bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B contact tracing: what works?
Authors: Ash Thalia , Mascarenhas Lester , Furler John , Temple-Smith Meredith
Published: October 2018

In 2012, over 239000 people were living in Australia with chronic hepatitis B (CHB). Australia’s Second National Hepatitis B Strategy (2014) recommends testing contacts to increase identification of people with CHB, but it is generally poorly performed. CHB prevalence in Australia is increasing and contact tracing (CT) remains an untapped strategy for identifying infected individuals. A systematic CT system has been established in a government-funded primary health centre in Melbourne, which services 2000 refugees. This mixed-methods study aimed to describe the structure of the CT system, determine its effectiveness and identify enablers of success. The CT system’s structure was elicited from field notes. CT effectiveness (proportion of contacts traced and serologically confirmed as infected or immune to HBV) was determined by auditing clinical records. Semi-structured interviews with seven health professionals were thematically analysed to identify enablers of CT success. Overall, 122 CHB index cases had 420 contacts. And 90.0% (n=380) of 420 contacts were successfully traced, 68.0% (n=83) of index cases had 100% of their contacts successfully traced and 80.7% (n=339) of all contacts were immune; 28.8% (n=121) had evidence of previous exposure and 55.0% (n=231) had evidence of vaccination. Also, 8.1% (n=34) were chronically infected. Interviews elicited seven themes important to the success of the CT system: Teamwork; Organisation; Health professional expertise; Patient education; Centralisation of the system; Influence of patient culture; and Use of nurses in CT. Teamwork and Organisation were previously unidentified in the literature. This CT system is successful and could be implemented elsewhere, provided an organised, cohesive, nurse-led team is established.
Humans incorporate attention-dependent uncertainty into perceptual decisions and confidence
Authors: Denison Rachel N. , Adler William T. , Carrasco Marisa , Ma Wei Ji
Published: October 2018

Significance

We must routinely make decisions based on uncertain sensory information. Sometimes that uncertainty is related to our own cognitive state, such as when we are not paying attention. Do our decisions about what we perceive take into account our attentional state? Or are we blind to such internal sources of uncertainty, leading to poor decisions and overconfidence? We found that human observers take attention-dependent uncertainty into account when categorizing visual stimuli and reporting their confidence in a task in which uncertainty is relevant for performance. Moreover, they do so in an approximately Bayesian fashion. Human perceptual decision-making can therefore, at least in some cases, adjust in a statistically appropriate way to external and internal sources of uncertainty.
Cryo-ET reveals the macromolecular reorganization of
S. pombe
mitotic chromosomes in vivo
Authors: Cai Shujun , Chen Chen , Tan Zhi Yang , Huang Yinyi , Shi Jian , Gan Lu
Published: October 2018

Significance

It has long been known that chromosomes, which contain life’s genetic instructions, condense into discrete bodies when cells divide. Chromosome condensation is thought to shut down gene expression and is misregulated in many diseases. The molecular details of this process are unknown because the fundamental subunits of chromosomes, called nucleosomes, are too small and fragile to be seen by conventional microscopy. We used state-of-the-art 3D cryo-electron tomography to reveal how chromosomes condense within intact cells. We found evidence that condensation is uneven, resulting in porous chromosomes that allow cells to express a limited set of genes. Furthermore, our work and those of others suggest that chromatin dynamics at the molecular scale are an underappreciated component of chromosome function.
Neural reactivation in parietal cortex enhances memory for episodically linked information
Authors: Jonker Tanya R. , Dimsdale-Zucker Halle , Ritchey Maureen , Clarke Alex , Ranganath Charan
Published: October 2018

Significance

Recalling information is useful for more than just accessing memories; it is also a powerful way to enhance long-term memory. Using brain imaging, we discovered that, when trying to remember, people reactivate the specific information they are searching for, along with other information from the same event. The results demonstrate that memories of the past are organized in terms of integrated events and the act of recalling even a small part of an event engages brain networks that have powerful effects on the ability to retain information from the entire event.
Empirical evidence of mental health risks posed by climate change
Authors: Obradovich Nick , Migliorini Robyn , Paulus Martin P. , Rahwan Iyad
Published: October 2018

Significance

Wellbeing falters without sound mental health. Scholars have recently indicated that the impacts of climate change are likely to undermine mental health through a variety of direct and indirect mechanisms. Using daily meteorological data coupled with information from nearly 2 million randomly sampled US residents across a decade of data collection, we find that experience with hotter temperatures and added precipitation each worsen mental health, that multiyear warming associates with an increased prevalence of mental health issues, and that exposure to tropical cyclones, likely to increase in frequency and intensity in the future, is linked to worsened mental health. These results provide added large-scale evidence to the growing literature linking climate change and mental health.
MRI-based assessment of function and dysfunction in myelinated axons
Authors: Spees William M. , Lin Tsen-Hsuan , Sun Peng , Song Chunyu , George Ajit , Gary Sam E. , Yang Hsin-Chieh , Song Sheng-Kwei
Published: October 2018

Significance

Blood-oxygen-level-dependent (BOLD) fMRI has proven to be extremely powerful for studying brain function, but is essentially limited to applications in gray matter. This work investigates the underlying mechanisms responsible for MRI-based signal changes in myelinated axonal fibers of perfused bullfrog sciatic nerves. Simultaneous in-magnet recording of compound action potentials (CAPs) and MRI data acquisition reveal that the diffusion fMRI response is linearly proportional to the number of electrical impulses. Increased restricted diffusion fraction (from diffusion basis spectrum imaging) could be related to submyelinic vacuole formation observed by electron microscopy of perfused nerves fixed resting or undergoing stimulation. Microstructural changes and osmotically driven redistribution of tissue water play a crucial role in the observed diffusion fMRI response in myelinated fibers.
Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti–PD-L1)
Authors: Kowanetz Marcin , Zou Wei , Gettinger Scott N. , Koeppen Hartmut , Kockx Mark , Schmid Peter , Kadel Edward E. , Wistuba Ignacio , Chaft Jamie , Rizvi Naiyer A. , Spigel David R. , Spira Alexander , Hirsch Fred R. , Cohen Victor , Smith Dustin , Boyd Zach , Miley Natasha , Flynn Susan , Leveque Vincent , Shames David S. , Ballinger Marcus , Mocci Simonetta , Shankar Geetha , Funke Roel , Hampton Garret , Sandler Alan , Amler Lukas , Mellman Ira , Chen Daniel S. , Hegde Priti S.
Published: October 2018

Significance

Programmed death-ligand 1 (PD-L1) expression on tumor cells and tumor-infiltrating immune cells is regulated by distinct mechanisms and has nonredundant roles in regulating anticancer immunity, and PD-L1 on both cell types is important for predicting best response to atezolizumab in non-small cell lung cancer.
Randomly distributed embedding making short-term high-dimensional data predictable
Authors: Ma Huanfei , Leng Siyang , Aihara Kazuyuki , Lin Wei , Chen Luonan
Published: October 2018

Significance

Making accurate forecast or prediction is a challenging task in the big data era, in particular for those datasets involving high-dimensional variables but short-term time series points, and these datasets are omnipresent in many fields. In this work, a model-free framework, named as “randomly distributed embedding” (RDE), is proposed to accurately predict future dynamics based on such short-term but high-dimensional data. The RDE framework creates the distribution information from the interactions among high-dimensional variables to compensate for the lack of time points in real applications. Instead of roughly predicting a single trial of future values, this framework achieves the accurate prediction by using the distribution information.
Changes in temperature alter the relationship between biodiversity and ecosystem functioning
Authors: García Francisca C. , Bestion Elvire , Warfield Ruth , Yvon-Durocher Gabriel
Published: October 2018

Significance

Empirical evidence for the response of ecosystem functioning to the combined effects of warming and biodiversity loss is scarce. We show that warming and biodiversity loss interact synergistically, impairing the functioning of microbial communities. We found that as temperatures departed from ambient conditions more species were required to maintain ecosystem functioning. Our results suggest interspecific complementarity increased under thermal stress and high-diversity communities that seemed functionally redundant at ambient temperature became more functionally unique as temperatures changed. Biodiversity may therefore be even more important than previously anticipated when considering the impacts of multiple facets of environmental change.
Mountain snowpack response to different levels of warming
Authors: Huning Laurie S. , AghaKouchak Amir
Published: October 2018

Significance

Across the world, the seasonal montane snowpack stores and releases substantial amounts of water annually. As the global temperature is projected to rise, it becomes increasingly important to assess the vulnerability of the mountain snowpack. We therefore turn to the historical record to understand the extent to which snow water equivalent (SWE) and its centroid respond to different levels of warming. Using a probabilistic framework, we show that even a 1.0 or 2.0 °C increase in average temperature leads to approximately a 20 to 40% increase in the likelihood of below average SWE. We also quantify changes in the distribution of the amount of SWE and where it is stored elevationally across the mountain range given warmer winters.
Histone methylation regulator PTIP is required to maintain normal and leukemic bone marrow niches
Authors: Das Prosun , Veazey Kylee J. , Van Hieu T. , Kaushik Saakshi , Lin Kevin , Lu Yue , Ishii Masaru , Kikuta Junichi , Ge Kai , Nussenzweig Andre , Santos Margarida A.
Published: October 2018

Significance

Osteoclasts play an essential role in bone homeostasis. Understanding how osteoclast differentiation is regulated is important in the context of pathological bone conditions and the hematopoietic stem cell (HSC) niche. We show that PTIP directly promotes chromatin changes required for
Pparγ
expression, a transcription factor essential for osteoclastogenesis. Deletion of PTIP disrupts the integrity of the bone marrow (BM) niche, leading to a reduction of HSCs in the BM. Furthermore, a PTIP-deficient BM microenvironment decreases the number of acute myeloid leukemia-initiating cells in the BM and increases survival upon transplantation. Taken together, our data identify PTIP as an epigenetic regulator of osteoclastogenesis that is required for the integrity of the BM niche to sustain both normal hematopoiesis and leukemia.
Functional and evolutionary characterization of a secondary metabolite gene cluster in budding yeasts
Authors: Krause David J. , Kominek Jacek , Opulente Dana A. , Shen Xing-Xing , Zhou Xiaofan , Langdon Quinn K. , DeVirgilio Jeremy , Hulfachor Amanda Beth , Kurtzman Cletus P. , Rokas Antonis , Hittinger Chris Todd
Published: October 2018

Significance

Evolutionary and comparative genomics, combined with reverse genetics, have the power to identify and characterize new biology. Here, we use these approaches in several nontraditional model species of budding yeasts to characterize a budding yeast secondary metabolite gene cluster, a set of genes responsible for production and reutilization of the siderophore pulcherrimin. We also use this information to assign roles in pulcherrimin utilization for two previously uncharacterizedSaccharomyces cerevisiaegenes. The evolution of this gene cluster in budding yeasts suggests an ecological role for pulcherrimin akin to other microbial public goods systems.
Entropic contribution to enhanced thermal stability in the thermostable P450 CYP119
Authors: Liu Zhuo , Lemmonds Sara , Huang Juan , Tyagi Madhusudan , Hong Liang , Jain Nitin
Published: October 2018

Significance

Understanding the thermodynamic factors responsible for enhanced stability of thermophilic cytochrome P450 enzymes is significant in their development as efficient catalysts for high-temperature monooxygenation reactions. These factors are usually inferred from structural comparison with mesophilic P450s and invoke rigidifying enthalpic interactions as primary thermodynamic determinants for thermostability. Using the thermophilic P450 CYP119 as an example, the present work, however, questions this enthalpy-driven notion of P450 thermostability and provides strong experimental evidence that their thermostability may actually be entropy-driven due to increased flexibility in the folded state relative to mesophilic P450s and that this flexibility is partitioned effectively between functional activity and thermal stability. This represents a major paradigm shift in understanding the basis of thermostability in thermophilic P450s.
Faults and associated karst collapse suggest conduits for fluid flow that influence hydraulic fracturing-induced seismicity
Authors: Galloway Elwyn , Hauck Tyler , Corlett Hilary , Pană Dinu , Schultz Ryan
Published: October 2018

Significance

Induced earthquakes can be caused by hydraulic fracturing (HF). However, the exact means by which stress changes are transferred to seismogenic faults are unknown. This paper provides evidence that a case of induced earthquakes in southern Alberta responded to increased pore pressure on a fault in hydraulic communication with the HF operation. Reflection-seismic and drill core data provide evidence that fluid flow along this fault caused strata underlying the target reservoir to dissolve, causing a karst collapse in the geological past. We suggest that seismogenic and hydraulically active faults are geologically rare and that the injection of fluid directly into them is even rarer, potentially explaining the small percentage of HF wells that cause induced earthquakes.
Distinct facial expressions represent pain and pleasure across cultures
Authors: Chen Chaona , Crivelli Carlos , Garrod Oliver G. B. , Schyns Philippe G. , Fernández-Dols José-Miguel , Jack Rachael E.
Published: October 2018

Significance

Humans often use facial expressions to communicate social messages. However, observational studies report that people experiencing pain or orgasm produce facial expressions that are indistinguishable, which questions their role as an effective tool for communication. Here, we investigate this counterintuitive finding using a new data-driven approach to model the mental representations of facial expressions of pain and orgasm in individuals from two different cultures. Using complementary analyses, we show that representations of pain and orgasm are distinct in each culture. We also show that pain is represented with similar face movements across cultures, whereas orgasm shows differences. Our findings therefore inform understanding of the possible communicative role of facial expressions of pain and orgasm, and how culture could shape their representation.
Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia
Authors: Nour Matthew M. , Dahoun Tarik , Schwartenbeck Philipp , Adams Rick A. , FitzGerald Thomas H. B. , Coello Christopher , Wall Matthew B. , Dolan Raymond J. , Howes Oliver D.
Published: October 2018

Significance

To survive in changing environments animals must use sensory information to form accurate representations of the world. Surprising sensory information might signal that our current beliefs about the world are inaccurate, motivating a belief update. Here, we investigate the neuroanatomical and neurochemical mechanisms underlying the brain’s ability to update beliefs following informative sensory cues. Using multimodal brain imaging in healthy human participants, we demonstrate that dopamine is strongly related to neural signals encoding belief updates, and that belief updating itself is closely related to the expression of individual differences in paranoid ideation. Our results shed new light on the role of dopamine in making inferences and are relevant for understanding psychotic disorders such as schizophrenia, where dopamine function is disrupted.
DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members
Authors: Garrett Andrew M. , Khalil Andre , Walton David O. , Burgess Robert W.
Published: October 2018

Significance

Cell adhesion molecules (CAMs) provide highly specific cell-surface recognition signals by which developing neurons interact with specific partners. However, these CAMs are common between neurons of the same type, and without a mechanism of self-avoidance or of homotypic avoidance, developing neurons will excessively adhere with themselves. This self-avoidance can be promoted by extreme molecular diversity, such as that of
Dscam1
(Down syndrome cell adhesion molecule 1) in flies, which gives neurons distinct barcodes. Mouse
Dscam,
on the other hand, promotes self-avoidance without molecular diversity. Here, we provide evidence that DSCAM can functionally interact with other CAMs, called cadherins and protocadherins, to act like a general “nonstick” signal. Through this “adhesive masking” mechanism, DSCAM allows neurons to develop their appropriate shapes, positions, and connections.
Regnase-1 controls colon epithelial regeneration via regulation of mTOR and purine metabolism
Authors: Nagahama Yasuharu , Shimoda Mayuko , Mao Guoliang , Singh Shailendra Kumar , Kozakai Yuuki , Sun Xin , Motooka Daisuke , Nakamura Shota , Tanaka Hiroki , Satoh Takashi , Maeda Kazuhiko , Akira Shizuo
Published: October 2018

Significance

Idiopathic inflammatory bowel disease (IBD) is associated with the gut microbiota and immune system of the host; however, the precise pathogenesis of IBD is poorly defined. We show that specific deletion of the endoribonuclease Regnase-1 in intestinal epithelial cells relieves the symptoms of experimental colitis during acute inflammation. Regnase-1 deficiency potentiates mTOR signaling and purine metabolism in the colon epithelium. These data provide insight into the role of epithelial Regnase-1 in IBD.
Genetic variation in the
SIM1
locus is associated with erectile dysfunction
Authors: Jorgenson Eric , Matharu Navneet , Palmer Melody R. , Yin Jie , Shan Jun , Hoffmann Thomas J. , Thai Khanh K. , Zhou Xujia , Hotaling James M. , Jarvik Gail P. , Ahituv Nadav , Wessells Hunter , Van Den Eeden Stephen K.
Published: October 2018

Significance

Erectile dysfunction is a common condition of men in middle and older ages. Twin studies suggest that about one-third of the risk is due to genetic factors, independent of other known erectile dysfunction risk factors. However, studies that have searched for specific genetic contributors have been limited due to small sample sizes, candidate gene approaches, and weak phenotyping. As a result, there are no confirmed genetic risk factors for erectile dysfunction. This study finds a specific genetic cause for erectile dysfunction.
Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated mRNA decay pathway
Authors: Wada Masami , Lokugamage Kumari G. , Nakagawa Keisuke , Narayanan Krishna , Makino Shinji
Published: October 2018

Significance

Coronaviruses (CoVs) are important pathogens for humans and domestic animals. The development of effective countermeasures against CoVs requires an understanding of the host pathways that regulate viral gene expression and the viral subversion mechanisms. However, little is known about how the stability of viral mRNAs is controlled. We show that the nonsense-mediated decay (NMD) pathway, which primarily targets aberrant cellular mRNAs for degradation, also induced the degradation of CoV mRNAs that are of cytoplasmic origin. Our study further suggests the importance of CoV-induced inhibition of the NMD pathway, mediated by a viral protein, for efficient CoV replication. The present study highlights an interplay between the NMD pathway and CoVs that modulates viral replication by controlling the stability of viral mRNAs.
Elongation factor P is required to maintain proteome homeostasis at high growth rate
Authors: Tollerson Rodney , Witzky Anne , Ibba Michael
Published: October 2018

Significance

Adaptation to rapidly changing environments is essential for cellular fitness and is a critical component in pathogenesis. Translational control has important roles for fitness in a range of environments and requires multiple factors for efficient responses. One such factor is the translation elongation factor (EF)-P, which alleviates ribosome pausing at polyproline motifs. Our findings show that EF-P-mediated relief of ribosome queuing is integral in environmentally driven changes to translation rates. We observe that ribosome pausing leads to changes in protein yield only under rapid growth conditions, demonstrating that effects resulting from ribosome queuing correlate directly with translational demand. These results provide physiological context to previous studies establishing EF-P as a critical factor in cell growth and virulence.
Language education in and for a multilingual Europe
Authors: Byram Michael
Published: October 2018

As Europe becomes ever more heterogeneous in population and languages, education systems have to change and the teaching of languages has to evolve in terms of policies and methodologies. The specific nature of the European situation includes the presence of European organisations – notably the European Union and the Council of Europe – which impact on policy and methodology at state level, leading to a degree of similarity and harmonisation. The analysis here focuses first on policies and to what extent they take account of changes in societies, and second on changes in the aims and purposes of teaching, and the consequent changes in didactics. Some language policy-making is static and takes little note of change but there is some which takes account of the fluidity of contemporary societies and in particular the ways in which they respond to migration and the languages of migrants. Future directions might give language teaching a role in citizenship education as education systems strive to help create inclusive multilingual societies.
Plurilingual identities
Authors: Hu Adelheid
Published: October 2018

The aim of this paper is to get a clearer understanding about the developments in the research domain of plurilingual education, and especially to gain insights about which steps towards an integrative and identity-oriented language education have been achieved. In a first part, the focus lies on the concept of identity itself, and the way it relates to language and language/intercultural learning. I will then discuss other influential concepts, such as the concept of plurilingualism itself (in contrast to multilingualism), the idea of language repertoires and of translanguaging. In a second part I will concentrate on some equally influential pedagogical and curricular developments such as the “language portraits” or the project “Wege zur Mehrsprachigkeit” (Ways to Multilingualism) that had been developed already in the 1990s in the German state of North Rhine-Westphalia. I will finally take a closer look at existing empirical research that focuses on the learners’ whole language repertoires. This research sheds light on the learners’ and teachers’ perceptions of plurilingualism, and investigates in how far the language repertoires are taken into account within the classroom. While this research focus has been rare until the turn of the millennium, there are now clear signs that the awareness for integrative research perspectives on language learning and teaching has been growing.
Models of multilingual competence
Authors: Hufeisen Britta
Published: October 2018

In this article, I will discuss the notions of first language(s) L1, first foreign language L2 and second foreign language L3, also including further foreign language(s) Lx or Ln and the question of what multilanguage competency means in terms of ‘using’ or even ‘mastering’ a language. A level of C2 in all skills does not appear to be a prerequisite. I will present some of the older models, and some more recent models that reflect social and individual plurilingualism, multiple language learning, and plurilingual speech production. The models have been drawn from a very wide range of research disciplines, including psycholinguistics, sociolinguistics, applied linguistics, teaching-learning research and foreign language teaching methodology. In their respective fields, they serve as theoretical bases and are evaluated during the conduct of pertinent studies. I will use a model to demonstrate the interaction between model formation and the results of data-led research, which are included in the further development of the model.
The multilingual turn in foreign language education
Authors: Melo-Pfeifer Sílvia
Published: October 2018

The multilingual turn in language education has been frequently referred to in recent research. However, the meaning of ‘multilingualism’ is far from being unequivocally understood, which points to a multiplicity of perceptions about what multilingual individuals, multilingual education, multilingual competence and policies to promote multilingualism are. I suggest that a line can be drawn to distinguish between social and individual multilingualism (the latter is also called ‘plurilingualism’) and that, if individual multilingualism is to be achieved, namely by frequenting a school system, the offer of several foreign languages in the school curriculum or the generalization of CLIL approaches are steps forward but not enough to ensure a plurilingual competence. Instead, it is a change of the teaching and learning habitus and paradigms that is needed, namely through the spread of pluralistic approaches to languages and cultures. Furthermore, I claim that English, because it is being taught and learnt globally as the first foreign language, has a pivotal role to play in the development of learners’ plurilingual competence. By encouraging, from the very beginning, the establishment of relationships between languages and varieties, a certain way of teaching English could prepare an integrated learning of subsequent languages. Finally, I discuss the consequences of “Teaching Other Languages to Speakers of English” (TOLSE) instead of the more commonly used “Teaching English to Speakers of Other Languages” (TESOL) and the open questions it points to, that can inspire further research.
English as a lingua franca at the multilingual university
Authors: Mueller Jessica Terese
Published: October 2018

Through an explorative study, we have begun to examine what other languages can be found at the University of Hamburg and what roles these languages play alongside German and English in university instruction. In the first portion of the data collection process, 1454 students and 341 instructors shared information about their multilingual resources, their attitudes and motivation regarding English as a lingua franca, multilingualism and German as a foreign language via an online questionnaire. Initial results show that multilingually raised participants tended to report higher levels of language proficiency in more languages and exhibit important differences related to their attitudes towards and motivations for learning English compared to their monolingually raised peers.
Effect of mutation of C-terminal and heme binding region of Arabidopsis catalase on the import to peroxisomes
Authors: Fujikawa Yukichi , Suekawa Marina , Endo Satoshi , Fukami Youjirou , Mano Shoji , Nishimura Mikio , Esaka Muneharu
Published: October 2018

We evaluated the import of Arabidopsis catalase to peroxisomes under homogenous transient expression. The amino acids at −11 to −4 from the C-terminus are necessary for catalase import. The results are in agreement with the previous work under stable expression. We first demonstrate that heme-binding sites are important for peroxisomal import, suggesting the importance of catalase folding.

Abbreviations: AtCat: Arabidopsis catalase; PTS: peroxisomal targeting signal; PEX: Peroxin
Quantitation and sensory properties of three newly identified pyroglutamyl oligopeptides in sake
Authors: Hashizume Katsumi , Ito Toshihiko , Nagae Yusuke , Tokiwano Tetsuo
Published: October 2018

Three new peptides: (pGlu)L-ethyl, (pGlu)LFGP-ethyl and (pGlu)LFNP-ethyl, were identified in the search for pyroglutamyl oligopeptide ethyl esters in sake. The ethyl esterified peptides in sake were quantitated using stable isotope dilution analysis and additional quantitation of (pGlu)L was performed using an external standard method. The concentrations of (pGlu)L-ethyl and (pGlu)L in 33 commercial sake samples ranged from 0.16 to 1.57 mg/L and 1.49 to 7.55 mg/L, respectively. The sensory properties of the pyroglutamyl oligopeptide ethyl esters and corresponding non-esterified peptides were examined: the estimated difference threshold of (pGlu)L (2.0 mg/L) and (pGlu)L-ethyl (0.267 mg/L) was exceeded in 32 and 26 samples, respectively. Estimated thresholds of (pGlu)LFGP-ethyl and (pGlu)LFNP-ethyl were often lower than the levels in quantitated sake samples. The sensory effects of these pyroglutamyl dipeptides on a model sake quality may be negative because of their unpleasant taste, however, (pGlu)LFNP-ethyl may be positive because of its mild taste.
Remedies for improving Great Lakes Remedial Action Plans: A Policy Delphi study
Authors: McLaughlin Chris , Krantzberg Gail
Published: October 2018

Remedial Action Plans continue to be the principal program to operationalize an ecosystem approach to the restoration of degraded locations across the Laurentian Great Lakes called Areas of Concern. Initiated in 1985, the progress of Remedial Action Plans on balance has been slow and disappointing. The Remedial Action Plan program has been continued following revisions to the Great Lakes Water Quality Agreement in 2012 despite very little systematic inspection of its strengths and limitations. Further, the 2012 Agreement calls for a “nearshore framework” with no clarity on the process for understanding place-based governance methods as developed under these Remedial Action Plans. In this context, we conducted a three-round anonymous online Policy Delphi study involving several dozen experts in the development and implementation of Remedial Action Plans from across the Great Lakes basin within government, industry, academia and civil society. Round 1 collected their direct knowledge of the strengths and limitations of Remedial Action Plans. We distilled that knowledge and asked study participants in Round 2 to further reflect on what worked and what did not work in their experience as Remedial Action Plan practitioners. We found an expected diversity of opinion on what ails the program in Round 2, but an unexpected consensus on the desire to move forward with seven governance options that emerged and were ranked by participants in Round 3. Rankings also indicated a consensus that the options were somewhat feasible and likely to succeed as enhancements to the current governance of Remedial Action Plans. Importantly, the results relate to both the structure and attributes of these collaborative processes, and we therefore stress the need to focus on the predominant tendencies and characteristics that underline Remedial Action Plan processes. These findings will have broad significance for evolving place-based nearshore restoration strategies in the Great Lakes and elsewhere as such programs are initiated.
Eutrophication in three Canadian Areas of Concern: Phytoplankton and major nutrient interactions
Authors: Munawar M. , Fitzpatrick M. A. J.
Published: October 2018

The Bay of Quinte, Hamilton Harbour and Toronto Harbour are all coastal regions of Lake Ontario that have experienced eutrophication and all have been designated as ‘Areas of Concern’ under the terms of the Great Lakes Water Quality Agreement. An assessment of the phytoplankton communities in relation to nutrient (P,N,Si) regimes was undertaken during 2015 (Bay of Quinte) and 2016 (Hamilton Harbour and Toronto Harbour) in order to compare and contrast the dynamics of eutrophication in the three ecosystems. Bay of Quinte was found to be phosphorus and silica enriched, but nitrogen limited which resulted in a phytoplankton community dominated by both filamentous diatoms and diazotrophic (N–fixing) cyanobacteria. Hamiton Harbour was phosphorus and nitrogen enriched, but silica depleted with a community dominated by small and large phytoflagellates in addition to experiencing cyanobacteria blooms. Toronto Harbour, by contrast, showed only moderate phosphorus enrichment and no nitrogen limitation, but some silica depletion; phytoplankton was dominated by smaller flagellates and pennate diatoms. Our findings suggest that while phosphorus was a key factor causing cultural eutrophication, other nutrients including nitrogen and silica also had important roles in determining the biomass and composition of the algal standing crop. Future management activities need to consider how the interactions of phosphorus with other nutrients (nitrogen, silica) affect the dynamics of the phytoplankton community in order to promote the recovery of eutrophic ecosystems.
Kinesin-binding–triggered conformation switching of microtubules contributes to polarized transport
Authors: Shima Tomohiro , Morikawa Manatsu , Kaneshiro Junichi , Kambara Taketoshi , Kamimura Shinji , Yagi Toshiki , Iwamoto Hiroyuki , Uemura Sotaro , Shigematsu Hideki , Shirouzu Mikako , Ichimura Taro , Watanabe Tomonobu M. , Nitta Ryo , Okada Yasushi , Hirokawa Nobutaka
Published: October 2018

Kinesin-1, the founding member of the kinesin superfamily of proteins, is known to use only a subset of microtubules for transport in living cells. This biased use of microtubules is proposed as the guidance cue for polarized transport in neurons, but the underlying mechanisms are still poorly understood. Here, we report that kinesin-1 binding changes the microtubule lattice and promotes further kinesin-1 binding. This high-affinity state requires the binding of kinesin-1 in the nucleotide-free state. Microtubules return to the initial low-affinity state by washing out the binding kinesin-1 or by the binding of non-hydrolyzable ATP analogue AMPPNP to kinesin-1. X-ray fiber diffraction, fluorescence speckle microscopy, and second-harmonic generation microscopy, as well as cryo-EM, collectively demonstrated that the binding of nucleotide-free kinesin-1 to GDP microtubules changes the conformation of the GDP microtubule to a conformation resembling the GTP microtubule.
Kinetics of adult hematopoietic stem cell differentiation in vivo
Authors: Upadhaya Samik , Sawai Catherine M. , Papalexi Efthymia , Rashidfarrokhi Ali , Jang Geunhyo , Chattopadhyay Pratip , Satija Rahul , Reizis Boris
Published: October 2018

Adult hematopoiesis has been studied in terms of progenitor differentiation potentials, whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSCs) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady-state. Labeled cells, comprising primarily long-term HSCs and some short-term HSCs, produced megakaryocytic lineage progeny within 1 wk in a process that required only two to three cell divisions. Erythroid and myeloid progeny emerged simultaneously by 2 wk and included a progenitor population with expression features of both lineages. Myeloid progenitors at this stage showed diversification into granulocytic, monocytic, and dendritic cell types, and rare intermediate cell states could be detected. In contrast, lymphoid differentiation was virtually absent within the first 3 wk of tracing. These results show that continuous differentiation of HSCs rapidly produces major hematopoietic lineages and cell types and reveal fundamental kinetic differences between megakaryocytic, erythroid, myeloid, and lymphoid differentiation.
On the Explanatory Depth and Pragmatic Value of Coarse-Grained, Probabilistic, Causal Explanations
Authors: Kinney David
Published: October 2018

This article considers the thesis that a more proportional relationship between a cause and its effect yields a more abstract causal explanation of that effect, thereby producing a deeper explanation. This thesis has important implications for choosing the optimal granularity of explanation for a given explanandum. In this article, I argue that this thesis is not generally true of probabilistic causal relationships. In light of this finding, I propose a pragmatic measure of explanatory depth. This measure uses a decision-theoretic model of information pricing to determine the optimal granularity of explanation for a given explanandum, agent, and decision problem.
Stochastic gravitational wave backgrounds
Authors: Christensen Nelson
Published: October 2018

A stochastic background of gravitational waves could be created by the superposition of a large number of independent sources. The physical processes occurring at the earliest moments of the universe certainly created a stochastic background that exists, at some level, today. This is analogous to the cosmic microwave background, which is an electromagnetic record of the early universe. The recent observations of gravitational waves by the Advanced LIGO and Advanced Virgo detectors imply that there is also a stochastic background that has been created by binary black hole and binary neutron star mergers over the history of the universe. Whether the stochastic background is observed directly, or upper limits placed on it in specific frequency bands, important astrophysical and cosmological statements about it can be made. This review will summarize the current state of research of the stochastic background, from the sources of these gravitational waves to the current methods used to observe them.
Torsional waves driven by convection and jets in Earth’s liquid core
Authors: Teed R J , Jones C A , Tobias S M
Published: October 2018

Turbulence and waves in Earth’s iron-rich liquid outer core are believed to be responsible for the generation of the geomagnetic field via dynamo action. When waves break upon the mantle they cause a shift in the rotation rate of Earth’s solid exterior and contribute to variations in the length-of-day on a ∼6-yr timescale. Though the outer core cannot be probed by direct observation, such torsional waves are believed to propagate along Earth’s radial magnetic field, but as yet no self-consistent mechanism for their generation has been determined. Here we provide evidence of a realistic physical excitation mechanism for torsional waves observed in numerical simulations. We find that inefficient convection above and below the solid inner core traps buoyant fluid forming a density gradient between pole and equator, similar to that observed in Earth’s atmosphere. Consequently, a shearing jet stream—a ‘thermal wind’—is formed near the inner core; evidence of such a jet has recently been found. Owing to the sharp density gradient and influence of magnetic field, convection at this location is able to operate with the turnover frequency required to generate waves. Amplified by the jet it then triggers a train of oscillations. Our results demonstrate a plausible mechanism for generating torsional waves under Earth-like conditions and thus further cement their importance for Earth’s core dynamics.
Trends and inequalities in maternal and child health in a Brazilian city: methodology and sociodemographic description of four population-based birth cohort studies, 1982–2015
Authors: Bertoldi Andréa Dâmaso , Barros Fernando C , Hallal Pedro R C , Mielke Gregore I , Oliveira Paula D , Maia Maria Fatima S , Horta Bernardo L , Gonçalves Helen , Barros Aluísio J D , Tovo-Rodrigues Luciana , Murray Joseph , Victora Cesar G ,   Pelotas Cohorts Study Group, Menezes Ana M B , Matijasevich Alicia , Bassani Diego , Wehrmeister Fernando C , Santos Iná S , Assunção Maria Cecilia F , Silveira Mariangela F , Domingues Marlos Rodrigues
Published: October 2018

Background

Few low-middle-income countries have data from comparable birth cohort studies spanning over time. We report on the methods used by the Pelotas cohorts (1982, 1993, 2004 and 2015) and describe time trends in sociodemographic characteristics of the participant families.

Methods

During the four study years, all maternity hospitals in the city were visited daily, and all urban women giving birth were enrolled. Data on socioeconomic and demographic characteristics were collected using standardized questionnaires, including data on maternal and paternal skin colour, age and schooling, maternal marital status, family income and household characteristics. The analyses included comparisons of time trends and of socioeconomic and ethnic group inequalities.

Results

Despite a near 50% increase in the city’s population between 1982 and 2015, the total number of births declined from 6011 to 4387. The proportion of mothers aged ≥35 years increased from 9.9% to 14.8%, and average maternal schooling from 6.5 [standard deviation (SD) 4.2] to 10.1 (SD 4.0) years. Treated water was available in 95.3% of households in 1982 and 99.3% in 2015. Three-quarters of the families had a refrigerator in 1982, compared with 98.3% in 2015. Absolute income-related inequalities in maternal schooling, household crowding, household appliances and access to treated water were markedly reduced between 1982 and 2015. Maternal skin colour was associated with inequalities in age at childbearing and schooling, as well as with household characteristics.

Conclusions

During the 33-year period, there were positive changes in social and environmental determinants of health, including income, education, fertility and characteristics of the home environment. Socioeconomic inequality was also reduced.
Development and evaluation of a matheuristic for the combined beam angle and dose distribution problem in radiotherapy planning
Authors: Obal Thalita Monteiro , Irawan Chandra Ade , Jones Dylan , Ouelhadj Djamila , Florentino Helenice Oliveira , Gryczak Vania , Volpi Neida Maria Patias , Wilhelm Volmir Eugenio
Published: October 2018

Radiotherapy planning is vital for ensuring the maximum level of effectiveness of treatment. In the planning task, there are at least two connected decision problems that can be modelled and solved using operational research techniques: determining the best position of the radiotherapy machine (beam angle problem) and the optimal dose delivered through each beam (dose distribution problem). This paper presents a mathematical optimization model for solving the combined beam angle and dose distribution problems in the presence of multiple objectives. A matheuristic based on Tabu Search (called TSrad) is developed to solve realistic large-scale instances. The performance of the proposed method is assessed on two prostate cancer instances, namely a single computed tomography (CT) slice and a set of CT slices (three-dimensional problem). For the single-slice problem, the results of TSrad are compared to the optimal solutions obtained by an exact method. Our experiments show that TSrad is able to achieve optimality for some instances. For the multi-slice problem, our experiments show that TSrad produces viable solutions that can be attained in a reasonable computational time.
A convergent finite volume method for the Kuramoto equation and related nonlocal conservation laws
Authors: Chatterjee N , Fjordholm U S
Published: October 2018

We derive and study a Lax–Friedrichs-type finite volume method for a large class of nonlocal continuity equations in multiple dimensions. We prove that the method converges weakly to the measure-valued solution and converges strongly if the initial data is of bounded variation. Several numerical examples for the kinetic Kuramoto equation are provided, demonstrating that the method works well for both regular and singular data.
Inclusion of Plasma Prolactin Levels in Current Risk Prediction Models of Premenopausal and Postmenopausal Breast Cancer
Authors: Gabrielson Marike , Ubhayasekera Kumari , Ek Bo , Andersson Franko Mikael , Eriksson Mikael , Czene Kamila , Bergquist Jonas , Hall Per
Published: October 2018

Background

Circulating plasma prolactin is associated with breast cancer risk and may improve our ability to identify high-risk women. Mammographic density is a strong risk factor for breast cancer, but the association with prolactin is unclear. We studied the association between breast cancer, established breast cancer risk factors and plasma prolactin, and improvement of risk prediction by adding prolactin.

Methods

We conducted a nested case-control study including 721 breast cancer patients and 1400 age-matched controls. Plasma prolactin levels were assayed using immunoassay and mammographic density measured by STRATUS. Odds ratios (ORs) were calculated by multivariable adjusted logistic regression, and improvement in the area under the curve for the risk of breast cancer by adding prolactin to established risk models. Statistical tests were two-sided.

Results

In multivariable adjusted analyses, prolactin was associated with risk of premenopausal (OR, top vs bottom quintile = 1.9; 1.88 (95% confidence interval [CI] = 1.08 to 3.26) but not with postmenopausal breast cancer. In postmenopausal cases prolactin increased by 10.6% per cBIRADS category (Ptrend = .03). In combined analyses of prolactin and mammographic density, ORs for women in the highest vs lowest tertile of both was 3.2 (95% CI = 1.3 to 7.7) for premenopausal women and 2.44 (95% CI = 1.44 to 4.14) for postmenopausal women. Adding prolactin to current risk models improved the area under the curve of the Gail model (+2.4 units, P = .02), Tyrer-Cuzick model (+3.8, P = .02), and the CAD2Y model (+1.7, P = .008) in premenopausal women.

Conclusion

Circulating plasma prolactin and mammographic density appear independently associated with breast cancer risk among premenopausal women, and prolactin may improve risk prediction by current risk models.