bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the Alzheimer’s Association Web Site to Improve Knowledge of Alzheimer’s Disease in Health Care Providers
Authors: Hughes Matthew L. , Lowe Deborah A. , Shine Hannah E. , Carpenter Brian D. , Balsis Steve
Published: November 2014

Background:

The purpose of the current study was to investigate whether an informative Web site is effective at producing higher scores for an individual’s knowledge of Alzheimer’s disease (AD) relative to those who do not visit a Web site.

Methods:

A total of 552 participants completed the study on Amazon’s Mechanical Turk; half were randomly assigned to visit alz.org , while a control group did not. Both groups were given the AD Knowledge Scale (ADKS) to assess their knowledge of AD.

Results:

Participants who visited alz.org scored significantly higher on the ADKS than those in the control group. Participants who were health care workers demonstrated higher scores than others in the experimental condition. Findings indicate that the Alzheimer’s Association Web site is effective at producing higher scores for AD knowledge relative to no Web site at all and that it is especially helpful for health care workers compared to those who are not health care workers.
Knowledge of the Heart: Ethical Implications of Sociological Research With Emotion
Authors: Prosser Brenton
Published: November 2014

Emotions have been the subject of social science research for many decades. Predominantly, this research has been orientated around research on emotion. While this genre of research focuses on emotion as a topic of inquiry, I propose that research with emotion can contribute to different ways of understanding social experience. Due to a different epistemological foundation, different methodological approaches are required with different ethical implications. This article will define research with and on emotion, before providing examples of the former. Based on these examples, this article explores ethical implications. The article concludes with a brief reflection on the benefits of sociological research with emotion, against which the many challenges should be assessed.
Ensemble forecasting of irregular leadership change
Authors: Beger Andreas , Dorff Cassy L , Ward Michael D
Published: November 2014

Using updated Archigos Data, as well as structural and event data, we construct a split-population duration model of irregular leadership changes. These are leadership changes that occur outside of the normal, legal framework for leadership transitions. Our model was estimated in March 2014 and produced probability estimates of leadership changes in many countries in the world. We used a wisdom-of-the-crowds approach to combining estimates from various different models. Ukraine and Thailand are among those in which we had the highest predictions for irregular change of leaders.
Capability of coupled CdSe/TiO2 heterogeneous structure for photocatalytic degradation and photoconductivity
Authors: Zhang Miao , Xu Yanyan , Lv Jianguo , Yang Lei , Jiang Xishun , He Gang , Song Xueping , Sun Zhaoqi
Published: November 2014

Highly ordered TiO2 nanotube arrays (TiO2-NTAs), with a uniform tube size on titanium substrate, were obtained by means of reoxidation and annealing. A composite structure, CdSe quantum dots@TiO2 nanotube arrays (CdSe QDs@TiO2-NTAs), was fabricated by assembling CdSe quantum dots into TiO2-NTAs via cyclic voltammetry electrochemical deposition. The X-ray diffractometer (XRD), field-emission scanning electron microscope (SEM), and transmission electron microscope (TEM) were carried out for the determination of the composition and structure of the tubular layers. Optical properties were investigated by ultraviolet-visible spectrophotometer (UV-Vis). Photocurrent response under visible light illumination and photocatalytic activity of samples by degradation of methyl orange were measured. The results demonstrated that the photo absorption of the composite film shifted to the visible region, and the photocurrent intensity was greatly enhanced due to the assembly of CdSe QDs. Especially, photocurrent achieved a maximum of 1.853 μA/cm2 after five voltammetry cycles of all samples. After irradiation under ultra violet-visible light for 2 h, the degradation rate of composition to methyl orange (MO) reached 88.20%, demonstrating that the CdSe QDs@TiO2-NTAs exhibited higher photocatalytic activity.
Defining hospital markets – an application to the German hospital sector
Authors: Hentschker Corinna , Mennicken Roman , Schmid Andreas
Published: November 2014

The correct definition of the product market and of the geographic market is a prerequisite for assessing market structures in antitrust cases. For hospital markets, both dimensions are controversially discussed in the literature. Using data for the German hospital market we aim at elaborating the need for differentiating the product market and at investigating the effects of different thresholds for the delineation of the geographic market based on patient flows. Thereby we contribute to the scarce empirical evidence on the structure of the German hospital market. We find that the German hospital sector is highly concentrated, confirming the results of a singular prior study. Furthermore, using a very general product market definition such as “acute in-patient care” averages out severe discrepancies that become visible when concentration is considered on the level of individual diagnoses. In contrast, varying thresholds for the definition of the geographic market has only impact on the level of concentration, while the correlation remains high. Our results underline the need for more empirical research concerning the definition of the product market for hospital services.

JEL classification: I11, K21, L11, L40.
The Delay Effect in a Stochastic Multiplier–Accelerator Model
Authors: Dassios Ioannis K , Zimbidis Alexandros A , Kontzalis Charalambos P
Published: November 2014

This paper extends the classical Samuelson multiplier–accelerator model for national economy. Actually, this new modeling structure removes the basic shortcoming of the original model producing stable business cycles when realistic values of the parameters (multiplier, accelerator) are entered into the system of equations. Under this new approach, we introduce some kind of randomness and memory into the system. We assume that consumption, private investment and governmental expenditure depend upon the national income values of the last n (

n
>
1

) years and further assume that multiplier and accelerator factors are stochastic variables. Then stochastic delayed difference equations of higher order are employed to describe the model, while the respective solutions of higher order polynomials for the expectation of national income variables correspond to the typical observed business cycles of real economy. Stability and controllability conditions are investigated while numerical examples provide further insight and better understanding as regards the control actions, system design, and produced business cycles.
Lipid raft-associated β-adducin is required for PSGL-1-mediated neutrophil rolling on P-selectin
Authors: Xu Tingshuang , Liu Wenai , Yang Chen , Ba Xueqing , Wang Xiaoguang , Jiang Yong , Zeng Xianlu
Published: November 2014

Lipid rafts, a liquid-ordered plasma membrane microdomain, are related to cell-surface receptor function. PSGL-1, a major surface receptor protein for leukocyte, also acts as a signaling receptor in leukocyte rolling. To investigate the role of lipid raft in PSGL-1 signaling in human neutrophils, we quantitatively analyzed lipid raft proteome of human promyelocytic leukemia cell line HL-60 cells and identified a lipid raft-associated protein β-adducin. PSGL-1 ligation induced dissociation of the raft-associated protein β-adducin from lipid rafts and actin, as well as phosphorylation of β-adducin, indicating a transient uncoupling of lipid rafts from the actin cytoskeleton. Knockdown of β-adducin greatly attenuated HL-60 cells rolling on P-selectin. We also showed that Src kinase is crucial for PSGL-1 ligation-induced β-adducin phosphorylation and relocation. Taken together, these results show that β-adducin is a pivotal lipid raft-associated protein in PSGL-1-mediated neutrophil rolling on P-selectin.
Adaptive prediction filtering in t-x-y domain for random noise attenuation using regularized nonstationary autoregression
Authors: Liu Yang , Liu Ning , Liu Cai
Published: November 2014

Many natural phenomena, including geologic events and geophysical data, are fundamentally nonstationary. They may exhibit stationarity on a short timescale but eventually alter their behavior in time and space. We developed a 2D [Formula: see text] adaptive prediction filter (APF) and further extended this to a 3D [Formula: see text] version for random noise attenuation based on regularized nonstationary autoregression (RNA). Instead of patching, a popular method for handling nonstationarity, we obtained smoothly nonstationary APF coefficients by solving a global regularized least-squares problem. We used shaping regularization to control the smoothness of the coefficients of APF. Three-dimensional space-noncausal [Formula: see text] APF uses neighboring traces around the target traces in the 3D seismic cube to predict noise-free signal, so it provided more accurate prediction results than the 2D version. In comparison with other denoising methods, such as frequency-space deconvolution, time-space prediction filter, and frequency-space RNA, we tested the feasibility of our method in reducing seismic random noise on three synthetic data sets. Results of applying the proposed method to seismic field data demonstrated that nonstationary [Formula: see text] APF was effective in practice.
King V. Burwell: Desperately Seeking Ambiguity in Clear Statutory Text
Authors: Adler Jonathan H. , Cannon Michael F.
Published: November 2014

Does the Patient Protection and Affordable Care Act (ACA) of 2010 authorize tax credits within the thirty-six states that failed to establish health insurance exchanges? That is the question presented in Pruitt v. Burwell, Halbig v. Burwell, King v. Burwell, and Indiana v. IRS. The plaintiffs argue that the statute is clear and forecloses any possibility of tax credits in federal exchanges. The government argues that the statute plainly authorizes tax credits in federal exchanges, or is at least ambiguous on the question. Mere disagreement is not evidence of ambiguity. Reaching the truth requires wading deep into each side's arguments. Whether the relevant text is viewed in isolation or in its full statutory context, the ACA authorizes tax credits only in exchanges established by the states.
Three Words and the Future of the Affordable Care Act
Authors: Bagley Nicholas
Published: November 2014

As an essential part of its effort to achieve near universal coverage, the Affordable Care Act (ACA) extends sizable tax credits to most people who buy insurance on the newly established health care exchanges. Yet several lawsuits have been filed challenging the availability of those tax credits in the thirty-four states that refused to set up their own exchanges. The lawsuits are premised on a strained interpretation of the ACA that, if accepted, would make a hash of other provisions of the statute and undermine its effort to extend coverage to the uninsured. The courts should reject this latest effort to dismantle a critical feature of the ACA.
North Korea's Vinalon City: Industrialism as Socialist Everyday Life
Authors: Kim Cheehyung Harrison
Published: November 2014

In the early 1960s, the synthetic fiber vinalon became North Korea's national fiber, a product that symbolized the independence and ingenuity of its state-led socialism, from the raw materials needed to make it (the abundant coal and limestone) to the person who invented it (the colonial chemist Ri Sŭnggi, scouted by North Korea in 1950). The Vinalon Factory near Hamhŭng City—a factory originally built by a Japanese chemical company and a city rebuilt with the assistance of East Germany—also became a national emblem of its own, as a factory that arose solely from the toil of the North Korean people. The history of vinalon is a confluence of the colonial industrial system, the postliberation nationalist ideology of state building, the dynamics of multinational postwar reconstruction, and the monopoly of economy and politics by the regime of Kim Il Sung. Vinalon City, as the immense factory was called, was a transnational object par excellence, but at the same time, it was immutably localized for the ordinary North Korean people, replete with its labor heroes who achieved superhuman levels of productivity. This industrial narrative has a dimension of concrete, everyday reality, as vinalon is worn as clothing and produced by the workers. The everyday dimension is precisely where the ideological workings of state power are hidden. Furthermore, the history of vinalon reveals a characteristic of ideology of work—the subsumption of life by labor—a characteristic that is certainly not limited to North Korea.
The Visual Representations of the Barefoot Doctor: Between Medical Policy and Political Struggles
Authors: Pang Laikwan
Published: November 2014

Exploring the visual representations of the barefoot doctors in China's Cultural Revolution, this article demonstrates how a medical policy is visualized and politicized, and it also shows how the visual culture of the time was richer than it has been assumed. This article meanders through different visual means such as propaganda posters and cinema in order to explore the difficult relationships between politics and policy, as well as the uneasy position occupied by femininity on the national political stage. Focusing on the barefoot doctor as a case study, this article provides a specific angle for us to understand the intense dynamics between culture and politics in the Cultural Revolution.
Asymmetric Synthesis of Stigmatellin and Crocacin C
Authors: Infante-Rodriguez Carolina , Domon Lisianne , Breuilles Pascal , Uguen Daniel
Published: November 2014

The crystalline sulfone 18 (X-ray analysis), prepared from the monoacetate product [i.e., (+)-12; 98.2% ee] of the lipase PS-catalyzed acetylation of anti,anti-2,4-dimethyl-1,3,5-pentantriol (19a), has been elaborated either to crocacin C (10) or stigmatellin (1), thereby providing a convenient divergent access to these two natural antibiotics.
Recognising and combating compassion fatigue in nursing
Authors: Mendes Aysha
Published: November 2014

In this monthly column, Aysha Mendes explores the reasons why nurses may feel compassion fatigue and ways NHS organisations and nurses themselves can engage in activities that will help them renew their emotional energy
Research Roundup
Authors: Costello John
Published: November 2014

Synopses of a selection of recently published research articles of relevance to palliative care.
Training renal staff to feel confident to respond to distressed patients
Authors: Brand Sarah , Coyne Emma , Tomlin Matthew , Rigby Mark
Published: November 2014

Psychological distress is common among those with renal disease. Nottingham University Hospitals NHS Trust's renal and transplant unit has implemented communication skills training to improve the skills of staff, support them in dealing with distressed patients, and improve care offered to patients and carers.
First priority of care: recognising and communicating the end of life
Authors: Mendes Aysha
Published: November 2014

The Liverpool Care Pathway has been recently phased out in favour of new priorities of care. In this new regular column, Aysha Mendes delves into the rapidly evolving world of end-of-life care and explores what it all means for renal nurses who are caring for patients with end-stage renal disease.
Fiber-optic magnetometry with randomly oriented spins
Authors: Fedotov I. V. , Doronina-Amitonova L. V. , Sidorov-Biryukov D. A. , Safronov N. A. , Levchenko A. O. , Zibrov S. A. , Blakley S. , Perez Esther , Akimov A. V. , Fedotov A. B. , Hemmer P. , Sakoda K. , Velichansky V. L. , Scully M. O. , Zheltikov A. M.
Published: November 2014

We demonstrate fiber-optic magnetometry using a random ensemble of nitrogen-vacancy (NV) centers in nanodiamond coupled to a tapered optical fiber, which provides a waveguide delivery of optical fields for the initialization, polarization, and readout of the electron spin in NV centers.
Assessment and Correction of Turbidity Effects on Raman Observations of Chemicals in Aqueous Solutions
Authors: Sinfield Joseph V. , Monwuba Chike K.
Published: November 2014

Improvements in diode laser, fiber optic, and data acquisition technologies are enabling increased use of Raman spectroscopic techniques for both in lab and in situ water analysis. Aqueous media encountered in the natural environment often contain suspended solids that can interfere with spectroscopic measurements, yet removal of these solids, for example, via filtration, can have even greater adverse effects on the extent to which subsequent measurements are representative of actual field conditions. In this context, this study focuses on evaluation of turbidity effects on Raman spectroscopic measurements of two common environmental pollutants in aqueous solution: ammonium nitrate and trichloroethylene. The former is typically encountered in the runoff from agricultural operations and is a strong scatterer that has no significant influence on the Raman spectrum of water. The latter is a commonly encountered pollutant at contaminated sites associated with degreasing and cleaning operations and is a weak scatterer that has a significant influence on the Raman spectrum of water. Raman observations of each compound in aqueous solutions of varying turbidity created by doping samples with silica flour with grain sizes ranging from 1.6 to 5.0 μm were employed to develop relationships between observed Raman signal strength and turbidity level. Shared characteristics of these relationships were then employed to define generalized correction methods for the effect of turbidity on Raman observations of compounds in aqueous solution.
An Investigation into the Structure and Chemical Properties of Formamidine Sulfinic Acid
Authors: Lewis David , Mama John , Hawkes Jamie
Published: November 2014

The use of formamidine sulfinic acid in the textile industry goes back many years, particularly as an agent for the reduction or “vatting” of vat dyes, to form the water-soluble leuco species, when dyeing or printing cellulosic fibers. Many workers have labeled this agent as thiourea dioxide and theorized that its reducing power developed through the existence of two isomeric forms: thiourea dioxide (the sulfone), and formamidine sulfinate. This article has used solid and solution Fourier transform infrared (FT-IR) spectroscopy to show that the name thiourea dioxide is a misnomer since the compound does not exist in the six-valent state, but is stabilized in the four-valent state by formation of a strong internal zwitterion as shown in the article.
Improving Near-Infrared Prediction Model Robustness with Support Vector Machine Regression: A Pharmaceutical Tablet Assay Example
Authors: Igne Benoît , Drennen James K. , Anderson Carl A.
Published: November 2014

Changes in raw materials and process wear and tear can have significant effects on the prediction error of near-infrared calibration models. When the variability that is present during routine manufacturing is not included in the calibration, test, and validation sets, the long-term performance and robustness of the model will be limited. Nonlinearity is a major source of interference. In near-infrared spectroscopy, nonlinearity can arise from light path-length differences that can come from differences in particle size or density. The usefulness of support vector machine (SVM) regression to handle nonlinearity and improve the robustness of calibration models in scenarios where the calibration set did not include all the variability present in test was evaluated. Compared to partial least squares (PLS) regression, SVM regression was less affected by physical (particle size) and chemical (moisture) differences. The linearity of the SVM predicted values was also improved. Nevertheless, although visualization and interpretation tools have been developed to enhance the usability of SVM-based methods, work is yet to be done to provide chemometricians in the pharmaceutical industry with a regression method that can supplement PLS-based methods.
Microarray Chip Development Using Infrared Imaging for the Identification of Catfish Species
Authors: Handy Sara M. , Chizhikov Vladimir , Yakes Betsy Jean , Paul Stephen Z. , Deeds Jonathan R. , Mossoba Magdi M.
Published: November 2014

Several families of catfish species are extensively aquacultured around the world; however, only those from the family Ictaluridae can be labeled as catfish in the United States. Non-Ictalurid catfish species that are marketed as “catfish” in the USA are considered misbranded. Misbranding in general has led to an increased interest in developing deoxyribonucleic acid (DNA)-based methods such as DNA barcoding, polymerase chain reaction restriction fragment length polymorphism, and DNA microarrays with fluorescence detection for the identification of fish species. In this proof-of-concept study, DNA microarrays coupled with a newly developed mid-infrared imaging detection method were applied to the identification of seven species of catfish for the first time. Species-specific DNA probes targeting three regions per species of the cytochrome c oxidase 1 (barcoding) gene were developed and printed as microarrays on glass slides. Deoxyribonucleic acid targets labeled with biotin were hybridized to their complementary probes using a strategy that allowed the selective formation of a silver layer on hybridized spots needed for detection. Using this three-probe format, the seven species were all identified correctly, even when a limited number of false positive spots were observed. Raman spectroscopy was employed to further characterize the arrays.
Temporal Evolution of Photothermal-Induced Rayleigh Wave and Plate Deformation as an Interference in the Transient Kinetics of Photoinduced Carrier Recombination of a Rutile Titanium Dioxide Single Crystal
Authors: Zhu Gangbei , Zhu Ming , Weng Yuxiang
Published: November 2014

The dynamic properties of photothermal processes occurring after the initial photogenerated carrier recombination in the flash photolysis of a semiconductor plate sample probed with a reflected infrared beam are reported in this work. Transient kinetics pertaining to the photothermal processes always appear as interfering signals in that of the photogenerated carrier recombination and should be distinguished and excluded. We observed that the photothermal-induced Rayleigh wave occurs immediately after the photogenerated carrier recombination that is then followed by the photothermal-induced flexural vibration of the sample substrate with a set of intrinsic frequencies as reported in our previous work (Appl. Spectrosc. 2013. 67(5): 506–512). When these two faster types of waves decay, the transient decaying signal from the plate deformation due to the inhomogeneous temperature field remains for much longer than 22 ms. Thus, all three types of the photothermal dynamic processes of different temporal properties induced by the pulsed laser on an absorbing semiconductor thin plate are clearly identified.
A human factors perspective on medical device alarms: problems with operating alarming devices and responding to device alarms
Authors: Lange Kathrin , Nowak Miriam , Lauer Wolfgang
Published: November 2014

Medical devices emit alarms when a problem with the device or with the patient needs to be addressed by healthcare personnel. At present, problems with device alarms are frequently discussed in the literature, the main message being that patient safety is compromised because device alarms are not as effective and safe as they should – and could – be. There is a general consensus that alarm-related hazards result, to a considerable degree, from the interactions of human users with the device. The present paper addresses key aspects of human perception and cognition that may relate to both operating alarming devices and responding to device alarms. Recent publications suggested solutions to alarm-related hazards associated with usage errors based on assumptions on the causal relations between, for example, alarm management and human perception, cognition, and responding. However, although there is face validity in many of these assumptions, future research should provide objective empirical evidence in order to deepen our understanding of the actual causal relationships, and hence improve and expand the possibilities for taking appropriate action.
Numerical Solution of Singular Patterns in One-dimensional Gray-Scott-like Models
Authors: Owolabi Kolade M. , Patidar Kailash C.
Published: November 2014

In this paper, numerical simulations of coupled one-dimensional Gray-Scott model for pulse splitting process, self-replicating patterns and unsteady oscillatory fronts associated with autocatalytic reaction-diffusion equations as well as homoclinic stripe patterns, self-replicating pulse and other chaotic dynamics in Gierer-Meinhardt equations [12] are investigated. Our major approach is the use of higher order exponential time differencing Runge-Kutta (ETDRK) scheme that was earlier proposed by Cox and Matthews [5], which was later presented as a result of instability in a modified form by Krogstad [24] to solve stiff semi-linear problems. The semi-linear problems under consideration in this context are split into linear, which harbors the stiffest part of the dynamical system and nonlinear part that varies slowly than the linear part. For the spatial discretization, we employ higher-order symmetric finite difference scheme and solve the resulting system of ODEs with higher-order ETDRK method. Numerical examples are given to illustrate the accuracy and implementation of the methods, results and error comparisons with other standard schemes are well presented.
Revisiting intradural spinal cord stimulation: an introduction to a novel intradural spinal cord stimulation device
Authors: Dalm Brian D. , Viljoen Sephanus V. , Dahdaleh Nader S. , Reddy Chandan G. , Brennan Timothy J. , Oya Hiroyuki , Wilson Saul , Safayi Sina , Jeffery Nicholas D. , Gilles George T. , Howard Matthew A.
Published: November 2014

Background: Spinal cord stimulation has been in use for decades and is growing as a therapeutic treatment option. A significant problem arising from the epidural location of the lead is electrical shunting through the cerebrospinal fluid, providing sub-optimal delivery of the electrical current specifically to the Aβ fibers of the dorsal column.

Objective: Our goal is to design a safe and effective intradural spinal cord stimulator (SCS) that places the stimulating electrodes directly against the pia similar to what is currently employed with the auditory brainstem implant.

Methods: We have reviewed the literature on the early original intradural SCSs and designed, built, and tested an improved device that seeks to overcome the limitations the existing epidural stimulators.

Results: In particular, we have shown that the present design of our device allows for motion of the spinal cord without the device being displaced itself, exerts a surface pressure on the spinal cord surface that is below what would cause ischemia or vessel injury, activates somato-sensory evoked potentials at a lower threshold than epidural stimulation, and (iv) does not cause deleterious neurological deficits in a chronic ovine model of intradural stimulator implantation.

Conclusion: While further studies to prove long-term safety and durability of the device are underway, we believe that revisiting an intradural approach to spinal cord stimulation may continue to improve our ability to treat certain chronic pain states and possibly the spasticity associated with spinal cord injuries.
Yen-BSR: A New Approach for the Choice of Routes in WDM Networks
Authors: Santos A. F. , Almeida R. C. , Assis K. D. R.
Published: November 2014

In this paper we propose to use an iterative algorithm for optimizing the fixed-alternate shortest path routing in the dynamic routing and wavelength assignment (RWA) problem in wavelength routing optical networks. The algorithm performance is compared, in terms of blocking probability, with the Dijkstra and Yen traditional algorithms, as well as with the recently proposed best among the shortest routes (BSR) algorithm. The results suggest that it is feasible to choose an appropriate set of routes for each pair of nodes (source, destination), among the shortest paths and efficiently balance the network load. For all studied scenarios, the proposed heuristic achieved superior performance.
Here Comes Everybody: Anthropological Hyperbole in Some Recent Novels
Authors: Kläger Florian
Published: November 2014

In a number of recent British novels, readers encounter startlingly hyperbolic representations of characters and settings, indicative of an ambition to represent the human condition comprehensively. This essay reads this phenomenon in the context of recent critical commentary on the novel that has engaged with various kinds of universalisms (‘hysterical realism,’ ‘cosmopolitan’ and ‘cosmodernist’ novels, and ‘traumatological’ fiction). It suggests that the texts discussed here, Winterson’s The Stone Gods (2007), Crumey’s Sputnik Caledonia (2008), and McEwan’s Solar (2010), do not (only) aim at negotiating the place of individuals in globalized society and the dread of impersonal catastrophes, but at spelling out an anthropology: by way of autopoetological self-valorization, literature is presented as a prime medium of human relations to the world, answering to an essential anthropological deficiency.
Cued Memory Reactivation during Slow-Wave Sleep Promotes Explicit Knowledge of a Motor Sequence
Authors: Cousins James N. , El-Deredy Wael , Parkes Laura M. , Hennies Nora , Lewis Penelope A.
Published: November 2014

Memories are gradually consolidated after initial encoding, and this can sometimes lead to a transition from implicit to explicit knowledge. The exact physiological processes underlying this reorganization remain unclear. Here, we used a serial reaction time task to determine whether targeted memory reactivation (TMR) of specific memory traces during slow-wave sleep promotes the emergence of explicit knowledge. Human participants learned two 12-item sequences of button presses (A and B). These differed in both cue order and in the auditory tones associated with each of the four fingers (one sequence had four higher-pitched tones). Subsequent overnight sleep was monitored, and the tones associated with one learned sequence were replayed during slow-wave sleep. After waking, participants demonstrated greater explicit knowledge (p= 0.005) and more improved procedural skill (p= 0.04) for the cued sequence relative to the uncued sequence. Furthermore, fast spindles (13.5–15 Hz) at task-related motor regions predicted overnight enhancement in procedural skill (r= 0.71,p= 0.01). Auditory cues had no effect on post-sleep memory performance in a control group who received TMR before sleep. These findings suggest that TMR during sleep can alter memory representations and promote the emergence of explicit knowledge, supporting the notion that reactivation during sleep is a key mechanism in this process.
GluN2B-Containing NMDA Receptors Promote Glutamate Synapse Development in Hippocampal Interneurons
Authors: Kelsch Wolfgang , Li Zhijun , Wieland Sebastian , Senkov Oleg , Herb Anne , Göngrich Christina , Monyer Hannah
Published: November 2014

In postnatal development, GluN2B-containing NMDARs are critical for the functional maturation of glutamatergic synapses. GluN2B-containing NMDARs prevail until the second postnatal week when GluN2A subunits are progressively added, conferring mature properties to NMDARs. In cortical principal neurons, deletion of GluN2B results in an increase in functional AMPAR synapses, suggesting that GluN2B-containing NMDARs set a brake on glutamate synapse maturation. The function of GluN2B in the maturation of glutamatergic inputs to cortical interneurons is not known. To examine the function of GluN2B in interneurons, we generated mutant mice with conditional deletion of GluN2B in interneurons (GluN2BΔGAD67). In GluN2BΔGAD67mice interneurons distributed normally in cortical brain regions. After the second postnatal week, GluN2BΔGAD67mice developed hippocampal seizures and died shortly thereafter. Before the onset of seizures, GluN2B-deficient hippocampal interneurons received fewer glutamatergic synaptic inputs than littermate controls, indicating that GluN2B-containing NMDARs positively regulate the maturation of glutamatergic input synapses in interneurons. These findings suggest that GluN2B-containing NMDARs keep the circuit activity under control by promoting the maturation of excitatory synapses in interneurons.
Regulation of Hippocampal Synaptic Strength by Glial xCT
Authors: Williams Leena E. , Featherstone David E.
Published: November 2014

Most extracellular glutamate in the brain is released by xCT, a glial antiporter that exports glutamate and imports cystine. The function of xCT, and extracellular glutamate in general, remains unclear. Several lines of evidence suggest that glutamate from xCT could act in a paracrine fashion to suppress glutamatergic synapse strength by triggering removal of postsynaptic glutamate receptors. To test this idea, we used whole-cell patch-clamp electrophysiology and immunohistochemistry to quantify receptor number and synapse function in xCT knock-out mouse hippocampal CA3-CA1 synapses. Consistent with the hypothesis that xCT suppresses glutamate receptor number and synapse strength, xCT knock-out synapses showed increased AMPA receptor abundance with concomitant large enhancements of spontaneous and evoked synaptic transmission. We saw no evidence for changes in GABA receptor abundance or the overall number of glutamatergic synapses. The xCT knock-out phenotype was replicated by incubating slices in the xCT inhibitor (S)-4-carboxyphenylglycine, and consistent with the idea that xCT works by regulating extracellular glutamate, the xCT knock-out phenotype could be reproduced in controls by incubating the slices in glutamate-free aCSF. We conclude that glutamate secreted via xCT suppresses glutamatergic synapse strength by triggering removal of postsynaptic AMPA receptors.
PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts
Authors: Lee Sooyeon , Amici Stephanie , Tavori Hagai , Zeng Waylon M. , Freeland Steven , Fazio Sergio , Notterpek Lucia
Published: November 2014

Haploinsufficiency of peripheral myelin protein 22 (PMP22) causes hereditary neuropathy with liability to pressure palsies, a peripheral nerve lesion induced by minimal trauma or compression. As PMP22 is localized to cholesterol-enriched membrane domains that are closely linked with the underlying actin network, we asked whether the myelin instability associated with PMP22 deficiency could be mediated by involvement of the protein in actin-dependent cellular functions and/or lipid raft integrity. In peripheral nerves and cells from mice with PMP22 deletion, we assessed the organization of filamentous actin (F-actin), and actin-dependent cellular functions. Usingin vitromodels, we discovered that, in the absence of PMP22, the migration and adhesion capacity of Schwann cells and fibroblasts are similarly impaired. Furthermore, PMP22-deficient Schwann cells produce shortened myelin internodes, and display compressed axial cell length and collapsed lamellipodia. During early postnatal development, F-actin-enriched Schmidt-Lanterman incisures do not form properly in nerves from PMP22−/−mice, and the expression and localization of molecules associated with uncompacted myelin domains and lipid rafts, including flotillin-1, cholesterol, and GM1 ganglioside, are altered. In addition, we identified changes in the levels and distribution of cholesterol and ApoE when PMP22 is absent. Significantly, cholesterol supplementation of the culture medium corrects the elongation and migration deficits of PMP22−/−Schwann cells, suggesting that the observed functional impairments are directly linked with cholesterol deficiency of the plasma membrane. Our findings support a novel role for PMP22 in the linkage of the actin cytoskeleton with the plasma membrane, likely through regulating the cholesterol content of lipid rafts.
RTCB-1 Mediates Neuroprotection via XBP-1 mRNA Splicing in the Unfolded Protein Response Pathway
Authors: Ray Arpita , Zhang Siyuan , Rentas Courtney , Caldwell Kim A. , Caldwell Guy A.
Published: November 2014

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is characterized by the degeneration of dopamine (DA) neurons and age-dependent formation of protein inclusions that contain the α-synuclein (α-syn) protein. RNA interference (RNAi) screening usingCaenorhabditis elegansidentified RTCB-1, an uncharacterized gene product, as one of several significant modifiers of α-syn protein misfolding. RTCB-1 is the worm ortholog of the human HSPC117 protein, a component of RNA trafficking granules in mammalian neurons. Here we show that RTCB-1 protectsC. elegansDA neurons from age-dependent degeneration induced by human α-syn. Moreover, neuronal-specific RNAi depletion ofrtcb-1enhanced α-syn-induced degeneration. Similar results were obtained when worms were exposed to the DA neurotoxin 6-hydroxydopamine. HSPC117 has been characterized recently as an essential subunit of the human tRNA splicing ligase complex. tRNA ligases have alternative functions in RNA repair and nonconventional mRNA splicing events. For example, in yeast, unconventional splicing ofHAC1, a transcription factor that controls the unfolded protein response (UPR), is mediated by a tRNA ligase. InC. elegans, we demonstrate that RTCB-1 is necessary forxbp-1(worm homolog ofHAC1) mRNA splicing. Moreover, using a RNA ligase-dead mutant, we determine that the ligase activity of worm RTCB-1 is required for its neuroprotective role, which, in turn, is mediated through XBP-1 in the UPR pathway. Collectively, these studies highlight the mechanistic intersection of RNA processing and proteostasis in mediating neuroprotection.
Proton-Mediated Block of Ca2+Channels during Multivesicular Release Regulates Short-Term Plasticity at an Auditory Hair Cell Synapse
Authors: Cho Soyoun , von Gersdorff Henrique
Published: November 2014

Synaptic vesicles release both neurotransmitter and protons during exocytosis, which may result in a transient acidification of the synaptic cleft that can block Ca2+channels located close to the sites of exocytosis. Evidence for this effect has been reported for retinal ribbon-type synapses, but not for hair cell ribbon synapses. Here, we report evidence for proton release from bullfrog auditory hair cells when they are held at more physiological,in vivo–like holding potentials (Vh= −60 mV) that facilitate multivesicular release. During paired recordings of hair cells and afferent fibers, L-type voltage-gated Ca2+currents showed a transient block, which was highly correlated with the EPSC amplitude (or the amount of glutamate release). This effect was masked atVh= −90 mV due to the presence of a T-type Ca2+current and blocked by strong pH buffering with HEPES or TABS. Increasing vesicular pH with internal methylamine in hair cells also abolished the transient block. High concentrations of intracellular Ca2+buffer (10 mmBAPTA) greatly reduced exocytosis and abolished the transient block of the Ca2+current. We estimate that this transient block is due to the rapid multivesicular release of ∼600–1300 H+ions per synaptic ribbon. Finally, during a train of depolarizing pulses, paired pulse plasticity was significantly changed by using 40 mmHEPES in addition to bicarbonate buffer. We propose that this transient block of Ca2+current leads to more efficient exocytosis per Ca2+ion influx and it may contribute to spike adaptation at the auditory nerve.
Partial Loss of Presenilin Impairs Age-Dependent Neuronal Survival in the Cerebral Cortex
Authors: Watanabe Hirotaka , Iqbal Minah , Zheng Jin , Wines-Samuelson Mary , Shen Jie
Published: November 2014

Mutations in thepresenilin(PSEN1andPSEN2) genes are linked to familial Alzheimer's disease (AD) and cause loss of its essential function. Complete inactivation of presenilins in excitatory neurons of the adult mouse cerebral cortex results in progressive memory impairment and age-dependent neurodegeneration, recapitulating key features of AD. In this study, we examine the effects of varying presenilin dosage on cortical neuron survival by generatingpresenilin-1conditional knock-out (PS1cKO) mice carrying two, one, or zero copies of thePS2gene. We found thatPS1cKO;PS2+/−mice at 16 months exhibit marked neurodegeneration in the cerebral cortex with ∼17% reduction of cortical volume and neuron number, as well as astrogliosis and microgliosis compared with ∼50% reduction of cortical volume and neuron number inPS1cKO;PS2−/−mice. Moreover, there are more apoptotic neurons labeled by activated caspase-3 immunoreactivity and TUNEL assay inPS1cKO;PS2+/−mice at 16 months, whereas apoptotic neurons are increased in thePS1cKO;PS2−/−cerebral cortex at 4 months. The accumulation of the C-terminal fragments of the amyloid precursor protein is inversely correlated with PS dosage. Interestingly, levels of PS2 are higher in the cerebral cortex ofPS1cKO mice, suggesting a compensatory upregulation that may provide protection against neurodegeneration in these mice. Together, our findings show that partial to complete loss of presenilin activity causes progressively more severe neurodegeneration in the mouse cerebral cortex during aging, suggesting that impaired presenilin function byPSENmutations may lead to neurodegeneration and dementia in AD.
Cytosolic RNA:DNA hybrids activate the cGAS–STING axis
Authors: Mankan Arun K , Schmidt Tobias , Chauhan Dhruv , Goldeck Marion , Höning Klara , Gaidt Moritz , Kubarenko Andrew V , Andreeva Liudmila , Hopfner Karl‐Peter , Hornung Veit
Published: November 2014

Intracellular recognition of non‐self and also self‐nucleic acids can result in the initiation of potent pro‐inflammatory and antiviral cytokine responses. Most recently, cGAS was shown to be critical for the recognition of cytoplasmic dsDNA. Binding of dsDNA to cGAS results in the synthesis of cGAMP(2′–5′), which then binds to the endoplasmic reticulum resident protein STING. This initiates a signaling cascade that triggers the induction of an antiviral immune response. While most studies on intracellular nucleic acids have focused on dsRNA or dsDNA, it has remained unexplored whether cytosolic RNA:DNA hybrids are also sensed by the innate immune system. Studying synthetic RNA:DNA hybrids, we indeed observed a strong type I interferon response upon cytosolic delivery of this class of molecule. Studies in THP‐1 knockout cells revealed that the recognition of RNA:DNA hybrids is completely attributable to the cGAS–STING pathway. Moreover, in vitro studies showed that recombinant cGAS produced cGAMP upon RNA:DNA hybrid recognition. Altogether, our results introduce RNA:DNA hybrids as a novel class of intracellular PAMP molecules and describe an alternative cGAS ligand next to dsDNA.
An update on novel mechanisms of primary aldosteronism
Authors: Zennaro Maria-Christina , Boulkroun Sheerazed , Fernandes-Rosa Fabio
Published: November 2014

Primary aldosteronism (PA) is the most common and curable form of secondary hypertension. It is caused in the majority of cases by either unilateral aldosterone overproduction due to an aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia. Recent advances in genome technology have allowed researchers to unravel part of the genetic abnormalities underlying the development of APA and familial hyperaldosteronism. Recurrent somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D) and ATPases (ATP1A1 and ATP2B3) regulating intracellular ionic homeostasis and cell membrane potential have been identified in APA. Similar germline mutations of KCNJ5 were identified in a severe familial form of PA, familial hyperaldosteronism type 3 (FH3), whereas de novo germline CACNA1D mutations were found in two cases of hyperaldosteronism associated with a complex neurological disorder. These results have allowed a pathophysiological model of APA development to be established. This model involves modifications in intracellular ionic homeostasis and membrane potential, accounting for ∼50% of all tumors, associated with specific gender differences and severity of PA. In this review, we describe the different genetic abnormalities associated with PA and discuss the mechanisms whereby they lead to increased aldosterone production and cell proliferation. We also address some of the foreseeable consequences that genetic knowledge may contribute to improve diagnosis and patient care.
Cooperation of DLC1 and CDK6 Affects Breast Cancer Clinical Outcome
Authors: Dai Xiaofeng , Li Lu , Liu Xiuxia , Hu Weiguo , Yang Yankun , Bai Zhonghu
Published: November 2014

Low DLC1 expression is found to frequently co-occur with aberrant expression of cell cycle genes including CDK6 in human lung and colon cancer. Here, we explore the influence of the synergistic effect of DLC1 and CDK6 on human breast cancer survival at the genetic, transcriptional, and translational levels. We found that high DLC1 and low CDK6 expression are associated with good prognosis. The DLC1 intronic SNP rs561681 is found to fit a recessive model, complying with the tumor suppressive role of DLC1. The heterozygote of the DLC1 SNP is found to increase the hazard when the CDK6 intronic SNP rs3731343 is rare homozygous, and it becomes protective when rs3731343 is common homozygous. We propose that DLC1 expression is the lowest in patients harboring the rare homozygote of rs561681 and functional DLC1 is the lowest when rs561681 is heterozygous and rs3731343 is rare homozygous. We are the first to report such synergistic effects of DLC1 and CDK6 on breast cancer survival at the transcriptional level, the overdominant model fitted by the SNP pair, and the dominant negative effect at the translational level. These findings link the germline genetic polymorphisms and synergistic effect of DLC1 and CDK6 with breast cancer progression, which provide the basis for experimentally elucidating the mechanisms driving differential tumor progression and avail in tailoring the clinical treatments for such patients based on their genetic susceptibility.
Influence of Magnetic Field on Magnetic Properties of Electrodeposited Co-Ni-P Nanowires
Authors: Tu Le Tuan , Thiem Luu Van , Thang Pham Duc
Published: November 2014

The magnetic properties in Co-Ni-P nanowires arrays with diameter of 200 nm were investigated. All the samples were prepared by electrodeposition method with pH of 5.5 and at room temperature. During the deposition, a magnetic field in range of 0 - 750 Oe was applied parallel to the wires axis. The crystalline structure and morphology of the samples were characterized by X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM), respectively. The hysteresis loops were measured at room temperature using vibrating sample magnetometry (VSM). The mixture of hcp phases of the Co-Ni-P based nanowires has been indicated by the XRD pattern. The obtained results show that with 750 Oe magnetic field applied during deposition we can obtain maximum coercivity value (2180 Oe). The \(M_{r}/M_{s}\) ratio was rapid increased when the magnetic field changed from 0 Oe to 750 Oe.