bluuebunny/crossref_metadata_2025 huggingface dataset:
Composition–controlled Synthesis of PtCuNPs Shells on Copper Nanowires as Electrocatalysts
Authors: Cheng Daojian , Wu Dengfeng , Xu Haoxiang , Fisher Adrian
Published: September 2016

PtCuNPs‐shells with adjustable composition on copper nanowires (CuNWs) are synthesized in an organic solvent. Transmission electron microscopy, X‐ray diffraction, energy dispersive spectroscopy, and X‐ray photoelectron spectroscopy (XPS) measurement techniques are used to analyze the structure and surface composition of the as‐prepared PtCuNPs‐coated CuNWs (PtCu/CuNWs). The XPS results verify that the incorporation of Cu in the PtCuNPs‐shells modified electronic state of Pt, which could further tune the formic acid oxidation (FAO) activity. Electrochemical measurements show that their FAO activities are strongly dependent on the PtCuNPs‐shells composition. Our results show that PtCu/CuNWs with atom Pt:Cu ratio of 2:15 (PtCu/CuNWs‐(2:15)) have the optimal shell composition and show the best FAO performance, with a specific activity of 0.92 mA cmPt−2 and a mass activity of 0.54 A mgpt−1 at 0.5 V (vs. RHE), which are 6.6‐ and 6.0‐fold enhancements over those of the commercial Pt/C (0.14 mA cmPt−2 and 0.09 A mgpt−1) catalyst.
Pd‐Catalyzed Reductive Carbonylation‐Ring Closure of Aryl Halides: A Direct Approach for Synthesis of Benzimidazoles
Authors: Etemadi‐Davan Elham , Iranpoor Nasser , Khalili Dariush
Published: September 2016

A novel protocol is reported for the facile one‐pot benzimidazole derivatives formation from Pd‐catalyzed reaction of aryl halides (X=I, Br, ‐Cl), Fe(CO)5, and o‐diaminobenzene or o‐nitroaniline. Aryl halides are first converted to aryl aldehydes using Fe(CO)5 which then undergo ring closure with o‐diaminobenzene or o‐nitroaniline in DMF at 110 °C under Ar. In the case of o‐nitroaniline, the reduction of the nitro group takes place before the cyclization step in the presence of reducing agents such as Fe(CO)5, released CO, Pd(0) and also P(III) in the reaction mixture. There is no need for employing P(III) ligand in case of aryl iodides while P(III) ligand is necessary for aryl bromides and chlorides to facilitate the reaction. In this reaction, Fe(CO)5 is not only responsible as the CO source and reduction of ‐NO2 functionality in o‐nitroaniline, but also produces iron oxides residue in the reaction which are responsible for the dehydrogenation step.
Syntheses, Crystal Structure, Luminescence, Porosity and Magnetic Properties of Three‐Dimensional Lanthanide Coordination Polymers with 2‐Aminoterepthalic Acid
Authors: Kariem Mukaddus , Yawer Mohd , Sharma Swati , Sheikh Haq N.
Published: September 2016

Ten isomorphous coordination polymers (CPs) with the formula [Ln2(ATPA)3(DEF)2]n Ln=Ce (1), Pr(2), Nd (3), Eu (5), Gd (6) and [Ln(ATPA)1.5(DEF)]n Ln=Sm (4), Tb (7), Dy (8), Ho (9) and Y(10) (H2ATPA=2‐aminoterepthalic acid and DEF=diethyl formamide) have been synthesized by the self assembly of Ln(III) ions, 2‐aminoterepthalate and DEF under solvothermal condition. These polymers have been systematically characterized by single‐crystal X‐ray diffraction, FTIR, PXRD, thermogravimetric (TGA) and elemental analyses. Structure analyses of CPs 1–10 reveal that all CPs crystallize in the monoclinic space group C2/c system and form 3D framework with difference in coordination numbers. The CPs 1 & 2 exhibit eight coordination numbers whereas CPs 3–10 show seven coordination number with different geometries. TGA indicate thermal stability and robustness of the synthesized CPs. The Sm (4), Eu (5), Tb (7) and Dy (8) polymers emit strong ligand sensitized characteristic f‐f luminescence. Analyses of magnetic susceptibility data of CPs 4, 6, 7 & 8 at variable temperatures and applied magnetic fields reveal weak ferromagnetic interactions at low temperatures.
Biodegradable Dendronized Polymers for Efficient mRNA Delivery
Authors: Oldenhuis Nathan J. , Eldredge Alexander C. , Burts Alan O. , Ryu Keun Ah , Chung Jae , Johnson Mark E. , Guan Zhibin
Published: September 2016

As chemically modified messenger RNAs become less immunogenic and more stable against RNases, the need for synthetic vectors that can efficiently deliver mRNA into cells has increased significantly. Based on a dendronized polypeptide (denpol) architecture, we describe here the development of a synthetic vector system for efficient delivery of mRNAs. The optimized denpols show high efficiency of mRNA delivery to a variety of cells including primary murine dendritic cells (BMDCs), giving it potential use for anti‐tumor immunotherapy.
Intracellular Transport Studies of Picolinate Macrocyclic Copper and Lanthanide Complexes
Authors: Porqueras Diego Santo Domingo , Beyler Maryline , Tripier Raphaël , Salerno Milena
Published: September 2016

In vivo molecular imaging involves different techniques to image cellular biochemical processes. Metal complexes can be used as cell‐permeable medical imaging agents. In this work we studied the cytotoxicity and the cellular incorporation kinetics of two recently synthesized picolinate macrocyclic complexes, [Eu(do2pa)]+ and [Cu(te1pa)]+. Both complexes are able to enter inside the cells. The intracellular concentration (Ci) of [Eu(do2pa)]+ is ∼5 times the extracellular concentration (Ce). In the case of [Cu(te1pa)]+, the ratio Ci/Ce is approximately 1.4. Furthermore, the results suggest that these complexes are not substrates of P‐gp, an efflux transport protein involved in the mechanisms of multidrug resistance in cancer cells and in the low permeability of blood‐brain barrier. The results obtained here, added to their physicochemical properties, let us propose that the complexes studied could be suitable platforms for the synthesis of cell‐permeable MRI contrast agents or PET tracers.
The Impact of the ‘Austrian’ Mutation of the Amyloid Precursor Protein Transmembrane Helix is Communicated to the Hinge Region
Authors: Stelzer Walter , Scharnagl Christina , Leurs Ulrike , Rand Kasper D. , Langosch Dieter
Published: September 2016

The transmembrane helix of the amyloid precursor protein is subject to proteolytic cleavages by γ‐secretase at different sites resulting in Aβ peptides of different length and toxicity. A number of point mutations within this transmembrane helix alter the cleavage pattern thus enhancing production of toxic Aβ peptide species that are at the root of familial Alzheimer's disease. Here, we investigated how one of the most devastating mutations, the ‘Austrian’ mutation T43I, affects this transmembrane helix. Site‐resolved deuterium/hydrogen amide exchange experiments reveal that the mutation destabilizes amide hydrogen bonds in the hinge which connects dimerization and cleavage regions. Weaker intrahelical hydrogen bonds at the hinge may enhance helix bending and thereby affect recognition of the transmembrane substrate by the enzyme and/or presentation of its cleavage sites to the catalytic cleft.
A computational methodology to calculate the required power in disc crushers
Authors: Zuñiga J.M. , Mantari J.L.
Published: September 2016

This study aims to contribute to the estimation of power consumption in a disintegration process in disc crushers (fixed and mobile). The study covers the dynamic analysis of forces acting on the particles and the mobile disc. A detailed analysis of the resultant force on the particles was performed. Finally, the consumed power is calculated with the forces acting on the mobile disc. The calculated power is a key aspect in the design of disc crusher machines.

Highlights Estimation of power consumption in a disintegration process in disc crushers. Dynamic analysis of forces acting on the particles and the disc crusher. Detailed analysis of the resultant force on the particles was performed. The consumed power is calculated with the forces acting on the mobile disc. The calculated power is a key aspect in the design of disc crusher machines.
Independent Component Analysis of Resting-State Functional Magnetic Resonance Imaging in Pedophiles
Authors: Cantor J.M. , Lafaille S.J. , Hannah J. , Kucyi A. , Soh D.W. , Girard T.A. , Mikulis D.J.
Published: September 2016

Introduction

Neuroimaging and other studies have changed the common view that pedophilia is a result of childhood sexual abuse and instead is a neurologic phenomenon with prenatal origins. Previous research has identified differences in the structural connectivity of the brain in pedophilia.

Aim

To identify analogous differences in functional connectivity.

Methods

Functional magnetic resonance images were recorded from three groups of participants while they were at rest: pedophilic men with a history of sexual offenses against children (n = 37) and two control groups: non-pedophilic men who committed non-sexual offenses (n = 28) and non-pedophilic men with no criminal history (n = 39).

Main Outcome Measure

Functional magnetic resonance imaging data were subjected to independent component analysis to identify known functional networks of the brain, and groups were compared to identify differences in connectivity with those networks (or “components”).

Results

The pedophilic group demonstrated wide-ranging increases in functional connectivity with the default mode network compared with controls and regional differences (increases and decreases) with the frontoparietal network. Of these brain regions (total = 23), 20 have been identified by meta-analytic studies to respond to sexually relevant stimuli. Conversely, of the brain areas known to be those that respond to sexual stimuli, nearly all emerged in the present data as significantly different in pedophiles.

Conclusion

This study confirms the presence of significant differences in the functional connectivity of the brain in pedophilia consistent with previously reported differences in structural connectivity. The connectivity differences detected here and elsewhere are opposite in direction from those associated with anti-sociality, arguing against anti-sociality and for pedophilia as the source of the neuroanatomic differences detected.
The Impact of Midurethral Sling Surgery on Sexual Activity and Function in Women with Stress Urinary Incontinence
Authors: Mengerink Bianca B. , Van Leijsen Sanne A.L. , Vierhout Mark E. , Inthout Joanna , Mol Ben W.J. , Milani Alfredo L. , Roovers Jan-Paul W.R. , Van Eijndhoven Hugo W.F. , Van Der Vaart Carl H. , Van Gestel Iris , Hartog Francis E. , Heesakkers John F.A. , Kluivers Kirsten B.
Published: September 2016

Introduction

Stress urinary incontinence has a negative impact on sexual function.

Aim

To assess the effect of midurethral sling surgery on sexual activity and function in women with stress urinary incontinence.

Methods

This is a secondary analysis of the Value of Urodynamics Prior to Stress Incontinence Surgery (VUSIS-II) study, which assessed the value of urodynamics in women with (predominantly) stress urinary incontinence. Patients who underwent retropubic or transobturator sling surgery were included in the present study if information was available on sexual activity before and 12 months after surgery. Data were collected from a self-report validated questionnaire combined with non-validated questions. The association between midurethral sling surgery and sexual function (coital incontinence, satisfaction, and dyspareunia) was compared with McNemar χ2 tests for nominal data and paired t-tests for ordinal data. Potentially influential factors were analyzed with univariable and multivariable logistic regression analyses.

Main Outcome Measures

Changes in sexual activity and sexual function after midurethral sling surgery.

Results

Information on sexual activity was available in 293 of the 578 women (51%) included in the VUSIS-II study. At baseline, 252 of 293 patients (86%) were sexually active vs 244 of 293 (83%) after 12 months. More patients with cured stress urinary incontinence were sexually active postoperatively (213 of 247 [86%] vs 31 of 46 [67%], P < .01). There was a significant decrease in coital incontinence (120 of 236 [51%] preoperatively vs 16 of 236 [7%] postoperatively, P < .01). De novo dyspareunia was present in 21 of 238 women (9%). There was a greater improvement in coital incontinence after placement of the retropubic sling compared with the transobturator sling (odds ratio = 2.04, 95% CI = 1.10–3.80, P = .02).

Conclusion

These data show that midurethral sling surgery has an overall positive influence on sexual function in women with stress urinary incontinence. The retropubic sling is more effective than the transobturator sling for improvement of coital incontinence. De novo dyspareunia was present in 1 of 11 women.
Distinct subpopulations of hepatitis C virus infectious cells with different levels of intracellular hepatitis C virus core protein
Authors: Wang Shu‐Chi , Yang Jeng‐Fu , Wang Chao‐Ling , Huang Chung‐Feng , Lin Yu‐Yin , Chen Yi‐You , Lo Chung‐Ting , Lee Po‐Yen , Wu Kuan‐Ta , Lin Chia‐I. , Hsieh Meng‐Hsuan , Chuang Hung‐Yi , Ho Chi‐Kung , Yu Ming‐Lung , Dai Chia‐Yen
Published: September 2016

Chronic infection by hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). Despite the clear clinical importance of virus‐associated HCC, the underlying molecular mechanisms remain largely unclarified. Oxidative stress, in particular, DNA lesions associated with oxidative damage, plays a major role in carcinogenesis, and is strongly linked to the development of many cancers, including HCC. However, in identifying hepatocytes with HCV viral RNA, estimates of the median proportion of HCV‐infected hepatocytes have been found as high as 40% in patients with chronic HCV infection. In order to explore the gene alternation and association between different viral loads of HCV‐infected cells, we established a method to dissect high and low viral load cells and examined the expression of DNA damage‐related genes using a quantitative polymerase chain reaction array. We found distinct expression patterns of DNA damage‐related genes between high and low viral load cells. This study provides a new method for future study on virus‐associated gene expression research.
Weakly nonlinear analysis of thermoacoustic instabilities in annular combustors
Authors: Ghirardo G. , Juniper M. P. , Moeck J. P.
Published: September 2016

Rotationally symmetric annular combustors are of practical importance because they generically resemble combustion chambers in gas turbines, in which thermoacoustically driven oscillations are a major concern. We focus on azimuthal thermoacoustic oscillations and model the fluctuating heat release rate as being dependent only on the local pressure in the combustion chamber. We study the dynamics of the annular combustor with a finite number of compact flames equispaced around the annulus, and characterize the flames’ response with a describing function. We discuss the existence, amplitude and the stability of standing and spinning waves, as a function of: (i) the number of the burners; (ii) the acoustic damping in the chamber; (iii) the flame response. We present the implications for industrial applications and the future direction of investigations. We then present as an example the first theoretical study of thermoacoustic triggering in annular combustors, which shows that rotationally symmetric annular chambers that are thermoacoustically unstable do not experience only stable spinning solutions, but can also experience stable standing solutions. We finally test the theory on one experiment with good agreement.
Higher-order flow modes in turbulent Rayleigh–Bénard convection
Authors: Xi Heng-Dong , Zhang Yi-Bao , Hao Jian-Tao , Xia Ke-Qing
Published: September 2016

We present experimental studies of higher-order modes of the flow in turbulent thermal convection in cells of aspect ratio ($\unicode[STIX]{x1D6E4}$) 1 and 0.5. The working fluid is water with the Prandtl number ($Pr$) kept at around 5.0. The Rayleigh number ($Ra$) ranges from $9\times 10^{8}$ to $6\times 10^{9}$ for $\unicode[STIX]{x1D6E4}=1$ and from $1.6\times 10^{10}$ to $7.2\times 10^{10}$ for $\unicode[STIX]{x1D6E4}=0.5$. We found that in $\unicode[STIX]{x1D6E4}=1$ cells, the first mode, which corresponds to the large-scale circulation (LSC), dominates the flow. The second mode (quadrupole mode), the third mode (sextupole mode) and the fourth mode (octupole mode) are very weak, on average these higher-order modes each contains less than 4 % of the total flow energy. In $\unicode[STIX]{x1D6E4}=0.5$ cells, the first mode is still the strongest but less dominant, the second mode becomes stronger which contains 13.7 % of the total flow energy and the third and the fourth modes are also stronger (containing 6.5 % and 1.1 % of the total flow energy respectively). It is found that during a reversal/cessation, the amplitude of the second mode and the remaining modes experiences a rapid increase followed by a decrease, which is opposite to the behaviour of the amplitude of the first mode – it decreases to almost zero then rebounds. In addition, it is found that during the cessation (reversal) of the LSC, the second mode dominates, containing 51.3 % (50.1 %) of the total flow energy, which reveals that the commonly called cessation event is not the cessation of the entire flow but only the cessation of the first mode (LSC). The experiment reveals that the second mode and the remaining higher-order modes play important roles in the dynamical process of the reversal/cessation of the LSC. We also show direct evidence that the first mode is more efficient for heat transfer. Furthermore, our study reveals that, during the cessation/reversal of the LSC, $Nu$ drops to its local minimum and the minimum of $Nu$ is ahead of the minimum of the amplitude of the LSC; and reversals can be distinguished from cessations in terms of global heat transport. A direct velocity measurement reveals the flow structure of the first- and higher-order modes.
Popular Medicine and Empirics in Greece, 1900–1950: An Oral History Approach
Authors: Hionidou Violetta
Published: September 2016

Western literature has focused on medical plurality but also on the pervasive existence of quacks who managed to survive from at least the eighteenth to the twentieth century. Focal points of their practices have been their efforts at enrichment and their extensive advertising. In Greece, empirical, untrained healers in the first half of the twentieth century do not fit in with this picture. They did not ask for payment, although they did accept ‘gifts’; they did not advertise their practice; and they had fixed places of residence. Licensed physicians did not undertake a concerted attack against them, as happened in the West against the quacks, and neither did the state. In this paper, it is argued that both the protection offered by their localities to resident popular healers and the healers’ lack of demand for monetary payment were jointly responsible for the lack of prosecutions of popular healers. Moreover, the linking of popular medicine with ancient traditions, as put forward by influential folklore studies, also reduced the likelihood of an aggressive discourse against the popular healers. Although the Greek situation in the early twentieth century contrasts with the historiography on quacks, it is much more in line with that on wise women and cunning-folk. It is thus the identification of these groups of healers in Greece and elsewhere, mostly through the use of oral histories but also through folklore studies, that reveals a different story from that of the aggressive discourse of medical men against quacks.
The Institutional Influence on the Location Strategies of Multinational Enterprises from Emerging Economies: Evidence from China's Cross-border Mergers and Acquisitions
Authors: Buckley Peter J. , Yu Pei , Liu Qing , Munjal Surender , Tao Pan
Published: September 2016

This study investigates the institutional influence on the location strategies of Chinese cross-border mergers and acquisitions (M&A) during the period 1985–2011 across 150 economies using Heckman's two-stage model. The results suggest that Chinese Multinational Enterprises (MNEs) are ‘shortsighted’ and show perverse behaviour towards host country risk when deciding on the location of host country and volume of investment undertaken through M&As, which may damage the firm's long-term profitability.
Letter to the Editor
Authors: Zhou Steven Shijin , Zhou Abby Jingzi
Published: September 2016

Two articles published in MOR recently have been about Chinese innovation (i.e., Augier, Guo, & Rowen, 2016; Luo & Child, 2015). The first paper argues that Chinese innovations are different from Western innovations because they have greater emphasis on imitating existing technologies. It raises a question about ‘how China's history, culture, institutions, and organizations aid or hinder innovation’. However, the second paper argues that enterprises in emerging economies in general, and Chinese enterprises in particular, benefit from a unique compositional capability (composition-based view [CBV]) with a focus on the competitive advantages gained from innovations created by combining existing resources in novel ways. These two papers seem to engage in a debate over whether and how Chinese firms are capable of innovation.
Art and Archaeology
Authors: Spivey Nigel
Published: September 2016

It is an obvious strategy of revisionism, in Classical archaeology: to see what J. J. Winckelmann said about this or that object, or sort of object, and then to measure ‘how far we have come’, in terms of interpretative enlightenment since the late eighteenth century. With the great Nilotic mosaic of Palestrina, that strategy looks at first sight promising enough. Winckelmann's theory was that it must represent a heroic narrative – specifically, the curious variant of Helen's abduction in which Paris carries off merely aneidolon, while the real Helen is secreted by the gods to Egypt and eventually retrieved from there by Menelaus (for details of the story, see Euripides’Helen). Winckelmann proposed Menelaus to be the foreground figure in greenish armour holding up a drinking-horn, Helen the lady attendant with a ladle – but there was little else to support his reading, and so alternative theories have multiplied (naturally enough – since the date of the mosaic is not absolutely established). In this case, however, it seems we are still short of a satisfactory resolution. By including discussion of the mosaic in her survey ofEgypt in Italy, Molly Swetnam-Burland admits that it could as easily post- as pre-date Rome's annexation of the Ptolemaic kingdom; and yet she does not want it to be generically categorized as a sample ofnilotica. ‘Representations of Egypt were rarely if ever to be considered in isolation’ (154). This could be the motto of her study, which explores how objects and ideas from and about Egypt became ‘recontextualized’ by the Romans. We may not have a definitive account for the Palestrina mosaic, but overall the results of this approach are worth reading. Analysis of the process whereby the first two obelisks were brought from Egypt to Rome, for example, demands that we do not content ourselves with seeing these transplanted megaliths as simply the trophies ofAegypto capta, nor just signs of Rome's attempt to rival Alexandria, but part of a claim by Augustus to pharaonic/cosmic powers. The author does not confine herself to archaeology: a substantial section of the book is devoted to an analysis of Juvenal's Satire 15.
Individual movements between local coastal populations of bottlenose dolphins (Tursiops truncatus) in the northern and eastern Black Sea
Authors: Gladilina Elena , Shpak Olga , Serbin Valentin , Kryukova Anna , Glazov Dmitry , Gol'din Pavel
Published: September 2016

The Black Sea subspecies of the bottlenose dolphin (Tursiops truncatus ponticus) is threatened and has a small range. Its population structure is little known: it possibly includes a few local coastal populations. We assessed connectivity between coastal groupings in six localities along 800 km of the coastline based on records of photo-identified animals between 2004 and 2014. Abundance of these groupings, as estimated, ranged between 76 and 174 individually distinctive dolphins. In total, there were 350 identified individuals, of which 91 (26%) were resighted within the same areas. However, only three cases of individual movements between local coastal populations were recorded at the distances between 135 and 325 km. Therefore, despite the absence of physical barriers, the coastal Black Sea population is fragmented into numerous resident or locally migrating groupings with site fidelity. These local populations are loosely connected to each other with rare movements between them. This fragmentation can be a factor contributing to short-term fluctuations in abundance of Black Sea bottlenose dolphins and their decline in some localities, despite the potentially high population growth rate.
Climate, lactation, and treatment factors influence faecal shedding ofEscherichia coliO157 pathotypes in dairy cows
Authors: STENKAMP-STRAHM C. , McCONNEL C. , RAO S. , MAGNUSON R. , HYATT D. R. , LINKE L.
Published: September 2016

Among pathogens shed by cattle,Escherichia coliO157 ranks highest in those causing human illness. To date, prevalence and risk factors for O157 shedding have been assessed in feedlot, but not dairy cattle. The study aimed to determine prevalence levels and risk factors for O157 atypical enteropathogenicE. coli(aEPEC) and enterohaemorrhagicE. coli(EHEC) shedding in dairy cattle. Dairy cattle (n= 899) within the first 21 days of lactation were sampled monthly over the course of 1 year, on three dry lot dairies surrounding Fort Collins, CO. During visits multiple factors were measured (disease history, pharmaceutical use, climate measures, etc.), and cattle faeces were collected and assessed for presence of O157 and virulence genes. Logistic regression analysis was performed using O157 outcomes and measured factors. Prevalence of O157 aEPEC was 3·7%, while EHEC was 3·0%. Many potential risk factors were highly correlated, and used to build separate multivariable models. An increase in humidity was positively associated with aEPEC, while fluid faeces and history of disease showed a negative association. Meanwhile, an increase in temperature and antibiotic treatment was positively associated with EHEC, while more days in milk, higher hygiene score and cow contact were negatively associated. These results may guide mitigation strategies that reduce O157 shedding, and contamination of the human food chain.
Giving Voice to Consciousness
Authors: FINS JOSEPH J.
Published: September 2016

In the 2015 David Kopf Lecture on Neuroethics of the Society for Neuroscience, Dr. Joseph Fins presents his work on neuroethics and disorders of consciousness through the experience of Maggie and Nancy Worthen, a young woman who sustained a severe brain injury and her mother who cared for her. The central protagonists in his book,Rights Come to Mind: Brain Injury, Ethics and the Struggle for Consciousness(Cambridge University Press, 2015), their experience is emblematic of the challenges faced by families touched by severe brain injury and the possibility for improved diagnosis and treatment offered by progress in neuroscience. By telling their story, and those of other families interviewed as part of the research forRights Come to Mind,Fins calls for improved care for this population arguing that this is both an access to care issue and a civil and disability rights issue worthy of greater societal attention.
The Effects of Closed-Loop Medical Devices on the Autonomy and Accountability of Persons and Systems
Authors: KELLMEYER PHILIPP , COCHRANE THOMAS , MÜLLER OLIVER , MITCHELL CHRISTINE , BALL TONIO , FINS JOSEPH J. , BILLER-ANDORNO NIKOLA
Published: September 2016

Closed-loop medical devices such as brain-computer interfaces are an emerging and rapidly advancing neurotechnology. The target patients for brain-computer interfaces (BCIs) are often severely paralyzed, and thus particularly vulnerable in terms of personal autonomy, decisionmaking capacity, and agency. Here we analyze the effects of closed-loop medical devices on the autonomy and accountability of both persons (as patients or research participants) and neurotechnological closed-loop medical systems. We show that although BCIs can strengthen patient autonomy by preserving or restoring communicative abilities and/or motor control, closed-loop devices may also create challenges for moral and legal accountability. We advocate the development of a comprehensive ethical and legal framework to address the challenges of emerging closed-loop neurotechnologies like BCIs and stress the centrality of informed consent and refusal as a means to foster accountability. We propose the creation of an international neuroethics task force with members from medical neuroscience, neuroengineering, computer science, medical law, and medical ethics, as well as representatives of patient advocacy groups and the public.
Culture, the Crack’d Mirror, and the Neuroethics of Disease
Authors: GILLETT GRANT
Published: September 2016

Human beings are sensorimotor coupled to the actual world and also attuned to the symbolic world of culture and the techniques of adaptation that culture provides. The self-image and self-shaping mediated by that mirror directly affects the neurocognitive structures that integrate human neural activity and reshape its processing capacities through top-down or autopoietic effects. Thus a crack’d mirror, which disrupts the processes of enactive self-configuration, can be disabling for an individual. That is exactly what happens in postcolonial or immigration contexts in which individuals’ cultural adaptations are marginalized and disconnected in diverse and often painful and disorienting ways. The crack’d mirror is therefore a powerful trope for neuroethics and helps us understand the social and moral pathologies of many indigenous and immigrant communities.
Patient Requests for Off-Label Bioprediction of Dementia
Authors: BAUM MATTHEW L.
Published: September 2016

In 2012, the FDA approved for the differential diagnosis of Alzheimer’s disease a brain-imaging technology, Amyvid-PET (aka florbetapir-PET), capable of non-invasively estimating the burden of amyloid plaques; this approval for one indication renders the technology a candidate for off-label use for another indication according to a physician’s judgment. What should a physician do if an educated, pro-active, and concerned patient requests off-label use of Amyvid-PET to help her estimate the likelihood that her mild memory complaints are “just normal aging” or are likely to profoundly worsen? I consider reasons that a physician might justify denial of such a request, including concerns of safety, uncertain benefit, and fair resource allocation, but cautiously conclude that there may be certain cases where off-label bioprediction would be permissible.
Assessing Decision-Making Capacity in Patients with Communication Impairments
Authors: CAIRNCROSS MOLLY , PETERSON ANDREW , LAZOSKY ANDREA , GOFTON TENEILLE , WEIJER CHARLES
Published: September 2016

The ethical principle of autonomy requires physicians to respect patient autonomy when present, and to protect the patient who lacks autonomy. Fulfilling this ethical obligation when a patient has a communication impairment presents considerable challenges. Standard methods for evaluating decision-making capacity require a semistructured interview. Some patients with communication impairments are unable to engage in a semistructured interview and are at risk of the wrongful loss of autonomy. In this article, we present a general strategy for assessing decision-making capacity in patients with communication impairments. We derive this strategy by reflecting on a particular case. The strategy involves three steps: (1) determining the reliability of communication, (2) widening the bandwidth of communication, and (3) using compensatory measures of decision-making capacity. We argue that this strategy may be useful for assessing decision-making capacity and preserving autonomy in some patients with communication impairments.
Ethical Challenges in Contemporary FASD Research and Practice
Authors: DI PIETRO NINA , DE VRIES JANTINA , PAOLOZZA ANGELINA , REID DOROTHY , REYNOLDS JAMES N. , SALMON AMY , WILSON MARSHA , STEIN DAN J. , ILLES JUDY
Published: September 2016

Fetal alcohol spectrum disorder (FASD) is increasingly recognized as a growing public health issue worldwide. Although more research is needed on both the diagnosis and treatment of FASD, and a broader and more culturally diverse range of services are needed to support those who suffer from FASD and their families, both research and practice for FASD raise significant ethical issues. In response, from the point of view of both research and clinical neuroethics, we provide a framework that emphasizes the need to maximize benefits and minimize harm, promote justice, and foster respect for persons within a global context.
Commentary: Old Self vs. New Self
Authors: Beasley Kara D.
Published: September 2016

Implantation of deep brain stimulator (DBS) leads for Gilles de Tourette syndrome was first described by Visser-Vanderwalle et al., with a reported 70%–90% decrease in tic frequency.1 Since that time, several targets, including the basal/ganglia and striatum, have been described. The target remains experimental, and in this case, leads were implanted under an investigator-initiated research protocol. Ms. L. reported an excellent intraoperative reduction in the “urge to tic” that persisted for 15 weeks postoperatively, indicating that the leads were well placed. Furthermore, although her tic frequency has increased, it remains improved from baseline and returns to baseline when stimulation is discontinued. Although her response does not represent what her treatment team would consider the “desired medical/therapeutic outcomes,” there is no question that the patient recognizes benefit from her stimulation. In fact, she clearly states that “it’s like I’ve felt a new way and don’t want to go back to the old way.”
Commentary: The Value of Patient Benefit: Consideration of Framing Contingencies to Guide the Ethical Use of DBS—a Case Analysis
Authors: Giordano James
Published: September 2016

Here we have a case in which (1) the outcome(s) for the patient do not comport with the projected—or initially defined—outcomes of the research study, and (2) these outcomes represent cognitive and behavioral effects that are positively interpreted by the patient, but not by the patient’s immediate family. The 6Cs approach, which frames the technique or technology—and its effects—within defined considerations of domains and dimensions, can be used as part of a multistep approach to addressing issues arising from the use of neurotechnology.1The approach recommends that the medical team consider the following domains and dimensions when engaging neuroethical analyses:

•

Thecapacitiesand limitations of current neuroscience and technology (neuroS/T), and the capacity of the patient

•

Theconsequencesincurred by neuroS/T on recipients, families, and society in the short, intermediate, and long term

•

Thecharacterof the recipient (e.g., patterns of cognition, emotion, and behavior) affected by neuroS/T

•

Thecontinuityof research and clinical care

•

Thecontextsof need and value that influence the use or nonuse of neuroS/T

•

Consentthrough provision of the most information possible2
Adenovirus-mediated Foxp3 expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model
Authors: Park Soojin , Chung Hwan-Suck , Shin Dasom , Jung Kyung-Hwa , Lee Hyunil , Moon Junghee , Bae Hyunsu
Published: September 2016

Foxp3 is a master regulator of CD4+CD25+ regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma. Th2 cytokine and immune cell profiles of bronchoalveolar lavage fluid (BALF), as well as serum IgE levels, were analyzed. Histological analyses were also conducted to demonstrate the effects of Foxp3 expression on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Adenoviral Foxp3 was expressed only in lung epithelial cells, and not in CD4+ or CD8+ cells. BALF from Foxp3 gene-delivered mice showed significantly reduced numbers of total immune cells, eosinophils, neutrophils, macrophages and lymphocytes in response to cockroach allergen or OVA. In addition, Foxp3 expression in the lung reduced the levels of Th2 cytokines and IgE in BALF and serum, respectively. Moreover, histopathological analysis also showed that Foxp3 expression substantially inhibited eosinophil infiltration into the airways, goblet cell hyperplasia and smooth muscle cell hypertrophy. Furthermore, when Tregs were depleted by diphtheria toxin in Foxp3DTR mice, the anti-asthmatic functions of Foxp3 were not altered in OVA-challenged asthma models. In this study, our results suggest that Foxp3 expression in lung epithelial cells, and not in Tregs, inhibited OVA- and cockroach extract-induced asthma.
Diversity is the question, not the answer
Authors: Shade Ashley
Published: September 2016

Local diversity (within-sample or alpha diversity) is often implicated as a cause of success or failure of a microbial community. However, the relationships between diversity and emergent properties of a community, such as its stability, productivity or invasibility, are much more nuanced. I argue that diversity without context provides limited insights into the mechanisms underpinning community patterns. I provide examples from traditional and microbial ecology to discuss common complications and assumptions about within-sample diversity that may prevent us from digging deeper into the more specific mechanisms underpinning community outcomes. I suggest that measurement of diversity should serve as a starting point for further inquiry of ecological mechanisms rather than an ‘answer’ to community outcomes.
Efficient hydrogen evolution by ternary molybdenum sulfoselenide particles on self-standing porous nickel diselenide foam
Authors: Zhou Haiqing , Yu Fang , Huang Yufeng , Sun Jingying , Zhu Zhuan , Nielsen Robert J. , He Ran , Bao Jiming , Goddard III William A. , Chen Shuo , Ren Zhifeng
Published: September 2016

With the massive consumption of fossil fuels and its detrimental impact on the environment, methods of generating clean power are urgent. Hydrogen is an ideal carrier for renewable energy; however, hydrogen generation is inefficient because of the lack of robust catalysts that are substantially cheaper than platinum. Therefore, robust and durable earth-abundant and cost-effective catalysts are desirable for hydrogen generation from water splitting via hydrogen evolution reaction. Here we report an active and durable earth-abundant transition metal dichalcogenide-based hybrid catalyst that exhibits high hydrogen evolution activity approaching the state-of-the-art platinum catalysts, and superior to those of most transition metal dichalcogenides (molybdenum sulfide, cobalt diselenide and so on). Our material is fabricated by growing ternary molybdenum sulfoselenide particles on self-standing porous nickel diselenide foam. This advance provides a different pathway to design cheap, efficient and sizable hydrogen-evolving electrode by simultaneously tuning the number of catalytic edge sites, porosity, heteroatom doping and electrical conductivity.
Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes
Authors: Lees John A. , Vehkala Minna , Välimäki Niko , Harris Simon R. , Chewapreecha Claire , Croucher Nicholas J. , Marttinen Pekka , Davies Mark R. , Steer Andrew C. , Tong Steven Y. C. , Honkela Antti , Parkhill Julian , Bentley Stephen D. , Corander Jukka
Published: September 2016

Bacterial genomes vary extensively in terms of both gene content and gene sequence. This plasticity hampers the use of traditional SNP-based methods for identifying all genetic associations with phenotypic variation. Here we introduce a computationally scalable and widely applicable statistical method (SEER) for the identification of sequence elements that are significantly enriched in a phenotype of interest. SEER is applicable to tens of thousands of genomes by counting variable-length k-mers using a distributed string-mining algorithm. Robust options are provided for association analysis that also correct for the clonal population structure of bacteria. Using large collections of genomes of the major human pathogens Streptococcus pneumoniae and Streptococcus pyogenes, SEER identifies relevant previously characterized resistance determinants for several antibiotics and discovers potential novel factors related to the invasiveness of S. pyogenes. We thus demonstrate that our method can answer important biologically and medically relevant questions.
Enhancement of orbital ordering and spin polarization by controlling the dimensionality of the octahedra network
Authors: Gu Mingqiang , Wang Kang , Wang Yiming , Xie Qiyun , Cai Hongling , Zhang Guo-Ping , Wu Xiaoshan
Published: September 2016

Two-dimensional (2D) systems have been widely investigated with perovskite superlattices because they show excellent epitaxy. A challenging question is naturally raised: whether lower dimensionality, e.g., one dimension (1D) and zero dimension (0D), can be achieved by perovskites? In this work, we propose a way to control the dimensionality of the octahedra network in perovskite superlattices by selecting the substrate orientation and superlattice period. Taking SrTiO3/SrRuO3 as an example, we demonstrate that the 1D structure is in a 1D Ising state, which is paramagnetic, while the 0D structure is ferromagnetic insulator with fully saturated magnetic moment on the Ru sites. New phenomena in the magnetic and electronic properties are observed, including large strain response, half-metallicity, and orbital-selective quantum confinement effects.
Mycobacterium tuberculosis components expressed during chronic infection of the lung contribute to long-term control of pulmonary tuberculosis in mice
Authors: Counoupas Claudio , Pinto Rachel , Nagalingam Gayathri , Hill-Cawthorne Grant A , Feng Carl G , Britton Warwick J , Triccas James A
Published: September 2016

Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, yet current control strategies, including the existing BCG vaccine, have had little impact on disease control. The tubercle bacillus modifies protein expression to adapt to chronic infection of the host, and this can potentially be exploited to develop novel therapeutics. We identified the gene encoding the first step of the Mycobacterium tuberculosis sulphur assimilation pathway, cysD, as highly induced during chronic infection in the mouse lung, suggesting therapies based on CysD could be used to target infection. Vaccination with the composite vaccine CysVac2, a fusion of CysD and the immunogenic Ag85B of M. tuberculosis, resulted in the generation of multifunctional CD4+ T cells (interferon (IFN)-γ+TNF+IL-2+IL-17+) in the lung both pre- and post-aerosol challenge with M. tuberculosis. CysVac2 conferred significant protection against pulmonary M. tuberculosis challenge and was particularly effective at controlling late-stage infection, a property not shared by BCG. CysVac2 delivered as a booster following BCG vaccination afforded greater protection against M. tuberculosis challenge than BCG alone. The antigenic components of CysVac2 were conserved amongst M. tuberculosis strains, and protective efficacy afforded by CysVac2 was observed across varying murine MHC haplotypes. Strikingly, administration of CysVac2 to mice previously infected with M. tuberculosis reduced bacterial load and immunopathology in the lung compared with BCG-vaccinated mice. These results indicate that CysVac2 warrants further investigation to assess its potential to control pulmonary TB in humans.
Retraction Note: Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma
Authors: Liu Ping , Sun Liang , Zhou Dong-sheng , Zhang Peng , Wang Yong-hui , Li Dong , Li Qing-hu , Feng Rong-jie
Published: September 2016

Scientific Reports 5: Article number: 17387; published online: 01 December 2015; updated: 16 September 2016. The authors of this Article have requested that it be retracted. During attempts to scale up the experiments for clinical studies, we could not reproduce the apoptosis (Figure 4) and cell cycle distribution results reported in the paper.
Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation
Authors: Blondel Marc , Soubigou Flavie , Evrard Justine , Nguyen Phu hai , Hasin Naushaba , Chédin Stéphane , Gillet Reynald , Contesse Marie-Astrid , Friocourt Gaëlle , Stahl Guillaume , Jones Gary W. , Voisset Cécile
Published: September 2016

6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI+] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI+]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other for [PSI+] propagation. Our data also provide insight into new functions for the ribosome in basal thermotolerance and heat-shocked protein refolding. PFAR is thus an evolutionarily conserved cell component implicated in the prion life cycle, and we propose that it could be a potential therapeutic target for human protein misfolding diseases.
The diagnostic accuracy of pericardial and urinary lipoarabinomannan (LAM) assays in patients with suspected tuberculous pericarditis
Authors: Pandie Shaheen , Peter Jonathan G. , Kerbelker Zita S. , Meldau Richard , Theron Grant , Govender Ureshnie , Ntsekhe Mpiko , Dheda Keertan , Mayosi Bongani M.
Published: September 2016

We evaluated the diagnostic accuracy of urinary and pericardial fluid (PF) lipoarabinomannan (LAM) assays in tuberculous pericarditis (TBP). From October 2009 through September 2012, 151 patients with TBP were enrolled. Mycobacterium tuberculosis culture and/or pericardial histology were the reference standard for definite TBP. 49% (74/151), 33.1% (50/151) and 17.9% (27/151) of patients had definite-, probable-, and non-TB respectively; 69.5% (105/151) were HIV positive. LAM ELISA had the following sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value and negative predictive values (95% confidence interval): urinary - 17.4% (9.1–30.7), 93.8% (71.7–98.9), 2.8 (0.1–63.3), 0.9 (0.8–0.9), 88.9% (56.5–98.0), and 28.3% (17.9–41.6); PF - 11.6% (6.0–21.3), 88% (70.0–95.8), 0.9 (0.08–12.0), 1.0 (0.9–1.1), 72.7% (43.4–90.1), and 26.6% (18.2–36.9). Sensitivity increased with a CD4 ≤ 100 cells/mm3 from 3.5% to 50% (p < 0.001) for urinary LAM ELISA; for urinary LAM strip test, grade 1 and 2 cut-points performed similarly, irrespective of HIV status or CD4 count. For PF LAM strip tests, switching cut-points from grade 1 to 2 significantly reduced test sensitivity (54.5% versus 19.7%; p < 0.001). Urinary and PF LAM assays have low sensitivity but high specificity for diagnosis of TBP. The sensitivity of urinary LAM is increased in HIV-infected patients with a CD4 ≤ 100 cells/mm3.