bluuebunny/crossref_metadata_2025_split huggingface dataset:
A yeast platform for high-level synthesis of natural and unnatural tetrahydroisoquinoline alkaloids
Authors: Pyne Michael E. , Kevvai Kaspar , Grewal Parbir S. , Narcross Lauren , Choi Brian , Bourgeois Leanne , Dueber John E. , Martin Vincent J. J. 
Published: December 2019

ABSTRACTThe tetrahydroisoquinoline (THIQ) moiety is a privileged substructure of many bioactive natural products and semi-synthetic analogues. The plant kingdom manufactures more than 3,000 THIQ alkaloids, including the opioids morphine and codeine. While microbial species have been engineered to synthesize a few compounds from the benzylisoquinoline alkaloid (BIA) family of THIQs, low product titers impede industrial viability and limit access to the full chemical space. Here we report a THIQ platform by increasing yeast production of the central BIA intermediate (S)-reticuline to more than 3 g L-1, a 38,000-fold improvement over our first-generation strain. Gains in BIA output coincided with the formation of several substituted THIQs derived from host amino acid catabolism. Enabled by this activity, we repurposed the yeast Ehrlich pathway and demonstrate the synthesis of an array of unnatural THIQ scaffolds. This work provides a blueprint for synthesizing new privileged structures and will enable the targeted overproduction of thousands of THIQ products, including natural and semi-synthetic opioids.
Efficient Homology-directed Repair with Circular ssDNA Donors
Authors: Iyer Sukanya , Mir Aamir , Vega-Badillo Joel , Roscoe Benjamin P. , Ibraheim Raed , Zhu Lihua Julie , Lee Jooyoung , Liu Pengpeng , Luk Kevin , Mintzer Esther , Soares de Brito Josias , Zamore Philip D. , Sontheimer Erik J. , Wolfe Scot A. 
Published: December 2019

AbstractWhile genome editing has been revolutionized by the advent of CRISPR-based nucleases, difficulties in achieving efficient, nuclease-mediated, homology-directed repair (HDR) still limit many applications. Commonly used DNA donors such as plasmids suffer from low HDR efficiencies in many cell types, as well as integration at unintended sites. In contrast, single-stranded DNA (ssDNA) donors can produce efficient HDR with minimal off-target integration. Here, we describe the use of ssDNA phage to efficiently and inexpensively produce long circular ssDNA (cssDNA) donors. These cssDNA donors serve as efficient HDR templates when used with Cas9 or Cas12a, with integration frequencies superior to linear ssDNA (lssDNA) donors. To evaluate the relative efficiencies of imprecise and precise repair for a suite of different Cas9 or Cas12a nucleases, we have developed a modified Traffic Light Reporter (TLR) system [TLR-Multi-Cas Variant 1 (MCV1)] that permits side-by-side comparisons of different nuclease systems. We used this system to assess editing and HDR efficiencies of different nuclease platforms with distinct DNA donor types. We then extended the analysis of DNA donor types to evaluate efficiencies of fluorescent tag knock-ins at endogenous sites in HEK293T and K562 cells. Our results show that cssDNA templates produce efficient and robust insertion of reporter tags. Targeting efficiency is high, allowing production of biallelic integrants using cssDNA donors. cssDNA donors also outcompete lssDNA donors in template-driven repair at the target site. These data demonstrate that circular donors provide an efficient, cost-effective method to achieve knock-ins in mammalian cell lines.
Role of post-trial visual feedback on unintentional force drift during isometric finger force production tasks
Authors: Balamurugan S , Rachaveti Dhanush , SKM Varadhan 
Published: December 2019

AbstractForce produced during an isometric finger force production task tends to drift towards a lower magnitude when visual information is occluded. This phenomenon of drift in force without one’s awareness is called unintentional drift. The present study used epilogue, a particular case of post-trial visual feedback, and compared the unintentional drift for two conditions, i.e., with and without the epilogue. For this purpose, fourteen healthy participants were recruited for the experiments and were instructed to produce fingertip forces using four fingers of the right hand with the target line at 15% MVC. A trial lasted for sixteen seconds, where for the initial eight seconds, there is visual feedback followed by the visual occlusion period. The results showed a significant reduction in unintentional drift for the condition involving epilogue when compared to no epilogue. This reduction in drift is due to the shift in the referent configuration parameter by the phenomenon of RC back coupling. Further, we also claim that there might be a distribution of λs or RCs, based on the history of tuning of the control parameter by the central controller. This distribution of λs selected by the central controller in a redundant environment based on the epilogue resulted in a reduction of unintentional drift.
Trans-acting role of the leader peptide peTrpL in posttranscriptional regulation of multiresistance
Authors: Melior Hendrik , Li Siqi , Förstner Konrad U. , Azarderakhsh Saina , Barth-Weber Susanne , Evguenieva-Hackenberg Elena 
Published: December 2019

AbstractBacterial ribosome-dependent attenuators are widespread posttranscriptional regulators. They harbour small upstream ORFs (uORFs) encoding leader peptides, for which no functions in trans are known yet. In the soil-dwelling plant symbiont Sinorhizobium meliloti, the tryptophan biosynthesis gene trpE(G) is preceded by the uORF trpL and is regulated by transcription attenuation according to tryptophan availability. However, trpLE(G) transcription is initiated independently of the tryptophan level in the cell, thereby ensuring a largely tryptophan-independent production of the leader peptide peTrpL. We provide evidence that peTrpL plays a role in the differential posttranscriptional regulation of the smeABR operon encoding the major multidrug efflux pump SmeAB and the TtgR-type transcription repressor SmeR. We show that peTrpL is involved in a tetracycline-dependent smeR mRNA destabilization and forms an antibiotic-dependent ribonucleoprotein (ARNP) complex with smeR and its antisense RNA (asRNA). Induction of asRNA transcription, ARNP formation and smeR downregulation were promoted by several antibiotics and the flavonoid genistein, and the resistance to these antimicrobial compounds was increased by peTrpL. The role of peTrpL in resistance is conserved in other soil Alphaproteobacteria.
BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome activity
Authors: Bittner Zsófia A. , Liu Xiao , Shankar Sangeetha , Tapia-Abellán Ana , Kalbacher Hubert , Andreeva Liudmila , Mangan Matthew , Düwell Peter , Lovotti Marta , Bosch Karlotta , Dickhöfer Sabine , Marcu Ana , Stevanović Stefan , Herster Franziska , Löffler Markus W. , Wolz Olaf-Oliver , Schilling Nadine A. , Kümmerle-Deschner Jasmin , Wagner Samuel , Delor Anita , Grimbacher Bodo , Wu Hao , Latz Eicke , Weber Alexander N. R. 
Published: December 2019

AbstractActivity of the NLRP3 inflammasome, a critical mediator of inflammation (1), is controlled by accessory proteins (2, 3), post-translational modifications (4, 5), cellular localization (6, 7) and oligomerization (8). How these factors relate, is unclear. We show that the established drug target, Bruton’s Tyrosine Kinase (BTK) (2, 9), integrates several levels of NLRP3 regulation: BTK phosphorylation of four conserved tyrosine residues, by neutralizing the charge of a polybasic linker region, weakens the interaction of NLRP3 with Golgi phospholipids and may thus guide NLRP3 cytosolic localization. BTK activity also promotes NLRP3 oligomerization and subsequent formation of inflammasomes. As NLRP3 tyrosine modification ultimately also impacts on IL-1β release, we propose BTK-mediated, charge-switch-based NLRP3 regulation as a novel and therapeutically tractable step in the control of inflammation.One Sentence SummaryMulti-phosphorylation of NLRP3 by Bruton’s tyrosine kinase modulates NLRP3 cellular localization, inflammasome assembly, and IL-1β release.
Experience and relatedness influence mating interactions in a simultaneously hermaphroditic snail,Physa gyrina
Authors: McCarthy Thomas M. 
Published: December 2019

AbstractThe means by which animals assess potential mates is an important issue in studies of reproductive systems. I tested whether an individual’s previous experiences and the relatedness of mates affected mating behavior in a simultaneous hermaphrodite snail,Physa gyrina. Previous work with this species showed reduced reproductive success resulting from both strong outbreeding and inbreeding. Thus, I predicted that individuals should prefer partners of intermediate relatedness. During activity trials, snails moved longer distances when exposed to chemical cues from conspecifics of lesser relatedness. Furthermore, during mating interactions, behavioral responses to relatedness varied with gender-role: male-role behaviors did not vary across relatedness treatments, while snails paired with either closely related or highly dissimilar partners increased their female-role resistance behaviors as interactions escalated. Experiences with their current partner also affected behavioral dynamics. Familiar pairs had fewer matings and longer latency times until a mating occurred than unfamiliar pairs. Snails acting in the female role also exhibited higher resistance rates in familiar pairs than in unfamiliar pairs. Previous, brief exposure to chemical cues in a non-mating context also influenced behavior during a subsequent mating interaction. Snails that were previously exposed to chemical cues from unfamiliar individuals tended to be more likely to occupy the male role following an encounter, and had significantly lower copulation frequencies and higher female-role resistance rates (i.e. were choosier) than those previously exposed to cues from familiar individuals. Overall, the results show that: 1) relatedness, past exposure to conspecific chemical cues, and experience with a current partner all influence mating behaviors in these snails; and 2) in these simultaneous hermaphrodites, an individual’s responses depend on whether it is occupying the male or female role.
The trade-offs of sharing pollinators: pollination service is determined by the community context
Authors: Cagua E. Fernando , Marrero Hugo J. , Tylianakis Jason M. , Stouffer Daniel B. 
Published: December 2019

AbstractA fundamental feature of pollination systems is the indirect facilitation and competition that arises when plants species share pollinators. When plants share pollinators, the pollination service can be influenced. This depends not only on how many partners plant species share, but also by multiple intertwined factors like the plant species’ abundance, visitation, or traits. These factors inherently operate at the community level. However, most of our understanding of how these factors may affect the pollination service is based on systems of up to a handful of species. By examining comprehensive empirical data in eleven natural communities, we show here that the pollination service is—surprisingly—only partially influenced by the number of shared pollinators. Instead, the factors that most influence the pollination service (abundance and visit effectiveness) also introduce a trade-off between the absolute amount of conspecific pollen received and the amount relative to heterospecific pollen. Importantly, the ways plants appear to balance these trade-offs depend strongly on the community context, as most species showed flexibility in the strategy they used to cope with competition for pollination.
The nucleus measures shape deformation for cellular proprioception and regulates adaptive morphodynamics
Authors: Venturini Valeria , Pezzano Fabio , Castro Frederic Català , Häkkinen Hanna-Maria , Jiménez-Delgado Senda , Colomer-Rosell Mariona , Sánchez Mónica Marro , Tolosa-Ramon Queralt , Paz-López Sonia , Valverde Miguel A. , Loza-Alvarez Pablo , Krieg Michael , Wieser Stefan , Ruprecht Verena 
Published: December 2019

AbstractThe physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within their local environment remains largely unknown. Here we show that the nucleus, the biggest cellular organelle, functions as a non-dissipative cellular shape deformation gauge that enables cells to continuously measure shape variations on the time scale of seconds. Inner nuclear membrane unfolding together with the relative spatial intracellular positioning of the nucleus provides physical information on the amplitude and type of cellular shape deformation. This adaptively activates a calcium-dependent mechano-transduction pathway, controlling the level of actomyosin contractility and migration plasticity. Our data support that the nucleus establishes a functional module for cellular proprioception that enables cells to sense shape variations for adapting cellular behaviour to their microenvironment.One Sentence SummaryThe nucleus functions as an active deformation sensor that enables cells to adapt their behavior to the tissue microenvironment.
Hacienda Flandes: Los Altibajos De Una Finca Cafetera Colombiana
Authors: Gonzalez Ana Cristina , Ossa Vesga Henry 
Published: December 2019

Supplementary materials
Las notas pedagógicas contienen materiales de lectura específicos para apoyar la discusión en clase.

Learning outcomes
Los estudiantes podrán comprender y explicar el concepto de una empresa familiar como un sistema dinámico: empresa, familia e individuos, cada uno con acciones y resultados; analizar las oportunidades y las amenazas para las empresas familiares a través de las generaciones; y formular estrategias para equilibrar las demandas de la empresa y de la familia.

Case overview/synopsis
Este caso cuenta la historia de dos generaciones de caficultores de la Hacienda Flandes, en la región cafetera de Colombia. Describe los factores externos e internos que afectaron el negocio familiar desde 1970 hasta 2013. El caso presenta los antecedentes y las consecuencias de las circunstancias medioambientales y de las decisiones de los miembros de la familia, y que llevaron el negocio desde la bonanza hasta el decaimiento y posteriormente a su posible reinvención. Se espera que los estudiantes, mediante el análisis de esta plantación de café familiar que se extiende varias generaciones, comprendan la importancia de la planeación estratégica en las empresas familiares, en el contexto de un ambiente cambiante y competitivo. Las empresas más comunes son las empresas familiares en las economías emergentes. En Latinoamérica, la mayoría de empresas familiares suelen ser más jóvenes que aquellas de Europa e incluso Norte América. Por lo tanto, las empresas familiares en estas economías pueden estar atravesando o pronto atravesarán una sucesión. La tasa de éxito de las sucesiones es baja, independientemente de la cultura o el país en el que se desarrolle la empresa. Este caso lidia con la preparación (o falta de preparación) de la siguiente generación para la administración de empresas familiares, y con las consecuencias de esto, y ayuda a los estudiantes a sugerir alternativas y mejores decisiones para dirigir empresas familiares en una economía emergente.

Complexity academic level
Cursos de MBA sobre empresas familiares y/o cursos de educación ejecutiva que se enfoquen en empresas familiares. El caso se puede usar en sesiones introductorias relacionadas con estrategia de empresas familiares.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 11: Strategy
Applying the Delphi method to determine best practices for outsourcing logistics in disaster relief
Authors: Gossler Timo , Falagara Sigala Ioanna , Wakolbinger Tina , Buber Renate 
Published: December 2019

PurposeThe purpose of this paper is to determine best practices of aid agencies for outsourcing logistics to commercial logistics service providers (LSPs) in disaster relief. Moreover, it evaluates the application of the Delphi method for research in humanitarian logistics.Design/methodology/approachThe paper is based on a two-round Delphi study with 31 experts from aid agencies and a complementary full-day focus group with 12 experts from aid agencies and LSPs.FindingsThe study revealed 12 best practices for outsourcing logistics in disaster relief and a compilation of more than 100 activities for putting these practices into action. Experts consider a proper balance between efficiency and compliance, a detailed contract and a detailed service request most important. Additionally, the Delphi method was found to be a promising technique for research on humanitarian logistics.Research limitations/implicationsBy critically examining the Delphi method, this study establishes the basis for a wider application of the technique in the field of humanitarian logistics. Furthermore, it can help to prioritize future research as the ranking of practices reflects the priorities of practitioners.Practical implicationsThe paper provides guidance to practitioners at aid agencies in charge of outsourcing logistics.Originality/valueThis research is one of the first in the field of humanitarian logistics to apply the Delphi method. Moreover, it addresses the lack of literature dealing with approaches for building successful cross-sectoral partnerships.
A comprehensive review of ultrasonic additive manufacturing
Authors: Hehr Adam , Norfolk Mark 
Published: December 2019

Purpose
This paper aims to comprehensively review ultrasonic additive manufacturing (UAM) process history, technology advancements, application areas and research areas. UAM, a hybrid 3D metal printing technology, uses ultrasonic energy to produce metallurgical bonds between layers of metal foils near room temperature. No melting occurs in the process – it is a solid-state 3D metal printing technology.

Design/methodology/approach
The paper is formatted chronologically to help readers better distinguish advancements and changes in the UAM process through the years. Contributions and advancements are summarized by academic or research institution following this chronological format.

Findings
This paper summarizes key physics of the process, characterization methods, mechanical properties, past and active research areas, process limitations and application areas.

Originality/value
This paper reviews the UAM process for the first time.
Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single‐center, open‐label, prospective randomized study
Authors: Okamoto Teppei , Hatakeyama Shingo , Konishi Sakae , Okita Kazutaka , Tanaka Yoshimi , Imanishi Kengo , Takashima Tooru , Saitoh Fumitada , Suzuki Tadashi , Ohyama Chikara 
Published: December 2019

AbstractThe efficacy and safety of zinc acetate hydrate (ZAH) for zinc supplementation in patients on maintenance hemodialysis (MHD) remains unknown. In this prospective, single‐center, open‐label, parallel‐group trial for MHD patients with serum zinc level <70 μg/dL, we compared ZAH (zinc; 50 mg/day) and polaprezinc (PPZ; zinc; 34 mg/day) beyond 6‐month administration in a 1:1 randomization manner. The ZAH and PPZ groups had 44 and 47 patients, respectively. At 3 months, the change rate of serum zinc levels in the ZAH group was significantly higher than that in the PPZ group. Three months after the study, serum copper levels significantly decreased in the ZAH group, but not in the PPZ group. No significant differences were noted in anemia management in either group. ZAH was superior to PPZ in increasing serum zinc levels. Clinicians should note the stronger decline in serum copper levels when using ZAH for MHD patients.
“Nerve” and violent encounters: An assessment of fearlessness in the face of danger
Authors: Melde Chris , Berg Mark T. , Esbensen Finn‐Aage 
Published: December 2019

AbstractThe findings from a large body of research on the ecology of violence indicate that individuals demonstrate a willingness to engage in violence to reduce their risk for violent victimization. Scholars have suggested that a reputation for toughness and aggression acts as an informal signal that deters mistreatment. Anderson (1999), in his street code thesis, in particular, argued that adherence to the street code functions as a signal that reduces violent victimization risk. Other research findings, however, reveal that the street code leads to an increase in victimization risk; moreover, violent offenders are routinely victimized at high rates given their lifestyle and routine activities. The evidence, therefore, does not show support for the position that a reputation for toughness or aggression effectively reduces violent victimization. In the current study, we operationalize the concept of nerve, which findings from criminological studies indicate is an important mechanism for protecting adolescents from victimization. Using data from the second national evaluation of the Gang Resistance Education and Training Program, we test this operationalization of nerve to determine whether the concept is associated with later violent offending and violent victimization in ways consistent with theory and research on the ecology of youth violence. Our results demonstrate support for the notion that nerve is positively associated with violent offending, whereas those at the highest levels of this construct experience fewer violent victimizations.
The cost to perform uterine fibroid embolisation in the Australian public hospital system
Authors: Clements Warren , Moriarty Heather K , Koukounaras Jim , Joseph Tim , Phan Tuan , Goh Gerard S 
Published: December 2019

AbstractIntroductionUterine fibroids have the potential to cause morbidity, and there is a substantial cost to both the healthcare system and society. There is support for minimally invasive intervention, and uterine fibroid embolisation (UFE) is an established cost‐effective option for women wishing for an alternative to surgery. There is a lack of local Australian costing data to compliment use in the public hospital system, and we offer a costing analysis of running a public hospital service.MethodsWe reviewed the costs for 10 sequential uterine fibroid embolisation cases, by assessing the direct and indirect hospital costs.ResultsThe total cost of providing a uterine fibroid embolisation service using our model in a public hospital including initial outpatient assessment, procedure costs, overnight hospital ward stay and outpatient follow‐up is $3995 per admission.ConclusionUsing our model, the overall cost to perform this procedure is low, and lower than prior estimates for surgical alternatives. We encourage government and regulatory bodies to support UFE through guidelines and remuneration models, and encourage more public Australian interventional radiology departments to offer this service.