optimal peptide for the PBD of Plk2. Proteins 2015; 83:1201–1208. © 2015 Wiley Periodicals, Inc.
Growth retardation ofEscherichia coliby artificial increase of intracellular ATP
Authors: Na Yoon-Ah , Lee Joo-Young , Bang Weon-Jeong , Lee Hyo Jung , Choi Su-In , Kwon Soon-Kyeong , Jung Kwang-Hwan , Kim Jihyun F , Kim Pil
Published: April 2015

Overexpression of phosphoenolpyruvate carboxykinase (PCK) was reported to cause the harboring of higher intracellular ATP concentration in Escherichia coli, accompanied with a slower growth rate. For systematic determination of the relationship between the artificial increase of ATP and growth retardation, PCKWT enzyme was directly evolved in vitro and further overexpressed. The evolved PCK67 showed a 60 % greater catalytic efficiency than that of PCKWT. Consequently, the PCK67-overexpressing E. coli showed the highest ATP concentration at the log phase of 1.45 μmol/gcell, with the slowest growth rate of 0.66 h−1, while the PCKWT-overexpressing cells displayed 1.00 μmol/gcell ATP concentration with the growth rate of 0.84 h−1 and the control had 0.28 μmol/gcell with 1.03 h−1. To find a plausible reason, PCK-overexpressing cells in a steady state during chemostat growth were applied to monitor intracellular reactive oxygen species (ROS). Higher amount of intracellular ROS were observed as the ATP levels increased. To confirm the hypothesis of slower growth rate without perturbation of the carbon flux by PCK-overexpression, phototrophic Gloeobacter rhodopsin (GR) was expressed. The GR-expressing strain under illumination harbored 81 % more ATP concentration along with 82 % higher ROS, with a 54 % slower maximum growth rate than the control, while both the GR-expressing strain under dark and dicarboxylate transporter (a control membrane protein)-expressing strain showed a lower ATP and increased ROS, and slower growth rate. Regardless of carbon flux changes, the artificial ATP increase was related to the ROS increase and it was reciprocally correlated to the maximum growth rate. To verify that the accumulated intracellular ROS were responsible for the growth retardation, glutathione was added to the medium to reduce the ROS. As a result, the growth retardation was restored by the addition of 0.1 mM glutathione. Anaerobic culture even enabled the artificial ATP-increased E. coli to grow faster than control. Collectively, it was concluded that artificial ATP increases inhibit the growth of E. coli due to the overproduction of ROS.
Comparative metabolic profiling reveals the key role of amino acids metabolism in the rapamycin overproduction by Streptomyces hygroscopicus
Authors: Wang Baohua , Liu Jiao , Liu Huanhuan , Huang Di , Wen Jianping
Published: April 2015

Rapamycin is an important natural macrolide antibiotic with antifungal, immunosuppressive and anticancer activity produced by Streptomyces hygroscopicus. In this study, a mutant strain obtained by ultraviolet mutagenesis displayed higher rapamycin production capacity compared to the wild-type S. hygroscopicus ATCC 29253. To gain insights into the mechanism of rapamycin overproduction, comparative metabolic profiling between the wild-type and mutant strain was performed. A total of 86 metabolites were identified by gas chromatography–mass spectrometry. Pattern recognition methods, including principal component analysis, partial least squares and partial least squares discriminant analysis, were employed to determine the key biomarkers. The results showed that 22 potential biomarkers were closely associated with the increase of rapamycin production and the tremendous metabolic difference was observed between the two strains. Furthermore, metabolic pathway analysis revealed that amino acids metabolism played an important role in the synthesis of rapamycin, especially lysine, valine, tryptophan, isoleucine, glutamate, arginine and ornithine. The inadequate supply of amino acids, or namely “nitrogen starvation” occurred in the mutant strain. Subsequently, the exogenous addition of amino acids into the fermentation medium of the mutant strain confirmed the above conclusion, and rapamycin production of the mutant strain increased to 426.7 mg/L after adding lysine, approximately 5.8-fold of that in the wild-type strain. Finally, the results of real-time PCR and enzyme activity assays demonstrated that dihydrodipicolinate synthase involved with lysine metabolism played vital role in the biosynthesis of rapamycin. These findings will provide a theoretical basis for further improving production of rapamycin.
Randomized Trial of Telegenetics vs. In‐Person Cancer Genetic Counseling: Cost, Patient Satisfaction and Attendance
Authors: Buchanan Adam H. , Datta Santanu K. , Skinner Celette Sugg , Hollowell Gail P. , Beresford Henry F. , Freeland Thomas , Rogers Benjamin , Boling John , Marcom P. Kelly , Adams Martha B.
Published: April 2015

Telegenetics—genetic counseling via live videoconferencing—can improve access to cancer genetic counseling (CGC) in underserved areas, but studies on cancer telegenetics have not applied randomized methodology or assessed cost. We report cost, patient satisfaction and CGC attendance from a randomized trial comparing telegenetics with in‐person CGC among individuals referred to CGC in four rural oncology clinics. Participants (n = 162) were randomized to receive CGC at their local oncology clinic in‐person or via telegenetics. Cost analyses included telegenetics system; mileage; and personnel costs for genetic counselor, IT specialist, and clinic personnel. CGC attendance was tracked via study database. Patient satisfaction was assessed 1 week post‐CGC via telephone survey using validated scales. Total costs were $106 per telegenetics patient and $244 per in‐person patient. Patient satisfaction did not differ by group on either satisfaction scale. In‐person patients were significantly more likely to attend CGC than telegenetics patients (89 vs. 79 %, p = 0.03), with bivariate analyses showing an association between lesser computer comfort and lower attendance rate (Chi‐square = 5.49, p = 0.02). Our randomized trial of telegenetics vs. in‐person counseling found that telegenetics cost less than in‐person counseling, with high satisfaction among those who attended. This study provides support for future randomized trials comparing multiple service delivery models on longer‐term psychosocial and behavioral outcomes.
Surgical Correction of Distal Radius Malunions using an Anatomic Radial Locking Plate
Authors: Hutchinson Alexander J. , Dunn John C. , Pirela-Cruz Miguel A.
Published: April 2015

Background

Correction of a distal radius fracture malunion is challenging technically. These malunions most classically deform dorsally, but often the deformity involves three planes. Methods Using an anatomically designed radial plate that takes into consideration the three planes, correction of the deformity can be obtained. In this video we see a patient with a classic dinner fork deformity that is associated with a dorsal malunion involving the distal radius. Correction of a distal radius malunion can be performed using a radial approach and an anatomic radial plate.

Results

The authors have used this technique for difficult distal radius fracture malunions and have achieved superb correction, returning patients to early range of motion and an active lifestyle.

Conclusions

Careful mobilization of the branches of the lateral antebrachial cutaneous nerve and the superficial branch of the radial nerve is required. This technique affords the surgeon excellent access to three sides of the radius to help perform this complex surgery.
Molecular markers of neuropsychological functioning and Alzheimer's disease
Authors: Edwards Melissa , Balldin Valerie Hobson , Hall James , O'Bryant Sid
Published: April 2015

Background

The current project sought to examine molecular markers of neuropsychological functioning among elders with and without Alzheimer's disease (AD) and determine the predictive ability of combined molecular markers and select neuropsychological tests in detecting disease presence.

Methods

Data were analyzed from 300 participants (n = 150, AD and n = 150, controls) enrolled in the Texas Alzheimer's Research and Care Consortium. Linear regression models were created to examine the link between the top five molecular markers from our AD blood profile and neuropsychological test scores. Logistical regressions were used to predict AD presence using serum biomarkers in combination with select neuropsychological measures.

Results

Using the neuropsychological test with the least amount of variance overlap with the molecular markers, the combined neuropsychological test and molecular markers was highly accurate in detecting AD presence.

Conclusion

This work provides the foundation for the generation of a point‐of‐care device that can be used to screen for AD.
Practice effects due to serial cognitive assessment: Implications for preclinical Alzheimer's disease randomized controlled trials
Authors: Goldberg Terry E. , Harvey Philip D. , Wesnes Keith A. , Snyder Peter J. , Schneider Lon S.
Published: April 2015

Introduction

Practice effects are characteristic of nearly all standard cognitive tasks when repeated during serial assessments and are frequently important confounders in clinical trials.

Methods

We summarize evidence that gains in neuropsychological test performance scores associated with practice effects occur as artifactual changes associated with serial testing within clinical trials. We identify and emphasize such gains in older, non–cognitively impaired individuals and estimate an effect size of 0.25 for composite cognitive measures in older populations assessed three times in a 6‐ to 12‐month period.

Results

We identified three complementary approaches that can be used to attenuate practice effects: (1) massed practice in a prebaseline period to reduce task familiarity effects; (2) tests designed to reduce practice‐related gains so that item‐specific driven improvements are minimized by using tasks that minimize strategy and/or maximize interitem interference; and (3) well‐matched alternate forms.

Discussion

We have drawn attention to and increased awareness of practice effect–related gains that could result in type 1 or type 2 errors in trials. Successfully managing practice effects will eliminate a large source of error and reduce the likelihood of misinterpretation of clinical trials outcomes.
A systematic review and meta‐analysis of 18F‐labeled amyloid imaging in Alzheimer's disease
Authors: Yeo Jing Ming , Waddell Briony , Khan Zubair , Pal Suvankar
Published: April 2015

Background

Amyloid imaging using fluorine 18–labeled tracers florbetapir, florbetaben, and flutemetamol has recently been reported in Alzheimer's disease (AD).

Methods

We systematically searched MEDLINE and EMBASE for relevant studies published from January 1980 to March 2014. Studies comparing imaging findings in AD and normal controls (NCs) were pooled in a meta‐analysis, calculating pooled weighted sensitivity, specificity, and diagnostic odds ratio (OR) using the DerSimonian‐Laird random‐effects model.

Results

Nineteen studies, investigating 682 patients with AD, met inclusion criteria. Meta‐analysis demonstrated a sensitivity of 89.6%, a specificity of 87.2%, and an OR of 91.7 for florbetapir in differentiating AD patients from NCs, and a sensitivity of 89.3%, a specificity of 87.6%, and a diagnostic OR of 69.9 for florbetaben. There were insufficient data to complete analyses for flutemetamol.

Conclusions

Results suggest favorable sensitivity and specificity of amyloid imaging with fluorine 18–labeled tracers in AD. Prospective studies are required to determine optimal imaging analysis methods and resolve outstanding clinical uncertainties.
Blood protein predictors of brain amyloid for enrichment in clinical trials?
Authors: Ashton Nicholas J. , Kiddle Steven J. , Graf John , Ward Malcolm , Baird Alison L. , Hye Abdul , Westwood Sarah , Wong Karyuan Vivian , Dobson Richard J. , Rabinovici Gil D. , Miller Bruce L. , Rosen Howard J. , Torres Andrew , Zhang Zhanpan , Thurfjell Lennart , Covin Antonia , Hehir Cristina Tan , Baker David , Bazenet Chantal , Lovestone Simon ,   AIBL Research Group
Published: April 2015

Background

Measures of neocortical amyloid burden (NAB) identify individuals who are at substantially greater risk of developing Alzheimer's disease (AD). Blood‐based biomarkers predicting NAB would have great utility for the enrichment of AD clinical trials, including large‐scale prevention trials.

Methods

Nontargeted proteomic discovery was applied to 78 subjects from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing with a range of NAB values. Technical and independent replications were performed by immunoassay.

Results

Seventeen discovery candidates were selected for technical replication. α2‐Macroglobulin, fibrinogen γ‐chain (FGG), and complement factor H‐related protein 1 were confirmed to be associated with NAB. In an independent cohort, FGG plasma levels combined with age predicted NAB had a sensitivity of 59% and specificity of 78%.

Conclusion

A single blood protein, FGG, combined with age, was shown to relate to NAB and therefore could have potential for enrichment of clinical trial populations.
Reduced plasma desmosterol‐to‐cholesterol ratio and longitudinal cognitive decline in Alzheimer's disease
Authors: Sato Yoshiaki , Bernier Francois , Yamanaka Yasukazu , Aoshima Ken , Oda Yoshiya , Ingelsson Martin , Lannfelt Lars , Miyashita Akinori , Kuwano Ryozo , Ikeuchi Takeshi
Published: April 2015

Background

We here examined whether plasma desmosterol‐to‐cholesterol ratio (DES/CHO) is decreased in patients with Alzheimer's disease (AD) and investigated the association between plasma DES/CHO and longitudinal cognitive decline.

Methods

Plasma DES/CHO of AD patients and age‐matched controls in a Japanese cross‐sectional cohort was determined. Plasma DES/CHO at baseline and follow‐up visits was assessed in relation to cognitive decline in Japanese and Swedish longitudinal cohorts.

Results

Plasma DES/CHO was significantly reduced in Japanese AD patients and significantly correlated with Mini‐Mental State Examination (MMSE) score. The longitudinal analysis revealed that plasma DES/CHO in AD patients shows a significant decrease at follow‐up intervals. The decline in plasma DES/CHO is larger in the AD group with rapid progression than in that with slow progression. The changes in plasma DES/CHO significantly correlated with changes in the MMSE score.

Conclusion

Plasma DES/CHO is decreased in AD patients and may serve as a longitudinal surrogate marker associated with cognitive decline.
Subjective memory complaints, cortical thinning, and cognitive dysfunction in middle‐age adults at risk of AD
Authors: Schultz Stephanie A. , Oh Jennifer M. , Koscik Rebecca L. , Dowling N. Maritza , Gallagher Catherine L. , Carlsson Cynthia M. , Bendlin Barbara B. , LaRue Asenath , Hermann Bruce P. , Rowley Howard A. , Asthana Sanjay , Sager Mark A. , Johnson Sterling C. , Okonkwo Ozioma C.
Published: April 2015

Background

Subjective memory complaints (SMCs) represent an individual's perception of subtle changes in memory in the absence of objective impairment in memory. However, it is not fully known whether persons with SMCs harbor brain alterations related to Alzheimer's disease (AD) or whether they indeed demonstrate poorer cognitive performance.

Methods

The participants were 261 middle‐age adults (mean age 54.30 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention, a registry of cognitively normal adults at risk of AD. They answered a question pertaining to subjective memory, completed a comprehensive neuropsychological examination, and subsequently underwent a volumetric magnetic resonance imaging scan. Cortical thickness measurements were derived from 10 a priori regions of interest involved in AD. Analyses of covariance were conducted to investigate the group differences in cortical thickness and neuropsychological measures.

Results

Compared with individuals without SMCs, those with SMCs had significant cortical thinning in the entorhinal, fusiform, posterior cingulate, and inferior parietal cortices and significantly reduced amygdala volume. Similarly, those with SMCs had significantly lower test scores on measures of Immediate Memory, Verbal Learning & Memory, and Verbal Ability. Additional adjustment for depressive symptoms (which differed between the groups) attenuated only the findings for the entorhinal cortex (P = .061) and Verbal Ability (P = .076).

Conclusion

At‐risk, cognitively healthy individuals with SMCs exhibit cortical thinning in brain regions affected by AD and poorer performance on objective memory tests. These findings suggest that, in some individuals, SMCs might represent the earliest stages of AD.
Neuroimaging referral for dementia diagnosis: The specialist's perspective in Ireland
Authors: Ciblis Aurelia S. , Butler Marie‐Louise , Bokde Arun L.W. , Mullins Paul G. , O'Neill Desmond , McNulty Jonathan P.
Published: April 2015

Background

Neuroimaging is an increasingly important tool in the diagnostic workup of dementia. Neurologists, geriatricians, and old‐age psychiatrists are involved in key tasks in the diagnostic process, frequently referring patients with suspected dementia for neuroimaging.

Methods

The research design was a postal survey of all geriatricians, old‐age psychiatrists, and neurologists in the Republic of Ireland (N = 176) as identified by the Irish Medical Directory 2011–2012 and supplementary listings.

Results

Almost 65% of specialists did not have access to 2‐[18F]fluoro‐2‐deoxy‐D‐glucose positron emission (FDG‐PET) or FDG‐PET/computed tomography (CT), and 80.3% did not have access to perfusion hexamethylpropyleneamine oxime single‐photon emission computed tomography (SPECT) or dopaminergic iodine‐123‐radiolabeled 2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane SPECT. Most specialists (88.7%) referred patients with mild cognitive impairment or suspected dementia for magnetic resonance imaging (MRI), 81.7% referred for CT, and 26.8% for FDG‐PET or FDG‐PET/CT. Only 44.6% of respondents were aware of dementia‐specific protocols for referrals for neuroimaging.

Conclusion

Specialist access to imaging modalities other than CT and MRI is restricted. Improved access may affect patient treatment and care.
Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease
Authors: Carlesimo Giovanni A. , Piras Fabrizio , Orfei Maria Donata , Iorio Mariangela , Caltagirone Carlo , Spalletta Gianfranco
Published: April 2015

Background

There is no consensus about which hippocampal subfields become atrophic earliest in the course of Alzheimer's disease (AD).

Methods

Thirty AD patients, 41 mild cognitive impairment (MCI) patients, and 38 healthy controls (HCs) underwent cerebral magnetic resonance imaging (with an automated segmentation protocol for the volumetric analysis of hippocampal subfields) and a test of immediate and delayed recall of a 15‐word list.

Results

The volumes of the presubiculum and subiculum presented the most remarkable reduction in the patient's groups. In the MCI group, only the volumes of presubiculum and subiculum predicted performance on the memory tests. In AD patients, the volumes of all hippocampal subfields (with the notable exception of the CA1) predicted memory scores.

Conclusions

Our data point to a prevalent atrophy of the presubicular‐subicular complex from the early phases of AD. This finding is consistent with neuropathological observations in AD patients and probably reflects the severe degeneration of the perforant pathway while penetrating the hippocampus through the subicular field in its course from the entorhinal cortex to the dentate gyrus.
Homocysteine but not Serum Amyloid A, Vitamin A and E Related to Increased Risk of Metabolic Syndrome in Post-Menopausal Thai Women
Authors: Suriyaprom Kanjana , Phonrat Benjaluck , Satitvipawee Pratana , Tungtrongchitr Anchalee , Tungtrongchitr Rungsunn
Published: April 2015

This study aims to investigate serum amyloid A, homocysteine, and biochemical-anthropometric measurements in post-menopausal women with and without metabolic syndrome (MS), and determine whether serum amyloid A and homocysteine are linked to MS among this group. This study was performed with 405 post-menopausal Thai volunteers with a mean age of 57.95 ± 5.90 years (135 subjects with MS and 270 subjects without MS). The levels of serum amyloid A, homocysteine, vitamins, glucose, and lipids were measured. Homocysteine levels were significantly higher in the group with MS than in that without MS (p < 0.001), whereas for serum amyloid A, vitamin A, vitamin E and vitamin B12, there were no significant differences. There were significant differences between the groups in folate, HDL-C, and anthropometric measurements (p < 0.001). Thirty seven percent of the group with MS and 14.1 % of the group without MS were classified as having hyperhomocysteinemia (p < 0.001). Furthermore, logistic regression analysis revealed that hyperhomocysteinemia (odds ratio (OR): 2.67, 95 % confidence interval (95 %CI): 1.57 - 4.58), low folate (OR: 1.79, 95 %CI: 1.11 - 2.89), and BMI (OR: 1.25, 95 %CI: 1.16 - 1.33) were significantly related to MS. These findings suggest that increased homocysteine levels and decreased folate concentrations may influence susceptibility to MS and this effect may be an early event in the development of cardiovascular diseases among post-menopausal women. Therefore, there is a need to evaluate homocysteine levels, especially among post-menopausal Thai women.