bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukotriene Enhances NMDA-Induced Inward Currents in Dorsal Horn Neurons of the Rat Spinal Cord after Peripheral Nerve Injury
Authors: Kiyoyuki Yasukuni , Taniguchi Wataru , Okubo Masamichi , Yamanaka Hiroki , Kobayashi Kimiko , Nishio Naoko , Nakatsuka Terumasa , Noguchi Koichi
Published: September 2015

Background

LTB4 is classified as a leukotriene (LT), a group of lipid mediators that are derived from arachidonic acid. It is recognized that leukotrienes are involved in the pathogenesis of many diseases, including peripheral inflammatory pain. However, little is known about the effects of leukotrienes on the spinal dorsal horn during neuropathic pain. Previously, we reported that there was increased expression of 5-lipoxygenase (5-LO) at spinal microglia, and the leukotriene B4 receptor 1 (BLT1), a high affinity receptor of LTB4, in spinal neurons in spared nerve injury (SNI) model rats. In the present study, we examined the effects of LTB4 on spinal dorsal horn neurons in both naïve and SNI model rats using patch-clamp methods.

Results

Bath application of LTB4 did not change AMPA receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs) or membrane potentials. However, we found that LTB4 enhanced the amplitude of NMDA receptor-mediated sEPSCs and significantly increased exogenous NMDA-induced inward currents in SNI model rats. This increase of inward currents could be inhibited by a selective LTB4 antagonist, U75302, as well as a GDP-β-S, a G-protein inhibitor. These results indicate that both increased LTB4 from spinal microglia or increased BLT1 in spinal neurons after peripheral nerve injury can enhance the activity of NMDA receptors through intracellular G-proteins in spinal dorsal horn neurons.

Conclusion

Our findings showed that LTB4, which may originate from microglia, can activate BLT1 receptors which are expressed on the membrane of spinal dorsal horn neurons during neuropathic pain. This glia-neuron interaction induces the enhancement of NMDA currents through intracellular G-proteins. The enhancement of NMDA receptor sensitivity of dorsal horn neurons may lead to central sensitization, leading to mechanical pain hypersensitivity.
A new insole measurement system to detect bending and torsional moments at the human foot during footwear condition: a technical report
Authors: Stief Thomas , Peikenkamp Klaus
Published: September 2015

Background

Stress occurring at the feet while wearing footwear is often determined using pressure measurement systems. However, other forms of stress, such as bending, torsional and shear loadings, cannot be detected in shoes during day‐to‐day activities. Nevertheless, the detection of these types of stresses would be helpful for understanding the mechanical aspects of various kinds of hard and soft tissue injuries. Therefore, we describe the development of a new measuring device that allows the reliable determination of bending and torsional load at the foot in shoes.

Methods

The system consists of a measuring insole and an analogue device with Bluetooth interface. The specific shape of the insole base layer, the positions of the strain gauges, and the interconnections between them have all been selected in such a way so as to isolate bending and torsional moment detections in the medial and lateral metatarsal region. The system was calibrated using a classical two‐point test procedure. A single case study was executed to evaluate the new device for practical use. This application consisted of one subject wearing neutral shoes walking on a treadmill.

Results

The calibration results (coefficients of determination R2 > 0.999) show that bending and torsional load can be reliably detected using the measurement system presented. In the single case study, alternating bending and torsional load can be detected during walking, and the shape of the detected bending moments can be confirmed by the measurements of Arndt et al. (J Biomech 35:621–8, 2002).

Conclusions

Despite some limitations, the presented device allows for the reliable determination of bending and torsional stresses at the foot in shoes.
Discrepant post filter ionized calcium concentrations by common blood gas analyzers in CRRT using regional citrate anticoagulation
Authors: Schwarzer Patrik , Kuhn Sven-Olaf , Stracke Sylvia , Gründling Matthias , Knigge Stephan , Selleng Sixten , Helm Maximilian , Friesecke Sigrun , Abel Peter , Kallner Anders , Nauck Matthias , Petersmann Astrid
Published: September 2015

Introduction

Ionized calcium (iCa) concentration is often used in critical care and measured using blood gas analyzers at the point of care. Controlling and adjusting regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) involves measuring the iCa concentration in two samples: systemic with physiological iCa concentrations and post filter samples with very low iCa concentrations. However, modern blood gas analyzers are optimized for physiological iCa concentrations which might make them less suitable for measuring low iCa in blood with a high concentration of citrate. We present results of iCa measurements from six different blood gas analyzers and the impact on clinical decisions based on the recommendations of the dialysis’ device manufacturer.

Method

The iCa concentrations of systemic and post filter samples were measured using six distinct, frequently used blood gas analyzers. We obtained iCa results of 74 systemic and 84 post filter samples from patients undergoing RCA for CRRT at the University Medicine of Greifswald.

Results

The systemic samples showed concordant results on all analyzers with median iCa concentrations ranging from 1.07 to 1.16 mmol/L. The medians of iCa concentrations for post filter samples ranged from 0.21 to 0.50 mmol/L. Results of >70 % of the post filter samples would lead to major differences in decisions regarding citrate flow depending on the instrument used.

Conclusion

Measurements of iCa in post filter samples may give misleading information in monitoring the RCA. Recommendations of the dialysis manufacturer need to be revised. Meanwhile, little weight should be given to post filter iCa. Reference methods for low iCa in whole blood containing citrate should be established.
Impact of Damping Scaling Factors on Direct Displacement-Based Design
Authors: Kong Cuiyan , Kowalsky Mervyn J.
Published: September 2015

Damping scaling factors (DSFs) play an important role in direct displacement-based design (DDBD) as they provide a means to establish displacement response spectra for damping values beyond 5%. Response spectra for multiple damping values are needed for DDBD as the approach relies on equivalent linearization, expressed in the form of effective stiffness and equivalent viscous damping, to establish design forces for prescribed performance limit states. In the past, DSFs based on the Eurocode have been employed for DDBD; however, recent research has resulted in more robust DSF models. This paper examines the accuracy of the current DSF equation used in DDBD across the parameters that are important for structural design. A nonlinear regression analysis is performed based on the data obtained by the Rezaeian et al. (2014) model, and a base shear adjustment factor (SAF) is proposed for application to the DDBD base shear equation.
Improved Approach for Modeling Nonlinear Site Response of Highly Strained Soils: Case Study of the Service Hall Array in Japan
Authors: Motamed Ramin , Stanton Kevin , Almufti Ibrahim , Ellison Kirk , Willford Michael
Published: September 2015

A nonlinear ground response analysis is conducted for the Niigata-ken Chuetsu-oki earthquake recorded at a free-field vertical array near the Kashiwazaki-Kariwa Nuclear Power Plant in Japan. A bidirectional site response analysis is carried out using LS-DYNA which allows user defined stress-strain relationships to dictate soil behavior subjected to dynamic loading. Dynamic soil behavior is characterized using a two-stage hyperbolic backbone curve implemented with modifications to consider the peak strength of soil layers as well as the strain at which the peak strength is fully mobilized. The effects of bidirectional input motions, strain rate, and the shape of the shear modulus degradation curves are investigated, and it is demonstrated that each factor can have a significant influence on the results.
Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With No Evidence of Disease After Complete Surgical Resection of Locally Advanced and/or Stage IV Melanoma: A Trial of the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group (E4697)
Authors: Lawson David H. , Lee Sandra , Zhao Fengmin , Tarhini Ahmad A. , Margolin Kim A. , Ernstoff Marc S. , Atkins Michael B. , Cohen Gary I. , Whiteside Theresa L. , Butterfield Lisa H. , Kirkwood John M.
Published: September 2015

Purpose

We conducted a double-blind, placebo-controlled trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) and peptide vaccination (PV) on relapse-free survival (RFS) and overall survival (OS) in patients with resected high-risk melanoma.

Patients and Methods

Patients with completely resected stage IV or high-risk stage III melanoma were grouped by human leukocyte antigen (HLA) -A2 status. HLA-A2–positive patients were randomly assigned to receive GM-CSF, PV, both, or placebo; HLA-A2–negative patients, GM-CSF or placebo. Treatment lasted for 1 year or until recurrence. Efficacy analyses were conducted in the intent-to-treat population.

Results

A total of 815 patients were enrolled. There were no significant improvements in OS (stratified log-rank P = .528; hazard ratio, 0.94; 95% repeated CI, 0.77 to 1.15) or RFS (P = .131; hazard ratio, 0.88; 95% CI, 0.74 to 1.04) in the patients assigned to GM-CSF (n = 408) versus those assigned to placebo (n = 407). The median OS times with GM-CSF versus placebo treatments were 69.6 months (95% CI, 53.4 to 83.5 months) versus 59.3 months (95% CI, 44.4 to 77.3 months); the 5-year OS probability rates were 52.3% (95% CI, 47.3% to 57.1%) versus 49.4% (95% CI, 44.3% to 54.3%), respectively. The median RFS times with GM-CSF versus placebo were 11.4 months (95% CI, 9.4 to 14.8 months) versus 8.8 months (95% CI, 7.5 to 11.2 months); the 5-year RFS probability rates were 31.2% (95% CI, 26.7% to 35.9%) versus 27.0% (95% CI, 22.7% to 31.5%), respectively. Exploratory analyses showed a trend toward improved OS in GM-CSF–treated patients with resected visceral metastases. When survival in HLA-A2–positive patients who received PV versus placebo was compared, RFS and OS were not significantly different. Treatment-related grade 3 or greater adverse events were similar between GM-CSF and placebo groups.

Conclusion

Neither adjuvant GM-CSF nor PV significantly improved RFS or OS in patients with high-risk resected melanoma. Exploratory analyses suggest that GM-CSF may be beneficial in patients with resected visceral metastases; this observation requires prospective validation.
Current Treatment Options for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Sacco Assuntina G. , Cohen Ezra E.
Published: September 2015

This review highlights the evidence-based data to support current best management practices for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Current limitations and areas of emerging therapeutics are also emphasized. The cornerstone of palliation for patients with R/M HNSCC is a platinum-based backbone. Platinum doublets induce higher response rates than single agents but do not demonstrate a survival advantage and are associated with increased toxicity. The only regimen to demonstrate survival superiority is platinum, fluorouracil, and cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR). EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only modest success in R/M HNSCC, illustrating the importance of identifying predictive biomarkers and finding ways to overcome mechanisms of resistance. Although phosphoinositide 3-kinase pathway alterations are present at a high rate in HNSCC, the identification of efficacious agents in patients with activating alterations has yet to be discovered. Immunotherapy represents an attractive treatment strategy for R/M HNSCC, with promising preliminary data from studies involving immune checkpoint blockade and toll-like receptor agonists. Human papillomavirus has a prognostic role in R/M disease; therefore, stratification of patients by human papillomavirus status in clinical trials is indicated. Although under-represented in clinical trials, elderly patients experience similar survival outcomes compared with younger patients, albeit with increased toxicity. Despite therapeutic advances, prognosis nonetheless remains poor for patients with R/M HNSCC. Enrollment of patients onto clinical trials to investigate novel therapeutics and identify predictive biomarkers is necessary to further refine and improve outcomes.
Analytical cell adhesion chromatography reveals impaired persistence of metastatic cell rolling adhesion to P-selectin
Authors: Oh Jaeho , Edwards Erin E. , McClatchey P. Mason , Thomas Susan N.
Published: September 2015

Selectins facilitate the recruitment of circulating cells from the bloodstream by mediating rolling adhesion, which initiates the cell-cell signaling that directs extravasation into surrounding tissues. To measure the relative efficiency of cell adhesion in shear flow for in vitro drug screening, we designed and implemented a microfluidic-based analytical cell adhesion chromatography system. The juxtaposition of instantaneous rolling velocities with elution times revealed that human metastatic cancer cells but not human leukocytes have a reduced capacity to sustain rolling adhesion with P-selectin. We define a new parameter, termed adhesion persistence, which is conceptually similar to migration persistence in the context of chemotaxis but instead describes the capacity of cells to resist the influence of shear flow and sustain rolling interactions with an adhesive substrate that may modulate the probability of extravasation. Among cell types assayed, adhesion persistence to P-selectin is specifically reduced in metastatic but not leukocyte-like cells in response to low-dose heparin. In conclusion, we demonstrate this as an effective methodology to identify selectin adhesion antagonist doses that modulate homing cell adhesion and engraftment in a cell subtype-selective manner.
Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility
Authors: Hu Meng-Wen , Wang Zhen-Bo , Teng Yan , Jiang Zong-Zhe , Ma Xue-Shan , Hou Ning , Cheng Xuan , Schatten Heide , Xu Xingzhi , Yang Xiao , Sun Qing-Yuan
Published: September 2015

Dynamic protein phosphorylation and dephosphorylation, mediated by a conserved cohort of protein kinases or phosphatases, regulate cell cycle progression. Among the well-known PP2A-like protein phosphatases, PP6 has been analyzed in mammalian mitosis recently identifying Aurora A as its key substrate. However, the functions of PP6 in meiosis are still entirely unknown. To identify the physiological role of PP6 in female gametogenesis, Ppp6cF/F mice were first generated and crossed with Zp3-Cre mice to selectively disrupt Ppp6c expression in oocytes. Here we report for the first time that PP6c was dispensable for oocyte meiotic maturation but essential for MII exit after fertilization, since depletion of PP6c caused abnormal MII spindle and disrupted MII cytokinesis, resulting in zygotes with high risk of aneuploidy, defective early embryonic development, thus severe subfertility. We also revealed that PP6 inactivation interfered with MII spindle formation and MII exit due to increased Aurora A activity, and Aurora A inhibition with MLN8237 could rescue the PP6c depletion phenotype. In conclusion, our findings uncover a hitherto unknown role for PP6 as an indispensable regulator of oocyte meiosis and female fertility.
Chiral Interaction between Bilirubin and Poly-l-lysine at Liquid–Liquid Interface
Authors: Matsuura Kimika , Watarai Hitoshi
Published: September 2015

Chiral interaction between bilirubin (BR) and poly-l-lysine (PLL) was investigated by a centrifugal liquid membrane-circular dichroism method. The interfacial self-aggregation of BR in pH 6 and the preferential interaction between the P form of BR and α-helix form of PLL at the interface under pH 10–12 were observed.
Collisional Reaction of Liquid Droplets: Amidation of Dansyl Chloride Observed by Fluorescence Enhancement
Authors: Suzuki Tomoko , Kohno Jun-ya
Published: September 2015

The collisional reaction of droplets is observed by time-resolved fluorescence spectroscopy. Colliding droplets of the reactant solutions are irradiated with a pulsed laser, and the resulting fluorescence spectra and images of the colliding droplets are observed as a function of the elapsed time from the collision. The amidation reaction of dansyl chloride with isopropylamine is observed through fluorescence enhancement on a microsecond time scale. The present method enables us to measure the early stages of reactions in solutions.
Conceptual Design of a Single-Crease Origami-Arc Inspired Movable Footbridge Structure
Authors: Nagy L. , Rhode-Barbarigos L. , Adriaenssens S. , Kilian A.
Published: September 2015

Origami, the craft of folding paper, has been a source of inspiration for developable foldable systems in various engineering disciplines. Origami-inspired segmented plate systems result in lightweight and stiff structures that change shape by folding. With curved-crease origami, a three-dimensional change in shape can arise from a single fold mechanism. In this paper, the curved-crease mechanism of a single-crease arc is investigated as the driver for the conceptual design of a movable footbridge. The folding mechanism is investigated using particle-spring models and small-scale physical models. The structural feasibility of a 40 m radius curved-crease origami-inspired movable footbridge is investigated using finite element analysis. Static analysis and sizing according to US footbridge design code are presented for the critical configurations of the footbridge. Results show that the footbridge can meet typical civil engineering design criteria and illustrate the potential of curved-crease folding mechanisms to inspire the development of movable structures.
A Fuzzy‐Based Decision Support Model for Selecting the Best Dialyser Flux in Haemodialysis
Authors: Öztürk Necla , Tozan Hakan
Published: September 2015

Decision making is an important procedure for every organization. The procedure is particularly challenging for complicated multi‐criteria problems. Selection of dialyser flux is one of the decisions routinely made for haemodialysis treatment provided for chronic kidney failure patients. This study provides a decision support model for selecting the best dialyser flux between high‐flux and low‐flux dialyser alternatives. The preferences of decision makers were collected via a questionnaire. A total of 45 questionnaires filled by dialysis physicians and nephrologists were assessed. A hybrid fuzzy‐based decision support software that enables the use of Analytic Hierarchy Process (AHP), Fuzzy Analytic Hierarchy Process (FAHP), Analytic Network Process (ANP), and Fuzzy Analytic Network Process (FANP) was used to evaluate the flux selection model. In conclusion, the results showed that a high‐flux dialyser is the best option for haemodialysis treatment.
Equipment and Energy Usage in a Large Teaching Hospital in Norway
Authors: Rohde Tarald , Martinez Robert
Published: September 2015

This article presents a study of how equipment is used in a Norwegian University hospital and suggests ways to reduce hospital energy consumption. Analysis of energy data from Norway’s newest teaching hospital showed that electricity consumption was up to 50 % of the whole‐building energy consumption. Much of this is due to the increasing energy intensity of hospital‐specific equipment. Measured power and reported usage patterns for equipment in the studied departments show daytime energy intensity of equipment at about 28.5 kBTU/ft2 per year (90 kWh/m2 per year), compared to building code standard value of only 14.9 kBTU/ft2 (47 kWh/m2 per year) for hospitals. This article intends to fill gaps in our understanding of how users and their equipment affect the energy balance in hospitals and suggests ways in which designers and equipment suppliers can help optimize energy performance while maintaining quality in the delivery of health services.
Productivity of Technological Waves in the USA Economy
Authors: Басовский  , Basovskiy Leonid , Басовская  , Basovskaya Elena
Published: September 2015

The paper presents econometric estimates of the productivity of technological

waves in the US economy. The phenomenon was dated due to modeling of

Kondratiev waves (cycles) that synchronize origin, dominance and death of

waves. Simulation of waves productivity revealed that the productivity of relict

waves in the US economy is 3610 Gehry-Hemis dollars 2005. Maximum

productivity of the fourth wave in the US economy is 3327 Gehry-Hemis dollars

2005. Maximum productivity of the fifth tech-nological wave in the US economy

is 21 thousand Gehry-Hemis dollars 2005. Maximum productivity of the sixth

technological wave in the US economy is 39 thousand Gehry-Hemis dollars in

2005.
Methods for Evaluating Risk Sensitivity of Investment Project
Authors: Сорокина  , Sorokina Natalia , Иванов  , Ivanov Miron
Published: September 2015

This article conducts the analysis of methods of project`s risk sensitivity

evaluation most frequently used by investment managers. Both quantitative

andqualitative methods were considered, and their main benefits, drawbacks

and areas of application were highlighted.
Current Features of Strategy Construction
Authors: Гераськина  , Geraskina A.
Published: September 2015

This article shows the main criteria of strategy’s efficiency. The most effective methods of strategy constructing, the ways to achieve goals and the main features of strategy formulation in modern conditions are presented. The basic disadvantages of traditional models of strategy formulation are shown: extrapolation the company’s performance over experience other organizations, resource-based view on strategic management, value chains, and the 3C’s model. Key features of current business environment are presented from the perspective of strategic management. The research develops the model of identifying direct competitor, possible and potential competitor, producer of substitute products, potential partner, and customers. The methods to evaluate their impact on the organization’s activities in the environment are presented. The basic disadvantages of the SWOT-analysis in the assessment of the external environment of organization on the basis of this model are shown.
United We Stand or Divided We Stand? Strategic Supplier Alliances Under Order Default Risk
Authors: Huang Xiao , Boyacı Tamer , Gümüş Mehmet , Ray Saibal , Zhang Dan
Published: September 2015

We study the alliance formation strategy among suppliers in a framework with one downstream firm and n upstream suppliers. Each supplier faces an exogenous random shock that may result in an order default. Each of them also has access to a recourse fund that can mitigate this risk. The suppliers can share the fund resources within an alliance, but they need to equitably allocate the profits of the alliance among the partners. In this context, suppliers need to decide whether to join larger alliances that have better chances of order fulfillment or smaller ones that may grant them higher profit allocations. We first analytically characterize the exact coalition-proof Nash-stable coalition structures that would arise for symmetric complementary or substitutable suppliers. Our analysis reveals that it is the appeal of default risk mitigation, rather than competition reduction, that motivates cooperation. In general, a riskier and/or less fragmented supply base favors larger alliances, whereas substitutable suppliers and customer demands with lower pass-through rates result in smaller ones. We then characterize the stable coalition structures for an asymmetric supplier base. We establish that grand coalition is more stable when the supplier base is more homogeneous in terms of their risk levels, rather than divided among a few highly risky suppliers and other low-risk ones. Going one step further, our investigation of endogenous recourse fund levels for the suppliers demonstrates how financing costs affect suppliers’ investments in risk-reducing resources and, consequently, their coalition formation strategy. Last, we discuss model generalizations and show that, in general, our insights are quite robust.

This paper was accepted by Serguei Netessine, operations management.
Dynamic Forecasting and Control Algorithms of Glaucoma Progression for Clinician Decision Support
Authors: Helm Jonathan E. , Lavieri Mariel S. , Van Oyen Mark P. , Stein Joshua D. , Musch David C.
Published: September 2015

In managing chronic diseases such as glaucoma, the timing of periodic examinations is crucial, as it may significantly impact patients’ outcomes. We address the question of when to monitor a glaucoma patient by integrating a dynamic, stochastic state space system model of disease evolution with novel optimization approaches to predict the likelihood of progression at any future time. Information about each patient’s disease state is learned sequentially through a series of noisy medical tests. This information is used to determine the best time to next test based on each patient’s individual disease trajectory as well as population information. We develop closed-form solutions and study structural properties of our algorithm. While some have proposed that fixed-interval monitoring can be improved upon, our methodology validates a sophisticated model-based approach to doing so. Based on data from two large-scale, 10+ years clinical trials, we show that our methods significantly outperform fixed-interval schedules and age-based threshold policies by achieving greater accuracy of identifying progression with fewer examinations. Although this work is motivated by our collaboration with glaucoma specialists, the methodology developed is applicable to a variety of chronic diseases.
Necessity of Future Information in Admission Control
Authors: Xu Kuang
Published: September 2015

We study the necessity of predictive information in a class of queueing admission control problems, where a system manager is allowed to divert incoming jobs up to a fixed rate, in order to minimize the queueing delay experienced by the admitted jobs.

Spencer et al. (2014) [Spencer J, Sudan M, Xu K (2014) Queuing with future information. Ann. Appl. Probab. 24(5):2091–2142.] show that the system’s delay performance can be significantly improved by having access to future information in the form of a lookahead window, during which the times of future arrivals and services are revealed. They prove that, while delay under an optimal online policy diverges to infinity in the heavy-traffic regime, it can stay bounded by making use of future information. However, the diversion polices of Spencer et al. (2014) require the length of the lookahead window to grow to infinity at a nontrivial rate in the heavy-traffic regime, and it remained open whether substantial performance improvement could still be achieved with less future information.

We resolve this question to a large extent by establishing an asymptotically tight lower bound on how much future information is necessary to achieve superior performance, which matches the upper bound of Spencer et al. (2014) up to a constant multiplicative factor. Our result hence demonstrates that the system’s heavy-traffic delay performance is highly sensitive to the amount of future information available. Our proof is based on analyzing certain excursion probabilities of the input sample paths, and exploiting a connection between a policy’s diversion decisions and subsequent server idling, which may be of independent interest for related dynamic resource allocation problems.
Redesigning incident reporting systems in the post-Mid-Staffordshire era
Authors: Smith Megan E
Published: September 2015

Incident reporting systems are vital to safe health care. Existing systems should be made simpler and more accessible, proper feedback given to those who complete reports and lessons learned from investigations shared more widely. A major shift in culture is required so health-care professionals feel safe completing incident reports.
Lasting power of attorney: a significant ethical responsibility
Authors: Lund Samantha
Published: September 2015

A lasting power of attorney makes decisions for another person who lacks the capacity to make the decision him-/herself. There are significant ethical issues which must be considered, not only so that the decision made is morally robust but also so that the individuals entrusted with this responsibility are adequately supported.
Some properties of thermostable amylase of four isolates of Bacillus licheniformis
Authors: DAWOOD ELHAM S. , IBRAHIM SIRAG A. , EL-NAGERABI SAIFELDIN A.F.
Published: September 2015

Abstract. Dawood ES, Ibrahim SA, El-Nagerabi SAF. 2015. Some properties of thermostable α-amylase of four isolates of Bacillus licheniformis. Nusantara Bioscience 7: 90-95. Amylases are one of the most important enzymes in the food industry and biotechnology. The present investigation was concerned with the production, purification and partial characterization of extracellular amylase from endogenous Sudanese Bacillus licheniformis isolate namely SUDK1, SUDK2, SUDK4, and SUDO. The extracted enzyme was partially purified using DEAD Sephadex A-25 gel filtration and the enzymatic reaction product was identified using thin layer chromatography. The results revealed that DEAE-Sephadex is an excellent and effective purification method and the activity of the partially purified enzymes (83.343-121.755 U/mg protein) compared to the crude extracts (4.626-7.250 U/mg protein) with increase of up to 16.8-18.3 folds. Amylase enzymes hydrolyze starch forming various maltooligosaccharides, such as maltose as major products and were identified as α- amylases. The enzyme's activity was optimum at 60-70°C and was active up to 90°C with residual activity of only 30-50%. All enzymes were stable between pH 6.0-9.0 with optimum activity at pH 7.0. The enzymes were stable and retained nearly all of their initial activities at -20°C at the end of 24 weeks and lost less than 60% of their initial activities at 4°C after 8 weeks. The Km values for this enzyme were 1.25-2.0 mg/mL which showed high affinity and needs only small amount of substrate to be saturated. Therefore, these α-amylases were thermostable at a wide range of temperature and pH values rendering them useful properties in food, feed, textiles, and relevant biotechnological industries.
Suppression of Meiotic Recombination by CENP-B Homologs inSchizosaccharomyces pombe
Authors: Johansen Peter , Cam Hugh P
Published: September 2015

Meiotic homologous recombination (HR) is not uniform across eukaryotic genomes, creating regions of HR hot- and coldspots. Previous study reveals that the Spo11 homolog Rec12 responsible for initiation of meiotic double-strand breaks in the fission yeast Schizosaccharomyces pombe is not targeted to Tf2 retrotransposons. However, whether Tf2s are HR coldspots is not known. Here, we show that the rates of HR across Tf2s are similar to a genome average but substantially increase in mutants deficient for the CENP-B homologs. Abp1, which is the most prominent of the CENP-B family members and acts as the primary determinant of HR suppression at Tf2s, is required to prevent gene conversion and maintain proper recombination exchange of homologous alleles flanking Tf2s. In addition, Abp1-mediated suppression of HR at Tf2s requires all three of its domains with distinct functions in transcriptional repression and higher-order genome organization. We demonstrate that HR suppression of Tf2s can be robustly maintained despite disruption to chromatin factors essential for transcriptional repression and nuclear organization of Tf2s. Intriguingly, we uncover a surprising cooperation between the histone methyltransferase Set1 responsible for histone H3 lysine 4 methylation and the nonhomologous end joining pathway in ensuring the suppression of HR at Tf2s. Our study identifies a molecular pathway involving functional cooperation between a transcription factor with epigenetic regulators and a DNA repair pathway to regulate meiotic recombination at interspersed repeats.
Dependence of Human Colorectal Cells Lacking the FBW7 Tumor Suppressor on the Spindle Assembly Checkpoint
Authors: Bailey Melanie L , Singh Tejomayee , Mero Patricia , Moffat Jason , Hieter Philip
Published: September 2015

FBW7 (F-box and WD repeat domain containing 7), also known as FBXW7 or hCDC4, is a tumor suppressor gene mutated in a broad spectrum of cancer cell types. As a component of the SCF E3 ubiquitin ligase, FBW7 is responsible for specifically recognizing phosphorylated substrates, many important for tumor progression, and targeting them for ubiquitin-mediated degradation. Although the role of FBW7 as a tumor suppressor is well established, less well studied is how FBW7-mutated cancer cells might be targeted for selective killing. To explore this further, we undertook a genome-wide RNAi screen using WT and FBW7 knockout colorectal cell lines and identified the spindle assembly checkpoint (SAC) protein BUBR1, as a candidate synthetic lethal target. We show here that asynchronous FBW7 knockout cells have increased levels of mitotic APC/C substrates and are sensitive to knockdown of not just BUBR1 but BUB1 and MPS1, other known SAC components, suggesting a dependence of these cells on the mitotic checkpoint. Consistent with this dependence, knockdown of BUBR1 in cells lacking FBW7 results in significant cell aneuploidy and increases in p53 levels. The FBW7 substrate cyclin E was necessary for the genetic interaction with BUBR1. In contrast, the establishment of this dependence on the SAC requires the deregulation of multiple substrates of FBW7. Our work suggests that FBW7 knockout cells are vulnerable in their dependence on the mitotic checkpoint and that this may be a good potential target to exploit in FBW7-mutated cancer cells.
Complementation of Yeast Genes with Human Genes as an Experimental Platform for Functional Testing of Human Genetic Variants
Authors: Hamza Akil , Tammpere Erik , Kofoed Megan , Keong Christelle , Chiang Jennifer , Giaever Guri , Nislow Corey , Hieter Philip
Published: September 2015

While the pace of discovery of human genetic variants in tumors, patients, and diverse populations has rapidly accelerated, deciphering their functional consequence has become rate-limiting. Using cross-species complementation, model organisms like the budding yeast, Saccharomyces cerevisiae, can be utilized to fill this gap and serve as a platform for testing human genetic variants. To this end, we performed two parallel screens, a one-to-one complementation screen for essential yeast genes implicated in chromosome instability and a pool-to-pool screen that queried all possible essential yeast genes for rescue of lethality by all possible human homologs. Our work identified 65 human cDNAs that can replace the null allele of essential yeast genes, including the nonorthologous pair yRFT1/hSEC61A1. We chose four human cDNAs (hLIG1, hSSRP1, hPPP1CA, and hPPP1CC) for which their yeast gene counterparts function in chromosome stability and assayed in yeast 35 tumor-specific missense mutations for growth defects and sensitivity to DNA-damaging agents. This resulted in a set of human–yeast gene complementation pairs that allow human genetic variants to be readily characterized in yeast, and a prioritized list of somatic mutations that could contribute to chromosome instability in human tumors. These data establish the utility of this cross-species experimental approach.
Assessment and strengthening of a Melbourne toll-way viaduct
Authors: Walsh Louis
Published: September 2015

Yarra Bridge and Gardiners Creek viaduct together form a major elevated structure in the Melbourne CityLink toll-way: the busiest route in the Victorian freeway system. Originally constructed in the 1960s, they have been twice widened and modified extensively. The original structures recently required to be upgraded to withstand current and anticipated future loading. This paper discusses the viaduct's load rating by way of a combination of analytical assessment and observation of the structures' actual condition followed by the development of preferred strengthening concepts in conjunction with the contractor and asset owner. The methods used, including concrete infill, carbon-fibre strengthening and external post-tensioning, were designed to be flexible so they could be modified where ‘as-constructed’ details were found to differ from the original design drawings. Remedial works were also designed to be carried out below deck level, avoiding disruption to toll-way traffic while minimising the impact on stakeholders below.
Generation of blood circulating DNA: the sources, peculiarities of circulation and structure
Authors: Bryzgunova O.E. , Laktionov P.P.
Published: September 2015

Extracellular nucleic acids (exNA) were described in blood of both healthy and illness people as early as in 1948, but staied overlooked until middle 60-th. Starting from the beginning of new millennium and mainly in the last 5 years exNA are intensively studied. Main attention is directed to investigation of exNA as the source of diagnostic material whereas the mechanisms of their generation, as well as mechanisms to providing long-term circulation of exNA in the bloodstream are not established unambiguously. According to some authors, the main source of circulating nucleic acids in blood are the processes of apoptosis and necrosis, while others refer to the possible nucleic acid secretion by healthy and tumor cells. Circulating DNA were found to be stable in the blood for a long time, escaping from the action of DNA hydrolyzing enzymes and are apparently packed in different supramolecular complexes. This review presents the opinions of various authors and evidence in favor of all the theories describingappearance of extracellular DNA, the features of the circulation and structure of the extracellular DNA and factors affecting the time of DNA circulation in blood
General anesthetics as a factor of effective neuroprotection in ischemic stroke models
Authors: Laletin V.S. , Bykov Y.N.
Published: September 2015

Stroke is the second leading cause of death in the world. Unfortunately, only a few drugs have been proved in clinical trials. Drug development of the last decade has been focused substantially on a promising and heterogeneous group of neuroprotective drugs. Hundreds of compounds were suggested as new putative neuroprotectors, which effectiveness was confirmed in preclinical trials only. At the present time discrepancy between results of preclinical studies and clinical trials requires careful analysis. One of the least evaluated and probably the most noticeable reasons is general anesthesia - an obligatory component of an overwhelming majority of existing animal stroke models. The aim of the review is to describe known mechanisms of common general anesthetics influence on ionotropic and metabotropic plasma membrane receptors, and key signal pathways involved in neuronal hypoxic-ischemic injury and survival
Protein-protein interactions of cytochromes P450 3A4 and 3A5 with their intermediate redox partners cytochromes b5
Authors: Gnedenko O.V. , Ivanov A.S. , Yablokov E.O. , Usanov S.A. , Mukha D.V. , Sergeev G.V. , Kuzikov A.V. , Moskaleva N.E. , Bulko T.V. , Shumyantseva V.V. , Archakov A.I.
Published: September 2015

Molecular interactions between proteins redox partners (cytochromes Р450 3А4, 3А5 and cytochrome b5) within the monooxygenase system, which is known to be involved in drug biotransformation, were investigated. Human cytochromes Р450 3A4 and 3А5 (CYP3A4 and CYP3A5) form complexes with various cytochromes b5: the microsomal (b5mc) and mitochondrial (b5om) forms of this protein, as well as with 2 “chimeric” proteins, b5(om-mc), b5(mc-om). Kinetic constants and equilibrium dissociation constants were determined by the SPR biosensor. Essential distinction between CYP3A4 and CYP3A5 was only observed upon their interactions with cytochrome b5om. Electroanalytical characteristics of electrodes with immobilized hemoproteins were obtained. The electrochemical analysis of CYP3A4, CYP3A5, b5mc, b5om, b5(om-mc), and b5(mc-om) immobilized on screen printed graphite electrodes modified with membranous matrix revealed that these proteins have very close reduction potentials -0.435  -0.350 V (vs. Ag/AgCl). Cytochrome b5mc was shown to be capable of stimulating the electrocatalytic activity of CYP3A4 in the presence of its substrate testosterone.
The selective toxic effect of dialdehyde derivatives of the pyrimidine nucleosides on human tumor cells
Authors: Efremova A.S. , Shram S.I. , Drenichev M.S. , Posypanova G.A. , Myasoedov N.F. , Mihaylov S.N.
Published: September 2015

The impact of a number of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian tumor cells (line SKOV-3) and normal human lung fibroblasts was investigated. It was shown that the dialdehyde derivatives of uridine, 1--D-eritrofuranozyl uracil and 3-O--D-ribofuranosyl-2-deoxythymidine, in contrast to their unoxidized counterparts, exert marked toxic effect on SKOV-3 cells. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1--D-eritrofuranozyl uracil demonstrated greatest differences in the cytotoxic effect on these cultures: inhibition of tumor SKOV-3 cells growth on 50% or more was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.
Increased manganese superoxide dismutase and cyclin B1 expression in carnosine-induced inhibition of glioblastoma cell proliferation
Authors: Rybakova Yu.S. , Kalen A.L. , Eckers J.C. , Fedorova T.N. , Goswami P.C. , Sarsour E.H.
Published: September 2015

Carnosine is an endogenous dipeptide with antiproliferative properties. Here we show that carnosine selectively inhibits proliferation of human glioblastoma cells (U-118-MG) compared to breast (MB231) and oral (Cal27 and FaDu) cancer cells. Carnosine-induced inhibition of U-118-MG proliferation is associated with a significant: decrease in cellular reactive oxygen species levels, increase in manganese superoxide dismutase (MnSOD) and increase in cyclin B1 expression resulting in G2-block. We conclude that the antiproliferative property of carnosine is due to its ability to enhance MnSOD and cyclin B1 expression. These results will be of significance to the potential application of carnosine in brain cancer therapy
Automated Real time Data Cleansing and Summarization; Case Study on Drilling Hook load Real time Data
Authors: Al Gharbi Salem H , Al sanie Faisal S. , Al Zayer Majed R
Published: September 2015

Real time data has become a vital component in drilling operations since it provides details that assist understanding of operational behavior. Real time data has played a big role in helping engineers maintain an optimized operational envelop to avoid drilling problems. It is well known that the amounts of data generated from real time tools (downhole and surface) are enormous; they bring other challenges such as managing and interpreting the high volume of data. The real time data is full of noise and it's difficult to process and analyze in real time. Cleansing and summarizing this huge volume of real time data is needed to improve the quality of the data for analysis and decision making in real time.

In this paper, hook load data will be a case study for automated real time data cleansing and summarization using statistical analysis techniques. This paper will present a technique for converting the drilling hook load real time data from 2D representation to 3D representation; the third dimension will be the data concentration, and this dimension will play a major role in allowing the dataset to self clean and summarize, which will provide an automated manner to clean the drilling real time data and summarize it.

This paper will show a set of real time data before and after applying this technique, and it will highlight how this technique was able to successfully clean and summarize a huge amount of real time data without losing trend descriptiveness.

This technique can prepare the real time data to be processed by a new level of advanced analytics applications that provide the drilling operation with real time prediction, simulation, and decision making solutions.
Trusted Data as a Company Asset
Authors: Flichy Philippe
Published: September 2015

Digital Oil Field's (DOF) practice's original promise was to gather data to help make better technical and business decisions. Some argue that a required step to enable a shift in the adoption of the DOF methodology is to treat data as an asset. Meaning data as an asset is as valuable as a physical asset. It should be maintained, protected, and respected in its own way with the same diligence we have for a field.

Here we are presenting why data is an asset.

With the advent of analytics, thanks to complex correlations “data can talk”; for it to be meaningful, data needs to be up to date, validated, and standardized so everyone can have access to a single version of the truth. Data is accepted and trusted if the process by which it has been validated is viewable and auditable. Enhancement and manipulations of this data need to be shared and stored centrally, not locally. The logic applied for its manipulation needs to be documented as well.

Trusted data means that each member of the team trusts each other's methodology to transform data into information. An enabler is the generation of meta-data to encapsulate this logic with the shared output.

Such fresh approaches to data validation and sharing will generate significant savings by eliminating duplicate efforts, increasing access time to information, and confidence in using the latest available source of information.

Ensuring this seamless access to information requires identifying where the sources of data are and developing aggregators to make it accessible to all in a standard manner from a single point. Creating this bridge to scattered data from multiple sources over many vendors is a complex task requiring domain expertise from a very heterogeneous set of people… It requires data ownership identification and bridging inconsistencies in data types and quality.

From the capture of data points and its validation to its refining and by-products, “Data as an asset” requires custodians of the integrity of the data, its storage and accessibility. “Data as an asset” means data is valuable and therefore needs to be protected from being misused or stolen. The fact we now “drink from the source” of data (getting data almost directly from the sensors) means we have to secure its acquisition and transmission very thoroughly and properly manage entitlement.

“Data as an asset” and the corollary technical data management it implies, will contribute to maximizing production and reserves; while also reducing costs by applying efficiencies, and connecting the field to the back office.