bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFICIENCY OF PPP IMPLEMENTATION IN BOSNIA AND HERZEGOVINA
Authors: Amović Goran
Published: October 2019

Bosnia and Herzegovina is among thecountries whose social and economic development needsgreatly exceed financial capacities of the public sector.Implementation and financing of capital projects of publicimportance such as: highways and road infrastructure(bridges, tunnels), railway lines, ports, airports, gaspipelines, refineries, power generation plants, social andmunicipal infrastructure (hospitals, schools, prisons, watersupply network, waste disposal) often lead to significantfiscal constraints. Financing investments in the context oflimited budget capacities requires a new approach andstrategy. In a situation where public sector in Bosnia andHerzegovina does not have enough resources necessary forthe efficient implementation of capital projects, there is aneed for engaging private capital. Public-privatepartnership, although a relatively new form of financing,opens significantly more opportunities for financingdevelopment, providing public services and meeting citizen’sneeds, which will be the subject of this paper.
EVOLUTION AND CONTEMPORARY TRENDS OF THE INTERNATIONAL MONETARY SYSTEM
Authors: Topić-Pavković Branka
Published: October 2019

The growth dynamics of international exchange and capital flows is conditioned by the efficiency of the international monetary system whose basic task is to provide for international liquidity and smooth international payments. The tendencies in international economic relations in the time of globalisation have determined further directions for the development of the international monetary system. The breakup of the Bretton-Woods System initiated  the establishment of a new European monetary system with the aim to stabilise the exchange rates and  improve further process of integration and international economic relations. In this research paper we have pointed out to the  fact  that economic interdependence of souvereign countries leads to coordination of macroeconomic policies, and that it  can motivate  monetary integration within the monetary policy. The objective of this research paper is to emphasize the stability of the international monetary system as a prerequisite for sustainable growth of national economies and monetary union. The contemporary international monetary system is characterised by the trend of reduced number of national currencies, as this is  a  logical conseqence of increasing European integrations, but also beacuase of significant economic advanatages. Simultaneously, the costs of the euro changeover and introduction of a common currency are lower if economic performances of member countries mutualy converge.
CULTURAL TOURISM AS A UNIQUE FORM OF SUSTAINABLE TOURISM – CULTURAL RESOURCES AS TOURISM OFFER FACTORS
Authors: Ristić Zoran
Published: October 2019

There is a worldwide trend of increasing interest in cultural tourism products, and the World Tourism Organization predicts that the cultural tourism market will be one of the five leading segments of the tourism market in the future. Local culture is an important feature of a tourist destination, and thanks to tourism, it becomes a flywheel of social and economic development. Cultural tourism is focused on cultural attractions and activities as the main reasons for traveling, and the participation of cultural tourism in all tourist movements is increasing. Thus in France, Italy, Spain, the United Kingdom, income from tourists whose primary goal is to get acquainted with cultural goods and cultural achievements exceed 1/3 of total tourism revenues. Starting from the above, this paper focuses on the analysis of the key problems of the development of cultural tourism and the possibilities of enriching tourist destinations with cultural offer through the development of a cultural product, as a way of increasing the value of a comprehensive tourist offer and attracting a large number of tourists. It concludes with a brief analysis of the key issues for this field of cultural policy in the Republic of Serbia and recommendations on how to make a tourist attraction from a cultural resource and to achieve greater satisfaction of the tourists with their stay in a destination.
THE IMPACT OF TECHNOLOGICAL DEVELOPMENT ON INSURANCE COMPANIES
Authors: Pušara Dejan
Published: October 2019

In the contemporary business environment, the fundamental parameter for the successful subsistence of the competitive advantages is keeping pace with the contemporary trends. This also applies to the insurance industry, regardless of how conservative it is considered to be. Information and Communication Technologies influence all business sectors of the insurance companies. The users are increasingly reaching for the Internet as tools of research of insurance prices and products, and possibilities are opening up for the insurers through the new distribution channels. Innovations of the existing products and the development of the new ones represent the driving force behind the evolution of the entire insurance sector. Investing in the modern technology through information systems and risk modeling software makes administrative work easier, and has a significant role in the strategic-business decision-making process.
Motor cortex signals for each arm are mixed across hemispheres and neurons yet partitioned within the population response
Authors: Ames Katherine Cora , Churchland Mark M
Published: October 2019

Motor cortex (M1) has lateralized outputs, yet neurons can be active during movements of either arm. What is the nature and role of activity across the two hemispheres? We recorded muscles and neurons bilaterally while monkeys cycled with each arm. Most neurons were active during movement of either arm. Responses were strongly arm-dependent, raising two possibilities. First, population-level signals might differ depending on the arm used. Second, the same population-level signals might be present, but distributed differently across neurons. The data supported this second hypothesis. Muscle activity was accurately predicted by activity in either the ipsilateral or contralateral hemisphere. More generally, we failed to find signals unique to the contralateral hemisphere. Yet if signals are shared across hemispheres, how do they avoid impacting the wrong arm? We found that activity related to each arm occupies a distinct subspace, enabling muscle-activity decoders to naturally ignore signals related to the other arm.
Modular organization of cerebellar climbing fiber inputs during goal-directed behavior
Authors: Tsutsumi Shinichiro , Hidaka Naoki , Isomura Yoshikazu , Matsuzaki Masanori , Sakimura Kenji , Kano Masanobu , Kitamura Kazuo
Published: October 2019

The cerebellum has a parasagittal modular architecture characterized by precisely organized climbing fiber (CF) projections that are congruent with alternating aldolase C/zebrin II expression. However, the behavioral relevance of CF inputs into individual modules remains poorly understood. Here, we used two-photon calcium imaging in the cerebellar hemisphere Crus II in mice performing an auditory go/no-go task to investigate the functional differences in CF inputs to modules. CF signals in medial modules show anticipatory decreases, early increases, secondary increases, and reward-related increases or decreases, which represent quick motor initiation, go cues, fast motor behavior, and positive reward outcomes. CF signals in lateral modules show early increases and reward-related decreases, which represent no-go and/or go cues and positive reward outcomes. The boundaries of CF functions broadly correspond to those of aldolase C patterning. These results indicate that spatially segregated CF inputs in different modules play distinct roles in the execution of goal-directed behavior.
Electrocorticographic dissociation of alpha and beta rhythmic activity in the human sensorimotor system
Authors: Stolk Arjen , Brinkman Loek , Vansteensel Mariska J , Aarnoutse Erik , Leijten Frans SS , Dijkerman Chris H , Knight Robert T , de Lange Floris P , Toni Ivan
Published: October 2019

This study uses electrocorticography in humans to assess how alpha- and beta-band rhythms modulate excitability of the sensorimotor cortex during psychophysically-controlled movement imagery. Both rhythms displayed effector-specific modulations, tracked spectral markers of action potentials in the local neuronal population, and showed spatially systematic phase relationships (traveling waves). Yet, alpha- and beta-band rhythms differed in their anatomical and functional properties, were weakly correlated, and traveled along opposite directions across the sensorimotor cortex. Increased alpha-band power in the somatosensory cortex ipsilateral to the selected arm was associated with spatially-unspecific inhibition. Decreased beta-band power over contralateral motor cortex was associated with a focal shift from relative inhibition to excitation. These observations indicate the relevance of both inhibition and disinhibition mechanisms for precise spatiotemporal coordination of movement-related neuronal populations, and illustrate how those mechanisms are implemented through the substantially different neurophysiological properties of sensorimotor alpha- and beta-band rhythms.
Solvent polarity mediates phytochemical yield and antioxidant capacity of Isatis tinctoria
Authors: Wakeel Abdul , Jan Sohail Ahmad , Ullah Ikram , Shinwari Zabta Khan , Xu Ming
Published: October 2019

Secondary metabolites have been extensively used in the treatment of various health problems. The role of solvent polarity on the phytochemical isolation and antioxidant capacity of Isatis tinctoria (woad) is elusive. In the present study, 14 solvents with different polarity were used in the extraction and total phenolic and flavonoid content (TPC and TFC) investigation. Ferricyanide, phosphomolybdenum, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods were used to calculate and compare the antioxidant/free radical scavenging capacity. Our results showed that solvent polarity greatly affects TPC and TFC yield, which is mainly increasing with increasing solvent polarity index and suddenly decreasing at very high polarity. The comparative results showed that TPC is directly correlated with reducing power, antioxidant, and free radical scavenging capacity. Taken together, we conclude that different woad plant parts contain different level of secondary metabolites with a specific polarity that requires a particular solvent with an appropriate polarity index for the extraction. The identification of these biologically active crude extracts and fractions are very important for the basic biological sciences, pharmaceutical applications, and future research for HPLC based active compounds isolation.
Optimizing drug selection in psychopharmacology based on 40 significant CYP2C19- and CYP2D6-biased adverse drug reactions of selective serotonin reuptake inhibitors
Authors: Eugene Andy R.
Published: October 2019

Background

Selective serotonin reuptake inhibitors (SSRIs) are among the most widely prescribed class of drugs in the practice of psychiatry. Cytochrome P450 (CYP) 2C19 and CYP2D6 are established as clinically relevant drug metabolizing enzymes (DMEs) that influence the pharmacokinetics of SSRIs and may either be grouped as being primarily metabolized by CYP2C19 or CYP2D6. The aim of this study is to test the hypothesis that the primary drug metabolizing pathway for SSRI antidepressants are associated with adverse drug reactions (ADRs) related to physiological modulation of organs with the highest gene tissue expression.

Methods

Post-marketing ADR cases were obtained from the United States Food and Drug Administration’s Adverse Events Reporting System from each of the four quarters for the years 2016 and 2017. Cases were grouped based on one of two primary pharmacokinetic pharmacogenomic pathway biomarkers CYP2C19 and CYP2D6. Citalopram, escitalopram, and sertraline were grouped as CYP2C19 substrates and fluvoxamine, fluoxetine, and paroxetine as CYP2D6 substrates. Logistic regression was computed for the reported SSRI ADRs associated with one of two aforementioned DMEs. All data homogenization and computations were performed in R for statistical programming.

Results

The most commonly reported ADR among the SSRIs was anxiety (n = 3,332). The top two ADRs associated with SSRIs metabolized by CYP2D6 are: nightmare (n = 983) reporting odds-ratio (OR) = 4.37 (95% confidence interval (CI) [3.67–5.20]) and panic attack (n = 1,243) OR = 2.43 (95% CI [2.11–2.79]). Contrastingly, the top two ADRs for CYP2C19 metabolized SSRIs are: electrocardiogram QT prolonged (n = 351) OR = 0.18 (95% CI [0.13–0.24]) and small for dates baby (n = 306) OR = 0.19 (95% CI [0.14–0.26]). The study tested and produced 40 statistically significant CYP2C19- and CYP2D6-biased ADRs. In overall context, the results suggest that CYPC19 SSRI substrates are associated with ADRs related to modulation of the autonomic nervous system, seizure, pain, erectile-dysfunction, and absorption. Contrastingly, CYP2D6 SSRI substrates are associated with ADRs related to nightmares, withdrawal syndrome, and de-realization of cognitive processes. The results of this study may aid as guidance to optimize drug selection in psychopharmacology.
One‐Step Scalable Fabrication of Graphene‐Integrated Micro‐Supercapacitors with Remarkable Flexibility and Exceptional Performance Uniformity
Authors: Shi Xiaoyu , Zhou Feng , Peng Jiaxi , Wu Ren'an , Wu Zhong‐Shuai , Bao Xinhe
Published: October 2019

The rapid development of miniature electronics has accelerated the demand for simplified and scalable production of micro‐supercapacitors (MSCs); however, the preparation of active materials, patterning microelectrodes, and subsequent modular integration of the reported MSCs are normally separated and are involved in multiple complex steps. Herein, a one‐step, cost‐effective strategy for fast and scalable fabrication of patterned laser‐induced graphene (LIG) for all‐solid‐state planar integrated MSCs (LIG‐MSCs) with various form factors of designable shape, exceptional flexibility, performance uniformity, superior modularization, and high‐temperature stability is demonstrated. Notably, using the conductive and porous LIG patterns composed of randomly stacked graphene nanosheets simultaneously acting as both microelectrodes and interconnects, the resulting LIG‐MSCs represent typical electrical double capacitive behavior, having an impressive areal capacitance of 0.62 mF cm−2 and long‐term stability without capacitance degeneration after 10 000 cycles. Furthermore, LIG‐MSCs display exceptional mechanical flexibility and adjustable voltage and capacitance output through arbitrary arrangement of cells connected in series and in parallel, indicative of exceptional performance customization. Moreover, all‐solid‐state LIG‐MSCs working at ionogel electrolyte exhibit highly stable performance even at high temperature of 100 °C, with 90% capacitance retention over 3000 cycles, suggestive of outstanding reliability. Therefore, the LIG‐MSCs offer tremendous opportunities for miniature power source‐integrated microelectronics.
From Highly Purified Boron Nitride to Boron Nitride‐Based Heterostructures: An Inorganic Precursor‐Based Strategy
Authors: Chen Hao , Yang Zhenzhen , Guo Wei , Dunlap John R. , Liang Jiyuan , Sun Yifan , Jie Kecheng , Wang Song , Fu Jie , Dai Sheng
Published: October 2019

The current approaches used to fabricate hexagonal boron nitrides (h‐BN) from boron trioxide and urea always results in contamination of the h‐BN product with carbon/oxygen. Thus, discovering a facile way of mass producing high‐purity h‐BN remains a challenge. A simple yet highly efficient thermal treatment approach to large‐scale fabrication of nanoporous h‐BN with high yield, high purity, and high crystallinity is described using NaNH2 and NaBH4 as the oxygen‐ and carbon‐free precursors. The unique properties of inorganic metal salts, i.e., high melting point and strong electrostatic interaction with carbon substrates, render this strategy suitable for the production of homogeneous h‐BN/mesoporous carbon and h‐BN/carbon nanotube heterostructures of high crystallinity, high h‐BN dispersity, and with a strong interfacial effect. These unique features make them promising candidates for supercapacitor applications, resulting a significantly enhanced specific capacitance. This study provides new insight into the fabrication of high‐purity h‐BN and h‐BN‐based heterostructures thus expanding their application in the field of energy storage and transformation.
Ultrasensitive and Highly Stretchable Multifunctional Strain Sensors with Timbre‐Recognition Ability Based on Vertical Graphene
Authors: Deng Caihao , Gao Peixiong , Lan Linfeng , He Penghui , Zhao Xin , Zheng Wei , Chen Wangshou , Zhong Xizhou , Wu Yunhui , Liu Lan , Peng Junbiao , Cao Yong
Published: October 2019

Stretchable/wearable strain sensors are attracting growing interest due to their broad applications in physical and physiological measurements. However, the development of a multifunctional highly stretchable sensor satisfying the requirements of ultrahigh sensitivity (able to distinguish sound frequency) remains a challenge. An ultrasensitive and highly stretchable multifunctional strain sensor with timbre‐recognition ability based on high‐crack‐density vertical graphene (VGr) is fabricated using an ultrasonic peeling (UP) method. It can distinguish frequencies of sounds higher than 2500 Hz. Detailed microscopic examinations reveal that their ultrahigh sensitivity stems from the formation of high‐density nanocracks in the graphitic base layer, which is bridged by the top branched VGr nanowalls. These nanocracks cut the VGr film into a large number of nanopieces, which increase the natural frequency of the sensors, enabling the sensors to distinguish the sound frequency. Demonstrations are presented to highlight the sensors' potential as wearable devices for human physiological signal and timbre detections. This is the first multifunctional highly stretchable strain sensor with timbre‐recognition ability.
Red/Far‐Red Light Switchable Cargo Attachment and Release in Bacteria‐Driven Microswimmers
Authors: Sentürk Oya Ilke , Schauer Oliver , Chen Fei , Sourjik Victor , Wegner Seraphine V.
Published: October 2019

In bacteria‐driven microswimmers, i.e., bacteriabots, artificial cargos are attached to flagellated chemotactic bacteria for active delivery with potential applications in biomedical technology. Controlling when and where bacteria bind and release their cargo is a critical step for bacteriabot fabrication and efficient cargo delivery/deposition at the target site. Toward this goal, photoregulating the cargo integration and release in bacteriabots using red and far‐red light, which are noninvasive stimuli with good tissue penetration and provide high spatiotemporal control, is proposed. In the bacteriabot design, the surfaces of E. coli and microsized model cargo particles with the proteins PhyB and PIF6, which bind to each other under red light and dissociate from each other under far‐red light are functionalized. Consequently, the engineered bacteria adhere and transport the model cargo under red light and release it on‐demand upon far‐red light illumination due to the photoswitchable PhyB–PIF6 protein interaction. Overall, the proof‐of‐concept for red/far‐red light switchable bacteriabots, which opens new possibilities in the photoregulation in biohybrid systems for bioengineering, targeted drug delivery, and lab‐on‐a‐chip devices, is demonstrated.
Synthesis of C2‐Phosphorylated Indoles via Metal‐Free 1,2‐Phosphorylation of 3‐Indolylmethanols with P(O)‐H Species
Authors: Zou Yun‐Xiang , Liu Xiao‐Yan , Zhang Jing , Yang Hong‐Li , Yang Xin‐Yue , Liu Xiao‐Ling , Chu Yi‐Wen , Chen Long
Published: October 2019

An efficient and practical method for synthesis of C2‐phosphorylated indoles has been disclosed via a metal‐free 1,2‐phosphorylation of 3‐indolylmethanols with H‐phosphine oxides or H‐phosphonates. This alternative protocol features a broad substrate scope with respect to both 3‐indolylmethanols derived from isatins, acyclic α‐keto amide, α‐keto ester, 1,2‐diketone and simple ketones and H‐phosphine oxides or H‐phosphonates, moderate to high yields and mild reaction conditions. Mechanistic studies indicate that this reaction proceeds via an unusual direct 1,2‐addition pathway, in which the existence of an electron‐withdrawing group adjacent to the hydroxyl group of 3‐indolylmethanols plays a decisive role.

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Robotic Hands with Intrinsic Tactile Sensing via 3D Printed Soft Pressure Sensors
Authors: Ntagios Markellos , Nassar Habib , Pullanchiyodan Abhilash , Navaraj William Taube , Dahiya Ravinder
Published: October 2019

Herein, the development of complex 3D intelligent structures such as robotic hands using innovative designs and multimaterial additive manufacturing technology is presented. The distal phalanges of the 3D printed hand presented herein have inherent soft capacitive touch or pressure sensors and embedded electronics. Materials such as thermoplastic polyurethane (TPU), silver paint, conductive polylactic acid composite, graphite ink, etc. are explored to develop five different variants of the sensors using a modified 3D printer, which is capable of extruding conductive ink, metal paste, and polymers. The best‐performing 3D printed soft capacitive touch sensors, formed with silver paint and soft rubber (Ecoflex 00‐30), are integrated on the distal phalanges of the 3D printed robotic hand. These sensors exhibit a stable response with sensitivity of 0.00348 kPa−1 for pressure <10 kPa and 0.00134 kPa−1 for higher pressure. To demonstrate the practical applicability, the 3D printed hand with embedded soft capacitive touch sensors is used for interacting with everyday objects. The tightly integrated sensing elements within the 3D printed structures, as presented herein, can pave the way for a new generation of truly smart material systems that can possibly change their appearance and shape autonomously.
User‐Friendly Copper‐Catalysed Reduction of Azides to Amines
Authors: Pimpasri Chaleena , White Andrew J. P. , Díez‐González Silvia
Published: October 2019

Three homoleptic copper(I) complexes have been prepared and applied to the reduction of organic azides. Under optimised conditions, complex [Cu(HPDIDMA)2]BF4 3 (HPDIDMA=2,6‐bis[N‐(4‐dimethylaminophenyl)carbaldimino]pyridine) could reduce a range of electron‐poor azides in a mixture of DMSO and water without the need of an additional H‐source.
Targeted Exosomes for Drug Delivery: Biomanufacturing, Surface Tagging, and Validation
Authors: Si Yingnan , Kim Seulhee , Zhang Eric , Tang Yawen , Jaskula‐Sztul Renata , Markert James M. , Chen Herbert , Zhou Lufang , Liu Xiaoguang (Margaret)
Published: October 2019

Exosomes hold great potential to deliver therapeutic reagents for cancer treatment due to its inherent low antigenicity. However, several technical barriers, such as low productivity and ineffective cancer targeting, need to be overcome before wide clinical applications. The present study aims at creating a new biomanufacturing platform of cancer‐targeted exosomes for drug delivery. Specifically, a scalable, robust, high‐yield, cell line based exosome production process is created in a stirred‐tank bioreactor, and an efficient surface tagging technique is developed to generate monoclonal antibody (mAb)‐exosomes. The in vitro characterization using transmission electron microscopy, NanoSight, and western blotting confirm the high quality of exosomes. Flow cytometry and confocal laser scanning microscopy demonstrate that mAb‐exosomes have strong surface binding to cancer cells. Furthermore, to validate the targeted drug delivery efficiency, romidepsin, a histone deacetylase inhibitor, is loaded into mAb‐exosomes. The in vitro anti‐cancer toxicity study shows high cytotoxicity of mAb‐exosome‐romidepsin to cancer cells. Finally, the in vivo study using tumor xenograft animal model validates the cancer targeting specificity, anti‐cancer efficacy, and drug delivery capability of the targeted exosomes. In summary, new techniques enabling targeted exosomes for drug delivery are developed to support large‐scale animal studies and to facilitate the translation from research to clinics.
Ethnic identity in our global society: Supporting youth physical and mental health and adjustment
Authors: Coutinho Maria Teresa
Published: October 2019

Ethnic identity development is a normative developmental process that youth experience in adolescence. Ethnicity refers to an individual's membership into a group with a common ancestry, including shared culture, place of origin, language, kinship, or values. Ethnic identity refers to one's identity or sense of self as a member of an ethnic group. Research evidence on ethnic identity in children and adolescents overwhelmingly points to its importance in supporting positive mental and physical health, academic, and social outcomes for youth. In this article, we describe the process of ethnic identity development and discuss strategies for caregivers, clinicians, and educators to support positive ethnic identity development in our youth.
Keep Your Eye On…
Authors: Knopf Alison
Published: October 2019

The effectiveness of lithium for youth with bipolar disorder

The power of inattention to predict problems 3 years later
Surgeon general says pregnant women and teens should not use marijuana
Authors: Knopf Alison
Published: October 2019

When U.S. Surgeon General Jerome Adams, M.D., issued an advisory in August saying that marijuana should not be used by pregnant women or adolescents, backing it up with scientific — not law enforcement — justifications, there should have been no controversy.
Carbon molecular sieve membranes for natural gas purification: Role of surface flow
Authors: Khan Shaihroz , Wang Kean , Feng Xianshe , Elkamel Ali
Published: October 2019

Carbon molecular sieve membranes (CMSM) were prepared from the pyrolysis of polyimide films within a temperature range of 600°C‐800°C under nitrogen stream. The membrane samples were characterized and tested for the permeation of He, CH4, CO2, and N2 at different pressures and temperatures, respectively. The CMSM700 membrane (pyrolyzed at 700°C) showed an ideal selectivity of ~ 11 for N2/CH4 with a permeability of 2.18 × 10−15 mol · m/m2 · s · Pa for N2. The separation mechanism for the N2/CH4 pair was shown to be largely molecular sieving rather than surface flow. The membrane showed an ideal selectivity of ~ 500 for the CO2/CH4 pair with a CO2 permeability of 9.72 × 10−14 mol · m/m2 · s · Pa. The permeability of He was lower than that of CO2, suggesting that the surface flow played a significant role in the CO2 permeation. The updated permeability‐selectivity tradeoff curves show that this CMSM membrane compared favourably with other membrane materials reported in the literature for the removal of N2 and CO2 from CH4 for natural gas upgrading.
Mitochondria‐Targeted Nanoscale MOFs for Improved Photodynamic Therapy
Authors: Gong Ming , Yang Jian , Zhuang Qixin , Li Yongsheng , Gu Jinlou
Published: October 2019

Due to the existence of hypoxic microenvironment, the efficacy of photodynamic therapy (PDT) is frequently weakened. As a result, targeted treatment toward oxygen‐rich mitochondria is considered as a promising cancer therapy. Herein, both triphenylphosphine (TPP) and folic acid (FA) are simultaneously grafted onto nanoscale metal‐organic frameworks (NMOFs) to realize dual‐targeting delivery of the nanoplatforms into cancer cells and their mitochondria via the proposed phosphorylation modification strategy. A large amount of highly efficient photosensitizer of porphyrinic molecules is integrated into the NMOFs with a uniform particle size of about 65 nm. Thanks to the strong Zr−O−P bonding, a dense coverage of phosphonate‐conjugating targeting molecules on NMOFs is obtained and each surficial unsaturated Zr−O cluster is adequately occupied. The resultant dual‐targeting NMOFs feature high biostability and biocompatibility, as well as improved cellular uptake and mitochondrial accumulation. The PDT efficacy of these dual‐targeting NMOFs is significantly improved with a low IC50 of 0.74 μM upon 10 min light radiation, which is at least four times higher than that of non‐targeting counterparts. This phosphorylation strategy would be hopeful for immobilizing a variety of biogenic groups on NMOFs to make them targetable to various specific organelles and to improve the therapy efficacy on related diseases.
Model Experiments for Flow Phenomena in Crystal Growth
Authors: Dadzis Kaspars , Pätzold Olf , Gerbeth Gunter
Published: October 2019

The concept of a physical model experiment is introduced and discussed in the context of melt and gas flows in bulk crystal growth processes. Such experiments allow one to "extract" selected physical phenomena from the full complexity of a real crystal growth process and “transfer” them to material systems with an easier access for experimental measurements. Model experiments for the main techniques of melt growth are summarized in a literature review, and the applicability of the results to real crystal growth systems is analyzed. Recent examples of model experiments for melt and gas flows in Czochralski growth of silicon are used to demonstrate the state of the art and show the potential of such experiments to improve the understanding of complex multi‐physical multi‐scale phenomena occurring in every crystal growth process.
Predicting functional responses in agro‐ecosystems from animal movement data to improve management of invasive pests
Authors: Wilber Mark Q. , Chinn Sarah M. , Beasley James C. , Boughton Raoul K. , Brook Ryan K. , Ditchkoff Stephen S. , Fischer Justin W. , Hartley Steve B. , Holmstrom Lindsey K. , Kilgo John C. , Lewis Jesse S. , Miller Ryan S. , Snow Nathan P. , VerCauteren Kurt C. , Wisely Samantha M. , Webb Colleen T. , Pepin Kim M.
Published: October 2019

Functional responses describe how changing resource availability affects consumer resource use, thus providing a mechanistic approach to prediction of the invasibility and potential damage of invasive alien species (IAS). However, functional responses can be context dependent, varying with resource characteristics and availability, consumer attributes, and environmental variables. Identifying context dependencies can allow invasion and damage risk to be predicted across different ecoregions. Understanding how ecological factors shape the functional response in agro‐ecosystems can improve predictions of hotspots of highest impact and inform strategies to mitigate damage across locations with varying crop types and availability. We linked heterogeneous movement data across different agro‐ecosystems to predict ecologically driven variability in the functional responses. We applied our approach to wild pigs (Sus scrofa), one of the most successful and detrimental IAS worldwide where agricultural resource depredation is an important driver of spread and establishment. We used continental‐scale movement data within agro‐ecosystems to quantify the functional response of agricultural resources relative to availability of crops and natural forage. We hypothesized that wild pigs would selectively use crops more often when natural forage resources were low. We also examined how individual attributes such as sex, crop type, and resource stimulus such as distance to crops altered the magnitude of the functional response. There was a strong agricultural functional response where crop use was an accelerating function of crop availability at low density (Type III) and was highly context dependent. As hypothesized, there was a reduced response of crop use with increasing crop availability when non‐agricultural resources were more available, emphasizing that crop damage levels are likely to be highly heterogeneous depending on surrounding natural resources and temporal availability of crops. We found significant effects of crop type and sex, with males spending 20% more time and visiting crops 58% more often than females, and both sexes showing different functional responses depending on crop type. Our application demonstrates how commonly collected animal movement data can be used to understand context dependencies in resource use to improve our understanding of pest foraging behavior, with implications for prioritizing spatiotemporal hotspots of potential economic loss in agro‐ecosystems.
Regional differences in kelp forest interaction chains are influenced by both diffuse and localized stressors
Authors: Udy J. A. , Wing S. R. , Jowett T. , O'Connell‐Milne S. A. , Durante L. M. , McMullin R. M. , Kolodzey S.
Published: October 2019

On temperate rocky reefs, overexploitation of high‐trophic‐level omnivores can result in the decimation of kelp forest habitats by releasing sea urchin population networks from top‐down control. However, the local dynamics of the resulting trophic cascades are context‐dependent. Here, we investigate the community‐wide patterns associated with both diffuse stressors and localized protection of high‐trophic‐level omnivores in kelp forest ecosystems by comparing communities among marine reserves and fished areas in two contrasting regions in terms of fishing intensity and land‐based stressors, Fiordland and the Marlborough Sounds, New Zealand. We find higher densities of the potential sea urchin predators, red rock lobsters (Jasus edwardsii) and banded wrasse (Notolabrus fucicola), in the Fiordland region, and larger effect sizes of fishing on the exploited fish communities in the Marlborough Sounds. Patterns in sea urchin density were consistent with the idea that high‐trophic‐level species, such as large fish and rock lobsters, regulate sea urchin population density, with lower densities of Evechinus chloroticus observed inside marine reserves, in both regions. Nevertheless, densities of E. chloroticus were generally high (>3 m2) in the Marlborough Sounds, likely above a grazing threshold in both fished and reserve sites. The proportion of habitat where sea urchins were absent was 29% in Marlborough Sounds and 90% in Fiordland. Consequently, we observe 49% barren habitat in Fiordland vs. 70%, and a larger effect of fishing on kelp community structure, in the Marlborough Sounds, where fishing effect sizes and land‐based stressors were more severe. We propose that a combination of diffuse stressors including regional overexploitation of important sea urchin predators, sedimentation, and warming of coastal waters likely contributed to regional differences in the responses of trophic interaction chains to localized reductions in fishing within marine reserves. The present study highlights how physiologically stressed and modified kelp forest ecosystems are more susceptible to detrimental phase shifts at a regional spatial scale.
Is it climate or chemistry? Soil fungal communities respond to soil nutrients in a multi‐year high‐resolution analysis
Authors: Burke David J. , Carrino‐Kyker Sarah R. , Burns Jean H.
Published: October 2019

Predicting potential responses of soil fungal communities and fungal diversity to environmental change is limited by relatively few long‐term data sets, despite the important role fungi play in ecosystem processes. In this study, we examined the relative importance of environmental factors (weather or climate factors and chemical factors) on fungal communities over a period of five years. We examined fungal communities in an old‐growth beech‐maple forest in northeastern Ohio, located within the snow belt of Lake Erie, which receives an average of 287 cm of snowfall. Soil was collected every month from long‐term plots and divided into different soil depths; a total of 1080 samples were collected and used for fungal community and chemical analysis. We used DNA fragment analysis methods to examine fungal community response to environmental factors, and used next‐generation sequencing to examine specific responses of fungal species and quantify diversity in forest soil. Tests for phylogenetic signal were used to explore whether fungal responses are similar among close relatives or divergent within clades. Fungal communities responded significantly to chemical factors such as soil phosphorus but responded weakly to climate factors such as soil temperature, suggesting that fungal community composition reflects temporal variation in microsite environmental conditions. Sequencing revealed high degrees of fungal species richness, with an average of 384 operational taxonomic units (OTUs) within each soil core and more than 1000 OTUs within our study site. Fungal taxa associated with phosphorus availability and soil moisture were also distributed broadly across fungal clades (e.g., Basidiomycota, Ascomycota). Our study suggests that microsite chemical factors (e.g., soil moisture, P availability) correlate more strongly with fungal community variation than climate factors (e.g., soil temperature). In addition, environmental responses were not conserved among close relatives, suggesting that relatedness may not be sufficient to predict potential responses to these factors.
Foraging ecology mediates response to ecological mismatch during migratory stopover
Authors: Tucker Anna M. , McGowan Conor P. , Catalano Matthew J. , DeRose‐Wilson Audrey , Robinson Robert A. , Zimmerman Jordan
Published: October 2019

Impacts of ecological mismatches should be most pronounced at points of the annual cycle when populations depend on a predictable, abundant, and aggregated food resource that changes in timing or distribution. The degree to which species specialize on a key prey item, therefore, should determine their sensitivity to mismatches. We evaluated the hypothesis that the effects of ecological mismatch during migratory stopover are mediated by a species’ foraging ecology by comparing two similar long‐distance migratory species that differ in their foraging strategies during stopover. We predicted that a specialist foraging strategy would make species more sensitive to effects of mismatch with a historically abundant prey, while an active, generalist foraging strategy should help buffer against changing local conditions. We estimated arrival times, start of mass gain, and rate of mass gain during spring stopover in Delaware Bay, USA. At this site, shorebirds feed on a temporally aggregated food resource (horseshoe crabLimulus polyphemuseggs), the timing of which is linked to water temperature; red knot (Calidris canutus rufa) specializes on these while the ruddy turnstone (Arenaria interpres) feeds more generally. We used a hierarchical nonlinear model to estimate the effect of mismatch between shorebird arrivals and timing of crab spawning on the timing and rate of mass gain over 22 yr. In years with cooler water temperature, crabs spawned later, which was associated with later and faster mass gain for the knots. Turnstones exhibited less inter‐annual variation in the timing and rate of mass gain than knots, and we found no relationship between mass gain dynamics and the availability of horseshoe crab eggs for this generalist species. Long‐distance migrants rely on predictable resources en route and even when these linkages are simple and predictable, populations can be vulnerable to change; these results suggest that generalist foraging strategies may buffer migratory species against phenological mismatch. We provide a framework to evaluate population responses to changes in prey phenology at sites vulnerable to climatic change.
Quality of service in IoT protocol as designs and its verification in PVS
Authors: Nawaz Muhammad Saqib , Sun Meng , Shahzad Basit , Lali M. Ikram Ullah , Umer Tariq , Wan Shaohua
Published: October 2019

Reliable data transmission during communication in Internet of things (IoT)–based systems has gained much interest in last few years due to the current growth and huge investment in such systems. Message Queue Telemetry Transport (MQTT) is an open publish/subscribe–based messaging protocol that is widely used for device communication in IoT. For data transmission between devices, different levels of quality of service (QoS) are used in MQTT. In this paper, we provide a formal model for MQTT protocol under the Unifying Theories of Programming (UTP) semantic framework, where QoS levels in MQTT are modeled as designs in UTP. Refinement and equivalence relations between QoS levels can be established naturally via implication between predicates. Moreover, Prototype Verification System (PVS) is used to encode the UTP design models and some important properties as well as the refinement relation between QoS levels is proved with the PVS proof assistant.
Energy modeling and adaptive sampling algorithms for energy‐harvesting powered nodes with sampling rate limitations
Authors: Gindullina Elvina , Badia Leonardo , Vilajosana Xavier
Published: October 2019

This article explores the implementation of different sampling strategies for a practical energy‐harvesting wireless device (sensor node) powered by a rechargeable battery. We look for a realistic yet effective sampling strategy that prevents packet delivery failures, which is simple enough to be implemented in low‐complexity hardware. The article proposes methods that balance erratic energy arrivals and include advantages of dynamic data‐driven approaches based on historical data. Due to the industrial requirements in terms of minimum acceptable sampling frequency, we also integrate sampling rate limits and verify the proposed methods. To do so, we simulated the operation of an industrial data logger powered with a solar panel relying on the enhanced state of the model for battery charging. Finally, the proposed methods are compared based on energy consumption over a year and the amount of packet delivery failures, thus showing how some modifications of available strategies achieve satisfactory performance in this sense.
Increased Fracture Risk in Women Treated With Aromatase Inhibitors Versus Tamoxifen: Beneficial Effect of Bisphosphonates
Authors: Pineda-Moncusí Marta , Garcia-Giralt Natalia , Diez-Perez Adolfo , Servitja Sonia , Tusquets Ignasi , Prieto-Alhambra Daniel , Nogués Xavier
Published: October 2019

Aromatase inhibitors have been associated with accelerated bone loss and an increased risk of osteoporotic fractures. Currently, bisphosphonates are recommended to reduce fracture risk in these patients. The aim of this study is to evaluate the fracture risk in breast cancer patients receiving aromatase inhibitors, compared to tamoxifen users, and to assess the effectiveness of oral bisphosphonates in reducing fracture risk. We performed an observational cohort study up to 10 years of follow-up. Data were extracted from primary care records in a population database. Women diagnosed with breast cancer between 2006 and 2015 and treated with tamoxifen or aromatase inhibitors (n = 36,472) were stratified according to low (without osteoporosis diagnosis nor bisphosphonates exposure) or high (with osteoporosis and/or treated with bisphosphonates) fracture risk. Cox models were used to calculate hazard ratios (HR [95% CI]) of fracture from the propensity score–matched patients. Sensitivity analyses account for competing risk of death were performed (subdistribution hazard ratio [SHR] [95% CI]). In postmenopausal women, fracture risk in aromatase inhibitor users showed an HR 1.40 [95% CI,1.05 to 1.87] and SHR 1.48 [95% CI, 1.11 to 1.98], compared to tamoxifen. Observing aromatase inhibitors patients at high risk of fracture, bisphosphonate-treated patients had an HR 0.73 [95% CI, 0.51 to 1.04] and SHR 0.69 [95% CI, 0.48 to 0.98] compared to nontreated. In conclusion, fracture risk in postmenopausal women during aromatase inhibitor treatment, in real-life conditions, was >40% compared to tamoxifen, corroborating previous randomized controlled trials results. In high-risk patients, bisphosphonate users had lower significant fracture incidence during aromatase inhibitor therapy than nonbisphosphonate users. Monitoring fracture risk and related risk factors in aromatase inhibitor patients is advisable. © 2019 American Society for Bone and Mineral Research.
Osteocalcin Regulates Arterial Calcification Via Altered Wnt Signaling and Glucose Metabolism
Authors: Rashdan Nabil A , Sim Alisia M , Cui Lin , Phadwal Kanchan , Roberts Fiona L , Carter Roderick , Ozdemir Derya D , Hohenstein Peter , Hung John , Kaczynski Jakub , Newby David E , Baker Andrew H , Karsenty Gerard , Morton Nicholas M , MacRae Vicky E
Published: October 2019

Arterial calcification is an important hallmark of cardiovascular disease and shares many similarities with skeletal mineralization. The bone-specific protein osteocalcin (OCN) is an established marker of vascular smooth muscle cell (VSMC) osteochondrogenic transdifferentiation and a known regulator of glucose metabolism. However, the role of OCN in controlling arterial calcification is unclear. We hypothesized that OCN regulates calcification in VSMCs and sought to identify the underpinning signaling pathways. Immunohistochemistry revealed OCN co-localization with VSMC calcification in human calcified carotid artery plaques. Additionally, 3 mM phosphate treatment stimulated OCN mRNA expression in cultured VSMCs (1.72-fold, p < 0.001). Phosphate-induced calcification was blunted in VSMCs derived from OCN null mice (Ocn−/−) compared with cells derived from wild-type (WT) mice (0.37-fold, p < 0.001). Ocn−/− VSMCs showed reduced mRNA expression of the osteogenic marker Runx2 (0.51-fold, p < 0.01) and the sodium-dependent phosphate transporter, PiT1 (0.70-fold, p < 0.001), with an increase in the calcification inhibitor Mgp (1.42-fold, p < 0.05) compared with WT. Ocn−/− VSMCs also showed reduced mRNA expression of Axin2 (0.13-fold, p < 0.001) and Cyclin D (0.71 fold, p < 0.01), markers of Wnt signaling. CHIR99021 (GSK3β inhibitor) treatment increased calcium deposition in WT and Ocn−/− VSMCs (1 μM, p < 0.001). Ocn−/− VSMCs, however, calcified less than WT cells (1 μM; 0.27-fold, p < 0.001). Ocn−/− VSMCs showed reduced mRNA expression of Glut1 (0.78-fold, p < 0.001), Hex1 (0.77-fold, p < 0.01), and Pdk4 (0.47-fold, p < 0.001). This was accompanied by reduced glucose uptake (0.38-fold, p < 0.05). Subsequent mitochondrial function assessment revealed increased ATP-linked respiration (1.29-fold, p < 0.05), spare respiratory capacity (1.59-fold, p < 0.01), and maximal respiration (1.52-fold, p < 0.001) in Ocn−/− versus WT VSMCs. Together these data suggest that OCN plays a crucial role in arterial calcification mediated by Wnt/β-catenin signaling through reduced maximal respiration. Mitochondrial dynamics may therefore represent a novel therapeutic target for clinical intervention. © 2019 American Society for Bone and Mineral Research.