bluuebunny/crossref_metadata_2025 huggingface dataset:
Vessels and landscapes: a special reciprocity
Authors: Platt Christopher
Published: September 2019

Here was the house, its heavy walls built of the stone of the mountain, plastered over by groping hands – in feeling and material nothing but an artificial reproduction of one of the many caverns in the mountain-side. I saw that essentially all architecture of the past, whether Egyptian or Roman, was nothing but the work of a sculptor dealing with abstract forms. The architect’s attempt really was to gather and pile up masses of building material, leaving empty hollows for human use […]. The room itself was a by-product.

(R. M. Schindler)

By 1911, Rudolph Schindler had concluded that all architecture in the West leading up to the early twentieth century had been fixated on structure and mass, in stark contrast to the new ‘space architecture’ he championed. His dismissive categorisation of the traditional room as some kind of evolutionary relative of the cave is a reminder of the moment when a strand of Western architecture blossomed from containment into openness; from a predictable past to an exciting and uncertain future – the gift of modern architecture.
THRESHOLD COINTEGRATION AND NONLINEAR ADJUSTMENT TO THE LAW OF ONE PRICE
Authors: Lo Ming Chien , Zivot Eric
Published: September 2019

Previous studies investigating threshold behavior in real-exchange-rate and price difference data have used rather ad hoc statistical methods and have focused on univariate threshold models for relative prices. We utilize a general multivariate threshold cointegration model and develop a systematic testing and estimation strategy for this model, building on the work of others. Using Monte Carlo experiments, we systematically compare the use of univariate and multivariate techniques for testing threshold cointegration, estimating various threshold models, and testing specifications. We apply our methodology to a large set of U.S. disaggregated CPI data. We find evidence of threshold cointegration mainly for tradable goods. However, the type of threshold nonlinearity that we find generally does not support the transaction-cost view of commodity arbitrage.
DECOMPOSITION OF ECONOMIC RELATIONSHIPS BY TIMESCALE USING WAVELETS
Authors: Ramsey James B. , Lampart Camille
Published: September 2019

Economists have long known that timescale matters in that the structure of
decisions as
to the relevant time horizon, degree of time aggregation,
strength of relationship, and
even the relevant variables differ by timescale.
Unfortunately, until recently it was
difficult to decompose economic
time series into orthogonal timescale components
except for the short or
long run in which the former is dominated by noise. Wavelets are used
to produce an orthogonal decomposition of some economic variables by timescale
over six different timescales. The relationship of interest is that
between money and income, i.e., velocity. We confirm that timescale
decomposition is very important for analyzing economic relationships. The
analysis indicates the importance of
recognizing variations in phase between
variables when investigating the relationships between them and throws
considerable light on the conflicting results that have been obtained in the
literature using Granger causality tests.
EDITOR'S PREFACE TO THE INTERVIEW SERIES
Authors: Barnett William A.
Published: September 2019

This interview with Wassily Leontief is the first to appear in
Macroeconomic Dynamics. Other interviews of importance to the history
of economic thought will appear occasionally in this journal. Since
this journal prizes the openness that characterizes the scientific
method, the views expressed by economists interviewed in this section may
span a broad range and will not necessarily represent the views of
the journal's editorial board or the primary focus of the journal.
However, in all cases in which Macroeconomic Dynamics publishes an
interview, the journal thereby evidences its deep respect for the
scholar whose interview we publish.
AN INTERVIEW WITH WASSILY LEONTIEF
Authors: Foley Interviewed by Duncan K.
Published: September 2019

Wassily Leontief is one of the central creators and shapers
of twentieth-century economics. He invented input-output
theory and the techniques for constructing input-output
tables from economic and technological data and
was responsible for making input-output tables the most
powerful and widely used tool of structural economic
analysis. The theory of input-output matrices played an
important role in the clarification of general equilibrium
theory in the 1940's and 1950's as well. Leontief has also
made fundamental and seminal contributions to the
theories of demand, international trade, and economic
dynamics. His research interests include monetary
economics, population, econometric method,
environmental economics, distribution, disarmament,
induced technical change, international capital
movements, growth, economic planning, and the Soviet and other socialist economies.
Leontief has played a vigorous part in formulating national and international policies addressing technology,
trade, population, arms control, and the environment. He has
also been a well-informed and influential critic of
contemporary economic method, theory, and practice. Leontief received the Nobel Memorial Prize for
Economics in 1973.

I met Wassily Leontief on April 14, 1997, at his apartment
high above Washington Square Park in New York City.
Leontief reclined on a sofa in the living room, with Mrs.
Leontief going about her business in the background,
occasionally asking after Leontief's comfort. Leontief's
voice on the tape ranges from an assertive forte to a
whispery piano. He is by turns animated, thoughtful,
puzzled, inspiring, and charming. A chiming clock
marking the passage of quarter-hours and characteristic
New York street noise occasionally obscure his words on
the tape. I have edited the transcript for continuity and
clarity.
ENDOGENOUS JUMPING AND ASSET PRICE DYNAMICS
Authors: Lim G. C. , Martin Vance L. , Teo Leslie E.
Published: September 2019

A model of asset price dynamics is derived in which large jumps in
stock prices are determined endogenously. An important property of
the model is that it can lead to
asset price distributions that are
multimodal. The model can explain how relatively
small changes in
dividends can lead to relatively large changes in asset prices and it can
be used to identify the time period in which bubbles begin and
end. The framework is applied to modeling the U.S. stock market crash
in October 1987. Some forecasting experiments also are conducted with
the result that the model is able to predict the
size of the eventual
crash in the aggregate stock price.
FAIRMODEL SITE
Authors: Fair Ray C.
Published: September 2019

The Internet has greatly expanded the way in which large-scale
structural macroeconometric models can be used and disseminated. This
note describes a site that has been created for this purpose:
http://fairmodel.econ.yale.edu.
IN MEMORIAM CARLA LUIJKS
Authors: Roberge Paul T.
Published: September 2019

Afrikaans linguistics suffered a major loss with the death of our colleague Carla Luijks, from cancer, on December 30, 2001, at the cruelly young age of 43 (two weeks shy of her 44th birthday).
Analysis of an Updated Paleointensity Database (QPI‐PINT) for 65–200 Ma: Implications for the Long‐Term History of Dipole Moment Through the Mesozoic
Authors: Kulakov E. V. , Sprain C. J. , Doubrovine P. V. , Smirnov A. V. , Paterson G. A. , Hawkins L. , Fairchild L. , Piispa E. J. , Biggin A. J.
Published: September 2019

The global paleointensity database for 65–200 Ma was analyzed using a modified suite of paleointensity quality criteria (QPI) such that the likely reliability of measurements is assessed objectively and as consistently as possible across the diverse data set. This interval was chosen because of dramatic extremes of geomagnetic polarity reversal frequency ranging from greater than 10 reversals per million years in the Jurassic hyperactivity period (155–171 Ma) to effectively zero during the Cretaceous Normal Superchron (CNS; 84–126 Ma). Various attempts to establish a relationship between the strength of Earth's magnetic field and the reversal frequency have been made by previous studies, but no consensus has yet been reached primarily because of large uncertainties in paleointensity estimates and sensitivity of these estimates to data selection approaches. It is critical to overcome this problem because the evolution of the dipole moment is a first order constraint on the behavior of the geodynamo. Here we show that conventional statistical tests and Bayesian changepoint modeling consistently indicate the strongest median/average virtual dipole moment during the CNS. In addition, the CNS and Jurassic hyperactivity period are characterized by the highest and lowest percentage of virtual dipole moments exceeding the overall median for the 65‐ to 200‐Ma interval, respectively. These observations suggest that the superchron dynamo was able to generate stronger fields than the dynamo operating in the frequently reversing regime. While the precise mechanism remains unclear, our results are compatible with the hypothesis that field strength and reversal rate variation are controlled by changes in core‐mantle boundary thermochemical conditions.
Modeling Megathrust Earthquakes Across Scales: One‐way Coupling From Geodynamics and Seismic Cycles to Dynamic Rupture
Authors: van Zelst I. , Wollherr S. , Gabriel A.‐A. , Madden E. H. , van Dinther Y.
Published: September 2019

Taking the full complexity of subduction zones into account is important for realistic modeling and hazard assessment of subduction zone seismicity and associated tsunamis. Studying seismicity requires numerical methods that span a large range of spatial and temporal scales. We present the first coupled framework that resolves subduction dynamics over millions of years and earthquake dynamics down to fractions of a second. Using a two‐dimensional geodynamic seismic cycle (SC) model, we model 4 million years of subduction followed by cycles of spontaneous megathrust events. At the initiation of one such SC event, we export the self‐consistent fault and surface geometry, fault stress and strength, and heterogeneous material properties to a dynamic rupture (DR) model. Coupling leads to spontaneous dynamic rupture nucleation, propagation, and arrest with the same spatial characteristics as in the SC model. It also results in a similar material‐dependent stress drop, although dynamic slip is significantly larger. The DR event shows a high degree of complexity, featuring various rupture styles and speeds, precursory phases, and fault reactivation. Compared to a coupled model with homogeneous material properties, accounting for realistic lithological contrasts doubles the amount of maximum slip, introduces local pulse‐like rupture episodes, and relocates the peak slip from near the downdip limit of the seismogenic zone to the updip limit. When an SC splay fault is included in the DR model, the rupture prefers the splay over the shallow megathrust, although wave reflections do activate the megathrust afterward.
The Burdwood Bank Circulation
Authors: Matano Ricardo P. , Palma Elbio D. , Combes Vincent
Published: September 2019

A suite of high‐resolution numerical simulations characterizes the oceanic circulation in the Burdwood Bank, a shallow seamount located in the northeastern end of the Drake Passage. Model analysis shows energetic upwelling and mixing uplifting deep and benthic waters into the photic layer. Tides and the Antarctic Circumpolar Current are the primary drivers of the bank's circulation. Tidal forcing is the main driver for the entrainment of deep waters into the upper layers of the bank and local wind forcing for the detrainment of these waters into the deep ocean. Passive tracer diagnostics suggest that the dynamical processes triggered by the Burdwood Bank could have a significant impact on local ecosystems and the biogeochemical balance of the southwestern Atlantic region, which is one of the most fertile portions of the Southern Ocean. Model results are robust—they are reproduced in a wide array of model configurations—but there is insufficient observational evidence to corroborate them. Satellite color imagery does not show substantial chlorophyll blooms in this region but it shows strong phytoplankton plumes emanating from the bank. There are several potential explanations for the chlorophyll deficit, including lack of light due to persistent cloud cover, deep mixing layers, fast ocean currents, and the likelihood that blooms, while extant, might not develop on the surface. None of these possibilities can be confirmed at this stage.
ISOW Spreading and Mixing as Revealed by Deep‐Argo Floats Launched in the Charlie‐Gibbs Fracture Zone
Authors: Racapé Virginie , Thierry Virginie , Mercier Herlé , Cabanes Cécile
Published: September 2019

To improve our understanding of deep circulation, we deployed five Deep‐Argo floats (0–4,000 m) in the Charlie‐Gibbs Fracture Zone (CGFZ), which channels the flow of Iceland‐Scotland Overflow Water (ISOW), a dense water mass of the North Atlantic Ocean. The floats were programed to drift at 2,750 dbar in the ISOW layer. The floats mainly moved westward in the CGFZ, although some of them followed different routes for few cycles depending on northward intrusions of the North Atlantic Current over the CGFZ. One float revealed a direct route for ISOW from CGFZ to the Deep Western Boundary Current at Flemish Cap. In the CGFZ, oxygen data acquired by the floats revealed that the ISOW layer, characterized by salinity higher than 34.94 and density greater than 27.8 kg/m, was mainly composed of the highly oxygenated ISOW and the less oxygenated North East Atlantic Deep Water (NEADW), a complex water mass from the East Atlantic. In the ISOW layer, the relative contribution of ISOW was generally larger in the northern valley than in the southern valley of CGFZ. Northward intrusions of the North Atlantic Current above the CGFZ increased the relative contribution of NEADW in the northern valley and favors mixing between ISOW and NEADW. The ISOW‐NEADW signal flowing westward from the CGFZ toward the Deep Western Boundary Current was progressively diluted by Labrador Sea Water and Denmark Strait Overflow Water. Oxygen measurements from Deep‐Argo floats are essential for a better understanding and characterization of the mixing and spreading of deep water masses.
Impact of Rescaling Approaches in Simple Fusion of Soil Moisture Products
Authors: Afshar M. H. , Yilmaz M. T. , Crow W. T.
Published: September 2019

In this study, the impact of various rescaling approaches in the framework of data fusion is explored. Four different soil moisture products (Advanced Scatterometer; Advanced Microwave Scanning Radiometer for EOS, AMSR‐E; Antecedent Precipitation Index; and Global Land Data Assimilation System‐NOAH) are fused. The systematic differences between products are removed before the fusion utilizing various rescaling approaches focusing on different methods (regression, variance/cumulative distribution function (CDF) matching, multivariate adaptive regression splines, and support vector machines based), stationarity assumptions (constant or time‐varying rescaling coefficients), and time‐frequency techniques (periodic or nonperiodic high‐ and low‐frequency components). Given that statistical descriptions (e.g., standard deviation and correlation coefficient) of reference data sets are utilized in rescaling approaches, the precision of the selected reference data set also impacts the final fused product precision. Experiments are validated over 542 soil moisture monitoring sites selected from the International Soil Moisture Network data sets between 2007 and 2011. Overall, results highlight the importance of reference data set selection—particularly that a more precise reference product yields a higher precision fused soil moisture product. This conclusion is sensitive neither to the number of fused products nor the rescaling procedure. Among rescaling approaches, the precision of fused products is most affected by the choice of rescaling stationary assumption and time‐frequency decomposition technique. Variations in rescaling methods have only a small impact on the precision of pair fused products. In contrast, utilizing a time‐varying stationary assumption and nonperiodic decomposition technique produces correlation improvements of 0.07 [−] and 0.02 [−], respectively, versus the other widely implemented rescaling approaches.
Sex-specific transcriptional and proteomic signatures in schizophrenia
Authors: Tiihonen Jari , Koskuvi Marja , Storvik Markus , Hyötyläinen Ida , Gao Yanyan , Puttonen Katja A. , Giniatullina Raisa , Poguzhelskaya Ekaterina , Ojansuu Ilkka , Vaurio Olli , Cannon Tyrone D. , Lönnqvist Jouko , Therman Sebastian , Suvisaari Jaana , Kaprio Jaakko , Cheng Lesley , Hill Andrew F. , Lähteenvuo Markku , Tohka Jussi , Giniatullin Rashid , Lehtonen Šárka , Koistinaho Jari
Published: September 2019

It has remained unclear why schizophrenia typically manifests after adolescence and which neurobiological mechanisms are underlying the cascade leading to the actual onset of the illness. Here we show that the use of induced pluripotent stem cell-derived neurons of monozygotic twins from pairs discordant for schizophrenia enhances disease-specific signal by minimizing genetic heterogeneity. In proteomic and pathway analyses, clinical illness is associated especially with altered glycosaminoglycan, GABAergic synapse, sialylation, and purine metabolism pathways. Although only 12% of all 19,462 genes are expressed differentially between healthy males and females, up to 61% of the illness-related genes are sex specific. These results on sex-specific genes are replicated in another dataset. This implies that the pathophysiology differs between males and females, and may explain why symptoms appear after adolescence when the expression of many sex-specific genes change, and suggests the need for sex-specific treatments.
Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites
Authors: Minkah Nana K. , Wilder Brandon K. , Sheikh Amina A. , Martinson Thomas , Wegmair Lisa , Vaughan Ashley M. , Kappe Stefan H. I.
Published: September 2019

Immunization with attenuated wholePlasmodiumsporozoites constitutes a promising vaccination strategy. Compared to replication-deficient parasites, immunization with replication-competent parasites confers better protection and also induces a type I IFN (IFN-1) response, but whether this IFN-1 response has beneficial or adverse effects on vaccine-induced adaptive immunity is not known. Here, we show that IFN-1 signaling-deficient mice immunized with replication-competent sporozoites exhibit superior protection against infection. This correlates with superior CD8 T cell memory including reduced expression of the exhaustion markers PD-1 and LAG-3 on these cells and increased numbers of memory CD8 T cells in the liver. Moreover, the adoptive transfer of memory CD8 T cells from the livers of previously immunized IFN-1 signaling-deficient mice confers greater protection against liver stage parasites. However, the detrimental role of IFN-1 signaling is not CD8 T cell intrinsic. Together, our data demonstrate that liver stage-engendered IFN-1 signaling impairs hepatic CD8 T cell memory via a CD8 T cell-extrinsic mechanism.
Rate and selectivity hysteresis during the carbon monoxide hydrogenation over promoted Co/MnOx catalysts
Authors: Xiang Yizhi , Kovarik Libor , Kruse Norbert
Published: September 2019

While cobalt-based catalysts have been used in industrial Fischer-Tropsch synthesis for decades, little is known about how the dynamics of the Co-Co2C phase transformation drive their performance. Here we report on the occurrence of hysteresis effects in the Fischer-Tropsch reaction over potassium promoted Co/MnOx catalyst. Both the reaction rate and the selectivity to chain-lengthened paraffins and terminally functionalized products (aldehydes, alcohols, olefins) show bistability when varying the hydrogen/carbon monoxide partial pressures back and forth from overall reducing to carbidizing conditions. While the carbon monoxide conversion and the selectivity to functionalized products follow clockwise hysteresis, the selectivity to paraffins shows counter-clockwise behavior. In situ X-ray diffraction demonstrates the activity/selectivity bistability to be driven by a Co-Co2C phase transformation. The conclusions are supported by High Resolution Transmission Electron Microscopy which identifies the Co-Co2C transformation, Mn5O8 layered topologies at low H2/CO partial pressure ratios, and MnO at high such ratios.
Experimental observation of flow fields around active Janus spheres
Authors: Campbell Andrew I. , Ebbens Stephen J. , Illien Pierre , Golestanian Ramin
Published: September 2019

The phoretic mechanisms at stake in the propulsion of asymmetric colloids have been the subject of debates during the past years. In particular, the importance of electrokinetic effects on the motility of Pt-PS Janus sphere was recently discussed. Here, we probe the hydrodynamic flow field around a catalytically active colloid using particle tracking velocimetry both in the freely swimming state and when kept stationary with an external force. Our measurements provide information about the fluid velocity in the vicinity of the surface of the colloid, and confirm a mechanism for propulsion that was proposed recently. In addition to offering a unified understanding of the nonequilibrium interfacial transport processes at stake, our results open the way to a thorough description of the hydrodynamic interactions between such active particles and understanding their collective dynamics.
Pareto rules for malaria super-spreaders and super-spreading
Authors: Cooper Laura , Kang Su Yun , Bisanzio Donal , Maxwell Kilama , Rodriguez-Barraquer Isabel , Greenhouse Bryan , Drakeley Chris , Arinaitwe Emmanuel , G. Staedke Sarah , Gething Peter W. , Eckhoff Philip , Reiner Robert C. , Hay Simon I. , Dorsey Grant , Kamya Moses R. , Lindsay Steven W. , Grenfell Bryan T. , Smith David L.
Published: September 2019

Heterogeneity in transmission is a challenge for infectious disease dynamics and control. An 80-20 “Pareto” rule has been proposed to describe this heterogeneity whereby 80% of transmission is accounted for by 20% of individuals, herein called super-spreaders. It is unclear, however, whether super-spreading can be attributed to certain individuals or whether it is an unpredictable and unavoidable feature of epidemics. Here, we investigate heterogeneous malaria transmission at three sites in Uganda and find that super-spreading is negatively correlated with overall malaria transmission intensity. Mosquito biting among humans is 90-10 at the lowest transmission intensities declining to less than 70-30 at the highest intensities. For super-spreaders, biting ranges from 70-30 down to 60-40. The difference, approximately half the total variance, is due to environmental stochasticity. Super-spreading is thus partly due to super-spreaders, but modest gains are expected from targeting super-spreaders.
Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration
Authors: Liu Xueping , Helenius Dorte , Skotte Line , Beaumont Robin N. , Wielscher Matthias , Geller Frank , Juodakis Julius , Mahajan Anubha , Bradfield Jonathan P. , Lin Frederick T. J. , Vogelezang Suzanne , Bustamante Mariona , Ahluwalia Tarunveer S. , Pitkänen Niina , Wang Carol A. , Bacelis Jonas , Borges Maria C. , Zhang Ge , Bedell Bruce A. , Rossi Robert M. , Skogstrand Kristin , Peng Shouneng , Thompson Wesley K. , Appadurai Vivek , Lawlor Debbie A. , Kalliala Ilkka , Power Christine , McCarthy Mark I. , Boyd Heather A. , Marazita Mary L. , Hakonarson Hakon , Hayes M. Geoffrey , Scholtens Denise M. , Rivadeneira Fernando , Jaddoe Vincent W. V. , Vinding Rebecca K. , Bisgaard Hans , Knight Bridget A. , Pahkala Katja , Raitakari Olli , Helgeland Øyvind , Johansson Stefan , Njølstad Pål R. , Fadista João , Schork Andrew J. , Nudel Ron , Miller Daniel E. , Chen Xiaoting , Weirauch Matthew T. , Mortensen Preben Bo , Børglum Anders D. , Nordentoft Merete , Mors Ole , Hao Ke , Ryckman Kelli K. , Hougaard David M. , Kottyan Leah C. , Pennell Craig E. , Lyytikainen Leo-Pekka , Bønnelykke Klaus , Vrijheid Martine , Felix Janine F. , Lowe William L. , Grant Struan F. A. , Hyppönen Elina , Jacobsson Bo , Jarvelin Marjo-Riitta , Muglia Louis J. , Murray Jeffrey C. , Freathy Rachel M. , Werge Thomas M. , Melbye Mads , Buil Alfonso , Feenstra Bjarke
Published: September 2019

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
Tumor-reprogrammed resident T cells resist radiation to control tumors
Authors: Arina Ainhoa , Beckett Michael , Fernandez Christian , Zheng Wenxin , Pitroda Sean , Chmura Steven J. , Luke Jason J. , Forde Martin , Hou Yuzhu , Burnette Byron , Mauceri Helena , Lowy Israel , Sims Tasha , Khodarev Nikolai , Fu Yang-Xin , Weichselbaum Ralph R.
Published: September 2019

Successful combinations of radiotherapy and immunotherapy depend on the presence of live T cells within the tumor; however, radiotherapy is believed to damage T cells. Here, based on longitudinal in vivo imaging and functional analysis, we report that a large proportion of T cells survive clinically relevant doses of radiation and show increased motility, and higher production of interferon gamma, compared with T cells from unirradiated tumors. Irradiated intratumoral T cells can mediate tumor control without newly-infiltrating T cells. Transcriptomic analysis suggests T cell reprogramming in the tumor microenvironment and similarities with tissue-resident memory T cells, which are more radio-resistant than circulating/lymphoid tissue T cells. TGFβ is a key upstream regulator of T cell reprogramming and contributes to intratumoral Tcell radio-resistance. These findings have implications for the design of radio-immunotherapy trials in that local irradiation is not inherently immunosuppressive, and irradiation of multiple tumors might optimize systemic effects of radiotherapy.
Improving mass spectrometry analysis of protein structures with arginine-selective chemical cross-linkers
Authors: Jones Alexander X. , Cao Yong , Tang Yu-Liang , Wang Jian-Hua , Ding Yue-He , Tan Hui , Chen Zhen-Lin , Fang Run-Qian , Yin Jili , Chen Rong-Chang , Zhu Xing , She Yang , Huang Niu , Shao Feng , Ye Keqiong , Sun Rui-Xiang , He Si-Min , Lei Xiaoguang , Dong Meng-Qiu
Published: September 2019

Chemical cross-linking of proteins coupled with mass spectrometry analysis (CXMS) is widely used to study protein-protein interactions (PPI), protein structures, and even protein dynamics. However, structural information provided by CXMS is still limited, partly because most CXMS experiments use lysine-lysine (K-K) cross-linkers. Although superb in selectivity and reactivity, they are ineffective for lysine deficient regions. Herein, we develop aromatic glyoxal cross-linkers (ArGOs) for arginine-arginine (R-R) cross-linking and the lysine-arginine (K-R) cross-linker KArGO. The R-R or K-R cross-links generated by ArGO or KArGO fit well with protein crystal structures and provide information not attainable by K-K cross-links. KArGO, in particular, is highly valuable for CXMS, with robust performance on a variety of samples including a kinase and two multi-protein complexes. In the case of the CNGP complex, KArGO cross-links covered as much of the PPI interface as R-R and K-K cross-links combined and improved the accuracy of Rosetta docking substantially.
Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease
Authors: Krashia Paraskevi , Cordella Alberto , Nobili Annalisa , La Barbera Livia , Federici Mauro , Leuti Alessandro , Campanelli Federica , Natale Giuseppina , Marino Gioia , Calabrese Valeria , Vedele Francescangelo , Ghiglieri Veronica , Picconi Barbara , Di Lazzaro Giulia , Schirinzi Tommaso , Sancesario Giulia , Casadei Nicolas , Riess Olaf , Bernardini Sergio , Pisani Antonio , Calabresi Paolo , Viscomi Maria Teresa , Serhan Charles Nicholas , Chiurchiù Valerio , D’Amelio Marcello , Mercuri Nicola Biagio
Published: September 2019

Neuroinflammation is one of the hallmarks of Parkinson’s disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD – to modulate disease progression – still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early-PD. Our results suggest there is an imbalance between neuroinflammatory and pro-resolving processes in PD.
Assisted reproductive technologies are associated with limited epigenetic variation at birth that largely resolves by adulthood
Authors: Novakovic Boris , Lewis Sharon , Halliday Jane , Kennedy Joanne , Burgner David P. , Czajko Anna , Kim Bowon , Sexton-Oates Alexandra , Juonala Markus , Hammarberg Karin , Amor David J. , Doyle Lex W. , Ranganathan Sarath , Welsh Liam , Cheung Michael , McBain John , McLachlan Robert , Saffery Richard
Published: September 2019

More than 7 million individuals have been conceived by Assisted Reproductive Technologies (ART) and there is clear evidence that ART is associated with a range of adverse early life outcomes, including rare imprinting disorders. The periconception period and early embryogenesis are associated with widespread epigenetic remodeling, which can be influenced by ART, with effects on the developmental trajectory in utero, and potentially on health throughout life. Here we profile genome-wide DNA methylation in blood collected in the newborn period and in adulthood (age 22–35 years) from a unique longitudinal cohort of ART-conceived individuals, previously shown to have no differences in health outcomes in early adulthood compared with non-ART-conceived individuals. We show evidence for specific ART-associated variation in methylation around birth, most of which occurred independently of embryo culturing. Importantly, ART-associated epigenetic variation at birth largely resolves by adulthood with no direct evidence that it impacts on development and health.
Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome
Authors: Yang Chao , Siebert Jason R. , Burns Robert , Gerbec Zachary J. , Bonacci Benedetta , Rymaszewski Amy , Rau Mary , Riese Matthew J. , Rao Sridhar , Carlson Karen-Sue , Routes John M. , Verbsky James W. , Thakar Monica S. , Malarkannan Subramaniam
Published: September 2019

Natural killer (NK) cells are critical to both innate and adaptive immunity. However, the development and heterogeneity of human NK cells are yet to be fully defined. Using single-cell RNA-sequencing technology, here we identify distinct NK populations in human bone marrow and blood, including one population expressing higher levels of immediate early genes indicative of a homeostatic activation. Functionally matured NK cells with high expression of CX3CR1, HAVCR2 (TIM-3), and ZEB2 represents terminally differentiated status with the unique transcriptional profile. Transcriptomic and pseudotime analyses identify a transitional population between CD56bright and CD56dim NK cells. Finally, a donor with GATA2T354M mutation exhibits reduced percentage of CD56bright NK cells with altered transcriptome and elevated cell death. These data expand our understanding of the heterogeneity and development of human NK cells.
Managing high fiber food waste for the cultivation of black soldier fly larvae
Authors: Palma Lydia , Fernandez-Bayo Jesus , Niemeier Deb , Pitesky Maurice , VanderGheynst Jean S.
Published: September 2019

Increases in global human population are leading to increasing demands for food production and waste management. Insect biomass is a sustainable alternative to traditional animal feeds when insects are produced on lignocellulosic by-products. Resources high in lignocellulose have high carbon to nitrogen ratios and require nitrogen supplementation to accelerate bioconversion. Here we report on studies that examine the influence of nitrogen supplementation of almond hull-based feedstocks on black soldier fly larvae (Hermetia illucens L.) cultivation and composition. Decreasing carbon to nitrogen ratio from 49 to 16 increased larvae harvest dry weight, specific larvae growth, and yield by 36%, 31%, and 51%, respectively. However, the decrease in carbon to nitrogen ratio decreased larvae methionine and cysteine contents by 11% and 13%, respectively. The findings demonstrate that carbon to nitrogen ratio can be managed to enhance bioconversion of lignocellulose to larvae, but that this management approach can reduce larvae amino acid content.
Consistently dated Atlantic sediment cores over the last 40 thousand years
Authors: Waelbroeck Claire , Lougheed Bryan C. , Vazquez Riveiros Natalia , Missiaen Lise , Pedro Joel , Dokken Trond , Hajdas Irka , Wacker Lukas , Abbott Peter , Dumoulin Jean-Pascal , Thil François , Eynaud Frédérique , Rossignol Linda , Fersi Wiem , Albuquerque Ana Luiza , Arz Helge , Austin William E. N. , Came Rosemarie , Carlson Anders E. , Collins James A. , Dennielou Bernard , Desprat Stéphanie , Dickson Alex , Elliot Mary , Farmer Christa , Giraudeau Jacques , Gottschalk Julia , Henderiks Jorijntje , Hughen Konrad , Jung Simon , Knutz Paul , Lebreiro Susana , Lund David C. , Lynch-Stieglitz Jean , Malaizé Bruno , Marchitto Thomas , Martínez-Méndez Gema , Mollenhauer Gesine , Naughton Filipa , Nave Silvia , Nürnberg Dirk , Oppo Delia , Peck Victoria , Peeters Frank J. C. , Penaud Aurélie , Portilho-Ramos Rodrigo da Costa , Repschläger Janne , Roberts Jenny , Rühlemann Carsten , Salgueiro Emilia , Sanchez Goni Maria Fernanda , Schönfeld Joachim , Scussolini Paolo , Skinner Luke C. , Skonieczny Charlotte , Thornalley David , Toucanne Samuel , Rooij David Van , Vidal Laurence , Voelker Antje H. L. , Wary Mélanie , Weldeab Syee , Ziegler Martin
Published: September 2019

Rapid changes in ocean circulation and climate have been observed in marine-sediment and ice cores over the last glacial period and deglaciation, highlighting the non-linear character of the climate system and underlining the possibility of rapid climate shifts in response to anthropogenic greenhouse gas forcing. To date, these rapid changes in climate and ocean circulation are still not fully explained. One obstacle hindering progress in our understanding of the interactions between past ocean circulation and climate changes is the difficulty of accurately dating marine cores. Here, we present a set of 92 marine sediment cores from the Atlantic Ocean for which we have established age-depth models that are consistent with the Greenland GICC05 ice core chronology, and computed the associated dating uncertainties, using a new deposition modeling technique. This is the first set of consistently dated marine sediment cores enabling paleoclimate scientists to evaluate leads/lags between circulation and climate changes over vast regions of the Atlantic Ocean. Moreover, this data set is of direct use in paleoclimate modeling studies.
Association between insulin resistance, hyperglycemia, and coronary artery disease according to the presence of diabetes
Authors: Cho Young-Rak , Ann Soe Hee , Won Ki-Bum , Park Gyung-Min , Kim Yong-Giun , Yang Dong Hyun , Kang Joon-Won , Lim Tae-Hwan , Kim Hong-Kyu , Choe Jaewon , Lee Seung-Whan , Kim Young-Hak , Kim Shin-Jae , Lee Sang-Gon
Published: September 2019

This study evaluated the relationship of insulin resistance (IR) and glycemic control status to the presence and severity of coronary artery disease (CAD) according to diabetes. The relationship of IR parameters including homeostatic model assessment of IR (HOMA-IR), triglyceride-glucose (TyG) index, and triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL), and hemoglobin A1C (HbA1C) level to CAD and obstructive CAD was evaluated in 5,764 asymptomatic subjects who underwent coronary computed tomographic angiography. Non-diabetics (n = 4768) and diabetics (n = 996) were stratified into four groups based on the quartiles of HOMA-IR and the TyG index and were grouped based on the TG/HDL cut-offs of 3.5, respectively. CAD and obstructive CAD were defined as the presence of any plaques and plaques with ≥50% stenosis, respectively. The prevalence of CAD (59.0% vs. 39.0%) and obstructive CAD (15.0% vs. 6.6%) was higher in diabetic than in non-diabetic patients (p < 0.001, respectively). In non-diabetic patients, the adjusted odds ratio for both CAD and obstructive CAD significantly increased, but only with higher TyG index quartiles. Unlike non-diabetics, the adjusted odds ratio for obstructive CAD significantly increased in diabetic patients with a TG/HDL level ≥ 3.5. The HbA1C, rather than IR parameters, was independently associated with both CAD and obstructive CAD in diabetics. In conclusion, among IR parameters, TyG index was independently associated with the presence of CAD and obstructive CAD in non-diabetic patients. In contrast, the glycemic control status, rather than IR, was importantly related to both CAD and obstructive CAD in established diabetic patients.
Compensatory task-specific hypersensitivity in bilateral planum temporale and right superior temporal gyrus during auditory rhythm and omission processing in Parkinson’s disease
Authors: Vikene Kjetil , Skeie Geir Olve , Specht Karsten
Published: September 2019

Persons with Parkinson’s disease have general timing deficits and have difficulties in rhythm discrimination tasks. The basal ganglia, a crucial part of Parkinson’s disease pathology, is believed to play an important role in rhythm and beat processing, with a possible modulation of basal ganglia activity by level of rhythmic complexity. As dysfunction in basal ganglia impacts function in other brain areas in Parkinson’s disease during temporal processing, investigating the neuronal basis for rhythm processing is important as it could shed light on the nature of basal ganglia dysfunction and compensatory mechanisms. We constructed an auditory beat-omission fMRI paradigm with two levels of rhythm complexity, to investigate if and where persons with Parkinson’s disease showed abnormal activation during rhythm and omission processing, and whether such activations were modulated by the level of rhythmic complexity. We found no effect of complexity, but found crucial group differences. For the processing of normal rhythm presentations, the Parkinson-group showed higher bilateral planum temporal activity, an area previously associated with the processing of complex patterns. For the omissions, the Parkinson-group showed higher activity in an area in the right superior temporal gyrus previously associated with detection of auditory omissions. We believe this shows a pattern of “hypersensitive” activity, indicative of task-specific, compensatory mechanisms in the processing of temporal auditory information in persons with Parkinson’s disease.
New perspectives for viability studies with high-content analysis Raman spectroscopy (HCA-RS)
Authors: Mondol Abdullah Saif , Töpfer Natalie , Rüger Jan , Neugebauer Ute , Popp Jürgen , Schie Iwan W.
Published: September 2019

Raman spectroscopy has been widely used in clinical and molecular biological studies, providing high chemical specificity without the necessity of labels and with little-to-no sample preparation. However, currently performed Raman-based studies of eukaryotic cells are still very laborious and time-consuming, resulting in a low number of sampled cells and questionable statistical validations. Furthermore, the approach requires a trained specialist to perform and analyze the experiments, rendering the method less attractive for most laboratories. In this work, we present a new high-content analysis Raman spectroscopy (HCA-RS) platform that overcomes the current challenges of conventional Raman spectroscopy implementations. HCA-RS allows sampling of a large number of cells under different physiological conditions without any user interaction. The performance of the approach is successfully demonstrated by the development of a Raman-based cell viability assay, i.e., the effect of doxorubicin concentration on monocytic THP-1 cells. A statistical model, principal component analysis combined with support vector machine (PCA-SVM), was found to successfully predict the percentage of viable cells in a mixed population and is in good agreement to results obtained by a standard cell viability assay. This study demonstrates the potential of Raman spectroscopy as a standard high-throughput tool for clinical and biological applications.
Resonance phenomena controlled by external feedback signals and additive noise in neural systems
Authors: Nobukawa Sou , Shibata Natsusaku , Nishimura Haruhiko , Doho Hirotaka , Wagatsuma Nobuhiko , Yamanishi Teruya
Published: September 2019

Chaotic resonance is a phenomenon that can replace the fluctuation source in stochastic resonance from additive noise to chaos. We previously developed a method to control the chaotic state for suitably generating chaotic resonance by external feedback even when the external adjustment of chaos is difficult, establishing a method named reduced region of orbit (RRO) feedback. However, a feedback signal was utilized only for dividing the merged attractor. In addition, the signal sensitivity in chaotic resonance induced by feedback signals and that of stochastic resonance by additive noise have not been compared. To merge the separated attractor, we propose a negative strength of the RRO feedback signal in a discrete neural system which is composed of excitatory and inhibitory neurons. We evaluate the features of chaotic resonance and compare it to stochastic resonance. The RRO feedback signal with negative strength can merge the separated attractor and induce chaotic resonance. We also confirm that additive noise induces stochastic resonance through attractor merging. The comparison of these resonance modalities verifies that chaotic resonance provides more applicability than stochastic resonance given its capability to handle attractor separation and merging.
Myoferlin silencing inhibits VEGFR2-mediated proliferation of metastatic clear cell renal cell carcinoma
Authors: An Hyo Jung , Song Dae Hyun , Koh Hyun Min , Kim Yu-Min , Ko Gyung Hyuck , Lee Jeong-Hee , Lee Jong Sil , Yang Jung Wook , Kim Min Hye , Seo Deok Ha , Jang Se Min , Kim Dong Chul
Published: September 2019

Recently, ramucirumab, a drug that targets vascular endothelial growth factor receptor (VEGFR), was clinically approved; therefore, we evaluated VEGFR2 expression and its predictive roles in tumor progression in clear cell renal cell carcinoma (CCRCC). Since we do not have many options for treating aggressive renal cell carcinoma patients, the application of anti-VEGFR2 therapy might be useful. Myoferlin (MYOF) is a 230 kDa transmembrane multi-C2-domain protein that contributes to plasma membrane repair, fusion, and endocytosis and is overexpressed in several invasive cancer cell lines, including breast, pancreas, and malignant melanoma. It forms a complex with VEGFR2 to inhibit VEGFR2 degradation. In this study, a total of 152 patients who had undergone nephrectomy for CCRCC were enrolled. Based on tissue microarray (TMA) blocks, the positive intensity and high proportion of MYOF showed a statistically significant correlation with the negative intensity (p < 0.001) and low proportion (p < 0.001) of VEGFR2, respectively. In addition, Fuhrman’s nuclear grade ≥3 showed a significant correlation with VEGFR2 expression. In multivariate analysis, CCRCC patients with positive MYOF and negative VEGFR2 expression demonstrated poor clinical outcomes. We confirmed that positive MYOF expression and negative VEGFR2 expression were positively correlated in this CCRCC population. Knocking down MYOF in Caki-1 cells resulted in the downregulation of VEGFR2 at both mRNA and protein levels. Wound healing assays revealed that the loss of MYOF in Caki-1 cells decreased cell confluence compared to that in control cells. We demonstrated that MYOF influences cellular proliferation of the metastatic CCRCC cell line by regulating VEGFR2 degradation. Combined therapies targeting the MYOF and VEGFR2 pathways might be effective against metastatic CCRCC to increase patient survival.
ETHE1 and MOCS1 deficiencies: Disruption of mitochondrial bioenergetics, dynamics, redox homeostasis and endoplasmic reticulum-mitochondria crosstalk in patient fibroblasts
Authors: Grings Mateus , Seminotti Bianca , Karunanidhi Anuradha , Ghaloul-Gonzalez Lina , Mohsen Al-Walid , Wipf Peter , Palmfeldt Johan , Vockley Jerry , Leipnitz Guilhian
Published: September 2019

Ethylmalonic encephalopathy protein 1 (ETHE1) and molybdenum cofactor (MoCo) deficiencies are hereditary disorders that affect the catabolism of sulfur-containing amino acids. ETHE1 deficiency is caused by mutations in the ETHE1 gene, while MoCo deficiency is due to mutations in one of three genes involved in MoCo biosynthesis (MOCS1, MOCS2 and GPHN). Patients with both disorders exhibit abnormalities of the mitochondrial respiratory chain, among other biochemical findings. However, the pathophysiology of the defects has not been elucidated. To characterize cellular derangements, mitochondrial bioenergetics, dynamics, endoplasmic reticulum (ER)-mitochondria communication, superoxide production and apoptosis were evaluated in fibroblasts from four patients with ETHE1 deficiency and one with MOCS1 deficiency. The effect of JP4-039, a promising mitochondrial-targeted antioxidant, was also tested on cells. Our data show that mitochondrial respiration was decreased in all patient cell lines. ATP depletion and increased mitochondrial mass was identified in the same cells, while variable alterations in mitochondrial fusion and fission were seen. High superoxide levels were found in all cells and were decreased by treatment with JP4-039, while the respiratory chain activity was increased by this antioxidant in cells in which it was impaired. The content of VDAC1 and IP3R, proteins involved in ER-mitochondria communication, was decreased, while DDIT3, a marker of ER stress, and apoptosis were increased in all cell lines. These data demonstrate that previously unrecognized broad disturbances of cellular function are involved in the pathophysiology of ETHE1 and MOCS1 deficiencies, and that reduction of mitochondrial superoxide by JP4-039 is a promising strategy for adjuvant therapy of these disorders.