bluuebunny/crossref_metadata_2025 huggingface dataset:
Perturbativity constraints on U(1)B−L and left-right models and implications for heavy gauge boson searches
Authors: Chauhan Garv , Dev P. S. Bhupal , Mohapatra Rabindra N. , Zhang Yongchao
Published: January 2019

Abstract

We derive perturbativity constraints on beyond standard model scenarios with extra gauge groups, such as SU(2) or U(1), whose generators contribute to the electric charge, and show that there are both upper and lower limits on the additional gauge couplings, from the requirement that the couplings remain perturbative up to the grand unification theory (GUT) scale. This leads to stringent constraints on the masses of the corresponding gauge bosons and their collider phenomenology. We specifically focus on the models based on

$$ SU{(2)}_L \times U{(1)}_{I_{3R}} \times U{(1)}_{B-L} $$

S
U

2

L

×

U

1

I

3
R

×

U

1

B
−
L

and the left-right symmetric models based on SU(2)
L
 × SU(2)
R
 × U(1)
B − L
, and discuss the implications of the perturbativity constraints for new gauge boson searches at current and future colliders. In particular, we find that the stringent flavor constraints in the scalar sector of left-right model set a lower bound on the right-handed scale v

R
≳ 10 TeV, if all the gauge and quartic couplings are to remain perturbative up to the GUT scale. This precludes the prospects of finding the Z

R
boson in the left-right model at the LHC, even in the high-luminosity phase, and leaves only a narrow window for the W

R
boson. A much broader allowed parameter space, with the right-handed scale v

R
up to ≃ 87 TeV, could be probed at the future 100 TeV collider.
A geometric dual of c-extremization
Authors: Couzens Christopher , Gauntlett Jerome P. , Martelli Dario , Sparks James
Published: January 2019

Abstract

We consider supersymmetric AdS3 × Y
7 and AdS2 × Y
9 solutions of type IIB and D = 11 supergravity, respectively, that are holographically dual to SCFTs with (0, 2) supersymmetry in two dimensions and

$$ \mathcal{N} $$

N

= 2 supersymmetry in one dimension. The geometry of Y
2n+1, which can be defined for n ≥ 3, shares many similarities with Sasaki-Einstein geometry, including the existence of a canonical R-symmetry Killing vector, but there are also some crucial differences. We show that the R-symmetry Killing vector may be determined by extremizing a function that depends only on certain global, topological data. In particular, assuming it exists, for n = 3 one can compute the central charge of an AdS3 × Y
7 solution without knowing its explicit form. We interpret this as a geometric dual of c-extremization in (0, 2) SCFTs. For the case of AdS2 × Y
9 solutions we show that the extremal problem can be used to obtain properties of the dual quantum mechanics, including obtaining the entropy of a class of supersymmetric black holes in AdS4. We also study many specific examples of the type AdS3 × T
2 × Y
5, including a new family of explicit supergravity solutions. In addition we discuss the possibility that the (0, 2) SCFTs dual to these solutions can arise from the compactification on T
2 of certain d = 4 quiver gauge theories associated with five-dimensional Sasaki-Einstein metrics and, surprisingly, come to a negative conclusion.
Short‐ and Long‐term Outcomes after Robotic and Laparoscopic Liver Resection for Malignancies: A Propensity Score‐Matched Study
Authors: Lim Chetana , Salloum Chady , Tudisco Antonella , Ricci Claudio , Osseis Michael , Napoli Niccolo , Lahat Eylon , Boggi Ugo , Azoulay Daniel
Published: January 2019

Objectives

A laparoscopic approach improves short‐term outcomes and maintains long‐term outcomes compared to an open approach. In turn, the recent development of robotic surgery raises the question whether it performs as well as laparoscopic surgery. The aim of this study was to compare the short‐ and long‐term outcomes of laparoscopic liver resection (LLR) and robotic liver resection (RLR) for malignancies.

Method

From 2011 to 2017, the study population included 111 patients in the LLR group and 61 in the RLR group. Short‐ and long‐term outcomes were compared before and after propensity score matching (PSM).

Results

Operative mortality rate was nil. The intraoperative blood transfusion rate was higher during RLR (15% vs. 2%, p = 0.0009). Major morbidity and hospital stay were not different between the two groups. The resection margin width (LLR 7 mm vs. RLR 10 mm, p = 0.13) and R1 resection rates (resection margin width < 1 mm; LLR 15% vs. RLR 11%, p = 0.49) were similar. After PSM (55 patients in each group), the blood transfusion, major morbidity, hospital stay and R1 resection were similar between the two groups. When considering the largest subset of patients with hepatocellular carcinoma including 114 patients (66%), the 3‐year overall survival rate was 80% in the LLR group and 97% in the RLR group (p = 0.10) and remained similar after PSM (p = 0.27). The 3‐year recurrence‐free survival rate was 50% in the LLR group and 64% in the RLR group (p = 0.30) and remained similar after PSM (p = 0.26).

Conclusions

No differences were found in blood transfusion, incidence of positive resection margins and long‐term outcomes between the two techniques. RLR does not compromise short‐term and oncologic outcomes in patients with liver cancers.
Biological conversion of propane to 2-propanol using group I and II methanotrophs as biocatalysts
Authors: Nguyen Thu Thi , Hwang In Yeub , Na Jeong Geol , Lee Eun Yeol
Published: January 2019

Propane is the main component of liquefied petroleum gas and is derived from crude oil processing. Methanotrophic bacteria can convert various alkanes using methane monooxygenase enzyme to primary alcohols. These are further oxidized to various aldehydes by alcohol dehydrogenases or methanol dehydrogenases. In this study, 2-propanol was produced from propane using the whole cells of Methylosinus trichosporium OB3b, Methylomicrobium alcaliphilum 20Z, and Methylomonas sp. DH-1 as the biocatalysts. The biocatalytic process of converting propane to 2-propanol was optimized by the use of several inhibitors and additives, such as EDTA, sodium phosphate, and sodium formate to prevent oxidation of 2-propanol to acetone and to enhance conversion of propane to propanol. The maximum titer of 2-propanol was 0.424 g/L, 0.311 g/L, and 0.610 g/L for Methylomonas sp. DH-1, M. alcaliphilum 20Z, and M. trichosporium OB3b whole cells, respectively. These results showed that type I and type II methanotrophs could be used as the potent biocatalyst for conversion of propane to propanol.
The Impact of Luther and the Reformation in the Portuguese Seaborne Empire: Asia and Brazil, 1520–1580
Authors: PAIVA JOSÉ PEDRO
Published: January 2019

This article assesses how Lutheran and other Reformation doctrines spread and were countered in the Portuguese seaborne empire. Portugal's inquisitorial and episcopal repression of ‘Lutherans’ was extended to Brazil and Asia, where it was supported by the Society of Jesus. The Portuguese empire's transcontinental connections favoured the emergence of interconnected histories, facilitating the circulation of books, engravings and beliefs and thus provided non-Portuguese people with links to the reformed world that spread amongst and disturbed the Portuguese living in India and Portuguese America. By opening up routes the Portuguese, paradoxically, functioned as vectors for other ways of interpreting Christianity.
Allies and Traitors: Vice-Presidents in Latin America
Authors: Marsteintredet Leiv , Uggla Fredrik
Published: January 2019

Vice-presidents in Latin America have often been at the centre of political turbulence. To prevent conflicts within the executive, most Latin American countries have therefore put in place formulae to elect presidents and vice-presidents on a joint electoral ticket. Still, it is common for presidential candidates to pick running mates from other parties in order to construct alliances and appeal to a broader set of voters. But the presence of such ‘external’ vice-presidents seems to increase the risk of presidential interruption in general and impeachment processes in particular. Accordingly, we argue that the frequently overlooked institution of the vice-president deserves attention as a possible intervening variable that can contribute to the explanation for government crises and their outcomes in Latin America.
What’s fair? Preferences for tax progressivity in the wake of the financial crisis
Authors: Limberg Julian
Published: January 2019

Progressive taxation is an effective redistributive tool in times of growing inequality. However, like all public policies, an increase in tax progressivity is unlikely if it lacks popular demand. Has the financial crisis affected the demand for progressive taxation? Building on research that has identified fairness beliefs as the main factor pushing for taxes on the rich, I argue that the Great Recession and states’ reactions to it have caused a general shift in tax policy preferences. As a consequence, demand for tax progressivity is higher in crisis countries. Multilevel analyses using survey data for 32 countries show support for my argument. These findings have important implications for our understanding of the politics of redistribution in the 21st century.
Caring relationships and their role in users’ choices: a study of users of Direct Payments in England
Authors: Rodrigues Ricardo
Published: January 2019

User choice in care for older people has assumed that care is like any other commodity; which is in contrast with the concept of care defined by the feminist and ethics of care literature, which includes a relational component beyond care tasks – caring relationships. This study aims to understand how caring relationships impact the decisions of older users of care and their perceived satisfaction. Semi-structured qualitative interviews were conducted with 24 Direct Payments (DPs) older users, including proxies, in three Local Authorities in the Greater London area. Users fell into three groups according to their use of DPs: those purchasing care from agencies, those employing acquaintances as Personal Assistants (PAs) and those employing strangers as PAs. Decisions on and perceived satisfaction with care were both influenced by caring relationships. All users recognised that caring relationships can have instrumental value in improving care delivery or allowing greater leeway in negotiating tasks. Many users placed intrinsic value on continuity of care and the development of close caring relationships and clearly favoured employing PAs. The latter involved higher levels of uncertainty, emotional investment and reciprocal gift exchanges. Agencies were often chosen due to users’ preference for more detached caring relationships. The findings confirm that caring relationships involving reciprocal emotional investment are an important outcome of care, with salient implications for user behaviour.
Examining the associations between children's receptive language skills and developmental domains in the United States and Turkey
Authors: GULER YILDIZ Tulin , GONEN Mubeccel , ULKER ERDEM Ayca , GARCIA Aileen , RAIKES Helen , ACAR Ibrahim H. , BURCAK Firdevs , TURAN Figen , CAN GUL Sadiye , DAVIS Dawn
Published: January 2019

This study examined the relations between receptive language development and other developmental domains of preschoolers from low-income families, through an inter-cultural perspective involving the United States and Turkey. A total of 471 children and their caregivers participated in Turkey, while 287 participated in the United States. Children's development was assessed using the Ages and Stages Questionnaire for both samples. Different versions of the Peabody Picture Vocabulary Test were used for Turkish and US samples, to measure receptive language development. Results revealed similar patterns, with some differences, between the two countries. Receptive language predicted only communication and personal–social scales in the Turkish sample, while the US children's receptive language skills were associated with communication, problem solving, personal–social, and fine and gross motor development scales. These results were discussed in the context of each country, and the comparative conclusions contribute to the extant literature by illustrating the importance of language for three domains.
Identifying critical psychotherapy targets in serious cardiac conditions: The importance of addressing coping with symptoms, healthcare navigation, and social support
Authors: Bekelman David B. , Knoepke Christopher E. , Turvey Carolyn
Published: January 2019

Objective

In seriously ill cardiac patients, several psychotherapy efficacy studies demonstrate little to no reduction in depression or improvement in quality of life, and little is known about how to improve psychotherapies to best address the range of patient needs. An interpersonal and behavioral activation psychotherapy was a key component of the Collaborative Care to Alleviate Symptoms and Adjust to Illness (CASA) multisite randomized clinical trial. Although depressive symptoms did improve in the CASA trial, questions remain about how best to tailor psychotherapies to the needs of seriously ill patient populations. The study objective was to describe psychosocial needs emerging during a clinical trial of a palliative care and interpersonal and behavioral activation psychotherapy intervention that were not specifically addressed by the psychotherapy.

Method

During the CASA trial, patient needs were prospectively tracked by the psychotherapist in each visit note using an a priori code list. Preplanned analysis of study data using directed content analysis was conducted analyzing the a priori code list, which were collapsed by team consensus into larger themes. The frequency of each code and theme were calculated into a percentage of visits.

Result

A total of 150 patients received one or more visits from the therapist and were included in the analysis. Participants screened positive for depressive disorder (47%), had poor heart failure-specific health status (mean Kansas City Cardiomyopathy Questionnaire score = 48.6; SD = 17.4), and multiple comorbidities (median 4.3). Common needs that emerged during the therapy included difficulty coping with fatigue (48%), pain (28%), and satisfaction issues with medical care (43%). The following broader themes emerged: social support (77% of sessions), unmet symptom needs (67%), healthcare navigation (48%), housing, legal, safety, and transportation (32%), and end of life (12%).

Significance of results

Coping with chronic symptoms and case management needs commonly emerged during psychotherapy visits. Future psychotherapy interventions in seriously ill populations should consider the importance of coping with chronic symptoms and case management.
Unveiling the association between Vitamin D Receptor and Poly Cystic Ovary Syndrome – a systematic review and meta-analysis
Authors: Deswal Ritu , Nanda Smiti , Dang Amita Suneja
Published: January 2019

Abstract. Background: Low Vitamin D status observed in the populations globally and its associations with diverse systems have kindled the interest for Vitamin D in medical literature in last two decades. Accumulating evidence manifest that deficiency of Vitamin D might be a causal factor in the pathogenesis of various features of Poly Cystic Ovary Syndrome (PCOS). This notion is supported by the fact that > 3 % of the human genome is regulated by vitamin D receptor (VDR). Therefore, this meta-analysis was carried out to quantify the magnitude of risk associated with VDR polymorphisms (BsmI, TaqI, FokI and ApaI) and PCOS susceptibility. Methods: Pub-med, EMBASE, Cochrane database, Science direct, Scirus, ISI web of knowledge and Google scholar were searched for all years until July 2016. The case control studies related to VDR polymorphism and PCOS risk were selected according to inclusion and exclusion criteria. Nine studies of the initial 553 hits reporting VDR polymorphism in PCOS were included. All statistical analysis was performed using the STATA 11.0 software and odd ratio with 95 % confidence intervals was used as effect size to assess the strength of associations. Results: Nine studies comprising 1558 cases and 1033 controls were included in this meta-analysis. Significant association between VDR Fok1 polymorphisms and PCOS risk was observed. In further stratified analysis, an increased risks were observed among Asian and African populations for Taq1 polymorphism. Apa1 and Bsm1 polymorphism was found not to be a risk factor for PCOS susceptibility. Conclusion: The FokI polymorphism is found to be a significant risk factor for PCOS.
geomIO: An Open‐Source MATLAB Toolbox to Create the Initial Configuration of 2‐D/3‐D Thermo‐Mechanical Simulations From 2‐D Vector Drawings
Authors: Bauville A. , Baumann T. S.
Published: January 2019

Creating the initial geometry and temperature configuration of 3‐D numerical simulations is a challenging task. Professional tools are expensive. They often have a steep learning curve and do mostly not interface with the numerical simulation software used by the geodynamics and tectonics academic community. There, we developed geometry Input/Output (geomIO), a MATLAB toolbox to create the initial configuration of geological models regarding model geometry and temperature structure. geomIO allows users to create a geo‐referenced 3‐D volume by drawing multiple 2‐D cross sections in a standard vector graphics editor. The volume is then used to assign material properties and set up initial temperature distribution on a set of vertices. In 2‐D mode, polygons can also be used to create a triangular mesh. In addition to the standard functionality, the gravity anomaly of any geometry created with geomIO can be calculated. In this paper, we give an overview of the basic functionalities of geomIO. We illustrate the strength of our software with advanced tectonic and geodynamic applications that could not have been performed with currently available free software. Applications include the Himalayan orogen, the Japanese subduction zones, present‐day salt diapirs, and small‐scale tectonic structures. We describe algorithms and file formats in the supporting information. The toolbox is user‐friendly and flexible. Users can use custom pipelines or preset data processing pipelines, so most applications require only a few lines of code. geomIO is distributed under the GNU General Public License and includes an online wiki with tutorials and additional examples.
Dust Sources of Last Glacial Chinese Loess Based on the Iron Mineralogy of Fractionated Source Samples
Authors: Jia Jia , Wang Youjun , Xia Dunsheng , Lu Hao , Gao Fuyuan
Published: January 2019

The Chinese Loess Plateau (CLP) is composed of an enormous volume of aeolian dust, the provenance of which is still debated. In the present study, we attempt to distinguish different sources of Last Glacial (LG) sediments of the CLP based on the iron mineralogical characteristics of different particle size fractions of surface samples from potential source areas in Northwest China. The result reveals that the iron mineral characteristics of the surface samples are spatially heterogeneous and that differences between sedimentary basins are greater than those within the basins. The contents of magnetite and goethite have a significant particle size dependency, but this is not the case for hematite. The iron mineralogical characteristics of the samples are closely related to the distribution of mountain ranges and tectonic activity in NW China. Basing on mathematical calculation, we propose that (i) the 8‐ to 31‐μm fractions, the major component of CLP loess, is a mixture of sediment weathering from NE Tibetan Plateau and Central Asian Orogenic Belt, with a majority from Tibetan Plateau; (ii) S. Alxa Plateau is the dominant source of 31‐ to 63‐μm fractions of CLP LG loess; (iii) the Qaidam Basin is the dominant source of 2‐ to 8‐μm fractions of CLP LG loess; and (iv) the material contribution from Ordos Plateau is limited to CLP LG loess, especially for the loess on the western CLP.
The Upper Stratospheric Solar Cycle Ozone Response
Authors: Ball W. T. , Rozanov E. V. , Alsing J. , Marsh D. R. , Tummon F. , Mortlock D. J. , Kinnison D. , Haigh J. D.
Published: January 2019

The solar cycle (SC) stratospheric ozone response is thought to influence surface weather and climate. To understand the chain of processes and ensure climate models adequately represent them, it is important to detect and quantify an accurate SC ozone response from observations. Chemistry climate models (CCMs) and observations display a range of upper stratosphere (1–10 hPa) zonally averaged spatial responses; this and the recommended data set for comparison remains disputed. Recent data‐merging advancements have led to more robust observational data. Using these data, we show that the observed SC signal exhibits an upper stratosphere U‐shaped spatial structure with lobes emanating from the tropics (5–10 hPa) to high altitudes at midlatitudes (1–3 hPa). We confirm this using two independent chemistry climate models in specified dynamics mode and an idealized timeslice experiment. We recommend the BASICv2 ozone composite to best represent historical upper stratospheric solar variability, and that those based on SBUV alone should not be used.
Magnetic Signatures of a Plume at Europa During the Galileo E26 Flyby
Authors: Arnold Hannes , Liuzzo Lucas , Simon Sven
Published: January 2019

We analyze the magnetic field perturbations observed near Jupiter's icy moon Europa by the Galileo spacecraft during the E26 flyby on 3 January 2000. In addition to the expected large‐scale signatures of magnetic fieldline draping and induction, the E26 data set contains various prominent structures on length scales much smaller than the moon's radius. By applying a hybrid (kinetic ions and fluid electrons) model of Europa's interaction with the impinging magnetospheric plasma, we demonstrate that these fine structures in the magnetic field are consistent with Galileo's passage through a water vapor plume whose source was located in Europa's orbital trailing, southern hemisphere. Considering the large‐scale asymmetries of Europa's global atmosphere alone is not sufficient to explain the observed magnetic signatures. Combined with the recent identification of a plume during the earlier E12 flyby of Galileo, our results provide strong evidence that plume activity at Europa was a persistent phenomenon during the Galileo era.
Excitation of Storm Time Pc5 ULF Waves by Ring Current Ions Based on the Drift‐Kinetic Simulation
Authors: Yamakawa T. , Seki K. , Amano T. , Takahashi N. , Miyoshi Y.
Published: January 2019

Storm time Pc5 waves are considered to be excited through the drift‐bounce resonance by ring current ions associated with the injection from the magnetotail. Using the Geospace Environment Modeling System for Integrated Studies–Ring Current simulation, a drift‐kinetic and self‐consistent model for ring current particles, we investigate the excitation mechanism of these waves in the inner magnetosphere. The power spectra of electromagnetic field fluctuations show the excitation of both poloidal and toroidal mode waves in Pc5 frequency range. It is found that these waves are fundamental mode waves with the azimuthal wave number m~ − 20 and excited through the drift resonance with the drifting ions with energies of 80–120 keV. The simulation indicates that global distribution of wave power coincides with the positive local growth rate mainly contributed by the positive phase space density gradient in energy.
Growing Spatial Scales of Synchronous River Flooding in Europe
Authors: Berghuijs Wouter R. , Allen Scott T. , Harrigan Shaun , Kirchner James W.
Published: January 2019

River flooding is a common hazard, causing billions of dollars in annual losses. Flood impacts are shaped by the spatial scale over which different rivers flood simultaneously, but this dimension of flood risk remains largely unknown. Using annual flood data from several thousand European rivers, we demonstrate that the flood synchrony scale—the distance over which multiple rivers flood near synchronously—far exceeds the size of individual drainage basins and varies regionally by more than an order of magnitude. These data also show that flood synchrony scales have grown by about 50% over the period 1960–2010. Detrended flood synchrony values are serially correlated, implying that years with spatially extensive floods tend to follow one another. These findings reveal that flood risks are correlated well beyond the individual drainage basins for which flood hazards are typically assessed and managed.
Recent Advancements and Remaining Challenges Associated With Inner Magnetosphere Cross‐Energy/Population Interactions (IMCEPI)
Authors: Yu Yiqun , Liemohn Mike W. , Jordanova Vania K. , Lemon Colby , Zhang Jichun
Published: January 2019

The geospace inner magnetosphere, within about 10 Earth radii, contains various plasma populations with energy from a few electron volts to megaelectron volts and plays important roles in regulating the energy density of the magnetosphere, the magnetic field configuration, and wave dynamics. As an integrated part of the magnetosphere, the inner magnetosphere region also ties to other regions and can change the global geospace circulation. Therefore, understanding both internal and external cross‐energy/population interactions can help further our knowledge of the inner magnetosphere dynamics and nonlinear feedback processes. In view of this, in the past 5 years (2014–2018), the Geospace Environment Modeling (GEM) Focus Group “inner magnetosphere cross‐energy/population interactions (IMCEPI)” has gathered and boosted community‐wide interactions among observation, simulation, and modeling studies. This commentary reports some major accomplishments of the interactive inner magnetosphere community that were advanced by the IMCEPI Focus Group discussions and layouts remaining challenges that need to be carried on.
α‐Chapman Scale Height: Longitudinal Variation and Global Modeling
Authors: Li Qiaoling , Liu Libo , Jiang Jinzhe , Li Wenbo , Huang He , Yu You , Li Jiacheng , Zhang Ruilong , Le Huijun , Chen Yiding
Published: January 2019

Scale height measures the altitude gradient of the electron density profile and relates with the ionospheric chemistry and dynamics, while its longitudinal variation has not been fully investigated in both statistical analyses and empirical modelings. In this study, 11‐year electron density profiles from Constellation Observing System for Meteorology, Ionosphere, and Climate radio occultations are collected to retrieve the α‐Chapman scale height (Hm) from the lower topside ionospheric electron density profile (within 200‐km altitudes above the peak height of F2 layer [hmF2]) by fitting α‐Chapman function with a constant scale height. The Hm shows evident longitudinal variations at midlatitudes, and its zonal structure shows a consistency with that of hmF2 during daytime, which indicates neutral winds change the ionospheric height and shape at the same time. Further, a global modeling of Hm named 2PCAFourier‐Hm is built based on a two‐layer Principle Component Analysis combined with Fourier regression analysis of its coefficients under low and moderated solar activity. Longitudinal variation is considered in the Hm's modeling, along with the variations of local time, latitude, day of the year, and solar activity. Overall, the model well captures the temporal and spatial variations of Hm with a root‐mean‐square error of 2.25 km and a correlation coefficient of 0.97 with respect to the Constellation Observing System for Meteorology, Ionosphere, and Climate observations.
Finding Sources of Uncertainty in the Spatial Pattern of Warming
Authors: Shultz David
Published: January 2019

The planet is heating up, but uncertainty still exists about how temperatures will change in specific regions. A new study examines sources of uncertainty in the meridional pattern of warming.
Atlantic Overturning Circulation Questions Abound
Authors: Perez Renellys , Srokosz Meric , Danabasoglu Gokhan
Published: January 2019

International AMOC Science Meeting; Miami, Florida, 24–27 July 2018
Mesenchymal stem cells in suppression or progression of hematologic malignancy: current status and challenges
Authors: Lee Myoung Woo , Ryu Somi , Kim Dae Seong , Lee Ji Won , Sung Ki Woong , Koo Hong Hoe , Yoo Keon Hee
Published: January 2019

Mesenchymal stem cells (MSCs) are known for being multi-potent. However, they also possess anticancer properties, which has prompted efforts to adapt MSCs for anticancer therapies. However, MSCs have also been widely implicated in pathways that contribute to tumor growth. Numerous studies have been conducted to adapt MSCs for further clinical use; however, the results have been inconclusive, possibly due to the heterogeneity of MSC populations. Moreover, the conflicting roles of MSCs in tumor inhibition and tumor growth impede their adaptation for anticancer therapies. Antitumorigenic and protumorigenic properties of MSCs in hematologic malignancies are not as well established as they are for solid malignancies, and data comparing them are still limited. Herein the effect of MSCs on hematologic malignancies, such as leukemia and lymphoma, their mechanisms, sources of MSCs, and their effects on different types of cancer, have been discussed. This review describes how MSCs preserve both antitumorigenic and protumorigenic effects, as they tend to not only inhibit tumor growth by suppressing tumor cell proliferation but also promote tumor growth by suppressing tumor cell apoptosis. Thus clinical studies trying to adapt MSCs for anticancer therapies should consider that MSCs could actually promote hematologic cancer progression. It is necessary to take extreme care while developing MSC-based cell therapies in order to boost anticancer properties while eliminating tumor-favoring effects. This review emphasizes that research on the therapeutic applications of MSCs must consider that they exert both antitumorigenic and protumorigenic effects on hematologic malignancies.
Live cell analysis at sea reveals divergent thermal performance between photosynthetic ocean microbial eukaryote populations
Authors: McInnes Allison Skinner , Laczka Olivier F , Baker Kirralee G , Larsson Michaela E , Robinson Charlotte M , Clark Jennifer S , Laiolo Leonardo , Alvarez Marco , Laverock Bonnie , Kremer Colin T , van Sebille Erik , Doblin Martina A
Published: January 2019

Experimentation at sea provides insight into which traits of ocean microbes are linked to performance in situ. Here we show distinct patterns in thermal tolerance of microbial phototrophs from adjacent water masses sampled in the south-west Pacific Ocean, determined using a fluorescent marker for reactive oxygen species (ROS). ROS content of pico-eukaryotes was assessed after 1, 5 and 25 h of incubation along a temperature gradient (15.6–32.1 °C). Pico-eukaryotes from the East Australian Current (EAC) had relatively constant ROS and showed greatest mortality after 25 h at 7 °C below ambient, whereas those from the Tasman Sea had elevated ROS in both warm and cool temperature extremes and greatest mortality at temperatures 6–10 °C above ambient, interpreted as the outcome of thermal stress. Tracking of water masses within an oceanographic circulation model showed populations had distinct thermal histories, with EAC pico-eukaryotes experiencing higher average temperatures for at least 1 week prior to sampling. While acclimatization and community assembly could both influence biological responses, this study clearly demonstrates that phenotypic divergence occurs along planktonic drift trajectories.
Evidence that inflammation promotes estradiol synthesis in human cerebellum during early childhood
Authors: Wright Christopher L. , Hoffman Jessica H. , McCarthy Margaret M.
Published: January 2019

Discovering and characterizing critical and sensitive periods in brain development is essential for unraveling the myriad variables that impact disease risk. In previous work, we identified a critical period in cerebellar development in the rat that depends upon an intrinsic gene expression program and links increased prostaglandin production to local estradiol synthesis by stimulating Cyp19a, the estradiol synthetic enzyme, aromatase. This intrinsic critical period is sensitive to disruption by either inflammation or administration of cyclooxygenase (COX) inhibitors, ultimately impacting Purkinje cell dendritic growth. In a first step towards determining if a similar sensitive period exists in humans, the same gene expression profile was characterized in post-mortem cerebellar tissue of 58 children aged 0 to 9 years. Subjects were categorized as experiencing inflammation or not at the time of death. In individuals experiencing inflammation and over 1 year of age, there was a significant increase in the messenger RNA (mRNA) of the COX-1 and COX-2 enzymes and this strongly correlated with mRNA levels of aromatase. A step-wise linear model accounted for 94% of the variance in aromatase mRNA levels by co-variance with the COX enzymes, prostaglandin E2 synthase and other inflammatory mediators (Toll-like receptor 4), and Purkinje cell markers (calbindin, estrogen receptor 2). The influence of inflammation on these measures was not seen in subjects younger than 1 year. These data suggest a sensitive period to inflammation in the human cerebellum begins at about 1 year of age and may provide insight into sources of vulnerability of very young children to either inflammation or drugs designed to treat it.
Autism spectrum disorders: let’s talk about glucose?
Authors: Hoirisch-Clapauch Silvia , Nardi Antonio E.
Published: January 2019

Autism spectrum disorders (ASD) are characterized by disconnectivity due to disordered neuronal migration, and by neuronal mitochondrial dysfunction. Different pathways involved in neuronal migration are affected by intrauterine hyperglycemia and hyperinsulinemia, while prolonged neonatal hypoglycemia may cause mitochondrial dysfunction. Our hypothesis was that conditions leading to intrauterine hyperglycemia or neonatal hypoglycemia would influence ASD pathogenesis. In this study, we identified risk factors for ASD by searching PubMed with the MeSH terms “autism spectrum disorder” and “risk factors”. We then analyzed the relationship between the risk factors and glucose abnormalities in the mother and the offspring. The relationship between glucose abnormalities and risk factors such as obesity, excessive maternal weight gain, or diabetes mellitus is evident. For risk factors such as malformations or exposure to selective serotonin reuptake inhibitors, the relationship is speculative. In rodents, for example, intrauterine hyperglycemia is associated with malformations, independent of maternal diabetes. In their turn, selective serotonin reuptake inhibitors reduce the signs of neonatal hypoglycemia. Going undetected, prolonged hypoglycemia may harm the neonatal brain. Importantly, our group demonstrated that either high-carbohydrate diets or physical inactivity the day before delivery may influence neonatal glycemia. In that study, of 158 neonates selected to be screened according to maternal lifestyle risk factors, 48 had hypoglycemia. Of note, five of them had not been identified with current screening programs. Controlled studies are needed to clarify whether maternal interventions aiming at maintaining glycemic control, together with screening programs for neonatal hypoglycemia based on maternal lifestyle risk factors and on exposure to specific prenatal medications can reduce the prevalence of ASD.
Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease
Authors: Dalmasso Maria Carolina , Brusco Luis Ignacio , Olivar Natividad , Muchnik Carolina , Hanses Claudia , Milz Esther , Becker Julian , Heilmann-Heimbach Stefanie , Hoffmann Per , Prestia Federico A. , Galeano Pablo , Avalos Mariana Soledad Sanchez , Martinez Luis Eduardo , Carulla Mariana Estela , Azurmendi Pablo Javier , Liberczuk Cynthia , Fezza Cristina , Sampaño Marcelo , Fierens Maria , Jemar Guillermo , Solis Patricia , Medel Nancy , Lisso Julieta , Sevillano Zulma , Bosco Paolo , Bossù Paola , Spalletta Gianfranco , Galimberti Daniela , Mancuso Michelangelo , Nacmias Benedetta , Sorbi Sandro , Mecocci Patrizia , Pilotto Alberto , Caffarra Paolo , Panza Francesco , Bullido Maria , Clarimon Jordi , Sánchez-Juan Pascual , Coto Eliecer , Sanchez-Garcia Florentino , Graff Caroline , Ingelsson Martin , Bellenguez Céline , Castaño Eduardo Miguel , Kairiyama Claudia , Politis Daniel Gustavo , Kochen Silvia , Scaro Horacio , Maier Wolfgang , Jessen Frank , Mangone Carlos Alberto , Lambert Jean-Charles , Morelli Laura , Ramirez Alfredo
Published: January 2019

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.
TBL1 is required for the mesenchymal phenotype of transformed breast cancer cells
Authors: Rivero Sabrina , Gómez-Marín Elena , Guerrero-Martínez José A. , García-Martínez Jorge , Reyes José C.
Published: January 2019

The epithelial-to-mesenchymal transition (EMT) and its reversion (MET) are related to tumor cell dissemination and migration, tumor circulating cell generation, cancer stem cells, chemoresistance, and metastasis formation. To identify chromatin and epigenetic factors possibly involved in the process of EMT, we compare the levels of expression of epigenetic genes in a transformed human breast epithelial cell line (HMEC-RAS) versus a stable clone of the same cell line expressing the EMT master regulator ZEB1 (HMEC-RAS-ZEB1). One of the factors strongly induced in the HMEC-RAS-ZEB1 cells was Transducin beta-like 1 (TBL1), a component of the NCoR complex, which has both corepressor and coactivator activities. We show that TBL1 interacts with ZEB1 and that both factors cooperate to repress the promoter of the epithelial gene E-cadherin (CDH1) and to autoactivate the ZEB1 promoter. Consistent with its central role, TBL1 is required for mesenchymal phenotypes of transformed breast epithelial and breast cancer cell lines of the claudin-low subtype. Importantly, a high expression of the TBL1 gene correlates with poor prognosis and increased proportion of metastasis in breast cancer patients, indicating that the level of TBL1 expression can be used as a prognostic marker.
Promoter-proximal pausing mediated by the exon junction complex regulates splicing
Authors: Akhtar Junaid , Kreim Nastasja , Marini Federico , Mohana Giriram , Brüne Daniel , Binder Harald , Roignant Jean-Yves
Published: January 2019

Promoter-proximal pausing of RNA polymerase II (Pol II) is a widespread transcriptional regulatory step across metazoans. Here we find that the nuclear exon junction complex (pre-EJC) is a critical and conserved regulator of this process. Depletion of pre-EJC subunits leads to a global decrease in Pol II pausing and to premature entry into elongation. This effect occurs, at least in part, via non-canonical recruitment of pre-EJC components at promoters. Failure to recruit the pre-EJC at promoters results in increased binding of the positive transcription elongation complex (P-TEFb) and in enhanced Pol II release. Notably, restoring pausing is sufficient to rescue exon skipping and the photoreceptor differentiation defect associated with depletion of pre-EJC components in vivo. We propose that the pre-EJC serves as an early transcriptional checkpoint to prevent premature entry into elongation, ensuring proper recruitment of RNA processing components that are necessary for exon definition.
Functional role of PGAM5 multimeric assemblies and their polymerization into filaments
Authors: Ruiz Karen , Thaker Tarjani M. , Agnew Christopher , Miller-Vedam Lakshmi , Trenker Raphael , Herrera Clara , Ingaramo Maria , Toso Daniel , Frost Adam , Jura Natalia
Published: January 2019

PGAM5 is a mitochondrial protein phosphatase whose genetic ablation in mice results in mitochondria-related disorders, including neurodegeneration. Functions of PGAM5 include regulation of mitophagy, cell death, metabolism and aging. However, mechanisms regulating PGAM5 activation and signaling are poorly understood. Using electron cryo-microscopy, we show that PGAM5 forms dodecamers in solution. We also present a crystal structure of PGAM5 that reveals the determinants of dodecamer formation. Furthermore, we observe PGAM5 dodecamer assembly into filaments both in vitro and in cells. We find that PGAM5 oligomerization into a dodecamer is not only essential for catalytic activation, but this form also plays a structural role on mitochondrial membranes, which is independent of phosphatase activity. Together, these findings suggest that modulation of the oligomerization of PGAM5 may be a regulatory switch of potential therapeutic interest.
Reductions in prefrontal activation predict off-topic utterances during speech production
Authors: Hoffman Paul
Published: January 2019

The ability to speak coherently is essential for effective communication but declines with age: older people more frequently produce tangential, off-topic speech. Little is known, however, about the neural systems that support coherence in speech production. Here, fMRI was used to investigate extended speech production in healthy older adults. Computational linguistic analyses were used to quantify the coherence of utterances produced in the scanner, allowing identification of the neural correlates of coherence for the first time. Highly coherent speech production was associated with increased activity in bilateral inferior prefrontal cortex (BA45), an area implicated in selection of task-relevant knowledge from semantic memory, and in bilateral rostrolateral prefrontal cortex (BA10), implicated more generally in planning of complex goal-directed behaviours. These findings demonstrate that neural activity during spontaneous speech production can be predicted from formal analysis of speech content, and that multiple prefrontal systems contribute to coherence in speech.
Anticancer polymers designed for killing dormant prostate cancer cells
Authors: Takahashi Haruko , Yumoto Kenji , Yasuhara Kazuma , Nadres Enrico T. , Kikuchi Yutaka , Buttitta Laura , Taichman Russell S. , Kuroda Kenichi
Published: January 2019

The discovery of anticancer therapeutics effective in eliminating dormant cells is a significant challenge in cancer biology. Here, we describe new synthetic polymer-based anticancer agents that mimic the mode of action of anticancer peptides. These anticancer polymers developed here are designed to capture the cationic, amphiphilic traits of anticancer peptides. The anticancer polymers are designed to target anionic lipids exposed on the cancer cell surfaces and act by disrupting the cancer cell membranes. Because the polymer mechanism is not dependent on cell proliferation, we hypothesized that the polymers were active against dormant cancer cells. The polymers exhibited cytotoxicity to proliferating prostate cancer. Importantly, the polymer killed dormant prostate cancer cells that were resistant to docetaxel. This study demonstrates a new approach to discover novel anticancer therapeutics.
Advanced measurement and diagnosis of the effect on the underlayer roughness for industrial standard metrology
Authors: Kim Jung-Hwan , Moon Seunghyun , Kim Ji-Woong , Lee Donggun , Park Byong Chon , Kim Dal-Hyun , Jeong Yoojin , Hand Sean , Osborne Jason , De Wolf Peter , Kim Youn Sang , Shin ChaeHo
Published: January 2019

In current nanoscale semiconductor fabrications, high dielectric materials and ultrathin multilayers have been selected to improve the performance of the devices. Thus, interface effects between films and the quantification of surface information are becoming key issues for determining the performance of the semiconductor devices. In this paper, we developed an easy, accurate, and nondestructive diagnosis to investigate the interface effect of hafnium oxide ultrathin films. A roughness scaling method that artificially modified silicon surfaces with a maximum peak-to-valley roughness range of a few nanometers was introduced to examine the effect on the underlayer roughness. The critical overlayer roughness was be defined by the transition of RMS roughness which was 0.18 nm for the 3 nm thick hafnium oxide film. Subsequently, for the inline diagnostic application of semiconductor fabrication, the roughness of a mass produced hafnium film was investigated. Finally, we confirmed that the result was below the threshold set by our critical roughness. The RMS roughness of the mass produced hafnium oxide film was 0.11 nm at a 500 nm field of view. Therefore, we expect that the quantified and standardized critical roughness managements will contribute to improvement of the production yield.
Studying the regression profiles of cervical tumours during radiotherapy treatment using a patient-specific multiscale model
Authors: Kyroudis Christos A. , Dionysiou Dimitra D. , Kolokotroni Eleni A. , Stamatakos Georgios S.
Published: January 2019

Apart from offering insight into the biomechanisms involved in cancer, many recent mathematical modeling efforts aspire to the ultimate goal of clinical translation, wherein models are designed to be used in the future as clinical decision support systems in the patient-individualized context. Most significant challenges are the integration of multiscale biodata and the patient-specific model parameterization. A central aim of this study was the design of a clinically-relevant parameterization methodology for a patient-specific computational model of cervical cancer response to radiotherapy treatment with concomitant cisplatin, built around a tumour features-based search of the parameter space. Additionally, a methodological framework for the predictive use of the model was designed, including a scoring method to quantitatively reflect the similarity and bilateral predictive ability of any two tumours in terms of their regression profile. The methodology was applied to the datasets of eight patients. Tumour scenarios in accordance with the available longitudinal data have been determined. Predictive investigations identified three patient cases, anyone of which can be used to predict the volumetric evolution throughout therapy of the tumours of the other two with very good results. Our observations show that the presented approach is promising in quantifiably differentiating tumours with distinct regression profiles.