bluuebunny/crossref_metadata_2025 huggingface dataset:
SICUREZZA E RELAZIONI INTERNAZIONALI: IL PARADIGMA REALISTA RIVISITATO
Authors: Cesa Marco
Published: May 2019

Introduzione

Anche se quello di sicurezza è un termine impiegato molto frequentemente negli studi di relazioni internazionali, in particolar modo negli ultimi decenni, la sua elaborazione concettuale è lungi dall'aver raggiunto un livello soddisfacente. Eppure, alcuni dei molti studi dedicati specificamente a tematiche contemporanee, come il controllo degli armamenti e la politica di difesa degli stati occidentali, e in primo luogo degli Stati Uniti, hanno fornito definizioni piò o meno esplicite e articolate. Così, ad esempio, Donald Brennan (1961, 8) sostiene che la sicurezza è composta, in proporzioni variabili, tanto dalla protezione della sopravvivenza nazionale, intesa questa nei suoi significati fisici, politici e degli standard di vita, quanto dal perseguimento dei fini di politica estera. Secondo Morton Berkowitz e P.G. Bock (1968, 40), invece, la sicurezza sarebbe una piò generica «capacità di una nazione di proteggere i suoi valori interni da minacce esterne».
Control of ethylene synthesis and ripening by sense and antisense genes in transgenic plants
Authors: Grierson Don
Published: May 2019

Synopsis

Ripening of tomato and other fruits involves changes in quality attributes that make them attractive to consumers. These alterations are brought about by the coordinated expression of specific genes. Ethylene, synthesised by cells of climacteric fruit at the onset of ripening, stimulates the expression of genes required for ripening to occur. Experiments with transgenic plants have shown that a 5′ flanking region from the fruit polygalacturonase (PG) gene directs the ripening-specific expression of foreign genes in tomato. Antisense genes have also been used to down-regulate expression of the PG gene, causing a reduction in pectin degradation during ripening. This reduction in PG has beneficial effects on fruit storage life and processing characteristics. Antisense technology has also been used to assign functions to previously unknown genes. This has led to the identification of the gene for ethylene forming enzyme (EFE) which catalyses the terminal step in ethylene synthesis. Detached fruit from tomato plants in which EFE is inhibited by antisense genes produce much less ethylene and ripening is greatly slowed. The rate of ripening can be restored by adding ethylene externally. These results raise the possibility of manipulating ripening of many fruits and also of controlling processes such as abscission and senescence of leaves and flowers.
Prospects for establishing a tomato gene tagging system using the maize transposonActivator (Ac)
Authors: Jones J. D. G. , Bishop G. , Carroll B. , Dickinson M. , English J. , Harrison K. , Jones D. , Scofield S. , Thomas C. M.
Published: May 2019

Synopsis

In tomato (Lycopersicon esculentumMill.), extensive variation can be observed in genes conditioning many plant functions including disease resistance, plant development, and fruit, leaf and hypocotyl pigmentation. Genes exist that confer resistance to viruses, nematodes, bacteria and fungi. There is great value in developing a facile system for isolating such genes, and we are attempting to create a tomato gene isolation system based on insertional mutagenesis with the maize transposonAc.Our chosen target genes (Cf-2,Cf-4,Cf-5 andCf-9) confer resistance to specific races of the fungusCladosporium fulvumCooke, the causal agent of leaf mould. We have used classical and molecular techniques to map three of these genes, correcting errors in previous reports.Ac-carrying T-DNA constructs have been developed to facilitate monitoring ofAcactivity in tomato, whereAcis extremely active. These constructs have been used in plant transformation experiments, and over 100 tomato lines carryingAchave been created. More than 20 T-DNAs carryingAchave been localised on the tomato genetic map by testing linkage to RFLP loci. This was carried out to exploit the preference ofAcfor transposition to linked sites in our tagging strategy.
Assessing and monitoring the risks of releasing genetically manipulated plants
Authors: Beringer John E. , Bale Mark J. , Hayes Paul K. , Lazarus Colin M.
Published: May 2019

Plants, animals and microorganisms are being manipulated to improve their characteristics for commercial purposes. Some manipulated organisms will be grown under containment and only released to the environment accidentally and, usually, in relatively small numbers. Others, such as crop plants, will be grown on a large scale in the open environment. There is concern that modified organisms may become pests, or will produce pests as a result of mating with other organisms in the environment.

This paper will discuss some of the issues involved in deciding whether genetically modified plants should be released to the environment or not.
Opportunities and problems in plant biotechnology – an overview
Authors: Hillman J. R.
Published: May 2019

In Chapter 11 of Our Mutual Friend, Dickens noted that “Mr Podsnap had even acquired a peculiar flourish of his right arm in often clearing the world of its most difficult problems, by sweeping them behind him”. With a surname redolent of a kitchen botanist, Mr Podsnap no doubt realised that problems are mere opportunities for the theatrically dextrous. Perhaps the act of sweeping provides forward momentum to capitalise on yet more problems. In plant biotechnology, many of the problems confronting mankind are opportunities to employ exciting science.
Second messenger systems as sites of drug action
Authors: Bowman W. C.
Published: May 2019

Synopsis:

Transmembrane signalling from cell surface receptors occurs by two broad mechanisms: (i) the rapid (ms) direct opening of an ion channel, where the ion channel is a component of the receptor complex (e.g. the nicotinic acetylcholine receptor); and (ii) the more slow (s) modulation of a membrane enzyme or more distant ion channel. Most of the examples of this second mechanism involve a GTP-binding protein or so–called G-protein, and the production of a second messenger. The production of nitric oxide is a special case in that it is eventually produced as a result of the activity of the second messenger ïnositol trisphosphate. The nitric oxide then diffuses into a second cell to give rise to the production of an additional ‘second’ messenger, cyclic GMP.

All of the surface receptors themselves exist as a number of subtypes. Additionally, most of the components of the second messenger systems – G-proteins, adenylyl cyclase, guanylyl cyclase, phosphoinositidase, C, inositol trisphosphate receptors, protein kinase A, protein kinase G, protein kinase C, cyclic nucleotide phosphodiesterases, and the enzymes involved in phosphatidylinositol resynthesis – occur in a number of isoforms. Furthermore, all the enzymes are controlled in their activity by a number of co-factors and other modulators. This diversity provides the potential for selective drug action, a potential which is already being exploited and which will be increasingly so in the near future.
Can cloned receptors aid drug research?
Authors: Hartig Paul R.
Published: May 2019

Synopsis:

Over 50 different neurotransmitter and hormone receptors have been cloned, transfected and characterised. Within the pharmaceutical industry, the thrust of this research is now moving from receptor cloning to focussed application of these new tools to the task of drug development. With human receptor clones now available, it is possible to target drug design to single human proteins from the inception of a drug-design project. A critical question is whether human genes will express a human pharmacology when expressed in non-human, non-neuronal cell lines. Relevant results from studies with the human serotonin 5-HT2 and 5-HT1D receptors are presented, including the cloning of a rat 5-HT1B receptor which is homologous to a human 5-HT1D receptor gene. Another issue is the relationship between agonist and antagonist binding sites. The ability to study individual human receptors in selected cell lines which are free from interfering receptors has helped to advance our understanding of this relationship. Studies comparing agonist and antagonist binding sites of the human 5-HT2 receptor are described. Finally, the fact that so many neurotransmitter receptors belong to the same gene superfamily, the G-protein-coupled or 7TM (7 transmembrane domain) receptor superfamily, allows us to form new insights about receptor structure and function. Examples where comparative studies of gene sequences are helping to predict pharmacological properties of drugs are described.
Guanine-nucleotide binding regulatory proteins as targets for novel drugs
Authors: Pyne N. J.
Published: May 2019

Guanine-nucleotide regulatory binding proteins (G-proteins) serve to transduce information from agonist-bound receptor complexes to either effector enzymes or ion-channels. Drugs that perturb the function of G-proteins may do so by one of four mechanisms, (i) They may exert negative intrinsic activity toward the G-protein. For instance, we have shown that incubation of isolated plasma-membranes with the β-adrenoceptor blocking drug sotalol blocked both GTP-stimulated and isoprenaline-stimulated adenylyl cyclase. This suggests that the empty β-adrenoceptor is capable of tonically stimulating Gsα, and therefore adenylyl cyclase; that is, empty β-adrenoceptors promote GDP-GTP exchange, (ii) They may perturb the GDP-GTP exchange reaction. For instance, certain PDE inhibitors, including SKF 94836 and rolipram, stimulate a marked increase in the pertussis toxin-catalysed NAD+-dependent ADP-ribosylation of Giα. This effect is similar to that of GDP, which promotes stabilisation of the αβγ holomer of Gi. The effect of these PDE inhibitors is completely reversed by GppNHp, which triggers afly dissociation by binding to the guanine-nucleotide binding domain of the G-protein. PDE inhibitors may serve as a class of drugs which perturb GDP-GTP exchange, (iii) They may trigger uncoupling of receptor-G-protein complexes. For instance, the polycationic drug mastoparan binds to the C-terminal end of the G-protein and mimics the effect of receptor activation by promoting GTP-γ-S binding, a reduction in pertussis toxin-catalysed ADP-ribosylation, and inhibition of adenylyl cyclase activity. Other agents, such as polyanionic drugs, bind to the receptor to promote uncoupling of receptor-mediated activation of certain G-proteins. (iv) They may alter the cross-talk mechanisms that operate between different receptor signalling systems. For instance, protein kinase C promotes the phosphorylation and inactivation of Gi. This leads to an unopposed stimulation of adenylyl cyclase via Gsand, therefore, enhanced sensitivity to agents such as glucagon. Protein kinase C inhibitors may be usefully exploited to modulate these processes which appear to be abberant in certain disease states.
Polyamine amide toxins as pharmacological tools and pharmaceutical agents
Authors: Blagbrough Ian S. , Usherwood Peter N. R.
Published: May 2019

Synopsis:

The polyamine amides comprise a newly-discovered class of compounds which exhibits considerable potential for the development of selective pharmacological tools and pharmaceutical agents. In mammals and other vertebrates, they are selective, non-competitive antagonists of ionotropic glutamate receptors, but they also interact with other ionotropic receptors (e.g. nicotinic acetylcholine receptors). Thus, they are channel blockers which are selective for cation channels. We report on synthetic studies undertaken to produce hybrid analogues of these toxins based upon the argiotoxins of spider venoms and the philanthotoxins of parasitic, predatory wasp venom. The synthesis and characterisation of a mono-acylated spermine is also described. In addition, an account of current views on the many possible sites and modes of actions of the polyamine amides is presented and their potential for therapeutic neurochemistry, e.g. for the possible treatment of ischaemic damage to the nervous system, is highlighted.
ON CUMULATIVE RESIDUAL EXTROPY
Authors: Jahanshahi S. M. A. , Zarei H. , Khammar A. H.
Published: May 2019

Recently, an alternative measure of uncertainty called extropy is proposed by Lad et al. [12]. The extropy is a dual of entropy which has been considered by researchers. In this article, we introduce an alternative measure of uncertainty of random variable which we call it cumulative residual extropy. This measure is based on the cumulative distribution function F. Some properties of the proposed measure, such as its estimation and applications, are studied. Finally, some numerical examples for illustrating the theory are included.
The Organization of Stepping in Patients with Parkinson’s Disease: Bradykinesia or Discoordination?
Authors: Beuter Anne , Carrière Lise , McFadyen Bradford , Gauthier Serge
Published: May 2019

The purpose of this experiment was to quantify and analyse multijoint coordination of patients with Parkinson’s disease (N=5) and control subjects (N=5) during forward and backward stepping motions executed at different cadences. Coordinates of reflective markers placed on the shoulder, hip, knee, ankle and metatarsal joints were recorded in the sagittal plane using a video motion analysis system. Kinematic and kinetic analyses provided angular displacements and velocities as well as joint moments of force and powers. Results suggest the presence of two types of discoordination: one type is velocity-dependent, hence related to bradykinesia, whereas the other type appears to reflect qualitatively different coordination patterns.
Crown of Microfilaments in the Extending Cytoplasmic Processes of Medulloblastoma Glial Progenitors
Authors: Maria Bernard L. , Cumming Robert , Sukhu Loretta
Published: May 2019

Microfilaments and microtubules play a part in the extension of neuronal processes but their roles in the formation of glial processes have not yet been determined. The objectives of this study were to determine the organization of microfilaments in differentiating glial progenitors (RB2 cells) and to study the effects of microfilament or microtubule disruption on process extension. Intense F-actin staining (crown of microfilaments) was observed at the leading edge of a small extending conical tip in differentiating RB2 cells, but was absent in process-bearing TE671 rhabdomyosarcoma cells. No significant difference was noted in the mean number of TE671 cells with processes treated with a microfilament disrupter from that of similarly treated controls. In contrast, a significant difference was noted in the mean number of RB2 cells with processes after microfilament disruption treatment from that of similarly treated controls. Microtubule disruption arrested extension and caused process retraction in both cell types. The results of this study demonstrate that microtubules play an equally important part in the extension and stabilization of the RB2 and TE671 processes. Moreover, the crown of microfilaments concentrated in the glial RB2 process (and not in the TE671 process) may be critical to its extension during differentiation.
Syringomyelia as a Complication of Tuberculous Meningitis
Authors: Fehlings Michael G. , Bernstein Mark
Published: May 2019

Tuberculous meningitis may rarely be followed by the development of syringomyelia despite appropriate chemotherapy. In the present paper, we report a case of tuberculous meningitis in a 23-year-old Vietnamese male complicated by a rapidly progressive myelopathy due to granulomatous arachnoiditis which culminated in the development of a syrinx. The relevant literature is reviewed. The present case supports the hypothesis that vasculitic thrombosis of spinal cord vessels leading to ischemic myelomalacia is the mechanism causing postinflammatory syringomyelia.
Inland Ship Trajectory Restoration by Recurrent Neural Network
Authors: Zhong Cheng , Jiang Zhonglian , Chu Xiumin , Liu Lei
Published: May 2019

The quality of Automatic Identification System (AIS) data is of fundamental importance for maritime situational awareness and navigation risk assessment. To improve operational efficiency, a deep learning method based on Bi-directional Long Short-Term Memory Recurrent Neural Networks (BLSTM-RNNs) is proposed and applied in AIS trajectory data restoration. Case studies have been conducted in two distinct reaches of the Yangtze River and the capability of the proposed method has been evaluated. Comparisons have been made between the BLSTM-RNNs-based method and the linear method and classic Artificial Neural Networks. Satisfactory results have been obtained by all methods in straight waterways while the BLSTM-RNNs-based method is superior in meandering waterways. Owing to the bi-directional prediction nature of the proposed method, ship trajectory restoration is favourable for complicated geometry and multiple missing points cases. The residual error of the proposed model is computed through Euclidean distance which decreases to an order of 10 m. It is considered that the present study could provide an alternative method for improving AIS data quality, thus ensuring its completeness and reliability.
Differential Returns to Labor in Indian Agriculture
Authors: Abler David G.
Published: May 2019

This article explores the speed of adjustment in Indian agricultural labor markets to changing economic circumstances. Agricultural wages in sixteen states during 1970–86 are analyzed. Results indicate that agricultural wages adjust quickly toward their long-run values, completing about one-fifth to one-fourth of the adjustment per year. Results also suggest strong linkages between the agricultural and nonagricultural labor markets. Interstate agricultural productivity differences have risen substantially in the last twenty-five years, and many feel this has led to a disintegration of the agricultural labor market. The findings suggest an indirect integration may be occurring through migration to nonagriculture.
Aggregate Analysis of Site-Specific Pollution Problems: The Case of Groundwater Contamination from Agriculture
Authors: Opaluch James J. , Segerson Kathleen
Published: May 2019

Control of nonpoint sources of pollution has traditionally been within the domain of local decision makers in recognition of the critical importance of site-specific issues. More recently attention has turned to the issue of what can and should be done at the regional or national level, while recognizing the importance of site-specific attributes. This paper describes and illustrates an approach for analysis of nonpoint pollution problems that focuses jointly at the aggregate and disaggregate levels of the problem. The approach is based on linking two tools of analysis, the microparameter distribution model and the Geographical Information Systems (GIS). Although there are significant challenges to be overcome in implementing such an approach, linkage of these two policy tools has considerable promise in dealing with site-specific issues within an aggregate framework. Furthermore, GIS is potentially an important source of data for economists to exploit, given the momentum of GIS systems throughout the nation and given the relatively disaggregate nature of the data.
A Decision Support System for Sustainable Farming
Authors: Ikerd John E.
Published: May 2019

U.S. farmers are faced with growing environmental concerns and rising costs associated with highly specialized farming operations. They are searching for farming systems that are both ecologically sound and economically viable. They are searching for sustainable systems of farming.
Recent Macroeconomic Developments and Their Impact on Agriculture
Authors: Monaco Ralph M.
Published: May 2019

The U.S. is nearing the end of its ninth recession since the Second World War. This recession was caused by events outside of the agricultural sector, and the recovery will be due to factors outside the sector. Yet agricultural production, costs, and income will be affected by general economic conditions. This paper reviews current general economic conditions and examines their implications for the agricultural sector.
Domain generating functions for solving constraint satisfaction problems
Authors: Major François , Lapalme Guy , Robert Cedergren
Published: May 2019

This paper presents an application of functional programming: searching a domain for elements which satisfy certain constraints. We give a very general formulation of the problem and describe ‘generate and test’, ‘backtracking’ and ‘forward checking’ algorithms. We then introduce the concept of domain generating functions to capture a common optimization during the search process: using partial solutions to reduce the size of the search space. We compare the efficiency of the original algorithms and those using domain generating functions first with the ‘classical’ n-queens example, and then with a problem having larger domains to search which was inspired by an application in macromolecular structure determination. Using algorithms coded in Miranda, Haskell and Common Lisp, we show that a high order (lazy) functional language is a useful and efficient tool for prototyping search methods in large complex domains.
Functional Pearls: On removing duplicates
Authors: Bird Richard S.
Published: May 2019

The function remdup (also called mkset in some functional languages) removes duplicates from a given list. The following definition of remdup is standard and leads to a quadratic time algorithm

The operator (—) used in the last expression subtracts one list from another; its definition is

Defined in this way remdup x returns the list of distinct elements of x in the order in which they first appear in x. In other words, the position of remdup JC as a subsequence of x is lexically the smallest among all possible solutions.

Now let us change the problem and ask that remdup simply return the lexically least solution. Note the subtle difference between this version and the previous one: before, it was the position of the subsequence that was lexically the least, now it is the subsequence itself. To make the distinction clear, consider x = [1,4,2,4,3]. With the original definition remdup x returns [1,4,2,3]; the lexically least subsequence, however, is [1,2,4,3].

The question we are interested in is this: can we also find a quadratic time algorithm for the new problem? The answer turns out to be yes, but justifying it requires a bit of work.
Resourcing Special Education Programs in Times of Economic Restraint
Authors: Sawatzki Max , Walsh Rosemary
Published: May 2019

In addressing the subject of resourcing special education programs in times of economic restraint, I want to say from the outset that I do not view the concept of “restraint” in a completely negative sense. In many ways it is in times of restraint that some of ourmostconstructiveand creative planning for effective service delivery occurs. It is at times such as these that we need to take a critical look at what we are doing in the area of program provision and to ask ourselves whether we are meeting needs and achieving outcomes, or whether, in fact, we could be doing better.
Wildlife trade and consumer preference for species rarity: an examination of caged-bird markets in Sumatra
Authors: Krishna Vijesh V. , Darras Kevin , Grass Ingo , Mulyani Yeni A. , Prawiradilaga Dewi M. , Tscharntke Teja , Qaim Matin
Published: May 2019

This study examines conservation effects of wildlife trade using demand and supply data from caged-bird markets in Sumatra, Indonesia. When consumers have a strong preference for species rarity, trade could result in wildlife overexploitation and species extinction. Results from a choice experiment show that buyers of caged birds indeed value species rarity. However, not all rare species are equally preferred. Species that are frequently traded lose their rarity value, even if rare in the wild. Analysis of time-series data collected from traders over a period of 20 months between 2013 and 2015 reveals an inelastic supply function for rare species, with market arrivals being insensitive to price changes. This may be due to a declining stock of rare species in the wild. Bird trade together with habitat loss can lead to extinction of a number of rare species in Indonesia. Several policy approaches on regulating caged-bird markets are discussed.
What is healthy eating? A qualitative exploration
Authors: Mete Rebecca , Shield Alison , Murray Kristen , Bacon Rachel , Kellett Jane
Published: May 2019

Objective:

The present study aimed to explore how healthy food choices are translated into everyday life by exploring definitions of healthy food choices, perceptions of own food choice, and healthy food choice drivers (facilitators) and barriers.

Design:

An exploratory qualitative study design was employed using semi-structured face-to-face interviews. Convenience sampling was used to recruit participants. Interviews were audio-recorded, transcribed verbatim and cross-checked for consistency. Thematic analysis was used to identify patterns emerging from the data.

Setting:

Canberra, Australia, October 2015–March 2016.

Participants:

A total of twenty-three participants aged 25–60 years were interviewed. The mean age was 38 years and the mean BMI was 29·1 kg/m2. All male participants (n4) were within the healthy weight range compared with 58 % of female participants, with 26 % being overweight and 16 % being obese.

Results:

(i) Healthy food choices are important but are not a daily priority; (ii) healthy eating information is known but can be difficult to apply into everyday life; (iii) popular diets are used in attempts to improve healthy eating; and (iv) social media inspires and connects people with healthy eating.

Conclusions:

Social media facilitates healthy food choices by providing access to healthy eating information. In addition to Facebook and Instagram, healthy eating blogs were highlighted as a source of nutrition information. Research should consider exploring the use of healthy eating blogs and whether these blogs can be used as a tool by dietitians to communicate procedural healthy eating information more effectively in the future.
Der OPD-KJ2-SF – Ein Instrument zur Erfassung der Achse Struktur der OPD-KJ-2 bei Jugendlichen im Selbsturteil
Authors: Schrobildgen Christian , Goth Kirstin , Weissensteiner Ruth , Lazari Olga , Schmeck Klaus
Published: May 2019

Zusammenfassung. Die Erfassung der Strukturdimensionen nach OPD-KJ-2 ist neben ihrer therapeutischen Relevanz vor dem Hintergrund ihrer inhaltlichen Nähe zu gegenwärtig diskutierten dimensionalen Herangehensweisen in der Diagnostik von Persönlichkeitsstörungen im DSM-5 und in der ICD-11 von hoher Aktualität. Im Rahmen dieser Studie erfolgte eine Evaluation der psychometrischen Gütekriterien des neu entwickelten Fragenbogens OPD-KJ-2-SF zur Erfassung der Strukturdimensionen im Jugendalter. Die Untersuchung wurde anhand einer gemischten klinischen und nichtklinischen Stichprobe (N = 589) durchgeführt. Der OPD-KJ2-SF zeigte sehr gute psychometrische Kennwerte mit guten Skalenreliabilitäten von .87 bis .98 Cronbachs Alpha auf Gesamt- und Hauptskalenebene. Alle Hauptskalen diskriminierten hoch signifikant mit Effektstärken (d) von 1.4 bis 1.6 zwischen den Schüler_innen und Patient_innen mit Persönlichkeitsstörungen. Der OPD-KJ2-SF erscheint als ein reliables und valides Instrument zur Erfassung von strukturellen Beeinträchtigungen im Jugendalter.
Resilienztraining für unbegleitete minderjährige Flüchtlinge
Authors: Scheiber Barbara , Greinz Gerda , Hillebrand Jan B. , Wilhelm Frank H. , Blechert Jens
Published: May 2019

Zusammenfassung. Die hohen Flüchtlingszahlen und die fortlaufende Ankunft schwer traumatisierter unbegleiteter minderjähriger Flüchtlinge (UMF) verschärfen die Suche nach wirksamen und niederschwelligen Präventions- und Interventionsprogrammen. Die vorliegende Pilotstudie evaluiert die Effektivität eines nicht-indizierten, sechs Sitzungen umfassenden Resilienztrainings für UMF. Teilnehmende (N = 55) wurden in einem randomisiert-kontrollierten Wartelistendesign vor (T1) und nach (T2) dem Gruppenprogramm untersucht. Abhängige Variablen waren das allgemeine Wohlbefinden sowie Symptome von Traumafolgestörungen. Weiter wurden aus mehreren Perspektiven (Teilnehmer, Dolmetscher, Gruppenleitende, Betreuende) qualitative Daten erfasst. Während Traumafolgestörungssymptome unverändert blieben, berichtete die Interventionsgruppe nach dem Programm einen Anstieg im Wohlbefinden, nicht jedoch die Kontrollgruppe. Die qualitativen Daten wiesen perspektivenübergreifend auf positive Veränderungen in mehreren Funktionsbereichen hin. Ein kurzes Resilienztraining hat somit das Potential Verbesserungen zu bewirken. Für eine Minderung von Traumafolgestörungssymptomen sind jedoch wohl längere bzw. traumaspezifischere Interventionen erforderlich.
Evidence for the Jeffrey Table
Authors: Wang Moyun , Zhu Mingyi
Published: May 2019

Abstract. Conditionals statements are a common and necessary component in natural languages. The research reported in this paper is on a fundamental question about singular conditionals. Is there an adequate account of people’s truth, falsity, and credibility (probability) judgments about these conditionals when their antecedents are false? Two experiments examined people’s quantitative credibility ratings and qualitative truth and falsity judgments for singular conditionals, if p then q, given false antecedent, not-p, cases. The results demonstrate that, when relevant knowledge about the conditional probability of q given p, P( q|p), is available to participants in not-p cases, they tend to make credibility ratings based on P( q|p), and to make “true” (or “false”) judgments at a high (or low) level of these credibility ratings. These findings favor the Jeffrey table account of these conditionals over the other existing accounts, including that of the de Finetti table.
Bridging the Gap Between Policy‐Driven Land Use Changes and Regional Climate Projections
Authors: Berckmans Julie , Hamdi Rafiq , Dendoncker Nicolas
Published: May 2019

Changes in the land surface interact with a changing climate. Moreover, the impact of land surface changes on the local and regional climate can be as large as the impact of increasing greenhouse gas emissions. The land surface‐climate interactions are best represented by high‐resolution models to capture the mesoscale circulation features. The future land surface changes are preferably represented by scenarios that illustrate plausible storylines. Furthermore, the impact of future urbanization is relevant for the highly urbanized region of Europe. In this study, we assess the interactions between climate and land surface dynamics by modeling the near‐future climate state for western Europe based on a policy‐driven land use change scenario at high resolution. The global climate model CNRM‐CM5.1 has been downscaled to the regional climate of western Europe by using ALARO‐SURFEX at 4‐km horizontal resolution. SURFEX provides a parameterization of the urban physical properties so that the impact of urban surfaces on the regional climate can be modeled realistically. Results are interpreted with respect to the near‐future climate change without land surface changes. The near future presents a uniform temperature increase of 0.3–0.6 °C. This is in contrast to changes by the land surface that are more heterogeneous in space and much stronger at the local scale. Deforestation and conversion to arable land diminishes climate change effects, whereas urbanization results in an enhancing effect of climate change. Moreover, urbanization is as big as the radiative forcing warming for minimum temperature.
Passing Object May Have Kicked Up Dust from a Planetary Disk
Authors: Redd Nola
Published: May 2019

The elongated tail of the SU Aurigae protoplanetary disk was likely formed as a result of a flyby from a substellar object.
Extreme Lake Level Changes on the Tibetan Plateau Associated With the 2015/2016 El Niño
Authors: Lei Yanbin , Zhu Yali , Wang Bin , Yao Tandong , Yang Kun , Zhang Xiaowen , Zhai Jianqing , Ma Ning
Published: May 2019

Although the impact of El Niño–Southern Oscillation on the Tibetan Plateau (TP) is reflected through stable isotopes of precipitation and ice cores, the hydroclimate response of TP lakes to El Niño–Southern Oscillation is seldom investigated. Here we show that significant lake water deficit occurred on the central TP (CTP) due to a dramatic decrease in precipitation 2016 El Ni/2016 El Niño event, followed by extreme lake water surplus in 2016 and 2017 over most of the TP (except the eastern CTP). Similar but weaker lake shrinkage and afterward expansion can also be found during historical El Niño events. Further exploration reveals that the CTP dry anomaly during El Niño events tends to bridge the dry anomalies over India and northern China, thereby forming a dry zone along the northwestern edge of the Asian monsoon domain. This study may shed light on the prediction of lake level changes on the TP.
High-fidelity replication of thermoplastic microneedles with open microfluidic channels
Authors: Faraji Rad Zahra , Nordon Robert E. , Anthony Carl J. , Bilston Lynne , Prewett Philip D. , Arns Ji-Youn , Arns Christoph H. , Zhang Liangchi , Davies Graham J.
Published: May 2019

Development of microneedles for unskilled and painless collection of blood or drug delivery addresses the quality of healthcare through early intervention at point-of-care. Microneedles with submicron to millimeter features have been fabricated from materials such as metals, silicon, and polymers by subtractive machining or etching. However, to date, large-scale manufacture of hollow microneedles has been limited by the cost and complexity of microfabrication techniques. This paper reports a novel manufacturing method that may overcome the complexity of hollow microneedle fabrication. Prototype microneedles with open microfluidic channels are fabricated by laser stereolithography. Thermoplastic replicas are manufactured from these templates by soft-embossing with high fidelity at submicron resolution. The manufacturing advantages are (a) direct printing from computer-aided design (CAD) drawing without the constraints imposed by subtractive machining or etching processes, (b) high-fidelity replication of prototype geometries with multiple reuses of elastomeric molds, (c) shorter manufacturing time compared to three-dimensional stereolithography, and (d) integration of microneedles with open-channel microfluidics. Future work will address development of open-channel microfluidics for drug delivery, fluid sampling and analysis.
Live-cell imaging reveals the relative contributions of antigen-presenting cell subsets to thymic central tolerance
Authors: Lancaster J. N. , Thyagarajan H. M. , Srinivasan J. , Li Y. , Hu Z. , Ehrlich L. I. R.
Published: May 2019

Both medullary thymic epithelial cells (mTEC) and dendritic cells (DC) present tissue-restricted antigens (TRA) to thymocytes to induce central tolerance, but the relative contributions of these antigen-presenting cell (APC) subsets remain unresolved. Here we developed a two-photon microscopy approach to observe thymocytes interacting with intact APCs presenting TRAs. We find that mTECs and DCs cooperate extensively to induce tolerance, with their relative contributions regulated by the cellular form of the TRA and the class of major histocompatibility complex (MHC) on which antigen is presented. Even when TRA expression is restricted to mTECs, DCs still present self-antigens at least as frequently as mTECs. Notably, the DC subset cDC2 efficiently acquires secreted mTEC-derived TRAs for cross-presentation on MHC-I. By directly imaging interactions between thymocytes and APCs, while monitoring intracellular signaling, this study reveals that distinct DC subsets and AIRE+ mTECs contribute substantially to presentation of diverse self-antigens for establishing central tolerance.
Forming attitudes via neural activity supporting affective episodic simulations
Authors: Benoit Roland G. , Paulus Philipp C. , Schacter Daniel L.
Published: May 2019

Humans have the adaptive capacity for imagining hypothetical episodes. Such episodic simulation is based on a neural network that includes the ventromedial prefrontal cortex (vmPFC). This network draws on existing knowledge (e.g., of familiar people and places) to construct imaginary events (e.g., meeting with the person at that place). Here, we test the hypothesis that a simulation changes attitudes towards its constituent elements. In two experiments, we demonstrate how imagining meeting liked versus disliked people (unconditioned stimuli, UCS) at initially neutral places (conditioned stimuli, CS) changes the value of these places. We further provide evidence that the vmPFC codes for representations of those elements (i.e., of individual people and places). Critically, attitude changes induced by the liked UCS are based on a transfer of positive affective value between the representations (i.e., from the UCS to the CS). Thereby, we reveal how mere imaginings shape attitudes towards elements (i.e., places) from our real-life environment.
Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism
Authors: Fox Nicholas G. , Yu Xiaodi , Feng Xidong , Bailey Henry J. , Martelli Alain , Nabhan Joseph F. , Strain-Damerell Claire , Bulawa Christine , Yue Wyatt W. , Han Seungil
Published: May 2019

The core machinery for de novo biosynthesis of iron-sulfur clusters (ISC), located in the mitochondria matrix, is a five-protein complex containing the cysteine desulfurase NFS1 that is activated by frataxin (FXN), scaffold protein ISCU, accessory protein ISD11, and acyl-carrier protein ACP. Deficiency in FXN leads to the loss-of-function neurodegenerative disorder Friedreich’s ataxia (FRDA). Here the 3.2 Å resolution cryo-electron microscopy structure of the FXN-bound active human complex, containing two copies of the NFS1-ISD11-ACP-ISCU-FXN hetero-pentamer, delineates the interactions of FXN with other component proteins of the complex. FXN binds at the interface of two NFS1 and one ISCU subunits, modifying the local environment of a bound zinc ion that would otherwise inhibit NFS1 activity in complexes without FXN. Our structure reveals how FXN facilitates ISC production through stabilizing key loop conformations of NFS1 and ISCU at the protein–protein interfaces, and suggests how FRDA clinical mutations affect complex formation and FXN activation.
Complete deconvolution of cellular mixtures based on linearity of transcriptional signatures
Authors: Zaitsev Konstantin , Bambouskova Monika , Swain Amanda , Artyomov Maxim N.
Published: May 2019

Changes in bulk transcriptional profiles of heterogeneous samples often reflect changes in proportions of individual cell types. Several robust techniques have been developed to dissect the composition of such mixed samples given transcriptional signatures of the pure components or their proportions. These approaches are insufficient, however, in situations when no information about individual mixture components is available. This problem is known as the  complete deconvolution problem, where the composition is revealed without any a priori knowledge about cell types and their proportions. Here, we identify a previously unrecognized property of tissue-specific genes – their mutual linearity – and use it to reveal the structure of the topological space of mixed transcriptional profiles and provide a noise-robust approach to the complete deconvolution problem. Furthermore, our analysis reveals systematic bias of all deconvolution techniques due to differences in cell size or RNA-content, and we demonstrate how to address this bias at the experimental design level.
Hexameric NuMA:LGN structures promote multivalent interactions required for planar epithelial divisions
Authors: Pirovano Laura , Culurgioni Simone , Carminati Manuel , Alfieri Andrea , Monzani Silvia , Cecatiello Valentina , Gaddoni Chiara , Rizzelli Francesca , Foadi James , Pasqualato Sebastiano , Mapelli Marina
Published: May 2019

Cortical force generators connect epithelial polarity sites with astral microtubules, allowing dynein movement to orient the mitotic spindle as astral microtubules depolymerize. Complexes of the LGN and NuMA proteins, fundamental components of force generators, are recruited to the cortex by Gαi-subunits of heterotrimeric G-proteins. They associate with dynein/dynactin and activate the motor activity pulling on astral microtubules. The architecture of cortical force generators is unknown. Here we report the crystal structure of NuMA:LGN hetero-hexamers, and unveil their role in promoting the assembly of active cortical dynein/dynactin motors that are required in orchestrating oriented divisions in polarized cells. Our work elucidates the basis for the structural organization of essential spindle orientation motors.
Targeting lonidamine to mitochondria mitigates lung tumorigenesis and brain metastasis
Authors: Cheng Gang , Zhang Qi , Pan Jing , Lee Yongik , Ouari Olivier , Hardy Micael , Zielonka Monika , Myers Charles R. , Zielonka Jacek , Weh Katherine , Chang Andrew C. , Chen Guoan , Kresty Laura , Kalyanaraman Balaraman , You Ming
Published: May 2019

Lung cancer often has a poor prognosis, with brain metastases a major reason for mortality. We modified lonidamine (LND), an antiglycolytic drug with limited efficacy, to mitochondria-targeted mito-lonidamine (Mito-LND) which is 100-fold more potent. Mito-LND, a tumor-selective inhibitor of oxidative phosphorylation, inhibits mitochondrial bioenergetics in lung cancer cells and mitigates lung cancer cell viability, growth, progression, and metastasis of lung cancer xenografts in mice. Mito-LND blocks lung tumor development and brain metastasis by inhibiting mitochondrial bioenergetics, stimulating the formation of reactive oxygen species, oxidizing mitochondrial peroxiredoxin, inactivating AKT/mTOR/p70S6K signaling, and inducing autophagic cell death in lung cancer cells. Mito-LND causes no toxicity in mice even when administered for eight weeks at 50 times the effective cancer inhibitory dose. Collectively, these findings show that mitochondrial targeting of LND is a promising therapeutic approach for investigating the role of autophagy in mitigating lung cancer development and brain metastasis.
Targeting cyclin-dependent kinases for the treatment of pulmonary arterial hypertension
Authors: Weiss Astrid , Neubauer Moritz Christian , Yerabolu Dinesh , Kojonazarov Baktybek , Schlueter Beate Christiane , Neubert Lavinia , Jonigk Danny , Baal Nelli , Ruppert Clemens , Dorfmuller Peter , Pullamsetti Soni Savai , Weissmann Norbert , Ghofrani Hossein-Ardeschir , Grimminger Friedrich , Seeger Werner , Schermuly Ralph Theo
Published: May 2019

Pulmonary arterial hypertension (PAH) is a devastating disease with poor prognosis and limited therapeutic options. We screened for pathways that may be responsible for the abnormal phenotype of pulmonary arterial smooth muscle cells (PASMCs), a major contributor of PAH pathobiology, and identified cyclin-dependent kinases (CDKs) as overactivated kinases in specimens derived from patients with idiopathic PAH. This increased CDK activity is confirmed at the level of mRNA and protein expression in human and experimental PAH, respectively. Specific CDK inhibition by dinaciclib and palbociclib decreases PASMC proliferation via cell cycle arrest and interference with the downstream CDK-Rb (retinoblastoma protein)-E2F signaling pathway. In two experimental models of PAH (i.e., monocrotaline and Su5416/hypoxia treated rats) palbociclib reverses the elevated right ventricular systolic pressure, reduces right heart hypertrophy, restores the cardiac index, and reduces pulmonary vascular remodeling. These results demonstrate that inhibition of CDKs by palbociclib may be a therapeutic strategy in PAH.
Proximity-induced surface superconductivity in Dirac semimetal Cd3As2
Authors: Huang Ce , Zhou Benjamin T. , Zhang Huiqin , Yang Bingjia , Liu Ran , Wang Hanwen , Wan Yimin , Huang Ke , Liao Zhiming , Zhang Enze , Liu Shanshan , Deng Qingsong , Chen Yanhui , Han Xiaodong , Zou Jin , Lin Xi , Han Zheng , Wang Yihua , Law Kam Tuen , Xiu Faxian
Published: May 2019

Cd3As2 is a three-dimensional Dirac semimetal with separated Dirac points in momentum space. In spite of extensive transport and spectroscopic studies on its exotic properties, the evidence of superconductivity in its surface states remains elusive. Here, we report the observation of proximity-induced surface superconductivity in Nb/Cd3As2 hybrid structures. Our four-terminal transport measurement identifies a pronounced proximity-induced pairing gap (gap size comparable to Nb) on the surfaces, which exhibits a flat conductance plateau in differential conductance spectra, consistent with our theoretical simulations. The surface supercurrent from Nb/Cd3As2/Nb junctions is also achieved with a Fraunhofer/SQUID-like pattern under out-of-plane/in-plane magnetic fields, respectively. The resultant mapping shows a predominant distribution on the top and bottom surfaces as the bulk carriers are depleted, which can be regarded as a higher dimensional analog of edge supercurrent in two-dimensional quantum spin Hall insulators. Our study provides the evidence of surface superconductivity in Dirac semimetals.
Anisotropic and self-healing hydrogels with multi-responsive actuating capability
Authors: Qin Haili , Zhang Tan , Li Na , Cong Huai-Ping , Yu Shu-Hong
Published: May 2019

Inspired by smart biological tissues, artificial muscle-like actuators offer fascinating prospects due to their distinctive shape transformation and self-healing function under external stimuli. However, further practical application is hindered by the lack of simple and general routes to fabricate ingenious soft materials with anisotropic responsiveness. Here, we describe a general in situ polymerization strategy for the fabrication of anisotropic hydrogels composed of highly-ordered lamellar network crosslinked by the metal nanostructure assemblies, accompanied with remarkably anisotropic performances on mechanical, optical, de-swelling and swelling behaviors. Owing to the dynamic thiolate-metal coordination as healing motifs, the composites exhibit rapid and efficient multi-responsive self-healing performance under NIR irradiation and low pH condition. Dependent on well-defined anisotropic structures, the hydrogel presents controllable solvent-responsive mechanical actuating performance. Impressively, the integrated device through a healing-induced assembly way can deliver more complicated, elaborate forms of actuation, demonstrating its great potentials as superior soft actuators like smart robots.
Uncertainty equality with quantum memory and its experimental verification
Authors: Wang Hengyan , Ma Zhihao , Wu Shengjun , Zheng Wenqiang , Cao Zhu , Chen Zhihua , Li Zhaokai , Fei Shao-Ming , Peng Xinhua , Vedral Vlatko , Du Jiangfeng
Published: May 2019

As a very fundamental principle in quantum physics, uncertainty principle has been studied intensively via various uncertainty inequalities. A natural and fundamental question is whether an equality exists for the uncertainty principle. Here we derive an entropic uncertainty equality relation for a bipartite system consisting of a quantum system and a coupled quantum memory, based on the information measure introduced by Brukner and Zeilinger (Phys. Rev. Lett. 83:3354, 1999). The equality indicates that the sum of measurement uncertainties over a complete set of mutually unbiased bases on a subsystem is equal to a total, fixed uncertainty determined by the initial bipartite state. For the special case where the system and the memory are the maximally entangled, all of the uncertainties related to each mutually unbiased base measurement are zero, which is substantially different from the uncertainty inequality relation. The results are meaningful for fundamental reasons and give rise to operational applications such as in quantum random number generation and quantum guessing games. Moreover, we experimentally verify the measurement uncertainty relation in the presence of quantum memory on a five-qubit spin system by directly measuring the corresponding quantum mechanical observables, rather than quantum state tomography in all the previous experiments of testing entropic uncertainty relations.