bluuebunny/crossref_metadata_2025 huggingface dataset:
AdS3 four-point functions from $$ \frac{1}{8} $$-BPS states
Authors: Bombini Alessandro , Galliani Andrea
Published: June 2019

Abstract

We compute four-point functions in the Heavy-Heavy-Light-Light limit involving a large family of

$$ \frac{1}{8} $$

1
8

-BPS heavy states whose dual supergravity solutions are explicitly known, avoiding the use of Witten diagrams. This is achieved by using the AdS/CFT dictionary of type IIB supergravity on AdS3 × S
3 × ℳ4 that maps supersymmetric heavy operators whose conformal dimension is the order of the central charge to explicit asymp-totically AdS supergravity solutions. Using the Ward Identities for the generators of the

$$ \mathcal{N}=\left(4,4\right) $$

N
=

4
4

superconformalSU(2)Kac-Moodyalgebra,wecanrelateallofthesefour-point functions to each other and to other known four-point functions involving

$$ \frac{1}{4} $$

1
4

-BPS heavy states, furnishing non-trivial checks of the computations. Finally, the Ward Identities can be employed to reconstruct the all-light four-point functions, providing the first holographic correlators of single-trace operators computed in AdS3 involving

$$ \frac{1}{8} $$

1
8

-BPS operators.
Boundaries and supercurrent multiplets in 3D Landau-Ginzburg models
Authors: Brunner Ilka , Schulz Jonathan , Tabler Alexander
Published: June 2019

Abstract

Theories with 3D

$$ \mathcal{N} = 2 $$

N

=

2

bulk supersymmetry may preserve a 2D

$$ \mathcal{N} = \left(0,\ 2\right) $$

N

=

0
,

2

subalgebra when a boundary is introduced, possibly with localized degrees of freedom. We propose generalized supercurrent multiplets with bulk and boundary parts adapted to such setups. Using their structure, we comment on implications for the

$$ {\overline{Q}}_{+} $$

Q
¯

+

-cohomology. As an example, we apply the developed framework to Landau-Ginzburg models. In these models, we study the role of boundary degrees of freedom and matrix factorizations. We verify our results using quantization.
Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL
Authors: Zhang Qiong , Hu Hui , Chen Si-Yi , Liu Chun-Jie , Hu Fei-Fei , Yu Jianming , Wu Yaohui , Guo An-Yuan
Published: June 2019

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8+ T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.
Genera of phytopathogenic fungi: GOPHY 3
Authors: Marin-Felix Y. , Hernández-Restrepo M. , Iturrieta-González I. , García D. , Gené J. , Groenewald J.Z. , Cai L. , Chen Q. , Quaedvlieg W. , Schumacher R.K. , Taylor P.W.J. , Ambers C. , Bonthond G. , Edwards J. , Krueger-Hadfield S.A. , Luangsa-ard J.J. , Morton L. , Moslemi A. , Sandoval-Denis M. , Tan Y.P. , Thangavel R. , Vaghefi N. , Cheewangkoon R. , Crous P.W.
Published: June 2019

This paper represents the third contribution in the Genera of Phytopathogenic Fungi (GOPHY) series. The series provides morphological descriptions, information about the pathology, distribution, hosts and disease symptoms for the treated genera, as well as primary and secondary DNA barcodes for the currently accepted species included in these. This third paper in the GOPHY series treats 21 genera of phytopathogenic fungi and their relatives including:Allophoma,Alternaria,Brunneosphaerella,Elsinoe,Exserohilum,Neosetophoma,Neostagonospora,Nothophoma,Parastagonospora,Phaeosphaeriopsis,Pleiocarpon,Pyrenophora,Ramichloridium,Seifertia,Seiridium,Septoriella,Setophoma,Stagonosporopsis,Stemphylium,TubakiaandZasmidium. This study includes three new genera, 42 new species, 23 new combinations, four new names, and three typifications of older names.
An Occupational Health Survey of British Mountain Guides Operating Internationally
Authors: Harkensee Christian , Hillebrandt David
Published: June 2019

Introduction

Professional mountain guides face significant occupational health risks, including injuries, accidents, environmental exposures, chronic musculoskeletal strain, and psychological stressors. This study aims to investigate these risks and their impact on the quality of life of a group of international British mountain guides.

Methods

This self-reported online survey included demographics; acute and chronic occupational conditions; and questions on general health, lifestyle, symptoms of post-traumatic stress disorder (PTSD), and quality of life based on the World Health Organization quality of life [WHOQOL-BREF] questionnaire.

Results

Responses were received from 67 (32%) of the approached guides. Knee pain (75%), back and neck pain (62%), hand/upper extremity problems (51%), and lower limb injuries (49%) were the most commonly reported individual occupational health problems. Chronic eye problems were reported by 8%, and 5% reported skin cancer. Twenty-nine percent were on regular medications, which were mainly analgesics for chronic musculoskeletal complaints. Mountain guides have a healthy lifestyle, with lower rates of being overweight/obese, alcohol consumption, and smoking than the average UK population. Fourteen (61%) of the 23 guides responding to the PTSD questions reported experiencing life-threatening traumatic incidents, and 4 (25%) of this subgroup appear to have had some symptoms of PTSD. The quality of life assessment showed that the studied mountain guides have a high quality of life.

Conclusions

Musculoskeletal problems are the main occupational health problems experienced by the study group. New findings include a low but important prevalence of ultraviolet radiation–associated conditions. One in 3 guides have experienced significant psychological trauma, and one quarter of these had symptoms of PTSD.
Perceived quality framework in product generation engineering: an automotive industry example
Authors: Stylidis Kostas , Bursac Nikola , Heitger Nicolas , Wickman Casper , Albers Albert , Söderberg Rikard
Published: June 2019

Perceived quality refers to customers’ cognitive and emotional responses to a particular design, often also associated with craftsmanship and customer satisfaction. Previous research defined a taxonomy of perceived quality and provided understanding about how engineering design decisions impact customer satisfaction. Furthermore, development of new products is frequently based on carrying over attributes of existing products, either from the same producer or from competitors. Previous research offered a new product development methodology combining variations of subsystems to carry over from existing products. This brief presents how these two lines of research combined to design the central console of the Porsche Panamera automobile and discusses the opportunities and challenges posed in the practical implementation of this research.
Non-modal analysis of coaxial jets
Authors: Montagnani D. , Auteri F.
Published: June 2019

In this work, we investigate the subcritical behaviour of a coaxial jet subject to small-amplitude perturbations at the inflow. We use the results of optimal harmonic analysis and dynamic-mode decomposition (DMD) of the flow fields at a Reynolds number, based on the diameter and maximum velocity of the inner inlet pipe, of $Re=200$, to show that, for a sufficiently low value of the Reynolds number, the coherent structures appearing in the perturbed dynamics of the nonlinear system can be effectively described in terms of the harmonic response of the flow. We also show that, for larger subcritical values of the Reynolds number, $Re=400$, a huge amplification of disturbances quickly makes nonlinear effects relevant. Large-scale, near-field coherent dynamics can be still interpreted as an evidence of the preferred response of the system, using DMD of the flow to describe the noise-driven transition to turbulence downstream. The influence of the axial velocity ratio and the rotational motion of the outer stream are assessed as well. Harmonic analysis successfully predicts the prevalence of rotating helical structures observed in the columnar flow for moderate swirl of the outer jet. Finally, we compare the receptivity of the nonlinear system to the optimal linear perturbations with its response to stochastic forcing. Optimal forcing is still more effective than white noise in driving the system to a turbulent state, where nonlinear dynamics prevails. We still conclude that linear optimal forcing may be relevant in investigating the transition to turbulence in coaxial jets, even if more about the transition process could be learnt from a more expensive nonlinear analysis.
Supervisor behavior and character: A simulation study of employee helpfulness
Authors: Francis Clare , Hollingworth David , Valentine Sean
Published: June 2019

Supervisor character and behavior are key components of an organization's ethical fabric that should play a role in employee helping behavior. However, research has not fully distinguished how these factors are interrelated. The current study explores these relationships by developing a deeper understanding of ethical language in organizations via thick ethical concepts found in simulation software, supported by affect control theory. Software formulae in these simulations were developed via empirical research conducted over several decades. Simulations provided predictions of employee helpfulness in response to encounters with supervisors of varying ethical characters, enacting a variety of behaviors. The likely impact of supervisor character on employee helpfulness is more substantial than the impact of supervisor behavior. New insights emerged related to underlying complexities of ethical languages, such as the role of cultural meanings of language terms. These outcomes, as well as the associated implications, research limitations, and suggestions for future research, are discussed.
Reconstructing directed graphs from generalized gauge actions on their Toeplitz algebras
Authors: Brownlowe Nathan , Laca Marcelo , Robertson Dave , Sims Aidan
Published: June 2019

We show how to reconstruct a finite directed graph E from its Toeplitz algebra, its gauge action, and the canonical finite-dimensional abelian subalgebra generated by the vertex projections. We also show that if E has no sinks, then we can recover E from its Toeplitz algebra and the generalized gauge action that has, for each vertex, an independent copy of the circle acting on the generators corresponding to edges emanating from that vertex. We show by example that it is not possible to recover E from its Toeplitz algebra and gauge action alone.
Entamoeba chiangraiensisn. sp. (Amoebozoa: Entamoebidae) isolated from the gut of Asian swamp eel (Monopterus albus) in northern Thailand
Authors: Jinatham Vasana , Popluechai Siam , Clark C. Graham , Gentekaki Eleni
Published: June 2019

The genusEntamoebacomprises mostly gut parasites and commensals of invertebrate and vertebrate animals including humans. Herein, we report a new species ofEntamoebaisolated from the gut of Asian swamp eels (Monopterus albus) in northern Thailand. Morphologically, the trophozoite is elongated and has a single prominent pseudopodium with no clear uroid. The trophozoite is actively motile, 30–50µm in length and 9–13µm in width. Observed cysts were uninucleate, ranging in size from 10 to 17.5µm in diameter. Chromatin forms a fine, even lining along the inner nuclear membrane. Fine radial spokes join the karyosome to peripheral chromatin. Size, host and nucleus morphology set our organism apart from other members of the genus reported from fish. The SSU rRNA gene sequences of the new isolates are the first molecular data of anEntamoebaspecies from fish. Phylogenetic analysis places the new organism as sister toEntamoeba invadens. Based on the distinct morphology and SSU rRNA gene sequence we describe it as a new species,Entamoeba chiangraiensis.
Development of CRISPR-Cas systems for genome editing and beyond
Authors: Zhang F.
Published: June 2019

The development of clustered regularly interspaced short-palindromic repeat (CRISPR)-Cas systems for genome editing has transformed the way life science research is conducted and holds enormous potential for the treatment of disease as well as for many aspects of biotechnology. Here, I provide a personal perspective on the development of CRISPR-Cas9 for genome editing within the broader context of the field and discuss our work to discover novel Cas effectors and develop them into additional molecular tools. The initial demonstration of Cas9-mediated genome editing launched the development of many other technologies, enabled new lines of biological inquiry, and motivated a deeper examination of natural CRISPR-Cas systems, including the discovery of new types of CRISPR-Cas systems. These new discoveries in turn spurred further technological developments. I review these exciting discoveries and technologies as well as provide an overview of the broad array of applications of these technologies in basic research and in the improvement of human health. It is clear that we are only just beginning to unravel the potential within microbial diversity, and it is quite likely that we will continue to discover other exciting phenomena, some of which it may be possible to repurpose as molecular technologies. The transformation of mysterious natural phenomena to powerful tools, however, takes a collective effort to discover, characterize, and engineer them, and it has been a privilege to join the numerous researchers who have contributed to this transformation of CRISPR-Cas systems.
Robust Hybrid Fractional Order Proportional Derivative Sliding Mode Controller for Robot Manipulator Based on Extended Grey Wolf Optimizer
Authors: Komijani Hossein , Masoumnezhad Mojtaba , Zanjireh Morteza Mohammadi , Mir Mahdi
Published: June 2019

This paper presents a novel robust hybrid fractional order proportional derivative sliding mode controller (HFOPDSMC) for 2-degree of freedom (2-DOF) robot manipulator based on extended grey wolf optimizer (EGWO). Sliding mode controller (SMC) is remarkably robust against the uncertainties and external disturbances and shows the valuable properties of accuracy. In this paper, a new fractional order sliding surface (FOSS) is defined. Integrating the fractional order proportional derivative controller (FOPDC) and a new sliding mode controller (FOSMC), a novel robust controller based on HFOPDSMC is proposed. The bounded model uncertainties are considered in the dynamics of the robot, and then the robustness of the controller is verified. The Lyapunov theory is utilized in order to show the stability of the proposed controller. In this paper, the EGWO is developed by adding the emphasis coefficients to the typical grey wolf optimizer (GWO). The GWO and EGWO, then, are applied to optimize the proposed control parameters which result in the optimized GWO-HFOPDSMC and EGWO-HFOPDSMC, respectively. The effectivenesses of the optimized controllers (GWO-HFOPDSMC and EGWO-HFOPDSMC) are completely verified by comparing the simulation results of the optimized controllers with the typical FOSMC and HFOPDSMC.
How do fruit productivity, fruit traits and dietary specialization affect the role of birds in a mutualistic network?
Authors: Malanotte Marcia L. , Machado-de-Souza Tiago , Campos Ricardo P. , Petkowicz Carmen L.O. , Varassin Isabela G.
Published: June 2019

Many plant traits might explain the different ecological and network roles of fruit-eating birds. We assessed the relationship of plant productivity, fruit traits (colour, seed size and nutritional quality) and dietary specialization, with the network roles of fruit-eating birds (number of partners, centrality and selectivity) in the Atlantic Forest, Brazil. We classified bird species according to their dietary specialization into three categories: obligate, partial and opportunistic fruit-eating birds. To test if network roles changed according to dietary specialization, fruit productivity and traits, we used a generalized linear model analysis. The selected 14 species of plant interacted with 52 bird species, which consumed 2199 fruits. The most central and generalist fruit-eating bird,Turdus albicolis, interacted with plants that produced more fruits, such asMiconia cinerascens, and had, on average, larger seeds, such asMyrcia splendens. The most selective birds interacted with fruits with a higher concentration of lipids and less intense colour, and plants that produced fewer fruits. Obligate fruit-eating birds, such asPatagioenas plumbea, were more selective than partial and opportunistic birds. Different plant traits are therefore related to the different network roles of fruit-eating birds in the Atlantic Forest, which are also dependent on bird dietary specialization.
Inter-Satellite Link Enhanced Orbit Determination for BeiDou-3
Authors: Yang Yufei , Yang Yuanxi , Hu Xiaogong , Chen Jinping , Guo Rui , Tang Chengpan , Zhou Shanshi , Zhao Liqian , Xu Junyi
Published: June 2019

The third generation of the BeiDou navigation satellite system (BDS-3) is a global navigation system, and is expected to be in full operation by 2020. High-precision orbits are a precondition for BDS-3 to provide a highly accurate service, which needs a global tracking and monitoring capability for the operational satellites. However, it is difficult for BDS to construct global ground monitoring stations. Fortunately, Ka-band Inter-Satellite Link (ISL) antennae fitted to the BDS-3 satellites can be used to extend the visible arc of the Medium Earth Orbit (MEO) satellites and to enhance the ground stations for orbit determination. This paper analyses the ISL-enhanced orbit determination for eight BDS-3 satellites, using the data from ten Chinese domestic stations and 13 international Global Navigation Satellite System (GNSS) Monitoring and Assessment System (iGMAS) overseas stations. The results show that the Three-Dimensional (3D) position Root Mean Square (RMS) error of the Overlapping Orbit Differences (OODs) is approximately 1 m when only ten regional stations are used. When the ISL measurements are added, the 3D position RMS error is decreased to 0·5 m, and the accuracy of the 24-hour orbit prediction can also be improved from 2 m to 0·7 m, which is even better than that of the orbits determined using globally distributed stations. It can be expected that with the subsequent launch of BDS-3 satellites and the increasing number of ISLs, the advantage of the ISL enhanced orbit determination will become more significant.
Real-time estimation of the influenza-associated excess mortality in Hong Kong
Authors: Wong Jessica Y. , Goldstein Edward , Fang Vicky J. , Cowling Benjamin J. , Wu Peng
Published: June 2019

Statistical models are commonly employed in the estimation of influenza-associated excess mortality that, due to various reasons, is often underestimated by laboratory-confirmed influenza deaths reported by healthcare facilities. However, methodology for timely and reliable estimation of that impact remains limited because of the delay in mortality data reporting. We explored real-time estimation of influenza-associated excess mortality by types/subtypes in each year between 2012 and 2018 in Hong Kong using linear regression models fitted to historical mortality and influenza surveillance data. We could predict that during the winter of 2017/2018, there were ~634 (95% confidence interval (CI): (190, 1033)) influenza-associated excess all-cause deaths in Hong Kong in population ⩾18 years, compared to 259 reported laboratory-confirmed deaths. We estimated that influenza was associated with substantial excess deaths in older adults, suggesting the implementation of control measures, such as administration of antivirals and vaccination, in that age group. The approach that we developed appears to provide robust real-time estimates of the impact of influenza circulation and complement surveillance data on laboratory-confirmed deaths. These results improve our understanding of the impact of influenza epidemics and provide a practical approach for a timely estimation of the mortality burden of influenza circulation during an ongoing epidemic.
Adoptees’ responses to separation from, and reunion with, their adoptive parent at age 4 years is associated with long-term persistence of autism symptoms following early severe institutional deprivation
Authors: Sonuga-Barke Edmund , Kennedy Mark , Golm Dennis , Knights Nicky , Kovshoff Hanna , Kreppner Jana , Kumsta Robert , Maughan Barbara , O'Connor Thomas G. , Schlotz Wolff
Published: June 2019

Institutionally deprived young children often display distinctive patterns of attachment, classified as insecure/other (INS/OTH), with their adoptive parents. The associations between INS/OTH and developmental trajectories of mental health and neurodevelopmental symptoms were examined. Age 4 attachment status was determined for 97 Romanian adoptees exposed to up to 24 months of deprivation in Romanian orphanages and 49 nondeprived UK adoptees. Autism, inattention/overactivity and disinhibited-social-engagement symptoms, emotional problems, and IQ were measured at 4, 6, 11, and 15 years and in young adulthood. Romanian adoptees with over 6 months deprivation (Rom>6) were more often classified as INS/OTH than UK and Romanian adoptees with less than 6 months deprivation combined. INS/OTH was associated with cognitive impairment at age 4 years. The interaction between deprivation, attachment status, and age for autism spectrum disorder assessment was significant, with greater symptom persistence in Rom>6 INS/OTH(+) than other groups. This effect was reduced when IQ at age 4 was controlled for. Age 4 INS/OTH in Rom>6 was associated with worse autism spectrum disorder outcomes up to two decades later. Its association with cognitive impairment at age 4 is consistent with INS/OTH being an early marker of this negative developmental trajectory, rather than its cause.
Numerical methods for Kohn–Sham density functional theory
Authors: Lin Lin , Lu Jianfeng , Ying Lexing
Published: June 2019

Kohn–Sham density functional theory (DFT) is the most widely used electronic structure theory. Despite significant progress in the past few decades, the numerical solution of Kohn–Sham DFT problems remains challenging, especially for large-scale systems. In this paper we review the basics as well as state-of-the-art numerical methods, and focus on the unique numerical challenges of DFT.
Logarithmic Sobolev inequalities in discrete product spaces
Authors: Marton Katalin
Published: June 2019

The aim of this paper is to prove an inequality between relative entropy and the sum of average conditional relative entropies of the following form: for a fixed probability measure q on , ( is a finite set), and any probability measure on ,
(*)
$$D(p||q){\rm{\le}}C \cdot \sum\limits_{i = 1}^n {{\rm{\mathbb{E}}}_p D(p_i ( \cdot |Y_1 ,{\rm{ }}...,{\rm{ }}Y_{i - 1} ,{\rm{ }}Y_{i + 1} ,...,{\rm{ }}Y_n )||q_i ( \cdot |Y_1 ,{\rm{ }}...,{\rm{ }}Y_{i - 1} ,{\rm{ }}Y_{i + 1} ,{\rm{ }}...,{\rm{ }}Y_n )),} $$
where pi(· |y1, …, yi−1, yi+1, …, yn) and qi(· |x1, …, xi−1, xi+1, …, xn) denote the local specifications for p resp. q, that is, the conditional distributions of the ith coordinate, given the other coordinates. The constant C depends on (the local specifications of) q.

The inequality (*) ismeaningful in product spaces, in both the discrete and the continuous case, and can be used to prove a logarithmic Sobolev inequality for q, provided uniform logarithmic Sobolev inequalities are available for qi(· |x1, …, xi−1, xi+1, …, xn), for all fixed i and fixed (x1, …, xi−1, xi+1, …, xn). Inequality (*) directly implies that the Gibbs sampler associated with q is a contraction for relative entropy.

In this paper we derive inequality (*), and thereby a logarithmic Sobolev inequality, in discrete product spaces, by proving inequalities for an appropriate Wasserstein-like distance.
Public Support for Increasing Women and Minority MPs
Authors: Bolzendahl Catherine , Coffé Hilde
Published: June 2019

Most democracies fail to provide equal representation and tend to have an overrepresentation of men from the upper class and the majority racial or ethnic group. We investigate public support for increasing the number of women and indigenous Māori members of parliament (MPs) in the New Zealand Parliament, both in general and through specific mechanisms such as quotas and reserved seats. We offer three explanations: descriptive (group identity), substantive (issue alignment), and symbolic (socioeconomic and political equity concerns). Using data from the 2014 New Zealand Election Study, we found that shared identity (descriptive) matters for all measures of increased representation, but especially for Māori respondent support of increased Māori MPs. Support for increasing the proportion of Māori MPs is also strongly driven by substantive concerns, as measured by support for keeping the Treaty of Waitangi in law. Support for increasing the number of women MPs is driven most strongly by symbolic concerns (measured as increased government social spending and efforts to reduce income differences). Overall, respondents favor retaining the current number of reserved seats for Māori MP representation, whereas informal efforts (rather than quotas) are strongly preferred for increasing the number of women MPs.
Wenn praktisches Handeln zum Bewertungsgegenstand wird
Authors: Rebmann Marius , Schlosser Daniela
Published: June 2019

Zusammenfassung. Die pädagogische Diagnostik im Skills Lab stellt Lehrende immer wieder vor große Herausforderungen. Doch wie kann Lernen und Bewerten im Skills Lab verankert werden und welche Möglichkeiten der pädagogischen Diagnostik bieten sich im sogenannten 3. Lernort an?
Pädagogische Diagnostik in der Pflegepraxis
Authors: Hofmann Jan , Gieseler Sabrina
Published: June 2019

Zusammenfassung. Damit die Auszubildenden in der Pflege einen möglichst umfangreichen Einblick in alle Bereiche der Pflege bekommen, müssen große Mengen an Abteilungen durchlaufen werden. Die Folge dieser gesetzlichen Festlegung sind regelmäßige Wechsel der Ausbildungsstationen oder auch Institutionen. Hier zeigt sich in Reflexionsgesprächen mit Auszubildenden und einarbeitenden Personen, dass der Integrationsprozess von Auszubildenden in neue Stationsteams voller Fallstricke, Missverständnisse und falschen Erwartungen steckt.
Parkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth
Authors: Chen Rongmin , Park Han-A , Mnatsakanyan Nelli , Niu Yulong , Licznerski Pawel , Wu Jing , Miranda Paige , Graham Morven , Tang Jack , Boon Agnita J. W. , Cossu Giovanni , Mandemakers Wim , Bonifati Vincenzo , Smith Peter J. S. , Alavian Kambiz N. , Jonas Elizabeth A.
Published: June 2019

Familial Parkinson’s disease (PD) protein DJ-1 mutations are linked to early onset PD. We have found that DJ-1 binds directly to the F1FO ATP synthase β subunit. DJ-1’s interaction with the β subunit decreased mitochondrial uncoupling and enhanced ATP production efficiency while in contrast mutations in DJ-1 or DJ-1 knockout increased mitochondrial uncoupling, and depolarized neuronal mitochondria. In mesencephalic DJ-1 KO cultures, there was a progressive loss of neuronal process extension. This was ameliorated by a pharmacological reagent, dexpramipexole, that binds to ATP synthase, closing a mitochondrial inner membrane leak and enhancing ATP synthase efficiency. ATP synthase c-subunit can form an uncoupling channel; we measured, therefore, ATP synthase F1 (β subunit) and c-subunit protein levels. We found that ATP synthase β subunit protein level in the DJ-1 KO neurons was approximately half that found in their wild-type counterparts, comprising a severe defect in ATP synthase stoichiometry and unmasking c-subunit. We suggest that DJ-1 enhances dopaminergic cell metabolism and growth by its regulation of ATP synthase protein components.
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe
Authors: Bery Nicolas , Legg Sandrine , Debreczeni Judit , Breed Jason , Embrey Kevin , Stubbs Christopher , Kolasinska-Zwierz Paulina , Barrett Nathalie , Marwood Rose , Watson Jo , Tart Jon , Overman Ross , Miller Ami , Phillips Christopher , Minter Ralph , Rabbitts Terence H.
Published: June 2019

Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that specifically inhibit the KRAS isoform by binding to an allosteric site encompassing the region around KRAS-specific residue histidine 95 at the helix α3/loop 7/helix α4 interface. We show that these DARPins specifically inhibit KRAS/effector interactions and the dependent downstream signalling pathways in cancer cells. Binding by the DARPins at that region influences KRAS/effector interactions in different ways, including KRAS nucleotide exchange and inhibiting KRAS dimerization at the plasma membrane. These results highlight the importance of targeting the α3/loop 7/α4 interface, a previously untargeted site in RAS, for specifically inhibiting KRAS function.
Abundance of bacterial Type VI secretion system components measured by targeted proteomics
Authors: Lin Lin , Lezan Emmanuelle , Schmidt Alexander , Basler Marek
Published: June 2019

The Type VI secretion system (T6SS) is important for bacterial competition as well as virulence in many Gram-negative bacteria and its dynamics and regulation varies significantly between species. To gain insights into the mechanisms regulating T6SS assembly, we apply targeted proteomics to determine the abundance of the key T6SS components in Vibrio cholerae, Pseudomonas aeruginosa and Acinetobacter baylyi. We show that while there are species specific exceptions, the abundance of most components is similar in all three bacteria and ranges from less than hundred to tens of thousands of copies per cell. The comparison of T6SS dynamics and protein abundance in V. cholerae grown under various conditions suggests that the critical component TssE and the secreted protein VasX are unstable and this diminishes T6SS assembly when protein synthesis is limited. Our quantitative analysis opens possibilities to build realistic models of T6SS assembly and to identify principles of T6SS regulation in various species.
Simulating multiple faceted variability in single cell RNA sequencing
Authors: Zhang Xiuwei , Xu Chenling , Yosef Nir
Published: June 2019

The abundance of new computational methods for processing and interpreting transcriptomes at a single cell level raises the need for in silico platforms for evaluation and validation. Here, we present SymSim, a simulator that explicitly models the processes that give rise to data observed in single cell RNA-Seq experiments. The components of the SymSim pipeline pertain to the three primary sources of variation in single cell RNA-Seq data: noise intrinsic to the process of transcription, extrinsic variation indicative of different cell states (both discrete and continuous), and technical variation due to low sensitivity and measurement noise and bias. We demonstrate how SymSim can be used for benchmarking methods for clustering, differential expression and trajectory inference, and for examining the effects of various parameters on their performance. We also show how SymSim can be used to evaluate the number of cells required to detect a rare population under various scenarios.
Identification of a genomic enhancer that enforces proper apoptosis induction in thymic negative selection
Authors: Hojo Miki Arai , Masuda Kyoko , Hojo Hiroaki , Nagahata Yosuke , Yasuda Keiko , Ohara Daiya , Takeuchi Yusuke , Hirota Keiji , Suzuki Yutaka , Kawamoto Hiroshi , Kawaoka Shinpei
Published: June 2019

During thymic negative selection, autoreactive thymocytes carrying T cell receptor (TCR) with overtly strong affinity to self-MHC/self-peptide are removed by Bim-dependent apoptosis, but how Bim is specifically regulated to link TCR activation and apoptosis induction is unclear. Here we identify a murine T cell-specific genomic enhancer EBAB (Bub1-Acoxl-Bim), whose deletion leads to accumulation of thymocytes expressing high affinity TCRs. Consistently, EBAB knockout mice have defective negative selection and fail to delete autoreactive thymocytes in various settings, with this defect accompanied by reduced Bim expression and apoptosis induction. By contrast, EBAB is dispensable for maintaining peripheral T cell homeostasis via Bim-dependent pathways. Our data thus implicate EBAB as an important, developmental stage-specific regulator of Bim expression and apoptosis induction to enforce thymic negative selection and suppress autoimmunity. Our study unravels a part of genomic enhancer codes that underlie complex and context-dependent gene regulation in TCR signaling.
Identifying the structure of Zn-N2 active sites and structural activation
Authors: Li Feng , Bu Yunfei , Han Gao-Feng , Noh Hyuk-Jun , Kim Seok-Jin , Ahmad Ishfaq , Lu Yalin , Zhang Peng , Jeong Hu Young , Fu Zhengping , Zhong Qin , Baek Jong-Beom
Published: June 2019

Identification of active sites is one of the main obstacles to rational design of catalysts for diverse applications. Fundamental insight into the identification of the structure of active sites and structural contributions for catalytic performance are still lacking. Recently, X-ray absorption spectroscopy (XAS) and density functional theory (DFT) provide important tools to disclose the electronic, geometric and catalytic natures of active sites. Herein, we demonstrate the structural identification of Zn-N2 active sites with both experimental/theoretical X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectra. Further DFT calculations reveal that the oxygen species activation on Zn-N2 active sites is significantly enhanced, which can accelerate the reduction of oxygen with high selectivity, according well with the experimental results. This work highlights the identification and investigation of Zn-N2 active sites, providing a regular principle to obtain deep insight into the nature of catalysts for various catalytic applications.
Pairfield fluctuations of a 2D Hubbard model
Authors: Maier Thomas A. , Scalapino Douglas J.
Published: June 2019

At temperatures above the superconducting transition temperature, the pairfield susceptibility provides information on the nature of the pairfield fluctuations. Here, we study the d-wave pairfield susceptibility of a 2D Hubbard model for a doping which has a pseudogap (PG) and for a doping which does not. In both cases, there will be a region of Kosterlitz–Thouless fluctuations as the transition at TKT is approached. Above this region, we find evidence for pairfield-order parameter-phase fluctuations for dopings with a PG and BCS Cooper pair fluctuations for dopings without a PG.
Activity/exercise-induced changes in the liver transcriptome after chronic spinal cord injury
Authors: Chariker Julia H. , Ohri Sujata Saraswat , Gomes Cynthia , Brabazon Fiona , Harman Kathryn A. , DeVeau Kathryn M. , Magnuson David S. K. , Hetman Michal , Petruska Jeffrey C. , Whittemore Scott R. , Rouchka Eric C.
Published: June 2019

Multi-organ dysfunction is a major complication after spinal cord injury (SCI). In addition to local injury within the spinal cord, SCI causes major disruption to the peripheral organ innervation and regulation. The liver contains sympathetic, parasympathetic, and small sensory axons. The bi-directional signaling of sensory dorsal root ganglion (DRG) neurons that provide both efferent and afferent information is of key importance as it allows sensory neurons and peripheral organs to affect each other. SCI-induced liver inflammation precedes and may exacerbate intraspinal inflammation and pathology after SCI, which may be modulated by activity and exercise. In this study, we collected comprehensive gene expression data through RNA sequencing of liver tissue from rats with chronic SCI to determine the effects of activity and exercise on those expression patterns. The sequenced data are of high quality and show a high alignment rate to the Rn6 genome. Gene expression is demonstrated for genes associated with known liver pathologies. UCSC Genome Browser expression tracks are provided with the data to facilitate exploration of the samples.
Hypothalamus-pituitary-gonad axis transcriptome profiling for sex differentiation in Acipenser sinensis
Authors: Du Hejun , Jian Jianbo , Wang Binzhong , Liu Xueqing , Chen Jianwei , Xiao Kan , Xia Jinquan , Yang Jing , Gao Yong , Chen Lei
Published: June 2019

Chinese sturgeon (Acipenser sinensis), a critically endangered Acipenseridae family member, is one of the largest anadromous, native fish in China. Numerous research programmes and protection agencies have focused on breeding and preserving this endangered species. However, available information is limited on the different stages of sex development, especially on the reproductive regulation of the hypothalamus-pituitary-gonad (HPG) axis of A. sinensis. To unravel the mechanism of gene interactions during sex differentiation and gonad development of A. sinensis, we performed transcriptome sequencing using HPG samples from male and female A. sinensis in two developmental stages. In this study, 271.19 Gb high-quality transcriptome data were obtained from 45 samples belonging to 15 individuals (six in stage I, six males and three females in stage II). These transcriptomic data will help us understand the reproductive regulation of the HPG axis in the development stages of A. sinensis and provide important reference data for genomic and genetic studies in A. sinensis and related species.
Carbon metabolism modulates the efficacy of drugs targeting the cytochrome bc1:aa3 in Mycobacterium tuberculosis
Authors: Kalia Nitin P. , Shi Lee Bei , Ab Rahman Nurlilah B. , Moraski Garrett C. , Miller Marvin J. , Pethe Kevin
Published: June 2019

The influence of carbon metabolism on oxidative phosphorylation is poorly understood in mycobacteria.M.tuberculosisexpresses two respiratory terminal oxidases, the cytochromebc1:aa3and the cytochromebdoxidase, which are jointly required for oxidative phosphorylation and mycobacterial viability. The essentiality of the cytochromebc1:aa3for optimum growth is illustrated by its vulnerability to chemical inhibition by the clinical drug candidate Q203 and several other chemical series. The cytochromebdoxidase is not strictly essential for growth but is required to maintain bioenergetics when the function of the cytochromebc1:aa3is compromised. In this study, we observed that the potency of drugs targeting the cytochromebc1:aa3is influenced by carbon metabolism. The efficacy of Q203 and related derivatives was alleviated by glycerol supplementation. The negative effect of glycerol supplementation on Q203 potency correlated with an upregulation of the cytochromebdoxidase-encodingcydABDCoperon. Upon deletion ofcydAB, the detrimental effect of glycerol on the potency of Q203 was abrogated. The same phenomenon was also observed in recent clinical isolates, but to a lesser extent compared to the laboratory-adapted strain H37Rv. This study reinforces the importance of optimizingin vitroculture conditions for drug evaluation in mycobacteria, a factor which appeared to be particularly essential for drugs targeting the cytochromebc1:aa3terminal oxidase.
First evidence for an association between joint hypermobility and excitability in a non-human species, the domestic dog
Authors: Bowen Jonathan , Fatjó Jaume , Serpell James A. , Bulbena-Cabré Andrea , Leighton Eldin , Bulbena Antoni
Published: June 2019

There is a well-established relationship between joint hypermobility and anxiety in humans, that has not previously been investigated in other species. A population of 5575 assistance dogs were scored for both hip hypermobility and 13 behaviour characteristics using previously validated methods. Our results suggest a positive association between hip joint hypermobility and emotional arousal in domestic dogs, which parallel results found in people.
An Unobtrusive and Calibration-free Blood Pressure Estimation Method using Photoplethysmography and Biometrics
Authors: Xing Xiaoman , Ma Zhimin , Zhang Mingyou , Zhou Ying , Dong Wenfei , Song Mingxuan
Published: June 2019

We introduce a novel paradigm to unobtrusively and optically measure blood pressure (BP) without calibration. The algorithm combines photoplethysmography (PPG) waveform analysis and biometrics to estimate BP, and was evaluated in subjects with various age, height, weight and BP levels (n = 1249). In the young population (<50 years old) with low, medium and high systolic blood pressures (SBP, <120 mmHg; 120–139 mmHg; ≥140 mmHg), the fitting errors are 6.3 ± 7.2, −3.9 ± 7.2 and −20.2 ± 14.2 mmHg for SBP respectively; In the older population (>50 years old) with the same categories, the fitting errors are 12.8 ± 9.0, 0.5 ± 8.2 and −14.6 ± 11.5 mmHg for SBP respectively. A simple personalized calibration reduces fitting errors significantly (n = 147), and good peripheral perfusion helps to improve the fitting accuracy. In conclusion, PPG may be used to calculate BP without calibration in certain populations. When calibrated, it shows great potential to serially monitor BP fluctuation, which can bring tremendous economic and health benefits.
Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals
Authors: Broughton Kathleen M. , Khieu Tiffany , Nguyen Nicky , Rosa Michael , Mohsin Sadia , Quijada Pearl , Wang Bingyan J. , Echeagaray Oscar H. , Kubli Dieter A. , Kim Taeyong , Firouzi Fareheh , Monsanto Megan M. , Gude Natalie A. , Adamson Robert M. , Dembitsky Walter P. , Davis Michael E. , Sussman Mark A.
Published: June 2019

Cardiomyocyte ploidy has been described but remains obscure in cardiac interstitial cells. Ploidy of c-kit+ cardiac interstitial cells was assessed using confocal, karyotypic, and flow cytometric technique. Notable differences were found between rodent (rat, mouse) c-kit+ cardiac interstitial cells possessing mononuclear tetraploid (4n) content, compared to large mammals (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in human c-kit+ cardiac interstitial cells and a mixture of diploid and tetraploid content in mouse. Downregulation of the p53 signaling pathway provides evidence why rodent, but not human, c-kit+ cardiac interstitial cells escape replicative senescence. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse c-kit+ cardiac interstitial cells, alluding to functional divergences. Collectively, these data reveal notable species-specific biological differences in c-kit+ cardiac interstitial cells, which could account for challenges in extrapolation of myocardial from preclinical studies to clinical trials.
Modulating an in situ fluorogenic reaction for the label-free ratiometric detection of biothiols
Authors: Zhang Haiqing , Xiao Yan , Zhang Xiuhua , Wang Shengfu
Published: June 2019

A label-free ratiometric method for biothiol detection is developed based on the modulation of fluorogenic reaction and the inner filter effect.
Instant detection of cyanide in seafood with a tryptophan based fluorescence probe
Authors: Hatai Joydev , Rahaman Sk. Atiur , Dasgupta Debdeep , Bandyopadhyay Subhajit
Published: June 2019

A fluorescent probe having thiocarbamate-linked tryptophan units was developed for the rapid visual detection of cyanide in seafood samples with a LOD of 2 ppb.
A novel method based on a Mask R-CNN model for processing dPCR images
Authors: Hu Zhenming , Fang Weibo , Gou Tong , Wu Wenshuai , Hu Jiumei , Zhou Shufang , Mu Ying
Published: June 2019

The flow of Mask R-CNN model for processing digital polymerase chain reaction (dPCR) fluorescence images.
A resettable supramolecular platform for constructing scalable encoders
Authors: Yang Chunrong , Yang Shu , Song Lingbo , Yao Ye , Lin Xiao , Cai Kaicong , Yang Qianfan , Tang Yalin
Published: June 2019

A supramolecular platform prototype for implementing resettable encoding functions was designed, which could be configured into a series of encoders, from 4-to-2 to 7-to-3, and even 14-to-4 ECs.
A self-assembled perylene diimide nanobelt for efficient visible-light-driven photocatalytic H2 evolution
Authors: Kong Kangyi , Zhang Shicong , Chu Yanmeng , Hu Yue , Yu Fengtao , Ye Haonan , Ding Haoran , Hua Jianli
Published: June 2019

In this paper, a supramolecular system (P-PMPDI) has been successfully developed for highly efficient photocatalytic hydrogen evolution. P-PMPDI showed a superior hydrogen evolution reaction rate of 11.7 mmol g−1 h−1 and a recorded AQY of 2.96% at 550 nm.
Enhancing the performance of germanium nanowire anodes for Li-ion batteries by direct growth on textured copper
Authors: Geaney Hugh , Bree Gerard , Stokes Killian , Collins Gearoid A. , Aminu Ibrahim Saana , Kennedy Tadhg , Ryan Kevin M.
Published: June 2019

Capacity retention of directly grown Ge nanowire anodes is enhanced by replacing stainless steel with textured Cu foil current collectors.
La3B14−: an inverse triple-decker lanthanide boron cluster
Authors: Chen Teng-Teng , Li Wan-Lu , Chen Wei-Jia , Li Jun , Wang Lai-Sheng
Published: June 2019

The relationship between the global minima of a tilted inverse triple-decker La3B14−and a perfect inverse triple decker La⋯B8⋯La⋯B8⋯La.
An efficient dynamic asymmetric catalytic system within a zinc-templated network
Authors: Serra-Pont Anna , Alfonso Ignacio , Solà Jordi , Jimeno Ciril
Published: June 2019

Enhanced cooperativity leading to high catalytic activity and stereoselectivity in the direct aldol reaction has been achieved through a complex network of simple species interacting reversibly.
π Complexes of P^P and P^N chelated gold(i)
Authors: Navarro Miquel , Toledo Alberto , Joost Maximilian , Amgoune Abderrahmane , Mallet-Ladeira Sonia , Bourissou Didier
Published: June 2019

Tricoordinate gold(i) π-complexes containing P-based chelating ligands (P^P and P^N) were prepared.
Bi4O5I2 flower/Bi2S3 nanorod heterojunctions for significantly enhanced photocatalytic performance
Authors: Hou Dongfang , Tang Fan , Ma Bingbing , Deng Min , Qiao Xiu-qing , Liu Yun-Lin , Li Dong-Sheng
Published: June 2019

The excellent photocatalytic reduction of Cr(vi) over Bi4O5I2/Bi2S3 heterojunctions is ascribed to the synergetic effects of Bi2S3 sensitization and intimate contact between Bi4O5I2 flowers and Bi2S3 nanorods.
New discovery in crystallography: correlation of terahertz time-domain spectra with crystal structures and photoluminescence properties of mononuclear/binuclear diimine–Cu(i)-phosphine complexes
Authors: Zhu Ning , Wang Guo , Lin Sen , Li Zhong-Feng , Xin Xiu-Lan , Yang Yu-Ping , Liu Min , Jin Qiong-Hua
Published: June 2019

A method was provided for qualitatively determining the photoluminescence quantum yield of diimine–Cu(i) complex by the waveform of terahertz time-domain spectroscopy.