bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion‐compensated tofts model suggests contrast leakage through aneurysm wall
Authors: Cantrell Charles G. , Vakil Parmede , Jeong Yong , Ansari Sameer A. , Carroll Timothy J.
Published: January 2017

Purpose

The purpose of this study was to investigate the diffusional transport of contrast agent and its effects on kinetic modeling of dynamic contrast enhanced (DCE) images.

Methods

We performed simulations of our diffusion‐compensated model and compared these results to human intracranial aneurysms (IAs). We derive an easy‐to‐use parameterization of diffusional effects that can provide an accurate estimate of diffusion corrected contrast agent leakage rates (ktrans). Finally, we performed re‐ansalysis of an existing data set to determine whether diffusion‐corrected kinetic parameters improve the identification of high‐risk IAs, thereby providing a new MRI‐based imaging metric of IA stability based on wall integrity.

Results

Probability distributions of simulated versus measured data show contrast leakage away from the aneurysm wall. Parameterization of diffusional effects on ktrans showed high correlation with long‐chain methods in both surrounding tissue and near the aneurysm wall (r2 = 0.91 and r2 = 0.90, respectively). Finally, size, ktrans, and (
) showed significant univariate relationships with rupture risk (P < 0.05).

Conclusions

We report the first evidence of diffusion‐compensated permeability modeling in intracranial aneurysms and propose a parameterization of diffusional effects on ktrans. Furthermore, a comparison of measured versus simulated data suggests that contrast leakage occurs across the aneurysm wall. Magn Reson Med 78:2388–2398, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Increased expression of triggering receptor expressed on myeloid cells‐1 in the population with obesity and insulin resistance
Authors: Subramanian Saravanan , Pallati Pradeep K. , Rai Vikrant , Sharma Poonam , Agrawal Devendra K. , Nandipati Kalyana C.
Published: January 2017

Objective

Triggering receptor expressed on myeloid cells (TREM)−1 has recently been recognized as one of the potent amplifiers of acute and chronic inflammation. However, the exact role of TREM‐1 in regard to insulin insensitivity is unknown.

Methods

mRNA transcripts and protein expression of TREM‐1, TREM‐2, and TREM‐1/TREM‐2 ratio were examined in the tissue biopsies (liver, omentum, and subcutaneous fat) and blood samples (neutrophils and monocytes) of subjects with obesity and diabetes (SO+ D+; n = 15), subjects with obesity but not diabetes (SO+ D−; n = 7), and subjects without obesity (BMI < 30) and diabetes (SO−D−; n = 5).

Results

The immunofluorescence and RT‐PCR revealed significant increase in TREM‐1, decrease in TREM‐2, and increase in the TREM1/TREM2 ratio in SO+ D+ group compared with other groups. Overall, increased liver TREM‐1 expression and soluble‐TREM‐1 were found in SO+ D+ group compared with SO+ D− group (100% vs. 57.14%, r = 0.582; P = 0.023). TREM‐1 was significantly increased in all subjects with obesity and those with HOMA‐IR index of >2.

Conclusions

TREM‐1 was found to be significantly higher in tissues biopsies and blood of subjects with obesity. Greater expression and activity of TREM‐1 suggest a possible role in the underlying pathophysiology of obesity and associated comorbidities.
Synthesis of C2‐Symmetric Diphosphormonoamidites and Their Use as Ligands in Rh‐Catalyzed Hydroformylation: Relationships between Activity and Hydrolysis Stability
Authors: Morales Torres Galina , Behrens Stephan , Michalik Dirk , Selent Detlef , Spannenberg Anke , Lühr Susan , Dyballa Katrin Marie , Franke Robert , Börner Armin
Published: January 2017

A series of diphosphoramidites has been synthetized with a piperazine, homopiperazine, and an acyclic 1,2‐diamine unit in the backbone. New compounds were tested alongside related N‐acyl phosphoramidites as ligands in the Rh‐catalyzed hydroformylation of n‐octenes to investigate their influence on the activity and regioselectivity. A subsequent study of their hydrolysis stability revealed that the most stable ligands induced the highest activity in the catalytic reaction.
MDM4 is a rational target for treating breast cancers with mutant p53
Authors: Miranda Panimaya Jeffreena , Buckley Daniel , Raghu Dinesh , Pang Jia‐Min B , Takano Elena A , Vijayakumaran Reshma , Teunisse Amina FAS , Posner Atara , Procter Tahlia , Herold Marco J , Gamell Cristina , Marine Jean‐Christophe , Fox Stephen B , Jochemsen Aart , Haupt Sue , Haupt Ygal
Published: January 2017

Mutation of the key tumour suppressor p53 defines a transition in the progression towards aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, the p53 mutation frequency exceeds 50% in triple‐negative BC. Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal‐like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells. We demonstrate that conditional knockdown (KD) of MDM4 provokes growth inhibition across a range of BC subtypes with mutant p53, including luminal, Her2+ and triple‐negative BCs. In vivo, MDM4 was shown to be crucial for the establishment and progression of tumours. This growth inhibition was mediated, at least in part, by the cell cycle inhibitor p27. Depletion of p27 together with MDM4 KD led to recovery of the proliferative capacity of cells that were growth‐inhibited by MDM4 KD alone. Consistently, we identified low levels of p27 expression in basal‐like tumours corresponding to high levels of MDM4 and p53. This predicts a signature for a subset of tumours that may be amenable to therapies targeted towards MDM4 and mutant p53. The therapeutic potential of MDM4 as a target in BC with mutant p53 was shown in vitro by use of a small‐molecule inhibitor. Overall, our study supports MDM4 as a novel therapeutic target for BC expressing mutant p53. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Investigating the heterogeneity of alkylating agents’ efficacy and toxicity between sexes: A systematic review and meta‐analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study)
Authors: Fresneau Brice , Hackshaw A. , Hawkins D.S. , Paulussen M. , Anderson J.R. , Judson I. , Litière S. , Dirksen U. , Lewis I. , van den Berg H. , Gaspar N. , Gelderblom H. , Whelan J. , Boddy A.V. , Wheatley K. , Pignon J.P. , De Vathaire F. , Le Deley M.C. , Le Teuff G.
Published: January 2017

Background

A marginal interaction between sex and the type of alkylating agent was observed for event‐free survival in the Euro‐EWING99‐R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta‐analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer.

Methods

A literature search produced two more eligible RCTs (EICESS92 and IRS‐IV). The endpoints were progression‐free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment‐by‐sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models.

Results

The meta‐analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro‐EWING99‐R1 (n = 856), EICESS92 (n = 155), and IRS‐IV (n = 517). There were 224 PFS events in Euro‐EWING99‐R1 and 200 in the validation set (EICESS92 + IRS‐IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment‐by‐sex interaction for PFS in Euro‐EWING99‐R1 (HR = 1.73, 95% CI = 1.00–3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55–1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment‐by‐sex interaction was not significant (HR = 1.31, 95% CI = 0.89–1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment‐by‐sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20).

Conclusion

Our meta‐analysis did not confirm the hypothesis of a treatment‐by‐sex interaction on efficacy or toxicity outcomes.
Respiratory muscle training improves respiratory muscle endurance but not exercise tolerance in children with cystic fibrosis
Authors: Bieli Christian , Summermatter Selina , Boutellier Urs , Moeller Alexander
Published: January 2017

Background

Respiratory muscle endurance (RME) training has been shown to increase exercise endurance and lung function in adults with cystic fibrosis (CF). We conducted an interventional study to investigate the effectiveness of RME training on CF‐related health outcomes in children.

Methods

In a crossover trial, 22 children, aged 9–18 years, with CF performed 8 weeks of RME training and standard chest physiotherapy in a randomized sequence separated by a 1 week washout period. All children underwent training sessions using the RME training device before beginning the study. The primary outcomes were RME (in minutes) and exercise endurance (in minutes). Data were analyzed according to the intention‐to‐treat principle.

Results

Sixteen of 22 children (73%) completed the study. Study dropouts tended to be older with more advanced lung disease. After RME training, respiratory muscle endurance significantly increased by 7.03 ± 8.15 min (mean ± standard deviation, P < 0.001), whereas exercise endurance was unchanged by RME training (0.80 ± 2.58 min, P = 0.169). No significant improvement in secondary outcomes (lung function, CF quality of life, and CF clinical score) were observed. The small sample size and short intervention time have to be acknowledged as limitations of our study.

Conclusions

RME training led to a significant increase in respiratory muscle endurance in children with CF. However, RME training did not improve exercise endurance or other CF‐related health outcomes. Thus, our results do not support the routine use of RME training in the care of children with CF. Future studies in larger populations and with prolonged intervention time may overcome the limitations of our study. Pediatr Pulmonol. 2017;52:331–336. © 2017 Wiley Periodicals, Inc.
High resolution crystal structures of human kynurenine aminotransferase‐I bound to PLP cofactor, and in complex with aminooxyacetate
Authors: Nadvi Naveed A. , Salam Noeris K. , Park Joohong , Akladios Fady N. , Kapoor Vimal , Collyer Charles A. , Gorrell Mark D. , Church William Bret
Published: January 2017

In this study, we report two high‐resolution structures of the pyridoxal 5′ phosphate (PLP)‐dependent enzyme kynurenine aminotransferase‐I (KAT‐I). One is the native structure with the cofactor in the PLP form bound to Lys247 with the highest resolution yet available for KAT‐I at 1.28 Å resolution, and the other with the general PLP‐dependent aminotransferase inhibitor, aminooxyacetate (AOAA) covalently bound to the cofactor at 1.54 Å. Only small conformational differences are observed in the vicinity of the aldimine (oxime) linkage with which the PLP forms the Schiff base with Lys247 in the 1.28 Å resolution native structure, in comparison to other native PLP‐bound structures. We also report the inhibition of KAT‐1 by AOAA and aminooxy‐phenylpropionic acid (AOPP), with IC50s of 13.1 and 5.7 μM, respectively. The crystal structure of the enzyme in complex with the inhibitor AOAA revealed that the cofactor is the PLP form with the external aldimine linkage. The location of this oxime with the PLP, which forms in place of the native internal aldimine linkage of PLP of the native KAT‐I, is away from the position of the native internal aldimine, with the free Lys247 substantially retaining the orientation of the native structure. Tyr101, at the active site, was observed in two conformations in both structures.
Regression analysis of mixed panel count data with dependent terminal events
Authors: Yu Guanglei , Zhu Liang , Li Yang , Sun Jianguo , Robison Leslie L.
Published: January 2017

Event history studies are commonly conducted in many fields, and a great deal of literature has been established for the analysis of the two types of data commonly arising from these studies: recurrent event data and panel count data. The former arises if all study subjects are followed continuously, while the latter means that each study subject is observed only at discrete time points. In reality, a third type of data, a mixture of the two types of the data earlier, may occur and furthermore, as with the first two types of the data, there may exist a dependent terminal event, which may preclude the occurrences of recurrent events of interest. This paper discusses regression analysis of mixed recurrent event and panel count data in the presence of a terminal event and an estimating equation‐based approach is proposed for estimation of regression parameters of interest. In addition, the asymptotic properties of the proposed estimator are established, and a simulation study conducted to assess the finite‐sample performance of the proposed method suggests that it works well in practical situations. Finally, the methodology is applied to a childhood cancer study that motivated this study. Copyright © 2017 John Wiley & Sons, Ltd.
Cooperative Strategies for Enhancing Performance of Photothermal Therapy (PTT) Agent: Optimizing Its Photothermal Conversion and Cell Internalization Ability
Authors: Du Baoji , Ma Chongbo , Ding Guanyu , Han Xu , Li Dan , Wang Erkang , Wang Jin
Published: January 2017

Photothermal conversion ability (PCA) and cell internalization ability (CIA) are two key factors for determining the performance of photothermal agents. The previous studies mostly focus on improving the PCA by exploring new photothermal nanomaterials. Herein, the authors take the hybrids of graphene and gold nanostar (GGN) as an example to investigate the gradually enhanced phototherapy effect by changing the PCA and CIA of photothermal therapy (PTT) agent simultaneously. Based on the GGN, the GGN and the reduced GGN protected by bovine serum albumin (BSA) or BSA‐FA (folic acid) are prepared, which are named as GGNB, rGGNB, and rGGNB‐FA, respectively. The rGGNB showed an enhanced PCA compared to GGNB, leading to strong cell ablation. On the other hand, the 1,2‐dioleoyl‐3‐trimethylammoniumpropan (DOTAP) can activate the endocytosis and promote the CIA of rGGNB, further help rGGNB to be more internalized into the cells. Finally, rGGNB‐FA with the target ability can make itself further internalized into the cells with the aid of DOTAP, which can significantly destroy the cancer cells even at the low laser density of 0.3 W cm−2. Therefore, a new angle of view is brought out for researching the PTT agents of high performance.
Sensitive Detection of Carcinoembryonic Antigen Using Stability‐Limited Few‐Layer Black Phosphorus as an Electron Donor and a Reservoir
Authors: Peng Jian , Lai Youqun , Chen Yuanyuan , Xu Jun , Sun Liping , Weng Jian
Published: January 2017

The instability of few‐layer black phosphorus (FL‐BP) hampers its further applications. Here, it can be demonstrated that the instability of FL‐BP can also be the advantage for application in biosensor. First, gold nanoparticle/FL‐BP (BP‐Au) hybrid is facilely synthesized by mixing Au precursor with FL‐BP. BP‐Au shows outstanding catalytic activity (K = 1120 s−1 g−1) and low activation energy (17.53 kJ mol−1) for reducing 4‐nitrophenol, which is attributed to the electron‐reservoir and electron‐donor properties of FL‐BP, and synergistic interaction of Au nanoparticles and FL‐BP. Oxidation of FL‐BP after catalytic reaction is further confirmed by transmission electron microscope, X‐ray photoelectron spectroscopy, and zeta potentials. Second, the catalytic activity of BP‐Au can be reversibly switched from “inactive” to “active” upon treatment with antibody and antigen in solution, thus providing a versatile platform for label‐free colorimetric detection of biomarkers. The sensor shows a wide detection range (1 pg mL−1 to –10 µg mL−1), high sensitivity (0.20 pg mL−1), and selectivity for detecting carcinoembryonic antigen (CEA). Finally, the biosensor has been used to detect CEA in colon and breast cancer clinical samples with satisfactory results. Therefore, the instability of BP can also be the advantage for application in detecting cancer biomarker in clinic.
Systems, Networks, and Policy
Authors: Johnson Jeffrey , Fortune Joyce , Bromley Jane
Published: January 2017

Systems theory is fundamental to understanding the dynamics of the complex social systems of concern to policy makers. A system is defined as: (1) an assembly of components, connected together in an organised way; (2) the components are affected by being in the system and the behaviour of the systems is changed if they leave it; (3) the organised assembly of components does something; and (4) the assembly has been identified as being of particular interest. Feedback is central to system behaviour at all levels, and can be responsible for systems behaving in complex and unpredictable ways. Systems can be represented by networks and there is a growing literature that shows how the behaviour of individuals is highly dependent on their social networks. This includes copying or following the advice of others when making decisions. Network theory gives insights into social phenomena such as the spread of information and the way people form social groups which then constrain their behaviour. It is emerging as a powerful way of examining the dynamics of social systems. Most systems relevant to policy have many levels, from the individual to local and national and international organisations and institutions. In many social systems the micro, meso and macrolevel dynamics are coupled, meaning that they cannot be studied or modified in isolation. Systems and network science allow computer simulations to be used to investigate possible system behaviour. This science can be made available to policy makers through policy informatics which involves computer-based simulation, data, visualisation, and interactive interfaces. The future of science-based policy making is seen to be through Global Systems Science which combines complex systems science and policy informatics to inform policy makers and facilitate citizen engagement. In this context, systems theory and network science are fundamental for modelling far-from-equilibrium systems for policy purposes.
A phase 1 study of the pharmacokinetics of nucleoside analog trifluridine and thymidine phosphorylase inhibitor tipiracil (components of TAS-102) vs trifluridine alone
Authors: Cleary James M. , Rosen Lee S. , Yoshida Kenichiro , Rasco Drew , Shapiro Geoffrey I. , Sun Weijing
Published: January 2017

Background Trifluridine, a thymidine-based chemotherapeutic, has limited bioavailability after clinical administration as it is rapidly degraded via thymidine phosphorylase. An oral combination tablet combines trifluridine with a potent thymidine phosphorylase inhibitor, tipiracil hydrochloride. This study’s objective was to evaluate whether trifluridine/tipiracil (TAS-102) administration increases trifluridine exposure vs trifluridine alone. Methods This open-label pharmacokinetic study randomly assigned patients with advanced solid tumors into two groups. On the morning of day 1, one group received a single 35 mg/m2 dose of trifluridine/tipiracil and the other group received a single 35-mg/m2 dose of trifluridine. Both groups received trifluridine/tipiracil 35 mg/m2 on the evening of day 1, then twice daily on days 2–5 and 8–12 in a 28-day cycle. Results Twenty patients received an initial one-time dose of trifluridine alone and 19 other patients received an initial dose of trifluridine/tipiracil. Trifluridine area under the curve (AUC0-last) and maximum observed plasma concentrations (Cmax) were approximately 37- and 22-fold higher, respectively, with trifluridine/tipiracil vs trifluridine alone. Plasma concentrations of the major metabolite of trifluridine were lower following the administration of trifluridine/tipiracil vs trifluridine alone. Conclusion Tipiracil administered in combination with trifluridine significantly increased exposure to trifluridine compared with trifluridine alone.
Intracohort cannibalism and methods for its mitigation in cultured freshwater fish
Authors: Duk Karolina , Pajdak Joanna , Terech-Majewska Elżbieta , Szarek Józef
Published: January 2017

Cannibalism is a common phenomenon that occurs in over 30 fish families. Most of the species are valuable objects of aquaculture and cannibalism is highly undesirable. Cannibalism is an aggressive behaviour, which can be caused by stress induced by various population and environmental factors and can occur in two main forms: early larval and late juvenile (or adult). Each of these forms can lead to severe losses of stock. Losses are caused not only by fish eating each other, but also by an increase in the number of infections (the result of body surface damage). It is important to understand the phenomenon of cannibalism in order to properly prevent, diagnose and reduce it. The main aim of this study was to present and examine some of the well-examined methods of cannibalism mitigation. Most of the methods consist of creating rearing conditions similar to natural conditions and to reduce stress. Moreover, because of large interspecies differences, similar methods can result in different effects depending on the species. Additional studies are needed to better understand the biology of each cultured species with particular emphasis on the impact of domestication, as well as to improve fish rearing conditions.
Advanced Analytical Dynamics
Authors: De Sapio Vincent
Published: January 2017

Providing a unique bridge between the foundations of analytical mechanics and application to multi-body dynamical systems, this textbook is particularly well suited for graduate students seeking an understanding of the theoretical underpinnings of analytical mechanics, as well as modern task space approaches for representing the resulting dynamics that can be exploited for real-world problems in areas such as biomechanics and robotics. Established principles in mechanics are presented in a thorough and modern way. The chapters build up from general mathematical foundations, an extensive treatment of kinematics, and then to a rigorous treatment of conservation and variational principles in mechanics. Parallels are drawn between the different approaches, providing the reader with insights that unify his or her understanding of analytical dynamics. Additionally, a unique treatment is presented on task space dynamical formulations that map traditional configuration space representations into more intuitive geometric spaces.
Party Mobilization and Electoral Systems
Authors: Lago Ignacio , Bermúdez Sandra , Guinjoan Marc , Rowe Kelly , Simón Pablo
Published: January 2017

How party strategies vary by electoral system remains largely unexplored in election studies. Using qualitative and quantitative data from Spanish national and European elections, we test how party strategies diverge between districted electoral systems and systems using a single national district. We use the number of visits to districts by the party leaders to determine if targeted party strategies are driven by district magnitude, the share of the population entitled to vote in every district, the number of districts or the strength of parties’ local organizations. Our results show that only the frequency of visits to districts by large parties are clearly affected by electoral systems and, more specifically, by the number of districts and district population.
Hegel and Husserl: Two Phenomenological Reactions to Kant
Authors: Rockmore Tom
Published: January 2017

The widespread tendency to understand phenomenology on a Husserlian model makes it incomparable with other views. I will use the term ‘phenomenology’ in a wider sense to refer to approaches to cognition based on phenomena. From the latter angle of vision, ’phenomenology’ includes not only Husserl and the Husserlians but also a wider selection of thinkers stretching back to early Greece. Although this will enlarge the scope of what counts as phenomenology, I will not be claiming that everyone is a phenomenologist. I will, however, be arguing that Kant, Hegel and Husserl are phenomenologists, or again phenomenological thinkers, and that Hegel and Husserl can be understood through their different reactions to Kantian phenomenology.
Cross-stream stereoscopic particle image velocimetry of a modified turbulent boundary layer over directional surface pattern
Authors: Kevin Kevin , Monty J. P. , Bai H. L. , Pathikonda G. , Nugroho B. , Barros J. M. , Christensen K. T. , Hutchins N.
Published: January 2017

A turbulent boundary layer developed over a herringbone patterned riblet surface is investigated using stereoscopic particle image velocimetry in the cross-stream plane at$Re_{\unicode[STIX]{x1D70F}}\approx 3900$. The three velocity components resulting from this experiment reveal a pronounced spanwise periodicity in all single-point velocity statistics. Consistent with previous hot-wire studies over similar-type riblets, we observe a weak time-average secondary flow in the form of$\unicode[STIX]{x1D6FF}$-filling streamwise vortices. The observed differences in the surface and secondary flow characteristics, compared to other heterogeneous-roughness studies, may suggest that different mechanisms are responsible for the flow modifications in this case. Observations of instantaneous velocity fields reveal modified and rearranged turbulence structures. The instantaneous snapshots also suggest that the time-average secondary flow may be an artefact arising from superpositions of much stronger instantaneous turbulent events enhanced by the surface texture. In addition, the observed instantaneous secondary motions seem to have promoted a free-stream-engulfing behaviour in the outer layer, which would indicate an increase turbulent/non-turbulent flow mixing. It is overall demonstrated that the presence of large-scale directionality in transitional surface roughness can cause a modification throughout the entire boundary layer, even when the roughness height is 0.5 % of the layer thickness.
AN ASSIMILATED APPROACH TO DISCHARGE FOR BREACH OF CONTRACT BY DELAY
Authors: Carter J.W. , Courtney Wayne , Tolhurst Gregory
Published: January 2017

The conflict between common law and equity on the question of when time should be regarded as being “of the essence” for the performance of a contract has often been debated, as has the impact of its resolution by the Judicature reforms in favour of equity's more relaxed approach. Even so, it is tolerably clear that the two approaches have been substantially assimilated within general principles of discharge for breach. If, as a matter of construction, a time stipulation is a condition, then time is of the essence. Alternatively, time may have become of the essence by an effective notice to perform served by a promisee. If the contract has been validly discharged on either basis, specific performance will not be ordered in favour of the promisor.1
Circles of Steel, Castles of Vanity: The Geopolitics of Military Bases on the South China Sea
Authors: McCoy Alfred W.
Published: January 2017

After four years of rising tensions over China's construction of military bases in the South China Sea, in July 2016 the Permanent Court of Arbitration issued a landmark decision layered with meaning, academic as well as diplomatic. “China's claims to historic rights, or other sovereign rights or jurisdiction,” wrote the panel of five judges, “with respect to the maritime areas … encompassed by the relevant part of the ‘nine-dash line’ are contrary to the Convention [on the Law of the Sea] and without lawful effect.” Writing with unambiguous clarity, the court ruled that China's dredging of these artificial islands for military bases gave it no right whatsoever to the surrounding seas and rebuked Beijing for infringing on waters that the Philippines should rightly control. China's claims to most of the South China Sea within that nine-dash line, which Beijing first published on maps at the height of the Cold War in 1953 and has pursued ever since, “were extinguished,” the court said, by the UN Convention (Gao and Jia 2013, 103–4;New York Times2016; Permanent Court of Arbitration 2016, 68–77, 116–17).
The jaguar's spots are darker than they appear: assessing the global conservation status of the jaguarPanthera onca
Authors: de la Torre J. Antonio , González-Maya José F. , Zarza Heliot , Ceballos Gerardo , Medellín Rodrigo A.
Published: January 2017

The IUCN Red List is widely used to guide conservation policy and practice. However, in most cases the evaluation of a species using IUCN Red List criteria takes into account only the global status of the species. Although subpopulations may be assessed using the IUCN categories and criteria, this rarely occurs, either because it is difficult to identify subpopulations or because of the effort involved. Using the jaguarPanthera oncaas a model we illustrate that wide-ranging species that are assigned a particular category of threat based on the IUCN Red List criteria may display considerable heterogeneity within individual taxa in terms of the level of risk they face. Using the information available on the conservation status of the species, we evaluated the jaguar's current geographical range and its subpopulations. We identified the most threatened subpopulations, using the extent of occurrence, area of occupancy, population size and the level of threat to each subpopulation. The main outcome of this analysis was that although a large subpopulation persists in Amazonia, virtually all others are threatened because of their small size, isolation, deficient protection and the high human population density. Based on this approach, future conservation efforts can be prioritized for the most threatened subpopulations. Based on our findings we recommend that for future Red List assessments assessors consider the value of undertaking assessments at the subpopulation level. For the jaguar, sub-global assessments should be included on the Red List as a matter of urgency.
Implication of reward alterations in the expression of negative symptoms in 22q11.2 deletion syndrome: a behavioural and DTI study
Authors: Dubourg L. , Schneider M. , Padula M. C. , Chambaz L. , Schaer M. , Eliez S.
Published: January 2017

Background

Alterations of the reward system have been proposed as one of the core mechanisms underlying the expression of negative symptoms in schizophrenia. Specifically, deficits in specific reward components and white matter (WM) integrity of the reward system have been highlighted. The putative link between negative symptoms and the hedonic experience, or structural connectivity of the reward system has never been examined in the 22q11.2 deletion syndrome (22q11DS), a condition with increased risk for psychosis.

Method

Anticipatory and consummatory dimensions of pleasure were assessed in participants with 22q11DS (N= 54) and healthy controls (N= 55). In patients with 22q11DS, the association between pleasure scores and positive or negative symptoms was investigated. Furthermore, WM integrity of the accumbofrontal tract was quantified using diffusion tensor imaging (DTI). Associations between DTI measures, pleasure dimensions and negative symptoms were examined.

Results

Patients with 22q11DS showed reduced anticipatory and consummatory pleasure compared to controls. Furthermore, anticipatory pleasure scores were negatively correlated to negative and positive symptoms in 22q11DS. WM microstructural changes of the accumbofrontal tract in terms of increased fractional anisotropy and reduced radial anisotropy were also identified in patients. However, no significant correlation between the DTI measures and pleasure dimensions or psychotic symptoms was observed.

Conclusions

This study revealed that participants with 22q11DS differed in their experience of pleasure compared to controls. The anticipatory pleasure component appears to be related to negative and positive symptom severity in patients. Alterations of WM integrity of the accumbofrontal tract seem to be related to myelination abnormalities in 22q11DS patients.
Meanings of ‘lifecycle robust neighbourhoods’: constructing versus attaching to places
Authors: VAN HEES SUSAN , HORSTMAN KLASIEN , JANSEN MARIA , RUWAARD DIRK
Published: January 2017

In Western welfare states, notions of age-friendly communities and ageing-in-place are increasingly important in new health policies. In the Netherlands, care reforms are modifying the former welfare state to be more participatory; local governments are seeking collaborative solutions. Municipalities and housing, care and welfare organisations in the southern part of the country developed the concept of ‘lifecycle robust neighbourhoods’, envisioned as places where older people can age-in-place. Although many scholars have used the concept ageing-in-place in their studies of neighbourhoods, we aim to unravel this concept further by exploring how this particular ageing policy plays out in practice. This paper explores what the development of ‘lifecycle robust neighbourhoods’ means in relation to notions of ageing-in-place and age-friendly communities. We used ethnography (interviews, observations and focus groups) to reveal how, on the one hand, the policy makers, housing, care and welfare directors and representatives of older people, as developers of ‘lifecycle robust neighbourhoods’ and, on the other hand, older people, give meaning to places to age-in-place. It becomes clear that ageing-in-place has a different meaning in policy discourses than in practice. While developers mainly considered place as something construable, older people emotionally attached to place through lived experiences.
The Erdős–Rothschild problem on edge-colourings with forbidden monochromatic cliques
Authors: PIKHURKO OLEG , STADEN KATHERINE , YILMA ZELEALEM B.
Published: January 2017

Let k := (k1,. . .,ks) be a sequence of natural numbers. For a graph G, let F(G;k) denote the number of colourings of the edges of G with colours 1,. . .,s such that, for every c ∈ {1,. . .,s}, the edges of colour c contain no clique of order kc. Write F(n;k) to denote the maximum of F(G;k) over all graphs G on n vertices. This problem was first considered by Erdős and Rothschild in 1974, but it has been solved only for a very small number of non-trivial cases.

We prove that, for every k and n, there is a complete multipartite graph G on n vertices with F(G;k) = F(n;k). Also, for every k we construct a finite optimisation problem whose maximum is equal to the limit of log2F(n;k)/${n\choose 2}$ as n tends to infinity. Our final result is a stability theorem for complete multipartite graphs G, describing the asymptotic structure of such G with F(G;k) = F(n;k) · 2o(n2) in terms of solutions to the optimisation problem.
Quantitative risk assessment of the introduction of rabies into Japan through the importation of dogs and cats worldwide
Authors: KWAN N. C. L. , SUGIURA K. , HOSOI Y. , YAMADA A. , SNARY E. L.
Published: January 2017

Japan has been free from rabies since 1958. A strict import regimen has been adopted since 2004 consisting of identification of an animal with microchip, two-time rabies vaccination, neutralizing antibody titration test and a waiting period of 180 days. The present study aims to quantitatively assess the risk of rabies introduction into Japan through the international importation of dogs and cats and hence provide evidence-based recommendations to strengthen the current rabies prevention system. A stochastic scenario tree model was developed and simulations were run using @RISK. The probability of infection in a single dog or cat imported into Japan is estimated to be 2·16 × 10−9 [90% prediction interval (PI) 6·65 × 10−11–6·48 × 10−9]. The number of years until the introduction of a rabies case is estimated to be 49 444 (90% PI 19 170–94 641) years. The current import regimen is effective in maintaining the very low risk of rabies introduction into Japan and responding to future changes including increases in import level and rabies prevalence in the world. However, non-compliance or smuggling activities could substantially increase the risk of rabies introduction. Therefore, policy amendment which could promote compliance is highly recommended. Scenario analysis demonstrated that the waiting period could be reduced to 90 days and the requirement for vaccination could be reduced to a single vaccination, but serological testing should not be stopped.
Effect of a group intervention for children and their parents who have cancer
Authors: Kobayashi Mariko , Heiney Sue P. , Osawa Kaori , Ozawa Miwa , Matsushima Eisuke
Published: January 2017

Objective:

Although support programs for children whose parents have cancer have been described and evaluated, formal research has not been conducted to document outcomes. We adapted a group intervention called CLIMB®, originally developed in the United States, and implemented it in Tokyo, Japan, for school-aged children and their parents with cancer. The purpose of this exploratory pilot study was to examine the feasibility, acceptability, and impact of the Japanese version of the CLIMB® Program on children's stress and parents' quality of life and psychosocial distress.

Methods:

We enrolled children and parents in six waves of replicate sets for the six-week group intervention. A total of 24 parents (23 mothers and 1 father) diagnosed with cancer and 38 school-aged children (27 girls and 11 boys) participated in our study. Intervention fidelity, including parent and child satisfaction with the program, was examined. The impact of the program was analyzed using a quasiexperimental within-subject design comparing pre- and posttest assessments of children and parents in separate analyses.

Results:

Both children and parents experienced high levels of satisfaction with the program. Children's posttraumatic stress symptoms related to a parent's illness decreased after the intervention as measured by the Posttraumatic Stress Disorder–Reaction Index. No difference was found in children's psychosocial stress. The Functional Assessment of Chronic Illness Therapy scores indicated that parents' quality of life improved after the intervention in all domains except for physical well-being. However, no differences were found in parents' psychological distress and posttraumatic stress symptoms.

Significance of results:

Our results suggest that the group intervention using the CLIMB® Program relieved children's posttraumatic stress symptoms and improved parents' quality of life. The intervention proved the feasibility of delivering the program using manuals and training. Further research is needed to provide more substantiation for the benefits of the program.
Evaluation of seed components of wild soybean (Glycine soja) collected in Japan using near-infrared reflectance spectroscopy
Authors: Wee Chi-Do , Hashiguchi Masatsugu , Ishigaki Genki , Muguerza Melody , Oba Chika , Abe Jun , Harada Kyuya , Akashi Ryo
Published: January 2017

Seed composition, including the protein, lipid and sucrose contents of 334 accessions of wild soybean (Glycine soja) collected in Japan, was evaluated using near-infrared reflectance spectroscopy (NIRS) technology. The distribution of protein, lipid and sucrose contents and correlations among these three classes of seed components were determined. Protein, lipid and sucrose levels ranged in accessions from 48.6 to 57.0, 9.0 to 14.3 and 1.24 to 3.53%, respectively. Average levels of protein, lipid and sucrose in the accessions were 54, 11 and 2.5%, respectively. High negative correlations were observed between the protein and lipid contents, and the protein and sucrose contents. Mean levels of the three constituents were compared among collection sites classified by climatic conditions. The total protein content of accessions from regions with a high annual mean temperature was high. The protein content of accessions from the II-1 region was higher than those from the III-3 region, and the sucrose content from the II-1 region was lower than those from regions III-2 and IV-3. The lipid content of plants from the II-1 region was lower than those from other regions, and the accessions in region II had a higher protein content and lower sucrose and lipid contents than the other regions. These results provide diverse and wide-ranged protein, lipid and sucrose contents information of Japanese wild soybean resources according to climatic region; thus, providing a foundation for the future development and selection of new soybean varieties with desired traits in global environmental changes.
Mill ownership and farmer's cooperative behavior: the case of Costa Rica coffee farmers
Authors: HOPFENSITZ ASTRID , MIQUEL-FLORENSA JOSEPA
Published: January 2017

We analyze how Costa Rican coffee farmer's behavior in an experimental public good game depends on the institutional structure of the farmers buying point (cooperativevs.privately owned mills), and on the background of their game partners (partners selling to the same type of mill or not). We find that cooperative farmers do not display more public good orientation than private market farmers when playing with partners from the same type of mill. However, though farmers selling to private mills make no difference with respect to the background of partners, farmers selling to cooperatives significantly decrease contributions when paired with non-cooperative members. Finally, we study how self-selection into a mechanism that punishes the lowest contributors effects contributions both inside the group and with partners of the opposite background, and we show that it increases contributions by cooperative farmers interacting with non-cooperative farmers by more than 100%.
Placental 11 β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression very early during human pregnancy
Authors: Salvante K. G. , Milano K. , Kliman H. J. , Nepomnaschy P. A.
Published: January 2017

Maternal physiologic stress during gestation has been reported to be associated with negative developmental outcomes, including intra-uterine growth restriction and reduced birth weight, which can impact postnatal development, behavior and health. The human fetus is partially protected from elevated cortisol exposure by placental 11 β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which oxidizes bioactive cortisol into bio-inactive cortisone. Importantly, despite the critical protective role hypothesized for 11β-HSD2, the onset of its placental expression has yet to be clearly established. To this aim, we present immunocytochemical analysis of placentas collected 3–6 weeks post-conception. 11β-HSD2 was present as early as 3 weeks post-conception in syncytiotrophoblasts, where most maternal–fetal exchange occurs, and in columnar epithelial cells encircling uterine endometrial glands, which provide early histiopathic nutrition to the embryo. 11β-HSD2 expression in these critical maternal–fetal exchange areas is consistent with its hypothesized protective role. Future studies should investigate the mechanisms that may modulate embryonic glucocorticoid exposure earlier, immediately post-conception.
PHLPP regulates hexokinase 2-dependent glucose metabolism in colon cancer cells
Authors: Xiong Xiaopeng , Wen Yang-An , Mitov Mihail I , C Oaks Mary , Miyamoto Shigeki , Gao Tianyan
Published: January 2017

Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect. Bioenergetic analysis using Seahorse Extracelluar Flux Analyzer revealed that silencing PHLPP expression induced a glycolytic shift in colon cancer cells. Mechanistically, we found that PHLPP formed a complex with Akt and hexokinase 2 (HK2) in the mitochondrial fraction of colon cancer cells and knockdown of PHLPP enhanced Akt-mediated phosphorylation and mitochondrial localization of HK2. Depletion of HK2 expression or treating cells with Akt and HK2 inhibitors reversed PHLPP loss-induced increase in glycolysis. Furthermore, PHLPP knockdown cells became addicted to glucose as a major energy source in that glucose starvation significantly decreased cancer cell survival. As HK2 is the key enzyme that determines the direction and magnitude of glucose flux, our study identified PHLPP as a novel regulator of glucose metabolism by controlling HK2 activity in colon cancer cells.
Metal/oxide interfacial effects on the selective oxidation of primary alcohols
Authors: Zhao Guofeng , Yang Fan , Chen Zongjia , Liu Qingfei , Ji Yongjun , Zhang Yi , Niu Zhiqiang , Mao Junjie , Bao Xinhe , Hu Peijun , Li Yadong
Published: January 2017

A main obstacle in the rational development of heterogeneous catalysts is the difficulty in identifying active sites. Here we show metal/oxide interfacial sites are highly active for the oxidation of benzyl alcohol and other industrially important primary alcohols on a range of metals and oxides combinations. Scanning tunnelling microscopy together with density functional theory calculations on FeO/Pt(111) reveals that benzyl alcohol enriches preferentially at the oxygen-terminated FeO/Pt(111) interface and undergoes readily O–H and C–H dissociations with the aid of interfacial oxygen, which is also validated in the model study of Cu2O/Ag(111). We demonstrate that the interfacial effects are independent of metal or oxide sizes and the way by which the interfaces were constructed. It inspires us to inversely support nano-oxides on micro-metals to make the structure more stable against sintering while the number of active sites is not sacrificed. The catalyst lifetime, by taking the inverse design, is thereby significantly prolonged.
Divergent prion strain evolution driven by PrPC expression level in transgenic mice
Authors: Le Dur Annick , Laï Thanh Lan , Stinnakre Marie-George , Laisné Aude , Chenais Nathalie , Rakotobe Sabine , Passet Bruno , Reine Fabienne , Soulier Solange , Herzog Laetitia , Tilly Gaëlle , Rézaei Human , Béringue Vincent , Vilotte Jean-Luc , Laude Hubert
Published: January 2017

Prions induce a fatal neurodegenerative disease in infected host brain based on the refolding and aggregation of the host-encoded prion protein PrPC into PrPSc. Structurally distinct PrPSc conformers can give rise to multiple prion strains. Constrained interactions between PrPC and different PrPSc strains can in turn lead to certain PrPSc (sub)populations being selected for cross-species transmission, or even produce mutation-like events. By contrast, prion strains are generally conserved when transmitted within the same species, or to transgenic mice expressing homologous PrPC. Here, we compare the strain properties of a representative sheep scrapie isolate transmitted to a panel of transgenic mouse lines expressing varying levels of homologous PrPC. While breeding true in mice expressing PrPC at near physiological levels, scrapie prions evolve consistently towards different strain components in mice beyond a certain threshold of PrPC overexpression. Our results support the view that PrPC gene dosage can influence prion evolution on homotypic transmission.