bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Analytics Tools for Sustainable Lifecycle Design: Current Status, Challenges, and Future Opportunities
Authors: Ramanujan Devarajan , Bernstein William Z. , Chandrasegaran Senthil K. , Ramani Karthik
Published: August 2017

The rapid rise in technologies for data collection has created an unmatched opportunity to advance the use of data-rich tools for lifecycle decision-making. However, the usefulness of these technologies is limited by the ability to translate lifecycle data into actionable insights for human decision-makers. This is especially true in the case of sustainable lifecycle design (SLD), as the assessment of environmental impacts, and the feasibility of making corresponding design changes, often relies on human expertise and intuition. Supporting human sensemaking in SLD requires the use of both data-driven and user-driven methods while exploring lifecycle data. A promising approach for combining the two is through the use of visual analytics (VA) tools. Such tools can leverage the ability of computer-based tools to gather, process, and summarize data along with the ability of human experts to guide analyses through domain knowledge or data-driven insight. In this paper, we review previous research that has created VA tools in SLD. We also highlight existing challenges and future opportunities for such tools in different lifecycle stages—design, manufacturing, distribution and supply chain, use-phase, end-of-life (EoL), as well as life cycle assessment (LCA). Our review shows that while the number of VA tools in SLD is relatively small, researchers are increasingly focusing on the subject matter. Our review also suggests that VA tools can address existing challenges in SLD and that significant future opportunities exist.
Nonlinear Analysis and Characteristic Variation of Self-Excited Vibration in the Vertical Rotor System Due to the Flexible Support of the Journal Bearing
Authors: Nishimura Atsushi , Inoue Tsuyoshi , Watanabe Yusuke
Published: August 2017

Various vibration problems occur in rotating machinery. Specifically, the large amplitude vibration may occur in the vertical pump using a journal bearing. In an actual vertical pump, the stator's structure supporting the pump shaft may be relatively flexible. In such a case, rotor's motion such as amplitude of the self-excited vibration is not able to be predicted accurately without considering the nonlinear fluid film force reacting in the relative motion between the shaft and the flexibly supported bearing stator. However, the vibration characteristics in such situations have not been explained theoretically so far. In this paper, the vibration characteristics of a vertical rotating shaft with journal bearing are investigated. The nonlinear steady-state vibration analysis of the self-excited vibration is demonstrated, and the influences of the parameters, such as fluid viscosity, radial clearance, and stiffness and damping coefficients of the flexible support of bearing stator, on the vibration characteristics of the system are explained. Moreover, these theoretical results of the self-excited vibration in the vertical rotating shaft with journal bearing are verified both numerically and experimentally.
Study on Wind-Induced Vibration Behavior of Railway Catenary in Spatial Stochastic Wind Field Based on Nonlinear Finite Element Procedure
Authors: Song Yang , Liu Zhigang , Duan Fuchuan , Lu Xiaobing , Wang Hongrui
Published: August 2017

Due to its long-span structure and large flexibility, an electrified railway catenary is very sensitive to environmental wind load, especially the time-varying stochastic wind, which may lead to a strong forced vibration of contact line and deteriorate the current collection quality of the pantograph–catenary system. In this paper, in order to study the wind-induced vibration behavior of railway catenary, a nonlinear finite element procedure is implemented to construct the model of catenary, which can properly describe the large nonlinear deformation and the nonsmooth nonlinearity of dropper. The spatial stochastic wind field is developed considering the fluctuating winds in along-wind, vertical-wind, and cross-wind directions. Using the empirical spectra suggested by Kaimal, Panofsky, and Tieleman, the fluctuating wind velocities in three directions are generated considering the temporal and spatial correlations. Based on fluid-induced vibration theory, the model of fluctuating forces acting on catenary are developed considering the spatial characteristics of catenary. The time- and frequency-domain analyses are conducted to study the wind-induced vibration behavior with different angles of wind deflection, different angles of attack, as well as different geometries of catenary. The effect of spatial wind load on contact force of pantograph–catenary system is also investigated.
Hysteresis of the Coanda Effect
Authors: Skotnicka-Siepsiak Aldona
Published: August 2017

For scientist, the Coanda effect has been an object of interest for a long time. All the time, some new applications of it are found although it has been more than a hundred years since Henri Coanda got a patent that was critical for that issue. Apart from aviation, it is more and more often used in ventilation systems to control the manner of air division and the design nozzles and ventilators. It is surprising, however, that a good command of that phenomenon and a need to apply it in different solutions did not entail a significant increase of the interest in the Coanda effect hysteresis, although it was mentioned for the first time by Newman in 1961. This article presents results of experimental measurements for a two-dimensional incompressible plane jet by an inclined plate. The hysteresis has been observed as a different jet behavior (a free jet or a jet attached to a flat plate) depending on the direction in which the plate deflection angle changes. The observed hysteresis area, defined by critical values for the αca attachment and αcd detachment angles, spanned from 8 deg to 14 deg. Its dependency on the Reynolds number has also been examined for Re ranging from 3500 to 26,500. Considering the Coanda effect hysteresis, a pressure distribution on the plate and the xR reattachment distance has been examined. The distribution of forces on a plate has been identified, which has facilitated a graphical mirroring of the Coanda effect hysteresis loop.
Warm Hydromechanical Deep Drawing of AA 5754-O and Optimization of
Process Parameters
Authors: Acar Doğan , Türköz Mevlüt , Gedikli Hasan , Halkacı Hüseyin Selçuk , Cora Ömer Necati
Published: August 2017

Warm hydromechanical deep drawing (WHDD) has increasingly been implemented by automotive industry due to its various benefits including mass reduction opportunities in auto body-in-white components and improved formability for lightweight alloys. In the first part of the current study, WHDD of AA 5754-O was studied. In order to obtain the highest formability, an optimization study was performed for AA 5754-O WHDD process parameters (tool temperature, hydraulic pressure (HP), and blank holder force (BHF) loading profiles) through finite element analysis (FEA) + experimentation approach. Results showed that the optimal temperature for punch is 25 °C and 300 °C for die and blank holder. In addition, HP was found to be more effective on formability when compared to BHF. Both fast increasing HP and blank holder loading profiles contributes to higher formability.
Design of Robust Double-Fuzzy-Summation Nonparallel Distributed Compensation Controller for Chaotic Power Systems
Authors: Vafamand Navid , Khooban Mohammad Hassan , Khayatian Alireza , Blabbjerg Frede
Published: August 2017

This paper studies a systematic linear matrix inequality (LMI) approach for controller design of nonlinear chaotic power systems. The presented method is based on a Takagi–Sugeno (TS) fuzzy model, a double-fuzzy-summation nonparallel distributed compensation (non-PDC) controller, and a double-fuzzy-summation nonquadratic Lyapunov function (NQLF). Since time derivatives of fuzzy membership functions (MFs) appear in the NQLF-based controller design conditions, local controller design criteria is considered, and sufficient conditions are formulated in terms of LMIs. Compared with the existing works in hand, the proposed LMI conditions provide less conservative results due to the special structure of the NQLF and the non-PDC controller in which two fuzzy summations are employed. To evaluate the effectiveness of the presented approach, two practical benchmark power systems, which exhibit chaotic behavior, are considered. Simulation results and hardware-in-the-loop illustrate the advantages of the proposed method compared with the recently published works.
An Experimental Validation of a New Method for Multimodel Identification
Authors: Messaoud Anis , Abdennour Ridha Ben
Published: August 2017

In this paper, we propose a new method for an optimal systematic determination of models' base for multimodel identification. This method is based on the neural classification of data set picked out on a considered nonlinear system. The obtained cluster centers are exploited to provide the weighting functions and to deduce the corresponding dispersions and their models' base. A simulation example and an experimental validation on a chemical reactor are presented to evaluate the effectiveness of the proposed method.
Impact of Dynamics on the Accuracies of Different Experimental Data-Processing Methods for Steady-State Heat Transfer Rate Measurement
Authors: Cheung Howard , Wang Shengwei
Published: August 2017

It is becoming often to measure steady-state heat transfer rate from thermal systems with variable speed and volume equipment and hence with fluctuating properties and mass flow rates. However, it is unclear if the conventional heat transfer rate measurement based on averages of temperature and pressure measurement is representative enough to represent the effect of system dynamics and measure their heat transfer rates accurately. This paper studied the issue by comparing its accuracy and uncertainty to that of alternative data-processing methods with theoretically less systematic bias. The comparison was conducted with steady-state data from a variable-speed ductless heat pump (DHP) system with occasional fluctuation of refrigerant flow and properties. The results show that the accuracy improvement brought by one alternative method is statistically significant albeit small in magnitude, and the other method may reduce uncertainty of the heat transfer rate measurement in tests with large periodic changes of measured variables. Nonetheless, both alternative methods are about 100 times more computationally expensive than the conventional averaging method, and averages of temperature and pressure measurement are still appropriate when computational resources are limited.
Synthesis and Singularity Analysis of N-UU Parallel Wrists: A Symmetric Space Approach
Authors: Wu Yuanqing , Carricato Marco
Published: August 2017

We report some recent advances in kinematics and singularity analysis of the mirror-symmetric N-UU parallel wrists using symmetric space theory. We show that both the finite displacement and infinitesimal singularity kinematics of a N-UU wrist are governed by the mirror symmetry property and half-angle property of the underlying motion manifold, which is a symmetric submanifold of the special Euclidean group SE(3). Our result is stronger than and may be considered a closure of Hunt's argument for instantaneous mirror symmetry in his pioneering exposition of constant velocity shaft couplings. Moreover, we show that the wrist can, to some extent, be treated as a spherical mechanism, even though dependent translation exists, and the singularity-free workspace of a N-UU wrist may be analytically derived. This leads to a straightforward optimal design for maximal singularity-free workspace.
Type Synthesis of Parallel Tracking Mechanism With Varied Axes by Modeling Its Finite Motions Algebraically
Authors: Qi Yang , Sun Tao , Song Yimin
Published: August 2017

Parallel tracking mechanism with varied axes has great potential in actuating antenna to track moving targets. Due to varied rotational axes, its finite motions have not been modeled algebraically. This makes its type synthesis remain a great challenge. Considering these issues, this paper proposes a conformal geometric algebra (CGA) based approach to model its finite motions in an algebraic manner and parametrically generate topological structures of available open-loop limbs. Finite motions of rigid body, articulated joints, and open-loop limbs are formulated by outer product of CGA. Then, finite motions of parallel tracking mechanism with varied axes are modeled algebraically by two independent rotations and four dependent motions with the assistance of kinematic analysis. Afterward, available four degrees-of-freedom (4-DoF) open-loop limbs are generated by using revolute joints to realize dependent motions, and available five degrees-of-freedom (5-DoF) open-loop limbs are obtained by adding one finite rotation to the generated open-loop limbs. Finally, assembly principles in terms of minimal number and combinations of available open-loop limbs are defined. Typical topological structures are synthesized and illustrated.
Biofunctionalized conductive polymers enable efficient CO
2
electroreduction
Authors: Coskun Halime , Aljabour Abdalaziz , De Luna Phil , Farka Dominik , Greunz Theresia , Stifter David , Kus Mahmut , Zheng Xueli , Liu Min , Hassel Achim W. , Schöfberger Wolfgang , Sargent Edward H. , Sariciftci Niyazi Serdar , Stadler Philipp
Published: August 2017

Conductive polydopamines represent bioinspired paradigm catalysts for efficiently recycling greenhouse gas CO
2
to synthetic fuel.
Recovery from the Middle East respiratory syndrome is associated with antibody and T cell responses
Authors: Zhao Jingxian , Alshukairi Abeer N. , Baharoon Salim A. , Ahmed Waleed A. , Bokhari Ahmad A. , Nehdi Atef M. , Layqah Laila A. , Alghamdi Mohammed G. , Al Gethamy Manal M. , Dada Ashraf M. , Khalid Imran , Boujelal Mohamad , Al Johani Sameera M. , Vogel Leatrice , Subbarao Kanta , Mangalam Ashutosh , Wu Chaorong , Ten Eyck Patrick , Perlman Stanley , Zhao Jincun
Published: August 2017

MERS-CoV T cell responses can be detected in MERS survivors in the absence of detectable virus-specific antibody.
A Fatty Acyl Coenzyme A Reductase Promotes Wax Ester Accumulation in Rhodococcus jostii RHA1
Authors: Round James , Roccor Raphael , Li Shu-Nan , Eltis Lindsay D.
Published: August 2017

Many rhodococci are oleaginous and, as such, have considerable potential for the sustainable production of lipid-based commodity chemicals. Herein, we demonstrated that
Rhodococcus jostii
RHA1, a soil bacterium that catabolizes a wide range of organic compounds, produced wax esters (WEs) up to 0.0002% of its cellular dry weight during exponential growth on glucose. These WEs were fully saturated and contained primarily 31 to 34 carbon atoms. Moreover, they were present at higher levels during exponential growth than under lipid-accumulating conditions. Bioinformatics analyses revealed that RHA1 contains a gene encoding a putative fatty acyl coenzyme A (acyl-CoA) reductase (FcrA). The purified enzyme catalyzed the NADPH-dependent transformation of stearoyl-CoA to stearyl alcohol with a specific activity of 45 ± 3 nmol/mg · min and dodecanal to dodecanol with a specific activity of 5,300 ± 300 nmol/mg · min. Deletion of
fcrA
did not affect WE accumulation when grown in either carbon- or nitrogen-limited medium. However, the Δ
fcrA
mutant accumulated less than 20% of the amount of WEs as the wild-type strain under conditions of nitric oxide stress. A strain of RHA1 overproducing FcrA accumulated WEs to ∼13% cellular dry weight under lipid-accumulating conditions, and their acyl moieties had longer average chain lengths than those in wild-type cells (C
17
versus C
16
). The results provide insight into the biosynthesis of WEs in rhodococci and facilitate the development of this genus for the production of high-value neutral lipids.

IMPORTANCE
Among the best-studied oleaginous bacteria, rhodococci have considerable potential for the sustainable production of lipid-based commodity chemicals, such as wax esters. However, many aspects of lipid synthesis in these bacteria are poorly understood. The current study identifies a key enzyme in wax ester synthesis in rhodococci and exploits it to significantly improve the yield of wax esters in bacteria. In so doing, this work contributes to the development of novel bioprocesses for an important class of oleochemicals that may ultimately allow us to phase out their unsustainable production from sources such as petroleum and palm oil.
Veillonella Catalase Protects the Growth of Fusobacterium nucleatum in Microaerophilic and Streptococcus gordonii-Resident Environments
Authors: Zhou Peng , Li Xiaoli , Huang I-Hsiu , Qi Fengxia
Published: August 2017

The oral biofilm is a multispecies community in which antagonism and mutualism coexist among friends and foes to keep an ecological balance of community members. The pioneer colonizers, such asStreptococcus gordonii, produce H2O2to inhibit the growth of competitors, like the mutans streptococci, as well as strict anaerobic middle and later colonizers of the dental biofilm. Interestingly,Veillonellaspecies, as early colonizers, physically interact (coaggregate) withS. gordonii. A putative catalase gene (catA) is found in most sequencedVeillonellaspecies; however, the function of this gene is unknown. In this study, we characterized the ecological function ofcatAfromVeillonella parvulaPK1910 by integrating it into the only transformable strain,Veillonella atypicaOK5, which iscatAnegative. The strain (OK5-catA) became more resistant to H2O2. Further studies demonstrated that thecatAgene expression is induced by the addition of H2O2or coculture withS. gordonii. Mixed-culture experiments further revealed that the transgenic OK5-catAstrain not only enhanced the growth ofFusobacterium nucleatum, a strict anaerobic periodontopathogen, under microaerophilic conditions, but it also rescuedF. nucleatumfrom killing byS. gordonii. A potential role of catalase in veillonellae in biofilm ecology and pathogenesis is discussed here.

IMPORTANCEVeillonellaspecies, as early colonizers, can coaggregate with many bacteria, including the initial colonizerStreptococcus gordoniiand periodontal pathogenFusobacterium nucleatum, during various stages of oral biofilm formation. In addition to providing binding sites for many microbes, our previous study also showed thatVeillonellaproduces nutrients for the survival and growth of periodontal pathogens. These findings indicate thatVeillonellaplays an important “bridging” role in the development of oral biofilms and the ecology of the human oral cavity. In this study, we demonstrated that the reducing activity ofVeillonellacan rescue the growth ofFusobacterium nucleatumnot only under microaerophilic conditions, but also in an environment in whichStreptococcus gordoniiis present. Thus, this study will provide a new insight for future studies on the mechanisms of human oral biofilm formation and the control of periodontal diseases.
A Novel Regulatory Pathway for K
+
Uptake in the Legume Symbiont Azorhizobium caulinodans in Which TrkJ Represses the
kdpFABC
Operon at High Extracellular K
+
Concentrations
Authors: Siarot Lowela , Toyazaki Hiroki , Hidaka Makoto , Kurumisawa Keigo , Hirakawa Tomoki , Morohashi Kengo , Aono Toshihiro
Published: August 2017

Bacteria have multiple K
+
uptake systems.
Escherichia coli
, for example, has three types of K
+
uptake systems, which include the low-K
+
-inducible KdpFABC system and two constitutive systems, Trk (TrkAG and TrkAH) and Kup.
Azorhizobium caulinodans
ORS571, a rhizobium that forms nitrogen-fixing nodules on the stems and roots of
Sesbania rostrata
, also has three types of K
+
uptake systems. Through phylogenetic analysis, we found that
A. caulinodans
has two genes homologous to
trkG
and
trkH
, designated
trkI
and
trkJ
. We also found that
trkI
is adjacent to
trkA
in the genome and these two genes are transcribed as an operon; however,
trkJ
is present at a distinct locus. Our results demonstrated that
trkAI
,
trkJ
, and
kup
were expressed in the wild-type stem nodules, whereas
kdpFABC
was not. Interestingly, Δ
kup
and Δ
kup
Δ
kdpA
mutants formed Fix
–
nodules, while the Δ
kup
Δ
trkA
Δ
trkI
Δ
trkJ
mutant formed Fix
+
nodules, suggesting that with the additional deletion of Trk system genes in the Δ
kup
mutant, Fix
+
nodule phenotypes were recovered.
kdpFABC
of the Δ
kup
Δ
trkJ
mutant was expressed in stem nodules, but not in the free-living state, under high-K
+
conditions. However,
kdpFABC
of the Δ
kup
Δ
trkA
Δ
trkI
Δ
trkJ
mutant was highly expressed even under high-K
+
conditions. The cytoplasmic K
+
levels in the Δ
kup
Δ
trkA
Δ
trkI
mutant, which did not express
kdpFABC
under high-K
+
conditions, were markedly lower than those in the Δ
kup
Δ
trkA
Δ
trkI
Δ
trkJ
mutant. Taking all these results into consideration, we propose that TrkJ is involved in the repression of
kdpFABC
in response to high external K
+
concentrations and that the TrkAI system is unable to function in stem nodules.

IMPORTANCE
K
+
is a major cytoplasmic cation in prokaryotic and eukaryotic cells. Bacteria have multiple K
+
uptake systems to control the cytoplasmic K
+
levels. In many bacteria, the K
+
uptake system KdpFABC is expressed under low-K
+
conditions. For years, many researchers have argued over how bacteria sense K
+
concentrations. Although KdpD of
Escherichia coli
is known to sense both cytoplasmic and extracellular K
+
concentrations, the detailed mechanism of K
+
sensing is still unclear. In this study, we propose that the transmembrane TrkJ protein of
Azorhizobium caulinodans
acts as a sensor for the extracellular K
+
concentration and that high extracellular K
+
concentrations repress the expression of KdpFABC via TrkJ.
Environmental Selection, Dispersal, and Organism Interactions Shape Community Assembly in High-Throughput Enrichment Culturing
Authors: Justice N. B. , Sczesnak A. , Hazen T. C. , Arkin A. P.
Published: August 2017

A central goal of microbial ecology is to identify and quantify the forces that lead to observed population distributions and dynamics. However, these forces, which include environmental selection, dispersal, and organism interactions, are often difficult to assess in natural environments. Here, we present a method that links microbial community structures with selective and stochastic forces through highly replicated subsampling and enrichment of a single environmental inoculum. Specifically, groundwater from a well-studied natural aquifer was serially diluted and inoculated into nearly 1,000 aerobic and anaerobic nitrate-reducing cultures, and the final community structures were evaluated with 16S rRNA gene amplicon sequencing. We analyzed the frequency and abundance of individual operational taxonomic units (OTUs) to understand how probabilistic immigration, relative fitness differences, environmental factors, and organismal interactions contributed to divergent distributions of community structures. We further used a most probable number (MPN) method to estimate the natural condition-dependent cultivable abundance of each of the nearly 400 OTU cultivated in our study and infer the relative fitness of each. Additionally, we infer condition-specific organism interactions and discuss how this high-replicate culturing approach is essential in dissecting the interplay between overlapping ecological forces and taxon-specific attributes that underpin microbial community assembly.

IMPORTANCE
Through highly replicated culturing, in which inocula are subsampled from a single environmental sample, we empirically determine how selective forces, interspecific interactions, relative fitness, and probabilistic dispersal shape bacterial communities. These methods offer a novel approach to untangle not only interspecific interactions but also taxon-specific fitness differences that manifest across different cultivation conditions and lead to the selection and enrichment of specific organisms. Additionally, we provide a method for estimating the number of cultivable units of each OTU in the original sample through the MPN approach.
A Commensal Bifidobacterium longum Strain Prevents Gluten-Related Immunopathology in Mice through Expression of a Serine Protease Inhibitor
Authors: McCarville J. L. , Dong J. , Caminero A. , Bermudez-Brito M. , Jury J. , Murray J. A. , Duboux S. , Steinmann M. , Delley M. , Tangyu M. , Langella P. , Mercenier A. , Bergonzelli G. , Verdu E. F.
Published: August 2017

Microbiota-modulating strategies, including probiotic administration, have been tested for the treatment of chronic gastrointestinal diseases despite limited information regarding their mechanisms of action. We previously demonstrated that patients with active celiac disease have decreased duodenal expression of elafin, a human serine protease inhibitor, and supplementation of elafin by a recombinant
Lactococcus lactis
strain prevents gliadin-induced immunopathology in the NOD/DQ8 mouse model of gluten sensitivity. The commensal probiotic strain
Bifidobacterium longum
NCC2705 produces a serine protease inhibitor (Srp) that exhibits immune-modulating properties. Here, we demonstrate that
B. longum
NCC2705, but not a
srp
knockout mutant, attenuates gliadin-induced immunopathology and impacts intestinal microbial composition in NOD/DQ8 mice. Our results highlight the beneficial effects of a serine protease inhibitor produced by commensal
B. longum
strains.

IMPORTANCE
Probiotic therapies have been widely used to treat gastrointestinal disorders with variable success and poor mechanistic insight. Delivery of specific anti-inflammatory molecules has been limited to the use of genetically modified organisms, which has raised some public and regulatory concerns. By examining a specific microbial product naturally expressed by a commensal bacterial strain, we provide insight into a mechanistic basis for the use of
B. longum
NCC2705 to help treat gluten-related disorders.
Indole Biodegradation in Acinetobacter sp. Strain O153: Genetic and Biochemical Characterization
Authors: Sadauskas Mikas , Vaitekūnas Justas , Gasparavičiūtė Renata , Meškys Rolandas
Published: August 2017

Indole is a molecule of considerable biochemical significance, acting as both an interspecies signal molecule and a building block of biological elements. Bacterial indole degradation has been demonstrated for a number of cases; however, very little is known about genes and proteins involved in this process. This study reports the cloning and initial functional characterization of genes (
iif
and
ant
cluster) responsible for indole biodegradation in
Acinetobacter
sp. strain O153. The catabolic cascade was reconstituted
in vitro
with recombinant proteins, and each protein was assigned an enzymatic function. Degradation starts with oxidation, mediated by the IifC and IifD flavin-dependent two-component oxygenase system. Formation of indigo is prevented by IifB, and the final product, anthranilic acid, is formed by IifA, an enzyme which is both structurally and functionally comparable to cofactor-independent oxygenases. Moreover, the
iif
cluster was identified in the genomes of a wide range of bacteria, suggesting the potential of widespread Iif-mediated indole degradation. This work provides novel insights into the genetic background of microbial indole biodegradation.

IMPORTANCE
The key finding of this research is identification of the genes responsible for microbial biodegradation of indole, a toxic
N
-heterocyclic compound. A large amount of indole is present in urban wastewater and sewage sludge, creating a demand for an efficient and eco-friendly means to eliminate this pollutant. A common strategy of oxidizing indole to indigo has the major drawback of producing insoluble material. Genes and proteins of
Acinetobacter
sp. strain O153 (DSM 103907) reported here pave the way for effective and indigo-free indole removal. In addition, this work suggests possible novel means of indole-mediated bacterial interactions and provides the basis for future research on indole metabolism.
Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery
Authors: Abdullah Hairil Rizal , Lien Victoria Peixin , Ong Hwee Kuan , Er Pei Ling , Hao Ying , Khan Shariq Ali , Liu Christopher Weiyang
Published: August 2017

Introduction

Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions—physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care.

Methods and analysis

This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission.

Ethics and dissemination

This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number:NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository.

Trial registration number

NCT02921932 (ClinicalTrials.gov)
Use of four asymmetric marks to orient the donor graft during Descemet's membrane endothelial keratoplasty
Authors: Matsuzawa Akiko , Hayashi Takahiko , Oyakawa Itaru , Yuda Kentaro , Shimizu Toshiki , Mizuki Nobuhisa , Yamada Norihiro , Kato Naoko
Published: August 2017

Introduction

Maintaining the correct orientation of the donor graft is important during Descemet's membrane endothelial keratoplasty (DMEK). We describe a new method of marking the donor graft prior to DMEK.

Methods

Twelve eyes of 10 patients with bullous keratopathy who underwent DMEK were retrospectively analysed. Donor discs were created by stripping the endothelium–Descemet's membrane layer from corneoscleral buttons. Four semicircular marks, two 1.0 mm and two 1.5 mm in diameter, were created at the edge of the donor disc. The small and large marks were paired. Each donor graft was inserted into the anterior chamber, unfolded and attached to the posterior corneal stroma with an air bubble.

Results

The inserted grafts were all appropriately orientated when attached to the back surfaces of the corneas. The two pairs of asymmetric marks afforded valuable guidance. Even when the graft was partially folded or decentred, and one pair of marks was obscured, the other pair was always visible to indicate graft orientation. Best spectacle-corrected visual acuity improved significantly in all patients (p<0.001). Compared with the preoperative endothelial cell density of the donor graft, that of the corneal endothelium had decreased 44.0%±10.0% by 6 months after surgery.

Conclusions

Two pairs of asymmetrical semicircular marks placed on the edge of the donor graft allowed appropriate graft orientation during DMEK.
The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers
Authors: Rowbotham Nicola J , Smith Sherie , Leighton Paul A , Rayner Oli C , Gathercole Katie , Elliott Zoe C , Nash Edward F , Daniels Tracey , Duff Alistair J A , Collins Sarah , Chandran Suja , Peaple Ursula , Hurley Matthew N , Brownlee Keith , Smyth Alan R
Published: August 2017

There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on 10 research priorities which will be attractive to funders.
Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke
Authors: Stephens William E
Published: August 2017

Background

Quantifying relative harm caused by inhaling the aerosol emissions of vapourised nicotine products compared with smoking combustible tobacco is an important issue for public health.

Methods

The cancer potencies of various nicotine-delivering aerosols are modelled using published chemical analyses of emissions and their associated inhalation unit risks. Potencies are compared using a conversion procedure for expressing smoke and e-cigarette vapours in common units. Lifetime cancer risks are calculated from potencies using daily consumption estimates.

Results

The aerosols form a spectrum of cancer potencies spanning five orders of magnitude from uncontaminated air to tobacco smoke. E-cigarette emissions span most of this range with the preponderance of products having potencies<1% of tobacco smoke and falling within two orders of magnitude of a medicinal nicotine inhaler; however, a small minority have much higher potencies. These high-risk results tend to be associated with high levels of carbonyls generated when excessive power is delivered to the atomiser coil. Samples of a prototype heat-not-burn device have lower cancer potencies than tobacco smoke by at least one order of magnitude, but higher potencies than most e-cigarettes. Mean lifetime risks decline in the sequence: combustible cigarettes >> heat-not-burn >> e-cigarettes (normal power)≥nicotine inhaler.

Conclusions

Optimal combinations of device settings, liquid formulation and vaping behaviour normally result in e-cigarette emissions with much less carcinogenic potency than tobacco smoke, notwithstanding there are circumstances in which the cancer risks of e-cigarette emissions can escalate, sometimes substantially. These circumstances are usually avoidable when the causes are known.
Targeting RNA-Polymerase I in Both Chemosensitive and Chemoresistant Populations in Epithelial Ovarian Cancer
Authors: Cornelison Robert , Dobbin Zachary C. , Katre Ashwini A. , Jeong Dae Hoon , Zhang Yinfeng , Chen Dongquan , Petrova Yuliya , Llaneza Danielle C. , Steg Adam D. , Parsons Laura , Schneider David A. , Landen Charles N.
Published: August 2017

Purpose: A hallmark of neoplasia is increased ribosome biogenesis, and targeting this process with RNA polymerase I (Pol I) inhibitors has shown some efficacy. We examined the contribution and potential targeting of ribosomal machinery in chemotherapy-resistant and -sensitive models of ovarian cancer.

Experimental Design: Pol I machinery expression was examined, and subsequently targeted with the Pol I inhibitor CX-5461, in ovarian cancer cell lines, an immortalized surface epithelial line, and patient-derived xenograft (PDX) models with and without chemotherapy. Effects on viability, Pol I occupancy of rDNA, ribosomal content, and chemosensitivity were examined.

Results: In PDX models, ribosomal machinery components were increased in chemotherapy-treated tumors compared with controls. Thirteen cell lines were sensitive to CX-5461, with IC50s 25 nmol/L–2 μmol/L. Interestingly, two chemoresistant lines were 10.5- and 5.5-fold more sensitive than parental lines. CX-5461 induced DNA damage checkpoint activation and G2–M arrest with increased γH2AX staining. Chemoresistant cells had 2- to 4-fold increased rDNA Pol I occupancy and increased rRNA synthesis, despite having slower proliferation rates, whereas ribosome abundance and translational efficiency were not impaired. In five PDX models treated with CX-5461, one showed a complete response, one a 55% reduction in tumor volume, and one maintained stable disease for 45 days.

Conclusions: Pol I inhibition with CX-5461 shows high activity in ovarian cancer cell lines and PDX models, with an enhanced effect on chemoresistant cells. Effects occur independent of proliferation rates or dormancy. This represents a novel therapeutic approach that may have preferential activity in chemoresistant populations. Clin Cancer Res; 23(21); 6529–40. ©2017 AACR.
Using Antigen-Specific B Cells to Combine Antibody and T Cell–Based Cancer Immunotherapy
Authors: Wennhold Kerstin , Thelen Martin , Schlößer Hans Anton , Haustein Natalie , Reuter Sabrina , Garcia-Marquez Maria , Lechner Axel , Kobold Sebastian , Rataj Felicitas , Utermöhlen Olaf , Chakupurakal Geothy , Theurich Sebastian , Hallek Michael , Abken Hinrich , Shimabukuro-Vornhagen Alexander , von Bergwelt-Baildon Michael
Published: August 2017

Cancer immunotherapy by therapeutic activation of T cells has demonstrated clinical potential. Approaches include checkpoint inhibitors and chimeric antigen receptor T cells. Here, we report the development of an alternative strategy for cellular immunotherapy that combines induction of a tumor-directed T-cell response and antibody secretion without the need for genetic engineering. CD40 ligand stimulation of murine tumor antigen-specific B cells, isolated by antigen-biotin tetramers, resulted in the development of an antigen-presenting phenotype and the induction of a tumor antigen-specific T-cell response. Differentiation of antigen-specific B cells into antibody-secreting plasma cells was achieved by stimulation with IL21, IL4, anti-CD40, and the specific antigen. Combined treatment of tumor-bearing mice with antigen-specific CD40-activated B cells and antigen-specific plasma cells induced a therapeutic antitumor immune response resulting in remission of established tumors. Human CEA or NY-ESO-1–specific B cells were detected in tumor-draining lymph nodes and were able to induce antigen-specific T-cell responses in vitro, indicating that this approach could be translated into clinical applications. Our results describe a technique for the exploitation of B-cell effector functions and provide the rationale for their use in combinatorial cancer immunotherapy. Cancer Immunol Res; 5(9); 730–43. ©2017 AACR.
Effect of Disclosing Genetic Risk for Coronary Heart Disease on Information Seeking and Sharing
Authors: Brown Sherry-Ann N. , Jouni Hayan , Marroush Tariq S. , Kullo Iftikhar J.
Published: August 2017

Background—

Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. We hypothesized that disclosing genetic risk for CHD to individuals influences information seeking and sharing.

Methods and Results—

The MI-GENES study (Myocardial Infarction Genes) randomized participants (n=203) aged 45 to 65 years who were at intermediate CHD risk based on conventional risk factors and not on statins to receive their conventional risk score alone or also a genetic risk score based on 28 variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys assessing information seeking were completed before and after risk disclosure. Information sharing was assessed post-disclosure. Six-month post-disclosure, genetic risk score participants were more likely than conventional risk score participants to visit a website to learn about CHD (odds ratio [OR], 4.88 [confidence interval (CI), 1.55–19.13];
P
=0.01), use the internet for information about how genetic factors affect CHD risk (OR, 2.11 [CI, 1.03–4.47];
P
=0.04), access their CHD risk via a patient portal (OR, 2.99 [CI, 1.35–7.04];
P
=0.01), and discuss their CHD risk with others (OR, 3.13 [CI, 1.41–7.47];
P
=0.01), particularly their siblings (OR, 1.92 [CI, 1.06–3.51];
P
=0.03), extended family (OR, 3.8 [CI, 1.37–12.38];
P=
0.01), coworkers (OR, 2.42 [CI, 1.09–5.76];
P
=0.03), and primary care provider (PCP; OR, 2.00 [CI, 1.08–3.75];
P
=0.03).

Conclusions—

Disclosure of a genetic risk score for CHD increased information seeking and sharing.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov/
. Unique identifier: NCT01936675.
Carotid Plaque Rupture Is Accompanied by an Increase in the Ratio of Serum circR-284 to miR-221 Levels
Authors: Bazan Hernan A. , Hatfield Samuel A. , Brug Aaron , Brooks Ashton J. , Lightell Daniel J. , Woods T. Cooper
Published: August 2017

Background—

Atherosclerotic plaque rupture is accompanied by an acute decrease in the carotid plaque expression of micro-RNAs (miRs)-221 and miR-222. Circular RNA (circR)-284 is a potential inhibitor of miR-221/miR-222 activity. We aimed to determine whether changes in the serum levels of these noncoding RNAs are observed in patients with asymptomatic high-grade carotid disease versus patients with acutely symptomatic carotid disease and recent ischemic stroke. Additionally, we tested the use of functionally related noncoding RNA pairs to enhance the discriminatory power of noncoding RNAs as circulating biomarkers.

Methods and Results—

Serum levels of miR-221, miR-222, miR-145, and circR-284 were measured in 24 asymptomatic (asymptomatic) and 17 acutely symptomatic patients ([urgent] ischemic cerebrovascular event within the previous 5 days) undergoing carotid endarterectomy. miR-221 was significantly lower, whereas circR-284 was elevated in the serum of the urgent compared with the asymptomatic group. The ratio of serum circR-284:miR-221 was significantly elevated in the urgent group (
P
=0.0002) and exhibited favorable characteristics as a biomarker indicative of carotid plaque rupture and stroke. A validation study in 112 patients (47 asymptomatic, 41 urgent, and 24 patients with a cerebrovascular event between 5 and 180 days of the carotid endarterectomy [symptomatic]) confirmed elevation of serum circR-284:miR-221 uniquely in the urgent group (
P
<0.001) and favorable sensitivity and specificity for detecting plaque rupture and stroke.

Conclusions—

Serum circR-284:miR-221 has potential as a diagnostic biomarker of carotid plaque rupture and stroke. Moreover, we demonstrate the use of functionally related pairs of circulating noncoding RNAs as biomarkers in cardiovascular disease.
Experimental Modeling Supports a Role for MyBP-HL as a Novel Myofilament Component in Arrhythmia and Dilated Cardiomyopathy
Authors: Barefield David Y. , Puckelwartz Megan J. , Kim Ellis Y. , Wilsbacher Lisa D. , Vo Andy H. , Waters Emily A. , Earley Judy U. , Hadhazy Michele , Dellefave-Castillo Lisa , Pesce Lorenzo L. , McNally Elizabeth M.
Published: August 2017

Background:

Cardiomyopathy and arrhythmias are under significant genetic influence. Here, we studied a family with dilated cardiomyopathy and associated conduction system disease in whom prior clinical cardiac gene panel testing was unrevealing.

Methods:

Whole-genome sequencing and induced pluripotent stem cells were used to examine a family with dilated cardiomyopathy and atrial and ventricular arrhythmias. We also characterized a mouse model with heterozygous and homozygous deletion of
Mybphl
.

Results:

Whole-genome sequencing identified a premature stop codon, R255X, in the
MYBPHL
gene encoding MyBP-HL (myosin-binding protein-H like), a novel member of the myosin-binding protein family.
MYBPHL
was found to have high atrial expression with low ventricular expression. We determined that MyBP-HL protein was myofilament associated in the atria, and truncated MyBP-HL protein failed to incorporate into the myofilament. Human cell modeling demonstrated reduced expression from the mutant
MYBPHL
allele. Echocardiography of
Mybphl
heterozygous and null mouse hearts exhibited a 36% reduction in fractional shortening and an increased diastolic ventricular chamber size. Atria weight normalized to total heart weight was significantly increased in
Mybphl
heterozygous and null mice. Using a reporter system, we detected robust expression of
Mybphl
in the atria, and in discrete puncta throughout the right ventricular wall and septum, as well. Telemetric electrocardiogram recordings in
Mybphl
mice revealed cardiac conduction system abnormalities with aberrant atrioventricular conduction and an increased rate of arrhythmia in heterozygous and null mice.

Conclusions:

The findings of reduced ventricular function and conduction system defects in
Mybphl
mice support that
MYBPHL
truncations may increase risk for human arrhythmias and cardiomyopathy.
Subclinical Atrial Fibrillation in Older Patients
Authors: Healey Jeff S. , Alings Marco , Ha Andrew , Leong-Sit Peter , Birnie David H. , de Graaf Jacob J. , Freericks Michel , Verma Atul , Wang Jia , Leong Darryl , Dokainish Hisham , Philippon Francois , Barake Walid , McIntyre William F. , Simek Kim , Hill Michael D. , Mehta Shamir R. , Carlson Mark , Smeele Frank , Pandey A. Shekhar , Connolly Stuart J.
Published: August 2017

Background:

Long-term continuous electrocardiographic monitoring shows a substantial prevalence of asymptomatic, subclinical atrial fibrillation (SCAF) in patients with pacemakers and patients with cryptogenic stroke. Whether SCAF is also common in other patients without these conditions is unknown.

Methods:

We implanted subcutaneous electrocardiographic monitors (St. Jude CONFIRM-AF) in patients ≥65 years of age attending cardiovascular or neurology outpatient clinics if they had no history of atrial fibrillation but had any of the following: CHA
2
DS
2
-VASc score of ≥2, sleep apnea, or body mass index >30 kg/m
2
. Eligibility also required either left atrial enlargement (≥4.4 cm or volume ≥58 mL) or increased (≥290 pg/mL) serum NT-proBNP (N-terminal pro–B-type natriuretic peptide). Patients were monitored for SCAF lasting ≥5 minutes.

Results:

Two hundred fifty-six patients were followed up for 16.3±3.8 months. Baseline age was 74±6 years; mean CHA
2
DS
2
-VASc score was 4.1±1.4; left atrial diameter averaged 4.7±0.8 cm; and 48% had a prior stroke, transient ischemic attack, or systemic embolism. SCAF ≥5 minutes was detected in 90 patients (detection rate, 34.4%/y; 95% confidence interval [CI], 27.7–42.3). Baseline predictors of SCAF were increased age (hazard ratio [HR] per decade, 1.55; 95% CI, 1.11–2.15), left atrial dimension (HR per centimeter diameter, 1.43; 95% CI, 1.09–1.86), and blood pressure (HR per 10 mm Hg, 0.87; 95% CI, 0.78–0.98), but not prior stroke. The rate of occurrence of SCAF in those with a history of stroke, systemic embolism, or transient ischemic attack was 39.4%/y versus 30.3%/y without (
P
=0.32). The cumulative SCAF detection rate was higher (51.9%/y) in those with left atrial volume above the median value of 73.5 mL.

Conclusions:

SCAF is frequently detected by continuous electrocardiographic monitoring in older patients without a history of atrial fibrillation who are attending outpatient cardiology and neurology clinics. Its clinical significance is unclear.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01694394.