bluuebunny/crossref_metadata_2025 huggingface dataset:
Gardens in the ancient Near East
Authors: Albenda Pauline
Published: December 2018

Gardens were a means of producing food, and they also served as pleasure gardens. Inscriptions of Assyrian kings mention the tree and flower varieties that were planted in the royal gardens and parks. The pictorial record provides evidence of how gardens may have appeared during the Neo‐Assyrian period.
Trade routes
Authors: Schörle Katia
Published: December 2018

Trade routes, as opposed to routes used for governmental, military, or civilian reasons, can be defined as preferential paths used by institutions or individuals (merchants, etc.) for the specific purpose of moving trade goods from their point of origin or production to their final destination or consumer. In the Roman Mediterranean, the development of maritime trade led to an increased use of maritime shipments in order to reduce general transport costs. Trade routes connected Rome to its provinces, but also connected the capital to regions far beyond the empire.
Minoanizing Paintings in the Eastern Mediterranean
Authors: von Rüden Constance
Published: December 2018

At several sites around the eastern Mediterranean, murals with stylistic and technical characteristics of Minoan and Mycenean wall paintings have been discovered since the mid‐twentieth century. These similarities have almost exclusively brought the question of itinerant craftspeople and their ethnicity into focus, but without tracing in detail how the different craft traditions were related. Recent research reveals a far more complex web of craft‐interactions than previously thought and shows the necessity of painstaking microstudies to understand the complex eastern Mediterranean interplay. Moreover, the rather Aegean perspective on the topic has marginalized the local architectural and social context of the paintings. The seemingly homogeneous eastern Mediterranean desire for a particular, Aegean‐related, endowment of elite architecture had often been overemphasized, while chronological, cultural, and social differences, and thus the variability in their consumption pattern and perception has largely been neglected.
Delitzsch, Friedrich (1850–1922)
Authors: Beckman Gary
Published: December 2018

An overview of the career of the Assyriologist and Biblicist Friedrich Delitzsch.
Persaios of Kition
Authors: Gourinat Jean‐Baptiste
Published: December 2018

Persaios of Kition (born ca. 300
bce
) was a Stoic philosopher and favorite pupil of Zeno of Kition. He was one of the few Stoic philosophers of the Hellenistic age who achieved real political influence and power as advisor to the Macedonian king Antigonos II Gonatas, and as archon of Corinth. He may have died defending Corinth against Aratos of Sikyon in 243
bce
, but it is also possible that he fled during the siege and escaped. He wrote several ethical and political treatises, including
Memorabilia
of Zeno, a work against Plato's
Laws
and a treatise
On kingship
.
Themis
Authors: Reggiani Nicola
Published: December 2018

With the term
themis
, ancient Greeks indicated both a legal and social concept and a divine notion. The former is related to juridical systems of oral tradition, where the
themistes
are the set of rules or norms that established rights and obligations within the society, constituting the background and the framework of a justice administered by the “kings” through debates and arbitrations. The latter embodies – through the goddess Themis – the abstract regulation that runs the entire cosmic order, with which the gods themselves must comply, and can well be regarded as a metaphysical elaboration of the former's mechanics. In both the human and the divine frameworks,
themis
is strictly connected with
dike
, “justice,” which literally is the pathway “showed” (
deiknumi
) by the decisions compliant with the
themistes
; according to Hesiod's
Theogony
, indeed, Dike is Themis’ daughter.
Khuzistan Chronicle
Authors: Wood Philip
Published: December 2018

The
Khuzistan Chronicle
was written in Syriac in East Syrian circles and covers the period ca. 590–660. It was probably composed as a record of contemporary events and mixes details from written sources with oral reports.
Alexamenos (inscription)
Authors: Siker Jeffrey S.
Published: December 2018

The Alexamenos graffito is a third‐century roughly‐etched caricature of a man named Alexamenos worshipping an ass‐headed man who is being crucified. The inscription reads “Alexamenos worships [his] god.” The crucified figure is most likely a depiction of Jesus, with an ass‐head to illustrate the foolishness of the Christian religion for worshipping a crucified man.
Labarum
Authors: Drake H. A.
Published: December 2018

Labarum is the name given to the talisman created by the emperor Constantine after his vision of the cross, usually dated to 312
ce
. Its most distinctive feature was a bejeweled Chi‐Rho at the top, a monogram for Christ. When carried into battle, it was said to terrify enemies into flight.
Sabinus (Masurius Sabinus)
Authors: Cascione Cosimo
Published: December 2018

The article examines the life and work of the jurist Masurius Sabinus, an equestrian who lived in the early Principate and whom Tiberius permitted to give legal answers publicly, a teacher and eponymous head of a group of legal experts, the so‐called “Sabinian school.” His masterpiece, thelibri tres iuris civilis, a short axiomatic treatise on civil law, was commented on by Pomponius, Paul, and Ulpian. His works show a strong interest in the past and were of great importance for ancient scholarship (in particular theNoctes Atticaeof Aulus Gellius).
Sardinia, Iron Age Sanctuaries
Authors: Hayne Jeremy
Published: December 2018

The appearance of large socioreligious sanctuaries in Sardinia at the start of the Iron Age heralds a new period in the Nuragic culture of the island. Alongside the construction of densely populated “proto‐urban” villages, they mark a break with the past Bronze Age culture and signal new ways of territorial management and religious organization that originated with water and well temples. They were also fundamental for the control and distribution of metal resources by the Nuragic elites.
ArtabanosIIof Parthia
Authors: Gregoratti Leonardo
Published: December 2018

Artabanos II of Parthia (10/11–38/41ce) put into action an effective policy aimed at opposing the power of the nobility and strengthening the position of the king. He individuated a series of solutions for the political crisis of the Arsacid rule that were to be adopted by his successors.
Polymer–spinel ferrite composite containing nickel, magnesium, and nickel–magnesium ions: Structural, magnetic, electrical, and thermal stability properties
Authors: Masoud Emad M. , El‐Bellihi Abdelhameed A. , Bayoumy Wafaa A. , Abdallah Amira S.
Published: December 2018

Firstly, three different nano ferrites (MgFe2O4, NiFe2O4, and Ni0.5Mg0.5Fe2O4) were synthesized using a combustion method. Secondly, polyaniline composites containing small amounts of those nano ferrites were prepared using in situ chemical polymerization method. Ferrite samples were characterized using X‐ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT‐IR) analyses. XRD analysis of ferrites exhibited well‐resolved broad peaks, which confirm the polycrystalline and mono‐phasic nature. FT‐IR confirmed the spinel structure of these ferrites. Polymer nano ferrites composites were also characterized using XRD, FT‐IR, thermal analysis (TG and DTA), and transmission electron microscope (TEM). Also, electrical (AC conductivity, dielectric constant, dielectric loss, and complex impedance) and magnetic properties were investigated for all nano composite samples. XRD analysis confirmed the formation of polymer nano composites. Moreover, the absorption bands of polyaniline were shifted in the presence of the three different ferrites, confirming the presence of interactions between the different phases in all composites. Additionally, different thermal stability behavior of nano composite samples was observed, which may be attributed to the nano ferrite type and the physical interactions nature with polymer matrix. The sample containing nano magnesium ferrite showed the core–shell structure by TEM. The same sample exhibited the highest values of both AC conductivity (1.01 × 10−4 ohm−1 cm−1) and magnetization saturation (3.38 emu/g) at room temperature. In comparison with other similar composites containing large amounts of the same ferrite, the investigated sample showed a good magnetization saturation value and thermal stability behavior.
Functional surfaces for efficient differentiation of neural stem/progenitor cells into dopaminergic neurons
Authors: Nakaji‐Hirabayashi Tadashi , Fujimoto Kurumi , Yoshikawa Chiaki , Kitano Hiromi
Published: December 2018

Various techniques and systems have been reported for the efficient differentiation of neural stem/progenitor cells into dopaminergic neurons. Although a comparatively high percentage of dopaminergic neurons can be obtained using these techniques, the differentiated cells display varied cellular phenotypes such as astrocytes and oligodendrocytes. Generation of highly pure dopaminergic neurons is important for cell‐based therapy and in vitro evaluation of dopaminergic neuron function. In this study, we developed a culture surface anchored with several neurotrophic factors and a neuronal cell‐adhesive protein for efficient differentiation of neural stem/progenitor cells into dopaminergic neurons. Oligohistidine‐fused brain‐derived neurotrophic factor and glial cell line–derived neurotrophic factor, synthesized using genetic engineering, were co‐immobilized on the surface via metal chelation. To facilitate cell adhesion, a cell‐adhesive chimeric protein derived from laminin (LN‐G) was also immobilized on the surface. Approximately 40% of the cells cultured for 14 days with these protein‐immobilized substrates expressed tyrosine hydroxylase, a marker of dopaminergic neurons, with a three‐fold increase in differentiation efficiency than that reported previously. In addition, the number of tyrosine hydroxylase‐positive cells increased to approximately 80% of the culture after 30 days. These cells secreted dopamine and expressed dopaminergic neuron‐specific genes. Interestingly, cell types (glial cells and oligodendrocytes) other than neuronal cells (immature and mature dopaminergic neurons) were not detected on the protein‐anchored surface. Our results demonstrate that highly pure dopaminergic neurons can be exclusively obtained using the novel substrate without extra purification steps such as cell sorting. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 860–871, 2019.
Translating advances in organ‐on‐a‐chip technology for supporting organs
Authors: Ashammakhi Nureddin , Elkhammas Elmahdi , Hasan Anwarul
Published: December 2018

Organ‐on‐a‐chip platforms have recently seen tremendous progress. They have found potential applications in the study of physiology and pathology of tissues, drug toxicity, and development of tissue models for replacement of animal studies. However, their potential role in organ transplantation has hardly been discussed, so far. Organ transplantation represents a major medical advancement of the twenty‐first century, yet it suffers from limitation due to the shortage of organ supply. Very often, organs harvested from donor's body are deemed non‐usable because of being damaged or “marginal”. Recently, developments of bioartificial devices such as artificial placenta and renal assist‐devices have shown that it is possible to develop novel bioartificial organ support systems that can support the healing of damaged or marginal organs prior to their transplantation. In the current article, we introduce a novel concept for building bioartificial organ assist devices and systems by integrating arrays of numerous organ‐on‐a‐chip platforms. The new system can be used in organ repair centers as means for temporary organ support and functional enhancement. We have also briefly reviewed the relevant organ‐on‐a‐chip platforms developed so far, and related literature to form a basis for developing our new concept, device and its application. The proposed system may help to increase the number of organs available for transplantation and improve transplantation outcomes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2006–2018, 2019.
Evaluation of antimicrobial, antibiofilm and carbonic anhydrase inhibition profiles of 1,3‐bis‐chalcone derivatives
Authors: Tutar Uğur , Koçyiğit Ümit M. , Gezegen Hayreddin
Published: December 2018

A series of 1,3‐bis‐chalcone derivatives (3a‐i, 6a‐i and
8) were synthesized and evaluated antimicrobial, antibiofilm and carbonic anhydrase inhibition activities. In this evaluation,
6f was found to be the most active compound showing the same effect as the positive control against
Bacillus subtilis and
Streptococcus pyogenes in terms of antimicrobial activity. Biofilm structures formed by microorganisms were damaged by compounds at the minimum inhibitory concentration value between 0.5% and 97%.1,3‐bis‐chalcones (
3a‐i, 6a‐i and
8) showed good inhibitory action against human (h) carbonic anhydrase (CA) isoforms I and II. hCA I and II were effectively inhibited by these compounds, with
K
i values in the range of 94.33 ± 13.26 to 787.38 ± 82.64 nM for hCA I, and of 100.37 ± 11.41 to 801.76 ± 91.11 nM for hCA II, respectively. In contrast, acetazolamide clinically used as CA inhibitor showed
K
i value of 1054.38 ± 207.33 nM against hCA I, and 983.78 ± 251.08 nM against hCA II, respectively.
Do physical disabilities differentiate between suicidal ideation and attempts? An examination within the lens of the ideation to action framework of suicide
Authors: Khazem Lauren R. , Anestis Michael D.
Published: December 2018

Objectives

This study examined histories of suicidality among those with and without physical disabilities. Physical disabilities were anticipated to differentiate those with a history of suicide attempts from those with a history of ideation only after accounting for the presence of health conditions and other correlates.

Methods

Participants were 374 adults (M
age = 36.08; 55.61% female; 84 with at least one physical disability) who completed a series of online questionnaires. Multinomial logistic regressions were conducted to examine the effect of the presence of physical disabilities on states of suicidality.

Results

The presence of a physical disability was associated with significantly increased odds of suicide attempts when compared to those with suicidal ideation only. This association was no longer significant when chronic pain conditions were classified as health conditions.

Conclusion

Physical disability may be a factor differentiating between ideators and attempt survivors.
“Do I feel threatened? No… I’m learning!”—Affective and relational dynamics in science professional development
Authors: Finkelstein Carla , Jaber Lama Z. , Dini Vesal
Published: December 2018

This paper focuses on interactions in a science professional development (PD) course in which participating teachers engaged in doing science. Whereas the PD design of this course aligned with research on effective PD practices, we found that these practices did not sufficiently account for the affective and relational dynamics that unfolded in the PD interactions. In this paper we explore how critical discourse analysis (CDA) can be used both to theorize and analyze the affective and relational work happening in PD, through the critical lenses of power and positioning. Our analysis surfaces tensions between participants and facilitators, as well as among participants, which often related to their notions of disciplinary expertise. More important, our analysis shows that attunement to affective and relational dynamics, including explicit attention to communication norms, is essential for engendering productive learning opportunities within PD spaces. We discuss the implications of this study for teacher educators and PD facilitators, and we end with directions for future research on affective and relational dynamics in teacher learning.
Uncovering the Main Root Cause: The Mindset Factor
Authors: Park Jong-Dae
Published: December 2018

In this chapter, the author shifts gear to a whole different level of ‘mind over matter‘, postulating that there is such thing as the principle, overarching root cause of Africa’s underdevelopment: the people’s ‘mindset’. He draws on the Korea’s experience, and the parallels between the Korean experience and the circumstances of Sub-Saharan African countries, to make the case appealing and pertinent. The problematic mindsets or the ‘syndromes’ that are counterproductive to development are identified and explained. These include the dependency syndrome, ‘backtracking syndrome’, ‘what’s-in-it-for-me syndrome‘, lack of action and implementation, the commission culture, etc. This chapter offers a rare look into the mindset issue from an analytical context.
The Essence of the Korean Model of Development
Authors: Park Jong-Dae
Published: December 2018

In this chapter, the author produces a much-needed conceptualized Korean development model featuring all the crucial elements characterizing Korea’s development—foundational, psychological, economic and socio-political—in an organized structure. He dissects South Korea’s transformational path into different stages, both in the economic and the socio-political realms, and indicates their principal driving forces or logics, namely ‘economic discrimination’ and ‘development-mindedness’. The model is derived from the ‘building-block’ process of understanding Korea and also incorporates human factors like Koreans’ ‘egalitarian spirit’. This conceptual model captures the essence of South Korea’s compressed economic and socio-political development.
Influence of a hybrid digital toolset on the creative behaviors of designers in early-stage design
Authors: Zboinska Malgorzata A.
Published: December 2018

The purpose of this research was to investigate how diversification of the repertoire of digital design techniques affects the creative behaviors of designers in the early design phases. The principal results of practice-based pilot experiments on the subject indicate three key properties of the hybrid digital tooling strategy. The strategy features intelligent human-machine integration, facilitating three different types of synergies between the designer and the digital media: human-dominated, machine-dominated, and a balanced human-machine collaboration. This strategy also boosts the cognitive behaviors of the designer by triggering divergent, transformative and convergent design activities and allowing for work on various abstraction levels. In addition, the strategy stimulates the explorative behaviors of the designer by encouraging the production of and interaction with a wide range of design representations, including physical and digital, dynamic and static objects. Thus, working with a broader range of digital modeling techniques can positively influence the creativity of designers in the early conception stages.

Highlights The hybrid digital toolset positively affects the creative behaviors of designers. The toolset boosts the cognitive and visual thinking behaviors. The toolset features intelligent human-machine synergies. The toolset aids interactions with the design representations. The toolset supports early-stage conceptual architectural design.
A law of large numbers for branching Markov processes by the ergodicity of ancestral lineages
Authors: Marguet Aline
Published: December 2018

We are interested in the dynamic of a structured branching population where the trait of each individual moves according to a Markov process. The rate of division of each individual is a function of its trait and when a branching event occurs, the trait of a descendant at birth depends on the trait of the mother. We prove a law of large numbers for the empirical distribution of ancestral trajectories. It ensures that the empirical measure converges to the mean value of the spine which is a time-inhomogeneous Markov process describing the trait of a typical individual along its ancestral lineage. Our approach relies on ergodicity arguments for this time-inhomogeneous Markov process. We apply this technique on the example of a size-structured population with exponential growth in varying environment.
Recombinant Human Soluble Thrombomodulin in Sepsis-Induced Coagulopathy: An Updated Systematic Review and Meta-Analysis
Authors: Yamakawa Kazuma , Murao Shuhei , Aihara Morio
Published: December 2018

Background Clinical effectiveness of recombinant human soluble thrombomodulin (rhTM) in sepsis or sepsis-induced coagulopathy remains a matter of dispute. Recently, the Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial, the latest multinational multi-centre phase III randomized controlled trial, was completed.

Objective This article assesses the benefits and harms of rhTM therapy in sepsis-induced coagulopathy by updating our previous systematic review.

Methods We performed a systematic review and meta-analysis of rhTM therapy for sepsis-induced coagulopathy in randomized controlled trials. All-cause 28-day mortality as efficacy and serious bleeding complications as the adverse effect were measured as primary outcomes. We assessed the certainty of a body of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results We analysed five trials enrolling 1,762 patients. Approximately 13% reduction in the risk of mortality was observed in the rhTM group, but the difference was not significant (relative risk, 0.87; 95% confidence interval, 0.74–1.03; p = 0.10; I
2 = 0%). Risk of serious bleeding complications did not increase with rhTM administration. We judged the certainty of evidence as moderate for mortality and low for serious bleeding. Trial sequential analysis indicated that only 42.0% of the required information size is actually available at this stage to reject or accept low risk-of-bias trials examining the anticipated effect for all-cause mortality.

Conclusion Even in this updated review including the latest SCARLET trial, we currently cannot make any declarative judgments about the beneficial effects of rhTM in sepsis-induced coagulopathy, although some favourable effects were suggested.
Managing Anti-Platelet Therapy in Thrombocytopaenic Patients with Haematological Malignancy: A Multinational Clinical Vignette-Based Experiment
Authors: Leader Avi , Ten Cate Vincent , Ten Cate-Hoek Arina , Spectre Galia , Beckers Erik , Raanani Pia , Giaccherini Cinzia , Pereg David , Schouten Harry , Falanga Anna , Ten Cate Hugo
Published: December 2018

Data on anti-platelet therapy (APT) for prevention of atherothrombotic events in thrombocytopaenic cancer patients is lacking. We aimed to identify patient and physician characteristics associated with APT management in thrombocytopaenic patients with haematological malignancy. A clinical vignette-based experiment was designed. Eleven haematologists were interviewed, identifying five variable categories. Next, 18 hypothetical vignettes were generated. Each physician received three vignettes and chose to: hold all APT; continue APT without platelet transfusion support; or continue APT with platelet transfusion support. The survey was distributed to haematologists and thrombosis specialists in three countries. Multivariate cluster robust Poisson regression models were used to calculate relative risks (RRs) of using one management option (over the other) for each variable in comparison to a reference variable. A total of 145 physicians answered 434 cases. Clinicians were more likely to hold APT in case of 20,000/µL platelets (vs. 40,000/µL; RR for continuing: 0.82 [95% confidence interval: 0.75–0.91]), recent major gastrointestinal bleeding (vs. none; RR 0.81 [0.72–0.92]) and when the physician worked at a university-affiliated community hospital (vs. non-academic community hospital; RR 0.84 [0.72–0.98]). Clinicians were more likely to continue APT in ST elevation myocardial infarction with dual APT (vs. unstable angina with single APT; RR 1.31 [1.18–1.45]) and when there were institutional protocols guiding management (vs. none; RR 1.15 [1.03–1.27]). When APT was continued, increased platelet transfusion targets were used in 34%. In summary, the decision process is complex and affected by multiple patient and physician characteristics. Platelet transfusions were frequently chosen to support APT, although no evidence supports this practice.
Human aquaporin 4 gating dynamics under axially oriented electric-field impulses: A non-equilibrium molecular-dynamics study
Authors: Bernardi Mario , Marracino Paolo , Ghaani Mohammad Reza , Liberti Micaela , Del Signore Federico , Burnham Christian J. , Gárate José-Antonio , Apollonio Francesca , English Niall J.
Published: December 2018

Human aquaporin 4 has been studied using non-equilibrium molecular dynamics simulations in the absence and presence of pulses of external electric fields. The pulses were 100 ns in duration and 0.005–0.015 V/Å in intensity acting along the pores’ axes. Water diffusivity and the dipolar response of various residues of interest within the pores have been studied. Results show relatively little change in levels of water permeability per se within aquaporin channels during axially oriented field impulses, although care must be taken with regard to statistical certainty. However, the spatial variation of water permeability vis-à-vis electric-field intensity within the milieu of the channels, as revealed by heterogeneity in diffusivity-map gradients, indicates the possibility of somewhat enhanced diffusivity, owing to several residues being affected substantially by external fields, particularly for HIS 201 and 95 and ILE 93. This has the effect of increasing slightly intra-pore water diffusivity in the “pore-mouths” locale, albeit rendering it more spatially uniform overall vis-à-vis zero-field conditions (via manipulation of the selectivity filter).
Non-thermal air plasma jets at atmospheric pressure: The flow-dependent propagation in the afterglow
Authors: Wu Shuqun , Liu Xueyuan , Mao Wenhao , Chen Wen , Liu Chang , Zhang Chaohai
Published: December 2018

With a bare pin-to-nozzle electrode configuration, an ac-driven non-thermal air plasma jet with a length of several centimeters is generated. Depending on the gas flow rate, the propagation speed of these plasma columns is in the range of 100–350 m/s, which is close to the gas flow velocity. This indicates that the propagation of the plasma jet is determined by the transport of long lifetime species by gas flow instead of the electron-impact excitation and ionization of molecules under a high electric field. In comparison to the N2, O2, and Ar plasma jets, the length of the air plasma jet is much shorter than that of the N2 plasma jet but longer than that of the O2 and Ar plasma jets. A simple kinetic model reveals that the N2 (A3Σ) metastable plays a crucial role in sustaining the length of the N2 and air plasma jets, whose lifetime is strongly dependent on the quenching effect of O2, O, and NO as well as the compensation from the three-body recombination of nitrogen atoms. Based on the flow-dependent mechanism of the plasma jet, a visually uniform air plasma brush with a width of 2.8 cm and a length of 1.6 cm and a visually uniform N2 plasma brush with a width of 4 cm and a length of 4.4 cm have been demonstrated.
Kojiglycosylceramide commonly contained in Japanese traditional fermented foods alters cholesterol metabolism in obese mice
Authors: Hamajima Hiroshi , Tanaka Masaru , Miyagawa Miyuki , Sakamoto Mayuko , Nakamura Tsuyoshi , Yanagita Teruyoshi , Nishimukai Megumi , Mitsutake Susumu , Nakayama Jiro , Nagao Koji , Kitagaki Hiroshi
Published: December 2018

Koji, which is manufactured by proliferating non-pathogenic fungus Aspergillus oryzae on steamed rice, is the base for Japanese traditional fermented foods. We have revealed that koji and related Japanese fermented foods and drinks such as amazake, shio-koji, unfiltered sake and miso contain abundant glycosylceramide. Here, we report that feeding of koji glycosylceramide to obese mice alters the cholesterol metabolism . Liver cholesterol was significantly decreased in obese mice fed with koji glycosylceramide. We hypothesized that their liver cholesterol was decreased because it was converted to bile acids. Consistent with the hypothesis, many bile acids were increased in the cecum and feces of obese mice fed with koji glycosylceramide. Expressions of CYP7A1 and ABCG8 involved in the metabolism of cholesterol were significantly increased in the liver of mice fed with koji glycosylceramide. Therefore, it was considered that koji glycosylceramide affects the cholesterol metabolism in obese mice.
Optimal proximal augmented Lagrangian method and its application to full Jacobian splitting for multi-block separable convex minimization problems
Authors: He Bingsheng , Ma Feng , Yuan Xiaoming
Published: December 2018

The augmented Lagrangian method (ALM) is fundamental in solving convex programming problems with linear constraints. The proximal version of ALM, which regularizes ALM’s subproblem over the primal variable at each iteration by an additional positive-definite quadratic proximal term, has been well studied in the literature. In this paper we show that it is not necessary to employ a positive-definite quadratic proximal term for the proximal ALM and the convergence can be still ensured if the positive definiteness is relaxed to indefiniteness by reducing the proximal parameter. An indefinite proximal version of the ALM is thus proposed for the generic setting of convex programming problems with linear constraints. We show that our relaxation is optimal in the sense that the proximal parameter cannot be further reduced. The consideration of indefinite proximal regularization is particularly meaningful for generating larger step sizes in solving ALM’s primal subproblems. When the model under discussion is separable in the sense that its objective function consists of finitely many additive function components without coupled variables, it is desired to decompose each ALM’s subproblem over the primal variable in Jacobian manner, replacing the original one by a sequence of easier and smaller decomposed subproblems, so that parallel computation can be applied. This full Jacobian splitting version of the ALM is known to be not necessarily convergent, and it has been studied in the literature that its convergence can be ensured if all the decomposed subproblems are further regularized by sufficiently large proximal terms. But how small the proximal parameter could be is still open. The other purpose of this paper is to show the smallest proximal parameter for the full Jacobian splitting version of ALM for solving multi-block separable convex minimization models.
Firms’ method of pay and the retention of apprentices
Authors: Rinawi Miriam , Backes-Gellner Uschi
Published: December 2018

The new training literature views regulated labour markets as critical for firms’ willingness to participate in apprenticeship training. These regulations allow training firms to retain their apprenticeship graduates at the end of the training period and recoup training costs. Yet, in spite of an only loosely regulated labour market, many Swiss firms offer and pay for training. Using representative data from a large employer–employee survey, we investigate whether these firms use performance pay to retain their graduates. We find that both the magnitude and the likelihood of performance pay are significantly related to a firm’s retention success.
Partial Scleral Rupture Presenting 4 Years After Laser in Situ Keratomileusis
Authors: LaMattina Kara C. , Feder Robert S. , Koreishi Anjum F. , Goldstein Debra A.
Published: December 2018

Purpose:

To report a case of partial scleral rupture after laser in situ keratomileusis (LASIK) surgery.

Methods:

This is a retrospective case report describing a late complication of LASIK surgery.

Results:

A 32-year-old white woman with a history of LASIK surgery performed with a mechanical microkeratome 4 years previously presented for evaluation of partial bilateral scleral ruptures. An arcuate filtering bleb along the contour of the cornea was found on the right eye with associated hypotony and corneal astigmatism. There were no signs or symptoms of prior inflammation, and rheumatologic workup was negative. Imaging revealed scleral microbreaks in the absence of adjacent thinning.

Conclusions:

The pattern and location of thinning without findings consistent with inflammatory disease suggest that the partial bilateral scleral rupture was because of mechanical damage at the time of LASIK, possibly compounded by the hormonal changes of pregnancy.
Congenital Dacryocystocele: A Major Review
Authors: Singh Swati , Ali Mohammad Javed
Published: December 2018

Purpose:

To provide a systematic review of the literature on congenital dacryocystoceles (CDCs) and summarize their presentations, investigations, management, and outcomes.

Methods:

The authors performed a PubMed search of all articles published in English on CDCs. Data captured include demographics, clinical presentations, investigations, management modalities, complications, and outcomes. Fourteen major series (10 or more than 10 cases) and 89 isolated case reports/series on CDCs with a collective patient pool of 1,063 were studied in detail. Specific emphasis was laid on addressing the controversial issues including initial conservative versus surgical management and the role of endoscopic evaluation.

Results:

Numerous terminologies have been used to describe CDC. Congenital dacryocystoceles are rare variants of congenital nasolacrimal duct obstructions and comprise of 0.1% to 0.3% of all such cases. There is a female predilection (64.2%, 683/1,063) and the mean age at presentation is at 7 days of birth. Initial conservative treatment can be a viable option in the absence of an acute dacryocystitis or a respiratory distress. Endoscopy-assisted probing appears to have better outcomes as compared with the in-office probing. Congenital dacryocystoceles with acute dacryocystitis are preferably managed with intravenous antibiotics and an early probing under endoscopy guidance to avoid missing intranasal cysts. Marsupialization is the preferred technique in the management of intranasal cysts. Silicone intubation was rarely used and has no definitive indications. Dacryocystorhinostomy is very rarely needed in the management of CDC.

Conclusions:

Congenital dacryocystocele is a commonly accepted term and its use should be advocated to enhance uniformity in reporting. Endoscopic evaluation of CDC is useful in the diagnosis and treatment of associated intranasal cysts and enhances the rates of successful outcomes.
Comparing the aftereffects of motion and causality across visual co-ordinates
Authors: Gallagher Regan , Arnold Derek H.
Published: December 2018

Albert Michotte (1946/1963) introduced causality into the realm of experimental phenomenology. He disputed Hume's (1739/1978) claim that the impression of causality comes only from conscious inference. Since then, causality adaptation studies have suggested that the visual perception of causality undergoes sensory adaptation, akin to the retinally-specific aftereffects of motion or orientation adaptation. Here we present 5 Experiments that, together, dispute a view of retinotopically-mapped neural populations dedicated to causality detection. We first point to key issues in previous studies of causality adaptation. Then we extend the basic causality adaptation paradigm to show that causality aftereffects occur in spatially global visual space. We directly compare causality aftereffects to the motion aftereffect to show important differences in their coordinate mapping. Our data point to a role for cognitive inferences as being an important aspect of causality aftereffects, despite causal impressions being tightly constrained by sensory perception.
More than a flying syringe: Using functional traits in vector-borne disease research
Authors: Cator Lauren J. , Johnson Leah R. , Mordecai Erin A. , Moustaid Fadoua El , Smallwood Thomas R.C. , LaDeau Shannon L. , Johansson Michael A. , Hudson Peter J. , Boots Michael , Thomas Matthew B. , Power Alison G. , Pawar Samraat
Published: December 2018

Many important endemic and emerging diseases are vector-borne. The functional traits of vectors affect not just pathogen transmission rates, but also the fitness and population dynamics of these animals themselves. Increasing empirical evidence suggests that vector traits vary significantly at time scales relevant to transmission dynamics. Currently, an understanding of how this variation in key traits impacts transmission is hindered by a lack of both empirical data and theoretical methods for mechanistically incorporating traits into transmission models. Here, we present a framework for incorporating both intrinsic and environment-driven variation in vector traits into empirical and theoretical vector-borne disease research. This framework mechanistically captures the effect of trait variation on vector fitness, the correlation between vector traits, and how these together determine transmission dynamics. We illustrate how trait-based vector-borne disease modelling can make novel predictions, and identify key steps and challenges in the construction, empirical parameterisation and validation of such models, as well as the organization and prioritization of data collection efforts.
Biophysical characterizations of the recognition of the AAUAAA polyadenylation signal
Authors: Hamilton Keith , Sun Yadong , Tong Liang
Published: December 2018

Most eukaryotic messenger RNA precursors must undergo 3'-end cleavage and polyadenylation for maturation. We and others recently reported the structure of the AAUAAA polyadenylation signal (PAS) in complex with the protein factors CPSF-30, WDR33 and CPSF-160, revealing the molecular mechanism for this recognition. Here we have characterized in detail the interactions between the PAS RNA and the protein factors using fluorescence polarization experiments. Our studies show that AAUAAA is recognized with ~1 nM affinity by the CPSF-160-WDR33-CPSF-30 ternary complex. Variations in the RNA sequence can greatly reduce the affinity. Similarly, mutations of residues that have van der Waals interactions with the bases of AAUAAA also lead to substantial reductions in affinity. Finally, our studies confirm that both CPSF-30 and WDR33 are required for binding the PAS RNA, and determine a ~7 nM affinity between CPSF-30 and the CPSF-160-WDR33 binary complex.
Crustaceans as hosts of parasites throughout the Phanerozoic
Authors: Klompmaker Adiel A. , Robins Cristina M. , Portell Roger W. , De Angeli Antonio
Published: December 2018

The fossil record of crustaceans as hosts of parasites has yielded three confirmed associations: epicaridean isopod-induced swellings on Jurassic-Recent decapod crustaceans, feminization of Cretaceous and Miocene male crabs possibly caused by rhizocephalan barnacles, and presumed pentastomids on/in Silurian ostracods. Cestode platyhelminth hooks and swellings by entoniscid isopods may be recognized in the future. Relative to 2014, we report an increase of 41% to 124 fossil decapod species with epicaridean-induced swellings in the branchial chamber (ichnotaxon Kanthyloma crusta). Furthermore, using a Late Jurassic (Tithonian) decapod assemblage from Austria, we find (1) no correlation between genus abundance and prevalence of K. crusta, (2) host preference for some galatheoid taxa (as for a mid-Cretaceous assemblage from Spain), and (3) a larger median size of parasitized versus non-parasitized specimens for two selected species. The latter result may be caused by infestation throughout ontogeny rather than exclusively in juveniles and/or possible selection for the larger sex.
Predictive modeling of susceptibility to substance abuse, mortality and drug-drug interactions in opioid patients
Authors: Vunikili Ramya , Glicksberg Benjamin S , Johnson Kipp W , Dudley Joel , Subramanian Lakshminarayanan , Khader Shameer
Published: December 2018

Opioid addiction causes high degree of morbidity and mortality. Preemptive identification of patients at risk of opioid dependence and developing intelligent clinical decisions to deprescribe opioids to the vulnerable patient population may help in reducing the burden. Identifying patients susceptible to mortality due to opioid-induced side effects and understanding the landscape of drug-drug interaction pairs aggravating opioid usage are significant, yet, unexplored research questions. In this study, we present a collection of predictive models to identify patients at risk of opioid abuse, mortality and drug-drug interactions in the context of opioid usage. Using publicly available dataset from MIMIC-III, we developed predictive models (opioid abuse models a=Logistic Regression; b=Extreme Gradient Boosting and mortality model= Extreme Gradient Boosting) and identified potential drug-drug interaction patterns. To enable the translational value of our work, the predictive model and all associated software code is provided. This repository could be used to build clinical decision aids and thus improve the optimization of prescription rates for vulnerable population.
Autocrine STAT3 activation in HPV positive cervical cancer through a virus-driven Akt - NF?B - IL-6 signalling axis
Authors: Morgan Ethan Luc , Macdonald Andrew
Published: December 2018

Persistent human papillomavirus (HPV) infection is the leading cause of cervical cancer. Although the fundamental link between HPV infection and oncogenesis is established, the specific mechanisms of virus-mediated transformation remain poorly understood. We previously demonstrated that the HPV encoded E6 protein increases the activity of the proto-oncogenic transcription factor STAT3 in primary human keratinocytes; however, the molecular basis for STAT3 activation in cervical cancer remains unclear. Here, we show that STAT3 phosphorylation in HPV positive cervical cancer cells is mediated primarily via autocrine activation by the pro-inflammatory cytokine Interleukin 6 (IL-6). Antibody-mediated blockade of IL-6 signalling in HPV positive cells inhibits STAT3 phosphorylation, whereas both recombinant IL-6 and conditioned media from HPV positive cells leads to increased STAT3 phosphorylation within HPV negative cervical cancer cells. Interestingly, we demonstrate that non-conventional activation of the transcription factor NF?B, involving the protein kinase Akt, is required for IL-6 production and subsequent STAT3 activation. Our data provides new insights into the molecular re-wiring of cancer cells by HPV E6. We reveal that activation of an IL-6 signalling axis drives the autocrine and paracrine phosphorylation of STAT3 within HPV positive cervical cancers cells. Greater understanding of this pathway provides a potential opportunity for the use of existing clinically approved drugs for the treatment of HPV-mediated cervical cancer.
Fluorescence Microscopy of Piezo1 in Droplet Hydrogel Bilayers
Authors: Jaggers Oskar B. , Ridone Pietro , Martinac Boris , Baker Matthew A. B.
Published: December 2018

Mechanosensitive ion channels are membrane gated pores which are activated by mechanical stimuli. The focus of this study is on Piezo1, a newly discovered, large, mammalian, mechanosensitive ion channel, which has been linked to diseases such as dehydrated hereditary stomatocytosis (Xerocytosis) and lymphatic dysplasia. Here we utilize an established in-vitro artificial bilayer system to interrogate single Piezo1 channel activity. The droplet-hydrogel bilayer (DHB) system uniquely allows the simultaneous recording of electrical activity and fluorescence imaging of labelled protein. We successfully reconstituted fluorescently labelled Piezo1 ion channels in DHBs and verified activity using electrophysiology in the same system. We demonstrate successful insertion and activation of hPiezo1-GFP in bilayers of varying composition. Furthermore, we compare the Piezo1 bilayer reconstitution with measurements of insertion and activation of KcsA channels to reproduce the channel conductances reported in the literature. Together, our results showcase the use of DHBs for future experiments allowing simultaneous measurements of ion channel gating while visualising the channel proteins using fluorescence.
Rescue of DNA damage in cells after constricted migration reveals bimodal mechano-regulation of cell cycle
Authors: Xia Yuntao , Pfeifer Charlotte R , Zhu Kuangzheng , Irianto Jerome , Liu Dazhen , Pannell Kalia , Chen Emily J , Dooling Lawrence J , Greenberg Roger A , Discher Dennis E
Published: December 2018

Migration through constrictions can clearly rupture nuclei and mis-localize nuclear proteins but damage to DNA remains uncertain as does any effect on cell cycle. Here, myosin-II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent delay in cell cycle is unaffected. Co-overexpression of multiple DNA repair factors and antioxidant inhibition of break formation also have partial effects, independent of rupture. Complete rescue of both DNA damage and cell cycle delay by myosin inhibition plus antioxidant reveals a bimodal dependence of cell cycle on DNA damage. Migration through custom-etched pores yields the same bimodal, with ~4-um pores causing intermediate levels of damage and cell cycle delay. Micronuclei (generated in faulty division) of the smallest diameter appear similar to ruptured nuclei, with high DNA damage and entry of chromatin-binding cGAS (cyclic-GMP-AMP-synthase) from cytoplasm but low repair factor levels. Increased genomic variation after constricted migration is quantified in expanding clones and is consistent with (mis)repair of excess DNA damage and subsequent proliferation.
The third-generation tetracycline, KBP-7072, exploits and reveals a new potential of the primary tetracycline binding pocket
Authors: Kaminishi Tatsuya , Schedlbauer Andreas , Ochoa-Lizarralde Borja , de Astigarraga Elisa , Çapuni Retina , Yang Fred , Benn Vincent , Liu Qingmei , Tan Xiaojuan , Zhang Min , Connell Sean R. , Fucini Paola
Published: December 2018

Antibiotic resistance is a growing threat to human health requiring the discovery or development of new anti-infectives. As such, KBP-7072 is a novel tetracycline derivative that exhibits broad-spectrum activity against Gram-positive and -negative bacterial strains. To determine the mechanism of action of KBP-7072 and understand how its unique C9 extension can be used to combat the growing problem of antibiotic resistance we determined the structure of KBP-7072 bound to the bacterial 30S ribosomal subunit, the inhibitory target of typical tetracyclines. We show that KBP-7072 binds to the primary tetracycline binding site on the 30S ribosomal subunit consistent with it acting as a protein synthesis inhibitor that blocks A-site occupation. Moreover, the unique chemical nature of KBP-7072s C9 extension leads to a distinctive interaction pattern with the 30S subunit that distinguishes KBP-7072 from the third-generation tetracycline, Tigecycline, and thus expands the interaction potential of the primary tetracycline binding pocket.
Structural basis of sterol recognition by human hedgehog receptor PTCH1
Authors: Qi Chao , Minin Giulio Di , Vercellino Irene , Wutz Anton , Korkhov Volodymyr M.
Published: December 2018

Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog (ShhN) to its receptor Patched (PTCH1) activates the signaling pathway. Here, we describe a 3.4 Å cryo-EM structure of the human PTCH1 bound to ShhNC24II, a modified hedgehog ligand mimicking its palmitoylated form. The membrane-embedded part of PTCH1 is surrounded by ten sterol molecules at the inner and outer lipid bilayer portion of the protein. The annular sterols interact at multiple sites with both the sterol sensing domain, SSD, and the SSD-like domain, SSDL, which are located on opposite sides of PTCH1. The structure reveals a possible route for sterol translocation across the lipid bilayer by PTCH1 and homologous transporters.