bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-magnetic field effects on laser-driven wakefield electron acceleration in axially magnetized ion channel
Authors: Kargarian A. , Hajisharifi K.
Published: October 2020

In this paper, we have investigated the relativistic electron acceleration by plasma wave in an axially magnetized plasma by considering the self-magnetic field effects. We show that the optimum value of an external axial magnetic field could increase the electron energy gain more than 40% than that obtained in the absence of the magnetic field. Moreover, results demonstrate that the self-magnetic field produced by the electric current of the energetic electrons plays a significant role in the plasma wakefield acceleration of electron. In this regard, it will be shown that taking into account the self-magnetic field can increase the electron energy gain up to 36% for the case with self-magnetic field amplitude Ωs = 0.3 and even up to higher energies for the systems containing stronger self-magnetic field. The effects of plasma wave amplitude and phase, the ion channel field magnitude, and the electron initial kinetic energy on the acceleration of relativistic electron have also been investigated. A scaling law for the optimization of the electron energy is eventually proposed.
State-adjacent Professionals: How Chinese Lawyers Participate in Political Life
Authors: Liu Lawrence J. , Stern Rachel E.
Published: October 2020

This article complicates the conventional wisdom that Chinese lawyers are either politically liberal activists or apolitical hired guns by training our attention on the group of lawyers who choose to stand adjacent to the state and participate in governance. Through an examination of how and why winners of the state-sanctioned Outstanding Lawyer Award participate in politics, we illustrate how state-adjacent lawyers provide the state with information and persuade others to behave in ways the state considers appropriate. Although proximity to power affords some social and professional benefits, award winners are also motivated by a commitment to improving Chinese society. By highlighting the political role played by lawyers who serve as a bridge between state and society, we open the door to future research on the relationship between the state and professionals in other industries and countries, and call for continued attention to how inequality shapes opportunities for political participation in China.
Creative Destruction and the Social (Re) Construction of Heritage
Authors: Avrami Erica
Published: October 2020

In an era when war, acts of terror, and the potentially catastrophic effects of climate change loom large in the public conscience, the conservation community is grappling with the associated loss of the historic built environment and potential responses. But the built environment—at least some aspects of it—is becoming progressively obsolete due to environmental and social changes. Coastal sea-level rise, inefficient resource and land use, and the role of the built environment in perpetuating social exclusion raise questions about the potential value of destruction and the opportunities it affords for reframing spatial memory and historical narrative in more just and sustainable ways. The heritage field’s preoccupation with the physical, place-based fabric will be challenged in the face of this obsolescence, compelling a reexamination of attitudes toward destruction and reconstruction. This article borrows loosely from Joseph Schumpeter’s economic concept of creative destruction to explore the ways in which both innovation and new lenses on history and memory may be borne of change, loss, and obsolescence. Using the discourse surrounding past and contemporary North American cases, it examines some fundamental ideas regarding capital in the built environment and the economic value of destruction. It also explores the negative social consequences of destruction and the historical influence cum perspective of the heritage enterprise and posits potentially positive values and opportunities engendered through destruction. Finally, it reimagines how approaches to reconstruction by the heritage field may contribute to more socially just and sustainable futures.
Psychology and World Heritage? Reflections on Time, Memory, and Imagination for a Heritage Context
Authors: Benson Ciarán
Published: October 2020

Concepts of memory—specifically notions of collective memory—are associated in heritage studies with the central idea of authenticity. In this article I review what is relevant in the psychology of memory to these discourses, and reflect on this association of collective memory and authenticity in heritage studies, notably in the 1994 Nara Document on Authenticity. Concepts of time are central to this review. The idea of world heritage is, it is suggested, a future-oriented ideal for a common humanity. The metaphorical underpinnings of our vernacular uses of time-concepts, such as past and future, are examined. Psychological considerations of memory as retrieval or reconstruction are then outlined. The distinction between kinds of memory, notably episodic and semantic memory, is then presented. These, it is argued, are building blocks for collective memory, which, in turn, is the seedbed for the underemphasized but potent idea of collective imagination. If the primary function of memory is actually oriented to the future, then imagination is what puts kinds of memory to work in both predicting and creating the future. Our ability to imagine—to mentally project forward—is heavily dependent on what we know—that is, on semantic memory. The article concludes with some reflections on the policy implications of this analysis for the visitor to world heritage sites.
Bloch wave homogenisation of quasiperiodic media
Authors: SIVAJI GANESH SISTA , TEWARY VIVEK
Published: October 2020

Quasiperiodic media is a class of almost periodic media which is generated from periodic media through a ‘cut and project’ procedure. Quasiperiodic media displays some extraordinary optical, electronic and conductivity properties which call for the development of methods to analyse their microstructures and effective behaviour. In this paper, we develop the method of Bloch wave homogenisation for quasiperiodic media. Bloch waves are typically defined through a direct integral decomposition of periodic operators. A suitable direct integral decomposition is not available for almost periodic operators. To remedy this, we lift a quasiperiodic operator to a degenerate periodic operator in higher dimensions. Approximate Bloch waves are obtained for a regularised version of the degenerate operator. Homogenised coefficients for quasiperiodic media are obtained from the first Bloch eigenvalue of the regularised operator in the limit of regularisation parameter going to zero. A notion of quasiperiodic Bloch transform is defined and employed to obtain homogenisation limit for an equation with highly oscillating quasiperiodic coefficients.
Were the central Negev settlements suppliers or importers of Gaza wines?
Authors: Seligman Jon
Published: October 2020

In 2011 during a study tour of Sobata (Shivta), a debate took place concerning the likelihood that the central Negev settlements of Elusa, Sobata, Oboda, Ruheiba and Nessana (fig. 1) were significant partners in the trade of prestige Gaza wines during the 5th and 6th c. A.D. I challenged the participants as to whether these sites’ production facilities were of sufficient magnitude to produce a wine surplus for shipping across the Roman world and whether the transport of a bulk product in relatively heavy amphoras to the seaports at Gaza and Ashqelon c.100-120 km distant was both physically feasible and economically viable in the absence of paved roads. This paper will analyse a series of factors, including demography, agricultural technology, wine production capacity and transport possibilities to evaluate the region’s potential and the likelihood of these settlements playing a part in the wine trade of Gaza and Ashqelon.
Deep-water shipwrecks in the East Mediterranean: a microcosm of Late Roman exchange
Authors: Brennan Michael L. , Davis Dan , Opaiţ Andrei , Stay Marshall
Published: October 2020

Deep-water shipwrecks provide an opportunity to investigate ships away from the destructive dynamics of coastlines and approaches to harbors where most ancient wrecks to date have been found. Such exploration expands the potential for finding wrecks of periods for which relatively few are known. One such period is the 6th and 7th c. in the E Mediterranean. Studies of cargo assemblages from the few known wrecks of the later Roman period reveal a partial picture of interlinked and overlapping trade networks that incorporated major and minor ports in the adjacent provinces.1 Various trading modes may be discerned, including cabotage, short-haul trade, inter-regional commerce, and private long-haul trade. Largely missing thus far are the wrecks of ships that participated in the annona transport, the “backbone of Late Roman shipping”.2 Each year, an enormous fleet of private ships under state contract hauled thousands of shiploads of Egyptian grain from Alexandria to Constantinople for public distribution,3 but no shipwrecks explicitly associated with these fleets have been found. Also largely invisible are the non-commercial transports associated with the annona militaris, the fiscal supply of foodstuffs destined for armies stationed on the empire‘s borders. The state supply-system became more formalized in 536 when Justinian created the quaestura exercitus, a prefecture that was granted administrative control and jurisdiction of Moesia Secunda, Scythia, Caria, the Aegean islands, and Cyprus.4 Evidence suggests that the quaestor‘s main task was to ensure the supply, by sea, of agricultural products from the Aegean and NE Mediterranean to troops on the Danube frontier.5 While no definitive grain ships have been found in the E Mediterranean — what M. McCormick has called the “annona paradox”6 —, shipwrecks with the larger cargoes expected of state supply have remained rather elusive.
Lead pollution and the Roman economy
Authors: Pavlyshyn Damian , Johnstone Iain , Saller Richard
Published: October 2020

More than a decade ago, the Oxford Roman Economy Project (OXREP)1 and the Cambridge economic history of the Greco-Roman world put the question of the performance of the Roman economy at the center of historical debate, prompting a flood of books and articles attempting to assess the degree of growth in the economy.2 The issue is of sufficient importance that it has figured in the narratives of economists analyzing the impact of institutional frameworks on the potential for growth.3 As the debate has continued, there has been some convergence: most historians would agree that there was some Smithian growth as evidenced by urbanization and trade, while acknowledging that production remained predominantly agricultural and based primarily on somatic energy (i.e., human and animal).4 This is, of course, a very broad framework that does not differentiate the Roman empire from other complex pre-industrial societies. The challenge is to refine the analysis in order to put content into the broad description of “modest though significant growth”5 and to offer a deeper understanding of the dynamics of the economy.
Myth and eponymy on the tetrarchic frieze from Nicomedia
Authors: Şare Ağtürk Tuna
Published: October 2020

Situated at the NE corner of the Propontis, Nicomedia (modern İzmit) was a major urban centre throughout history. Since the ancient city is buried directly beneath the modern industrial Turkish one, little was known archaeologically until recently1 when a series of painted reliefs, part of a continuous marble frieze of which c.55 m in length have been uncovered, was discovered in the Çukurbağ district. They contain a remarkable combination of imperial, agonistic and mythological scenes.2 The depictions on the frieze, precious examples of tetrarchic art, shed light not only on the socio-political history of the Later Empire but also on the creation, self-identification and reception of a new tetrarchic capital.3 The marble frieze seems to have decorated an imperial complex dating to the late 3rd and early 4th c. when Nicomedia was Diocletian‘s administrative capital for the eastern Roman empire. Among the scenes on the frieze, the group of blocks representing an adventus with Diocletian and Maximian has been published in detail, and a monograph on the Diocletianic complex is under preparation. The present article will examine the mythological depictions on the frieze.
Can American Egalitarianism Survive A Globalized Economy?
Authors: Rorty Richard
Published: October 2020

Most of the infrequent contacts between CEO’s and philosophy professors take place on airplanes. These contacts take the form of exchanges of life-stories between seatmates, exchanges which mitigate the boredom of the flight. Such exchanges provide one of the few ways in which inhabitants of the world of business and inhabitants of the academy get a sense of what the other is doing.

Professors who work in fast-breaking fields like molecular biology or neopragmatist philosophy are always flying off to conferences in places like Sao Paulo, Taipei or Vienna. Our trans-oceanic flights are usually in economy class, but we nevertheless have our reward. When we return home we find that the airlines have sent us upgrade certificates for domestic air travel. This means that we can sometimes go first class to conferences in places like Los Angeles or Seattle. We thus get to sit next to richer and more important people.
PROCEDURAL RIGHTS AND FACTUAL ACCURACY
Authors: Stewart Hamish
Published: October 2020

People have procedural rights because states are under a duty of political morality to provide them with fair procedures for settling disputes about the application of the laws. This obligation flows from the state's duty to treat each person as a free and equal member of the legal order. Yet adherence to procedural rights can impede accuracy in fact-finding, which in turn can result in poor protection for substantive rights. So the state also has a duty to provide a reasonable degree of accuracy in fact-finding. The legal order should therefore strive to improve the accuracy of fact-finding, within the constraints imposed by procedural rights people have. Nevertheless, the duty to provide reasonably accurate procedures is subordinate to the duty to provide procedural rights because the settlement of disputes among free persons must be conducted in a manner that respects their status as free persons.
Latent Factor Structure and Measurement Invariance of the NIH Toolbox Cognition Battery in an Alzheimer’s Disease Research Sample
Authors: Ma Yue , Carlsson Cynthia M. , Wahoske Michelle L. , Blazel Hanna M. , Chappell Richard J. , Johnson Sterling C. , Asthana Sanjay , Gleason Carey E.
Published: October 2020

Objective:

This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer’s disease (AD) research sample.

Method:

The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45–94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA). Two groups were classified for each variable (diagnosis or demographic factors). The confirmed factor model was next tested for each group with CFA. If the factor structure was the same between the groups, measurement invariance was then tested using a hierarchical series of nested two-group CFA models.

Results:

A two-factor model capturing fluid cognition (executive function, processing speed, and memory) versus crystalized cognition (language) fit well for the whole sample and each group except for those with age < 65. This model generally had measurement invariance across sex, race/ethnicity, and education, and partial invariance across diagnosis. For individuals with age < 65, the language factor remained intact while the fluid cognition was separated into two factors: (1) executive function/processing speed and (2) memory.

Conclusions:

The findings mostly supported the utility of the battery in AD research, yet revealed challenges in measuring memory for AD participants and longitudinal change in fluid cognition.
Kant’s Critical Theory of the Best Possible World
Authors: Krishnan Maya
Published: October 2020

In this article I argue that the Critical Kant endorses the claim that God creates the best possible world, and that this claim is best understood as committing him to the view that God creates an infinitely valuable world. Kant’s understudied Critical theory of the best possible world differs significantly from his better-known quasi-Leibnizian pre-Critical account insofar as it uses an axiological rather than ontological metric for the goodness of worlds. The axiological metric introduces unique challenges for a Kantian account of the best possible world. These challenges are in turn resolved via an infinite value interpretation.
AMENABILITY AND ORLICZ FIGÀ-TALAMANCA HERZ ALGEBRAS
Authors: LAL RATTAN , KUMAR N. SHRAVAN
Published: October 2020

In this paper, we characterize amenability of locally compact groups in terms of the properties of Orlicz Figà-Talamanca Herz algebras.
Could the Last Interglacial Constrain Projections of Future Antarctic Ice Mass Loss and Sea‐Level Rise?
Authors: Gilford Daniel M. , Ashe Erica L. , DeConto Robert M. , Kopp Robert E. , Pollard David , Rovere Alessio
Published: October 2020

Previous studies have interpreted Last Interglacial (LIG; ∼129–116 ka) sea‐level estimates in multiple different ways to calibrate projections of future Antarctic ice‐sheet (AIS) mass loss and associated sea‐level rise. This study systematically explores the extent to which LIG constraints could inform future Antarctic contributions to sea‐level rise. We develop a Gaussian process emulator of an ice‐sheet model to produce continuous probabilistic projections of Antarctic sea‐level contributions over the LIG and a future high‐emissions scenario. We use a Bayesian approach conditioning emulator projections on a set of LIG constraints to find associated likelihoods of model parameterizations. LIG estimates inform both the probability of past and future ice‐sheet instabilities and projections of future sea‐level rise through 2150. Although best‐available LIG estimates do not meaningfully constrain Antarctic mass loss projections or physical processes until 2060, they become increasingly informative over the next 130 years. Uncertainties of up to 50 cm remain in future projections even if LIG Antarctic mass loss is precisely known (±5 cm), indicating that there is a limit to how informative the LIG could be for ice‐sheet model future projections. The efficacy of LIG constraints on Antarctic mass loss also depends on assumptions about the Greenland ice sheet and LIG sea‐level chronology. However, improved field measurements and understanding of LIG sea levels still have potential to improve future sea‐level projections, highlighting the importance of continued observational efforts.
Record of the Late Paleozoic Ice Age From Tarim, China
Authors: Yu H. C. , Qiu K. F. , Li M. , Santosh M. , Zhao Z. G. , Huang Y. Q.
Published: October 2020

The late Paleozoic ice age was one of the three major glaciations in the Phanerozoic. However, the influence and characteristics of this glaciation and deglaciation remain unclear. In this study, we present lithostratigraphy, biostratigraphy, and chemostratigraphy during the Late Mississippian to the Early Permian in Tarim, Northwestern China. Tarim records two Gondwana glacial events in the Serpukhovian‐Moscovian (Glacial II) and the Asselian‐Sakmarian (Glacial III). Together with the global evidence of isotopes and sea level changes, multipulsed growth and decay of Glacial II and III are confirmed. The Serpukhovian isotopic pattern in Tarim exhibits a negative δ13C excursion of −6.6‰, which is comparable to those recorded in other continents. This negative excursion and contemporaneous sea level fall are triggered by the expansion of the ice sheets of Glacial II. The glaciation maximum is marked by the global sea level fall during the Bashkirian. A two‐stage transgression and positive shifts of δ13C from the Tarim and Laurussia represent evidence of stepwise deglaciation of Glacial II during the Moscovian. Positive δ18O excursions in Tarim and other two global sections from Laurussia and the regression during early Asselian to early Sakmarian are linked to the Glacial III, confirming this event is of global origin. The eustatic rise and the negative δ18O shifts indicate the retreat of this Gondwana glacier in late Sakmarian. These continuous data sets in Tarim coupled with time equivalent stratigraphy and geochemical records provide insights into the multistage evolution of the discrete Glacial II and III events.
To the Interchange Instability Criterion in the Magnetosphere in the Presence of Velocity Shear
Authors: Khazanov George V. , Krivorutsky Emanuel N. , Chen Margaret W. , Lemon Colby L.
Published: October 2020

In this paper, we address the issue of interchange instability excitation criterion in the magnetospheric plasma in the presence of the velocity shear using a magnetohydrodynamic approach. We conducted our analysis for the arbitrary β plasma configuration using a WKB approximation for wavelengths, λ, much smaller than the characteristic plasma inhomogeneity scale, L, and found two branches of waves. These two wave branches can exist due to the plasma velocity shear and one branch can be unstable for arbitrary angles between the plasma entropy parameter and magnetic flux tube volume gradients. The implications of these results for magnetospheric physics as well as comparison of our results with corresponding analysis of other authors are discussed.
Extracting a History of Global Fire Emissions for the Past Millennium From Ice Core Records of Acetylene, Ethane, and Methane
Authors: Nicewonger Melinda R. , Aydin Murat , Prather Michael J. , Saltzman Eric S.
Published: October 2020

Biomass burning is an important component of the Earth system in terms of global biogeochemistry, atmospheric composition, climate, terrestrial ecology, and land use. This study examines published ice core trace gas measurements of acetylene, ethane, and methane, which have been used as proxies for paleofire emissions. We investigate the consistency of these records for the past 1,000 years in terms of (1) temporal trends in global fire emissions and (2) quantitative estimates for changes in global burning (dry matter burned per year). Three‐dimensional transport and box models were used to construct emissions scenarios for the trace gases consistent with each ice core record. Burning histories were inferred from trace gas emissions by accounting for biome‐specific emission factors for each trace gas. The temporal trends in fire inferred from the trace gases are in reasonable agreement, with a large decline in biomass burning emissions from the Medieval Period (MP: 1000–1500 CE) to the Little Ice Age (LIA: 1650–1750 CE). However, the three trace gas ice core records do not yield a consistent fire history, even assuming dramatic (and unrealistic) changes in the spatial distribution of fire and biomes. Substantial changes in other factors such as meteorological transport or atmospheric photochemical lifetimes appear to be required to reconcile the trace gas records.
ExpoKids: An R-based tool for characterizing aggregate chemical exposure during childhood
Authors: Dai Mona , Euling Susan Y. , Phillips Linda , Rice Glenn E.
Published: October 2020

Background

Aggregate exposure, the combined exposures to a single chemical from all pathways, is a critical children’s health issue.

Objective

The primary objective is to develop a tool to illustrate potential differences in aggregate exposure at various childhood lifestages and the adult lifestage.

Methods

We developed ExpoKids (an R-based tool) using oral exposure estimates across lifestages generated by US EPA’s Exposure Factors Interactive Resource for Scenarios Tool (ExpoFIRST).

Results

ExpoKids is applied to illustrate aggregate oral exposure, for ten media, as average daily doses (ADD) and lifetime average daily doses (LADD) in five graphs organized across seven postnatal childhood lifestages and the adult lifestage. This data visualization tool conveys ExpoFIRST findings, from available exposure data, to highlight the relative contributions of media and lifestages to chemical exposure. To evaluate the effectiveness of ExpoKids, three chemical case examples (di[2-ethylhexyl] phthalate [DEHP], manganese, and endosulfan) were explored. Data available from the published literature and databases for each case example were used to explore research questions regarding media and lifestage contributions to aggregate exposure.

Significance

These illustrative case examples demonstrate ExpoKids’ versatile application to explore a diverse set of children’s health risk assessment and management questions by visually depicting specific media and lifestage contributions to aggregate exposure.
Fusing MEMS technology with lab-on-chip: nanoliter-scale silicon microcavity arrays for digital DNA quantification and multiplex testing
Authors: Podbiel Daniel , Laermer Franz , Zengerle Roland , Hoffmann Jochen
Published: October 2020

We report on the development of a microfluidic multiplexing technology for highly parallelized sample analysis via quantitative polymerase chain reaction (PCR) in an array of 96 nanoliter-scale microcavities made from silicon. This PCR array technology features fully automatable aliquoting microfluidics, a robust sample compartmentalization up to temperatures of 95 °C, and an application-specific prestorage of reagents within the 25 nl microcavities. The here presented hybrid silicon–polymer microfluidic chip allows both a rapid thermal cycling of the liquid compartments and a real-time fluorescence read-out for a tracking of the individual amplification reactions taking place inside the microcavities. We demonstrate that the technology provides very low reagent carryover of prestored reagents < 6 × 10−2 and a cross talk rate < 1 × 10−3 per PCR cycle, which facilitate a multi-targeted sample analysis via geometric multiplexing. Furthermore, we apply this PCR array technology to introduce a novel digital PCR-based DNA quantification method: by taking the assay-specific amplification characteristics like the limit of detection into account, the method allows for an absolute gene target quantification by means of a statistical analysis of the amplification results.
A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer
Authors: Creelan Benjamin C. , Yeh Tammie C. , Kim Sang-We , Nogami Naoyuki , Kim Dong-Wan , Chow Laura Q. M. , Kanda Shintaro , Taylor Rosemary , Tang Weifeng , Tang Mei , Angell Helen K. , Roudier Martine P. , Marotti Marcelo , Gibbons Don L.
Published: October 2020

Background

EGFR tyrosine kinase inhibitors (TKIs) induce cytolysis and release of tumour proteins, which can stimulate antigen-specific T cells. The safety and efficacy of durvalumab and gefitinib in combination for TKI-naive patients with advancedEGFRm NSCLC was evaluated.

Methods

This Phase 1 open-label, multicentre trial (NCT02088112) was conducted in 56 patients with NSCLC. Dose expansion permitted TKI-naive patients, primarily with activating L858R or Ex19delEGFRm. Arms 1 + 1a received concurrent therapy; Arm 2 received 4 weeks of gefitinib induction followed by concurrent therapy.

Results

From dose escalation, the recommended dose of durvalumab was 10 mg/kg Q2W with 250 mg QD gefitinib. Pharmacokinetics were as expected, consistent with inhibition of soluble PD-L1 and no treatment-emergent immunogenicity. In dose expansion, 35% of patients had elevated liver enzymes leading to drug discontinuation. In Arms 1 + 1a, objective response rate was 63.3% (95% CI: 43.9–80.1), median progression-free survival (PFS) was 10.1 months (95% CI: 5.5–15.2) and median response duration was 9.2 months (95% CI: 3.7–14.0).

Conclusions

Durvalumab and gefitinib in combination had higher toxicity than either agent alone. No significant increase in PFS was detected compared with historical controls. Therefore, concurrent PD-L1 inhibitors with gefitinib should be generally avoided in TKI-naive patients withEGFRm NSCLC.
Clinically and biologically relevant subgroups of Wilms tumour defined by genomic and epigenomic analyses
Authors: Brzezinski Jack , Choufani Sanaa , Romao Rodrigo , Shuman Cheryl , Chen Haiying , Cunanan Joanna , Bagli Darius , Grant Ronald , Lorenzo Armando , Weksberg Rosanna
Published: October 2020

Background

Although cure rates for Wilms tumours (WT) are high, many patients receive therapy with attendant long-term complications. Our goal was to stratify WT using genome-wide analyses to identify candidate molecular features for patients who would benefit from a reduction in therapy.

Methods

We generated DNA methylation and exome sequencing data on WT–kidney pairs (n = 57) and unpaired tumours (n = 27) collected either at our centre or by the Children’s Oncology Group. Samples were divided into a discovery set (n = 32) and validation set (n = 52).

Results

Analysis of DNA methylation revealed two subgroups of WT with distinct features. Subgroup A has a similar DNA methylation profile to mature kidney, while Subgroup B has genome-wide dysregulation of DNA methylation. The rate of non-synonymous missense mutations and segmental chromosomal aberrations was higher in Subgroup B tumours, suggesting that this group has genome instability related to its epigenetic state. Subgroup A had a higher proportion of cases of bilateral disease. Tumours with high-risk histology or from patients who relapsed were only found in Subgroup B.

Conclusion

We have identified subgroup-specific molecular events that could inform future work supporting more targeted therapeutic approaches and patient stratification. We propose a novel developmental tumour model based on these findings.
Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency
Authors: Werner-Klein Melanie , Grujovic Ana , Irlbeck Christoph , Obradović Milan , Hoffmann Martin , Koerkel-Qu Huiqin , Lu Xin , Treitschke Steffi , Köstler Cäcilia , Botteron Catherine , Weidele Kathrin , Werno Christian , Polzer Bernhard , Kirsch Stefan , Gužvić Miodrag , Warfsmann Jens , Honarnejad Kamran , Czyz Zbigniew , Feliciello Giancarlo , Blochberger Isabell , Grunewald Sandra , Schneider Elisabeth , Haunschild Gundula , Patwary Nina , Guetter Severin , Huber Sandra , Rack Brigitte , Harbeck Nadia , Buchholz Stefan , Rümmele Petra , Heine Norbert , Rose-John Stefan , Klein Christoph A.
Published: October 2020

Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130. Responsiveness to IL6 trans-signals is found to be niche-dependent as bone marrow stromal and endosteal cells down-regulate gp130 in premalignant mammary epithelial cells as opposed to vascular niche cells.PIK3CAactivation renders cells independent from IL6 trans-signaling. Consistent with a bottleneck function of microenvironmental DCC control, we findPIK3CAmutations highly associated with late-stage metastatic cells while being extremely rare in early DCCs. Our data suggest that the initial steps of metastasis formation are often not cancer cell-autonomous, but also depend on microenvironmental signals.
Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome
Authors: Hollis Robert L. , Thomson John P. , Stanley Barbara , Churchman Michael , Meynert Alison M. , Rye Tzyvia , Bartos Clare , Iida Yasushi , Croy Ian , Mackean Melanie , Nussey Fiona , Okamoto Aikou , Semple Colin A. , Gourley Charlie , Herrington C. Simon
Published: October 2020

Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency of mutation in CTNNB1 (43%), PIK3CA (43%), ARID1A (36%), PTEN (29%), KRAS (26%), TP53 (26%) and SOX8 (19%), a recurrently-mutated gene previously unreported in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy is constructed, identifying clinically distinct EnOC subtypes: cases with TP53 mutation demonstrate greater genomic complexity, are commonly FIGO stage III/IV at diagnosis (48%), are frequently incompletely debulked (44%) and demonstrate inferior survival; conversely, cases with CTNNB1 mutation, which is mutually exclusive with TP53 mutation, demonstrate low genomic complexity and excellent clinical outcome, and are predominantly stage I/II at diagnosis (89%) and completely resected (87%). Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.
A comparative study of asleep and awake deep brain stimulation robot-assisted surgery for Parkinson’s disease
Authors: Jin Hai , Gong Shun , Tao Yingqun , Huo Hua , Sun Xiao , Song Dandan , Xu Ming , Xu Zhaozhu , Liu Yang , Wang Shimiao , Yuan Lijia , Wang Tingting , Song Weilong , Pan He
Published: October 2020

To compare the differences between asleep and awake robot-assisted deep brain stimulation (DBS) surgery for Parkinson’s Disease (PD), we conducted this retrospective cohort study included 153 PD patients undergoing bilateral robot-assisted DBS from June 2017 to August 2019, of which 58 cases were performed under general anesthesia (GA) and 95 cases under local anesthesia (LA). Procedure duration, stimulation parameters, electrode implantation accuracy, intracranial air, intraoperative electrophysiological signal length, complications, and Unified PD Rating Scale (UPDRS) measurements were recorded and compared. The clinical evaluation was conducted by two raters who were blinded to the choice of anesthesia. Procedure duration was significantly shorter in the GA group, while on stimulation off medication motor scores (UPDRS-III) were significantly improved in both the GA and LA group. ANCOVA covariated for the baseline UPDRS-III and levodopa challenge exhibited no significant differences. In terms of amplitude, frequency, and pulse width, the stimulation parameters used for DBS power-on were similar. There were no significant differences in electrode implantation accuracy, intraoperative electrophysiological signal length, or intracerebral hemorrhage (no occurrences in either group). The pneumocephalus volume was significantly smaller in the GA group. Six patients exhibited transient throat discomfort associated with tracheal intubation in the GA group. The occurrence of surgical incision infection was similar in both groups. Compared with the awake group, the asleep group exhibited a shorter procedure duration with a similar electrode implantation accuracy and short-term motor improvement. Robot-assisted asleep DBS surgery is a promising surgical method for PD.
lncRNAKB, a knowledgebase of tissue-specific functional annotation and trait association of long noncoding RNA
Authors: Seifuddin Fayaz , Singh Komudi , Suresh Abhilash , Judy Jennifer T. , Chen Yun-Ching , Chaitankar Vijender , Tunc Ilker , Ruan Xiangbo , Li Ping , Chen Yi , Cao Haiming , Lee Richard S. , Goes Fernando S. , Zandi Peter P. , Jafri M. Saleet , Pirooznia Mehdi
Published: October 2020

Long non-coding RNA Knowledgebase (lncRNAKB) is an integrated resource for exploring lncRNA biology in the context of tissue-specificity and disease association. A systematic integration of annotations from six independent databases resulted in 77,199 human lncRNA (224,286 transcripts). The user-friendly knowledgebase covers a comprehensive breadth and depth of lncRNA annotation. lncRNAKB is a compendium of expression patterns, derived from analysis of RNA-seq data in thousands of samples across 31 solid human normal tissues (GTEx). Thousands of co-expression modules identified via network analysis and pathway enrichment to delineate lncRNA function are also accessible. Millions of expression quantitative trait loci (cis-eQTL) computed using whole genome sequence genotype data (GTEx) can be downloaded at lncRNAKB that also includes tissue-specificity, phylogenetic conservation and coding potential scores. Tissue-specific lncRNA-trait associations encompassing 323 GWAS (UK Biobank) are also provided. LncRNAKB is accessible at http://www.lncrnakb.org/, and the data are freely available through Open Science Framework (https://doi.org/10.17605/OSF.IO/RU4D2).
Data segmentation based on the local intrinsic dimension
Authors: Allegra Michele , Facco Elena , Denti Francesco , Laio Alessandro , Mira Antonietta
Published: October 2020

One of the founding paradigms of machine learning is that a small number of variables is often sufficient to describe high-dimensional data. The minimum number of variables required is called the intrinsic dimension (ID) of the data. Contrary to common intuition, there are cases where the ID varies within the same data set. This fact has been highlighted in technical discussions, but seldom exploited to analyze large data sets and obtain insight into their structure. Here we develop a robust approach to discriminate regions with different local IDs and segment the points accordingly. Our approach is computationally efficient and can be proficiently used even on large data sets. We find that many real-world data sets contain regions with widely heterogeneous dimensions. These regions host points differing in core properties: folded versus unfolded configurations in a protein molecular dynamics trajectory, active versus non-active regions in brain imaging data, and firms with different financial risk in company balance sheets. A simple topological feature, the local ID, is thus sufficient to achieve an unsupervised segmentation of high-dimensional data, complementary to the one given by clustering algorithms.
The cognitive effects of a promised bonus do not depend on dopamine synthesis capacity
Authors: Hofmans Lieke , van den Bosch Ruben , Määttä Jessica I. , Verkes Robbert-Jan , Aarts Esther , Cools Roshan
Published: October 2020

Reward motivation is known to enhance cognitive control. However, detrimental effects have also been observed, which have been attributed to overdosing of already high baseline dopamine levels by further dopamine increases elicited by reward cues. Aarts et al. (2014) indeed demonstrated, in 14 individuals, that reward effects depended on striatal dopamine synthesis capacity, measured with [18F]FMT-PET: promised reward improved Stroop control in low-dopamine individuals, while impairing it in high-dopamine individuals. Here, we aimed to assess this same effect in 44 new participants, who had previously undergone an [18F]DOPA-PET scan to quantify dopamine synthesis capacity. This sample performed the exact same rewarded Stroop paradigm as in the prior study. However, we did not find any correlation between reward effects on cognitive control and striatal dopamine synthesis capacity. Critical differences between the radiotracers [18F]DOPA and [18F]FMT are discussed, as the discrepancy between the current and our previous findings might reflect the use of the potentially less sensitive [18F]DOPA radiotracer in the current study.
Disruption of NREM sleep and sleep-related spatial memory consolidation in mice lacking adult hippocampal neurogenesis
Authors: Sippel D. , Schwabedal J. , Snyder J. C. , Oyanedel C. N. , Bernas S. N. , Garthe A. , Tröndle A. , Storch A. , Kempermann G. , Brandt M. D.
Published: October 2020

Cellular plasticity at the structural level and sleep at the behavioural level are both essential for memory formation. The link between the two is not well understood. A functional connection between adult neurogenesis and hippocampus-dependent memory consolidation during NREM sleep has been hypothesized but not experimentally shown. Here, we present evidence that during a three-day learning session in the Morris water maze task a genetic knockout model of adult neurogenesis (Cyclin D2−/−) showed changes in sleep macro- and microstructure. Sleep EEG analyses revealed a lower total sleep time and NREM fraction in Cyclin D2−/− mice as well as an impairment of sleep specific neuronal oscillations that are associated with memory consolidation. Better performance in the memory task was associated with specific sleep parameters in wild-type, but not in Cyclin D2−/− mice. In wild-type animals the number of proliferating cells correlated with the amount of NREM sleep. The lack of adult neurogenesis led to changes in sleep architecture and oscillations that represent the dialog between hippocampus and neocortex during sleep. We suggest that adult neurogenesis—as a key event of hippocampal plasticity—might play an important role for sleep-dependent memory consolidation and modulates learning-induced changes of sleep macro- and microstructure.
Geophysical early warning of salt precipitation during geological carbon sequestration
Authors: Falcon-Suarez Ismael Himar , Livo Kurt , Callow Ben , Marin-Moreno Hector , Prasad Manika , Best Angus Ian
Published: October 2020

Sequestration of industrial carbon dioxide (CO2) in deep geological saline aquifers is needed to mitigate global greenhouse gas emissions; monitoring the mechanical integrity of reservoir formations is essential for effective and safe operations. Clogging of fluid transport pathways in rocks from CO2-induced salt precipitation reduces injectivity and potentially compromises the reservoir storage integrity through pore fluid pressure build-up. Here, we show that early warning of salt precipitation can be achieved through geophysical remote sensing. From elastic P- and S-wave velocity and electrical resistivity monitoring during controlled laboratory CO2 injection experiments into brine-saturated quartz-sandstone of high porosity (29%) and permeability (1660 mD), and X-ray CT imaging of pore-scale salt precipitation, we were able to observe, for the first time, how CO2-induced salt precipitation leads to detectable geophysical signatures. We inferred salt-induced rock changes from (i) strain changes, (ii) a permanent ~ 1.5% decrease in wave velocities, linking the geophysical signatures to salt volume fraction through geophysical models, and (iii) increases of porosity (by ~ 6%) and permeability (~ 7%). Despite over 10% salt saturation, no clogging effects were observed, which suggests salt precipitation could extend to large sub-surface regions without loss of CO2 injectivity into high porosity and permeability saline sandstone aquifers.
COVID-19 lockdown and its latency in Northern Italy: seismic evidence and socio-economic interpretation
Authors: Piccinini Davide , Giunchi Carlo , Olivieri Marco , Frattini Federico , Di Giovanni Matteo , Prodi Giorgio , Chiarabba Claudio
Published: October 2020

The Italian Government has decreed a series of progressive restrictions to delay the COVID-19 pandemic diffusion in Italy since March 10, 2020, including limitation in individual mobility and the closure of social, cultural, economic and industrial activities. Here we show the lockdown effect in Northern Italy, the COVID-19 most affected area, as revealed by noise variation at seismic stations. The reaction to lockdown was slow and not homogeneous with spots of negligible noise reduction, especially in the first week. A fresh interpretation of seismic noise variations in terms of socio-economic indicators sheds new light on the lockdown efficacy pointing to the causes of such delay: the noise reduction is significant where non strategic activities prevails, while it is small or negligible where dense population and strategic activities are present. These results are crucial for the a posteriori interpretation of the pandemic diffusion and the efficacy of differently targeted political actions.
Climatic oscillations in Quaternary have shaped the co-evolutionary patterns between the Norway spruce and its host-associated herbivore
Authors: Goczał Jakub , Oleksa Andrzej , Rossa Robert , Chybicki Igor , Meyza Katarzyna , Plewa Radosław , Landvik Matti , Gobbi Mauro , Hoch Gernot , Tamutis Vytautas , Balalaikins Maksims , Telnov Dmitry , Dascălu Maria-Magdalena , Tofilski Adam
Published: October 2020

During the Last Glacial Maximum in the Northern Hemisphere, expanding ice sheets forced a large number of plants, including trees, to retreat from their primary distribution areas. Many host-associated herbivores migrated along with their host plants. Long-lasting geographic isolation between glacial refugia could have been led to the allopatric speciation in separated populations. Here, we have studied whether the migration history of the Norway sprucePicea abiesin Quaternary has affected its host-associated herbivorous beetle—Monochamus sartor. By using microsatellite markers accompanied by the geometric morphometrics analysis of wing venation, we have revealed the clear geographic structure ofM. sartorin Eurasia, encompassing two main clusters: southern (Alpine–Carpathian) and eastern (including northeastern Europe and Asia), which reflects the northern and southern ecotypes of its host. The two beetles’ lineages probably diverged during the Pleniglacial (57,000—15,000 BC) when their host tree species was undergoing significant range fragmentation and experienced secondary contact during post-glacial recolonization of spruce in the Holocene. A secondary contact of divergent lineages ofM.sartor has resulted in the formation of the hybrid zone in northeastern Europe. Our findings suggest that the climatic oscillations during the Pleistocene have driven an insect-plant co-evolutionary process, and have contributed to the formation of the unique biodiversity of Europe.
The role of cat eye narrowing movements in cat–human communication
Authors: Humphrey Tasmin , Proops Leanne , Forman Jemma , Spooner Rebecca , McComb Karen
Published: October 2020

Domestic animals are sensitive to human cues that facilitate inter-specific communication, including cues to emotional state. The eyes are important in signalling emotions, with the act of narrowing the eyes appearing to be associated with positive emotional communication in a range of species. This study examines the communicatory significance of a widely reported cat behaviour that involves eye narrowing, referred to as the slow blink sequence. Slow blink sequences typically involve a series of half-blinks followed by either a prolonged eye narrow or an eye closure. Our first experiment revealed that cat half-blinks and eye narrowing occurred more frequently in response to owners’ slow blink stimuli towards their cats (compared to no owner–cat interaction). In a second experiment, this time where an experimenter provided the slow blink stimulus, cats had a higher propensity to approach the experimenter after a slow blink interaction than when they had adopted a neutral expression. Collectively, our results suggest that slow blink sequences may function as a form of positive emotional communication between cats and humans.