bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐Distance Agreement
Authors: Bhatt Rajesh , Keine Stefan
Published: November 2017

Long‐distance agreement (LDA) refers to agreement between a functional head in the extended projection of one lexical head with an argument of another lexical head. LDA is found in a variety of languages, including Indo‐Aryan (Hindi/Urdu, Kashmiri, Kutchi), Basque, Tsez, Chukotko‐Kamchatkan, and native North American languages (Innu‐aimûn, Passamaquoddy). All instances of LDA described in the literature share a number of properties. First, LDA uses the same primitives as local agreement. Every element that may control LDA may also trigger local agreement. The morphological forms of LDA are also found in local agreement. Second, LDA is generally optional. This is all the more relevant because local agreement is always obligatory in these languages. Third, a verb can agree with an element in a lower clause, but not with one in a higher clause.

Virtually all studies on LDA converge in that they treat it as local in some sense. The following general lines of analysis have been proposed. First, the LDA controller is (possibly covertly) moved into the matrix clause and triggers agreement from there. Second, the LDA trigger moves to the edge of the embedded clause and agrees from there. Third, LDA depends on whether or not a locality boundary (i.e., phase head) is projected in the embedded clause (restructuring). Fourth, the LDA controller triggers local agreement with a functional head in the embedded clause. A matrix head subsequently agrees with the embedded functional head. Fifth, a silent pronoun coreferent with the embedded object is inserted into the matrix clause and triggers local agreement there. These lines of analysis are not mutually exclusive.

LDA has been argued to provide evidence against Upward Agree. It furthermore is crucial for the general question of syntactic locality. It also raises the general problem of optionality in syntax, in particular since the optionality of agreement appears to correlate with distance.
Across‐the‐Board Phenomena
Authors: de Vries Mark
Published: November 2017

Across‐the‐Board (ATB) phenomena in linguistics, can generally be defined as one‐to‐many correspondences. Standard examples involvewh‐extraction out of two or more coordinated clauses or phrases at once, as inWhich teacher did John like _ and Sue hate _?Such configurations violate an otherwise valid bi‐uniqueness principle: an antecedent licenses one and only one dependent element; furthermore, they are at variance with the alleged island status of coordinate structures. As such, ATB phenomena constitute an intriguing syntactic puzzle. There are diverse views on the nature and explanation of ATB, as well as on the question of which construction types can be subsumed under it. Coordination is clearly an important factor, since ATB does not normally involve hierarchically different positions, with the possible exception of parasitic gaps and a few other construction types. It has also been claimed that ATB phenomena extend to certain cases of ellipsis, including Right Node Raising. Apart from this, it is evident that various types of features, including case, can be spread over multiple conjuncts, and that binding by some antecedent outscoping the entire coordination phrase may concern pronominal variables in more than one conjunct at once. This raises the question of whether some kind of multidimensional representation is required for coordinate structures. Related topics to be discussed from the current perspective are forward versus backward multiple dependencies, and split antecedents.
Focus Movement
Authors: Szendrői Kriszta
Published: November 2017

A language has a focus construction if a focused constituent (at least optionally) appears in a non‐canonical syntactic position. Jackendoff's (1972) invention, the [focus] feature, and Chomsky's (1976) observation that focus gives rise to weak crossover effects paved the way for an analysis of focus constructions as instances of focus movement. For presentational purposes the analyses can be divided into three groups, which also by‐and‐large correspond to their order of appearance.

The first group of analyses, which includes for instance Horvath (1986), regards the often‐attested adjacency requirement between the focus and the V (or other functional head, like I or C) as the crucial characteristic of focus constructions. Characteristics of focus movement in this approach are explained by the notion of government. One of the main advantages of this view is that it is able to accommodate both preverbal and postverbal focus positions with some degree of explanatory adequacy.

The second group of analyses, starting from Rizzi's (1997) influential paper on Italian focus, comprises the cartographic approach to focus movement. The approach stems from the close proximity between focus movement andwh‐movement. Its main tenet is that focus movement is triggered by a syntactic [focus] feature, and it targets a designated unique, pre‐determined syntactic position: the specifier of a functional Focus head. One immediate advantage of such a view is that it easily accounts for the quantificational properties of focus constructions.

The third set of analyses can be grouped under the umbrella term, interface approaches. These approaches stem from recognizing the fact that a syntactic [focus] feature is a direct violation of Chomsky's (1995) Inclusiveness Principle, and that if focus movement is triggered by such a feature then the autonomy of syntax cannot be maintained. One set of interface analyses concentrates on the syntax‐prosody interface and seeks to explain focus movement by making reference to the seemingly universal property of focus that if a language has a stress system, focus always bears main stress. The second set of analyses concentrates on the syntax‐semantics/pragmatics interface and either seeks to explain focus movement in terms of mapping principles between syntax and semantics/pragmatics, or gives up the idea of information structurally‐motivated movement altogether.
The Landscape of Negative Dependencies: Negative Concord and N‐Words
Authors: Giannakidou Anastasia , Zeijlstra Hedde
Published: November 2017

This chapter updates an earlier discussion of n‐words and negative concord (NC) offered by the first author. Our goal here is to address the considerable developments in the area of n‐words and NC that took place since 2006. As the title suggests, we study negative dependencies within the context of negative dependencies. We have chosen this term as a theory‐neutral way to refer to phenomena that in one way or another involve dependency of an expression on the presence of negation. Several major negative dependencies can be distinguished; negative polarity, NC, negative quantifiers in Germanic languages, and even the expression of negation itself have been discussed in this context. Negative dependencies form a landscape: they share a space as grammatical phenomena, for instance sensitivity to the presence of negation – but, at the same time, the dependencies are not identical. For instance, the need for negation of a negative polarity item such asanydoes not derive from the same source as the need of negation for an n‐word, which has a more narrow distribution thanany. And within the class of n‐words (the main focus of this chapter) there is considerable variation as well. Our approach is inspired by a long tradition of polarity research that acknowledges diversity and the fact that polarity phenomena are lexically driven. In presenting the phenomena, we apply a compositional perspective by connecting the nature of the sensitivity to the morphosyntactic, semantic, or pragmatic properties of the negation‐sensitive items.
Complementizer‐Trace Effects
Authors: Pesetsky David
Published: November 2017

Perlmutter observed that Englishwh‐movement obeys a puzzling constraint: an asymmetry between subject extraction and non‐subject extraction that interacts with the complementizer system. Whilewh‐extraction of a non‐subject from a finite embedded clause is compatible with the presence or absence of the wordthatintroducing the clause, extraction of the subject is possible only whenthatis omitted:

a.✓Who do you think that Sue met ____?/✓Who do you think Sue met ____?b.*Who do you think that ____ met Sue?/✓Who do you think ____ met Sue?The effect has come to be known as the “that‐trace effect,” a member of a family of possibly broader sets of phenomena, all called “complementizer‐trace effects.” A strong poverty of the stimulus argument makes it clear that these phenomena are rooted in innate properties of human language. The discovery of these effects in multiple diverse and unrelated languages reinforces this conclusion, especially when coupled with the availability of independently supported explanations for the absence of similar effects in other specific languages. On the other hand, quite distinct accounts have been offered for complementizer‐trace effects, and there is no consensus yet as to which of these approaches is most likely to prove correct.Linear accountshave been proposed that specifically bar extraction from positions right‐adjacent to elements of the complementizer system; these accounts are supported by claimed interactions with the presence/absence of prosodic boundaries between the two. Alternativestructure‐based accountsthat have proved influential include structural locality requirements on extraction sites that occupy particular syntactic positions – as well as proposals that take an opposite approach, banning movement that is too local. Thus, although the importance of complementizer‐trace effects for linguistic theory is clear, the deeper source of these effects remains a matter of controversy.
Reflexive Marking in Romance: Voice and Feature Deficiency
Authors: Dobrovie‐Sorin Carmen
Published: November 2017

The various meanings of SE/SI‐marked verbs (reflexive, inchoative, middle, and passive) are described with the aim of pointing out the most prominent empirical generalizations across Romance languages. An important number of pages is devoted to the distinction between the impersonal clitic subject SE/SI (assigned nominative) found in the major Romance languages with the exception of Romanian, and the homophonous passivizing accusative SE/SI. The analysis of SE/SI is subject to numerous theoretical debates concerning the status of SE/SI (voice marker or pronominal clitic?); the distinction between unaccusative, unergative, and transitive configurations; passivization; and, related to passivization, the (non‐)realization of the external argument of passives in a subject‐like position.
Subjunctives
Authors: Quer Josep
Published: November 2017

Subjunctive clauses have been shown to display a number of syntactic properties that distinguish them from indicative ones. The ways subjunctive clauses are overtly marked differ from language to language, but the options basically reduce to specialized verbal endings, designated inflectional particles or complementizers, or a combination thereof, and some languages without overt subjunctive marking also show those properties. Despite being often taken as a single category, subjunctive dependents do not behave as a uniform class, but quite robust general types are identified (volitional type, operator‐licensed type and presuppositional type). Probably the most striking property of subjunctive clauses is that they seem to be more transparent than indicative ones to some dependencies: subject obviation or disjoint reference effect between embedded and main clause subjects, long distance binding of anaphors and NPI‐licensing from the superordinate clause, and subject raising across a finite domain. The different analyses have modeled such transparency in essentially three different ways: associating subjunctive with defective Tense, arguing for the presence of a particular operator or establishing a direct parallel to dependent nominals (indefinites or polarity items). The syntactic analysis of subjunctive dependents has focused on the proper implementation of Mood features in the syntax, resulting in some cases in the postulation of a dedicated projection MoodP, and it has proposed particular derivations that subjunctive forms impose vis‐à‐vis indicative ones, giving rise to idiosyncratic phenomena such as subject inversion or C‐deletion in some languages. The relation to control structures has been studied with special interest in languages that lack infinitival clauses and only have subjunctive dependents. Despite the heterogeneity of the class “subjunctive” within a language and crosslinguistically, the explorations of its properties has led to a better understanding of the syntax of embedding and has triggered very interesting research on their semantics as well.
Object Shift in Scandinavian
Authors: Vikner Sten
Published: November 2017

As set out in section 1, this chapter takes 'object shift' to only refer to the kind of object shift typically found in the Scandinavian languages (following the original use of the term in Holmberg 1986, 165), to the exclusion of, for example, scrambling as found in Afrikaans, Dutch, Frisian, German, and Yiddish.

Section 2 reviews a number of properties and restrictions that apply to object shift but not to scrambling: for example that the verb has to leave the VP, section 2.1.1; that prepositions, particles, and indirect objects block object shift, section 2.1.2; that object shift does not license parasitic gaps, section 2.2; and that only DPs (or almost only DPs) undergo object shift, section 2.4. Finally, the potential landing sites were discussed in section 2.4.

The difference between Icelandic object shift, which applies to all DPs, and object shift in the other Scandinavian languages, which only applies to pronouns, is discussed in section 3.4.

The bulk of the chapter discusses the various suggestions as to key factors in the analysis of object shift and the restrictions which it underlies: case in section 3, equidistance in section 4, focus/interpretation in section 5, and prosody in section 6.
Remnant Movement
Authors: Thiersch Craig
Published: November 2017

This chapter deals with incomplete category fronting, that is, with the appearance in a topic position of what seems to be a constituent lacking some of its parts, which appear elsewhere in the clause. There have been several approaches to these constructions: (1) extraction of the subpart to a position elsewhere in the clause and subsequent topicalization of the full constituent, which now contains a trace of the subpart (remnant movement); (2) base‐generating the subpart elsewhere and topicalizing the rest (without a trace of the subpart); (3) copying the full constituent to the “topic” position and deleting (different) parts of the two copies (distributed deletion). While I discuss (2) and (3) briefly, I concentrate on (1), hence the title of the chapter.
Reproducibility of radioactive iodine uptake (RAIU) measurements
Authors: Pelletier‐Galarneau Matthieu , Martineau Patrick , Klein Ran , Henderson Matthew , Zuckier Lionel S.
Published: November 2017

Background

Measurement of radioactive iodine uptake (RAIU) is an important aspect of the assessment and treatment of patients with hyperthyroidism. Its uncertainty affects how much of a true change in RAIU can be detected as well as appropriateness of the therapy dosage upon which it is based. In this study, a method of estimating the reproducibility and least significant change (LSC) values for RAIU measurements, and the implications of the values observed are discussed, with emphasis on application to quality assurance initiatives.

Methods

We prospectively studied 36 consecutive patients referred for RAIU measurements. Twenty‐four hours after oral administration of 370 kBq of 131I‐NaI in capsule form, RAIU measurements were obtained in duplicate using a thyroid probe uptake system. Assessment of reproducibility was performed using root‐mean‐square standard deviation.

Results

Average difference between duplicated RAIU measurements in our study cohort was −0.1 ± 1.6% and ranged from −4.8% to 3.1%. Reproducibility of probe‐based RAIU measurement was calculated to be 1.1% and 95% LSC was 3.2%.

Conclusion

In our clinic, probe‐based RAIU is a reproducible and relatively precise measurement. Using the method we have outlined, each institution can perform reproducibility assessment and compute the LSC of RAIU measurements based on its own staff, iodine isotope, equipment, protocols, and patient population. These values are useful in the assessment of serial change in RAIU, and as more experience is accumulated, can serve as benchmarks to be used in quality assurance initiatives.
Scalable Production and Cryostorage of Organoids Using Core–Shell Decoupled Hydrogel Capsules
Authors: Lu Yen‐Chun , Fu Dah‐Jiun , An Duo , Chiu Alan , Schwartz Robert , Nikitin Alexander Yu. , Ma Minglin
Published: November 2017

Organoids, organ‐mimicking multicellular structures derived from pluripotent stem cells or organ progenitors, have recently emerged as an important system for both studies of stem cell biology and development of potential therapeutics; however, a large‐scale culture of organoids and cryopreservation for whole organoids, a prerequisite for their industrial and clinical applications, has remained a challenge. Current organoid culture systems relying on embedding the stem or progenitor cells in bulk extracellular matrix (ECM) hydrogels (e.g., Matrigel) have limited surface area for mass transfer and are not suitable for large‐scale productions. Here, a capsule‐based, scalable organoid production and cryopreservation platform is demonstrated. The capsules have a core–shell structure where the core consists of Matrigel that supports the growth of organoids, and the alginate shell forms robust spherical capsules, enabling suspension culture in stirred bioreactors. Compared with conventional, bulk ECM hydrogels, the capsules, which can be produced continuously by a two‐fluidic electrostatic cospraying method, provide better mass transfer through both diffusion and convection. The core–shell structure of the capsules also leads to better cell recovery after cryopreservation of organoids probably through prevention of intracellular ice formation.
Comment on “Structural and Electrical Properties of Atomic Layer Deposited Al‐Doped ZnO Films”
Authors: Saha Debabrata , Misra Pankaj , Joshi Mukesh , Kukreja Lalit Mohan
Published: November 2017

In a recent report,Lee et al. have proposed an “effective field model” for extrinsic doping to explain the electrical properties of Al‐doped zinc oxide (ZnO) films grown by atomic layer deposition (ALD).They have introduced the doping model by considering the layered structure of the ALD‐grown films as observed in the transmission electron microscopy measurements. However, in the present comment, we have demonstrated that the suggested doping model is misleading in which physically inconsistent assumptions are considered throughout. Herein, a reasonable interpretation of the electrical properties and doping mechanism of the ALD‐grown films by taking into consideration the theoretical formulations of the disordered electronic system is suggested.
Colorectal Cancer Diagnosis Using Enzyme‐Sensitive Ratiometric Fluorescence Dye and Antibody–Quantum Dot Conjugates for Multiplexed Detection
Authors: Park Youngrong , Ryu Yeon‐Mi , Wang Taejun , Jung Yebin , Kim Sohee , Hwang Sekyu , Park Joonhyuck , Bae Dong‐Jun , Kim Jaeil , Moon Heejo , Lim Hyun‐Suk , Kim Sang‐Yeob , Chung Euiheon , Kim Ki Hean , Kim Sungjee , Myung Seung‐Jae
Published: November 2017

A rapid and accurate molecular fluorescence imaging technique will greatly reduce cancer mortality by overcoming the detection limit of the naked eye in colonoscopy. Two imaging probes are reported that can be co‐used for colonoscopic diagnosis: a fluorescent molecular probe, cresyl violet–glutamic acid derivative, that ratiometrically switches between two fluorescent colors in response to the enzyme activity of λ‐glutamyltranspeptidase and an antibody quantum dot probe that is a conjugate of biocompatible AgInS2 quantum dot with matrix metalloproteinase 14 antibodies. Validity of the probes is confirmed using human colon cancer cell lines, ex vivo mouse model tissues, and patient tumor colon tissues in which the tumor lesions are well‐visualized in less than five minutes. Co‐application of the two probes onto fresh colon tissues affords accurate visualization of carcinomas and also hyperplasia and adenoma regions. Fresh human colon adenoma tissues are also valuated, where the two probes show complementary diagnoses of cancer. Two‐photon microscopy shows the time‐dependent depth profiles of the two probes. Both rapidly permeate and populate most at 10–20 µm from the surface. Extensive toxicity studies are performed for the two probes at cellular level and also at the organ level using a small animal model.
Kinetically Controlled Coprecipitation for General Fast Synthesis of Sandwiched Metal Hydroxide Nanosheets/Graphene Composites toward Efficient Water Splitting
Authors: Tang Tang , Jiang Wen‐Jie , Niu Shuai , Liu Ning , Luo Hao , Zhang Qiang , Wen Wu , Chen Yu‐Yun , Huang Lin‐Bo , Gao Feng , Hu Jin‐Song
Published: November 2017

The development of cost‐effective and applicable strategies for producing efficient oxygen evolution reaction (OER) electrocatalysts is crucial to advance electrochemical water splitting. Herein, a kinetically controlled room‐temperature coprecipitation is developed as a general strategy to produce a variety of sandwich‐type metal hydroxide/graphene composites. Specifically, well‐defined α‐phase nickel cobalt hydroxide nanosheets are vertically assembled on the entire graphene surface (NiCo‐HS@G) to provide plenty of accessible active sites and enable facile gas escaping. The tight contact between NiCo‐HS and graphene promises effective electron transfer and remarkable durability. It is discovered that Ni doping adjusts the nanosheet morphology to augment active sites and effectively modulates the electronic structure of Co center to favor the adsorption of oxygen species. Consequently, NiCo‐HS@G exhibits superior electrocatalytic activity and durability for OER with a very low overpotential of 259 mV at 10 mA cm−2. Furthermore, a practical water electrolyzer demonstrates a small cell voltage of 1.51 V to stably achieve the current density of 10 mA cm−2, and 1.68 V to 50 mA cm−2. Such superior electrocatalytic performance indicates that this facile and manageable strategy with low energy consumption may open up opportunities for the cost‐effective mass production of various metal hydroxides/graphene nanocomposites with desirable morphology and competing performance for diverse applications.
Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding
Authors: Hickman DaShawn A. , Pawlowski Christa L. , Sekhon Ujjal D. S. , Marks Joyann , Gupta Anirban Sen
Published: November 2017

Bleeding complications arising from trauma, surgery, and as congenital, disease‐associated, or drug‐induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf‐life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf‐life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state‐of‐art is provided, and challenges and opportunities to help advancement of the field are discussed.
High‐Throughput Phase‐Field Design of High‐Energy‐Density Polymer Nanocomposites
Authors: Shen Zhong‐Hui , Wang Jian‐Jun , Lin Yuanhua , Nan Ce‐Wen , Chen Long‐Qing , Shen Yang
Published: November 2017

Understanding the dielectric breakdown behavior of polymer nanocomposites is crucial to the design of high‐energy‐density dielectric materials with reliable performances. It is however challenging to predict the breakdown behavior due to the complicated factors involved in this highly nonequilibrium process. In this work, a comprehensive phase‐field model is developed to investigate the breakdown behavior of polymer nanocomposites under electrostatic stimuli. It is found that the breakdown strength and path significantly depend on the microstructure of the nanocomposite. The predicted breakdown strengths for polymer nanocomposites with specific microstructures agree with existing experimental measurements. Using this phase‐field model, a high throughput calculation is performed to seek the optimal microstructure. Based on the high‐throughput calculation, a sandwich microstructure for PVDF–BaTiO3 nanocomposite is designed, where the upper and lower layers are filled with parallel nanosheets and the middle layer is filled with vertical nanofibers. It has an enhanced energy density of 2.44 times that of the pure PVDF polymer. The present work provides a computational approach for understanding the electrostatic breakdown, and it is expected to stimulate future experimental efforts on synthesizing polymer nanocomposites with novel microstructures to achieve high performances.
Metal‐Free One‐Pot Synthesis of (Tetrahydro)Quinolines through Three‐Component Assembly of Arenediazonium Salts, Nitriles, and Styrenes
Authors: Youn So Won , Yoo Huen Ji , Lee Eun Mi , Lee Seo Young
Published: November 2017

A highly efficient and convenient metal‐free, one‐pot synthesis of diversely substituted (tetrahydro)quinolines has been achieved through a three‐component assembly reaction of arenediazonium salts, nitriles, and styrenes. In sharp contrast to the prior works with the same reagent blend, the formation of N‐arylnitrilium intermediates from arenediazonium salts and nitriles was followed by reaction with styrenes, leading to 3,4‐dihydroquinolinium salts as a common intermediate. These could be further transformed to quinolines and tetrahydroquinolines depending on the reaction conditions. The advantages of this protocol include its simplicity, metal‐free and mild conditions, readily available starting materials, and good functional group tolerance.

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Iron‐Sulfate‐Catalyzed Direct Dehydrogenative Coupling Cyanation of Secondary Phenylamines
Authors: Huang Mingming , Deng Qingfu , Gao Qin , Shi Jian , Zhang Xiaohui , Xiong Yan
Published: November 2017

A direct dehydrogenative coupling cyanation of secondary phenylamines was developed under iron sulfate catalysis by utilizing trimethylsilyl cyanide as a cyano source and tert‐butyl hydroperoxide as oxidant. A variety of α‐aminonitriles, which commonly serve as versatile synthetically important intermediates, were synthesized in isolated yields of up to 90 %. Based on control experiments, the cyanation mechanism might involve a single‐electron transfer and a subsequent formation of an iminium ion.
Fabrication of composite films with poly(methyl methacrylate) and incompletely condensed cage‐silsesquioxane fillers
Authors: Yuasa Sota , Sato Yuri , Imoto Hiroaki , Naka Kensuke
Published: November 2017

Polyhedral oligomeric silsesquioxane (POSS) is a promising nanofiller for tuning properties of optically transparent polymer materials. On the other hand, traditional completely condensed POSS (CC‐POSS) has a fundamental problem for fabricating optically transparent composite films; CC‐POSS has high crystallinity due to its symmetrical structure, resulting in aggregation in the polymer matrices. In this work, we have demonstrated that incompletely‐condensed POSS (IC‐POSS), which has an open‐cage structure, can be well dispersed in a poly(methyl methacrylate) (PMMA) matrix. IC‐POSS with various substituents were readily synthesized, and their composite films of PMMA were fabricated by solution‐casting method. High transparency was achieved with up to 30 wt % of the IC‐POSS fillers, while the CC‐POSS analogues caused phase separation with 10 wt % loading. Addition of the IC‐POSS fillers can improve thermal stability and control glass transition temperature by the substituent structure. Additionally, refractive index was tuned from 1.485 to 1.513. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46033.
Detection of Subclinical Arthritis in Mice by a Thrombin Receptor–Derived Imaging Agent
Authors: Friedman Beth , Whitney Michael A. , Savariar Elamprakash N. , Caneda Christa , Steinbach Paul , Xiong Qing , Hingorani Dina V. , Crisp Jessica , Adams Stephen R. , Kenner Michael , Lippert Csilla N. , Nguyen Quyen T. , Guma Monica , Tsien Roger Y. , Corr Maripat
Published: November 2017

Objective

Functional imaging of synovitis could improve both early detection of rheumatoid arthritis (RA) and long‐term outcomes. Given the intersection of inflammation with coagulation protease activation, this study was undertaken to examine coagulation protease activities in arthritic mice with a dual‐fluorescence ratiometric activatable cell‐penetrating peptide (RACPP) that has a linker, norleucine (Nle)‐TPRSFL, with a cleavage site for thrombin.

Methods

K/BxN‐transgenic mice with chronic arthritis and mice with day 1 passive serum‐transfer arthritis were imaged in vivo for Cy5:Cy7 emission ratiometric fluorescence from proteolytic cleavage and activation of RACPPNleTPRSFL. Joint thickness in mice with serum‐transfer arthritis was measured from days 0 to 10. The cleavage‐evoked release of Cy5‐tagged tissue‐adhesive fragments enabled microscopic correlation with immunohistochemistry for inflammatory markers. Thrombin dependence of ratiometric fluorescence was tested by ex vivo application of RACPPNleTPRSFL and argatroban to cryosections obtained from mouse hind paws on day 1 of serum‐transfer arthritis.

Results

In chronic arthritis, RACPPNleTPRSFL fluorescence ratios of Cy5:Cy7 emission were significantly higher in diseased swollen ankles of K/BxN‐transgenic mice than in normal mouse ankles. A high ratio of RACPPNleTPRSFL fluorescence in mouse ankles and toes on day 1 of serum‐transfer arthritis correlated with subsequent joint swelling. Foci of high ratiometric fluorescence localized to inflammation, as demarcated by immune reactivity for citrullinated histones, macrophages, mast cells, and neutrophils, in soft tissue on day 1 of serum‐transfer arthritis. Ex vivo application of RACPPNleTPRSFL to cryosections obtained from mice on day 1 of serum‐transfer arthritis produced ratiometric fluorescence that was inhibited by argatroban.

Conclusion

RACPPNleTPRSFL activation detects established experimental arthritis, and the detection of inflammation by RACPPNleTPRSFL on day 1 of serum‐transfer arthritis correlates with disease progression.
Interacting fields and flows: Magnetic hot Jupiters
Authors: Daley‐Yates S. , Stevens I. R.
Published: November 2017

We present magnetohydrodynamic (MHD) simulations of the magnetic interactions between a solar‐type star and short‐period hot Jupiter exoplanets using the publicly available MHD code PLUTO. It has been predicted that emission due to magnetic interactions such as the electron cyclotron maser instability (ECMI) will be observable. In our simulations, a planetary outflow, due to UV evaporation of the exoplanets atmosphere, results in the build‐up of circumplanetary material. We predict the ECMI emission and determine that the emission is prevented from escaping the system. This is due to the evaporated material leading to a high plasma frequency in the vicinity of the planet, which inhibits the ECMI process.
Autism spectrum disorder and birth spacing: Findings from the study to explore early development (SEED)
Authors: Schieve Laura A. , Tian Lin H. , Drews‐Botsch Carolyn , Windham Gayle C. , Newschaffer Craig , Daniels Julie L. , Lee Li‐Ching , Croen Lisa A. , Danielle Fallin M.
Published: November 2017

Previous studies of autism spectrum disorder (ASD) and birth spacing had limitations; few examined phenotypic case subtypes or explored underlying mechanisms for associations and none assessed whether other (non‐ASD) developmental disabilities (DDs) were associated with birth spacing. We assessed associations between inter‐pregnancy interval (IPI) and both ASD and other DDs using data from the Study to Explore Early Development, a multi‐site case‐control study with rigorous case‐finding and case‐classification methods and detailed data collection on maternal reproductive history. Our sample included 356 ASD cases, 627 DD cases, and 524 population (POP) controls born in second or later births. ASD and DD cases were further sub‐divided according to whether the child had intellectual disability (ID). ASD cases were also sub‐divided by ASD symptom severity, and DD cases were subdivided by presence of some ASD symptoms (indicated on an autism screener). Odds ratios, adjusted for maternal‐child sociodemographic factors, (aORs) and 95% confidence intervals were derived from logistic regression models. Among term births, ASD was associated with both IPI <18 months (aOR 1.5 [1.1–2.2]) and ≥60 months (1.5 [0.99–2.4]). Both short and long IPI associations were stronger among ASD cases with high severity scores (aORs 2.0 [1.3–3.3] and 1.8 [0.99–3.2], respectively). Associations were unchanged after adding several factors potentially related to the causal pathway to regression models. DD was not associated with either short or long IPI—overall, among term births, or in any subgroup examined. These findings extend those from previous studies and further inform recommendations on optimal pregnancy spacing. Autism Res 2018, 11: 81–94. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

We investigated whether the amount of time between pregnancies was associated autism spectrum disorder (ASD) or other developmental disabilities (DD) in children. ASD was increased in second and later‐born children who were conceived less than 18 months or 60 or more months after the mother's previous birth. Other DDs were not associated with birth spacing.
BIM in der Hochschullehre
Authors: Brokbals Stefanie , Čadež Ivan
Published: November 2017

Die Digitalisierung der Bauwirtschaft und die damit einhergehende Implementierung von Building Information Modeling (BIM) ist aktuell eine der größten Herausforderungen in der deutschen Bauwirtschaft. Ein wesentlicher Erfolgsfaktor dabei sind die – jedoch noch fehlenden – (Nachwuchs‐)Kräfte. Dies wurde von den Hochschulen erkannt, sodass BIM bereits an vielen Hochschulen gelehrt wird.

Im ersten Teil des Berichts werden der Status quo und die Entwicklung von BIM‐Lehre an Hochschulen über die letzten zwei Jahre (2015–2017) dargestellt. Im Jahr 2015 wurde an 28 von 69 (41 %) der Hochschulen BIM gelehrt. In den letzten zwei Jahren stieg die Anzahl der BIM‐lehrenden Hochschulen auf 41 (59 %) an. Darüber hinaus wurden u. a. die Unterschiede zwischen Universitäten und Fachhochschulen sowie zwischen den Studiengängen der Architektur und des Bauingenieurwesens untersucht.

Im zweiten Teil des Berichts werden die im Rahmen der Untersuchung definierten Soll‐Lehrinhalte den ermittelten Ist‐Lehrinhalten an den Hochschulen gegenübergestellt, um so den Handlungsbedarf herauszustellen. Abschließend werden auf Basis der Ergebnisse Handlungsempfehlungen für die Hochschulen vorgeschlagen. Beispielhaft ist dabei der Ausbau von interdisziplinären BIM‐Projekten zu nennen, bei denen vor allem die durch BIM veränderten Arbeits‐ und Kommunikationsprozesse den Studierenden vermittelt werden sollen.
Corn stover cannot simultaneously meet both the volume and GHG reduction requirements of the renewable fuel standard
Authors: Kim Seungdo , Zhang Xuesong , Dale Bruce , Reddy Ashwan Daram , Jones Curtis Dinneen , Cronin Keith , Izaurralde Roberto Cesar , Runge Troy , Sharara Mahmoud
Published: November 2017

Corn stover is expected to supply much of the cellulosic biomass required to meet the 61 billion liters per year target under the US Energy Independence and Security Act. The Act also requires that cellulosic biofuels achieve a greenhouse gas (GHG) reduction of 60% compared to gasoline. If corn stover is harvested for biofuels, it can no longer help replenish soil organic matter, and net soil carbon emissions increase. So meeting the GHG reduction target is a concern. We studied the effect of stover removal on overall GHG emissions of corn stover ethanol systems in the 12‐state Corn Belt region. Even at a stover removal rate of 66%, no more than 20 billion liters can be annually produced while simultaneously satisfying the 60% GHG reduction. Moreover, no GHG reduction relative to gasoline occurs in short time periods. The GHG benefits of corn stover ethanol only appear after longer time periods. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd
Development and validation of a simple solid‐phase extraction method coupled with liquid chromatography–triple quadrupole tandem mass spectrometry for simultaneous determination of lincomycin, tylosin A and tylosin B in royal jelly
Authors: Zheng Weijia , Park Jin‐A , Abd El‐Aty A. M. , Kim Seong‐Kwan , Cho Sang‐Hyun , Choi Jeong‐Min , Warda Mohamad , Wang Jing , Shim Jae‐Han , Shin Ho‐Chul
Published: November 2017

We have developed an analytical method for the determination of lincomycin, tylosin A and tylosin B residues in royal jelly using liquid chromatography–triple quadrupole tandem mass spectrometry analysis. For extraction and purification, we employed 1% trifluoroacetic acid and 0.1 m Na2EDTA solutions along with an Oasis HLB cartridge. The target antibiotics were well separated in a Kinetex EVO C18 reversed‐phase analytical column using a combination of 0.1% formate acid in ultrapure water (A) and acetonitrile (B) as the mobile phase. Good linearity was achieved over the tested concentration range (5–50 μg/kg) in matrix‐matched standard calibration. The coefficients of determination (R2) were 0.9933, 0.9933 and 0.996, for tylosin A, tylosin B and lincomycin, respectively. Fortified royal jelly spiked with three different concentrations of the tested antibiotics (5, 10 and 20 μg/kg) yielded recoveries in the range 80.94–109.26% with relative standard deviations ≤4%. The proposed method was applied to monitor 11 brand of royal jelly collected from domestic markets and an imported brand from New Zealand; all the samples tested negative for lincomycin, tylosin A and tylosin B residues. In conclusion, 1% trifluoroacetic acid and 0.1 m Na2EDTA aqueous solvents combined with solid‐phase extraction could effectively complete the sample preparation process for royal jelly before analysis. The developed approach can be applied for a routine analysis of lincomycin, tylosin A and tylosin B residues in royal jelly.
Identification of cytochrome P450 isoforms involved in the metabolism of artocarpin and assessment of its drug–drug interaction
Authors: Qu Wei , Liu Xuezheng
Published: November 2017

Artocarpin isolated from an agricultural plant Artocarpus communis has shows anti‐inflammation and anticancer activities. In this study, we utilized recombinant human UDP‐glucuronosyltransferasesupersomes (UGTs) and human liver microsomes to explore its inhibitory effect on UGTs and cytochrome p450 enzymes (CYPs). Chemical inhibition studies and screening assays with recombinant human CYPs were used to identify if CYP isoform is involved in artocarpin metabolism. Artocarpin showed strong inhibition against UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, CYP2C8 and CYP3A4. In particular, artocarpin exhibited competitive inhibition against CYP3A4 and noncompetitive inhibition against UGT1A3 and UGT1A7. The half inhibition concentration values for CYP3A4, UGT1A3 and UGT1A7 were 4.67, 3.82 and 4.82 μm, and the inhibition kinetic parameters for them were 0.78, 2.67 and 3.14 μm, respectively. After artocarpin was incubated in human liver microsomes and determined by HPLC, we observed its main metabolites (M1 and M2). In addition, we proved that CYP2D6 played the key role in the biotransformation of artocarpin in human liver microsomes. The result of molecular docking further confirmed that artocarpin interacted with CYP2D6, CYP2C8 and CYP3A4 through hydrogen bonds. This study provided preliminary results for further research on artocarpin or artocarpin‐containing herbs.
Effect of early hospital readmission and comorbid conditions on subsequent long‐term mortality after transient ischemic attack
Authors: Yousufuddin Mohammed , Young Nathan , Keenan Lawrence , Olson Tammy , Shultz Jessica , Doyle Taylor , Ahmmad Eimad , Arumaithurai Kogulavadanan , Takahashi Paul , Murad Mohammad Hassan
Published: November 2017

Background

The implications of early readmission on long‐term mortality after transient ischemic attack (TIA) are not known. We aimed at examining the effect of 180‐day readmission on subsequent long‐term mortality after index hospitalization for TIA.

Methods

A retrospective study of patients hospitalized for first‐ever TIA at Mayo Clinic from 2000 through 2017. Patients readmitted within 180 days postdischarge were compared with those not readmitted in long‐term risk of death.

Results

Of 251 TIA patients aged 73 ± 15 years with 1509 person‐years of follow‐up, 65 (26%) were readmitted within 180 days of discharge and 125 died during a median follow‐up of 5.7 years. The mortality was 10 vs. 7 deaths per 100 person‐years in patients who were readmitted compared to those who were not readmitted with hazard ratio (HR) 1.73 (95% confidence interval [CI] 1.13–2.66). Other competing predictors of mortality were age ≥65 years (HR 5.70, 95% CI 2.72–11.96), cancer (HR 1.65, 95% CI 1.03–3.38), chronic obstructive pulmonary disease (HR 1.90, 95% CI 1.07–3.38), heart failure (HR 3.03, 95% CI 1.82–5.06), dementia (HR 5.87, 95% CI 3.27–10.52), creatinine ≥1.4 mg/dl (HR 1.89, 95% CI 1.17–3.06), and hemoglobin level <10 g/dl (HR 2.80, 95% CI 1.20–6.66).

Conclusions

Hospital readmission within 180 days of discharge from index TIA was associated with increased risk of death several years after initial readmission. Older age and several comorbidities identified during index hospitalization also confer increased risk for long‐term mortality.
CD226 deficiency improves cognitive functions and ameliorates anxiety‐like behaviors in mice
Authors: Fang Liang , Jin Jingyi , Chen Ping , Wang Ning , Zeng Hanyu , Jin Boquan , Li Hui , Chen Lihua
Published: November 2017

Background

CD226 is a cell surface adhesion molecule expressed in the immune system and central nervous system. Although the role of CD226 in the function of immune cells has been well studied, there has been no report on the potential functional significance of CD226 in neural cells.

Methods

We investigated the role of CD226 on the cognitive function and behaviors using CD226 knockout (CD226KO) and wild‐type mice. The spatial learning and memory were characterized using Morris water maze test, and the behaviors were evaluated using open field and elevated plus maze tests. IL‐10 expression in the hippocampus was measured using RT‐PCR and ELISA.

Results

The results showed that CD226KO mice displayed increased spatial learning and memory than the wild‐type controls. We also found that genetic deletion of CD226 resulted in decreased anxiety‐like behaviors. In addition, the hippocampal expression level of IL‐10 was increased in the CD226KO mice compared with the WT mice.

Conclusions

Our findings suggest that CD226 plays an important role in the modulation of cognition and anxiety in mice.
Four New Acylated Iridoid Glycosides from the Aerial Part of Veronicastrum sibiricum and Their Antioxidant Response Element‐Inducing Activity
Authors: Kim Myeong Il , Kim Chul Young
Published: November 2017

Four new (1 – 4) and one known (5) acylated iridoid glycosides were isolated from the aerial parts of Veronicastrum sibiricum (L.) Pennell. The chemical structures of the isolated compounds were determined to be 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosyl‐10‐O‐bergaptol‐5,7‐bisdeoxycynanchoside (1), 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylpaulownioside (2), 2″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylcatalpol (3), 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylaucubin (4), and 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylcatalpol (5) using spectroscopic techniques. Among these compounds, compound 5 increased antioxidant response element (ARE) luciferase activity.
Unexpected disseminated histoplasmosis detected by bone marrow biopsy in a solid organ transplant patient
Authors: Simon Caroline T. , Murga‐Zamalloa Carlos A. , Bachman Michael A. , Petty Lindsay A. , Choi Sarah M.
Published: November 2017

Key Clinical Message

Disseminated histoplasmosis and hemophagocytic lymphohistiocytosis show overlapping features, which require careful contextual interpretation. Histopathologic evaluation can potentially rapidly identify cases of possible histoplasmosis. A high index of clinical suspicion, particularly in endemic areas and in a setting of immunosuppression, is critical to appropriate diagnosis and treatment.
Enhancing the Rate Performance of a Li3VO4 Anode through Cu Doping
Authors: Wang Kan , Fu Haoyu , Li Zhuoyu , Xia Mengyang , Liang Xiaoqiang , Qi Ruijie , Cao Guozhong , Lu Xianmao
Published: November 2017

Li3VO4 (LVO), as an emerging anode material for lithium‐ion batteries (LIBs), offers distinct advantages because of its high theoretical specific capacity (590 mAh g−1), high ionic conductivity, and small volume change during lithiation/delithiation. However, the low electronic conductivity of LVO severely limits its viable application in LIBs. In this work, we doped LVO with Cu2+ ions through a simple solution reaction method, aiming to improve its electronic conductivity and electrochemical performances as a LIB anode. Among various dopant concentrations, LVO doped with 10 % Cu (LVO‐0.10Cu) showed the highest Li‐ion diffusion coefficient (2.79×10−14 cm2 s−1) and specific surface area (16.1 m2 g−1), as well as lowest charge‐transfer resistance. High reversible capacities of 440, 420, 379, and 335 mAh g−1 were achieved at current densities of 1, 2, 4, and 8 A g−1, respectively. In particular, the capacity of LVO‐0.10Cu at 8 A g−1 was twice as high as that of pristine LVO (335 vs. 168 mAh g−1). The significantly enhanced electrochemical performance of Cu‐doped LVO can be attributed to lattice expansion and improved electronic conductivity afforded by Cu‐doping.
Highly Efficient Synthesis of a Staphylococcus aureus Targeting Payload to Enable the First Antibody–Antibiotic Conjugate
Authors: Linghu Xin , Segraves Nathaniel L. , Abramovich Ifat , Wong Nicholas , Müller Barbara , Neubauer Nadja , Fantasia Serena , Rieth Sebastian , Bachmann Stephan , Jansen Michael , Sowell C. Gregory , Askin David , Koenig Stefan G. , Gosselin Francis
Published: November 2017

A practical synthesis of the complex payload for an anti‐Staphylococcus aureus THIOMABTM antibody–antibiotic conjugate (TAC) is described. The route takes advantage of a delicate oxidative condensation, achieved using a semi‐continuous flow procedure. It allows for the generation of kilogram quantities of a key intermediate to enable a mild nucleophilic aromatic substitution to the tertiary amine free drug. The linker component is introduced as a benzylic chloride, which allows formation of the quaternary ammonium salt linker‐drug. This chemical process surmounts numerous synthetic challenges and navigates deeply colored and unstable compounds to support clinical studies to counter S. aureus bacterial infections.