bluuebunny/crossref_metadata_2025 huggingface dataset:
A double exponentially weighted moving average chart based on likelihood ratio for monitoring an inflated Pareto process
Authors: Bizuneh Berihun , Wang Fu‐Kwun
Published: March 2019

In this paper, we present a new chart called a likelihood ratio based double exponentially weighted moving average (LR_DEWMA) chart to monitor the shape parameter of the inflated Pareto process. Three other control charts such as the Shewhart type, the classical cumulative sum (CUSUM), and the likelihood ratio based EWMA (LR_EWMA) charts are also investigated. The performance of the control charts is evaluated by the average run length (ARL) and standard deviation of run lengths (SDRL) computed through the Monte Carlo simulation approach. Moreover, the median run length (MRL) and some other run length (RL) percentiles are also considered in some cases. Different charts have shown the best performance in different cases. In detecting smaller shifts, while the LR_DEWMA chart outperformed the other charts in terms of ARL and MRL, the CUSUM chart has shown the best performance in terms of SDRL and IQR of RLs. The application of the proposed control charts is illustrated using a chromatography analyses data from the food industry.
The Akaike information criterion: Background, derivation, properties, application, interpretation, and refinements
Authors: Cavanaugh Joseph E. , Neath Andrew A.
Published: March 2019

The Akaike information criterion (AIC) is one of the most ubiquitous tools in statistical modeling. The first model selection criterion to gain widespread acceptance, AIC was introduced in 1973 by Hirotugu Akaike as an extension to the maximum likelihood principle. Maximum likelihood is conventionally applied to estimate the parameters of a model once the structure and dimension of the model have been formulated. Akaike's seminal idea was to combine into a single procedure the process of estimation with structural and dimensional determination. This article reviews the conceptual and theoretical foundations for AIC, discusses its properties and its predictive interpretation, and provides a synopsis of important practical issues pertinent to its application. Comparisons and delineations are drawn between AIC and its primary competitor, the Bayesian information criterion (BIC). In addition, the article covers refinements of AIC for settings where the asymptotic conditions and model specification assumptions that underlie the justification of AIC may be violated.

This article is categorized under:

Software for Computational Statistics > Artificial Intelligence and Expert Systems

Statistical Models > Model Selection

Statistical and Graphical Methods of Data Analysis > Modeling Methods and Algorithms

Statistical and Graphical Methods of Data Analysis > Information Theoretic Methods
Fundamental solution for extended dislocation in one‐dimensional piezoelectric quasicrystal and application to fracture analysis
Authors: Fan CuiYing , Chen Shuai , Xu GuangTao , Zhang QiaoYun
Published: March 2019

In this paper, we derive a fundamental solution for extended dislocations of one‐dimensional (1D) hexagonal piezoelectric quasicrystals. Based on the Stroh formalism, the fundamental solutions for 1D hexagonal piezoelectric quasicrystals expressing by extended dislocations, including phonon, electric, and phason dislocations, are obtained. Then, by considering the continuously distributed dislocations to be a crack, the crack opening displacement, intensity factor, and energy release rate of the extended dislocation are expressed. Numerical calculations are used to confirm the validity of the theory and to investigate the effect of different parameters on the energy release rate.
POPE FRANCIS, TRUE RELIGION, AND RELIGIOUS LIBERTY
Authors: Harrison Joel
Published: March 2019

This article examines Pope Francis's understanding of the relationship between church and state, the ends of civil authority, and the importance of religious liberty. It argues that Francis challenges claims made by legal and religious scholars that civil authority must be neutral as to religious ends. Francis, the article contends, uses the categories of idolatry and solidarity as opposing ends that are cultivated by civil authorities caring for, most notably, the economy and the environment. Both are religious. Idolatry is the solipsistic pursuit of created things as an ultimate end and solidarity entails living in communion with God and others. The article further considers how these arguments have shaped Francis's views on religious liberty. Francis points to the importance of civil authorities respecting conscientious objection, the desirability of cultivating healthy pluralism, and religious liberty as securing the end of solidarity. This presents two challenges: first, to recent legal scholarship questioning the special importance of religious liberty; and second, to the exercise of religious liberty itself. If religious liberty is protected for the end of solidarity, can it be exercised wrongly? The article concludes by considering the Supreme Court's 2014 Hobby Lobby decision.
Modern pollen-vegetation relationships along a steep temperature gradient in the Tropical Andes of Ecuador
Authors: Hagemans Kimberley , Tóth Claudia-Dana , Ormaza Manuela , Gosling William D. , Urrego Dunia H. , León-Yánez Susana , Wagner-Cremer Friederike , Donders Timme H.
Published: March 2019

The characterization of modern pollen rain assemblages along environmental gradients is an essential prerequisite for reliable interpretations of fossil pollen records. In this study, we identify pollen-vegetation relationships using modern pollen rain assemblages in moss polsters (n = 13) and lake sediment surface samples (n = 11) along a steep temperature gradient of 7°C (3100–4200 m above sea level) on the western Andean Cordillera, Ecuador. The pollen rain is correlated to vascular plant abundance data recorded in vegetation relevées (n = 13). Results show that pollen spectra from both moss polsters and sediment surface samples reflect changes in species composition along the temperature gradient, despite overrepresentation of upper montane forest taxa in the latter. Estimated pollen transport distance for a lake (Laguna Llaviucu) situated in a steep upper montane forest valley is 1–2 km, while a lake (Laguna Pallcacocha) in the páramo captures pollen input from a distance of up to 10–40 km. Weinmannia spp., Podocarpus spp., and Hedyosmum sp. are indicators of local upper montane forest vegetation, while Phlegmariurus spp. and Plantago spp. are indicators for local páramo vegetation.
Le participe passé et la construction analytique des temps verbaux en français
Authors: Bres Jacques , Le Bellec Christel
Published: March 2019

Le présent article défend la thèse selon laquelle (i) le participe passé est une forme purement aspectuelle représentant le temps interne du procès sur la borne terminale de sa phase processuelle ; (ii) cette représentationdétensivedu temps interne, qu’il ne partage avec aucune autre forme verbale, permet de rendre compte des trois principales constructions dans lesquelles entre le participe passé : l’emploi nu, la construction du passif périphrastique, la construction analytique. C’est à l’analyse du rôle du participe passé dans la construction analytique, du fait de son aspect détensif, qu’est consacré le présent article.
An asymptotic bound for the strong chromatic number
Authors: Lo Allan , Sanhueza-Matamala Nicolás
Published: March 2019

The strong chromatic number χs(G) of a graph G on n vertices is the least number r with the following property: after adding $r\lceil n/r\rceil-n$ isolated vertices to G and taking the union with any collection of spanning disjoint copies of Kr in the same vertex set, the resulting graph has a proper vertex colouring with r colours. We show that for every c > 0 and every graph G on n vertices with Δ(G) ≥ cn, χs(G) ≤ (2+o(1))Δ(G), which is asymptotically best possible.
The importance of trace minerals copper, manganese, selenium and zinc in bovine sperm–zona pellucida binding
Authors: Anchordoquy Juan Patricio , Anchordoquy Juan Mateo , Lizarraga Raúl Martín , Nikoloff Noelia , Pascua Ana Malen , Furnus Cecilia Cristina
Published: March 2019

Sperm–zona pellucida (ZP) binding is a necessary event for successful fertilization. The aim of this study was to determine the effect of trace minerals such as copper (Cu), manganese (Mn), selenium (Se) and zinc (Zn) on bovine spermatozoa binding to ZP. Sperm viability, functional membrane integrity, acrosomal status (AS), total antioxidant capacity (TAC) and sperm lipid peroxidation (LPO) were also evaluated. For the present study,in vitrofertilization (IVF) medium was supplemented with Cu (0.4 µg/ml Cu), Mn (5 ng/ml Mn), Se (100 ng/ml Se), Zn (0.8 µg/ml Zn), all minerals (Cu+Mn+Se+Zn), or tested without supplement (Control). Considerably more sperm bound to ZP when Cu, Se or Zn were added to the IVF medium, but there were no difference compared with the Control, Mn and Cu+Mn+Se+Zn groups. After 1 h of incubation, viability was increased by the addition of Cu, Mn and Se with respect to the Control but, after 2 h, viability was higher only with the addition of Mn to IVF medium. Functional membrane integrity improved in sperm treated with Cu. Acrosome integrity was higher in sperm treated with Zn after 1 h of incubation. LPO was significantly higher in sperm treated with Cu or Cu+Mn+Se+Zn. The mean TACs of sperm treated with Cu, Mn, Zn or Cu+Mn+Se+Zn were lower than in the Control. In conclusion, the results obtained in the present study determined that the presence of Cu, Se and Zn in the IVF medium increased the number of spermatozoa bound to the ZP, highlighting the importance of these minerals in the fertilization process.
How could Expert Involvement Compensate for an Incomplete Capability of Legitimization through Democratic Representation? Debating the Grounds for Political Legitimacy in the EU
Authors: Caspers Lena , Strandberg Urban
Published: March 2019

This article contributes to the scholarly as well as societal decades-long debate on the state of democracy in the EU. The objective is to problematize, discuss, and come up with constructive ideas on the role of expert groups in the processes of legitimization of decision-making within the EU. The analysis is guided by a general research question: how could expert involvement compensate for an incomplete capability of legitimization through democratic representation? The empirical analysis of expert influence in decision-making is guided by a new modelling of the so-called Epistemic Community approach. The case chosen to illustrate the model is the authorization process of the emergency contraceptive ellaOne, within the institutional setting of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency. The empirical material consists of interviews with eight members of the CHMP. To guide the empirical analysis the paper introduces a two-dimensional model of the epistemic community approach, which distinguishes between the institutional preconditions and the ideational motivations of expert groups. The results indicate that the experts within the CHMP had an influence on the policy-making process thanks to favourable institutional preconditions as well as ideational motivations of the experts themselves. Our conclusion is that there is a need for ‘institutional engineering’ as regards the involvement of experts in decision-making, to sustain the legitimacy of expert involvement, and level out the institutional conditions for experts’ influence on policy-making within the EU.
The Negative Effects Questionnaire: psychometric properties of an instrument for assessing negative effects in psychological treatments
Authors: Rozental Alexander , Kottorp Anders , Forsström David , Månsson Kristoffer , Boettcher Johanna , Andersson Gerhard , Furmark Tomas , Carlbring Per
Published: March 2019

Background:

Psychological treatments provide many benefits for patients with psychiatric disorders, but research also suggests that negative effects might occur from the interventions involved. The Negative Effects Questionnaire (NEQ) has previously been developed as a way of determining the occurrence and characteristics of such incidents, consisting of 32 items and six factors. However, the NEQ has yet to be examined using modern test theory, which could help to improve the understanding of how well the instrument works psychometrically.

Aims:

The current study investigated the reliability and validity of the NEQ from both a person and item perspective, establishing goodness-of-fit, item bias, and scale precision.

Method:

The NEQ was distributed to 564 patients in five clinical trials at post-treatment. Data were analysed using Rasch analysis, i.e. a modern test theory application.

Results:

(1) the NEQ exhibits fairness in testing across sociodemographics, (2) shows comparable validity for a final and condensed scale of 20 instead of 32 items, (3) uses a rating scale that advances monotonically in steps of 0 to 4, and (4) is suitable for monitoring negative effects on an item-level.

Conclusions:

The NEQ is proposed as a useful instrument for investigating negative effects in psychological treatments, and its newer shorter format could facilitate its use in clinical and research settings. However, further research is needed to explore the relationship between negative effects and treatment outcome, as well as to test it in more diverse patient populations.
The Art of Chieftaincy in the Writings of Pashtun Tribal Rulers
Authors: PELEVIN MIKHAIL
Published: March 2019

The article surveys the views of Pashtun military-administrative elite on governance in the works of Khushḥāl Khān Khaṫak (d. 1689) and Afżal Khān Khaṫak (d. circa 1740). The texts under discussion pertain to the universal literary genre of “Mirrors for Princes”(naṣīḥat al-mulūk)and include the Khaṫak chieftains’ didactical writings in prose and verse, as well as still poorly studied documents on real politics from Afżal Khān's historiographical compilation “The Ornamented History”(Tārīkh-i muraṣṣaʿ). Rooted in the medieval Persian classics, early modern Pashto “mirrors” are distinguished by local ethnocultural peculiarities which manifest in shifting the very subject from statesmanship to chieftaincy and declaring regulations of the Pashtun unwritten Code of Honour. The study proves that the outlook and behavioural patterns of Pashtun tribal rulers stemmed from a combination, partly eclectic and contradictory, of Islamic precepts, feudal ideologies of the Mughal administrative system, and norms of the Pashtun customary law(Pashtunwali).
Swimming with wealthy sharks: longevity, volatility and the value of risk pooling
Authors: Milevsky Moshe A.
Published: March 2019

Whovalueslife annuities more? Is it the healthy retiree who expects to live long and might become a centenarian, or is the unhealthy retiree with a short life expectancy more likely to appreciate the pooling of longevity risk? What if the unhealthy retiree is pooled with someone who is much healthier and forced to pay an implicit loading? To answer these and related questions this paper examines the empirical conditions under which retirees benefit (or may not) from longevity risk pooling by linking theeconomicsof annuity equivalent wealth toactuariallymodels of aging. I focus attention on theCompensation Law of Mortalitywhich implies that individuals with higher relative mortality (e.g., lower income) age more slowly and experience greater longevity uncertainty. Ergo, they place higher utility value on the annuity. The impetus for this research today is the increasing evidence on the growing disparity in longevity expectations between rich and poor.
Music and Socialism: Three Moments
Authors: DROTT ERIC
Published: March 2019

This article asks how we might map the complex relations between music and socialism. If an abiding concern of socialism is the collective appropriation of the means of production, what are the points at which music might participate in this project? Three moments from the history of music's entanglements with socialism shed light on this question. The first considers music's role in workers’ struggles in Europec. 1900. Here what is at stake is how music and musical associations (most notably workers’ choruses) were mobilized as a tool in the struggle to socialize the means of production. A second vignette turns to France after May 1968, when music itself became a site of political intervention. Here what is at stake is the struggle to socialize the means of musical production, part of the struggle to institute a truly democratic culture. The third vignette turns its attentions to the proximate future, considering music's place in emerging forms of digital capitalism. Crucial in this regard is the way music is being transformed into a means of production in its own right – a means, that is, of producing the kinds of subjects required by contemporary capitalism – as well as the political constraints and possibilities these shifts present for a socialism of the future.
Music for Socialism, London 1977
Authors: PIEKUT BENJAMIN
Published: March 2019

Members of the rock band Henry Cow co-founded Music for Socialism in early 1977 with the assistance of several associates in London's cultural left. Their first large event, a socialist festival of music at the Battersea Arts Centre, gathered folk musicians, feminists, punks, improvisers, and electronic musicians in a confabulation of workshops, performances, and debates. The organization would continue to produce events and publications examining the relationship between left politics and music for the next eighteen months. Drawing on published sources, archival documents, and interviews, this article documents and analyzes the activities of Music for Socialism, filling out the picture of a fascinating, fractious organization that has too often served as a thin caricature of abstruse failure compared with the better resourced, more successful, and well-documented Rock Against Racism. As important as the latter was to anti-racist activism during the rise of the National Front, it was not concerned with the issues that Music for Socialism considered most important – namely, how musical forms embody their own politics and how musicians might control their means of production. Affiliated with the Socialist Workers Party (UK), Rock Against Racism produced massive benefit concerts and rallies against the fascist right, drawing together musicians and audiences from punk and reggae. The much smaller events of Music for Socialism enrolled musicians from a range of popular music genres and often placed as much emphasis on discussion and debate as they did on having a good time. The organization's struggles, I will suggest, had less to do with ideological rigidity than it did with the itineracy and penury of musicians and intellectuals lacking support from the music industry, governmental arts funding, labor organizations, or academia.
The Russian Revolution and Music
Authors: FAIRCLOUGH PAULINE
Published: March 2019

Nearly thirty years since the collapse of the Soviet Union, we have got used to seeing the Bolshevik Revolution as the prelude to a failed political experiment, albeit one that lasted a remarkably long time. But why do we see it as a failure? After all, the Soviet Union was a vast empire regarded as the military equal of the United States, feared and hated by successive US presidents, whose influence extended far beyond Soviet borders to include regimes in Africa, South East Asia, Central and South America. Had Mikhail Gorbachev not been removed in 1991, and had the Soviet system been able to reform itself into something like the form of communism we see today in China, no one would regard those seventy-plus years of Soviet power as a failure at all. What is meant by failure, in truth, is not really military or economic failure so much as a failure to sustain and uphold the ideals of equality and social justice that originally drew so many to the communist cause. The haemorrhaging of members from the Communist Party of Great Britain (CPGB) in 1956, for instance, was a result of widespread feelings of shock and disgust after Nikita Khrushchev's revelations at the Twenty-First Party Conference that year, at which he delivered his so-called ‘secret speech’ condemning Stalin's regime. For those who left the CPGB, and other communist parties across Western Europe, it was painful to realize that what they had for decades dismissed as ‘anti-Soviet propaganda’ had in fact been accurate reportage. Most shocking of all was learning that the mass arrests and disappearances of the 1930s, and even the show trials of prominent Politburo and party members, were not proportionate, if regrettable, responses to plots to murder Stalin and overthrow Soviet power at all, but rather Stalinist crimes of epic and tragic proportions. Right up to the end of the Communist regime in Russia, reports of political and religious repression, the continued use of the Gulag system, confinement and forced treatment of dissidents in mental hospitals, literary and other cultural censorship continued to filter through the Iron Curtain.
Stratigraphic Control of Frontal Décollement Level and Structural Vergence and Implications for Tsunamigenic Earthquake Hazard in Sumatra, Indonesia
Authors: Bradley Kyle , Qin Yanfang , Carton Hélène , Hananto Nugroho , Villanueva‐Robles Fernando , Leclerc Fréderique , Shengji Wei , Tapponier Paul , Sieh Kerry , Singh Satish
Published: March 2019

Propagation of fault rupture to the seafloor is a likely cause of enhanced tsunami generation during megathrust earthquakes. New, high‐resolution seismic reflection profiles and swath bathymetry collected across the northern limit of the Mw 7.8, 25 October 2010 Mentawai tsunami earthquake rupture reveal significant and systematic lateral variations in both the stratigraphic level of the frontal Sunda megathrust and the vergence of its frontal ramp faults. Where ramp faults are uniformly seaward vergent, the décollement resides on top of a strong reflector marking the inferred top of pelagic sediments. Where ramp faults are bivergent (both landward and seaward), the décollement is localized within the subducting clastic sequence, above a xseismically transparent unit inferred to be distal fan muds. Where ramp faults are uniformly landward vergent, the décollement is directly on top of the oceanic crust of the subducting Investigator Fracture Zone. Enhanced surface uplift and tsunamigenesis during the 2010 tsunamigenic earthquake appear to have coincided with propagation of rupture into frontal areas with well‐developed structural bivergence. Frontal bivergence is a geological signal of low basal traction during accrual of slip, and offshore of Sumatra this structural style may mark areas of enhanced tsunami hazard posed by small‐magnitude, shallow megathrust ruptures that propagate into the incoming terrigenous sequence at near‐trench levels.
β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma
Authors: Zhang Guangya , He Jiangping , Ye Xiaofei , Zhu Jing , Hu Xi , Shen Minyan , Ma Yuru , Mao Ziming , Song Huaidong , Chen Fengling
Published: March 2019

Hepatocellular carcinoma (HCC), a common liver malignancy worldwide, has high morbidity and mortality. β-Thujaplicin, a tropolone derivative, has been used in some health-care products and clinical adjuvant drugs, but its use for HCC is unknown. In this study, we found that β-Thujaplicin inhibits the growth of HCC cells, but not normal liver cells, with nanomolar potency. Mechanistically, we found that β-Thujaplicin could induce autophagy, as judged by western blot, confocal microscopy, and transmission electron microscopy. Further using β-Thujaplicin combined with an autophagy blocker or agonist treatment HepG2 cells, we found that β-Thujaplicin induced autophagic cell death (ACD) mediated by ROS caused inhibition of the Akt-mTOR signaling pathway. Moreover, β-Thujaplicin triggered HepG2 apoptosis and increased cleaved PARP1, cleaved caspase-3, and Bax/Bcl-2 ratio, which indicated that β-Thujaplicin induced apoptosis mediated by the mitochondrial-dependent pathway. We also found that increased expression of p21 and decreased expression of CDK7, Cyclin D1, and Cyclin A2 participating in β-Thujaplicin caused the S-phase arrest. It seems that β-Thujaplicin exerts these functions by ROS-mediated p38/ERK MAPK but not by JNK signaling pathway activation. Consistent with in vitro findings, our in vivo study verified that β-Thujaplicin treatment significantly reduced HepG2 tumor xenograft growth. Taken together these findings suggest that β-Thujaplicin have an ability of anti-HCC cells and may conducively promote the development of novel anti-cancer agents.
Author Correction: Post-stroke insomnia in community-dwelling patients with chronic motor stroke: Physiological evidence and implications for stroke care
Authors: Sterr A. , Kuhn M. , Nissen C. , Ettine D. , Funk S. , Feige B. , Umarova R. , Urbach H. , Weiller C. , Riemann D.
Published: March 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper
Absence of the proteoglycan decorin reduces glucose tolerance in overfed male mice
Authors: Svärd Jessica , Røst Therese H. , Sommervoll Camilla E. N. , Haugen Christine , Gudbrandsen Oddrun A. , Mellgren Anne E. , Rødahl Eyvind , Fernø Johan , Dankel Simon N. , Sagen Jørn V. , Mellgren Gunnar
Published: March 2019

Studies have implicated the extracellular matrix (ECM) of adipose tissue in insulin resistance. The proteoglycan decorin, a component of ECM, has been associated with glucose tolerance, but possible causal effects on metabolism remain to be explored. We here sought to determine metabolic consequences of loss of decorin in mice (DcnKO). DcnKO mice were fed a low-fat (LF) or high-fat (HF) diet for 10 weeks and body weight and food intake was recorded. An intraperitoneal glucose tolerance test was performed after eight weeks. Blood samples and adipose, liver and muscle tissues were collected at sacrifice. Global gene expression was measured in adipose tissue, and expression of decorin was also analyzed in human adipose samples. DcnKO mice showed increased feed efficiency during overfeeding and impaired glucose tolerance. Adipose leptin mRNA and circulating leptin levels were elevated in DcnKO mice, along with a downregulation of genes involved in ECM organization and triglyceride biosynthesis, and an upregulation of adipose genes involved in complement and coagulation cascades. Consistent with a protective metabolic role for decorin, in obese patients we found increased adipose decorin expression after profound fat loss, particularly in the stromal vascular fraction. Loss of decorin in mice caused impaired glucose tolerance in association with increased feed efficiency and altered gene expression in adipose tissue. Our data provide evidence that decorin is an important factor for maintaining glucose tolerance.
A transient window of hypothyroidism alters neural progenitor cells and results in abnormal brain development
Authors: O’Shaughnessy Katherine L. , Thomas Susan E. , Spring Stephanie R. , Ford Jermaine L. , Ford Richard L. , Gilbert Mary E.
Published: March 2019

Cortical heterotopias are clusters of ectopic neurons in the brain and are associated with neurodevelopmental disorders like epilepsy and learning disabilities. We have previously characterized the robust penetrance of a heterotopia in a rat model, induced by thyroid hormone (TH) disruption during gestation. However, the specific mechanism by which maternal TH insufficiency results in this birth defect remains unknown. Here we first determined the developmental window susceptible to endocrine disruption and describe a cellular mechanism responsible for heterotopia formation. We show that five days of maternal goitrogen treatment (10 ppm propylthiouracil) during the perinatal period (GD19-PN2) induces a periventricular heterotopia in 100% of the offspring. Beginning in the early postnatal brain, neurons begin to aggregate near the ventricles of treated animals. In parallel, transcriptional and architectural changes of this region were observed including decreased Sonic hedgehog (Shh) expression, abnormal cell adhesion, and altered radial glia morphology. As the ventricular epithelium is juxtaposed to two sources of brain THs, the cerebrospinal fluid and vasculature, this progenitor niche may be especially susceptible to TH disruption. This work highlights the spatiotemporal vulnerabilities of the developing brain and demonstrates that a transient period of TH perturbation is sufficient to induce a congenital abnormality.
Microscale Temperature Shaping Using Spatial Light Modulation on Gold Nanoparticles
Authors: Durdevic Ljiljana , Robert Hadrien M. L. , Wattellier Benoit , Monneret Serge , Baffou Guillaume
Published: March 2019

Heating on the microscale using focused lasers gave rise to recent applications, e.g., in biomedicine, biology and microfluidics, especially using gold nanoparticles as efficient nanoabsorbers of light. However, such an approach naturally leads to nonuniform, Gaussian-like temperature distributions due to the diffusive nature of heat. Here, we report on an experimental means to generate arbitrary distributions of temperature profiles on the micrometric scale (e.g. uniform, linear, parabolic, etc) consisting in illuminating a uniform gold nanoparticle distribution on a planar substrate using spatially contrasted laser beams, shaped using a spatial light modulator (SLM). We explain how to compute the light pattern and the SLM interferogram to achieve the desired temperature distribution, and demonstrate the approach by carrying out temperature measurements using quantitative wavefront sensing.
Utilization of the high spatial-frequency component in adaptive beam shaping by using a virtual diagonal phase grating
Authors: Nakata Yoshiki , Osawa Kazuhito , Miyanaga Noriaki
Published: March 2019

A square flattop beam is a fundamental shape that is in high demand in various applications, such as ultra-high-power lasers, uniform surface processing and medical engineering. In this experiment, a new and simple scheme of the adaptive beam shaping system to generate a square flattop shape with high uniformity and edge steepness using virtual diagonal phase grating encoded on a spatial-light modulator and a 4f system is proposed. The grating vector kg is non-parallel to the normal vectors kx and ky of the objective beam profile to be extracted; thus, the residual and extracted components hit separately on the Fourier plane of the 4f system. Consequently, using a spatial-frequency filter passing components parallel to kx and ky, the residual components are blocked by the filter without loss of the high spatial-frequency domain of the extracted component. When the width of the filter was 1.0 mm, the edge of the shaped beam increased in height within 20 μm, which is less than 20% of that obtained with conventional vertical phase grating.
The Impact of Shift Work on Sleep, Alertness and Performance in Healthcare Workers
Authors: Ganesan Saranea , Magee Michelle , Stone Julia E. , Mulhall Megan D. , Collins Allison , Howard Mark E. , Lockley Steven W. , Rajaratnam Shantha M. W. , Sletten Tracey L.
Published: March 2019

Shift work is associated with impaired alertness and performance due to sleep loss and circadian misalignment. This study examined sleep between shift types (day, evening, night), and alertness and performance during day and night shifts in 52 intensive care workers. Sleep and wake duration between shifts were evaluated using wrist actigraphs and diaries. Subjective sleepiness (Karolinska Sleepiness Scale, KSS) and Psychomotor Vigilance Test (PVT) performance were examined during day shift, and on the first and subsequent night shifts (3rd, 4th or 5th). Circadian phase was assessed using urinary 6-sulphatoxymelatonin rhythms. Sleep was most restricted between consecutive night shifts (5.74 ± 1.30 h), consecutive day shifts (5.83 ± 0.92 h) and between evening and day shifts (5.20 ± 0.90 h). KSS and PVT mean reaction times were higher at the end of the first and subsequent night shift compared to day shift, with KSS highest at the end of the first night. On nights, working during the circadian acrophase of the urinary melatonin rhythm led to poorer outcomes on the KSS and PVT. In rotating shift workers, early day shifts can be associated with similar sleep restriction to night shifts, particularly when scheduled immediately following an evening shift. Alertness and performance remain most impaired during night shifts given the lack of circadian adaptation to night work. Although healthcare workers perceive themselves to be less alert on the first night shift compared to subsequent night shifts, objective performance is equally impaired on subsequent nights.
CXCL4/PF4 is a predictive biomarker of cardiac differentiation potential of human induced pluripotent stem cells
Authors: Ohashi Fumiya , Miyagawa Shigeru , Yasuda Satoshi , Miura Takumi , Kuroda Takuya , Itoh Masayoshi , Kawaji Hideya , Ito Emiko , Yoshida Shohei , Saito Atsuhiro , Sameshima Tadashi , Kawai Jun , Sawa Yoshiki , Sato Yoji
Published: March 2019

Selection of human induced pluripotent stem cell (hiPSC) lines with high cardiac differentiation potential is important for regenerative therapy and drug screening. We aimed to identify biomarkers for predicting cardiac differentiation potential of hiPSC lines by comparing the gene expression profiles of six undifferentiated hiPSC lines with different cardiac differentiation capabilities. We used three platforms of gene expression analysis, namely, cap analysis of gene expression (CAGE), mRNA array, and microRNA array to efficiently screen biomarkers related to cardiac differentiation of hiPSCs. Statistical analysis revealed candidate biomarker genes with significant correlation between the gene expression levels in the undifferentiated hiPSCs and their cardiac differentiation potential. Of the candidate genes, PF4 was validated as a biomarker expressed in undifferentiated hiPSCs with high potential for cardiac differentiation in 13 additional hiPSC lines. Our observations suggest that PF4 may be a useful biomarker for selecting hiPSC lines appropriate for the generation of cardiomyocytes.
Memantine prodrug as a new agent for Alzheimer’s Disease
Authors: Sestito Simona , Daniele Simona , Pietrobono Deborah , Citi Valentina , Bellusci Lorenza , Chiellini Grazia , Calderone Vincenzo , Martini Claudia , Rapposelli Simona
Published: March 2019

Hydrogen sulphide has recently drawn much attention due to its potent anti-inflammatory and neuroprotective roles in brain functions. The purpose of the current study was to exploit these beneficial properties of H2S to design a new agent for the treatment of Alzheimer’s disease (AD). To pursue our aims, we replaced the free amine group of memantine with an isothiocyanate functionality as a putative H2S-donor moiety. The new chemical entity, named memit, was then tested in vitro to determine whether it retains the pharmacological profile of the “native drug”, while also providing a source of H2S in the CNS. Indeed, Memit showed the ability to release H2S through a cysteine-mediated mechanism, thus generating memantine. Moreover, the new hybrid molecule exerts protective effects against neuronal inflammation and induces a drastic fall in ROS production. In addition, memit was also able to reduce the Aβ(1-42) self-induced aggregation and exerted cytoprotective effect against Aβ oligomers-induced damage in both human neurons and rat microglia cells. Finally, similarly to memantine, the new compound promotes autophagy, a complex process required for cellular homeostasis in cell survival that results to be altered in neurodegenerative diseases. In conclusion, our study revealed that memit is a prodrug of memantine. Further in vivo studies will be necessary to fully investigate the synergic or cumulative effects due to the H2S-releasing moiety and the native drug.
Pistacia vera L. oleoresin and levofloxacin is a synergistic combination against resistant Helicobacter pylori strains
Authors: Di Lodovico Silvia , Napoli Edoardo , Di Campli Emanuela , Di Fermo Paola , Gentile Davide , Ruberto Giuseppe , Nostro Antonia , Marini Emanuela , Cellini Luigina , Di Giulio Mara
Published: March 2019

The increasing multidrug resistance in Helicobacter pylori, also correlated to its biofilm‐forming ability, underlines the need to search novel strategies to improve the eradication rate. Natural compounds are proposed as antibiotic-resistant-breakers capable to restore the efficacy of conventional drugs. Aim of this work was to evaluate the capability of Pistacia vera L. oleoresin (ORS) to synergize with levofloxacin (LVX) against resistant H. pylori strains. The antimicrobial activity of P. vera L. ORS and LVX and their combinations was determined by MIC/MBC (in neutral and acidic environments) and checkerboard tests. The anti-biofilm effect was determined by biomass quantification. In vivo Galleria mellonella model was used to confirm in vitro data. Pistacia vera L. ORS and LVX MICs ranged respectively from 780 to 3120 mg/l and from 0.12 to 2.00 mg/l, at pH 7.0 and 5.5. MBCs were similar to MICs. Pistacia vera L. ORS was able to synergize with LVX, restoring its effectiveness in LVX resistant strains. Pistacia vera L. ORS, LVX and their synergistic combinations displayed significant biofilm reduction. Pistacia vera L. ORS and LVX, showed protective effect against H. pylori infection on G. mellonella (62% and 63% of survival, respectively). Pistacia vera L. ORS can be considered a promising potentiator to restore the effectiveness of LVX tackling the H. pylori antibiotic resistance phenomenon.
Scaling in vitro activity of CYP3A7 suggests human fetal livers do not clear retinoic acid entering from maternal circulation
Authors: Topletz Ariel R. , Zhong Guo , Isoherranen Nina
Published: March 2019

All-trans-retinoic acid (atRA), the active metabolite of vitamin A, is a critical signaling molecule during embryonic and fetal development and is necessary for maternal health. Fetal exposure to endogenous atRA is tightly regulated during gestation in a tissue specific manner and maternal exposure to exogenous retinoids during pregnancy is teratogenic. The clearance of atRA is primarily mediated by the cytochrome P450 (CYP) 26 enzymes, which play an essential role in controlling retinoid gradients during organogenesis. We hypothesized that CYP26 enzymes in the human fetal liver also function as a protective barrier to prevent maternal atRA reaching fetal circulation. Using human fetal liver tissue, we found that the mRNA of CYP26A1 and CYP26B1 enzymes is expressed in the human fetal liver. However, based on inhibition studies, metabolite profiles and correlation of atRA metabolism with testosterone hydroxylation, clearance of atRA in the fetal livers was mediated by CYP3A7. Based on in vitro-to-in vivo scaling, atRA clearance in the fetal liver was quantitatively minimal, thus providing an insufficient maternal-fetal barrier for atRA exposure.
PAmiRDB: A web resource for plant miRNAs targeting viruses
Authors: Satish Deepshikha , Mukherjee Sunil Kumar , Gupta Dinesh
Published: March 2019

MicroRNAs (miRNAs) have emerged to be essential constituents of host antiviral-defense mechanisms. The miRNA mediated antiviral mechanism was first experimentally established in animals, which proved that host miRNAs regulate viral gene expression by targeting the animal virus mRNAs. There are comparatively fewer reports about such interactions in plants, however, artificial miRNA studies prove that miRNAs play similar antiviral role in plants too. To explore the extent of this phenomenon in plant genomes, and in the absence of any publicly available resource for prediction of plant miRNAs targeting viruses, we were motivated to predict such interactions of plant miRNAs and viral genes. The intriguing results of the predictions are compiled as a database, which we have named as PAmiRDB. The current version of PAmiRDB includes more than 2600 plant miRNAs and their specific interactions with corresponding targets in approximately 500 viral species (predominantly from the major plant-infecting virus families of geminiviruses and potyviruses). PAmiRDB is a database of known plant miRNAs and their predicted targets in virus genomes. The innovative database query-interface enables global and comprehensive investigation of such predicted interactions between host miRNAs and viral genes. The database integrated-tools also helps researchers to design experiments to confirm such interactions. PAmiRDB is available at http://bioinfo.icgeb.res.in/pamirdb
Clarifying photoluminescence decay dynamics of self-assembled quantum dots
Authors: Man Minh Tan , Lee Hong Seok
Published: March 2019

We studied the temperature-dependent photoluminescence (PL) and time-resolved PL spectra of multilayer CdTe/ZnTe quantum dots (QDs) to understand their carrier dynamics. We demonstrated a method of enhancing the confinement of carriers in CdTe QDs by modulating the number of stacked layers, leading to enhanced acoustic phonons up to 67 μeV and reducing the optical phonon coupling to 20 meV with an average phonon energy of 20 meV. The temperature-dependent decay time could be explained using a simple model of the thermal redistribution of carrier states. Thermal escape from hole states during multiphonon scattering occurred only at high temperatures, whereas blue shifts and enhanced PL intensity were expected to enhance the electron–phonon coupling and confinement-induced mixing among discrete state and continuum states with separation energies of 3.5–7.4 meV. Time-resolved PL measurements probed the electric field screening effect as a function of the strain distribution in QDs and was established to be 2.5 ± 0.2 MV/cm.
Copy number alterations in B-cell development genes, drug resistance, and clinical outcome in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Steeghs Elisabeth M. P. , Boer Judith M. , Hoogkamer Alex Q. , Boeree Aurélie , de Haas Valerie , de Groot-Kruseman Hester A. , Horstmann Martin A. , Escherich Gabriele , Pieters Rob , den Boer Monique L.
Published: March 2019

Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is associated with a high frequency of copy number alterations (CNAs) in IKZF1, EBF1, PAX5, CDKN2A/B, RB1, BTG1, ETV6, and/or the PAR1 region (henceforth: B-cell development genes). We aimed to gain insight in the association between CNAs in these genes, clinical outcome parameters, and cellular drug resistance. 71% of newly diagnosed pediatric BCP-ALL cases harbored one or more CNAs in these B-cell development genes. The distribution and clinical relevance of these CNAs was highly subtype-dependent. In the DCOG-ALL10 cohort, only loss of IKZF1 associated as single marker with unfavorable outcome parameters and cellular drug resistance. Prednisolone resistance was observed in IKZF1-deleted primary high hyperdiploid cells (~1500-fold), while thiopurine resistance was detected in IKZF1-deleted primary BCR-ABL1-like and non-BCR-ABL1-like B-other cells (~2.7-fold). The previously described risk stratification classifiers, i.e. IKZF1plus and integrated cytogenetic and CNA classification, both predicted unfavorable outcome in the DCOG-ALL10 cohort, and associated with ex vivo drug cellular resistance to thiopurines, or L-asparaginase and thiopurines, respectively. This resistance could be attributed to overrepresentation of BCR-ABL1-like cases in these risk groups. Taken together, our data indicate that the prognostic value of CNAs in B-cell development genes is linked to subtype-related drug responses.
Vagrant birds as a dispersal vector in transoceanic range expansion of vascular plants
Authors: Kalwij Jesse M. , Medan Diego , Kellermann Jürgen , Greve Michelle , Chown Steven L.
Published: March 2019

Birds are thought to be important vectors underlying the disjunct distribution patterns of some terrestrial biota. Here, we investigate the role of birds in the colonisation by Ochetophila trinervis (Rhamnaceae), a vascular plant from the southern Andes, of sub-Antarctic Marion Island. The location of O. trinervis on the island far from human activities, in combination with a reconstruction of island visitors’ travel history, precludes an anthropogenic introduction. Notably, three bird species occurring in the southern Andes inland have been observed as vagrants on Marion Island, with the barn swallow Hirundo rustica as the most common one. This vagrant displays long-distance migratory behaviour, eats seeds when insects are in short supply, and has started breeding in South America since the 1980s. Since naturalised O. trinervis has never been found outside the southern Andes and its diaspores are incapable of surviving in seawater or dispersing by wind, a natural avian dispersal event from the Andes to Marion Island, a distance of >7500 km, remains the only probable explanation. Although one self-incompatible shrub seems doomed to remain solitary, its mere establishment on a Southern Ocean island demonstrates the potential of vagrancy as a driver of extreme long-distance dispersal of terrestrial biota.
Evolution of sexually-transferred steroids and mating-induced phenotypes in Anopheles mosquitoes
Authors: Pondeville Emilie , Puchot Nicolas , Lang Michael , Cherrier Floriane , Schaffner Francis , Dauphin-Villemant Chantal , Bischoff Emmanuel , Bourgouin Catherine
Published: March 2019

Human malaria, which remains a major public health problem, is transmitted by a subset of Anopheles mosquitoes belonging to only three out of eight subgenera: Anopheles, Cellia and Nyssorhynchus. Unlike almost every other insect species, males of some Anopheles species produce steroid hormones which are transferred to females during copulation to influence their reproduction. Steroids are consequently a potential target for malaria vector control. Here, we analysed the evolution of sexually-transferred steroids and their effects on female reproductive traits across Anopheles by using a set of 16 mosquito species (five Anopheles, eight Cellia, and three Nyssorhynchus), including malaria vector and non-vector species. We show that male steroid production and transfer are specific to the Cellia and therefore represent a synapomorphy of this subgenus. Furthermore, we show that mating-induced effects in females are variable across species and differences are not correlated with sexually-transferred steroids or with Anopheles ability to transmit human malaria. Overall, our findings highlight that Anopheles mosquitoes have evolved different reproductive strategies, independently of being a malaria vector or not.