bluuebunny/crossref_metadata_2025 huggingface dataset:
OIL PRICE FORECASTS FOR THE LONG TERM: EXPERT OUTLOOKS, MODELS, OR BOTH?
Authors: Bernard Jean-Thomas , Khalaf Lynda , Kichian Maral , Yelou Clement
Published: June 2017

Little is known about the accuracy of expert outlooks, so heavily relied upon by industry participants and policy makers, regarding the future path of oil prices. Using the regular publications by the Energy Information Administration (EIA), we examine the accuracy of annual recursive oil price forecasts generated by the National Energy Modeling System model of the Agency for forecast horizons of up to 15 years. Our results reveal that the EIA model outperforms the benchmark random walk model around the two ends of the forecast horizon spectrum. Additionally, at the longer horizons, simple econometric forecasting models often produce similar, if not better accuracy than the EIA model. Time varying such specifications generally also exhibit stability in their forecast performance. Finally, although combining forecasts does not change the overall patterns, some additional accuracy gains are obtained at intermediate horizons, and in some cases, forecast performance stability is also achieved.
THE ROLE OF EDUCATION SIGNALING IN EXPLAINING THE GROWTH OF THE COLLEGE WAGE PREMIUM
Authors: Zheng Yu
Published: June 2017

This paper incorporates an education signaling mechanism into a dynamic model of production and asks if “higher education as a signal” helps explain the simultaneous increase in the supply and price of skilled relative to unskilled labor in the United States since 1980. The key mechanism is that if college degrees serve as a signal of unobservable talent and talent is productive at the workplace, then improved access to college will enable a higher fraction of the population to signal talent by completing college, resulting in degrees being a better signal about talent and a widening skill premium. When I assess the contribution of signaling in the model calibrated to the US economy from 1980 to 2003, I find that about 10% of the increase in the skill premium can be attributed to the signaling mechanism, after adjusting for the potential decline in the quality of college graduates.
UNBUNDLING FINANCIAL IMPERFECTIONS: LENDING FRICTIONS VS. TRADING FRICTIONS
Authors: Uras Burak R.
Published: June 2017

Two essential imperfections determine the degree of the financial sector development in an economy: lending frictions, which constrain the ability to extend loans to borrowers; and, trading frictions, which constrain the trading of these loans in secondary markets. I develop a dynamic general equilibrium model where long-term investment is the engine of growth to study macroeconomic consequences of financial development. In the model, long-term loans are extended to entrepreneurs in a primary market and then traded in a secondary market among financiers. In competitive equilibria, reductions in either lending or trading frictions enlarge the financial sector. Although financial deepening through low-cost lending is always welfare improving, financial deepening stimulated by low-cost trading could be detrimental to the society. I illustrate that a model qualitatively consistent with the U.S. financial development episode of the last 30 years should exhibit disproportionately large reductions in trading frictions relative to lending frictions.
Rotating alfalfa with dry bean as an alternative to corn-soybean rotations in organic systems in the Upper Midwest
Authors: Tautges Nicole , Flavin Claire , Michaels Thomas , Ehlke Nancy , Lamb John , Jungers Jacob , Sheaffer Craig
Published: June 2017

Dry bean (Phaseolus vulgaris) can be grown as a local food source and as an alternative to soybean (Glycine max) to diversify organic crop rotations. To understand the benefits of diversification of organic cropping systems, the effects of preceding alfalfa (Medicago sativa) and corn (Zea mays) crops on yields of five dry bean types and one soybean type, and the effect of bean type on following spring wheat (Triticum aestivum) yields, were tested at four Minnesota locations. Dry bean and soybean yields following alfalfa were 25% greater than yields following corn at two of four locations, though bean yields following corn were greater at one location. A preceding alfalfa crop benefited bean yields at locations where hog manure or no manure was applied to corn, whereas bean yields following corn fertilized with cow manure were similar to or greater than bean yields following alfalfa. Among dry bean types, black bean yielded similarly to soybean at three of four locations, but dark red kidney bean consistently yielded 25–65% lower than soybean. Navy, pinto and heirloom dry bean types yielded similarly to soybean at two of four locations. Across locations, weed biomass was 3–15 times greater in dry bean than in soybean and dry bean yield response to weed competition varied among bean types. However, dry bean, regardless of the preceding crop, demonstrated the potential to produce yields comparable with soybean in organic systems and the substitution of dry bean for soybean did not affect subsequent wheat yields. More studies are needed to identify nitrogen fertility dynamics in organic systems as they relate to dry bean yield.
Standards, Networks, and the Political Economy of International Lawmaking: A Response to Stavros Gadinis
Authors: Stephan Paul B.
Published: June 2017

Three Pathways to Global Standards broadens our understanding of structures that undergird international cooperation. Stavros Gadinis argues that different kinds of lawmaking networks propagate differently. Private networks depend on market success, in the sense that the demand for their products rests on competition in the private sector. Regulators succeed when they cooperate with true peers. States use power to work their will. I have some second-order criticisms of the article, offered in the spirit of respectful engagement with good scholarship. These reservations, however, do not detract from a view that Gadinis has identified significant issues in international relations and has proposed useful theses about them as well as good strategies for their validation.
Conventionality Control the New Doctrine of the Inter-American Court of Human Rights
Authors: Mac-Gregor Eduardo Ferrer
Published: June 2017

One of the most recent and most effective efforts of the Inter-American Court of Human Rights (Inter-American Court) to increase the level of compliance with the American Convention on Human Rights (ACHR) has been the creation of the “conventionality control” doctrine. The Inter-American Court describes this as a “mechanism for the application of International Law,” mainly “International Human Rights Law, and specifically the American Convention and its sources, including this Court’s jurisprudence.”
Democracy and Rights in Gelman v. Uruguay
Authors: Gargarella Roberto
Published: June 2017

On 24 February 2011, the Inter-American Court of Human Rights (IACtHR) issued its decision in Gelman v. Uruguay, condemning Uruguay for the forced disappearance of María Claudia García Iruretagoyena de Gelman and the kidnapping of her daughter Macarena Gelman during the military dictatorship. In the decision, the Court ordered Uruguay to remove all obstacles that enabled those responsible for the crimes to go unpunished. Accordingly, it declared that Law 15848 on the Expiry of Punitive Claims of the State (“Expiry Law”), a 1986 amnesty law that prevented the prosecution of people who had committed serious human rights violations during the military dictatorship, was incompatible with the American Convention on Human Rights and the Inter-American Convention on Forced Disappearance of Persons, and therefore lacked legal effect. That the law had been passed democratically and subsequently reaffirmed two times by popular referendums did not change the Court’s evaluation or impede the Court from annulling it.
Energy, Consumption, and the Amorality of Energy Law
Authors: Davies Lincoln L.
Published: June 2017

As the world turns its attention to Paris this December, all eyes will be on international decisionmakers, including those from the United States, to see if meaningful progress on climate change can finally be made. Climate change, of course, is the great environmental challenge of our time, a challenge that is irrevocably bound up with energy production and consumption. This “super wicked” problem long has been seen as a political, economic, ecological, and social one. However, as Pope Francis’ encyclical makes clear, it is a moral problem as well.
Horizontal Enforcement and the ILC’s Proposed Draft Articles on the Immunity of State Officials from Foreign Criminal Jurisdiction
Authors: Keitner Chimène I.
Published: June 2017

The Nuremberg principles affirmed by the U.N. General Assembly and formulated by the International Law Commission (ILC) provide that “[t]he fact that a person who committed an act which constitutes a crime under international law acted as Head of State or responsible Government official does not relieve him (sic) from responsibility under international law.” Few would dispute this basic principle. More contested is the question of who has authority to impose consequences on individuals for international crimes committed on behalf of states. This is because, if an individual has acted with actual or apparent state authority, imposing consequences on the individual without her state’s consent runs counter to traditional notions of state sovereignty and noninterference.
Aggression, Affected States, and a Right to Participate: A Response to Koh and Buchwald
Authors: Williams Sarah
Published: June 2017

At the review conference in Kampala, States Parties adopted three new provisions on the crime of aggression for inclusion in the Rome Statute, as well as consequential amendments to the Elements of Crimes. However, states parties did not consider revisions to the procedural arrangements that may be required to accommodate the crime of aggression. The crime of aggression requires a link to states, being limited to acts of aggression by one state against another state. The individuals that can be charged with the crime of aggression are persons “in a position effectively to exercise control over or to direct the political or military action of a State.” The crime is also connected to the international security framework, in particular the UN Charter. Given that aggression is intrinsically linked to state acts, it is “likely that the ICC [International Criminal Court] would need relevant states to cooperate, present evidence, and argue the case.” Yet the existing framework does not include an adequate right of participation for affected states. This contribution suggests one possible revision to provide a clearer legal basis for states to participate directly in ICC proceedings in respect of the crime of aggression.
Panelists, Arbitrators, Judges: A Response to Joost Pauwelyn
Authors: Sacerdoti Giorgio
Published: June 2017

I must state from the outset that I am not convinced that an analysis like the one conducted by Joost Pauwelyn, though valuable from a statistical and quantitative point of view, is really apt to explain the different functioning of legal institutions, their efficiency in term of results achieved in relation to objectives, the satisfaction of the various group of users and the reasons for their being subjected to criticism. The different architecture of the trade and investment systems reflects different constituencies, objectives and needs. Praise and criticism come from different groups of users and nonusers, and they change over time due to changing perceptions, objectives, and interests.
Judging from Venus: A Response to Joost Pauwelyn
Authors: Marceau Gabrielle , Quinn Catherine , Hoyos Juan Pablo Moya
Published: June 2017

In this short response, we offer some additional context to the appointment of government officials as World Trade Organization (WTO) panelists, some information on the role of the Secretariat and areas of cross-fertilization.

The Involvement of Panel Members Working for Government

Pauwelyn emphasizes that a significant proportion of WTO panel members have a substantial government background. His numbers indicate that for the period 1995-2014, 88 percent of WTO panelists had worked a minimum of “three years in government as diplomats, negotiators, bureaucrats, ministers and so on.” However, if we look at whether the panelists are employed by governments, either as diplomats or trade specialists, at the time of their appointment as WTO panelists, the figure changes dramatically: only about 50 percent of WTO panelists are employed in government at the time of their nomination. In accordance with Article 8.9 of the Dispute Settlement Understanding (DSU), the procedural rules applicable to WTO dispute settlement proceedings, panelists serve in their individual capacities and not as government representatives.
Why Sexual Assault in Intimate Relationships Must be Criminalized as Required by International Human Rights Law: A Response to the Symposium Comments
Authors: Randall Melanie , Venkatesh Vasanthi
Published: June 2017

Ending the marital rape exemption in criminal law is a demand for legal equality and autonomy for women, rights that are enshrined in international human rights law. Drawing on international human rights law as a source of authority for challenging the marital rape exception in criminal law allows feminist and other social justice organizations, within their specific national and local contexts, to seek greater state action and accountability toward ending this form of violence against women and this violation of women’s human rights. In this reply, we challenge the arguments in the symposium that oppose or caution against criminalizing sexual violence in intimate relationships as a necessary legal strategy, and that refute our view that ending the marital rape exemption is required by international human rights law.
The Asian Summer Monsoon Launches Pollutants Around the Globe
Authors: Wheeling Kate
Published: June 2017

New research provides a comprehensive overview of the effect of the Asian summer monsoon (ASM) on atmospheric composition throughout the life cycle of the ASM anticyclone.
Multiplex gene regulation by CRISPR-ddCpf1
Authors: Zhang Xiaochun , Wang Jingman , Cheng Qiuxiang , Zheng Xuan , Zhao Guoping , Wang Jin
Published: June 2017

The clustered regularly interspaced short palindromic repeats (CRISPR)/dCas9 system has been widely applied in both transcriptional regulation and epigenetic studies. However, for multiple targets, independent expression of multiple single guide RNAs (sgRNAs) is needed, which is less convenient. To address the problem, we employed a DNase-dead Cpf1 mutant (ddCpf1) for multiplex gene regulation. We demonstrated that ddCpf1 alone could be employed for gene repression in Escherichia coli, and the repression was more effective with CRISPR RNAs (crRNAs) specifically targeting to the template strand of its target genes, which was different from that of dCas9. When targeting the promoter region, both strands showed effective repression by the ddCpf1/crRNA complex. The whole-transcriptome RNA-seq technique was further employed to demonstrate the high specificity of ddCpf1-mediated repression. Besides, we proved that the remaining RNase activity in ddCpf1 was capable of processing a precursor CRISPR array to simply generate multiple mature crRNAs in vivo, facilitating multiplex gene regulation. With the employment of this multiplex gene regulation strategy, we also showed how to quickly screen a library of candidate targets, that is, the two-component systems in E. coli. Therefore, based on our findings here, the CRISPR-ddCpf1 system may be further developed and widely applied in both biological research and clinical studies.
A molecular portrait of microsatellite instability across multiple cancers
Authors: Cortes-Ciriano Isidro , Lee Sejoon , Park Woong-Yang , Kim Tae-Min , Park Peter J.
Published: June 2017

Microsatellite instability (MSI) refers to the hypermutability of short repetitive sequences in the genome caused by impaired DNA mismatch repair. Although MSI has been studied for decades, large amounts of sequencing data now available allows us to examine the molecular fingerprints of MSI in greater detail. Here, we analyse ∼8,000 exomes and ∼1,000 whole genomes of cancer patients across 23 cancer types. Our analysis reveals that the frequency of MSI events is highly variable within and across tumour types. We also identify genes in DNA repair and oncogenic pathways recurrently subject to MSI and uncover non-coding loci that frequently display MSI. Finally, we propose a highly accurate exome-based predictive model for the MSI phenotype. These results advance our understanding of the genomic drivers and consequences of MSI, and our comprehensive catalogue of tumour-type-specific MSI loci will enable panel-based MSI testing to identify patients who are likely to benefit from immunotherapy.
Global metabolic interaction network of the human gut microbiota for context-specific community-scale analysis
Authors: Sung Jaeyun , Kim Seunghyeon , Cabatbat Josephine Jill T. , Jang Sungho , Jin Yong-Su , Jung Gyoo Yeol , Chia Nicholas , Kim Pan-Jun
Published: June 2017

A system-level framework of complex microbe–microbe and host–microbe chemical cross-talk would help elucidate the role of our gut microbiota in health and disease. Here we report a literature-curated interspecies network of the human gut microbiota, called NJS16. This is an extensive data resource composed of ∼570 microbial species and 3 human cell types metabolically interacting through >4,400 small-molecule transport and macromolecule degradation events. Based on the contents of our network, we develop a mathematical approach to elucidate representative microbial and metabolic features of the gut microbial community in a given population, such as a disease cohort. Applying this strategy to microbiome data from type 2 diabetes patients reveals a context-specific infrastructure of the gut microbial ecosystem, core microbial entities with large metabolic influence, and frequently produced metabolic compounds that might indicate relevant community metabolic processes. Our network presents a foundation towards integrative investigations of community-scale microbial activities within the human gut.
Extreme temperatures in Southeast Asia caused by El Niño and worsened by global warming
Authors: Thirumalai Kaustubh , DiNezio Pedro N. , Okumura Yuko , Deser Clara
Published: June 2017

In April 2016, southeast Asia experienced surface air temperatures (SATs) that surpassed national records, exacerbated energy consumption, disrupted agriculture and caused severe human discomfort. Here we show using observations and an ensemble of global warming simulations the combined impact of the El Niño/Southern Oscillation (ENSO) phenomenon and long-term warming on regional SAT extremes. We find a robust relationship between ENSO and southeast Asian SATs wherein virtually all April extremes occur during El Niño years. We then quantify the relative contributions of long-term warming and the 2015–16 El Niño to the extreme April 2016 SATs. The results indicate that global warming increases the likelihood of record-breaking April extremes where we estimate that 29% of the 2016 anomaly was caused by warming and 49% by El Niño. These post-Niño Aprils can potentially be anticipated a few months in advance, and thus, help societies prepare for the projected continued increases in extremes.
Possible absence of critical thickness and size effect in ultrathin perovskite ferroelectric films
Authors: Gao Peng , Zhang Zhangyuan , Li Mingqiang , Ishikawa Ryo , Feng Bin , Liu Heng-Jui , Huang Yen-Lin , Shibata Naoya , Ma Xiumei , Chen Shulin , Zhang Jingmin , Liu Kaihui , Wang En-Ge , Yu Dapeng , Liao Lei , Chu Ying-Hao , Ikuhara Yuichi
Published: June 2017

Although the size effect in ferroelectric thin films has been known for long time, the underlying mechanism is not yet fully understood and whether or not there is a critical thickness below which the ferroelectricity vanishes is still under debate. Here, we directly measure the thickness-dependent polarization in ultrathin PbZr0.2Ti0.8O3 films via quantitative annular bright field imaging. We find that the polarization is significantly suppressed for films <10-unit cells thick (∼4 nm). However, approximately the polarization never vanishes. The residual polarization is ∼16 μCcm−2 (∼17%) at 1.5-unit cells (∼0.6 nm) thick film on bare SrTiO3 and ∼22 μCcm−2 at 2-unit cells thick film on SrTiO3 with SrRuO3 electrode. The residual polarization in these ultrathin films is mainly attributed to the robust covalent Pb–O bond. Our atomic study provides new insights into mechanistic understanding of nanoscale ferroelectricity and the size effects.
Multimode entanglement in reconfigurable graph states using optical frequency combs
Authors: Cai Y. , Roslund J. , Ferrini G. , Arzani F. , Xu X. , Fabre C. , Treps N.
Published: June 2017

Multimode entanglement is an essential resource for quantum information processing and quantum metrology. However, multimode entangled states are generally constructed by targeting a specific graph configuration. This yields to a fixed experimental setup that therefore exhibits reduced versatility and scalability. Here we demonstrate an optical on-demand, reconfigurable multimode entangled state, using an intrinsically multimode quantum resource and a homodyne detection apparatus. Without altering either the initial squeezing source or experimental architecture, we realize the construction of thirteen cluster states of various sizes and connectivities as well as the implementation of a secret sharing protocol. In particular, this system enables the interrogation of quantum correlations and fluctuations for any multimode Gaussian state. This initiates an avenue for implementing on-demand quantum information processing by only adapting the measurement process and not the experimental layout.
Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
Authors: Axelsson A. S. , Mahdi T. , Nenonen H. A. , Singh T. , Hänzelmann S. , Wendt A. , Bagge A. , Reinbothe T. M. , Millstein J. , Yang X. , Zhang B. , Gusmao E. G. , Shu L. , Szabat M. , Tang Y. , Wang J. , Salö S. , Eliasson L. , Artner I. , Fex M. , Johnson J. D. , Wollheim C. B. , Derry J.M.J. , Mecham B. , Spégel P. , Mulder H. , Costa I.G. , Zhang E. , Rosengren A. H.
Published: June 2017

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.
Split-BioID a conditional proteomics approach to monitor the composition of spatiotemporally defined protein complexes
Authors: Schopp Isabel Myriam , Amaya Ramirez Cinthia Claudia , Debeljak Jerneja , Kreibich Elisa , Skribbe Merle , Wild Klemens , Béthune Julien
Published: June 2017

Understanding the function of the thousands of cellular proteins is a central question in molecular cell biology. As proteins are typically part of multiple dynamic and often overlapping macromolecular complexes exerting distinct functions, the identification of protein–protein interactions (PPI) and their assignment to specific complexes is a crucial but challenging task. We present a protein fragments complementation assay integrated with the proximity-dependent biotinylation technique BioID. Activated on the interaction of two proteins, split-BioID is a conditional proteomics approach that allows in a single and simple assay to both experimentally validate binary PPI and to unbiasedly identify additional interacting factors. Applying our method to the miRNA-mediated silencing pathway, we can probe the proteomes of two distinct functional complexes containing the Ago2 protein and uncover the protein GIGYF2 as a regulator of miRNA-mediated translation repression. Hence, we provide a novel tool to study dynamic spatiotemporally defined protein complexes in their native cellular environment.
Single-peptide DNA-dependent RNA polymerase homologous to multi-subunit RNA polymerase
Authors: Forrest David , James Katherine , Yuzenkova Yulia , Zenkin Nikolay
Published: June 2017

Transcription in all living organisms is accomplished by multi-subunit RNA polymerases (msRNAPs). msRNAPs are highly conserved in evolution and invariably share a ∼400 kDa five-subunit catalytic core. Here we characterize a hypothetical ∼100 kDa single-chain protein, YonO, encoded by the SPβ prophage ofBacillus subtilis. YonO shares very distant homology with msRNAPs, but no homology with single-subunit polymerases. We show that despite homology to only a few amino acids of msRNAP, and the absence of most of the conserved domains, YonO is a highly processive DNA-dependent RNA polymerase. We demonstrate that YonO is abona fideRNAP of the SPβ bacteriophage that specifically transcribes its late genes, and thus represents a novel type of bacteriophage RNAPs. YonO and related proteins present in various bacteria and bacteriophages have diverged from msRNAPs before the Last Universal Common Ancestor, and, thus, may resemble the single-subunit ancestor of all msRNAPs.
IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours
Authors: Seo Hyungseok , Jeon Insu , Kim Byung-Seok , Park Myunghwan , Bae Eun-Ah , Song Boyeong , Koh Choong-Hyun , Shin Kwang-Soo , Kim Il-Kyu , Choi Kiyoung , Oh Taegwon , Min Jiyoun , Min Byung Soh , Han Yoon Dae , Kang Suk-Jo , Shin Sang Joon , Chung Yeonseok , Kang Chang-Yuil
Published: June 2017

During cancer immunoediting, loss of major histocompatibility complex class I (MHC-I) in neoplasm contributes to the evasion of tumours from host immune system. Recent studies have demonstrated that most natural killer (NK) cells that are found in advanced cancers are defective, releasing the malignant MHC-I-deficient tumours from NK-cell-dependent immune control. Here, we show that a natural killer T (NKT)-cell-ligand-loaded tumour-antigen expressing antigen-presenting cell (APC)-based vaccine effectively eradicates these advanced tumours. During this process, we find that the co-expression of Tim-3 and PD-1 marks functionally exhausted NK cells in advanced tumours and that MHC-I downregulation in tumours is closely associated with the induction of NK-cell exhaustion in both tumour-bearing mice and cancer patients. Furthermore, the recovery of NK-cell function by IL-21 is critical for the anti-tumour effects of the vaccine against advanced tumours. These results reveal the process involved in the induction of NK-cell dysfunction in advanced cancers and provide a guidance for the development of strategies for cancer immunotherapy.
Improving the DNA specificity and applicability of base editing through protein engineering and protein delivery
Authors: Rees Holly A. , Komor Alexis C. , Yeh Wei-Hsi , Caetano-Lopes Joana , Warman Matthew , Edge Albert S. B. , Liu David R.
Published: June 2017

We recently developed base editing, a genome-editing approach that enables the programmable conversion of one base pair into another without double-stranded DNA cleavage, excess stochastic insertions and deletions, or dependence on homology-directed repair. The application of base editing is limited by off-target activity and reliance on intracellular DNA delivery. Here we describe two advances that address these limitations. First, we greatly reduce off-target base editing by installing mutations into our third-generation base editor (BE3) to generate a high-fidelity base editor (HF-BE3). Next, we purify and deliver BE3 and HF-BE3 as ribonucleoprotein (RNP) complexes into mammalian cells, establishing DNA-free base editing. RNP delivery of BE3 confers higher specificity even than plasmid transfection of HF-BE3, while maintaining comparable on-target editing levels. Finally, we apply these advances to deliver BE3 RNPs into both zebrafish embryos and the inner ear of live mice to achieve specific, DNA-free base editing in vivo.
Isolation, Detection, and Quantification of Cancer Biomarkers in HPV-Associated Malignancies
Authors: Inan Hakan , Wang Shuqi , Inci Fatih , Baday Murat , Zangar Richard , Kesiraju Sailaja , Anderson Karen S. , Cunningham Brian T. , Demirci Utkan
Published: June 2017

Human Papillomavirus (HPV) infection has been recognized as the main etiologic factor in the development of various cancers including penile, vulva, oropharyngeal and cervical cancers. In the development of cancer, persistent HPV infections induce E6 and E7 oncoproteins, which promote cell proliferation and carcinogenesis resulting elevated levels of host antibodies (e.g., anti-HPV16 E7 antibody). Currently, these cancers are clinically diagnosed using invasive biopsy-based tests, which are performed only in centralized labs by experienced clinical staff using time-consuming and expensive tools and technologies. Therefore, these obstacles constrain their utilization at primary care clinics and in remote settings, where resources are limited. Here, we present a rapid, inexpensive, reliable, easy-to-use, customized immunoassay platform following a microfluidic filter device to detect and quantify anti-HPV16 E7 antibodies from whole blood as a non-invasive assisting technology for diagnosis of HPV-associated malignancies, especially, at primary healthcare and remote settings. The platform can detect and quantify anti-HPV16 E7 antibody down to 2.87 ng/mL. We further validated our immunoassay in clinical patient samples and it provided significantly high responses as compared to control samples. Thus, it can be potentially implemented as a pretesting tool to identify high-risk groups for broad monitoring of HPV-associated cancers in resource-constrained settings.
Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies
Authors: de Mesquita Fernanda Cristina , Guixé-Muntet Sergi , Fernández-Iglesias Anabel , Maeso-Díaz Raquel , Vila Sergi , Hide Diana , Ortega-Ribera Martí , Rosa José Luís , García-Pagán Juan Carlos , Bosch Jaime , de Oliveira Jarbas Rodrigues , Gracia-Sancho Jordi
Published: June 2017

Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Human and rat HSC were in vitro treated with liraglutide, or vehicle, and their phenotype, viability and proliferation were evaluated. In addition, liraglutide or vehicle was administered to rats with CLD. Liver microvascular function, fibrosis, HSC phenotype and sinusoidal endothelial phenotype were determined. Additionally, the effects of liraglutide on HSC phenotype were analysed in human precision-cut liver slices. Liraglutide markedly improved HSC phenotype and diminished cell proliferation. Cirrhotic rats receiving liraglutide exhibited significantly improved liver microvascular function, as evidenced by lower portal pressure, improved intrahepatic vascular resistance, and marked ameliorations in fibrosis, HSC phenotype and endothelial function. The anti-fibrotic effects of liraglutide were confirmed in human liver tissue and, although requiring further investigation, its underlying molecular mechanisms suggested a GLP1-R-independent and NF-κB-Sox9-dependent one. This study demonstrates for the first time that liraglutide improves the liver sinusoidal milieu in pre-clinical models of cirrhosis, encouraging its clinical evaluation in the treatment of chronic liver disease.
Comparisons of the biodistribution and toxicological examinations after repeated intravenous administration of silver and gold nanoparticles in mice
Authors: Yang Lin , Kuang Huijuan , Zhang Wanyi , Aguilar Zoraida P. , Wei Hua , Xu Hengyi
Published: June 2017

Nanoparticles (NPs) size, surface functionalization, and concentration were claimed to contribute to distribution and toxicity outcomes of NPs in vivo. However, intrinsic chemical compositions of NPs caused inconsistent biodistribution and toxic profiles which attracted little attention. In this study, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) were used to determine the biodistribution, toxickinetic, and genotoxicity variances in murine animals. The results demonstrated AgNPs and AuNPs were primarily deposited in the mononuclear phagocyte system (MPS) such as the liver and spleen. In particular, AuNPs seemed to be prominently stored in the liver, whereas AgNPs preferentially accumulated in more organs such as the heart, lung, kidney, etc. Also, the circulation in the blood and fecal excretions showed higher AgNPs contents in comparison with the AuNPs. Measurements of the mouse body and organ mass, hematology and biochemistry evaluation, and histopathological examinations indicated slight toxic difference between the AgNPs and AuNPs over a period of two months. RT-qPCR data revealed that AgNPs induced greater changes in gene expression with relevance to oxidative stress, apoptosis, and ion transport. Our observations proved that the NPs chemical composition played a critical role in their in vivo biodistribution and toxicity.
Combining Catalytic Microparticles with Droplets Formed by Phase Coexistence: Adsorption and Activity of Natural Clays at the Aqueous/Aqueous Interface
Authors: Pir Cakmak Fatma , Keating Christine D.
Published: June 2017

Natural clay particles have been hypothesized as catalysts on the early Earth, potentially facilitating the formation of early organic (bio) molecules. Association of clay particles with droplets formed by liquid-liquid phase separation could provide a physical mechanism for compartmentalization of inorganic catalysts in primitive protocells. Here we explore the distribution of natural clay mineral particles in poly(ethylene glycol) (PEG)/dextran (Dx) aqueous two-phase systems (ATPS). We compared the three main types of natural clay: kaolinite, montmorillonite and illite, all of which are aluminosilicates of similar composition and surface charge. The three clay types differ in particle size, crystal structure, and their accumulation at the ATPS interface and ability to stabilize droplets against coalescence. Illite and kaolinite accumulated at the aqueous/aqueous interface, stabilizing droplets against coalescence but not preventing their eventual sedimentation due to the mass of adsorbed particles. The ability of each clay-containing ATPS to catalyze reaction of o-phenylenediamine with peroxide to form 2,3-diaminophenazone was evaluated. We observed modest rate increases for this reaction in the presence of clay-containing ATPS over clay in buffer alone, with illite outperforming the other clays. These findings are encouraging because they support the potential of combining catalytic mineral particles with aqueous microcompartments to form primitive microreactors.
On the phonon dissipation contribution to nanoscale friction by direct contact
Authors: de Mello S. R. Sales , da Costa M. E. H. Maia , Menezes C. M. , Boeira C. D. , Freire Jr F. L. , Alvarez F. , Figueroa C. A.
Published: June 2017

The friction phenomenon is a ubiquitous manifestation of nature. Models considering phononic, electronic, magnetic, and electrostatic interactions are invoked to explain the fundamental forces involved in the friction phenomenon. In order to establish the incidence of the phonon prompting at the nanoscale friction by direct contact, we study a diamond spherical dome sliding on carbon thin films containing different amount of deuterium and hydrogen. The friction coefficient decreases by substituting hydrogen by deuterium atoms. This result is consistent with an energy dissipation vibration local mechanism from a disordered distribution of bond terminators.
Transmission of Induced Chromosomal Aberrations through Successive Mitotic Divisions in Human Lymphocytes after In Vitro and ﻿In﻿ Vivo Radiation
Authors: Kaddour Akram , Colicchio Bruno , Buron Diane , El Maalouf Elie , Laplagne Eric , Borie Claire , Ricoul Michelle , Lenain Aude , Hempel William M. , Morat Luc , Al Jawhari Mustafa , Cuceu Corina , Heidingsfelder Leonhard , Jeandidier Eric , Deschênes Georges , Dieterlen Alain , El May Michèle , Girinsky Theodore , Bennaceur-Griscelli Annelise , Carde Patrice , Sabatier Laure , M’kacher Radhia
Published: June 2017

The mechanisms behind the transmission of chromosomal aberrations (CA) remain unclear, despite a large body of work and major technological advances in chromosome identification. We reevaluated the transmission of CA to second- and third-division cells by telomere and centromere (TC) staining followed by M-FISH. We scored CA in lymphocytes of healthy donors after in vitro irradiation and those of cancer patients treated by radiation therapy more than 12 years before. Our data demonstrate, for the first time, that dicentric chromosomes (DCs) decreased by approximately 50% per division. DCs with two centromeres in close proximity were more efficiently transmitted, representing 70% of persistent DCs in ≥M3 cells. Only 1/3 of acentric chromosomes (ACs), ACs with four telomeres, and interstitial ACs, were paired in M2 cells and associated with specific DCs configurations. In lymphocytes of cancer patients, 82% of detected DCs were characterized by these specific configurations. Our findings demonstrate the high stability of DCs with two centromeres in close proximity during cell division. The frequency of telomere deletion increased during cell cycle progression playing an important role in chromosomal instability. These findings could be exploited in the follow-up of exposed populations.
Changes in novel haematological parameters following thermal injury: A prospective observational cohort study
Authors: Dinsdale R. J. , Devi A. , Hampson P. , Wearn C. M. , Bamford A. L. , Hazeldine J. , Bishop J. , Ahmed S. , Watson C. , Lord J. M. , Moiemen N. , Harrison P.
Published: June 2017

The mortality caused by sepsis is high following thermal injury. Diagnosis is difficult due to the ongoing systemic inflammatory response. Previous studies suggest that cellular parameters may show promise as diagnostic markers of sepsis. The aim of this study was to evaluate the effect of thermal injury on novel haematological parameters and to study their association with clinical outcomes. Haematological analysis was performed using a Sysmex XN-1000 analyser on blood samples acquired on the day of the thermal injury to 12 months post-injury in 39 patients (15–95% TBSA). Platelet counts had a nadir at day 3 followed by a rebound thrombocytosis at day 21, with nadir values significantly lower in septic patients. Measurements of extended neutrophil parameters (NEUT-Y and NEUT-RI) demonstrated that septic patients had significantly higher levels of neutrophil nucleic acid content. A combination of platelet impedance count (PLT-I) and NEUT-Y at day 3 post-injury exhibited good discriminatory power for the identifying septic patients (AUROC = 0.915, 95% CI [0.827, 1.000]). Importantly, the model had improved performance when adjusted for mortality with an AUROC of 0.974 (0.931, 1.000). A combination of PLT-I and NEUT-Y show potential for the early diagnosis of sepsis post-burn injury. Importantly, these tests can be performed rapidly and require a small volume of whole blood highlighting their potential utility in clinical practice.
APOE gene polymorphism in long-lived individuals from a central China population
Authors: Liu Guodong , Liu Xiang , Yu Pulin , Wang Qi , Wang Hua , Li Chenfang , Ye Guangming , Wu Xiaoling , Tan Chunling
Published: June 2017

Previous studies from European and East Asian cohorts reported conflicting results over whether and how the frequencies of the three common alleles, ε2, ε3 and ε4, of the apolioprotein E gene (APOE), in long-lived individuals differ from those in younger age groups. This study was the first to analyse these frequencies of long-lived individuals from central China. Genotyping of APOE alleles and genotypes was carried out in 70 long-lived individuals and 204 younger controls. No difference in the frequency of any APOE allele or genotype was found between the long-lived participants and their younger controls, but the long-lived group seemed to have a higher ε4 frequency (15.71%) than the 24–50 and 51–75 age groups (10.2% and 11.32%, P > 0.05). Notably, when compared with two other Chinese studies, the central China long-lived group had a higher ε4 frequency than its southern and eastern China counterparts (15.71% vs. 2.82% and 2.54%, P < 0.05). It is not clear to what extent population substructure or lifestyles contributed to these divergent findings. A clear understanding of the contribution of APOE polymorphisms to longevity in the Han Chinese population may be achieved only through large scale studies with participants from well-defined regional clusters.
Internal gradient distributions: A susceptibility-derived tensor delivering morphologies by magnetic resonance
Authors: Álvarez Gonzalo A. , Shemesh Noam , Frydman Lucio
Published: June 2017

Nuclear magnetic resonance is a powerful tool for probing the structures of chemical and biological systems. Combined with field gradients it leads to NMR imaging (MRI), a widespread tool in non-invasive examinations. Sensitivity usually limits MRI’s spatial resolution to tens of micrometers, but other sources of information like those delivered by constrained diffusion processes, enable one extract morphological information down to micron and sub-micron scales. We report here on a new method that also exploits diffusion – isotropic or anisotropic– to sense morphological parameters in the nm-mm range, based on distributions of susceptibility-induced magnetic field gradients. A theoretical framework is developed to define this source of information, leading to the proposition of internal gradient-distribution tensors. Gradient-based spin-echo sequences are designed to measure these new observables. These methods can be used to map orientations even when dealing with unconstrained diffusion, as is here demonstrated with studies of structured systems, including tissues.
In–situ XRD and EDS method study on the oxidation behaviour of Ni–Cu sulphide ore
Authors: Li Guangshi , Cheng Hongwei , Xiong Xiaolu , Lu Xionggang , Xu Cong , Lu Changyuan , Zou Xingli , Xu Qian
Published: June 2017

The oxidation mechanism of sulfides is the key issue during the sulphide–metallurgy process. In this study, the phase transformation and element migration were clearly demonstrated by in–situ laboratory–based X–ray diffraction (XRD) and energy–dispersive X–ray spectroscopy (EDS), respectively. The reaction sequence and a four–step oxidation mechanism were proposed and identified. The elemental distribution demonstrated that at a low temperature, the Fe atoms diffused outward and the Ni/Cu atoms migrated toward the inner core, whereas the opposite diffusion processes were observed at a higher temperature. Importantly, the unique visual presentation of the oxidation behaviour provided by the combination of in–situ XRD and EDS might be useful for optimising the process parameters to improve the Ni/Cu extraction efficiency during Ni–Cu sulphide metallurgy.
Characterisation of a stable laboratory co-culture of acidophilic nanoorganisms
Authors: Krause Susanne , Bremges Andreas , Münch Philipp C. , McHardy Alice C. , Gescher Johannes
Published: June 2017

This study describes the laboratory cultivation of ARMAN (Archaeal Richmond Mine Acidophilic Nanoorganisms). After 2.5 years of successive transfers in an anoxic medium containing ferric sulfate as an electron acceptor, a consortium was attained that is comprised of two members of the order Thermoplasmatales, a member of a proposed ARMAN group, as well as a fungus. The 16S rRNA identity of one archaeon is only 91.6% compared to the most closely related isolate Thermogymnomonas acidicola. Hence, this organism is the first member of a new genus. The enrichment culture is dominated by this microorganism and the ARMAN. The third archaeon in the community seems to be present in minor quantities and has a 100% 16S rRNA identity to the recently isolated Cuniculiplasma divulgatum. The enriched ARMAN species is most probably incapable of sugar metabolism because the key genes for sugar catabolism and anabolism could not be identified in the metagenome. Metatranscriptomic analysis suggests that the TCA cycle funneled with amino acids is the main metabolic pathway used by the archaea of the community. Microscopic analysis revealed that growth of the ARMAN is supported by the formation of cell aggregates. These might enable feeding of the ARMAN by or on other community members.
Single-point Mutation of an Histidine-aspartic Domain-containing Gene involving in Chloroplast Ribosome Biogenesis Leads to White Fine Stripe Leaf in Rice
Authors: Ge Changwei , Wang Li , Ye Weijun , Wu Liwen , Cui Yongtao , Chen Ping , Pan Jiangjie , Zhang Dong , Hu Jiang , Zeng Dali , Dong Guojun , Qian Qian , Guo Longbiao , Xue Dawei
Published: June 2017

Plant leaves are a crucial organ associated closely with chloroplast development, photosynthesis rate and crop productivity. In this study, a white fine stripe leaf 1 (wfsl1) mutant was isolated and characterized from the japonica rice Zhonghua11 (ZH11) after ethyl methanesulfonate mutagenesis. The wfsl1 displayed white fine stripe leaves since tillering stage and abnormal chloroplast structure. Map-based cloning and Bioinformatic analysis indicated that WFSL1 on chromosome 1 contains an “A” to “T” substitution in protein coding region, and encodes a putative metal-dependent phosphohydrolase with HD domain at the N-terminus. WFSL1 was targeted to the chloroplasts and had higher expression in mature leaves and sheaths. RNA-seq analysis revealed that chloroplast development and photosynthesis genes were significantly affected in wfsl1 plants. Levels of WFSL1 and chloroplast encoded proteins were decreased in wfsl1 mutants via western blot analysis. Compared with WT, wfsl1 exhibits lower Chl content and defective in biogenesis of chloroplast ribosomes, which resulted in reduced grain yield. Taken together, our results show that WFSL1 is critical for chloroplast development, ribosome biogenesis, and light energy utilization, finally affects grain yield.