bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking the Concept of a “Durable Solution”: Sahrawi Refugee Camps Four Decades On
Authors: Martín Carmen Gómez
Published: March 2017

The Sahrawi people, who have long lived in the western part of the Sahara, have been housed in refugee camps in Tindouf, Algeria, since 1975—the year that Morocco took de facto control of Western Sahara. Their situation poses many questions, including those regarding the status of their state-in-exile, the role of the Sahrawi Arab Democratic Republic, and the length of their displacement. The conditions in the Tindouf camps present a paradigmatic case study of the liminal space inhabited by long-term refugees. Over the decades, residents have transformed these camps into a state-like structure with their own political and administrative institutions, which has enabled the international community to gain time to search for an acceptable political solution to the long-term conflict between the Polisario Front (the Sahrawi rebel national liberation movement) and the Moroccan government. The existence of a state-like structure, however, should not itself be understood as the ultimate solution for the thousands of people in these camps, who are currently living in extreme poverty, surviving on increasingly meager international aid, and enduring an exceptionally long wait for the favorable conditions whereby they may return to their place of origin.
Shame on EU? Europe, RtoP, and the Politics of Refugee Protection
Authors: Bulley Dan
Published: March 2017

The EU's politics of protecting refugees through deals such as that struck with Turkey in 2016 have been vilified by human rights campaigners. This article asks whether a full engagement with the Responsibility to Protect (RtoP) could offer the EU a way out of its current ethical and political malaise. It argues against such a proposition for two reasons. First, the EU already proclaims a long list of values that it asserts both contributed to its founding and continues to guide its actions; the addition of RtoP, which contains no obligations to protect refugees in other territories, would add little. Second, when the logic underlying the EU and RtoP's politics of protection are examined, a similarity emerges which would make such supplementation redundant. Both primarily entail a solidarity with, and a bolstering of, the sovereign capacity of the modern state. All that is offered to refugees, and other suffering populations, is a minimalist humanitarian solidarity through the “outsourcing” of protection. Neither the EU's ethos nor RtoP can therefore provide the firm ethical grounds from which to build protection for the figure most clearly failed by modern states—the refugee.
Immigration Ethics and the Context of Justice
Authors: Bosniak Linda
Published: March 2017

By now one might hope that the robust body of theoretical work recently published on immigration ethics would have taken general political philosophy a long way from the prevailing Rawlsian-style insularity premise, according to which society is “a closed system isolated from other societies” into which persons “enter only by birth and exit only by death.” But there are still a great many political theorists whose focus is unreflectively endogenous and who assume away questions of states’ constitutive scope and boundaries. One of the signal merits of David Miller's new book,Strangers in Our Midst, is that it lucidly demonstrates why ignoring state boundary constitution is untenable for political theory. Miller shows that foundational debates in political philosophy are inescapably related, both as premise and entailment, to many normative immigration questions.
China–GOES (Article 21.5): Time to Clarify the Standard for Price Suppression and Price Depression in AD/CVD Investigations
Authors: QIN JULIA , VANDENBUSSCHE HYLKE
Published: March 2017

This dispute concerns the measures China took to implement the Dispute Settlement Body's rulings inChina–GOES, which had found a number of violations with respect to China's antidumping and countervailing duties imposed on grain oriented flat-rolled electrical steel (GOES) imported from the United States. In this compliance proceeding, the United States claimed that the Redetermination issued by China's Ministry of Commerce (MOFCOM) continued to violate WTO law. At the center of the dispute were MOFCOM's findings that the US imports had the effect of suppressing and/or depressing the prices of domestic like products. While the Panel reached the conclusion that the MOFCOM findings were inconsistent with WTO rules, it did not clarify the criteria for determining such price effects. In this comment, we call for the adoption of a clearer and more objective standard for determining price suppression and price depression in antidumping and countervailing duty investigations, via the tools of economic modeling.
Risk and Regulatory Calibration: WTO Compliance Review of the US Dolphin–Safe Tuna Labeling Regime
Authors: COGLIANESE CARY , SAPIR ANDRÉ
Published: March 2017

In a series of recent disputes arising under the TBT Agreement, the Appellate Body has interpreted Article 2.1 to provide that discriminatory and trade-distortive regulation could be permissible if based upon a ‘legitimate regulatory distinction’. In its recent compliance decision in the US–Tuna II dispute, the AB reaffirmed its view that regulatory distinctions embedded in the US dolphin-safe tuna-labeling regime were not legitimate because they were not sufficiently calibrated to the risks to dolphins associated with different tuna fishing conditions. This paper analyzes the AB's application of the notion of risk-based regulation in the US–Tuna II dispute and finds the AB's reasoning lacking in coherence. Although risk analysis and calibration can in principle play useful roles in TBT cases, the AB needs to provide more explicit and careful guidance to WTO members and to panels to avoid the kind of ad hoc decision-making exhibited throughout the US–Tuna II dispute.
Tape Work and Memory Work in Post-War Germany
Authors: SPRIGGE MARTHA
Published: March 2017

Sonic traces of the Third Reich have held significant memorial power in post-war Germany. This article traces three works that sample one of the most well-known recordings from the Nazi period: Joseph Goebbels's declaration of Total War, delivered on 18 February 1943, and broadcast on newsreel and radio the following week. In both message and material, this recording epitomizes Friedrich Kittler's claim that tape is a military technology. The works examined span different memory debates in post-war Germany: Bernd Alois Zimmermann realizedRequiem für einen jungen Dichter(1967–9) as West Germans were engaging in the first public discussions of the Holocaust, Georg Katzer'sMein 1989(1990) is an East German composer's early response to the fall of the Berlin Wall, while Marcel Beyer's novelFlughunde(The Karnau Tapes, 1995) reveals the continued attempt to address the legacy of the Third Reich after German Reunification. Analysed together, these works create new configurations of discourse about wartime memory, moving away from geopolitical contours. Each of these artists transforms tape's wartime uses – namely dissemination and encryption – into forms of memorial labour. Through their physical and conceptual manipulations of tape, these artists create less deterministic readings of the Nazi past.
Reich on Tape: The Performance ofViolin Phase
Authors: AUNER JOSEPH
Published: March 2017

The score of Steve Reich'sViolin Phasespecifies that the performer is to recapitulate aspects of the composer's creative process in the studio. Working with a four-channel tape recorder, the violinist and a sound engineer are given detailed directions for creating the basic tape loop that generates the performance tape used in live performance. And yet – no doubt due to the scarcity of appropriate tape recorders – most present-day performers ofViolin Phaseuse looping hardware or software that make it possible to dispense with many of the instructions in the score, including the necessity of having the engineer on stage. That this significant change in performance practice seemingly passes for the most part without notice demonstrates how the decades-long ubiquity of tape has been replaced by a kind of invisibility, through which the particularities of the medium have been subsumed into more generalized notions of fixed media. I argue that the specific materialities of tape and tape machines are not incidental toViolin Phase, but are central to its composition, performance, and reception. A focus on the role of tape, and indeed on the roll of tape itself, can illuminate this and other pieces as well as Reich's deep involvement with music technologies throughout his career.
Telematic Tape: Notes on Maryanne Amacher'sCity-Links(1967–1980)
Authors: CIMINI AMY
Published: March 2017

Reel-to-reel recordings and 15 kilocycle telelinks converge in Maryanne Amacher's telematic installation seriesCity-Links(1967–81). As long-duration recordings of urban sites,City-Linksqueries the musicality of ambient sound on tape, a question of critical importance to many composers of the period. But as expressly telematic tape,City-Linksembeds these recordings within a transforming US telecommunications industry where expanded long-distance dialing relied on the high-tech labour and gendered discipline of telephone operators, enrolling tapes’ ambient sounding in broader questions about the technological mediation of gender, listening and long-distance embodiment duringCity-Linkslate 1960s and 1970s span. An extended reconstruction of oneCity-Links's tape's tactile qualities interprets this complex interimplication as a kind of telematic ‘weave’, with a spatiotemporal warp shuttling between the weft of environmental sounds and their technical traces.
Cassette Tape Revival as Creative Anachronism
Authors: DEMERS JOANNA
Published: March 2017

Listeners of a certain age tend to think that the cassette tape fell out of favour sometime during the 1990s, but is experiencing a revival of sorts as curious Millennials discover the pleasures of mixtapes and decaying media. But cassette tapes have been in constant use since their invention in 1963. Outside of North America and Western Europe, the tape is still the predominant phonographic medium, and is unseating hard drives as the preferred medium for data storage. For whom, then, is this a revival? My article argues that the tape revival is less an attempt at neutral recuperation of the past than a purposeful rewriting of history. Cassettes are particularly potent because they signify death and decay more forcefully even than vinyl. Their acoustic imperfections and mechanical frailties are now aestheticized in novels and contemporary popular music. Even curated listening experiences, from podcasts to streaming services, are designed to replicate the mixtape. The second era of the cassette tape represents another example of Simon Reynolds’ concept of retromania, and can be fruitfully understood as a chapter in the evolving story of phonographic waste.
Clinical and diagnostic aspects of lymphedema
Authors: Keo Hong H. , Gretener Silvia B. , Staub Daniel
Published: March 2017

Abstract. Lymphedema is a chronic, progressive, and common but often unrecognized condition. The diagnosis of lymphatic disease on clinical grounds alone remains a challenge. Without proper diagnosis, therapy is often delayed, allowing disease progression. There is a need for a practical diagnostic algorithm and its imaging technique to guide clinical decision-making. The aim of this topical review is to provide a practical approach for assessing patients with suspected lymphedema and to give a critical appraisal of currently available imaging modalities that are applied in clinical practice to diagnose and map lymphatic disease.
Eine Einführung in die Plausible-Values-Technik für die psychologische Forschung
Authors: Lüdtke Oliver , Robitzsch Alexander
Published: March 2017

Zusammenfassung. In der psychologischen Forschung durchgeführte Messungen zur Erfassung von Konstrukten sind meistens mit einem Messfehler behaftet. Diese Messfehler führen zu verzerrten Schätzern von Populationsparametern und deren Standardfehlern. In den letzten Jahrzehnten hat sich im Bereich der Large-Scale-Assessments mit der Plausible-Values-Technik ein Verfahren zur Korrektur von messfehlerbehafteten Zusammenhängen zwischen latenten Variablen und beobachteten Kovariaten etabliert. Der vorliegende Beitrag führt anhand eines einfachen Beispiels aus der Klassischen Testtheorie in dieses komplexe statistische Verfahren ein. Es wird gezeigt, dass alternative Verfahren zur Schätzung von Personenwerten im Allgemeinen zu verzerrten Schätzungen von Zusammenhängen auf Populationsebene führen. In einer Simulationsstudie werden diese Befunde auf ein IRT-Modell für dichotome Indikatoren übertragen. Aus diagnostischer Sicht wird betont, dass Plausible Values nicht zur Schätzung von individuellen Fähigkeitsausprägungen verwendet werden sollen. Abschließend werden methodische Herausforderungen bei der Anwendung der Plausible-Values-Technik sowie das Potential für die psychologische Forschung diskutiert.
Confirmatory Factor Analysis of the Maslach Burnout	Inventory
Authors: de Beer Leon T. , Bianchi Renzo
Published: March 2017

Abstract. In the Maslach Burnout Inventory (MBI), burnout is conceptualized as a combination of emotional exhaustion, depersonalization, and personal accomplishment. However, the factorial structure for the MBI remains controversial. We examined the factorial structure of the MBI, relying on Bayesian structural equation modeling (BSEM). BSEM allows the investigator to take into account sources of influence such as approximately-zero factor cross-loadings and between-item residual covariances. Data from a convenience sample of 5,575 French teachers were mobilized. One-, two-, three-, and bi-factor models were tested using BSEM. Maximum likelihood (ML) estimation was also implemented to examine the robustness of the BSEM analysis. The BSEM analysis showed that a two-factor model, consisting of a burnout factor combining emotional exhaustion and depersonalization and a separate personal accomplishment factor, best fitted the data. ML estimation showed a substantial enhancement of model fit when information derived from the BSEM analysis was incorporated. The MBI appears to be underlain by a unified factor involving the emotional exhaustion and depersonalization items and a separate factor involving the personal accomplishment items. These findings are compatible with a research practice that involves combining the emotional exhaustion and depersonalization dimensions of burnout and considering personal accomplishment individually.
Experimental Test Validation
Authors: Krumm Stefan , Hüffmeier Joachim , Lievens Filip
Published: March 2017

Abstract. Although the vast majority of validation studies rely on correlational validity evidence, there is an increased recognition that validity should also focus on whether variations in the focal psychological attribute lead to variations in the measurement outcomes. Therefore, calls have been made that validity evidence should also be gathered through experiments. Existing experimental validation strategies focus on manipulating psychological attributes and their effects on measurement outcomes. In the current manuscript, we present an additional and complementary approach that focuses on manipulating test elements (instead of psychological attributes) that are considered indispensable for test functioning. Examples from personality, situational judgment, emotional intelligence, and reading comprehension domains are presented to illustrate our approach. The presented approach is integrated into existing validation strategies.
A Social Identity Approach to Leadership Development
Authors: Alexander Haslam S. , Steffens Niklas K. , Peters Kim , Boyce Rosalie A. , Mallett Clifford J. , Fransen Katrien
Published: March 2017

Abstract. Social identity research shows that leadership is a process of group identity development but has not examined how leaders can manage group identities in the workplace. The 5R leadership development program addresses this issue. This takes leaders through a five-stage process of (1) Readying: explaining the importance of social identity processes for leadership; (2) Reflecting: identifying important workplace social identities; (3) Representing: clarifying goals and aspirations associated with different subgroup identities; (4) Realizing: identifying superordinate goals and developing strategies to achieve both them and subgroup goals; and (5) Reporting: assessing progress toward goals. Results of a longitudinal study indicate that 5R is a useful framework for leadership development that translates insights from social identity theorizing into structured intervention.
PI3Kδ and PI3Kγ isoforms have distinct functions in regulating pro-tumoural signalling in the multiple myeloma microenvironment
Authors: Piddock R E , Loughran N , Marlein C R , Robinson S D , Edwards D R , Yu S , Pillinger G E , Zhou Z , Zaitseva L , Auger M J , Rushworth S A , Bowles K M
Published: March 2017

Phosphoinositide-3-kinase and protein kinase B (PI3K-AKT) is upregulated in multiple myeloma (MM). Using a combination of short hairpin RNA (shRNA) lentivirus-mediated knockdown and pharmacologic isoform-specific inhibition we investigated the role of the PI3K p110γ (PI3Kγ) subunit in regulating MM proliferation and bone marrow microenvironment-induced MM interactions. We compared this with inhibition of the PI3K p110δ (PI3kδ) subunit and with combined PI3kδ/γ dual inhibition. We found that MM cell adhesion and migration were PI3Kγ-specific functions, with PI3kδ inhibition having no effect in MM adhesion or migration assays. At concentration of the dual PI3Kδ/γ inhibitor duvelisib, which can be achieved in vivo we saw a decrease in AKT phosphorylation at s473 after tumour activation by bone marrow stromal cells (BMSC) and interleukin-6. Moreover, after drug treatment of BMSC/tumour co-culture activation assays only dual PI3kδ/γ inhibition was able to induce MM apoptosis. shRNA lentiviral-mediated targeting of either PI3Kδ or PI3Kγ alone, or both in combination, increased survival of NSG mice xeno-transplanted with MM cells. Moreover, treatment with duvelisib reduced MM tumour burden in vivo. We report that PI3Kδ and PI3Kγ isoforms have distinct functions in MM and that combined PI3kδ/γ isoform inhibition has anti-MM activity. Here we provide a scientific rationale for trials of dual PI3kδ/γ inhibition in patients with MM.
Microbiome effects on immunity, health and disease in the lung
Authors: Shukla Shakti D , Budden Kurtis F , Neal Rachael , Hansbro Philip M
Published: March 2017

Chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), are among the leading causes of mortality and morbidity worldwide. In the past decade, the interest in the role of microbiome in maintaining lung health and in respiratory diseases has grown exponentially. The advent of sophisticated multiomics techniques has enabled the identification and characterisation of microbiota and their roles in respiratory health and disease. Furthermore, associations between the microbiome of the lung and gut, as well as the immune cells and mediators that may link these two mucosal sites, appear to be important in the pathogenesis of lung conditions. Here we review the recent evidence of the role of normal gastrointestinal and respiratory microbiome in health and how dysbiosis affects chronic pulmonary diseases. The potential implications of host and environmental factors such as age, gender, diet and use of antibiotics on the composition and overall functionality of microbiome are also discussed. We summarise how microbiota may mediate the dynamic process of immune development and/or regulation focusing on recent data from both clinical human studies and translational animal studies. This furthers the understanding of the pathogenesis of chronic pulmonary diseases and may yield novel avenues for the utilisation of microbiota as potential therapeutic interventions.
Divergent extremes but convergent recovery of bacterial and archaeal soil communities to an ongoing subterranean coal mine fire
Authors: Lee Sang-Hoon , Sorensen Jackson W , Grady Keara L , Tobin Tammy C , Shade Ashley
Published: March 2017

Press disturbances are stressors that are extended or ongoing relative to the generation times of community members, and, due to their longevity, have the potential to alter communities beyond the possibility of recovery. They also provide key opportunities to investigate ecological resilience and to probe biological limits in the face of prolonged stressors. The underground coal mine fire in Centralia, Pennsylvania has been burning since 1962 and severely alters the overlying surface soils by elevating temperatures and depositing coal combustion pollutants. As the fire burns along the coal seams to disturb new soils, previously disturbed soils return to ambient temperatures, resulting in a chronosequence of fire impact. We used 16S rRNA gene sequencing to examine bacterial and archaeal soil community responses along two active fire fronts in Centralia, and investigated the influences of assembly processes (selection, dispersal and drift) on community outcomes. The hottest soils harbored the most variable and divergent communities, despite their reduced diversity. Recovered soils converged toward similar community structures, demonstrating resilience within 10–20 years and exhibiting near-complete return to reference communities. Measured soil properties (selection), local dispersal, and neutral community assembly models could not explain the divergences of communities observed at temperature extremes, yet beta-null modeling suggested that communities at temperature extremes follow niche-based processes rather than null. We hypothesize that priority effects from responsive seed bank transitions may be key in explaining the multiple equilibria observed among communities at extreme temperatures. These results suggest that soils generally have an intrinsic capacity for robustness to varied disturbances, even to press disturbances considered to be ‘extreme’, compounded, or incongruent with natural conditions.
Membrane vesicle-mediated bacterial communication
Authors: Toyofuku Masanori , Morinaga Kana , Hashimoto Yohei , Uhl Jenny , Shimamura Hiroko , Inaba Hideki , Schmitt-Kopplin Philippe , Eberl Leo , Nomura Nobuhiko
Published: March 2017

The classical quorum-sensing (QS) model is based on the assumption that diffusible signaling molecules accumulate in the culture medium until they reach a critical concentration upon which expression of target genes is triggered. Here we demonstrate that the hydrophobic signal N-hexadecanoyl-L-homoserine lactone, which is produced by Paracoccus sp., is released from cells by the aid of membrane vesicles (MVs). Packed into MVs, the signal is not only solubilized in an aqueous environment but is also delivered with varying propensities to different bacteria. We propose a novel MV-based mechanism for binary trafficking of hydrophobic signal molecules, which may be particularly relevant for bacteria that live in open aqueous environments.
Theory of optimal balance predicts and explains the amplitude and decay time of synaptic inhibition
Authors: Kim Jaekyung K. , Fiorillo Christopher D.
Published: March 2017

Synaptic inhibition counterbalances excitation, but it is not known what constitutes optimal inhibition. We previously proposed that perfect balance is achieved when the peak of an excitatory postsynaptic potential (EPSP) is exactly at spike threshold, so that the slightest variation in excitation determines whether a spike is generated. Using simulations, we show that the optimal inhibitory postsynaptic conductance (IPSG) increases in amplitude and decay rate as synaptic excitation increases from 1 to 800 Hz. As further proposed by theory, we show that optimal IPSG parameters can be learned through anti-Hebbian rules. Finally, we compare our theoretical optima to published experimental data from 21 types of neurons, in which rates of synaptic excitation and IPSG decay times vary by factors of about 100 (5–600 Hz) and 50 (1–50 ms), respectively. From an infinite range of possible decay times, theory predicted experimental decay times within less than a factor of 2. Across a distinct set of 15 types of neuron recorded in vivo, theory predicted the amplitude of synaptic inhibition within a factor of 1.7. Thus, the theory can explain biophysical quantities from first principles.
Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19
Authors: Emmanouilidis Leonidas , Schütz Ulrike , Tripsianes Konstantinos , Madl Tobias , Radke Juliane , Rucktäschel Robert , Wilmanns Matthias , Schliebs Wolfgang , Erdmann Ralf , Sattler Michael
Published: March 2017

The transport of peroxisomal membrane proteins (PMPs) requires the soluble PEX19 protein as chaperone and import receptor. Recognition of cargo PMPs by the C-terminal domain (CTD) of PEX19 is required for peroxisome biogenesis in vivo. Farnesylation at a C-terminal CaaX motif in PEX19 enhances the PMP interaction, but the underlying molecular mechanisms are unknown. Here, we report the NMR-derived structure of the farnesylated human PEX19 CTD, which reveals that the farnesyl moiety is buried in an internal hydrophobic cavity. This induces substantial conformational changes that allosterically reshape the PEX19 surface to form two hydrophobic pockets for the recognition of conserved aromatic/aliphatic side chains in PMPs. Mutations of PEX19 residues that either mediate farnesyl contacts or are directly involved in PMP recognition abolish cargo binding and cannot complement a ΔPEX19 phenotype in human Zellweger patient fibroblasts. Our results demonstrate an allosteric mechanism for the modulation of protein function by farnesylation.
Engineering fungal de novo fatty acid synthesis for short chain fatty acid production
Authors: Gajewski Jan , Pavlovic Renata , Fischer Manuel , Boles Eckhard , Grininger Martin
Published: March 2017

Fatty acids (FAs) are considered strategically important platform compounds that can be accessed by sustainable microbial approaches. Here we report the reprogramming of chain-length control of Saccharomyces cerevisiae fatty acid synthase (FAS). Aiming for short-chain FAs (SCFAs) producing baker’s yeast, we perform a highly rational and minimally invasive protein engineering approach that leaves the molecular mechanisms of FASs unchanged. Finally, we identify five mutations that can turn baker’s yeast into a SCFA producing system. Without any further pathway engineering, we achieve yields in extracellular concentrations of SCFAs, mainly hexanoic acid (C6-FA) and octanoic acid (C8-FA), of 464 mg l−1 in total. Furthermore, we succeed in the specific production of C6- or C8-FA in extracellular concentrations of 72 and 245 mg l−1, respectively. The presented technology is applicable far beyond baker’s yeast, and can be plugged into essentially all currently available FA overproducing microorganisms.
Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors
Authors: Jongbloets Bart C. , Lemstra Suzanne , Schellino Roberta , Broekhoven Mark H. , Parkash Jyoti , Hellemons Anita J. C. G. M. , Mao Tianyi , Giacobini Paolo , van Praag Henriette , De Marchis Silvia , Ramakers Geert M. J. , Pasterkamp R. Jeroen
Published: March 2017

The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Despite strong expression in the mature brain, the role of Sema7A in the adult remains poorly defined. Here we show that Sema7A utilizes different cell surface receptors to control the proliferation and differentiation of neural progenitors in the adult hippocampal dentate gyrus (DG), one of the select regions of the mature brain where neurogenesis occurs. PlexinC1 is selectively expressed in early neural progenitors in the adult mouse DG and mediates the inhibitory effects of Sema7A on progenitor proliferation. Subsequently, during differentiation of adult-born DG granule cells, Sema7A promotes dendrite growth, complexity and spine development through β1-subunit-containing integrin receptors. Our data identify Sema7A as a key regulator of adult hippocampal neurogenesis, providing an example of how differential receptor usage spatiotemporally controls and diversifies the effects of guidance cues in the adult brain.
In vivo gastrointestinal drug-release monitoring through second near-infrared window fluorescent bioimaging with orally delivered microcarriers
Authors: Wang Rui , Zhou Lei , Wang Wenxing , Li Xiaomin , Zhang Fan
Published: March 2017

Non-invasive monitoring of gastrointestinal drug release in vivo is extremely challenging because of the limited spatial resolution and long scanning time of existing bioimaging modalities, such as X-ray radiation and magnetic resonance. Here, we report a novel microcarrier that can retain drugs and withstand the harsh conditions of gastrointestinal tract. Significantly, we can track the microcarrier fate and semi-quantitatively monitor the content of drug released in vivo in real time by measuring the fluorescence signals in the second near-infrared window of lanthanide-based downconversion nanoparticles with an absorption competition-induced emission bioimaging system. The microcarriers show a prolonged residence time of up to 72 h in the gastrointestinal tract, releasing up to 62% of their content. Moreover, minimal deposition of the microcarriers is found in non-target organs, such as the liver, spleen and kidney. These findings provide novel insights for the development of therapeutic and bioimaging strategies of orally administered drugs.
Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate
Authors: Huang Chun-Kai , Chang Po-Hao , Kuo Wen-Hung , Chen Chi-Long , Jeng Yung-Ming , Chang King-Jen , Shew Jin-Yuh , Hu Chun-Mei , Lee Wen-Hwa
Published: March 2017

Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitro and in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.
Templated bilayer self-assembly of fully conjugated π-expanded macrocyclic oligothiophenes complexed with fullerenes
Authors: Cojal González José D. , Iyoda Masahiko , Rabe Jürgen P.
Published: March 2017

Fully conjugated macrocyclic oligothiophenes exhibit a combination of highly attractive structural, optical and electronic properties, and multifunctional molecular thin film architectures thereof are envisioned. However, control over the self-assembly of such systems becomes increasingly challenging, the more complex the target structures are. Here we show a robust self-assembly based on hierarchical non-covalent interactions. A self-assembled monolayer of hydrogen-bonded trimesic acid at the interface between an organic solution and graphite provides host-sites for the epitaxial ordering of Saturn-like complexes of fullerenes with oligothiophene macrocycles in mono- and bilayers. STM tomography verifies the formation of the templated layers. Molecular dynamics simulations corroborate the conformational stability and assign the adsorption sites of the adlayers. Scanning tunnelling spectroscopy determines their rectification characteristics. Current–voltage characteristics reveal the modification of the rectifying properties of the macrocycles by the formation of donor–acceptor complexes in a densely packed all-self-assembled supramolecular nanostructure.
A molecule-like PtAu24(SC6H13)18 nanocluster as an electrocatalyst for hydrogen production
Authors: Kwak Kyuju , Choi Woojun , Tang Qing , Kim Minseok , Lee Yongjin , Jiang De-en , Lee Dongil
Published: March 2017

The theoretically predicted volcano plot for hydrogen production shows the best catalyst as the one that ensures that the hydrogen binding step is thermodynamically neutral. However, the experimental realization of this concept has suffered from the inherent surface heterogeneity of solid catalysts. It is even more challenging for molecular catalysts because of their complex chemical environment. Here, we report that the thermoneutral catalyst can be prepared by simple doping of a platinum atom into a molecule-like gold nanocluster. The catalytic activity of the resulting bimetallic nanocluster, PtAu24(SC6H13)18, for the hydrogen production is found to be significantly higher than reported catalysts. It is even better than the benchmarking platinum catalyst. The molecule-like bimetallic nanocluster represents a class of catalysts that bridge homogeneous and heterogeneous catalysis and may provide a platform for the discovery of finely optimized catalysts.
Spatio-temporal dynamics of a planktonic system and chlorophyll distribution in a 2D spatial domain: matching model and data
Authors: Valenti Davide , Denaro Giovanni , Ferreri Rosalia , Genovese Simona , Aronica Salvatore , Mazzola Salvatore , Bonanno Angelo , Basilone Gualtiero , Spagnolo Bernardo
Published: March 2017

Field data on chlorophyll distribution are investigated in a two-dimensional spatial domain of the Mediterranean Sea by using for phytoplankton abundances an advection-diffusion-reaction model, which includes real values for physical and biological variables. The study exploits indeed hydrological and nutrients data acquired in situ, and includes intraspecific competition for limiting factors, i.e. light intensity and phosphate concentration. As a result, the model allows to analyze how both the velocity field of marine currents and the two components of turbulent diffusivity affect the spatial distributions of phytoplankton abundances in the Modified Atlantic Water, the upper layer of the water column of the Mediterranean Sea. Specifically, the spatio-temporal dynamics of four phytoplankton populations, responsible for about 80% of the total chlorophyll a, are reproduced. Results for phytoplankton abundances obtained by the model are converted in chlorophyll a concentrations and compared with field data collected in twelve marine sites along the Cape Passero (Sicily)- Misurata (Libya) transect. Statistical checks indicate a good agreement between theoretical and experimental distributions of chlorophyll concentration. The study can be extended to predict the spatio-temporal behaviour of the primary production, and to prevent the consequent decline of some fish species in the Mediterranean Sea.
Addressing rainfall data selection uncertainty using connections between rainfall and streamflow
Authors: Levy Morgan C. , Cohn Avery , Lopes Alan Vaz , Thompson Sally E.
Published: March 2017

Studies of the hydroclimate at regional scales rely on spatial rainfall data products, derived from remotely-sensed (RS) andin-situ(IS, rain gauge) observations. Because regional rainfall cannot be directly measured, spatial data products are biased. These biases pose a source of uncertainty in environmental analyses, attributable to the choices made by data-users in selecting a representation of rainfall. We use the rainforest-savanna transition region in Brazil to show differences in the statistics describing rainfall across nine RS and interpolated-IS daily rainfall datasets covering the period of 1998–2013. These differences propagate into estimates of temporal trends in monthly rainfall and descriptive hydroclimate indices. Rainfall trends from different datasets are inconsistent at river basin scales, and the magnitude of index differences is comparable to the estimated bias in global climate model projections. To address this uncertainty, we evaluate the correspondence of different rainfall datasets with streamflow from 89 river basins. We demonstrate that direct empirical comparisons between rainfall and streamflow provide a method for evaluating rainfall dataset performance across multiple areal (basin) units. These results highlight the need for users of rainfall datasets to quantify this “data selection uncertainty” problem, and either justify data use choices, or report the uncertainty in derived results.
In-Situ Stretching Patterned Graphene Nanoribbons in the Transmission Electron Microscope
Authors: Liao Zhongquan , Medrano Sandonas Leonardo , Zhang Tao , Gall Martin , Dianat Arezoo , Gutierrez Rafael , Mühle Uwe , Gluch Jürgen , Jordan Rainer , Cuniberti Gianaurelio , Zschech Ehrenfried
Published: March 2017

The mechanical response of patterned graphene nanoribbons (GNRs) with a width less than 100 nm was studied in-situ using quantitative tensile testing in a transmission electron microscope (TEM). A high degree of crystallinity was confirmed for patterned nanoribbons before and after the in-situ experiment by selected area electron diffraction (SAED) patterns. However, the maximum local true strain of the nanoribbons was determined to be only about 3%. The simultaneously recorded low-loss electron energy loss spectrum (EELS) on the stretched nanoribbons did not reveal any bandgap opening. Density Functional Based Tight Binding (DFTB) simulation was conducted to predict a feasible bandgap opening as a function of width in GNRs at low strain. The bandgap of unstrained armchair graphene nanoribbons (AGNRs) vanished for a width of about 14.75 nm, and this critical width was reduced to 11.21 nm for a strain level of 2.2%. The measured low tensile failure strain may limit the practical capability of tuning the bandgap of patterned graphene nanostructures by strain engineering, and therefore, it should be considered in bandgap design for graphene-based electronic devices by strain engineering.
Elemental Contrast X-ray Tomography Using Ross Filter Pairs with a Polychromatic Laboratory Source
Authors: Arhatari Benedicta D. , Gureyev Timur E. , Abbey Brian
Published: March 2017

The majority of current laboratory based X-ray sources are polychromatic and are not tuneable. This lack of monochromaticity limits the range of applications for these sources and in particular it reduces the elemental specificity of laboratory based X-ray imaging experiments. Here we present a solution to this problem based on the use of Ross filter pairs. Although such Ross filter arrangements have been applied in proof-of-principle spectroscopy experiments, to date there have been no reports of this approach used for full-field X-ray imaging. Here we report on the experimental demonstration of Ross filter pairs being used for quasi-monochromatic, full-field imaging. This arrangement has several important benefits for laboratory based X-ray imaging including, as we demonstrate, elemental contrast enhancement. The method is demonstrated both for two-dimensional radiography and for three-dimensional X-ray tomography.
An analysis of Echinacea chloroplast genomes: Implications for future botanical identification
Authors: Zhang Ning , Erickson David L. , Ramachandran Padmini , Ottesen Andrea R. , Timme Ruth E. , Funk Vicki A. , Luo Yan , Handy Sara M.
Published: March 2017

Echinacea is a common botanical used in dietary supplements, primarily to treat upper respiratory tract infections and to support immune function. There are currently thought to be nine species in the genus Echinacea. Due to very low molecular divergence among sister species, traditional DNA barcoding has not been successful for differentiation of Echinacea species. Here, we present the use of full chloroplast genomes to distinguish between all 9 reported species. Total DNA was extracted from specimens stored at the National Museum of Natural History, Smithsonian Institution, which had been collected from the wild with species identification documented by experts in the field. We used Next Generation Sequencing (NGS) and CLC Genomics Workbench to assemble complete chloroplast genomes for all nine species. Full chloroplasts unambiguously differentiated all nine species, compared with the very few single nucleotide polymorphisms (SNPs) available with core DNA barcoding markers. SNPs for any two Echinacea chloroplast genomes ranged from 181 to 910, and provided robust data for unambiguous species delimitation. Implications for DNA-based species identification assays derived from chloroplast genome sequences are discussed in light of product safety, adulteration and quality issues.
Modeling the air-soil exchange, secondary emissions and residues in soil of polychlorinated biphenyls in China
Authors: Cui Song , Fu Qiang , Li Yi-Fan , Ma Jianmin , Tian Chongguo , Liu Liyan , Zhang Leiming
Published: March 2017

The present study investigated the environmental distribution and fate of low molecular weight (LMW) polychlorinated biphenyls (PCBs) in China using the ChnGIPERM (Chinese Gridded Industrial Pollutants Emission and Residue Model), in which the air-soil exchange, spatial-temporal variations and the heterogeneity of secondary emission and residue in the non-source areas were studied. The model simulated the temporal and spatial variations of the PCB28 concentration in soils and air which agreed well with historical monitoring data across China. The long-range atmospheric transport (LRAT) and temperature was identified as the major factor affecting the distribution patterns of the secondary emissions and residues. Soil residue was considered as important environmental fate of PCB28. However, the intensity of an emissions source and the distance with non-source area strongly affected the spatial and temporal variations of PCB28 residues in soil. Several factors strongly impacted the distribution characteristics and air-soil exchange of PCB28, including emission patterns, atmospheric transport, soil organic carbon (SOC), soil vertical transfer, ambient temperature, and precipitation.
Comparison of orofacial pain of patients with different stages of precancer and oral cancer
Authors: Yang Yanjie , Zhang Peipei , Li Wenlu
Published: March 2017

Orofacial pain impairs a patient's speech, swallowing, eating and interpersonal relations. Thirty-seven patients with a premalignant oral lesion, 124 patients with oral squamous cell carcinoma (OSSC), and 21 patients with a recurrence of OSSC were evaluated for their orofacial pain. The University of California San Francisco Oral Cancer Pain Questionnaire was administered to these patients at their initial visit, before they were prescribed analgesics for pain and before any treatment. Significant differences with respect to orofacial pain between the groups could be evaluatedwere observed. Patients with recurrence had the highest facial pain and patients with precancer had the lowest. Patients with OSSC and recurrence of OSSC reported significant levels of orofacial pain and functional restriction because of pain. Moreover, patients with recurrence of OSSC experienced significantly higher function-related pain, rather than pain qualities. These findings suggest that an important predictor for recurrence of OSSC may be the onset of orofacial pain that is exacerbated during function. The present study examined orofacial pain depending on the disease severity of precancer and oral cancer patients. Earlier recognition of symptoms of OSSC may improve early detection of its recurrence.
Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor
Authors: Alvarez-Breckenridge Christopher , Miller Julie J. , Nayyar Naema , Gill Corey M. , Kaneb Andrew , D’Andrea Megan , Le Long P. , Lee Jesse , Cheng Ju , Zheng Zongli , Butler William E. , Multani Pratik , Chow Maneval Edna , Ha Paek Sun , Toyota Brian D. , Dias-Santagata Dora , Santagata Sandro , Romero Javier , Shaw Alice T. , Farago Anna F. , Yip Stephen , Cahill Daniel P. , Batchelor Tracy T. , Iafrate A. John , Brastianos Priscilla K.
Published: March 2017

Glioneuronal tumors constitute a histologically diverse group of primary central nervous system neoplasms that are typically slow-growing and managed conservatively. Genetic alterations associated with glioneuronal tumors include BRAF mutations and oncogenic fusions. To further characterize this group of tumors, we collected a cohort of 26 glioneuronal tumors and performed in-depth genomic analysis. We identified mutations in BRAF (34%) and oncogenic fusions (30%), consistent with previously published reports. In addition, we discovered novel oncogenic fusions involving members of the NTRK gene family in a subset of our cohort. One-patient with BCAN exon 13 fused to NTRK1 exon 11 initially underwent a subtotal resection for a 4th ventricular glioneuronal tumor but ultimately required additional therapy due to progressive, symptomatic disease. Given the patient’s targetable fusion, the patient was enrolled on a clinical trial with entrectinib, a pan-Trk, ROS1, and ALK (anaplastic lymphoma kinase) inhibitor. The patient was treated for 11 months and during this time volumetric analysis of the lesion demonstrated a maximum reduction of 60% in the contrast-enhancing tumor compared to his pre-treatment magnetic resonance imaging study. The radiologic response was associated with resolution of his clinical symptoms and was maintained for 11 months on treatment. This report of a BCAN-NTRK1 fusion in glioneuronal tumors highlights its clinical importance as a novel, targetable alteration.
Central role of lactate and proton in cancer cell resistance to glucose deprivation and its clinical translation
Authors: Hu Xun , Chao Ming , Wu Hao
Published: March 2017

Targeting common weaknesses of cancer is an important strategy for cancer therapy. Glucose is a nutrient that maintains essential cellular metabolism, supporting cancer cell survival, growth and proliferation. Depriving glucose rapidly kills cancer cells. Most cancer cells possess a feature called Warburg effect, which refers to that cancer cells even with ample oxygen exhibit an exceptionally high glycolysis rate and convert most incoming glucose to lactate. Although it is recognized that Warburg effect confers growth advantage to cancer cells when glucose supply is sufficient, this feature could be considered as a fatal weakness of cancer cells when glucose supply is a problem. As glucose supply in many solid tumors is poor, and as most cancer cells have exceptionally high glycolytic capacity, maximizing cancer cell glycolysis rate would possibly exhaust intratumoral glucose, leading cancer cell to death. Lactate and proton are two common factors in solid tumors, they jointly protect cancer cells against glucose deprivation, and they are also powerful regulators dictating glucose metabolic phenotypes of cancer cells. Disrupting the joint action of lactate and proton, for example, by means of bicarbonate infusion into tumor, could maximize cancer cell glycolytic rate to rapidly use up glucose, expose their vulnerability to glucose deprivation and ultimately kill cancer cells. A pilot clinical study demonstrated that this approach achieved a remarkable improvement in local control of large and huge hepatocellular carcinoma.