bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Influence of Substitution Patterns in Thioether‐Based Luminophores with Aggregation‐Induced Emission Properties
Authors: Stelzer Jacqueline , Vallet Cecilia , Sowa Andrea , Gonzalez‐Abradelo Dario , Riebe Steffen , Daniliuc Constantin G. , Ehlers Martin , Strassert Cristian. A. , Knauer Shirley K. , Voskuhl Jens
Published: January 2018

In this work we present a full study on the influence of substitution patterns in aromatic thioether‐based luminogens with aggregation induced emission properties. To this end nine different compounds, either with nitrile groups in ortho, meta or para positions as well as phenol groups in different positions were synthesized and investigated concerning their photophysical properties. Besides that, eight compounds were obtained as single crystals for X‐ray analysis to get a deeper understanding on the packing parameters, secondary interactions as well their influence on the properties of these compounds. Time dependent density functional theory calculations helped to understand the distribution of the frontier orbitals. Moreover, these nanostructures were analysed concerning their applicability as cellular markers. We could thus show that indeed subtle differences in shape and substitution pattern dramatically influence the photophysical properties as well as cellular uptake of the compounds.
Regulation of Charge Carrier Dynamics in ZnO Microarchitecture‐Based UV/Visible Photodetector via Photonic‐Strain Induced Effects
Authors: Purusothaman Yuvasree , Alluri Nagamalleswara Rao , Chandrasekhar Arunkumar , Vivekananthan Venkateswaran , Kim Sang‐Jae
Published: January 2018

A feasible, morphological influence on photoresponse behavior of ZnO microarchitectures such as microwire (MW), coral‐like microstrip (CMS), fibril‐like clustered microwire (F‐MW) grown by one‐step carrier gas/metal catalyst “free” vapor transport technique is reported. Among them, ZnO F‐MW exhibits higher photocurrent (IPh) response, i.e., IPh/ZnO F‐MW > IPh/ZnO CMS > IPh/ZnO MW. The unique structural alignment of ZnO F‐MW has enhanced the IPh from 14.2 to 186, 221, 290 µA upon various light intensities such as 0 to 6, 11, 17 mW cm−2 at λ405 nm. Herein, the nature of the as‐fabricated ZnO photodetector (PD) is also demonstrated modulated by tuning the inner crystals piezoelectric potential through the piezo‐phototronic effect. The IPh response of PD decreases monotonically by introducing compressive strain along the length of the device, which is due to the synergistic effect between the induced piezoelectric polarization and photogenerated charge carriers across the metal–semiconductor interface. The current behavior observed at the two interfaces acting as the source (S) and drain (D) is carefully investigated by analyzing the Schottky barrier heights (ΦSB). This work can pave the way for the development of geometrically modified strain induced performances of PD to promote next generation self‐powered optoelectronic integrated devices and switches.
Recent Advances of Flexible Data Storage Devices Based on Organic Nanoscaled Materials
Authors: Zhou Li , Mao Jingyu , Ren Yi , Han Su‐Ting , Roy Vellaisamy A. L. , Zhou Ye
Published: January 2018

Following the trend of miniaturization as per Moore's law, and facing the strong demand of next‐generation electronic devices that should be highly portable, wearable, transplantable, and lightweight, growing endeavors have been made to develop novel flexible data storage devices possessing nonvolatile ability, high‐density storage, high‐switching speed, and reliable endurance properties. Nonvolatile organic data storage devices including memory devices on the basis of floating‐gate, charge‐trapping, and ferroelectric architectures, as well as organic resistive memory are believed to be favorable candidates for future data storage applications. In this Review, typical information on device structure, memory characteristics, device operation mechanisms, mechanical properties, challenges, and recent progress of the above categories of flexible data storage devices based on organic nanoscaled materials is summarized.
Voltage‐Gated Nanoparticle Transport and Collisions in Attoliter‐Volume Nanopore Electrode Arrays
Authors: Fu Kaiyu , Han Donghoon , Crouch Garrison M. , Kwon Seung‐Ryong , Bohn Paul W.
Published: January 2018

Single nanoparticle analysis can reveal how particle‐to‐particle heterogeneity affects ensemble properties derived from traditional bulk measurements. High‐bandwidth, low noise electrochemical measurements are needed to examine the fast heterogeneous electron‐transfer behavior of single nanoparticles with sufficient fidelity to resolve the behavior of individual nanoparticles. Herein, nanopore electrode arrays (NEAs) are fabricated in which each pore supports two vertically spaced, individually addressable electrodes. The top ring electrode serves as a particle gate to control the transport of silver nanoparticles (AgNPs) within individual attoliter volume NEAs nanopores, as shown by redox collisions of AgNPs collisions at the bottom disk electrode. The AgNP‐nanoporeis system has wide‐ranging technological applications as well as fundamental interest, since the transport of AgNPs within the NEA mimics the transport of ions through cell membranes via voltage‐gated ion channels. A voltage threshold is observed above which AgNPs are able to access the bottom electrode of the NEAs, i.e., a minimum potential at the gate electrode is required to switch between few and many observed collision events on the collector electrode. It is further shown that this threshold voltage is strongly dependent on the applied voltage at both electrodes as well as the size of AgNPs, as shown both experimentally and through finite‐element modeling. Overall, this study provides a precise method of monitoring nanoparticle transport and in situ redox reactions within nanoconfined spaces at the single particle level.
Durable transition structure for long integral abutment bridges
Authors: Eichwalder Bernhard , Kollegger Johann
Published: January 2018

The construction of integral abutment bridges is becoming more common. Since these bridge structures have no expansion joints or bearings, it is possible to build low‐maintenance and long‐lasting structures. The length of most existing integral abutment bridges does not exceed 20 m, but larger lengths are also increasingly being implemented. Structures up to approximately 70 m are considered to be unproblematic. In longer integral abutment bridges, problems often occur in regard to surface cracks and settlements behind the abutments. To address these challenges, intensive research work has been conducted. A new jointless roadway transition structure for long integral abutment bridges has been developed at the Institute of Structural Engineering of TU Wien. The design principle of the new transition structure is based on the distribution of the deformations, which occur in the bridge due to temperature changes, shrinkage, creep, and external loading, over a longer area behind the abutment. Because the deformations are distributed, it is possible to build a seamless pavement structure across the expansion joint, from the bridge to the embankment. The Research Center for Road Engineering, TU Wien, has developed a special multilayer bituminous pavement structure just for this purpose. Based on the design considerations for the transition structure, a full‐scale prototype was built. The prototype was tested at various construction stages to obtain relevant data for practical use.
Oral Reading Accuracy: Findings and Implications From Recent Research
Authors: Rodgers Emily , D'Agostino Jerome V. , Kelly Robert H. , Mikita Clara
Published: January 2018

The three accuracy ranges for oral reading—easy, instructional level, and hard—are familiar to almost everyone who teaches young students just learning to read. It may come as a surprise to learn, then, that no study has yet been conducted with beginning readers to support our well‐accepted views about accuracy ranges and their role in reading development. What accuracy range is optimal? Does it really matter if a student reads with less than 90% accuracy? In this article, the authors share what they learned when they explored these questions about oral reading accuracy and student progress.
Short‐ and Long‐Term (10‐year) Results of an Organized, Population‐Based Breast Cancer Screening Program: Comparative, Observational Study from Hungary
Authors: Tóth Dezső , Varga Zsolt , Tóth Judit , Árkosy Péter , Sebő Éva
Published: January 2018

Background

A nationwide breast cancer screening program was introduced in Hungary in the year 2002 for women aged 45–65 years to be performed biannually.

Methods

To investigate and report the short‐term and 10‐year follow‐up results, we analyzed our Breast Unit’s prospectively led database of screened (Group A) and age‐matched symptomatic (Group B) patients from 2002 to 2007. We compared the clinicopathologic features of tumors and the impact of screening on surgical treatment, as well as the overall (OS), disease‐specific (DSS) and disease‐free survival (DFS) of different groups.

Results

Data from 208 screen‐detected and 101 symptomatic patients between 45 and 65 years of age were examined. Screen‐detected women were younger (54 vs. 58.5 years; p = 0.001) had significantly smaller tumors (15.5 vs. 17 mm; p = 0.044), and more breast‐conserving surgery (68.8 vs. 59.4%; p = 0.032). Survival statistics were not statistically different at the median follow‐up of 123 months; however, there was a trend toward improved DFS in Group A (82.7 vs. 74.3%; p = 0.074).

Conclusions

Our study showed a significant reduction in rates of mastectomy in the screen‐detected group in the short term, which does not translate into better survival rates based on initial long‐term data. In order to realize the real advantage of this newly enstated screening program, a longer period of investigation is needed.
Incidence and Predictors of Unsuspected Recurrent Laryngeal Nerve Lymph Node Metastases After Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma
Authors: Li Zhi‐Gang , Zhang Xiao‐Bin , Wen Yu‐Wen , Liu Yun‐Hen , Chao Yin‐Kai
Published: January 2018

Background

Radical lymph node (LN) dissection along the recurrent laryngeal nerve (RLN) area carries a substantial morbidity rate, and its usefulness in neoadjuvant chemoradiotherapy (nCRT)‐treated esophageal cancer patients remains unclear.

Methods

This study was conducted in two Asian thoracic surgery centers. Patients with esophageal squamous cell carcinoma (ESCC) who were judged to be ycN‐RLN(−) after nCRT and received bilateral RLN LN dissection were eligible. The incidence of unsuspected RLN LN involvement was analyzed, and we used least absolute shrinkage and selection operator (LASSO) regression to identify its predictors.

Results

A total of 56 patients (53 males and 3 females; mean age: 55 years) were included. The upper mediastinum—including the bilateral RLN area—was covered by the radiation field in 48 (85.3%) patients. Although all of them were judged as ycN‐RLN(−), unsuspected RLN LN involvement was identified on pathological examination in 11 (19.6%) subjects, being the only positive nodal station in seven. LASSO regression identified the pre‐nCRT RLN LN(cN‐RLN) status as the only independent predictor of ypN‐RLN positivity; in contrast, neither the tumor location nor the radiation dose to the upper mediastinum were independently associated with ypN‐RLN(+). RLN nodal dissection resulted in positive LN discovery rates of 30.8 and 10% in ycN‐RLN(−) patients who had positive and negative cN‐RLNs before nCRT, respectively. Consequently, 23.1 and 6.7% of patients in each subgroup would have been understaged in the absence of RLN nodal dissection.

Conclusion

Nearly one‐fifth of ESCC patients who were judged to be ycN‐RLN(−) unexpectedly had positive ypN‐RLN. The pre‐nCRT cN‐RLN status plays a key role in the selection of patients that should undergo RLN LN dissection after nCRT.
In vivo biosensors: mechanisms, development, and applications
Authors: Shi Shuobo , Ang Ee Lui , Zhao Huimin
Published: January 2018

In vivo biosensors can recognize and respond to specific cellular stimuli. In recent years, biosensors have been increasingly used in metabolic engineering and synthetic biology, because they can be implemented in synthetic circuits to control the expression of reporter genes in response to specific cellular stimuli, such as a certain metabolite or a change in pH. There are many types of natural sensing devices, which can be generally divided into two main categories: protein-based and nucleic acid-based. Both can be obtained either by directly mining from natural genetic components or by engineering the existing genetic components for novel specificity or improved characteristics. A wide range of new technologies have enabled rapid engineering and discovery of new biosensors, which are paving the way for a new era of biotechnological progress. Here, we review recent advances in the design, optimization, and applications of in vivo biosensors in the field of metabolic engineering and synthetic biology.
One fits all?
Authors: Schiappacasse Paulina , Müller Bernhard
Published: January 2018

Resilience ranks high on the environmentally oriented research agenda on sustainable urban and regional development. The annual “Global Forum on Urban Resilience and Adaptation” has become a meeting point for academia and practice. The United Nations 2030 Agenda for Sustainable Development uses the term in two of their 17 Sustainable Development Goals, i.e., in Goal No. 9 on infrastructure as a basis for economic development and No. 11 on cities and human settlements. Moreover, resilience has become a prominent topic in the New Urban Agenda. Against this background, the article provides an overview of recent discussion on resilience. It scrutinizes how the concept has been used by different researchers from diverse disciplines with special reference to urban, regional and environmental studies. A systematic literature review on resilience was carried out in order to shed light on recent developments of thought and practice. All in all, 650 articles were reviewed. Following an introduction into the topic and description of the applied methodological approach, different facets of the debate on resilience are presented, and conclusions are drawn. It can be seen that the discussion of resilience needs more specificity, transdisciplinary approaches, and regional contextualization, especially in urban and regional development studies in the countries of the global south.
Apache Struts 2: how technical and development gaps caused the Equifax Breach
Authors: Luszcz Jeff
Published: January 2018

You already know the story: by identifying an Apache Struts CVE-2017-5638 vulnerability, criminals exposed the personal data of up to 143 million Equifax customers. What needs closer examination is the cause. The coding risk that opened up the door must be identified and closed. And just as important, companies need to examine their development processes for openings that let vulnerabilities in. Open source software (OSS) is widely used in software applications but rarely tracked in detail. Companies don't know what they don't know regarding open source and the breach teaches important lessons about the need to close that gap.

An Apache Struts vulnerability allowed hackers to steal data on 143 million Equifax customers. What needs closer examination is the cause.

The breach offers a reminder about how security practices play an important role in protecting a company, along with instituting security policies into engineering planning and processes. There's an opportunity for a conversation about stopping hackers in their tracks with tight processes, especially with regard to the use of open source software, explains Jeff Luszcz of Flexera.
Securing the blockchain against hackers
Authors: Boireau Olivier
Published: January 2018

Blockchain technology is transforming the way data is shared and value is transferred. However, there remain significant obstacles that must be overcome before blockchain is ready for mainstream adoption – most notably, security. How to protect both the cryptographic keys that allow access to the ledger and blockchain applications remains a top concern for any organisation or individual interested in using blockchain to transact anything of significant value.

Blockchain technology is transforming the way data is shared and value is transferred. However, security concerns must be overcome before it is ready for mainstream adoption.

Protecting cryptographic keys remains a top concern. Using hardware security modules (HSMs) and trusted computers in place of digital wallets and as blockchain nodes will give security-conscious users and organisations assurance that no matter what blockchain application they choose, they have the means to protect digital assets, argues Olivier Boireau of Design SHIFT.
Water wave overwash of a step
Authors: Skene D. M. , Bennetts L. G. , Wright M. , Meylan M. H. , Maki K. J.
Published: January 2018

Water wave overwash of a step by small steepness, regular incident waves is analysed using a computational fluid dynamics (CFD) model and a mathematical model, in two spatial dimensions. The CFD model is based on the two-phase, incompressible Navier–Stokes equations, and the mathematical model is based on the coupled potential-flow and nonlinear shallow-water theories. The CFD model is shown to predict vortices, breaking and overturning in the region where overwash is generated, and that the overwash develops into fast-travelling bores. The mathematical model is shown to predict bore heights and velocities that agree with the CFD model, despite neglecting the complicated dynamics where the overwash is generated. Evidence is provided to explain the agreement in terms of the underlying agreement of mass and energy fluxes.
Dispersion coefficient in an electro-osmotic flow of a viscoelastic fluid through a microchannel with a slowly varying wall zeta potential
Authors: Arcos J. C. , Méndez F. , Bautista E. G. , Bautista O.
Published: January 2018

The dispersion coefficient of a passive solute in a steady-state pure electro-osmotic flow (EOF) of a viscoelastic liquid, whose rheological behaviour follows the simplified Phan-Thien–Tanner (sPTT) model, along a parallel flat plate microchannel, is studied. The walls of the microchannel are assumed to have modulated and low $\unicode[STIX]{x1D701}$ potentials, which vary slowly in the axial direction in a sinusoidal manner. The flow field required to obtain the dispersion coefficient was solved using the lubrication approximation theory (LAT). The solution of the electric potential is based on the Debye–Hückel approximation for a symmetric $(z:z)$ electrolyte. The viscoelasticity of the fluid is observed to notably amplify the axial distribution of the effective dispersion coefficients due to the variation in the $\unicode[STIX]{x1D701}$ potentials of the walls. The problem was formulated for two cases: when the Debye layer thickness (EDL) was on the order of unity (thick EDL) and in the limit where the thickness of the EDL was very small compared with the height of the microchannel (thin EDL limit). Due to the coupling between the nonlinear governing equations and the sPTT fluid model, they were replaced by their approximate linearized forms and solved in the limit of $\unicode[STIX]{x1D700}\ll 1$ using the regular perturbation technique. Here $\unicode[STIX]{x1D700}$ is the amplitude of the sinusoidal function of the $\unicode[STIX]{x1D701}$ potentials. Additionally, the numerical solution of the simplified governing equations was also obtained for $\unicode[STIX]{x1D700}=O(1)$ and compared with the approximate solution, showing excellent agreement for $0\leqslant \unicode[STIX]{x1D700}\leqslant 0.3$. Note that the dispersion coefficient primarily depends on the Deborah number, on the ratio of the half-height of the microchannel to the Debye length, and on the assumed variation in the $\unicode[STIX]{x1D701}$ potentials of the walls.
Power and False Negatives in Qualitative Comparative Analysis: Foundations, Simulation and Estimation for Empirical Studies
Authors: Rohlfing Ingo
Published: January 2018

In Qualitative Comparative Analysis (QCA), empirical researchers use the consistency value as one, if not sole, criterion to decide whether an association between a term and an outcome is consistent with a set-relational claim. Braumoeller (2015) points out that the consistency value is unsuitable for this purpose. We need to know the probability of obtaining it under the null hypothesis of no systematic relation. He introduces permutation testing for estimating the $p$ value of a consistency score as a safeguard against false positives. In this paper, I introduce permutation-based power estimation as a safeguard against false-negative conclusions. Low power might lead to the false exclusion of truth table rows from the minimization procedure and the generation and interpretation of invalid solutions. For a variety of constellations between an alternative and null hypothesis and numbers of cases, simulations demonstrate that power estimates can range from 1 to 0. Ex post power analysis for 63 truth table analyses shows that even under the most favorable constellation of parameters, about half of them can be considered low-powered. This points to the value of estimating power and calculating the required number of cases before the truth table analysis.
Quantifying Change Over Time: Interpreting Time-varying Effects In Duration Analyses
Authors: Ruhe Constantin
Published: January 2018

Duration analyses in political science often model nonproportional hazards through interactions with analysis time. To facilitate their interpretation, methodologists have proposed methods to visualize time-varying coefficients or hazard ratios. While these techniques are a useful, initial postestimation step, I argue that they are insufficient to identify the overall impact of a time-varying effect and may lead to faulty inference when a coefficient changes its sign. I show how even significant changes of a coefficient’s sign do not imply that the overall effect is reversed over time. In order to enable a correct interpretation of time-varying effects in this context, researchers should visualize their results with survivor functions. I outline how survivor functions are calculated for models with time-varying effects and demonstrate the need for such a nuanced interpretation using the prominent finding of a time-varying effect of mediation on interstate conflict. The reanalysis of the data using the proposed visualization methods indicates that the conclusions of earlier mediation research are misleading. The example highlights how survivor functions are an essential tool to clarify the ambiguity inherent in time-varying coefficients in event history models.
The Creation of the Monnet Plan, 1945–1946: A Critical Re-Evaluation– ERRATUM
Authors: BRUNET LUC-ANDRÉ
Published: January 2018

The original version of this article was published with the incorrect author name. The author's name should have appeared as “Luc-André Brunet”.

We apologise to the authors and readers for this error and reproduce the entire corrected paper on the following pages.
VARIETIES OF LEFT RESTRICTION SEMIGROUPS
Authors: JONES PETER R.
Published: January 2018

Left restriction semigroups are the unary semigroups that abstractly characterize semigroups of partial maps on a set, where the unary operation associates to a map the identity element on its domain. They may be defined by a simple set of identities and the author initiated a study of the lattice of varieties of such semigroups, in parallel with the study of the lattice of varieties of two-sided restriction semigroups. In this work we study the subvariety$\mathbf{B}$generated by Brandt semigroups and the subvarieties generated by the five-element Brandt inverse semigroup$B_{2}$, its four-element restriction subsemigroup$B_{0}$and its three-element left restriction subsemigroup$D$. These have already been studied in the ‘plain’ semigroup context, in the inverse semigroup context (in the first two instances) and in the two-sided restriction semigroup context (in all but the last instance). The author has previously shown that in the last of these contexts, the behavior is pathological: ‘almost all’ finite restriction semigroups are inherently nonfinitely based. Here we show that this is not the case for left restriction semigroups, by exhibiting identities for the above varieties and for their joins with monoids (the analog of groups in this context). We do so by structural means involving subdirect decompositions into certain primitive semigroups. We also show that each identity has a simple structural interpretation.
The amyotrophic lateral sclerosis supportive care needs assessment instrument: Development and psychometric evaluation
Authors: Oh Juyeon , Oh Seong-il , Kim Jung A
Published: January 2018

Objective

The aim of the study is to develop an amyotrophic lateral sclerosis supportive care needs (ALSSCN) instrument based on Fitch's Supportive Care Needs Framework and to test its psychometric properties.

Method

This study consists of three parts: (1) item generation from the literature review and qualitative interview; (2) content validation; and (3) psychometric evaluation of the instrument. Participants who were diagnosed with ALS (n = 139) were recruited from two ALS clinics in Seoul, Korea, and Busan, Korea for the psychometric testing.

Result

The ALSSCN consisted of 37 items with seven domains: physical, psychological, emotional, spiritual, social, informational, and practical needs. The Cronbach's alpha of each domain ranged from 0.61 (social needs) to 0.90 (emotional needs). The intra-class correlation coefficient for test-retest was 0.89, indicating good test-retest reliability. The overall ALSSCN was significantly negatively correlated with the quality of life, which supported convergent validity. Confirmatory factor analysis of the ALSSCN supported a seven-factor model.

Significance of results

The ALSSCN has acceptable internal consistency, stability, and content and construct validity in a Korean ALS population. ALSSCN is a psychometrically sound measure and can be adopted by healthcare professionals, researchers, and administrators to comprehensively assess the perceived supportive care needs of patients with ALS.
THE LOGIC AND TOPOLOGY OF KANT’S TEMPORAL CONTINUUM
Authors: PINOSIO RICCARDO , VAN LAMBALGEN MICHIEL
Published: January 2018

In this paper we provide a mathematical model of Kant’s temporal continuum that yields formal correlates for Kant’s informal treatment of this concept in theCritique of Pure Reasonand in other works of his critical period. We show that the formal model satisfies Kant’s synthetic a priori principles for time (whose consistence is not obvious) and that it even illuminates what “faculties and functions” must be in place, as “conditions for the possibility of experience”, for time to satisfy such principles. We then present a mathematically precise account of Kant’s transcendental theory of time—the most precise account to date.

Moreover, we show that the Kantian continuum which we obtain has some affinities with the Brouwerian continuum but that it also has “infinitesimal intervals” consisting of nilpotent infinitesimals; these allow us to capture Kant’s theory of rest and motion in theMetaphysical Foundations of Natural Science.

While our focus is on Kant’s theory of time the material in this paper is more generally relevant for the problem of developing a rigorous theory of the phenomenological continuum, in the tradition of Whitehead, Russell, and Weyl among others.
Demenz-Früherkennung bei Menschen mit Intelligenzminderung – eine Pilotstudie zur Anwendbarkeit des Demenztests für Menschen mit Intelligenzminderung (DTIM)
Authors: Kuske Bettina , Müller Sandra Verena
Published: January 2018

Zusammenfassung. Im Rahmen dieser Studie wurde ein Untersuchungsverfahren zur Demenzfrüherkennung und Verlaufsdiagnostik bei Menschen mit Intelligenzminderung (IM) entwickelt, welches aus einer Fremdbefragung und einer neuropsychologischen Testung besteht. Die Anwendung des Demenztests für Menschen mit Intelligenzminderung (DTIM) wurde in einer prospektiven zweijährigen Verlaufsstudie evaluiert. 102 Personen mit unterschiedlichen Schweregraden einer Intelligenzminderung (IM) wurden zu vier Testzeitpunkten in sechsmonatigen Abständen untersucht. Anhand der individuellen Verlaufsprofile konnten vier Gruppen identifiziert werden: (1) Verdacht bestätigt, (2) Kein Verdacht bestätigt, (3) Verdacht nicht bestätigt und (4) Früher Verdacht. Der DTIM konnte bei 90 %-100 % aller Teilnehmenden mit leichter bis mittelschwerer IM und bis zu 50 % bei Menschen mit schwerer IM eingesetzt werden. Signifikante Unterschiede zeigten sich zwischen Gruppe 1 und 2 zu allen Messzeitpunkten.
Fabrication of 3D air-core MEMS inductors for very-high-frequency power conversions
Authors: Le Hoa Thanh , Mizushima Io , Nour Yasser , Tang Peter Torben , Knott Arnold , Ouyang Ziwei , Jensen Flemming , Han Anpan
Published: January 2018

We report a fabrication technology for 3D air-core inductors for small footprint and very-high-frequency power conversions. Our process is scalable and highly generic for fabricating inductors with a wide range of geometries and core shapes. We demonstrate spiral, solenoid, and toroidal inductors, a toroidal transformer and inductor with advanced geometries that cannot be produced by wire winding technology. The inductors are embedded in a silicon substrate and consist of through-silicon vias and suspended windings. The inductors fabricated with 20 and 25 turns and 280-350 μm heights on 4-16 mm2 footprints have an inductance from 34.2 to 44.6 nH and a quality factor from 10 to 13 at frequencies ranging from 30 to 72 MHz. The air-core inductors show threefold lower parasitic capacitance and up to a 140% higher-quality factor and a 230% higher-operation frequency than silicon-core inductors. A 33 MHz boost converter mounted with an air-core toroidal inductor achieves an efficiency of 68.2%, which is better than converters mounted with a Si-core inductor (64.1%). Our inductors show good thermal cycling stability, and they are mechanically stable after vibration and 2-m-drop tests.
Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice
Authors: Wang Jun , Hodes Georgia E. , Zhang Hongxing , Zhang Song , Zhao Wei , Golden Sam A. , Bi Weina , Menard Caroline , Kana Veronika , Leboeuf Marylene , Xie Marc , Bregman Dana , Pfau Madeline L. , Flanigan Meghan E. , Esteban-Fernández Adelaida , Yemul Shrishailam , Sharma Ali , Ho Lap , Dixon Richard , Merad Miriam , Han Ming-Hu , Russo Scott J. , Pasinetti Giulio M.
Published: January 2018

Major depressive disorder is associated with abnormalities in the brain and the immune system. Chronic stress in animals showed that epigenetic and inflammatory mechanisms play important roles in mediating resilience and susceptibility to depression. Here, through a high-throughput screening, we identify two phytochemicals, dihydrocaffeic acid (DHCA) and malvidin-3′-O-glucoside (Mal-gluc) that are effective in promoting resilience against stress by modulating brain synaptic plasticity and peripheral inflammation. DHCA/Mal-gluc also significantly reduces depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of hematopoietic progenitor cells from stress-susceptible mice. DHCA reduces pro-inflammatory interleukin 6 (IL-6) generations by inhibiting DNA methylation at the CpG-richIL-6sequences introns 1 and 3, while Mal-gluc modulates synaptic plasticity by increasing histone acetylation of the regulatory sequences of theRac1gene. Peripheral inflammation and synaptic maladaptation are in line with newly hypothesized clinical intervention targets for depression that are not addressed by currently available antidepressants.
Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer
Authors: Severson Tesa M. , Kim Yongsoo , Joosten Stacey E. P. , Schuurman Karianne , van der Groep Petra , Moelans Cathy B. , ter Hoeve Natalie D. , Manson Quirine F. , Martens John W. , van Deurzen Carolien H. M. , Barbe Ellis , Hedenfalk Ingrid , Bult Peter , Smit Vincent T. H. B. M. , Linn Sabine C. , van Diest Paul J. , Wessels Lodewyk , Zwart Wilbert
Published: January 2018

Male breast cancer (MBC) is rare and poorly characterized. Like the female counterpart, most MBCs are hormonally driven, but relapse after hormonal treatment is also noted. The pan-hormonal action of steroid hormonal receptors, including estrogen receptor alpha (ERα), androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) in this understudied tumor type remains wholly unexamined. This study reveals genomic cross-talk of steroid hormone receptor action and interplay in human tumors, here in the context of MBC, in relation to the female disease and patient outcome. Here we report the characterization of human breast tumors of both genders for cistromic make-up of hormonal regulation in human tumors, revealing genome-wide chromatin binding landscapes of ERα, AR, PR, GR, FOXA1, and GATA3 and enhancer-enriched histone mark H3K4me1. We integrate these data with transcriptomics to reveal gender-selective and genomic location-specific hormone receptor actions, which associate with survival in MBC patients.
Gene therapy for human glioblastoma using neurotropic JC virus-like particles as a gene delivery vector
Authors: Chao Chun-Nun , Yang Yu-Hsuan , Wu Mu-Sheng , Chou Ming-Chieh , Fang Chiung-Yao , Lin Mien-Chun , Tai Chien-Kuo , Shen Cheng-Huang , Chen Pei-Lain , Chang Deching , Wang Meilin
Published: January 2018

Glioblastoma multiforme (GBM), the most common malignant brain tumor, has a short period of survival even with recent multimodality treatment. The neurotropic JC polyomavirus (JCPyV) infects glial cells and oligodendrocytes and causes fatal progressive multifocal leukoencephalopathy in patients with AIDS. In this study, a possible gene therapy strategy for GBM using JCPyV virus-like particles (VLPs) as a gene delivery vector was investigated. We found that JCPyV VLPs were able to deliver the GFP reporter gene into tumor cells (U87-MG) for expression. In an orthotopic xenograft model, nude mice implanted with U87 cells expressing the near-infrared fluorescent protein and then treated by intratumoral injection of JCPyV VLPs carrying the thymidine kinase suicide gene, combined with ganciclovir administration, exhibited significantly prolonged survival and less tumor fluorescence during the experiment compared with controls. Furthermore, JCPyV VLPs were able to protect and deliver a suicide gene to distal subcutaneously implanted U87 cells in nude mice via blood circulation and inhibit tumor growth. These findings show that metastatic brain tumors can be targeted by JCPyV VLPs carrying a therapeutic gene, thus demonstrating the potential of JCPyV VLPs to serve as a gene therapy vector for the far highly treatment-refractory GBM.
Early skeletal colonization of the coral holobiont by the microboring Ulvophyceae Ostreobium sp.
Authors: Massé A. , Domart-Coulon I. , Golubic S. , Duché D. , Tribollet A.
Published: January 2018

Ostreobium sp. (Bryopsidales, Ulvophyceae) is a major microboring alga involved in tropical reef dissolution, with a proposed symbiotic lifestyle in living corals. However, its diversity and colonization dynamics in host’s early life stages remained unknown. Here, we mapped microborer distribution and abundance in skeletons of the branching coral Pocillopora damicornis from the onset of calcification in primary polyps (7 days) to budding juvenile colonies (1 and 3 months) growing on carbonate and non-carbonate substrates pre-colonized by natural biofilms, and compared them to adult colonies (in aquarium settings). Primary polyps were surprisingly already colonized by microboring filaments and their level of invasion depended on the nature of settlement substrate and the extent of its pre-colonization by microborers. Growth of early coral recruits was unaffected even when microborers were in close vicinity to the polyp tissue. In addition to morphotype observations, chloroplast-encoded rbcL gene sequence analyses revealed nine new Ostreobium clades (OTU99%) in Pocillopora coral. Recruits and adults shared one dominant rbcL clade, undetected in larvae, but also present in aquarium seawater, carbonate and non-carbonate settlement substrates, and in corals from reef settings. Our results show a substratum-dependent colonization by Ostreobium clades, and indicate horizontal transmission of Ostreobium-coral associations.
Hepatocellular carcinoma-targeting oncolytic adenovirus overcomes hypoxic tumor microenvironment and effectively disperses through both central and peripheral tumor regions
Authors: Yoon A-Rum , Hong JinWoo , Kim Minjung , Yun Chae-Ok
Published: January 2018

Cancer-specific promoter driven replication of oncolytic adenovirus (Ad) is cancer-specific, but shows low transcriptional activity. Thus, we generated several chimeric α-fetoprotein (AFP) promoter variants, containing reconstituted enhancer and silencer regions, to preferentially drive Ad replication in hepatocellular carcinoma (HCC). Modified AFP promoter, containing 2 enhancer A regions and a single enhancer B region (a2bm), showed strong and HCC-specific transcription. In AFP-positive HCCs, gene expression was 43- to 456-fold higher than those of control AFP promoter lacking enhancers. a2bm promoter was further modified by inserting multiple hypoxia-responsive elements (HRE) to generate Ha2bm promoter, which showed stronger transcriptional activity than a2bm promoter under hypoxic conditions. Ha2bm promoter-regulated oncolytic Ad (Ha2bm-d19) showed a stronger antitumor and proapoptotic effect than did a2bm promoter-regulated oncolytic Ad (a2bm-d19) in HCC xenograft tumors. Systemically administered Ha2bm-d19 caused no observable hepatotoxicity, whereas control replication-competent Ad, lacking cancer specificity (d19), induced significant hepatic damage. Ha2bm-d19 caused significantly lower expression of interleukin-6 than d19, showing that HCC-targeted delivery of Ad attenuates induction of the innate immune response against Ad. This chimeric AFP promoter enabled Ad to overcome the hypoxic tumor microenvironment and target HCC with high specificity, rendering it a promising candidate for the treatment of aggressive HCCs.
Tiny timekeepers witnessing high-rate exhumation processes
Authors: Zhong Xin , Moulas Evangelos , Tajčmanová Lucie
Published: January 2018

Tectonic forces and surface erosion lead to the exhumation of rocks from the Earth’s interior. Those rocks can be characterized by many variables including peak pressure and temperature, composition and exhumation duration. Among them, the duration of exhumation in different geological settings can vary by more than ten orders of magnitude (from hours to billion years). Constraining the duration is critical and often challenging in geological studies particularly for rapid magma ascent. Here, we show that the time information can be reconstructed using a simple combination of laser Raman spectroscopic data from mineral inclusions with mechanical solutions for viscous relaxation of the host. The application of our model to several representative geological settings yields best results for short events such as kimberlite magma ascent (less than ~4,500 hours) and a decompression lasting up to ~17 million years for high-pressure metamorphic rocks. This is the first precise time information obtained from direct microstructural observations applying a purely mechanical perspective. We show an unprecedented geological value of tiny mineral inclusions as timekeepers that contributes to a better understanding on the large-scale tectonic history and thus has significant implications for a new generation of geodynamic models.
DNA damage in leukocytes after internal ex-vivo irradiation of blood with the α-emitter Ra-223
Authors: Schumann Sarah , Eberlein Uta , Muhtadi Razan , Lassmann Michael , Scherthan Harry
Published: January 2018

Irradiation with high linear energy transfer α-emitters, like the clinically used Ra-223 dichloride, severely damages cells and induces complex DNA damage including closely spaced double-strand breaks (DSBs). As the hematopoietic system is an organ-at-risk for the treatment, knowledge about Ra-223-induced DNA damage in blood leukocytes is highly desirable. Therefore, 36 blood samples from six healthy volunteers were exposed ex-vivo (in solution) to different concentrations of Ra-223. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the decay, ranging from 0 to 142 mGy. γ-H2AX + 53BP1 co-staining and analysis was performed in leukocytes isolated from the irradiated blood samples. For DNA damage quantification, leukocyte samples were screened for occurrence of α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values, being in agreement with a negligible β-contribution (3.7%) to the total absorbed dose to the blood. Our calibration curve will contribute to the biodosimetry of Ra-223-treated patients and early after incorporation of α-emitters.
Associations between serum polybrominated diphenyl ethers and thyroid hormones in a cross sectional study of a remote Alaska Native population
Authors: Byrne Samuel C. , Miller Pamela , Seguinot-Medina Samarys , Waghiyi Vi , Buck C. Loren , von Hippel Frank A. , Carpenter David O.
Published: January 2018

Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants. Arctic indigenous peoples are exposed to PBDEs through a traditional diet high in marine mammals. PBDEs disrupt thyroid homeostasis. The aim of this study was to assess the relationship between serum PBDEs and thyroid function in a remote population of St. Lawrence Island Yupik. Serum samples were collected from 85 individuals from St. Lawrence Island, Alaska and measured for concentrations of PBDEs, free and total thyroxine (T4), free and total triiodothyronine (T3), and thyroid stimulating hormone (TSH). The relationships between PBDEs and thyroid hormones were assessed using multiple linear regression fit with generalized estimating equations. Serum concentrations of several Penta-BDE congeners (BDE-28/33, 47, and 100) were positively associated with concentrations of TSH and free T3, while serum concentration of BDE-153 was negatively associated with total T3 concentrations. Both BDE-47 and 153 remained significantly associated with thyroid hormones when BDE-47, BDE-153, and BDE-209 were covariates in the same model. There were no significant relationships between serum concentrations of PBDEs and either free or total T4. Individual PBDEs are associated with thyroid hormones in serum from a remote population of Alaska Natives, and directions of effect differ by congener.
The ciliopathy protein TALPID3/KIAA0586 acts upstream of Rab8 activation in zebrafish photoreceptor outer segment formation and maintenance
Authors: Ojeda Naharros Irene , Cristian Flavia B. , Zang Jingjing , Gesemann Matthias , Ingham Philip W. , Neuhauss Stephan C. F. , Bachmann-Gagescu Ruxandra
Published: January 2018

Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous microtubule-based organelles involved in signal transduction. Cilia are anchored inside the cell through basal bodies (BBs), modified centrioles also acting as microtubule-organization centers. Photoreceptors (PRs) are sensory neurons, whose primary cilium forms a highly specialized compartment called the outer segment (OS) responsible for sensing incoming light. Thus, ciliopathies often present with retinal degeneration. Mutations in KIAA0586/TALPID3 (TA3) cause Joubert syndrome, in which 30% of affected individuals develop retinal involvement. To elucidate the function of TALPID3 in PRs, we studied talpid3 zebrafish mutants and identified a progressive retinal degeneration phenotype. The majority of PRs lack OS development due to defects in BB positioning and docking at the apical cell surface. Intracellular accumulation of the photopigment opsin leads to PR cell death of moderate severity. Electroretinograms demonstrate severe visual impairement. A small subset of PRs display normally docked BBs and extended OSs through rescue by maternally-deposited Talpid3. While localization of the small GTPase Rab8a, which plays an important role in BB docking, appears unaffected in talpid3−/− PRs, overexpression of constitutively active Rab8a rescues OS formation, indicating that the role of Ta3 in early ciliogenesis lies upstream of Rab8a activation in PRs.
Polymerization-Induced Phase Separation Formation of Structured Hydrogel Particles via Microfluidics for Scar Therapeutics
Authors: Guo S. , Kang G. , Phan D. T. , Hsu M. N. , Por Y. C. , Chen C. H.
Published: January 2018

Excessive scar formation can form disabling contractures that result in a debilitating psychological outcome. Sustainable hydrophobic corticosteroid release in vivo is essential to regulate the wound healing process. Functional hydrogel particles are widely applied for sustainable release. However, due to the limited aqueous solubility of hydrophobic compounds, most of the corticosteroid is released from the hydrogels within seconds, causing undesirable scar formation and recurrence. In this study, a novel polymerization-induced phase separation is investigated to form well-defined polyethylene glycol diacrylate (PEGDA) core/alginate shell structured hydrogel particles using microfluidics without toxic organic solvents. Based on their wettability preference, hydrophobic corticosteroid-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles are compartmentalized in the PEGDA core during polymerization to control the corticosteroid release. The distribution of the PLGA nanoparticles is precisely regulated by the phase separation boundary and characterized using a fluorescent dye. The thickness of the shell and partition coefficients are determined using the UV intensity and irradiation period. Upon encapsulation of the PLGA nanoparticles within the poly(PEGDA) core, a long-term corticosteroid treatment is developed and effective scar therapeutic outcomes are evaluated using both in vitro and in vivo models.
TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin
Authors: Kanda Yusuke , Yamasaki Youhei , Sasaki-Yamaguchi Yoshie , Ida-Koga Noriko , Kamisuki Shinji , Sugawara Fumio , Nagumo Yoko , Usui Takeo
Published: January 2018

The delivery of hydrophilic macromolecules runs into difficulties such as penetration of the cell membrane lipid bilayer. Our prior experiment demonstrated that capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. Herein, we screened paracellular permeability enhancers other than capsaicin. As TJ opening by capsaicin is associated with Ca2+ influx, we first screened the compounds that induce Ca2+ influx in layered MDCK II cells, and then we determined the compounds’ abilities to open TJs. Our results identified several natural compounds with α,β-unsaturated moiety. A structure-activity relationship (SAR) analysis and the results of pretreatment with reducing reagent DTT suggested the importance of α,β-unsaturated moiety. We also examined the underlying mechanisms, and our findings suggest that the actin reorganization seen in capsaicin treatment is important for the reversibility of TJ opening. Furthermore, our analyses revealed that TRPA1 is involved in the Ca2+ influx and TJ permeability increase not only by an α,β-unsaturated compound but also by capsaicin. Our results indicate that the α,β-unsaturated moiety can be a potent pharmacophore for TJ opening.