bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the Cumulative Incidence Function of Dynamic Treatment Regimes
Authors: Yavuz Idil , Chng Yu , Wahed Abdus S.
Published: November 2016

Recently personalized medicine and dynamic treatment regimes have drawn considerable attention. Dynamic treatment regimes are rules that govern the treatment of subjects depending on their intermediate responses or covariates. Two-stage randomization is a useful set-up to gather data for making inference on such regimes. Meanwhile, the number of clinical trials involving competing risk censoring has risen, where subjects in a study are exposed to more than one possible failure and the specific event of interest may not be observed because of competing events. We aim to compare several treatment regimes from a two-stage randomized trial on survival outcomes that are subject to competing risk censoring. The cumulative incidence function (CIF) has been widely used to quantify the cumulative probability of occurrence of the target event over time. However, if we use only the data from those subjects who have followed a specific treatment regime to estimate the CIF, the resulting estimator may be biased. Hence, we propose alternative non-parametric estimators for the CIF by using inverse probability weighting, and we provide inference procedures including procedures to compare the CIFs from two treatment regimes. We show the practicality and advantages of the proposed estimators through numerical studies.
Heterozoan carbonate deposition on a steep basement escarpment (Late Miocene, Almería, south‐east Spain)
Authors: Sola Fernando , Puga‐Bernabéu Ángel , Aguirre Julio , Braga Juan C.
Published: November 2016

Heterozoan temperate‐water carbonates mixed with varying amounts of terrigenous grains and muddy matrix (Azagador limestone) accumulated on and at the toe of an inherited escarpment during the late Tortonian–early Messinian (late Miocene) at the western margin of the Almería–Níjar Basin in south‐east Spain. The escarpment was the eastern end of an uplifting antiform created by compressive folding of Triassic rocks of the Betic basement. Channelized coralline‐algal/bryozoan rudstone to coarse‐grained packstone, together with matrix‐supported conglomerate, are the dominant lithofacies in the higher outcrops, comprising the deposits on the slope. These sediments mainly fill small canyon‐shaped, half‐graben depressions formed by normal faults active before, during and after carbonate sedimentation. Roughly bedded and roughly laminated coralline‐algal/bryozoan rudstone to coarse‐grained packstone are the main lithofacies forming an apron of four small (kilometre‐scale) lobes at the toe of the south‐eastern side of the escarpment (Almería area). Channelized and roughly bedded coralline‐algal/bryozoan rudstone to coarse‐grained packstone, conglomerates, packstone and sandy silt accumulated in a small channel‐lobe system at the toe of the north‐eastern side of the escarpment (Las Balsas area). Carbonate particles and terrigenous grains were sourced from shallow‐water settings and displaced downslope by sediment density flows that preferentially followed the canyon‐shaped depressions. Roughly laminated rudstone to packstone formed by grain flows on the initially very steep slope, whereas the rest of the carbonate lithofacies were deposited by high‐density turbidite currents. The steep escarpment and related break‐in‐slope at the toe favoured hydraulic jumps and the subsequent deposition of coarse‐grained, low‐transport efficiency skeletal‐dominated sediment in the apron lobes. Accelerated uplift of the basement caused a relative sea‐level fall resulting in the formation of outer‐ramp carbonates on the apron lobes, which were in turn overlain by lower Messinian coral reefs. The Almería example is the first known ‘base of slope’ apron within temperate‐water carbonate systems.
Centre‐Periphery Conflict and Ideological Distance in Turkey
Authors: Röth Leonce , Kaiser André , Varol Çağan , Sadioğlu Uğur
Published: November 2016

This article integrates ideology into a game‐theoretical model of centre‐periphery bargains. Ideological differences between national and sub‐national elites constitute a major obstacle for the accommodation of autonomy claims. While reforms bringing about decentralization are often analysed systematically as well as through case studies, cases where, despite claims to autonomy, decentralization does not occur have been largely neglected by scholars of territorial politics. Turkey is such a ‘negative case’. We argue that ideological distance prevents national parties from accommodating peripheral authority claims. We test our expectation with a mixed‐methods approach that combines quantitative analysis of party positions with in‐depth qualitative analysis of party documents showing how the different ideological positions of national and Kurdish parties affect decentralization demand and national response in Turkey between 1987 and 2015. Our findings support the theoretical expectations, but also point to additional inferences. Whereas asymmetric authority demands have been widely ignored, symmetric local autonomy has become an important issue in territorial politics.
Soil organic carbon pools in ploughed and no‐till Alfisols of central Ohio
Authors: Nakajima T. , Shrestha R. K. , Jacinthe P.‐A. , Lal R. , Bilen S. , Dick W.
Published: November 2016

No‐till (NT) farming can restore the soil organic carbon (SOC) pool of agricultural soils, but the SOC pool size and retention rate can vary with soil type and duration of NT. Therefore, the objectives of this study were to determine the effects of NT and soil drainage characteristics on SOC accumulation across a series of NT fields on Alfisols in Ohio, USA. Sites under NT for 9 (NT9), 13 (NT13), 36 (NT36), 48 (NT48) and 49 (NT49) years were selected for the study. Soil was somewhat poorly drained at the NT48 site but moderately well drained at the other sites. The NT48 and NT49 on‐station sites were under continuous corn (Zea mays), while the other sites were farmers' fields in a corn–soybean (Glycine max) rotation. At each location, the SOC pool (0–30 cm) in the NT field was compared to that of an adjacent plough‐till (PT) and woodlot (WL). At the NT36, NT48 and NT49 sites, the retention rate of corn‐derived C was determined using stable C isotope (13C) techniques. In the 0‐ to 10‐cm soil layer, SOC concentration was significantly larger under NT than PT, but a tillage effect was rarely detected below that depth. Across sites, the SOC pool in that layer averaged 36.4, 20 and 40.8 Mg C/ha at the NT, PT and WL sites, respectively. For the 0‐ to 30‐cm layer, the SOC pool for NT (83.4 Mg C/ha) was still 57% greater than under PT. However, there was no consistent trend in the SOC pool with NT duration probably due to the legacy of past management practices and SOC content differences that may have existed among the study sites prior to their conversion to NT. The retention rate of corn‐derived C was 524, 263 and 203 kg C/ha/yr at the NT36, NT48 and NT49 sites. In contrast, the retention rate of corn‐C under PT averaged 25 and 153 kg C/ha/yr at the NT49 (moderately well‐drained) and NT48 (somewhat poorly drained) sites, respectively. The conversion from PT to NT resulted in greater retention of corn‐derived C. Thus, adoption of NT would be beneficial to SOC sequestration in agricultural soils of the region.
Natural variation for gene expression responses to abiotic stress in maize
Authors: Waters Amanda J. , Makarevitch Irina , Noshay Jaclyn , Burghardt Liana T. , Hirsch Candice N. , Hirsch Cory D. , Springer Nathan M.
Published: November 2016

Plants respond to abiotic stress through a variety of physiological, biochemical, and transcriptional mechanisms. Many genes exhibit altered levels of expression in response to abiotic stress, which requires concerted action of both cis‐ and trans‐regulatory features. In order to study the variability in transcriptome response to abiotic stress, RNA sequencing was performed using 14‐day‐old maize seedlings of inbreds B73, Mo17, Oh43, PH207 and B37 under control, cold and heat conditions. Large numbers of genes that responded differentially to stress between parental inbred lines were identified. RNA sequencing was also performed on similar tissues of the F1 hybrids produced by crossing B73 and each of the three other inbred lines. By evaluating allele‐specific transcript abundance in the F1 hybrids, we were able to measure the abundance of cis‐ and trans‐regulatory variation between genotypes for both steady‐state and stress‐responsive expression differences. Although examples of trans‐regulatory variation were observed, cis‐regulatory variation was more common for both steady‐state and stress‐responsive expression differences. The genes with cis‐allelic variation for response to cold or heat stress provided an opportunity to study the basis for regulatory diversity.
Cover Image, Volume 14, Issue 4
Authors: Noguchi S. , Kumazaki M. , Mori T. , Baba K. , Okuda M. , Mizuno T. , Akao Y.
Published: November 2016

The cover image, by Shunsuke Noguchi et al., is based on the Original Article Analysis of microRNA‐203 function in CREB/MITF/RAB27a pathway: comparison between canine and human melanoma cells, DOI: 10.1111/vco.12118.

image
Comparison of a rapid immunochromatographic assay with an immunofluorescent antibody test for detection of Leishmania infantum antibodies in dogs
Authors: Proverbio Daniela , Spada Eva , Perego Roberta , Baggiani Luciana , Bagnagatti De Giorgi Giada , Migliazzo Antonella , Vitale Fabrizio
Published: November 2016

Background

Identification of Leishmania infantum‐infected dogs is crucial for control of canine leishmaniosis. In particular, in areas where access to specialized laboratories is limited, the availability of reliable and rapid in‐clinic serologic tests may support immediate diagnosis in suspected cases and permit detection of asymptomatic canine carriers of L infantum infection.

Objective

The purpose of the study was to validate the immunochromatographic test (ICT) Anigen Rapid Leishmania Ab Test kit for detection of L infantum antibodies in naturally exposed dogs in comparison with the immunofluorescence antibody test (IFAT).

Methods

Serum samples from 66 dogs, including 20 healthy control dogs and 46 dogs suspected or confirmed with canine leishmaniosis, were measured by both tests. Anti‐Leishmania IgG titers ≥ 1:40 by IFAT were considered positive. Kappa statistic with a 95% CI was calculated to evaluate agreement between the 2 testing methods, and sensitivity, specificity, and positive and negative likelihood ratio were calculated.

Results

Anti‐L infantum IgG antibodies were found in 35 of 66 samples using the IFAT test (titers 1:40–1:5120). Thirty‐one out of 66 samples tested positive with the qualitative ICT. Four IFAT‐positive (titers < 1:80) samples were ICT‐negative. The Kappa value of 0.853 demonstrated very good agreement between the 2 tests.

Conclusion

The Anigen Rapid Leishmania Ab Test kit reliably identified canine sera with anti‐L infantum IgG antibody titers ≥ 1:40. The ICT requires neither special preparation of the serum nor specialized equipment and can be stored at ambient temperature. The test is applicable as a field test because it is easy to use and provides rapid results.
Epidermolysis bullosa simplex in sibling Eurasier dogs is caused by a PLEC non‐sense variant
Authors: Mauldin Elizabeth A. , Wang Ping , Olivry Thierry , Henthorn Paula S. , Casal Margret L.
Published: November 2016

Background

Plectin, a large linker protein found in many tissues, acts to connect components of the cytoskeleton to each other. In the epidermis, plectin binds keratin intermediate filaments to hemidesmosomes. A deficiency of plectin in the skin leads to blister formation in the basal layer and the disease epidermolysis bullosa simplex (EBS).

Hypothesis/Objectives

To describe a novel blistering disease that arose spontaneously in a litter of puppies.

Animals

Two female and one male 20‐day‐old Eurasier puppies, from a litter of six, were presented for evaluation of failure to thrive and then euthanized due to poor prognosis. The puppies had ulcers on the lips, tongue, nasal planum, paw pads and abdomen.

Results

Immunolabelling on frozen skin for basement membrane proteins revealed patchy and weak to absent staining for plectin as compared with strong linear staining in normal dogs. Ultrastructurally, hemidesmosomes were irregularly shaped and had loss of distinction between inner and outer plaques. Pedigree analysis supported an autosomal recessive mode of inheritance. A premature stop codon was discovered in exon 27 of PLEC that resulted in the production of a severely truncated protein.

Conclusion

The study describes the first documented spontaneous EBS associated with a PLEC variant in domestic animals.
Transport of Radioactive Soil and Waste to the Fukushima Interim Storage Facility—From Organizational Arrangement Perspectives
Authors: Nishimura Masahiro
Published: November 2016

The Ministry of the Environment of Japan started transport of radioactive soil and waste to the Fukushima Interim Storage Facility in March 2015 following the decontamination works from the Fukushima Dai-ichi Nuclear Power Station disaster in March 2011. Although it was an unprecedented challenge and seemed unfit for the ministry with mainly regulatory functions, the ministry prepared the transport plan and smoothly started the initial works. This article reviews the planning and initial implementation processes mainly from the organizational arrangement perspectives. In addition to the organization’s original expertise and experiences, the organization’s absorptive capacity that stemmed from organizational culture contributed to the smooth implementation. It is recommended that organization’s absorptive capacity be considered when setting up implementation arrangements for responses to an unprecedented challenge that requires quick decisions and flexible actions.
Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing
Authors: Kuo Anderson H. , Li Cun , Li Jinqi , Huber Hillary F. , Nathanielsz Peter W. , Clarke Geoffrey D.
Published: November 2016

Key points

Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short‐term and long‐term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental‐fetal development indicate a need for models in precocial species for translation to human development.

We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood.

Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls.

Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort.

Understanding early cardiac biomarkers of IUGR using non‐invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies.

Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years – human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two‐way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non‐human primate model. Further studies across the life span will determine progression of cardiac dysfunction.
Acute and chronic effects of noradrenergic enhancement on transcranial direct current stimulation‐induced neuroplasticity in humans
Authors: Kuo Hsiao‐I. , Paulus Walter , Batsikadze Giorgi , Jamil Asif , Kuo Min‐Fang , Nitsche Michael A.
Published: November 2016

Key points

Chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) increased and prolonged the long‐term potentiation‐like plasticity induced by anodal transcranial direct current stimulation (tDCS) for over 24 h.

Chronic administration of RBX converted cathodal tDCS‐induced long‐term depression‐like plasticity into facilitation for 120 min.

Chronic noradrenergic activity enhancement on plasticity of the human brain might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases.

Noradrenaline affects cognition and motor learning processes via its impact on long‐term potentiation (LTP) and depression (LTD). We aimed to explore the impact of single dose and chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) on plasticity induced by transcranial direct current stimulation (tDCS) in healthy humans via a double‐blinded, placebo‐controlled, randomized crossover study. Sixteen healthy volunteers received placebo or single dose RBX (8 mg) before anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took RBX (8 mg day−1) consecutively for 21 days. During this period, two additional interventions were performed (RBX with anodal or cathodal tDCS), to explore the impact of chronic RBX treatment on plasticity. Plasticity was monitored by motor‐evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic administration of RBX increased and prolonged the LTP‐like plasticity induced by anodal tDCS for over 24 h. Chronic RBX significantly converted cathodal tDCS‐induced LTD‐like plasticity into facilitation, as compared to the single dose condition, for 120 min after stimulation. The results show a prominent impact of chronic noradrenergic enhancement on plasticity of the human brain that might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases.
Tonotopic action potential tuning of maturing auditory neurons through endogenous ATP
Authors: Jovanovic Saša , Radulovic Tamara , Coddou Claudio , Dietz Beatrice , Nerlich Jana , Stojilkovic Stanko S. , Rübsamen Rudolf , Milenkovic Ivan
Published: November 2016

Key points

Following the genetically controlled formation of neuronal circuits, early firing activity guides the development of sensory maps in the auditory, visual and somatosensory system. However, it is not clear whether the activity of central auditory neurons is specifically regulated depending on the position within the sensory map.

In the ventral cochlear nucleus, the first central station along the auditory pathway, we describe a mechanism through which paracrine ATP signalling enhances firing in a cell‐specific and tonotopically‐determined manner.

Developmental down‐regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, suggesting a high‐to‐low frequency maturation pattern.

Facilitated action potential (AP) generation, measured as higher firing rate, shorter EPSP‐AP delay in vivo and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP.

The long lasting change in intrinsic neuronal excitability is mediated by the heteromeric P2X2/3 receptors.

Synaptic refinement and strengthening are activity‐dependent processes that establish orderly arranged cochleotopic maps throughout the central auditory system. The maturation of auditory brainstem circuits is guided by action potentials (APs) arising from the inner hair cells in the developing cochlea. The AP firing of developing central auditory neurons can be modulated by paracrine ATP signalling, as shown for the cochlear nucleus bushy cells and principal neurons in the medial nucleus of the trapezoid body. However, it is not clear whether neuronal activity may be specifically regulated with respect to the nuclear tonotopic position (i.e. sound frequency selectivity). Using slice recordings before hearing onset and in vivo recordings with iontophoretic drug applications after hearing onset, we show that cell‐specific purinergic modulation follows a precise tonotopic pattern in the ventral cochlear nucleus of developing gerbils. In high‐frequency regions, ATP responsiveness diminished before hearing onset. In low‐to‐mid frequency regions, ATP modulation persisted after hearing onset in a subset of low‐frequency bushy cells (characteristic frequency< 10 kHz). Down‐regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, thus suggesting a high‐to‐low frequency maturation pattern. Facilitated AP generation, measured as higher firing frequency, shorter EPSP‐AP delay in vivo, and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP. Finally, by combining recordings and pharmacology in vivo, in slices, and in human embryonic kidney 293 cells, it was shown that the long lasting change in intrinsic neuronal excitability is mediated by the P2X2/3R.
Preferable Workspace for Fatigue Life Improvement of Flexible-Joint Robots Under Percussive Riveting
Authors: Li Yuwen , Guo Shuai , Xi Fengfeng (Jeff)
Published: November 2016

This paper proposes a method to find the preferable workspace for fatigue life improvement of robots with flexible joints under percussive riveting. The development is motivated by the growing interest in using industrial robots to replace human operators for percussive riveting operations in aerospace assembly. A most important characteristic of robotic percussive riveting is the repetitive impacts generated by the percussive rivet gun. These impacts induce forced vibrations to the robot, and the joint shaft fatigue due to the resulting stress cycles must be prevented. This paper aims at finding the preferable workspace for fatigue life improvement of the robot, that is, the end-effector positions where the joint stresses are below the endurance limit. For this purpose, a structural dynamic model is established for the robot under percussive riveting. Then, an approximate analytical solution is formulated for the torsional stresses of the robot joints. Once the distributions of the stresses are obtained over the workspace, the preferable workspace for fatigue life improvement can be found by comparing the stresses with the endurance limit. Simulation studies are carried out for a mobile robot under percussive riveting. It is found that the dynamic response of the robot to the percussive riveting varies dramatically over the workspace. The method is then used to obtain the preferable positions of the robot end-effector for fatigue resistance.
Exponentially Dissipative Control for Singular Impulsive Dynamical Systems
Authors: Yang Li , Liu Xinzhi , Zhang Zhigang
Published: November 2016

This paper studies the problem of exponentially dissipative control for singular impulsive dynamical systems. Some necessary and sufficient conditions for exponential dissipativity of such systems are established in terms of linear matrix inequalities (LMIs). A state feedback controller is designed to make the closed-loop system exponentially dissipative. A numerical example is given to illustrate the feasibility of the method.
Using Dynamics to Consider Torque Constraints in Manipulator Planning With Heavy Loads
Authors: Chuy, Oscar Y. , Collins, Emmanuel G. , Sharma Aneesh , Kopinsky Ryan
Published: November 2016

Input constraints are active in robot trajectory planning when a mobile robot traverses mobility challenges such as steep hills that limit the acceleration of the robot due to the torque constraints of the motor or engine or in manipulator lifting tasks when the load is sufficiently heavy that the torque constraints of the robot's motor prevent it from statically supporting the load in regions of the robot's workspace. This paper presents a general methodology for solving these planning tasks using a minimum-time cost function and applies it to the problem of a multiple degrees-of-freedom (DOF) manipulator lifting a heavy load. Planning for these types of problems requires use of the robot's dynamic model. Here, we plan using sampling-based model predictive optimization (SBMPO), which is only practical if the planning can be done quickly. Hence, substantial attention is given to efficient computations by: (1) using the dynamic model without integrating it, (2) using optimal control theory to develop an “optimistic A* estimate of cost-to-goal,” which is in this case a rigorous lower bound on the minimum time from a current state to a goal state, and (3) using prior experience to speed up the computation of a new trajectory. The methodology is experimentally verified for heavy lifting using a two-link manipulator.
Asymptotic Solution and Trajectory Planning for Open-Loop Control of Mobile Robots
Authors: Whitman Alan , Clayton Garrett , Poultney Alexander , Ashrafiuon Hashem
Published: November 2016

A novel open-loop control method is presented for mobile robots based on an asymptotic inverse dynamic solution and trajectory planning. The method is based on quantification of sliding by a small nondimensional parameter. Asymptotic expansion of the equations yields the dominant nonslip solution along with a first-order correction for sliding. A trajectory planning is then introduced based on transitional circles between the robot initial states and target reference trajectory. The transitional trajectory ensures smooth convergence of the robot states to the target reference trajectory, which is essential for open-loop control. Experimental results with a differential drive mobile robot demonstrate the significant improvement of the controller performance when the first-order correction is included.
A Haptic Bilateral System for the Remote Human–Human Handshake
Authors: Pedemonte Nicolò , Laliberté Thierry , Gosselin Clément
Published: November 2016

The objective of this work is to develop a hardware and software system that allows two people to shake hands while being in different locations. To this end, a novel haptic interface that is capable of performing a robotic handshake was designed and built. In this paper, the communication system composed of two such interfaces is presented. The working principle of the haptic interface is first recalled. The attention is then focused on the development and the implementation of a control algorithm that allows bilateral interaction between the two users. Finally, the transparency of the system is qualitatively validated in terms of the exchanged forces and of the positions of the interfaces, through some preliminary experiments.
A comparison of two prospective risk analysis methods: Traditional FMEA and a modified healthcare FMEA
Authors: Rah Jeong‐Eun , Manger Ryan P. , Yock Adam D. , Kim Gwe‐Ya
Published: November 2016

Purpose:

To examine the abilities of a traditional failure mode and effects analysis (FMEA) and modified healthcare FMEA (m‐HFMEA) scoring methods by comparing the degree of congruence in identifying high risk failures.

Methods:

The authors applied two prospective methods of the quality management to surface image guided, linac‐based radiosurgery (SIG‐RS). For the traditional FMEA, decisions on how to improve an operation were based on the risk priority number (RPN). The RPN is a product of three indices: occurrence, severity, and detectability. The m‐HFMEA approach utilized two indices, severity and frequency. A risk inventory matrix was divided into four categories: very low, low, high, and very high. For high risk events, an additional evaluation was performed. Based upon the criticality of the process, it was decided if additional safety measures were needed and what they comprise.

Results:

The two methods were independently compared to determine if the results and rated risks matched. The authors’ results showed an agreement of 85% between FMEA and m‐HFMEA approaches for top 20 risks of SIG‐RS‐specific failure modes. The main differences between the two approaches were the distribution of the values and the observation that failure modes (52, 54, 154) with high m‐HFMEA scores do not necessarily have high FMEA‐RPN scores. In the m‐HFMEA analysis, when the risk score is determined, the basis of the established HFMEA Decision Tree™ or the failure mode should be more thoroughly investigated.

Conclusions:

m‐HFMEA is inductive because it requires the identification of the consequences from causes, and semi‐quantitative since it allows the prioritization of high risks and mitigation measures. It is therefore a useful tool for the prospective risk analysis method to radiotherapy.
A novel approach to evaluate spatial resolution of MRI clinical images for optimization and standardization of breast screening protocols
Authors: Borri Marco , Scurr Erica D. , Richardson Cheryl , Usher Marianne , Leach Martin O. , Schmidt Maria A.
Published: November 2016

Purpose:

Stringent quality assurance is required in MRI breast screening to ensure that different scanners and imaging protocols reach similar diagnostic performance. The authors propose a methodology, based on power spectrum analysis (PSA), to evaluate spatial resolution in clinical images. To demonstrate this approach, the authors have retrospectively compared two MRI sequences commonly employed in breast screening.

Methods:

In a novel approach to PSA, spatial frequency response curves (SFRCs) were extracted from the images. The SFRC characterizes spatial resolution describing the spatial frequency content of an image over a range of frequencies. Verification of the SFRCs was performed on MRI images of Eurospin agarose gel tubes acquired with different resolution settings. SFRCs of volunteer and patient images obtained with two clinical MRI sequences were then compared. The two sequences differed primarily in k‐space coverage pattern, which was either radial (RAD) or linear (LIN).

Results:

The computed SFRCs were able to demonstrate the differences between RAD and LIN sequences in relatively small groups of subjects. The curves showed a similar pattern of decay in both volunteer and patient images, indicating that the spatial frequency response is mainly determined by the imaging protocol and not by intersubject anatomical differences. The LIN protocol produced images with increased sharpness; this was reflected in the corresponding SFRCs, which showed a higher content of spatial frequencies associated with image details.

Conclusions:

The SFRC can provide an objective assessment of the presence of spatial details in the image and represent a useful quality assurance tool in the evaluation of different breast screening protocols. With a reference image, a comparative analysis of the SFRCs could ensure that equivalent image quality is achieved across different scanners and sites.
Identification and characterization of genes controlled by the sporulation-regulatory gene spo0H in Bacillus subtilis
Authors: Jaacks K J , Healy J , Losick R , Grossman A D
Published: November 2016

We describe a general strategy for the identification of genes that are controlled by a specific regulatory factor in vivo and the use of this strategy to identify genes in Bacillus subtilis that are controlled by spo0H, a regulatory gene required for the initiation of sporulation. The general strategy makes use of a cloned regulatory gene fused to an inducible promoter to control expression of the regulatory gene and random gene fusions to a reporter gene to monitor expression in the presence and absence of the regulatory gene product. spo0H encodes a sigma factor of RNA polymerase, sigma H, and is required for the extensive reprograming of gene expression during the transition from growth to stationary phase and during the initiation of sporulation. We identified 18 genes that are controlled by sigma H (csh genes) in vivo by monitoring expression of random gene fusions to lacZ, made by insertion mutagenesis with the transposon Tn917lac, in the presence and absence of sigma H. These genes had lower levels of expression in the absence of sigma H than in the presence of sigma H. Patterns of expression of the csh genes during growth and sporulation in wild-type and spo0H mutant cells indicated that other regulatory factors are probably involved in controlling expression of some of these genes. Three of the csh::Tn917lac insertion mutations caused noticeable phenotypes. One caused a defect in vegetative growth, but only in combination with a spo0H mutation. Two others caused a partial defect in sporulation. One of these also caused a defect in the development of genetic competence. Detailed characterization of some of the csh genes and their regulatory regions should help define the role of spo0H in the regulation of gene expression during the transition from growth to stationary phase and during the initiation of sporulation.
Cloning and sequencing of the gene encoding a 125-kilodalton surface-layer protein from Bacillus sphaericus 2362 and of a related cryptic gene
Authors: Bowditch R D , Baumann P , Yousten A A
Published: November 2016

Using the vector pGEM-4-blue, a 4,251-base-pair DNA fragment containing the gene for the surface (S)-layer protein of Bacillus sphaericus 2362 was cloned into Escherichia coli. Determination of the nucleotide sequence indicated an open reading frame (ORF) coding for a protein of 1,176 amino acids with a molecular size of 125 kilodaltons (kDa). A protein of this size which reacted with antibody to the 122-kDa S-layer protein of B. sphaericus was detected in cells of E. coli containing the recombinant plasmid. Analysis of the deduced amino acid sequence indicated a highly hydrophobic N-terminal region which had the characteristics of a leader peptide. The first amino acid of the N-terminal sequence of the 122-kDa S-layer protein followed the predicted cleavage site of the leader peptide in the 125-kDa protein. A sequence characteristic of promoters expressed during vegetative growth was found within a 177-base-pair region upstream from the ORF coding for the 125-kDa protein. This putative promoter may account for the expression of this gene during the vegetative growth of B. sphaericus and E. coli. The gene for the 125-kDa protein was followed by an inverted repeat characteristic of terminators. Downstream from this gene (11.2 kilobases) was an ORF coding for a putative 80-kDa protein having a high sequence similarity to the 125-kDa protein. Evidence was presented indicating that this gene is cryptic.
Mercury operon regulation by the merR gene of the organomercurial resistance system of plasmid pDU1358
Authors: Nucifora G , Chu L , Silver S , Misra T K
Published: November 2016

The structural basis for induction of the mercury resistance operon with inorganic mercury and with the organomercurial compound phenylmercuric acetate was addressed by DNA sequencing analysis and by lac fusion transcription experiments regulated by merR in trans from broad-spectrum-resistance plasmid pDU1358 (Hg2+ and phenylmercury responding). The lac fusion results were compared with those from a narrow-spectrum-resistance (Hg2+ responding but not phenylmercuric responding) operon and the pDU1358 merR deleted at the 3' end. The nucleotide sequence of the beginning region of the broad-spectrum mer operon of plasmid pDU1358 was determined, including that of the merR gene, the operator-promoter region, the merT and merP genes, and the first 60% of the merA gene. Comparison of this sequence with DNA sequences of narrow-spectrum mer operons from transposon Tn501 and plasmid R100 showed that a major difference occurred in the 3' 29 base pairs of the merR gene, resulting in unrelated C-terminal 10 amino acids. A hybrid mer operon consisting of the merR gene from pDU1358, a hybrid merA gene (determining mercuric reductase enzyme), and lacking the merB gene (determining phenylmercury lyase activity) was inducible by both phenylmercury and inorganic Hg2+. This shows that organomercurial lyase is not needed for induction by organomercurial compounds. A mutant form of pDU1358 merR missing the C-terminal 17 amino acids responded to inorganic Hg2+ but not to phenylmercury. Thus, the C-terminal region of the MerR protein of the pDU1358 mer operon is involved in the recognition of phenylmercury.
Methylation of 23S rRNA caused by tlrA (ermSF), a tylosin resistance determinant from Streptomyces fradiae
Authors: Zalacain M , Cundliffe E
Published: November 2016

Ribosomes from Streptomyces griseofuscus expressing tlrA, a resistance gene isolated from the tylosin producer Streptomyces fradiae, are resistant to macrolide and lincosamide antibiotics in vitro. The tlrA product was found to be a methylase that introduces two methyl groups into a single base within 23S rRNA, generating N6,N6-dimethyladenine at position 2058. This activity is therefore similar to the ermE resistance mechanism in Saccharopolyspora erythraea (formerly Streptomyces erythraeus).
Mechanism of biosynthesis of unsaturated fatty acids in Pseudomonas sp. strain E-3, a psychrotrophic bacterium
Authors: Wada M , Fukunaga N , Sasaki S
Published: November 2016

Biosynthesis of palmitic, palmitoleic, and cis-vaccenic acids in Pseudomonas sp. strain E-3 was investigated with in vitro and in vivo systems. [1-14C]palmitic acid was aerobically converted to palmitoleate and cis-vaccenate, and the radioactivities on their carboxyl carbons were 100 and 43%, respectively, of the total radioactivity in the fatty acids. Palmitoyl coenzyme A desaturase activity was found in the membrane fraction. [1-14C]stearic acid was converted to octadecenoate and C16 fatty acids. The octadecenoate contained oleate and cis-vaccenate, but only oleate was produced in the presence of cerulenin. [1-14C]lauric acid was aerobically converted to palmitate, palmitoleate, and cis-vaccenate. Under anaerobic conditions, palmitate (62%), palmitoleate (4%), and cis-vaccenate (34%) were produced from [1-14C]acetic acid, while they amounted to 48, 39, and 14%, respectively, under aerobic conditions. In these incorporation experiments, 3 to 19% of the added radioactivity was detected in released 14CO2, indicating that part of the added fatty acids were oxidatively decomposed. Partially purified fatty acid synthetase produced saturated and unsaturated fatty acids with chain lengths of C10 to C18. These results indicated that both aerobic and anaerobic mechanisms for the synthesis of unsaturated fatty acid are operating in this bacterium.
Molecular characterization of a fimbrial adhesin, F1845, mediating diffuse adherence of diarrhea-associated Escherichia coli to HEp-2 cells
Authors: Bilge S S , Clausen C R , Lau W , Moseley S L
Published: November 2016

A fimbrial adhesin, designated F1845, was found to be responsible for the diffuse HEp-2 cell adherence of a diarrheal Escherichia coli isolate. The genetic determinant of F1845 was cloned, and the order of the genes necessary for production of F1845 was determined by maxicell analysis. Five polypeptides with apparent sizes of 10, 95, 27, 15.5, and 14.3 kilodaltons (kDa) were found to be encoded in that order by the F1845 determinant. The nucleotide sequence of the 14.3-kDa subunit gene was determined and found to share extensive homology in its signal sequence with the gene encoding the structural subunit of the AFA-1 hemagglutinin of a uropathogenic E. coli strain (A. Labigne-Roussel, M.A. Schmidt, W. Walz, and S. Falkow, J. Bacteriol. 162:1285-1292, 1985) but not in the region encoding the mature protein. Southern blot hybridizations indicated that the F1845 determinants are of chromosomal origin. Hybridization studies using a probe from the region encoding the 95-kDa polypeptide indicated that related sequences may be plasmid associated in some strains and chromosomal in others. Additional hybridization studies of E. coli isolates possessing sequence homology to the F1845 determinant suggest that the sequences in the 5' region of the F1845 structural subunit gene are more highly conserved than sequences in the 3' region.
Overproduction and identification of the ftsQ gene product, an essential cell division protein in Escherichia coli K-12
Authors: Storts D R , Aparicio O M , Schoemaker J M , Markovitz A
Published: November 2016

ftsQ is an essential cell division gene in Escherichia coli. The ftsQ gene has been sequenced, and a presumptive open reading frame has been identified; however, no protein product has been observed (A.C. Robinson, D.J. Kenan, G.F. Hatfull, N.F. Sullivan, R. Spiegelberg, and W.D. Donachie, J. Bacteriol. 160:546-555, 1984, and Q.M. Yi, S. Rockenbach, J.E. Ward, Jr., and J. Lutkenhaus, J. Mol. Biol. 184:399-412, 1985). The ftsQ gene was isolated on a 970-base-pair EcoRI-PvuII fragment of the E. coli chromosome and used to construct a trp-lac (Ptac) transcriptional fusion in plasmid pKK223-3. The fused construct (pDSC78) complemented an ftsQ1(Ts) mutant strain in trans, restoring growth at 42 degrees C on low-salt medium. An ftsQ1(Ts) mutant strain transformed with pDSC78 appeared normal upon microscopic examination, with no indication of filamentation. The ftsQ gene product was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis of radiolabeled, isopropyl-beta-D-thiogalactopyranoside-induced maxicell and normal cell extracts. As predicted from the nucleotide sequence, the 970-base-pair EcoRI-PvuII fragment encoded a polypeptide of approximately 31,400 daltons. Analysis of the data obtained from pulse-chase experiments in maxicells and normal cells suggests that the FtsQ protein is stable. Most of the radiolabeled FtsQ protein from maxicells was found in the inner membrane. On the basis of available information, the prior inability to detect FtsQ can be attributed to low levels of transcription or translation rather than to proteolysis.
Isolation and mapping of Escherichia coli mutations conferring resistance to division inhibition protein DicB
Authors: Labie C , Bouché F , Bouché J P
Published: November 2016

Temperature-sensitive dicA mutants of Escherichia coli, dicA1(Ts), are blocked for cell division, owing to derepressed expression of a division inhibition gene, dicB. We isolated mutants which survived a high temperature in the dicA1 background and which survived induced expression of dicB carried by a high-copy-number plasmid. Most of the mutations conferred very slow growth on the cells. Two were mapped to the 90-min cluster of genes involved in translation and transcription, in or very close to gene rpoB. The majority of the other mutations were found to cause variable degrees of minicell formation and to map within or very close to the minB locus. Contrary to these mutations, the canonical min-1 mutation did not confer resistance to DicB.
Transcription of the isoamylase gene (iam) in Pseudomonas amyloderamosa SB-15
Authors: Fujita M , Amemura A , Futai M
Published: November 2016

S1 nuclease mapping of RNA prepared from Pseudomonas amyloderamosa SB-15 suggested that the iam gene coding for isoamylase (glycogen 6-glucanohydrolase [EC 3.2.1.68]) is transcribed from two promoters. The transcription start site for the upstream promoter (termed P1) was located -182 base pairs from the first nucleotide of the initiation codon of iam, whereas the start site for the downstream promoter (termed P2) was 99 base pairs downstream of the P1 start site. Transcriptions from these promoters were induced by maltose and were not repressed by glucose. The promoter regions contained sequences homologous to the consensus sequence recognized by sigma 54 RNA polymerase of enteric bacteria and found in promoters of other Pseudomonas species. Northern (RNA) hybridization provided evidence that the iam gene is transcribed as monocistronic mRNAs with an approximate size of 2.6 kilobases.
Sequence and overexpression of the menD gene from Escherichia coli
Authors: Popp J L
Published: November 2016

The menD gene of Escherichia coli codes for the first enzyme of menaquinone biosynthesis, 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) synthase. DNA sequence analysis of menD shows an open reading frame encoding a 52-kilodalton protein. Possible promoter and ribosome binding sites are present. Insertion of the menD gene into a tac promoter expression vector leads to nearly a 100-fold increase in the level of SHCHC synthase activity upon induction with isopropyl-beta-D-thiogalactoside (IPTG). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]methionine-labeled proteins shows a 61-kilodalton protein produced upon induction of the menD-containing expression vector. This is the first reported sequence analysis of a men gene and the first significant amplification of any of the menaquinone biosynthetic enzymes.
Genetic characterization of the pnuC gene, which encodes a component of the nicotinamide mononucleotide transport system in Salmonella typhimurium
Authors: Zhu N , Olivera B M , Roth J R
Published: November 2016

The pnuC gene, which encodes a component of the nicotinamide mononucleotide transport system, has been mapped and oriented. The gene order of the pnuC region, which is at min 17 of the Salmonella chromosome, is nadA-pnuC-aroG-gal. Polarity tests, with pnuC::Mu d-lac operon fusions, reveal that the pnuC gene is the promoter distal gene in an operon with the nadA gene, which encodes the second enzyme of the pyridine biosynthetic pathway. The nadA pnuC operon is regulated by the NadI repressor. The pnuC gene also has its own promoter, since strains with a nadA::Tn10d(Tc) insertion still express the pnuC gene at a low, unregulated level.
Mutations in the glnG gene of Escherichia coli that result in increased activity of nitrogen regulator I
Authors: Weglenski P , Ninfa A J , Ueno-Nishio S , Magasanik B
Published: November 2016

Mutations in the glnG gene of Escherichia coli that result in increased activity of nitrogen regulator I (NRI), the product of glnG, were obtained by two different selection procedures. The mutant proteins were purified and characterized. The concentrations of mutant proteins needed to activate transcription at the glnAp2 promoter were three to four times lower than that of the wild-type NRI. The rate of phosphorylation of these proteins and the stability of mutant NRI phosphate were found to be similar to those of the wild-type NRI. In one of the mutants, the site of the mutation was localized in the DNA region specifying the central domain of NRI.