bluuebunny/crossref_metadata_2025 huggingface dataset:
Which Line to Follow? The Utility of Different Line-Fitting Methods to Capture the Mechanism of Morphological Scaling
Authors: Shingleton Alexander W
Published: May 2019

Bivariate morphological scaling relationships describe how the sizes of two traits co-vary among adults in a population. In as much as body shape is reflected by the relative size of various traits within the body, morphological scaling relationships capture how body shape varies with size, and therefore have been used widely as descriptors of morphological variation within and among species. Despite their extensive use, there is continuing discussion over which line-fitting method should be used to describe linear morphological scaling relationships. Here I argue that the “best” line-fitting method is the one that most accurately captures the proximate developmental mechanisms that generate scaling relationships. Using mathematical modeling, I show that the “best” line-fitting method depends on the pattern of variation among individuals in the developmental mechanisms that regulate trait size. For Drosophila traits, this pattern of variation indicates that major axis regression is the best line-fitting method. For morphological traits in other animals, however, other line-fitting methods may be more accurate. I provide a simple web-based application for researchers to explore how different line-fitting methods perform on their own morphological data.
Transcranial Magnetic Stimulation Markers of Antidepressant Treatment in Adolescents With Major Depressive Disorder
Authors: Doruk Camsari Deniz , Lewis Charles P , Sonmez Ayse Irem , Nandakumar Aiswarya Laks , Gresbrink Marjorie A , Daskalakis Zafiris J , Croarkin Paul E
Published: May 2019

Background

The goal of this study was to examine baseline transcranial magnetic stimulation measures of cortical inhibition and excitability in depressed patients and characterize their longitudinal posttreatment changes.

Methods

Fifteen adolescents (age 13–17 years) with moderate to severe major depressive disorder and 22 healthy controls (age 9–17) underwent single- and paired-pulse transcranial magnetic stimulation and clinical assessments. Transcranial magnetic stimulation measures included short-interval intracortical inhibition (2 and 4 milliseconds), long-interval intracortical inhibition (100, 150, and 200 milliseconds), cortical silent period, and intracortical facilitation (10, 15, and 20 milliseconds). Ten participants with major depressive disorder initiated antidepressant treatment or had dose adjustments. These participants were reassessed after treatment. Depression symptom severity was measured with the Children’s Depression Rating Scale, Revised. Robust regression modeling compared healthy and depressed adolescents at baseline. Relationships between changes in cortical inhibition and changes in depressive symptom severity were assessed in the depressed adolescents receiving antidepressant treatment.

Results

Our results revealed that at baseline, short-interval intracortical inhibition-2 was significantly reduced (Padj = .01) in depressed participants, suggesting impaired cortical inhibition compared with healthy controls. At follow-up, improvement in Children’s Depression Rating Scale, Revised scores correlated with improvement in short-interval intracortical inhibition-4 amplitude (greater inhibition) after antidepressant treatment (R2 = 0.63; P = .01).

Conclusions

These results suggest that cortical inhibition measures may have promise as biomarkers in adolescents treated for depression.
An explanatory model of temperature influence on flowering through whole-plant accumulation of FLOWERING LOCUS T in Arabidopsis thaliana
Authors: Kinmonth-Schultz Hannah A , MacEwen Melissa J S , Seaton Daniel D , Millar Andrew J , Imaizumi Takato , Kim Soo-Hyung
Published: May 2019

We assessed mechanistic temperature influence on flowering by incorporating temperature-responsive flowering mechanisms across developmental age into an existing model. Temperature influences the leaf production rate as well as expression of FLOWERING LOCUS T (FT), a photoperiodic flowering regulator that is expressed in leaves. The Arabidopsis Framework Model incorporated temperature influence on leaf growth but ignored the consequences of leaf growth on and direct temperature influence of FT expression. We measured FT production in differently aged leaves and modified the model, adding mechanistic temperature influence on FT transcription, and causing whole-plant FT to accumulate with leaf growth. Our simulations suggest that in long days, the developmental stage (leaf number) at which the reproductive transition occurs is influenced by day length and temperature through FT, while temperature influences the rate of leaf production and the time (in days) the transition occurs. Further, we demonstrate that FT is mainly produced in the first 10 leaves in the Columbia (Col-0) accession, and that FT accumulation alone cannot explain flowering in conditions in which flowering is delayed. Our simulations supported our hypotheses that: (i) temperature regulation of FT, accumulated with leaf growth, is a component of thermal time, and (ii) incorporating mechanistic temperature regulation of FT can improve model predictions when temperatures change over time.
Associations between antimicrobial use and the faecal resistome on broiler farms from nine European countries
Authors: Luiken Roosmarijn E C , Van Gompel Liese , Munk Patrick , Sarrazin Steven , Joosten Philip , Dorado-García Alejandro , Borup Hansen Rasmus , Knudsen Berith E , Bossers Alex , Wagenaar Jaap A , Aarestrup Frank M , Dewulf Jeroen , Mevius Dik J , Heederik Dick J J , Smit Lidwien A M , Schmitt Heike ,   EFFORT consortium, Graveland Haitske , vanEssen Alieda , Gonzalez-Zorn Bruno , Moyano Gabriel , Sanders Pascal , Chauvin Claire , David Julie , Battisti Antonio , Caprioli Andrea , Blaha Thomas , Wadepohl Katharina , Brandt Maximiliane , Hald Tine , Ribeiro Duarte Ana Sofia , Wasyl Dariusz , Skarzyńska Magdalena , Zajac Magdalena , Daskalov Hristo , Saatkamp Helmut W , Stärk Katharina D C
Published: May 2019

Objectives

To determine associations between farm- and flock-level antimicrobial usage (AMU), farm biosecurity status and the abundance of faecal antimicrobial resistance genes (ARGs) on broiler farms.

Methods

In the cross-sectional pan-European EFFORT study, conventional broiler farms were visited and faeces, AMU information and biosecurity records were collected. The resistomes of pooled faecal samples were determined by metagenomic analysis for 176 farms. A meta-analysis approach was used to relate total and class-specific ARGs (expressed as fragments per kb reference per million bacterial fragments, FPKM) to AMU (treatment incidence per DDD, TIDDDvet) per country and subsequently across all countries. In a similar way, the association between biosecurity status (Biocheck.UGent) and the resistome was explored.

Results

Sixty-six (38%) flocks did not report group treatments but showed a similar resistome composition and roughly similar ARG levels to antimicrobial-treated flocks. Nevertheless, we found significant positive associations between β-lactam, tetracycline, macrolide and lincosamide, trimethoprim and aminoglycoside antimicrobial flock treatments and ARG clusters conferring resistance to the same class. Similar associations were found with purchased products. In gene-level analysis for β-lactams and macrolides, lincosamides and streptogramins, a significant positive association was found with the most abundant gene clusters blaTEM and erm(B). Little evidence was found for associations with biosecurity.

Conclusions

The faecal microbiome in European broilers contains a high diversity of ARGs, even in the absence of current antimicrobial selection pressure. Despite this, the relative abundance of genes and the composition of the resistome is positively related to AMU in European broiler farms for several antimicrobial classes.
Regulating Cross-Border Data Flows in a Data-Driven World: How WTO Law Can Contribute
Authors: Mitchell Andrew D , Mishra Neha
Published: May 2019

While the free cross-border movement of data is essential to many aspects of international trade, several countries have imposed restrictions on these data flows. The pre-internet rules of the World Trade Organization (`WTO') discipline some of these restrictions, but they are insufficient. Unfortunately, so are the electronic commerce chapters in modern preferential trade agreements. This article argues that reformed WTO rules, which take account of the policy challenges of the data-driven economy, are required. These reforms would facilitate internet openness while ensuring consumer and business trust, promoting digital inclusion of developing countries, and incorporating clear exceptions for legitimate domestic policies.
Information Sharing and Incentives in Organizations
Authors: de Bettignies Jean-Etienne , Zabojnik Jan
Published: May 2019

We study an organization, consisting of a manager and a worker, whose success depends on its ability to estimate a payoff-relevant but unknown parameter. If the manager has private information about this parameter, she has an incentive to conceal it from the worker in order to motivate him to search for additional information. Due to a time-inconsistency problem, the manager conceals her information more often than if she could commit to an information sharing policy, but even a manager with commitment power shares her information less than would be efficient. We also show that managers who are more likely to get informed are more willing to share their information and that unless the manager’s information substantially improves the worker’s productivity, managerial and worker abilities are substitutes in the firm’s profit function. (JEL D21 D82, L23)
Comparative functional skeletal morphology among three genera of shrews: implications for the evolution of locomotor behavior in the Soricinae (Eulipotyphla: Soricidae)
Authors: Woodman Neal , Wilken Alec T
Published: May 2019

The clade comprising the soricid tribes Blarinellini (Blarinella) and Blarinini (Blarina and Cryptotis) is notable within the Soricidae (Eulipotyphla) for the large proportion of reportedly semifossorial species. To better define locomotor modes among species in these two tribes, we quantified purported locomotor adaptations by calculating 23 functional indices from postcranial measurements obtained from museum specimens of Blarina and Blarinella and published measurements for 16 species of Cryptotis. We then analyzed relative ambulatory–fossorial function of each species using principal component analyses and mean percentile rank (MPR) analysis of the indices. Species within the Blarinellini–Blarinini clade exhibit a graded series of morphologies with four primary functional groupings that we classified as “ambulatory,” “intermediate,” “semifossorial,” and “fossorial.” To obtain a preliminary overview of evolution of locomotor modes in this group, we mapped MPRs on a composite phylogeny and examined the resulting patterns. That analysis revealed that the most recent common ancestor of the Blarinellini–Blarinini clade most likely had an intermediate or semifossorial locomotor morphology. Individual subclades subsequently evolved either more ambulatory or more fossorial morphologies. Hence, evolution of locomotor traits within this clade is complex. Multiple shifts in locomotor mode likely occurred, and no single directional tendency is apparent either among the major modes or in levels of complexity.
A Defense of the Phenomenological Account of Health and Illness
Authors: Svenaeus Fredrik
Published: May 2019

A large slice of contemporary phenomenology of medicine has been devoted to developing an account of health and illness that proceeds from the first-person perspective when attempting to understand the ill person in contrast and connection to the third-person perspective on his/her diseased body. A proof that this phenomenological account of health and illness, represented by philosophers, such as Drew Leder, Kay Toombs, Havi Carel, Hans-Georg Gadamer, Kevin Aho, and Fredrik Svenaeus, is becoming increasingly influential in philosophy of medicine and medical ethics is the criticism of it that has been voiced in some recent studies. In this article, two such critical contributions, proceeding from radically different premises and backgrounds, are discussed: Jonathan Sholl’s naturalistic critique and Talia Welsh’s Nietzschean critique. The aim is to defend the phenomenological account and clear up misunderstandings about what it amounts to and what we should be able to expect from it.
Pilot clinical study of ascorbic acid treatment in cardiac catheterization
Authors: Sun Lue , Igarashi Tomonori , Tetsuka Ryoya , Li Yun-Shan , Kawasaki Yuya , Kawai Kazuaki , Hirakawa Haruhisa , Tsuboi Koji , Nakamura Asako J , Moritake Takashi
Published: May 2019

Clinical radiodiagnosis and radiotherapy sometimes induce tissue damage and/or increase the risk of cancer in patients. However, in radiodiagnosis, a reduction in the exposure dose causes a blockier image that is not acceptable for diagnosis. Approximately 70% of DNA damage is induced via reactive oxygen species and/or radicals created during X-ray irradiation. Therefore, treatment with anti-oxidants and/or radical scavengers is considered to be effective in achieving a good balance between image quality and damage. However, few studies have examined the effect of using radical scavengers to reduce radiation damage in the clinical setting. In this study, we administrated 20 mg/kg ascorbic acid (AA) to patients before cardiac catheterization (CC) for diagnostic purposes. We analyzed changes in the number of phosphorylated H2AX (γH2AX) foci (a marker of DNA double-strand breaks) in lymphocytes, red blood cell glutathione levels, blood cell counts, and biochemical parameters. Unfortunately, we did not find satisfactory evidence to show that AA treatment reduces γH2AX foci formation immediately after CC. AA treatment did, however, cause a higher reduced/oxidized glutathione ratio than in the control arm immediately after CC. This is a preliminary study, but this result suggests that reducing radiation damage in clinical practice can be achieved using a biological approach.
Validation of the dicentric chromosome assay for radiation biological dosimetry in South Korea
Authors: Lee Younghyun , Jin Young Woo , Wilkins Ruth C , Jang Seongjae
Published: May 2019

The dicentric chromosome assay (DCA) is a well-established biodosimetry test to estimate exposure to ionizing radiation. The Korea Institute of Radiological and Medical Sciences (KIRAMS) established a DCA protocol as a medical response to radiation emergencies in South Korea. To maintain its accuracy and performance, intercomparison exercises with Health Canada (HC) have been conducted; herein, we aimed to validate our capacity of DCA analysis based on those results. Blood samples irradiated at HC were shipped to KIRAMS to assess the irradiation dose to blinded samples using conventional DCA full scoring and triage-based techniques (conventional DCA scoring in triage mode and DCA QuickScan method). Actual doses fell within the 95% confidence intervals of dose estimates for 70–100% of the blinded samples in 2015–2018. All methods discriminated binary dose categories, reflecting clinical significance. This DCA can be used as a reliable radiation biodosimetry tool in preparation for radiation accidents in South Korea.
Seroprotection rates of vaccine-preventable diseases among newly arrived Eritrean asylum seekers in Switzerland: a cross-sectional study
Authors: Staehelin Cornelia , Chernet Afona , Sydow Véronique , Piso Rein J , Suter-Riniker Franziska , Funez Sabine , Nickel Beatrice , Paris Daniel H , Labhardt Niklaus D
Published: May 2019

Background

According to 2016 World Health Organization and United Nations Children’s Fund country estimates, Eritrea has overall high vaccination coverage with immunization rates for three doses of diphtheria/tetanus/pertussis and polio vaccine of 95%, for two doses measles vaccine of 85% and for three doses hepatitis B vaccine of 85%. If confirmed, this could imply that routine basic vaccination of newly arrived Eritreans could be safely omitted.

Methods

We used stored serum samples from two cross-sectional studies that screened newly arrived Eritrean refugees for infectious diseases. Consenting refugees aged 16 years and older who registered in one of three neighbouring cantons in northwestern Switzerland were enrolled between January 2016 and December 2017. Antibody titers against the following vaccine-preventable diseases were measured (applied thresholds for seroprotection in brackets): diphtheria (>0.1 IU/ml), tetanus (>0.1 IU/ml), measles (>150 mIU/ml), rubella (only for women, >11 IU/ml), varicella (>50 mIU/ml), hepatitis B [hepatitis B surface antigen (HBsAg) Index >0.9, Hepatitis B core antibody (anti-HBc) Index >0.9 and antibodies to HBsAg (anti-HBs) >10 IE/L]. Differences between sex and age groups (≤25 and >25 years) were measured by Fisher’s exact test.

Results

We analysed samples of 133 study participants (20 women, 15%) with a median age of 25 years (range 16–61). Rates of seropositivity were as follows for women/men, respectively: diphtheria 57.9%/74.8% (difference non-significant), tetanus 94.8%/41.1% (P < 0.001), measles 73.7%/76.6% (non-significant), rubella in women 78.9%, varicella 89.5%/95.3% (non-significant), anti-HBc 15.8%/26.2% (non-significant) and anti-HBs 15.8%/17.8% (non-significant).

Conclusion

Seroprevalence for vaccine-preventable infections did not meet levels required to confer herd immunity in any of the human-to-human transmissible diseases that were studied. In general, the strategy proposed by the Federal Office of Public Health to offer basic immunization to all newly arrived refugees, including newly arriving Eritrean refugees, is justified.
Article 5—Mediation
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter explores Article 5 on mediation of the 2014 ICDR Rules. Mediation is a very effective alternative dispute-resolution process, in which the mediator assists the parties to settle their disputes by a process of discussion and narrowing differences. The mediator does not have the power to render binding decisions, rather the parties aim to reach agreement amongst themselves with the mediator’s assistance. Under Article 5, the ICDR may invite the parties to mediate or the parties may agree to mediate in accordance with the ICDR’s International Mediation Rules at any time while the arbitration proceedings are pending. The mediation shall in principle proceed in parallel with arbitration to avoid any delay. Ultimately, the 2014 ICDR Rules reflect a desire to encourage the parties to consider the benefits of mediation, particularly early in the dispute resolution process, without forcing them to mediate.
Article 7—Joinder
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter discusses Article 7 on joinder of the 2014 ICDR Rules. Article 7 allows a party to a pending arbitration to join an additional party by submitting a Notice of Arbitration against the additional party to the Administrator and at the same time to the additional party and all other parties. It further sets forth the conditions and formal requirements for adding an additional party to the pending arbitration. Ultimately, Article 7 deals with multi-party and multi-contract transaction disputes where not all concerned parties are part of the pending arbitral proceedings, but a full and efficient resolution of the entire dispute would benefit from the participation of all parties in one proceeding. Additionally, a joinder mitigates the risk of inconsistent decisions.
Article 10—Notices
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter looks at Article 10 of the ICDR Rules. Both the arbitral tribunal and the parties to an arbitration must communicate in an effective and pre-agreed manner to ensure the smooth conduct of arbitral proceedings. Article 10(1) addresses the practicalities regarding notification of all communications between the parties. Notably, it addresses the variety of forms of modern communication, paying particular attention to forms of electronic communication. Likewise, Article 10(1) is drafted in sufficiently broad terminology that permits the parties and the tribunal to communicate in a variety of ways. Meanwhile, Article 10(2) provides the framework for calculating periods of time and time limits under the Rules. By specifically defining when notice periods begin to run, and anticipating holiday and other interruptions, Article 10(2) pre-empts possible dilatory tactics and sets the parties’ expectations for prompt notification, service of documents, and other communications that are essential to the timely and effective functioning of an arbitration.
Article 18—Language of Arbitration
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter focuses on Article 18 of the ICDR Rules, which provides for the language of arbitration. Article 18 recognizes as binding the parties’ agreement—in the arbitration clause or otherwise—on a particular language in which the arbitration shall be conducted. However, where the parties have not specified the language of the arbitration, Article 18 provides that the language of the documents that contain the arbitration agreement is determinative of the language of the proceedings. Article 18 also permits the arbitrators to determine the language of the arbitration, recognizing that it may be appropriate, in some cases, to conduct the arbitration in more than one language. For example, it is not uncommon to require the parties to make submissions in one language, but to allow them to produce documents or witness statements in other languages without having to provide a translation.
Article 24—Interim Measures
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter discusses Article 24 of the ICDR Rules, which empowers the tribunal to order any interim or conservatory measures it deems necessary, including—but not limited to—injunctive relief and measures necessary for the protection of property. The measures may be intended to preserve evidence for use in the case, prevent property from being interfered with, or, more generally, to preserve the status quo pending determination of the dispute. In addition to empowering the tribunal to take such measures, Article 24(3) also states that a request to a judicial authority for interim measures is not inconsistent with the arbitration agreement. As the newly introduced Article 24(5) makes clear, Article 24 should not be confused with Article 6, which provides for ‘emergency measures of protection’ to be granted by an ‘emergency arbitrator’ where the tribunal has not yet been appointed.
Article 35—Fees and Expenses of Arbitral Tribunal
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter looks at Article 35 of the ICDR Rules, which concerns compensation of the arbitral tribunal. Under the ICDR Rules, the case Administrator at the ICDR takes the lead in ensuring that fee rates are agreed between all tribunal members and the parties. Those fees are almost always based on the arbitrators’ previously advised hourly rates, although the Administrator may intervene to modify rates to avoid any significant disparity. Similarly, although not formally required under the rules, throughout the arbitration and in the final costs of arbitration, the Administrator reviews the reasonableness of the arbitrators’ fees and expenses. In contrast to the equivalent provision in the AAA Commercial Rules, section R-55, the ICDR Rules envisage a more hands-on role to be played by the institution.
Article E-1—Scope of Expedited Procedures
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter discusses the provision for expedited procedures in the 2014 ICDR Rules. Prior to 2014, the AAA provided expedited procedures for some domestic cases and parties could agree to expedited rules, but there were no express provisions for expedited resolution of an international dispute. The introduction of the ICDR’s International Expedited Procedures (Expedited Procedures), and analogous provisions in other institutional rules, are a response to user demand for quicker and cheaper options in international arbitration. As such, the ICDR’s Expedited Procedures—like those at other institutions—have a number of features specifically aimed at controlling time and costs. These include shorter time periods for appointment of the arbitrator, filing of written submissions, holding a hearing, and rendering the award. With respect to costs, the ICDR has not introduced a separate fee schedule for arbitrations under the Expedited Procedures.
The Law of International Watercourses
Authors: Stephen C McCaffrey
Published: May 2019

This book is an authoritative guide to the rules of international law governing the navigational and non-navigational uses of international rivers, lakes, and groundwater. The continued growth of the world’s population places increasing demands on Earth’s finite supplies of fresh water. Because two or more States share many of the world’s most important drainage basins, competition for increasingly scarce fresh water resources will only increase. Agreements between the States sharing international watercourses are negotiated, and disputes over shared water are resolved, against the backdrop of the rules of international law governing the use of this precious resource. The basic legal rules governing the use of shared freshwater for purposes other than navigation are reflected in the 1997 UN Convention on the Law of the Non-Navigational Uses of International Watercourses. This book devotes a chapter to the 1997 Convention but also examines the factual and legal context in which the Convention should be understood, considers the more important rules of the Convention in some depth, and discusses specific issues that could not be addressed in a framework instrument of that kind. It reviews the major cases and controversies concerning international watercourses as a background against which to consider the basic substantive and procedural rights and obligations of States in the field. This new edition covers the implications of the 1997 Convention coming into force in August 2014, and the compatibility of the 1997 and 1992 Conventions.
Part I Introduction, 1 Human Use of Fresh Water and the Era of Water Scarcity
Authors: Stephen C McCaffrey
Published: May 2019

This introductory chapter discusses the importance of water to humans, its growing scarcity relative to human populations, and, consequently, the increasing potential for water-related conflicts between States. Humans are straining the limits of a resource essential to their survival. Moreover, humans are capable of altering natural conditions to the point that their neighbors are deprived of fresh water they need and have historically relied upon. While international law plays an important role in resolving conflicts between states, it can play an even more valuable role in preventing them, in establishing conditions that are conducive to cooperation among states sharing freshwater resources. Indeed, cooperation is itself a logical outgrowth of rules of international law applicable in this field.
Part II Evolution and Theoretical Bases of the Law of International Watercourses, 4 The Theoretical Bases of International Watercourse Law: An Examination of the Four Principal Theories
Authors: Stephen C McCaffrey
Published: May 2019

This chapter studies the four principal theoretical bases of the law of international watercourses, ranging from absolute territorial sovereignty to community of interest. This study yields several conclusions. First, there is virtually no support—in either state practice, judicial decisions, or the writings of commentators—for the isolationist and unilateralist theories of absolute territorial sovereignty and absolute territorial integrity. Second, the doctrine of limited territorial sovereignty—when the expression is properly understood—appears to come closest of the four theories to describing the actual situation produced by state practice. Finally, the community of interest theory has much to recommend it as a theoretical context for the law of international watercourses. The theory describes well the state of affairs existing among co-riparian states. It has also found expression in agreements establishing joint institutional mechanisms for the protection, management, and development of shared fresh water resources.
Part III The Major Cases and Controversies: A Survey of State Practice, 6 The Major Cases
Authors: Stephen C McCaffrey
Published: May 2019

This chapter explores cases bearing on the field of international watercourses that have been decided by the International Court of Justice or its predecessor. States have submitted only a few disputes concerning international watercourses to the International Court of Justice or its predecessor, though the pace is clearly picking up. There are doubtless many factors that explain this phenomenon, including reluctance to give a dispute a high international profile, reluctance to trust dispute resolution to a third party over whom states have no control, hesitancy about submitting a dispute to a tribunal composed of judges, the expense of litigating before the World Court, and the like. On the other hand, states are bringing an increasing number of cases of all kinds, including those concerning international watercourses, to the Court, indicating that it is becoming a more popular forum for the resolution of disputes.
Part IV Fundamental Rights and Obligations, A Substantive Obligations, 10 The Obligation to Prevent Harm to Other Riparian States
Authors: Stephen C McCaffrey
Published: May 2019

This chapter focuses on the “no-harm” obligation. Article 7 of the 1997 UN Watercourses Convention provides that in utilizing an international watercourse, states have an obligation to “prevent the causing of significant harm” to other states sharing the watercourse. The inclusion of this provision in the Convention, and especially its placement in a section of the Convention entitled “General Principles,” implies that it is one of the fundamental obligations in the field. Nevertheless, many questions surround the no-harm principle, particularly as it applies in the context of international watercourses. The chapter then addresses three preliminary matters. The first concerns the legal status of the no-harm principle and its relationship to equitable utilization. The second question concerns the meaning of “harm.” The third and final issue has to do with the way in which the operation of the no-harm rule has traditionally been conceived.
Part IV Fundamental Rights and Obligations, A Substantive Obligations, 11 The Obligation to Protect International Watercourses and Their Ecosystems
Authors: Stephen C McCaffrey
Published: May 2019

This chapter looks at the obligation not to cause significant pollution to other states sharing freshwater resources, and of the emerging obligation to protect the ecosystems of international watercourses. While problems of water pollution have perhaps received more attention in the literature, it seems probable that the protection of watercourse ecosystems is of wider significance, in terms of geography, meeting basic human needs, and sustainable development. Sustainable development was endorsed at the 1992 Earth Summit as the proper approach to reconciling economic development with protection of the environment. It aims at ensuring that economic development will not exhaust the very resources on which it, and human welfare itself, depend. Clean water and healthy aquatic ecosystems are cornerstones of this effort. International law has now progressed to the point that it protects those values.
Part IV Fundamental Rights and Obligations, B Procedural Obligations, 12 Procedural Obligations
Authors: Stephen C McCaffrey
Published: May 2019

This chapter addresses the procedural obligations relating to international watercourses. Even some of the most important “substantive” obligations have procedural components or aspects. This and the development of the procedural obligations themselves are no doubt due to the fact that international watercourses bind states together and require cooperation for their equitable and sustainable utilization as well as for their protection. Even if unilateral actions with regard to shared water resources do not produce a “tragedy of the commons,” they can easily lead to disputes, which may not be resolved easily if a use has become entrenched. This is perhaps why states in their practice have found it to be to their advantage to cooperate with their co-riparians with regard to the use and protection of their shared water resources. The benefits of, even the need for, such cooperation has also been recognized by international tribunals and by learned societies.
Part IV Fundamental Rights and Obligations, C Groundwater, 13 The Special Case of Groundwater
Authors: Stephen C McCaffrey
Published: May 2019

This chapter explores the legal principles and rules that govern the use of shared groundwater resources. The different characteristics and behavior of groundwater would seem to justify stricter standards and more stringent protection than is applicable to surface water. The current legal regime governing surface water, as expressed in the United Nations Watercourses Convention, may be sufficiently flexible to be capable of adaptation to the particular requirements of groundwater, but this situation should prevail only until a special regime can be tailored for international groundwater. The legal regime applicable to so-called confined transboundary groundwater is even less clear than that applicable to international groundwater that is related to surface water, but there is support for applying the same rules to the former type of groundwater as to the other forms discussed in this chapter.
Article 7
Authors: Murray Rachel
Published: May 2019

This section is about Article 7 of the African Charter on Human and Peoples’ Rights dealing with Right to a Fair Trial.
Article 19
Authors: Murray Rachel
Published: May 2019

This section is about Article 19 of the African Charter on Human and Peoples’ Rights dealing with Equality of Peoples.
Articles 41–44
Authors: Murray Rachel
Published: May 2019

This section is about Articles 41–44 of the African Charter on Human and Peoples’ Rights dealing with Appointment of Secretary, Election of Chair and Vice Chair, Voting, Privileges and Immunities.
Article 56
Authors: Murray Rachel
Published: May 2019

This section is about Article 56 of the African Charter on Human and Peoples’ Rights dealing with Admissibility of Individual Communications.
Article 58
Authors: Murray Rachel
Published: May 2019

This section is about Article 58 of the African Charter on Human and Peoples’ Rights dealing with Serious or Massive Violations and Emergencies.
Time-dependent spectral modelling of Markarian 421 during a violent outburst in 2010
Authors: Banerjee B , Joshi M , Majumdar P , Williamson K E , Jorstad S G , Marscher A P
Published: May 2019

We present the results of extensive modelling of the spectral energy distributions (SEDs) of the closest blazar (z = 0.031) Markarian 421 (Mrk 421) during a giant outburst in 2010 February. The source underwent rapid flux variations in both X-rays and very high energy (VHE) gamma rays as it evolved from a low-flux state on 2010 February 13–15 to a high-flux state on 2010 February 17. During this period, the source exhibited significant spectral hardening from X-rays to VHE gamma rays while exhibiting a ‘harder when brighter’ behaviour in these energy bands. We reproduce the broad-band SED using a time-dependent multizone leptonic jet model with radiation feedback. We find that an injection of the leptonic particle population with a single power-law energy distribution at shock fronts followed by energy losses in an inhomogeneous emission region is suitable for explaining the evolution of Mrk 421 from low- to high-flux state in 2010 February. The spectral states are successfully reproduced by a combination of a few key physical parameters, such as the maximum and minimum cut-offs and power-law slope of the electron injection energies, magnetic field strength, and bulk Lorentz factor of the emission region. The simulated light curves and spectral evolution of Mrk 421 during this period imply an almost linear correlation between X-ray flux at 1–10 keV energies and VHE gamma-ray flux above 200 GeV, as has been previously exhibited by this source. Through this study, a general trend that has emerged for the role of physical parameters is that, as the flare evolves from a low- to a high-flux state, higher bulk kinetic energy is injected into the system with a harder particle population and a lower magnetic field strength.
Outflows, inflows, and young stars in the inner 200 pc of the Seyfert galaxy NGC 2110
Authors: Diniz Marlon R , Riffel Rogemar A , Storchi-Bergmann Thaisa , Riffel Rogério
Published: May 2019

We present a 2D mapping of stellar population age components, emission-line fluxes, gas excitation, and kinematics within the inner ∼200 pc of the Seyfert 2 galaxy NGC 2110. We used the Gemini North Integral Field Spectrograph (NIFS) in the J and K bands at a spatial resolution of ∼22  pc. The unresolved nuclear continuum is originated in combined contributions of young stellar population (SP; age ≤ 100  Myr), a featureless AGN continuum and hot dust emission. The young-intermediate SP (100 < age ≤ 700 Myr) is distributed in a ring-shaped structure at ≈140  pc from the nucleus, which is roughly coincident with the lowest values of the stellar velocity dispersion. In the inner ≈115  pc the old SP (age > 2 Gyr) is dominant. The [Fe ii] $\lambda \, 1.2570\, \mu$m emission-line flux distribution is correlated with the radio emission and its kinematics comprise two components, one from gas rotating in the galaxy plane and another from gas in outflow within a bicone-oriented along north–south. These outflows seem to originate in the interaction of the radio jet with the ambient gas producing shocks that are the main excitation mechanism of the [Fe ii] emission. We estimate: (1) an ionized gas mass outflow rate of ∼0.5  M⊙ yr−1 at ∼70 pc from the nucleus; and (2) a kinetic power for the outflow of only 0.05 per cent of the AGN bolometric luminosity implying weak feedback effect on the galaxy.
Protein Interaction Z Score Assessment (PIZSA): an empirical scoring scheme for evaluation of protein–protein interactions
Authors: Roy Ankit A , Dhawanjewar Abhilesh S , Sharma Parichit , Singh Gulzar , Madhusudhan M S
Published: May 2019

Our web server, PIZSA (http://cospi.iiserpune.ac.in/pizsa), assesses the likelihood of protein–protein interactions by assigning a Z Score computed from interface residue contacts. Our score takes into account the optimal number of atoms that mediate the interaction between pairs of residues and whether these contacts emanate from the main chain or side chain. We tested the score on 174 native interactions for which 100 decoys each were constructed using ZDOCK. The native structure scored better than any of the decoys in 146 cases and was able to rank within the 95th percentile in 162 cases. This easily outperforms a competing method, CIPS. We also benchmarked our scoring scheme on 15 targets from the CAPRI dataset and found that our method had results comparable to that of CIPS. Further, our method is able to analyse higher order protein complexes without the need to explicitly identify chains as receptors or ligands. The PIZSA server is easy to use and could be used to score any input three-dimensional structure and provide a residue pair-wise break up of the results. Attractively, our server offers a platform for users to upload their own potentials and could serve as an ideal testing ground for this class of scoring schemes.
hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles
Authors: Fischl Harry , Neve Jonathan , Wang Zhiqiao , Patel Radhika , Louey Alastair , Tian Bin , Furger Andre
Published: May 2019

Alternative cleavage and polyadenylation (APA) can occur at more than half of all human genes, greatly enhancing the cellular repertoire of mRNA isoforms. As these isoforms can have altered stability, localisation and coding potential, deregulation of APA can disrupt gene expression and this has been linked to many diseases including cancer progression. How APA generates cancer-specific isoform profiles and what their physiological consequences are, however, is largely unclear. Here we use a subcellular fractionation approach to determine the nuclear and cytoplasmic APA profiles of successive stages of colon cancer using a cell line-based model. Using this approach, we show that during cancer progression specific APA profiles are established. We identify that overexpression of hnRNPC has a critical role in the establishment of APA profiles characteristic for metastatic colon cancer cells, by regulating poly(A) site selection in a subset of genes that have been implicated in cancer progression including MTHFD1L.
The dynamics of forming a triplex in an artificial telomere inferred by DNA mechanics
Authors: Li Ning , Wang Junli , Ma Kangkang , Liang Lin , Mi Lipei , Huang Wei , Ma Xiaofeng , Wang Zeyu , Zheng Wei , Xu Linyan , Chen Jun-Hu , Yu Zhongbo
Published: May 2019

A telomere carrying repetitive sequences ends with a single-stranded overhang. The G-rich overhang could fold back and bind in the major groove of its upstream duplex, forming an antiparallel triplex structure. The telomeric triplex has been proposed to function in protecting chromosome ends. However, we lack strategies to mechanically probe the dynamics of a telomeric triplex. Here, we show that the topological dynamics of a telomeric triplex involves 3′ overhang binding at the ds/ssDNA junction inferred by DNA mechanics. Assisted by click chemistry and branched polymerase chain reaction, we developed a rescue-rope-strategy for mechanically manipulating an artificial telomeric DNA with a free end. Using single-molecule magnetic tweezers, we identified a rarely forming (5%) telomeric triplex which pauses at an intermediate state upon unzipping the Watson–Crick paired duplex. Our findings revealed that a mechanically stable triplex formed in a telomeric DNA can resist a force of 20 pN for a few seconds in a physiological buffer. We also demonstrated that the rescue-rope-strategy assisted mechanical manipulation can directly rupture the interactions between the third strand and its targeting duplex in a DNA triplex. Our single-molecule rescue-rope-strategy will serve as a general tool to investigate telomere dynamics and further develop triplex-based biotechnologies.
A group II intron-encoded protein interacts with the cellular replicative machinery through the β-sliding clamp
Authors: García-Rodríguez Fernando M , Neira José L , Marcia Marco , Molina-Sánchez María D , Toro Nicolás
Published: May 2019

Group II introns are self-splicing mobile genetic retroelements. The spliced intron RNA and the intron-encoded protein (IEP) form ribonucleoprotein particles (RNPs) that recognize and invade specific DNA target sites. The IEP is a reverse transcriptase/maturase that may bear a C-terminal endonuclease domain enabling the RNP to cleave the target DNA strand to prime reverse transcription. However, some mobile introns, such as RmInt1, lack the En domain but nevertheless retrohome efficiently to transient single-stranded DNA target sites at a DNA replication fork. Their mobility is associated with host DNA replication, and they use the nascent lagging strand as a primer for reverse transcription. We searched for proteins that interact with RmInt1 RNPs and direct these RNPs to the DNA replication fork. Co-immunoprecipitation assays suggested that DnaN (the β-sliding clamp), a component of DNA polymerase III, interacts with the protein component of the RmInt1 RNP. Pulldown assays, far-western blots and biolayer interferometry supported this interaction. Peptide binding assays also identified a putative DnaN-interacting motif in the RmInt1 IEP structurally conserved in group II intron IEPs. Our results suggest that intron RNP interacts with the β-sliding clamp of the DNA replication machinery, favouring reverse splicing into the transient ssDNA at DNA replication forks.
A Drosophila cell-free system that senses DNA breaks and triggers phosphorylation signalling
Authors: Harpprecht Lisa , Baldi Sandro , Schauer Tamas , Schmidt Andreas , Bange Tanja , Robles Maria S , Kremmer Elisabeth , Imhof Axel , Becker Peter B
Published: May 2019

Preblastoderm Drosophila embryo development is characterized by fast cycles of nuclear divisions. Extracts from these embryos can be used to reconstitute complex chromatin with high efficiency. We now discovered that this chromatin assembly system contains activities that recognize unprotected DNA ends and signal DNA damage through phosphorylation. DNA ends are initially bound by Ku and MRN complexes. Within minutes, the phosphorylation of H2A.V (homologous to γH2A.X) initiates from DNA breaks and spreads over tens of thousands DNA base pairs. The γH2A.V phosphorylation remains tightly associated with the damaged DNA and does not spread to undamaged DNA in the same reaction. This first observation of long-range γH2A.X spreading along damaged chromatin in an in vitro system provides a unique opportunity for mechanistic dissection. Upon further incubation, DNA ends are rendered single-stranded and bound by the RPA complex. Phosphoproteome analyses reveal damage-dependent phosphorylation of numerous DNA-end-associated proteins including Ku70, RPA2, CHRAC16, the exonuclease Rrp1 and the telomer capping complex. Phosphorylation of spindle assembly checkpoint components and of microtubule-associated proteins required for centrosome integrity suggests this cell-free system recapitulates processes involved in the regulated elimination of fatally damaged syncytial nuclei.
High efficiency error suppression for accurate detection of low-frequency variants
Authors: Wang Ting Ting , Abelson Sagi , Zou Jinfeng , Li Tiantian , Zhao Zhen , Dick John E , Shlush Liran I , Pugh Trevor J , Bratman Scott V
Published: May 2019

Detection of cancer-associated somatic mutations has broad applications for oncology and precision medicine. However, this becomes challenging when cancer-derived DNA is in low abundance, such as in impure tissue specimens or in circulating cell-free DNA. Next-generation sequencing (NGS) is particularly prone to technical artefacts that can limit the accuracy for calling low-allele-frequency mutations. State-of-the-art methods to improve detection of low-frequency mutations often employ unique molecular identifiers (UMIs) for error suppression; however, these methods are highly inefficient as they depend on redundant sequencing to assemble consensus sequences. Here, we present a novel strategy to enhance the efficiency of UMI-based error suppression by retaining single reads (singletons) that can participate in consensus assembly. This ‘Singleton Correction’ methodology outperformed other UMI-based strategies in efficiency, leading to greater sensitivity with high specificity in a cell line dilution series. Significant benefits were seen with Singleton Correction at sequencing depths ≤16 000×. We validated the utility and generalizability of this approach in a cohort of >300 individuals whose peripheral blood DNA was subjected to hybrid capture sequencing at ∼5000× depth. Singleton Correction can be incorporated into existing UMI-based error suppression workflows to boost mutation detection accuracy, thus improving the cost-effectiveness and clinical impact of NGS.