bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can Human Flourishing Be Liberal?
Authors: Alexander Gregory S. 
Published: February 2019

The renewed interest in virtue ethics raises again a persistent question, namely, the relationship between the virtue ethics theory and liberalism as a political philosophy. Virtue ethicists focus on the good—i.e., human flourishing—and debate what constitutes that good. This focus creates a problem for liberals who are rights-oriented, which is the dominant form of contemporary liberalism.The recent and timely book by Menachem Mautner, Human Flourishing, Liberal Theory, and the Arts, reminds us, however, that liberalism comes in many stripes. There is no one liberalism. Rather, there are many liberalisms. I discuss three aspects of Mautner’s remarkable and important book: first, his conception of human flourishing and its relationship to liberalism; second, his argument that a liberal political order committed to human flourishing ought to promote the arts; and third, his argument that the liberalism of flourishing is better able than neutralist liberalism to compete with religion in providing what Mautner calls “Big Meaning.”
The Problem of Dependency of Corrective Justice: Corrective Entitlements and Private Transactions
Authors: Eenmaa-Dimitrieva Helen 
Published: February 2019

Several legal philosophers have argued that the principle of corrective justice provides the best explanation of various areas of the law—especially the law of torts. On the other hand, some philosophers of law and many economists of law have argued that the principle of corrective justice is not an independent principle of justice. I call this the problem of dependency. If the critics are right, the principle of corrective justice cannot be an explanation of a large area of our law as it claims to be.I argue that the increasingly complex forms of the problem of dependency that the critics have proposed lose their force once we have a better understanding of the principle of corrective justice and its relationships with other principles. The principle of corrective justice does not serve a conception of distributive justice or efficiency and can provide an explanation of a large area of our law despite the criticism. It does so independently as a principle of justice that is reflected in our legal practice.
Volatiles mediate host-selection in the corn hoppers Dalbulus maidis (Hemiptera: Cicadellidae) and Peregrinus maidis (Hemiptera: Delphacidae)
Authors: Coll Aráoz M.V. , Jacobi V.G. , Fernandez P.C. , Luft Albarracin E. , Virla E.G. , Hill J.G. , Catalán C.A.N. 
Published: February 2019

AbstractVolatile organic compounds (VOCs) released by plants are generally involved in host recognition and host selection for many phytophagous insects. However, for leafhoppers and planthoppers, host recognition is mainly thought to involve a phototactic response, but it is not clear if a host plant could be selected based on the volatile cues it emits. In this study we evaluated olfactory responses in dual choice tests of two Hemiptera species, Dalbulus maidis (De Long) (Cicadellidae) and Peregrinus maidis (Ashmead) (Delphacidae), vectors of maize-stunting diseases, to three maize (Zea mays L.) germplasms, a temperate and a tropical hybrid and a landrace. VOCs emitted by the germplasms were collected and identified using gas chromatography-mass spectrometry. The temperate hybrid released significantly more VOCs than the tropical hybrid and the landrace, and its volatile profile was dominated by (±)-linalool. D. maidis preferred odours emitted from the temperate hybrid, whereas P. maidis preferred odours from the tropical hybrid and the landrace over the temperate one. In order to test if linalool plays a role in the behavioural responses, we assayed this compound in combination with the tropical hybrid, to provide other contextual olfactory cues. D. maidis was attracted to the tropical hybrid plus a 0.0001% linalool solution, indicating that this compound could be part of a blend of attractants. Whereas addition of linalool resulted in a slight, though not significant, reduction in host VOC attractiveness for P. maidis. Both hopper species responded to olfactory cues in the absence of supplementary visual cues.
COCHIS: Stable and coherent implicits
Authors: SCHRIJVERS TOM , OLIVEIRA BRUNO C.D.S. , WADLER PHILIP , MARNTIROSIAN KOAR 
Published: February 2019

AbstractImplicit programming (IP) mechanisms infer values by type-directed resolution, making programs more compact and easier to read. Examples of IP mechanisms include Haskell’s type classes, Scala’s implicits, Agda’s instance arguments, Coq’s type classes and Rust’s traits. The design of IP mechanisms has led to heated debate: proponents of one school argue for the desirability of strong reasoning properties, while proponents of another school argue for the power and flexibility of local scoping or overlapping instances. The current state of affairs seems to indicate that the two goals are at odds with one another and cannot easily be reconciled. This paper presents COCHIS, the Calculus Of CoHerent ImplicitS, an improved variant of the implicit calculus that offers flexibility while preserving two key properties:coherenceandstability of type substitutions. COCHIS supports polymorphism, local scoping, overlapping instances, first-class instances and higher-order rules, while remaining type-safe, coherent and stable under type substitution. We introduce a logical formulation of how to resolve implicits, which is simple but ambiguous and incoherent, and a second formulation, which is less simple but unambiguous, coherent and stable. Every resolution of the second formulation is also a resolution of the first, but not conversely. Parts of the second formulation bear a close resemblance to a standard technique for proof search called focusing. Moreover, key for its coherence is a rigorous enforcement of determinism.
Taxing the bilingual mind: Effects of simultaneous interpreting experience on verbal and executive mechanisms
Authors: García Adolfo M. , Muñoz Edinson , Kogan Boris 
Published: February 2019

AbstractThis paper reviews the neurocognitive particularities of subjects with sustained experience in simultaneous interpreting, a highly demanding form of bilingual processing. The literature converges into three broad empirical patterns. First, significant neurocognitive differences, including behavioral enhancements in verbal and executive domains, are observable after only one or two years of training. Second, such effects, both in interpreting students and/or professional interpreters, seem robust for crucial linguistic (e.g., translation) and executive (e.g., working memory) aspects of the activity, but not for more marginally relevant ones (e.g., conflict resolution) – suggesting that they are non-generalizable beyond directly taxed functions. Third, though more tentatively, some of the observed verbal and executive effects seem to be mutually independent and uninfluenced by other bilingual-experience-related factors (e.g., L2 competence), which could highlight their distinctive relation with interpreting practice. In sum, this particular model of expertise sheds novel light on the adaptive capacity of cognitive systems in bilinguals.
Adults with familial hypercholesterolaemia have healthier dietary and lifestyle habits compared with their non-affected relatives: the SAFEHEART study
Authors: Arroyo-Olivares Raquel , Alonso Rodrigo , Quintana-Navarro Gracia , Fuentes-Jiménez Francisco , Mata Nelva , Muñiz-Grijalvo Ovidio , Díaz-Díaz José L , Zambón Daniel , Arrieta Francisco , García-Cruces Jesús , Garrido-Sanjuan Juan A , Banegas José R , Mata Pedro 
Published: February 2019

AbstractObjectiveHealthy lifestyle habits are the cornerstone in the management of familial hypercholesterolaemia (FH). Nevertheless, dietary studies on FH-affected populations are scarce. The present study analyses dietary habits, adherence to a Mediterranean diet pattern and physical activity in an adult population with FH and compares them with their non-affected relatives.DesignCross-sectional study.SettingData came from SAFEHEART, a nationwide study in Spain.ParticipantsIndividuals (n 3714) aged ≥18 years with a genetic diagnosis of FH (n2736) and their non-affected relatives (n 978). Food consumption was evaluated using a validated FFQ.ResultsTotal energy intake was lower in FH patients v. non-affected relatives (P<0·005). Percentage of energy from fats was also lower in the FH population (35 % in men, 36 % in women) v. those non-affected (38 % in both sexes, P<0·005), due to the lower consumption of saturated fats (12·1 % in FH patients, 13·2 % in non-affected, P<0·005). Consumption of sugars was lower in FH patients v. non-affected relatives (P<0·05). Consumption of vegetables, fish and skimmed milk was higher in the FH population (P<0·005). Patients with FH showed greater adherence to a Mediterranean diet pattern v. non-affected relatives (P<0·005). Active smoking was lower and moderate physical activity was higher in people with FH, especially women (P<0·005).ConclusionsAdult patients with FH report healthier lifestyles than their non-affected family members. They eat a healthier diet, perform more physical activity and smoke less. However, this patient group’s consumption of saturated fats and sugars still exceeds guidelines.
Evaluating a heat-tolerant wheat germplasm in a heat stress environment
Authors: Lordkaew Sittichai , Yimyam Narit , Wongtamee Anupong , Jamjod Sansanee , Rerkasem Benjavan 
Published: February 2019

AbstractHeat stress, a regular risk to wheat in the subtropics, is a growing threat in other wheat producing regions as the global temperature rises. This paper reports on three experiments evaluating 49 entries of the 13th High Temperature Wheat Yield Trial (13HTWYT) from the International Centre for Maize and Wheat Improvement (distributed in 2014), with Fang 60 as the local check, at two locations at Chiang Mai, Thailand, a designated representative of the wheat mega-environment 5, in which temperature for the coolest month averages &gt;17.5 °C and the crop is subjected to high temperature for the entire growing season. The wheat was grown in the lowland (elevation 330 m) at Chiang Mai University in (i) sand culture to simulate the condition of non-limiting nutrient and water supply and (ii) in the field and (iii) as an on-farm trial in the highlands (elevation 800 m) at Mae Wang district of Chiang Mai province. Heat tolerance in the wheat germplasm, recently developed for adaptation to high temperature, was indicated by longer pre-heading duration, and the positive correlation between days to heading and grain yield all three experiments. The longer time before heading enabled development of larger spikes that produced more seeds from more and larger spikelets and more competent florets. However, with the number of spikes that was either lower than or similar to Fang 60, none of the recently developed 13HTWYT entries out-yielded the local check from the 1970s.
Disruption of the FasL/Fas axis protects against inflammation-derived tumorigenesis in chronic liver disease
Authors: Cubero Francisco Javier , Woitok Marius Maximilian , Zoubek Miguel E. , de Bruin Alain , Hatting Maximilian , Trautwein Christian 
Published: February 2019

AbstractFas Ligand (FasL) and Fas (APO-1/CD95) are members of the TNFR superfamily and may trigger apoptosis. Here, we aimed to elucidate the functional role of Fas signaling in an experimental model of chronic liver disease, the hepatocyte-specific NEMO knockout (NEMOΔhepa) mice. We generated NEMOΔhepa /Faslpr mice, while NEMOΔhepa, NEMOf/f as well as Faslpranimals were used as controls, and characterized their phenotype during liver disease progression. Liver damage was evaluated by serum transaminases, histological, immunofluorescence procedures, and biochemical and molecular biology techniques. Proteins were detected by western Blot, expression of mRNA by RT-PCR, and infiltration of inflammatory cells was determined by FACs analysis, respectively. Faslpr mutation in NEMOΔhepa mice resulted in overall decreased liver injury, enhanced hepatocyte survival, and reduced proliferation at 8 weeks of age compared with NEMOΔhepa mice. Moreover, NEMOΔhepa/Faslpr animals elicited significantly decreased parameters of liver fibrosis, such as Collagen IA1, MMP2, and TIMP1, and reduced proinflammatory macrophages and cytokine expression. At 52 weeks of age, NEMOΔhepa/Faslpr exhibited less malignant growth as evidenced by reduced HCC burden associated with a significantly decreased number of nodules and LW/BW ratio and decreased myeloid populations. Deletion of TNFR1 further reduced tumor load of 52-weeks-old NEMOΔhepa/Faslpr mice. The functionality of FasL/Fas might affect inflammation-driven tumorigenesis in an experimental model of chronic liver disease. These results help to develop alternative therapeutic approaches and extend the limitations of tumor therapy against HCC.
Defective proteostasis in celiac disease as a new therapeutic target
Authors: Maiuri Luigi , Villella Valeria R , Piacentini Mauro , Raia Valeria , Kroemer Guido 
Published: February 2019

AbstractCystic fibrosis (CF) is a disease caused by loss-of-function mutations affecting the CF transmembrane conductance regulator (CFTR), a chloride channel. Recent evidence indicates that CFTR is inhibited by a gluten/gliadin-derived peptide (P31-43), causing an acquired state of CFTR inhibition within the gut that contributes to the pathogenesis of celiac disease (CD). Of note, CFTR inhibition does not only cause intra- and extracellular ion imbalances but also affects proteostasis by activating transglutaminase-2 (TGM2) and by disabling autophagy. These three phenomena (CFTR inhibition, TGM2 activation, and autophagy impairment) engage in multiple self-amplifying circuitries, thus forming an “infernal trio”. The trio hinders enterocytes from returning to homeostasis and instead locks them in an irreversible pro-inflammatory state that ultimately facilitates T lymphocyte-mediated immune responses against another gluten/gliadin-derived peptide (P57–68), which,upon deamidation by activated TGM2, becomes fully antigenic. Hence, the pathogenic protein gliadin exemplifies a food constituent the exceptional immunogenicity of which arises from a combination of antigenicity (conferred by deaminated P57–68) and adjuvanticity (conferred by P31-43). CF can be treated by agents targeting the “infernal trio” including CFTR potentiators, TGM2 inhibitors, and autophagy enhancers. We speculate that such agents may also be used for CD therapy and indeed could constitute close-to-etiological treatments of this enteropathy.
CIC protein instability contributes to tumorigenesis in glioblastoma
Authors: Bunda Severa , Heir Pardeep , Metcalf Julie , Li Annie Si Cong , Agnihotri Sameer , Pusch Stefan , Yasin Mamatjan , Li Mira , Burrell Kelly , Mansouri Sheila , Singh Olivia , Wilson Mark , Alamsahebpour Amir , Nejad Romina , Choi Bethany , Kim David , von Deimling Andreas , Zadeh Gelareh , Aldape Kenneth 
Published: February 2019

AbstractCapicua (CIC) is a transcriptional repressor that counteracts activation of genes downstream of receptor tyrosine kinase (RTK)/Ras/ERK signaling. It is well-established that tumorigenesis, especially in glioblastoma (GBM), is attributed to hyperactive RTK/Ras/ERK signaling. While CIC is mutated in other tumors, here we show that CIC has a tumor suppressive function in GBM through an alternative mechanism. We find that CIC protein levels are negligible in GBM due to continuous proteasome-mediated degradation, which is mediated by the E3 ligase PJA1 and show that this occurs through binding of CIC to its DNA target and phosphorylation on residue S173. PJA1 knockdown increased CIC stability and extended survival using in-vivo models of GBM. Deletion of the ERK binding site resulted in stabilization of CIC and increased therapeutic efficacy of ERK inhibition in GBM models. Our results provide a rationale to target CIC degradation in Ras/ERK-driven tumors, including GBM, to increase efficacy of ERK inhibitors.
Chaperone activation and client binding of a 2-cysteine peroxiredoxin
Authors: Teixeira Filipa , Tse Eric , Castro Helena , Makepeace Karl A. T. , Meinen Ben A. , Borchers Christoph H. , Poole Leslie B. , Bardwell James C. , Tomás Ana M. , Southworth Daniel R. , Jakob Ursula 
Published: February 2019

AbstractMany 2-Cys-peroxiredoxins (2-Cys-Prxs) are dual-function proteins, either acting as peroxidases under non-stress conditions or as chaperones during stress. The mechanism by which 2-Cys-Prxs switch functions remains to be defined. Our work focuses on Leishmania infantum mitochondrial 2-Cys-Prx, whose reduced, decameric subpopulation adopts chaperone function during heat shock, an activity that facilitates the transition from insects to warm-blooded host environments. Here, we have solved the cryo-EM structure of mTXNPx in complex with a thermally unfolded client protein, and revealed that the flexible N-termini of mTXNPx form a well-resolved central belt that contacts and encapsulates the unstructured client protein in the center of the decamer ring. In vivo and in vitro cross-linking studies provide further support for these interactions, and demonstrate that mTXNPx decamers undergo temperature-dependent structural rearrangements specifically at the dimer-dimer interfaces. These structural changes appear crucial for exposing chaperone-client binding sites that are buried in the peroxidase-active protein.
Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy
Authors: Caswell-Jin Jennifer L. , McNamara Katherine , Reiter Johannes G. , Sun Ruping , Hu Zheng , Ma Zhicheng , Ding Jie , Suarez Carlos J. , Tilk Susanne , Raghavendra Akshara , Forte Victoria , Chin Suet-Feung , Bardwell Helen , Provenzano Elena , Caldas Carlos , Lang Julie , West Robert , Tripathy Debu , Press Michael F. , Curtis Christina 
Published: February 2019

AbstractGenomic changes observed across treatment may result from either clonal evolution or geographically disparate sampling of heterogeneous tumors. Here we use computational modeling based on analysis of fifteen primary breast tumors and find that apparent clonal change between two tumor samples can frequently be explained by pre-treatment heterogeneity, such that at least two regions are necessary to detect treatment-induced clonal shifts. To assess for clonal replacement, we devise a summary statistic based on whole-exome sequencing of a pre-treatment biopsy and multi-region sampling of the post-treatment surgical specimen and apply this measure to five breast tumors treated with neoadjuvant HER2-targeted therapy. Two tumors underwent clonal replacement with treatment, and mathematical modeling indicates these two tumors had resistant subclones prior to treatment and rates of resistance-related genomic changes that were substantially larger than previous estimates. Our results provide a needed framework to incorporate primary tumor heterogeneity in investigating the evolution of resistance.
Electrochromic semiconductors as colorimetric SERS substrates with high reproducibility and renewability
Authors: Cong Shan , Wang Zhen , Gong Wenbin , Chen Zhigang , Lu Weibang , Lombardi John R. , Zhao Zhigang 
Published: February 2019

AbstractElectrochromic technology has been actively researched for displays, adjustable mirrors, smart windows, and other cutting-edge applications. However, it has never been proposed to overcome the critical problems in the field of surface-enhanced Raman scattering (SERS). Herein, we demonstrate a generic electrochromic strategy for ensuring the reproducibility and renewability of SERS substrates, which are both scientifically and technically important due to the great need for quantitative analysis, standardized production and low cost in SERS. This color-changing strategy is based on a unique quantitative relationship between the SERS signal amplification and the coloration degree within a certain range, in which the SERS activity of the substrate can be effectively inferred by judging the degree of color change. Our results may provide a first step toward the rational design of electrochromic SERS substrates with a high sensitivity, reproducibility, and renewability.
A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs
Authors: Stein Derek R. , Warner Bryce M. , Soule Geoff , Tierney Kevin , Frost Kathy L. , Booth Stephanie , Safronetz David 
Published: February 2019

AbstractThe World Health Organization has identified Lassa virus (LASV) as one of the top five pathogens to cause a severe outbreak in the near future. This study assesses the ability of a leading vaccine candidate, recombinant Vesicular stomatitis virus expressing LASV glycoprotein (VSVΔG/LASVGPC), and its ability to induce rapid and long-term immunity to lethal guinea pig-adapted LASV (GPA-LASV). Outbred guinea pigs were vaccinated with a single dose of VSVΔG/LASVGPC followed by a lethal challenge of GPA-LASV at 7, 14, 25, 189, and 355 days post-vaccination. Statistically significant rapid and long-term protection was achieved at all time points with 100% protection at days 7 and 14 post-vaccination. While 83 and 87% protection were achieved at 25 days and 6 months post-vaccination, respectively. When guinea pigs were challenged one year after vaccination 71% protection was achieved. Notable infectious virus was isolated from the serum and tissues of some but not all animals. Total LASVGPC-specific IgG titers were also measured on a monthly basis leading up to LASV challenge however, it is unclear if antibody alone correlates with short and long term survival. These studies confirm that a single dose of VSVΔG/LASVGPC can induce rapid and long-term protection from LASV infection in an aggressive outbred model of infection, and supports further development in non-human primates.
Metapopulation Model from Pathogen’s Perspective: A Versatile Framework to Quantify Pathogen Transfer and Circulation between Environment and Hosts
Authors: Chen Shi , Lanzas Cristina , Lee Chihoon , Zenarosa Gabriel L. , Arif Ahmed A. , Dulin Michael 
Published: February 2019

AbstractMetapopulation models have been primarily explored in infectious disease epidemiology to study host subpopulation movements and between-host contact structures. They also have the potential to investigate environmental pathogen transferring. In this study, we demonstrate that metapopulation models serve as an ideal modeling framework to characterize and quantify pathogen transfer between environment and hosts. It therefore unifies host, pathogen, and environment, collectively known as the epidemiological triad, a fundamental concept in epidemiology. We develop a customizable and generalized pathogen-transferring model where pathogens dwell in and transferring (via contact) between environment and hosts. We analyze three specific case studies: pure pathogen transferring without pathogen demography, source-sink dynamics, and pathogen control via external disinfection. We demonstrate how pathogens circulate in the system between environment and hosts, as well as evaluate different controlling efforts for healthcare-associated infections (HAIs). For pure pathogen transferring, system equilibria can be derived analytically to explicitly quantify long-term pathogen distribution in the system. For source-sink dynamics and pathogen control via disinfection, we demonstrate that complete eradication of pathogens can be achieved, but the rates of converging to system equilibria differ based on specific model parameterization. Direct host-host pathogen transferring and within-host dynamics can be future directions of this modeling framework by adding specific modules.