bluuebunny/crossref_metadata_2025 huggingface dataset:
Subaru High-z Exploration of Low-Luminosity Quasars (SHELLQs). VIII. A less biased view of the early co-evolution of black holes and host galaxies
Authors: Izumi Takuma , Onoue Masafusa , Matsuoka Yoshiki , Nagao Tohru , Strauss Michael A , Imanishi Masatoshi , Kashikawa Nobunari , Fujimoto Seiji , Kohno Kotaro , Toba Yoshiki , Umehata Hideki , Goto Tomotsugu , Ueda Yoshihiro , Shirakata Hikari , Silverman John D , Greene Jenny E , Harikane Yuichi , Hashimoto Yasuhiro , Ikarashi Soh , Iono Daisuke , Iwasawa Kazushi , Lee Chien-Hsiu , Minezaki Takeo , Nakanishi Kouichiro , Tamura Yoichi , Tang Ji-Jia , Taniguchi Akio
Published: August 2019

We present ALMA [C ii] line and far-infrared (FIR) continuum observations of three $z \gt 6$ low-luminosity quasars ($M_{\rm 1450} \gt -25$ mag) discovered by our Subaru Hyper Suprime-Cam (HSC) survey. The [C ii] line was detected in all three targets with luminosities of $(2.4\mbox{--}9.5) \times 10^8\, L_{\odot }$, about one order of magnitude smaller than optically luminous ($M_{\rm 1450} \lesssim -25$ mag) quasars. The FIR continuum luminosities range from $\lt 9 \times 10^{10}\, L_{\odot }$ (3 $\sigma$ limit) to ${\sim } 2 \times 10^{12}\, L_{\odot }$, indicating a wide range in star formation rates in these galaxies. Most of the HSC quasars studied thus far show [C ii]/ FIR luminosity ratios similar to local star-forming galaxies. Using the [C ii]-based dynamical mass ($M_{\rm dyn}$) as a surrogate for bulge stellar mass ($M_{\rm\, bulge}$), we find that a significant fraction of low-luminosity quasars are located on or even below the local $M_{\rm\, BH}$–$M_{\rm\, bulge}$ relation, particularly at the massive end of the galaxy mass distribution. In contrast, previous studies of optically luminous quasars have found that black holes are overmassive relative to the local relation. Given the low luminosities of our targets, we are exploring the nature of the early co-evolution of supermassive black holes and their hosts in a less biased way. Almost all of the quasars presented in this work are growing their black hole mass at a much higher pace at $z \sim 6$ than the parallel growth model, in which supermassive black holes and their hosts grow simultaneously to match the local $M_{\rm\, BH}$–$M_{\rm\, bulge}$ relation at all redshifts. As the low-luminosity quasars appear to realize the local co-evolutionary relation even at $z \sim 6$, they should have experienced vigorous starbursts prior to the currently observed quasar phase to catch up with the relation.
Are Negative Symptoms Merely the “Real World” Consequences of Deficits in Social Cognition?
Authors: Pelletier-Baldelli Andrea , Holt Daphne J
Published: August 2019

Many investigations have demonstrated that negative symptoms and social cognitive deficits in schizophrenia play a large role in determining functional outcomes and ultimately long-term prognosis. Given this, there is increasing interest in understanding the relationship between these two symptom domains, particularly since studies have consistently found moderate to large associations between them. This shared variance raises a key question: to what degree do these two categories of symptoms arise from overlapping or identical changes in brain function? In other words, do some or all negative symptoms represent merely the downstream effects of social cognition deficits on daily functioning? In this commentary, the evidence for and against this possibility, limitations of currently validated empirical measurements of these symptoms, and directions for further investigation of this hypothesis are discussed. Understanding the shared and distinct mechanisms of these disabling deficits will have important implications for the design of novel, personalized treatments for psychotic illness.
Race, Gender, and Poverty Governance: The Case of the U.S. Child Welfare System
Authors: Woodward Kerry C
Published: August 2019

This article argues that the U.S. child welfare system is a primary institution of racialized and gendered poverty governance, operating at the nexus of the assistive and punitive arms of the state. With attention to the ways race and gender structure the child welfare system, I apply the concept of neoliberal paternalism to examine state efforts to reform “bad” parents into “good neoliberal citizen-parents.” I highlight the increasingly decentralized and privatized child welfare workforce and its effects on governance. Finally, I explore the contradictions around expectations of “self-sufficiency.”
Complete Genome Sequence of Strain WHRI 3811 Race 1 of Xanthomonas campestris pv. campestris, the Causal Agent of Black Rot of Cruciferous Vegetables
Authors: Kong Congcong , Horta de Passo Vânia , Fang Zhiyuan , Yang Limei , Zhuang Mu , Zhang Yangyong , Wang Yong , Vicente Joana G. , Lv Honghao
Published: August 2019

Xanthomonas campestris pv. campestris is an important bacterial pathogen that causes black rot and brings about enormous production loss for cruciferous vegetables worldwide. Currently, genome sequences for only a few X. campestris pv. campestris isolates are available, most of which are draft sequences. Based on the next-generation sequencing and single-molecule sequencing in real time technologies, we present here the complete genome sequence of strain WHRI 3811 race 1 of X. campestris pv. campestris, which is a type strain that has been extensively used. The genome data will contribute to our understanding of X. campestris pv. campestris genomic features and pave the way for research on X. campestris pv. campestris–host interactions.
Nest predation predicts infanticide in a cooperatively breeding bird
Authors: Cheng Yi-Ru , Rubenstein Dustin R. , Shen Sheng-Feng
Published: August 2019

In cooperatively breeding species, social conflict is typically assumed to underlie destructive behaviours like infanticide. However, an untested alternative hypothesis in birds is that infanticide in the form of egg tossing may simply be a parental response to partial nest predation representing a life-history trade-off. We examined egg tossing behaviour in the colonial and cooperatively breeding grey-capped social weaver (
Pseudonigrita arnaudi
), a plural breeder in which pairs nest separately, often in the same tree. Using infrared nest cameras, we found that 78% of the tossing events from 2012 to 2017 were committed by parents, suggesting that social conflict is unlikely to be the main reason underlying egg tossing in this species. Instead, reductions in clutch size due to both natural and experimentally simulated predation induced parental egg tossing. Our study suggests that destructive behaviour in cooperatively breeding birds can be shaped by a variety of mechanisms beyond social conflict and that alternative hypotheses must be considered when studying the adaptive significance of infanticide in group-living species.
Experimentally flight-impaired females show higher levels of extra-pair paternity in the pied flycatcherFicedula hypoleuca
Authors: Plaza Mireia , Cantarero Alejandro , Gil Diego , Moreno Juan
Published: August 2019

There is no consensus yet on the reasons why females engage in extra-pair copulations (EPCs). In some species, females have been shown to accrue some indirect benefits, but these effects are not consistent across species and studies. The sexual conflict hypothesis posits that extra-pair paternity (EPP) is the result of strong selection for male pursuit of EPC without real benefits for females. In order to test this hypothesis, we experimentally reduced wing area (reversibly tying together some primary feathers), in a group of pied flycatcher females (Ficedula hypoleuca). The manipulation increases wing loading (body mass/wing area), which is negatively associated with flying ability, and thus with the capacity to escape from unwanted copulations. We compared the levels of EPP in this experimental group with those of a group of un-manipulated females. Experimental females almost doubled the proportion of extra-pair young (EPY) with respect to control females. In addition, more males sired EPY in experimental than in control broods containing EPY. These results suggest that in our study population, EPP could be partially a product of female capacity to avoid EPCs. We also discuss the alternative hypothesis that results might be due to an eventual reduction of female attractiveness.
Optimization of circadian responses with shorter and shorter millisecond flashes
Authors: Kaladchibachi Sevag , Negelspach David C. , Zeitzer Jamie M. , Fernandez Fabian
Published: August 2019

Recent work suggests that the circadian pacemaker responds optimally to millisecond flashes of light, not continuous light exposure as has been historically believed. It is unclear whether these responses are influenced by the physical characteristics of the pulsing. In the present study,
Drosophila
(
n
= 2199) were stimulated with 8, 16 or 120 ms flashes. For each duration, the energy content of the exposure was systematically varied by changing the pulse irradiance and the number of stimuli delivered over a fixed 15 min administration window (64 protocols surveyed in all). Results showed that per microjoule invested, 8 ms flashes were more effective at resetting the circadian activity rhythm than 16- and 120 ms flashes (i.e. left shift of the dose–response curve, as well as a higher estimated maximal response). These data suggest that the circadian pacemaker's photosensitivity declines within milliseconds of light contact. Further introduction of light beyond a floor of (at least) 8 ms leads to diminishing returns on phase-shifting.
Robust component: a robustness measure that incorporates access to critical facilities under disruptions
Authors: Dong Shangjia , Wang Haizhong , Mostafavi Ali , Gao Jianxi
Published: August 2019

The objective of this paper is to integrate the post-disaster network access to critical facilities into the network robustness assessment, considering the geographical exposure of infrastructure to natural hazards. Conventional percolation modelling that uses generating function to measure network robustness fails to characterize spatial networks due to the degree correlation. In addition, the giant component alone is not sufficient to represent the performance of transportation networks in the post-disaster setting, especially in terms of the access to critical facilities (i.e. emergency services). Furthermore, the failure probability of various links in the face of different hazards needs to be encapsulated in simulation. To bridge this gap, this paper proposed the metric robust component and a probabilistic link-removal strategy to assess network robustness through a percolation-based simulation framework. A case study has been conducted on the Portland Metro road network during an M9.0 earthquake scenario. The results revealed how the number of critical facilities severely impacts network robustness. Besides, earthquake-induced failures led to a two-phase percolation transition in robustness performance. The proposed robust component metric and simulation scheme can be generalized into a wide range of scenarios, thus enabling engineers to pinpoint the impact of disastrous disruption on network robustness. This research can also be generalized to identify critical facilities and sites for future development.
Macro-to-nanoscale investigation of wall-plate joints in the acorn barnacle
Semibalanus balanoides
: correlative imaging, biological form and function, and bioinspiration
Authors: Mitchell R. L. , Coleman M. , Davies P. , North L. , Pope E. C. , Pleydell-Pearce C. , Harris W. , Johnston R.
Published: August 2019

Correlative imaging combines information from multiple modalities (physical–chemical–mechanical properties) at various length scales (centimetre to nanometre) to understand the complex biological materials across dimensions (2D–3D). Here, we have used numerous coupled systems: X-ray microscopy (XRM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), optical light microscopy (LM) and focused ion beam (FIB-SEM) microscopy to ascertain the microstructural and crystallographic properties of the wall-plate joints in the barnacle
Semibalanus balanoides
. The exoskeleton is composed of six interlocking wall plates, and the interlocks between neighbouring plates (alae) allow barnacles to expand and grow while remaining sealed and structurally strong. Our results indicate that the ala contain functionally graded orientations and microstructures in their crystallography, which has implications for naturally functioning microstructures, potential natural strengthening and preferred oriented biomineralization. Elongated grains at the outer edge of the ala are oriented perpendicularly to the contact surface, and the
c
-axis rotates with the radius of the ala. Additionally, we identify for the first time three-dimensional nanoscale ala pore networks revealing that the pores are only visible at the tip of the ala and that pore thickening occurs on the inside (soft bodied) edge of the plates. The pore networks appear to have the same orientation as the oriented crystallography, and we deduce that the pore networks are probably organic channels and pockets, which are involved with the biomineralization process. Understanding these multiscale features contributes towards an understanding of the structural architecture in barnacles, but also their consideration for bioinspiration of human-made materials. The work demonstrates that correlative methods spanning different length scales, dimensions and modes enable the extension of the structure–property relationships in materials to form and function of organisms.
Physical flow effects can dictate plankton population dynamics
Authors: Woodward J. R. , Pitchford J. W. , Bees M. A.
Published: August 2019

Oceanic flows do not necessarily mix planktonic species. Differences in individual organisms’ physical and hydrodynamic properties can cause changes in drift normal to the mean flow, leading to segregation between species. This physically driven heterogeneity may have important consequences at the scale of population dynamics. Here, we describe how one form of physical forcing, circulating flows with different inertia effects between phytoplankton and zooplankton, can dramatically alter excitable plankton bloom dynamics. This may impact our understanding of the initiation and development of harmful algal blooms (HABs), which have significant negative ecological and socio-economic consequences. We study this system in detail, providing spatio-temporal dynamics for particular scenarios and summarizing large-scale behaviour via spatially averaged bifurcation diagrams. The key message is that, across a large range of parameter values, fluid flow can induce plankton blooms and mean-field population dynamics that are distinct from those predicted for well-mixed systems. The implications for oceanic population dynamic studies are manifest: we argue that the formation of HABs will depend strongly on the physical and biological state of the ecosystem, and that local increases in zooplankton heterogeneity are likely to precede phytoplankton blooms.
Guidance of zoospores by potassium gradient sensing mediates aggregation
Authors: Galiana Eric , Cohen Celine , Thomen Philippe , Etienne Catherine , Noblin Xavier
Published: August 2019

The biflagellate zoospores of some phytopathogenicPhytophthoraspecies spontaneously aggregate within minutes in suspension. We show here thatPhytophthora parasiticazoospores can form aggregates in response to a K+gradient with a particular geometric arrangement. Using time-lapse live imaging in macro- and microfluidic devices, we defined (i) spatio-temporal and concentration-scale changes in the gradient, correlated with (ii) the cell distribution and (iii) the metrics of zoospore motion (velocity, trajectory). In droplets, we found that K+-induced aggregates resulted from a single biphasic temporal sequence involving negative chemotaxis followed by bioconvection over a K+gradient concentration scale [0–17 mM]. Each K+-sensing cell moved into a region in which potassium concentration is below the threshold range of 1–4 mM, resulting in swarming. Once a critical population density had been achieved, the zoospores formed a plume that migrated downward, with fluid advection in its wake and aggregate formation on the support surface. In the microfluidic device, the density of zoospores escaping potassium was similar to that achieved in droplets. We discuss possible sources of K+gradients in the natural environment (zoospore population, microbiota, plant roots, soil particles), and implications for the events preceding inoculum formation on host plants.
Mitochondria—hubs for regulating cellular biochemistry: emerging concepts and networks
Authors: Anderson Alexander J. , Jackson Thomas D. , Stroud David A. , Stojanovski Diana
Published: August 2019

Mitochondria are iconic structures in biochemistry and cell biology, traditionally referred to as the powerhouse of the cell due to a central role in energy production. However, modern-day mitochondria are recognized as key players in eukaryotic cell biology and are known to regulate crucial cellular processes, including calcium signalling, cell metabolism and cell death, to name a few. In this review, we will discuss foundational knowledge in mitochondrial biology and provide snapshots of recent advances that showcase how mitochondrial function regulates other cellular responses.
Theoretical study on the toxicity of ‘Novichok’ agent candidates
Authors: Jeong Keunhong , Choi Junwon
Published: August 2019

The identities and properties of ‘Novichok’ (Russian for ‘newcomer’ or ‘novice’) agents allegedly used in the recent terrorist attack in the UK have not been well documented. Although several people previously involved in the synthesis of these materials claimed Novichok agents to be five to eight times more potent than VX, a deadly nerve agent, no open data on these species are currently available. To bridge this gap, we herein performed a theoretical study on several Novichok agent candidates and conducted natural population charge analysis to evaluate the possible mechanisms of their toxicity, suggesting that these agents might promote the ageing and deformation of acetylcholinesterase. Moreover, the reaction of Novichok agents with acetylcholinesterase serine was calculated to be most thermodynamically favoured for Novichok candidate A234. Thus, this work is believed to provide a basis for finding Novichok antidotes and should inspire further detoxification studies to prepare for possible terrorist attacks in the future.
Robust polyimide nano/microfibre aerogels welded by solvent-vapour for environmental applications
Authors: Shen Ying , Li Dawei , Deng Bingyao , Liu Qingsheng , Liu Huizhong , Wu Tong
Published: August 2019

Due to the high porosity, resilience and ultra-low density, polymer nanofibre-derived aerogels (NFAs) have been widely investigated in recent years. However, welding of the fibrous networks of NFAs, which has been proved extremely essential to their structural performance, still remains a major challenge. Herein, electrospun polyimide (PI) nano/microfibres were used as building blocks to construct hierarchically porous aerogels through a solid-templating technique. By further welding the adjacent nano/microfibres at their cross-points in a controllable fashion by solvent-vapour, super elasticity was achieved for the aerogels, with a recoverable ultimate strain of 80%. It is noteworthy that this process is free from cross-linking, heating and significant structure changing (i.e. chemical structure, crystallinity and fibrous network). Additionally, the porous structure of PI nano/microfibre aerogels (PI-N/MFAs) could be tuned by adjusting the organization of microfibres from a disordered/ordered cellular to a uniform structure. The as-obtained aerogels showed ultra-low density (4.81 mg cm
−3
), high porosity (99.66%), and comparable or higher recoverable compressive strain and stress relative to the other nanofibre-based aerogels. Furthermore, we showed the potential of such an aerogel for particle or aerosol filtration. PI nanofibre aerogels composite filters (PI-NFACFs) manifested excellent performance in PM
2.0
filtration (99.6% filtration efficiency with 115 Pa pressure drop). Therefore, this study brought a new perspective on the simple preparation of nanofibre-based aerogels for air filtration.
Response time of an avian prey to a simulated hawk attack is slower in darker conditions, but is independent of hawk colour morph
Authors: Nebel Carina , Sumasgutner Petra , Pajot Adrien , Amar Arjun
Published: August 2019

To avoid predation, many species rely on vision to detect predators and initiate an escape response. The ability to detect predators may be lower in darker light conditions or with darker backgrounds. For birds, however, this has never been experimentally tested. We test the hypothesis that the response time of avian prey (feral pigeon
Columbia livia f. domestica
) to a simulated hawk attack (taxidermy mounted colour-polymorphic black sparrowhawk
Accipiter melanoleucus
) will differ depending on light levels or background colour. We predict that response will be slower under darker conditions, which would translate into higher predation risk. The speed of response of prey in relation to light level or background colour may also interact with the colour of the predator, and this idea underpins a key hypothesis proposed for the maintenance of different colour morphs in polymorphic raptors. We therefore test whether the speed of reaction is influenced by the morph of the hawk (dark/light) in combination with light conditions (dull/bright), or background colours (black/white). We predict slowest responses to morphs under conditions that less contrast with the plumage of the hawk (e.g. light morph under bright light or white background). In support of our first hypothesis, pigeons reacted slower under duller light and with a black background. However, we found no support for the second hypothesis, with response times observed between the hawk-morphs being irrespective of light levels or background colour. Our findings experimentally confirm that birds detect avian predators less efficiently under darker conditions. These conditions, for example, might occur during early mornings or in dense forests, which could lead to changes in anti-predator behaviours. However, our results provide no support that different morphs may be maintained in a population due to differential selective advantages linked to improved hunting efficiencies in different conditions due to crypsis.
Bistable polar-orthotropic shallow shells
Authors: Sobota P. M. , Seffen K. A.
Published: August 2019

We investigate stabilizing and eschewing factors on bistability in polar-orthotropic shells in order to enhance morphing structures. The material law causes stress singularities when the circumferential stiffness is smaller than the radial stiffness (
β
< 1), requiring a careful choice of the trial functions in our Ritz approach, which employs a higher-order geometrically nonlinear analytical model. Bistability is found to strongly depend on the orthotropic ratio,
β
, and the in-plane support conditions. An investigation of their interaction offers a new perspective on the effect of the hoop stiffness on bistability: while usually perceived as promoting, it is shown to be only stabilizing insofar as it prevents radial expansions; however, if in-plane supports are present, it becomes a redundant feature. Closed-form approximations of the bistable threshold are then provided by single-curvature-term approaches. For significantly stiffer values of the radial stiffness, a strong coupling of the orthotropic ratio and the support conditions is revealed: while roller-supported shells are monostable, fixed-pinned ones are most disposed to stable inversions; insight is given by comparing to a simplified beam model. Eventually, we show that cutting a central hole is a suitable method to deal with stress singularities: while fixed-pinned shells are barely affected by a hole, the presence of a hole strongly favours bistable inversions in roller-supported shells.
The dynamics of men's cooperation and social status in a small-scale society
Authors: von Rueden Christopher R. , Redhead Daniel , O'Gorman Rick , Kaplan Hillard , Gurven Michael
Published: August 2019

We propose that networks of cooperation and allocation of social status co-emerge in human groups. We substantiate this hypothesis with one of the first longitudinal studies of cooperation in a preindustrial society, spanning 8 years. Using longitudinal social network analysis of cooperation among men, we find large effects of kinship, reciprocity and transitivity in the nomination of cooperation partners over time. Independent of these effects, we show that (i) higher-status individuals gain more cooperation partners, and (ii) individuals gain status by cooperating with individuals of higher status than themselves. We posit that human hierarchies are more egalitarian relative to other primates species, owing in part to greater interdependence between cooperation and status hierarchy.
Persistent Elevation of Electrical Pain Threshold following Continuous Theta Burst Stimulation over Primary Somatosensory Cortex in Humans
Authors: Rao Nishant , Chen Yen-Ting , Ramirez Regan , Tran John , Li Sheng , Parikh Pranav J.
Published: August 2019

Background

Primary somatosensory cortex (S1) is involved in pain processing and thus its suppression using neuromodulatory techniques such as continuous theta burst stimulation (cTBS) might be a potential pain management strategy in patients with neuropathic pain. S1 cTBS is known to elevate pain threshold in young adults. However, the persistence of this effect is unknown.

Objective/Hypothesis

We hypothesized persistent elevation of pain threshold following cTBS over S1 in healthy, young adults.

Methods

We recruited ten subjects in a sham-controlled crossover design and recorded their electrical pain threshold (EPT) for 40 min following cTBS over S1. We assessed corticospinal excitability (CSE) to rule out the involvement of primary motor cortex due to spread of current.

Results

cTBS over S1 elevated EPT without modulating CSE compared to sham stimulation. EPT was elevated for 40 min post-cTBS.

Conclusions

S1 can be focally targeted using cTBS for a longer lasting pain relief in patients.
Molecular signature of pruriceptive MrgprA3+ neurons
Authors: Xing Yanyan , Chen Junyu , Hilley Henry , Steele Haley , Yang Jingjing , Han Liang
Published: August 2019

Itch, initiated by the activation of sensory neurons, is frequently associated with dermatological or systemic diseases and significantly affects patient quality of life. MrgprA3+ sensory neurons have been identified as one of the major itch-sensing neuronal populations. Mounting evidence has demonstrated that peripheral pathological conditions induce physiological regulations of sensory neurons, which is critical for the maintenance of chronic itch sensation. However, the underlying molecular mechanisms are not clear. Here we performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis condition. Our results revealed the unique molecular signature of itch-sensing neurons and the distinct transcriptional profile changes that result in response to dermatitis. We found enrichment of nine Mrgpr family members and two histamine receptors in MrgprA3+ neurons, suggesting that MrgprA3+ neurons are the main, direct neuronal target for histamine and Mrgprs agonists. In addition, Ptpn6 and Pcdh12 were identified as novel and highly selective markers of MrgprA3+ neurons. We also discovered that MrgprA3+ neurons respond to skin dermatitis in a way that is unique from other sensory neurons by regulating a combination of transcriptional factors, ion channels, and key molecules involved in synaptic transmission. These results significantly increase our knowledge of itch transmission and uncover potentially novel targets for combating itch.
Engineering of Chimeric Antigen Receptor T Cells with integrin αEβ7 Results in Augmented Therapeutic Efficacy against E-cadherin positive tumor
Authors: Sun Hongxing , He Shan , Meng Lijun , Wang Ying , Zhang Hanghang , Liu Yongnian , Wang Jian , Tao Min , Barta Stefan K. , Dulaimi Essel , Fung Henry , Issa Jean-Pierre J. , Zheng Lei-Zhen , Zhang Yi
Published: August 2019

Integrin αEβ7 (CD103) can interact with E-cadherin and promote T cell retention in epithelial tissue. However, whether the expression of CD103 on chimeric antigen receptor (CAR)-T cells may augment T cell anti-tumor activity remains unknown. Using a preclinical model, we demonstrate that CD103 engineering of human CAR-T cells significantly improves their therapeutic effects on eliminating pre-established E-cadherin expressing tumor cells in immune deficient NOD.scid.Il2Rγcnull (NSG) mice. Human T cells that were engineered with CAR containing 4-1BB and CD3zeta intracellular signaling domains (named BBz) expressed reduced level of CD103 in mice model. Ex vivo assays confirmed the effect of 4-1BB on repressing CD103 expression in CAR-T cells. On the other hand, we generated CD103 expressing CAR-T cells by introducing the αE gene into the CAR structure (named CD103-BBz CAR-T cells). As compared to BBz CAR-T cells, CD103-BBz CAR-T cells produced higher levels of IL-2 and underwent greater expansion in cultures and acquired greater capacity to control the growth and metastasis of E-cadherin expressing lymphoma cells in NSG mice. This effect of CD103-BBz CAR-T cells was associated with their increased capacity to infiltrate into the tumor and persist in vivo, leading to significantly improved overall survival of lymphoma mice. Our findings suggest that engineering tumor-reactive T cells with CD103 may represent a novel strategy to improve adoptive T cells anti-tumor efficacy, and this strategy may have broad implication in the epithelial solid tumor treatment.

Highlights

CAR-T cells with 4-1BB costimulatory domain express reduced level of CD103

4-1BB signaling antagonist TGF-β1 induced CD103 expression

Ectopically expression of CD103 on CAR-T cells enhanced their anti-E-cadherin positive tumor capacity

Graphical Abstract:

Graphic Summary: The co-stimulatory molecule 4-1BB within the CAR protein potently suppresses CD103 expression. Engineering CAR-T cells with CD103 significantly enhances their capacity to proliferate and infiltrate into the solid tumor, leading to augmented anti-tumor immunity.
Vav1 is essential for HIF-1α activation in vascular response to ischemic stress
Authors: Min Yongfen , Hong Jaewoo , Wuest Todd , Lin P. Charles
Published: August 2019

Vascular response to hypoxia is a major determinant of organ function under stress, which is particularly critical for vital organs such as the heart. This study identifies Vav1 as a key vascular regulator of hypoxia. Vav1 is present in vascular endothelium and is essential for HIF-1 activation under hypoxia. It regulates HIF-1α stabilization through the p38/Siah2/PHD3 pathway. Consequently, Vav1 deficient mice are predisposed to sudden death under cardiac ischemia with increased coronary endothelial apoptosis. Moreover, Vav1 binds to VEGFR1 that carries Vav1 to lysosomes for degradation in normoxia. Hypoxia upregulates Vav1 through inhibition of protein degradation. These findings reveal that regulation of Vav1 by hypoxia is analogous to HIF-1α regulation. Both proteins are constitutively produced allowing for rapid responses when stress occurs, and constantly degraded in normoxia. Hypoxia stabilizes Vav1, which is required for HIF-1α accumulation. Together they mediate the vascular response to hypoxia and maintain tissue homeostasis.
Measuring significant changes in chromatin conformation with ACCOST
Authors: Cook Kate B. , Roch Karine Le , Vert Jean Philippe , Noble William Stafford
Published: August 2019

Chromatin conformation assays such as Hi-C cannot directly measure differences in 3D architecture between cell types or cell states. For this purpose, two or more Hi-C experiments must be carried out, but direct comparison of the resulting Hi-C matrices is confounded by several features of Hi-C data. Most notably, the genomic distance effect, whereby contacts between pairs of genomic loci that are proximal along the chromosome exhibit many more Hi-C contacts that distal pairs of loci, dominates every Hi-C matrix. Furthermore, the form that this distance effect takes often varies between different Hi-C experiments, even between replicate experiments. Thus, a statistical confidence measure designed to identify differential Hi-C contacts must accurately account for the genomic distance effect or risk being misled by large-scale but artifactual differences. ACCOST (Altered Chromatin Conformation STatistics) accomplishes this goal by extending the statistical model employed by DEseq, re-purposing the “size factors,” which were originally developed to account for differences in read depth between samples, to instead model the genomic distance effect. We show via analysis of simulated and real data that ACCOST provides unbiased statistical confidence estimates that compare favorably with competing methods such as diffHiC, FIND, and HiCcompare. ACCOST is freely available with an Apache license at https://bitbucket.org/noblelab/accost.
Using high-definition transcranial direct current stimulation to investigate the role of the dorsolateral prefrontal cortex in explicit sequence learning
Authors: Ballard Hannah K. , Eakin Sydney M. , Maldonado Ted , Bernard Jessica A.
Published: August 2019

Though we have a general understanding of the brain areas involved in motor sequence learning, there is more to discover about the neural mechanisms underlying skill acquisition. Skill acquisition may be subserved, in part, by interactions between the cerebellum and prefrontal cortex through a cerebello-thalamo-prefrontal network. In prior work, we investigated this network by targeting the cerebellum; here, we explored the consequence of stimulating the dorsolateral prefrontal cortex using high-definition transcranial direct current stimulation (HD-tDCS) before administering an explicit motor sequence learning paradigm. Using a mixed within- and between-subjects design, we employed anodal (n = 24) and cathodal (n = 25) HD-tDCS (relative to sham) to temporarily alter brain function and examine effects on skill acquisition. The results indicate that both anodal and cathodal prefrontal stimulation impedes motor sequence learning, relative to sham. These findings suggest an overall negative influence of active prefrontal stimulation on the acquisition of a sequential pattern of finger movements. Collectively, this provides novel insight on the role of the dorsolateral prefrontal cortex in initial skill acquisition, when cognitive processes such as working memory are used. Exploring methods that may improve motor learning is important in developing therapeutic strategies for motor-related diseases and rehabilitation.
Device for source position stabilization and beam parameter monitoring at inverse Compton X-ray sources
Authors: Günther Benedikt , Dierolf Martin , Achterhold Klaus , Pfeiffer Franz
Published: August 2019

Compact X-ray sources based on inverse Compton scattering provide brilliant and partially coherent X-rays in a laboratory environment. The cross section for inverse Compton scattering is very small, requiring high-power laser systems as well as small laser and electron beam sizes at the interaction point to generate sufficient flux. Therefore, these systems are very sensitive to distortions which change the overlap between the two beams. In order to monitor X-ray source position, size and flux in parallel to experiments, the beam-position monitor proposed here comprises a small knife edge whose image is acquired with an X-ray camera specifically designed to intercept only a very small fraction of the X-ray beam. Based on the source position drift recorded with the monitor, a closed-loop feedback stabilizes the X-ray source position by adjusting the laser beam trajectory. A decrease of long-term source position drifts by more than one order of magnitude is demonstrated with this device. Consequently, such a closed-loop feedback system which enables stabilization of source position drifts and flux of inverse Compton sources in parallel to experiments has a significant impact on the performance of these sources.
Gamification of assembly planning in virtual environment
Authors: Garbaya Samir , Romano Daniela M. , Hattar Gunjeet
Published: August 2019

Purpose

The purpose of this paper is to study the effect of the gamification of virtual assembly planning on the user performance, user experience and engagement.

Design/methodology/approach

A multi-touch table was used to manipulate virtual parts and gamification features were integrated into the virtual assembly environment. An experiment was conducted in two conditions: a gamified and a non-gamified virtual environment. Subjects had to assemble a virtual pump. The user performance was evaluated in terms of the number of errors, the feasibility of the generated assembly sequence and the user feedback.

Findings

The gamification reduced the number of errors and increased the score representing the number of right decisions. The results of the subjective and objective analysis showed that the number of errors decreased with engagement in the gamified assembly. The increase in the overall user experience reduced the number of errors. The subjective evaluation showed a significant difference between the gamified and the non-gamified assembly in terms of the level of engagement, the learning usability and the overall experience.

Research limitations/implications

The effective learning retention after training has not been tested, and longitudinal studies are necessary. The effect of the used gamification elements has been evaluated as a whole; further work could isolate the most beneficial features and add other elements that might be more beneficial for learning.

Originality/value

The research reported in this paper provides valuable insights into the gamification of virtual assembly using a low-cost multi-touch interface. The results are promising for training operators to assemble a product at the design stage.
Assembly variation analysis of compliant mechanisms by combining direct linearization method and Lagrange’s equations
Authors: Niu Zhihua , Li Zhimin , Jin Sun , Liu Tao
Published: August 2019

Purpose

This paper aims to carry out assembly variation analysis for mechanisms with compliant joints by considering deformations induced by manufactured deviations. Such an analysis procedure extends the application area of direct linearization method (DLM) to compliant mechanisms and also illustrates the dimensional interaction within multi-loop compliant structures.

Design/methodology/approach

By applying DLM to both geometrical equations and Lagrange’s equations of the second kind, an analytical deviation modeling method for mechanisms with compliant joints are proposed and further used for statistical assembly variation analysis. The precision of this method is verified by comparing it with finite element simulation and traditional DLM.

Findings

A new modeling method is proposed to represent kinematic relationships between joint deformations and parts/components deviations. Based on a case evaluation, the computational efficiency is improved greatly while the modeling accuracy is maintained at more than 94% rate comparing with the benchmark finite element simulation.

Originality/value

The Equilibrium Equations of Incremental Forces derived from Lagrange’s equations are proposed to quantitatively represent the relationships between manufactured deviations and assembly deformations. The present method extends the application area of DLM to compliant structures, such as automobile suspension systems and some Micro-Electro-Mechanical-Systems.
Statistical solution of inverse problems using a state reduction
Authors: Neumayer Markus , Suppan Thomas , Bretterklieber Thomas
Published: August 2019

Purpose

The application of statistical inversion theory provides a powerful approach for solving estimation problems including the ability for uncertainty quantification (UQ) by means of Markov chain Monte Carlo (MCMC) methods and Monte Carlo integration. This paper aims to analyze the application of a state reduction technique within different MCMC techniques to improve the computational efficiency and the tuning process of these algorithms.

Design/methodology/approach

A reduced state representation is constructed from a general prior distribution. For sampling the Metropolis Hastings (MH) Algorithm and the Gibbs sampler are used. Efficient proposal generation techniques and techniques for conditional sampling are proposed and evaluated for an exemplary inverse problem.

Findings

For the MH-algorithm, high acceptance rates can be obtained with a simple proposal kernel. For the Gibbs sampler, an efficient technique for conditional sampling was found. The state reduction scheme stabilizes the ill-posed inverse problem, allowing a solution without a dedicated prior distribution. The state reduction is suitable to represent general material distributions.

Practical implications

The state reduction scheme and the MCMC techniques can be applied in different imaging problems. The stabilizing nature of the state reduction improves the solution of ill-posed problems. The tuning of the MCMC methods is simplified.

Originality/value

The paper presents a method to improve the solution process of inverse problems within the Bayesian framework. The stabilization of the inverse problem due to the state reduction improves the solution. The approach simplifies the tuning of MCMC methods.
Converging resources and co-producing for innovation: evidence from healthcare services
Authors: Sehgal Sanjeewani , Gupta Garima
Published: August 2019

Purpose

The purpose of this paper is to examine healthcare organizations for the improvements in their existing services (incremental innovation) as well as for the new service developments (radical innovation) initiated through the utilization of resources and co-producing behavior.

Design/methodology/approach

The paper uses an SEM approach to analyze the responses obtained from 257 medical administrators of 50 hospitals registered with National Accreditation Board for Hospitals and Healthcare Providers.

Findings

The results reflect a positive and significant impact that is more driven by internal resources and is found to be stronger for incremental innovation in healthcare. The study also posits that resource utilization in conjunction with co-production activities has greater potential to bring innovation that is likely to succeed and stay inimitable.

Research limitations/implications

The paper outlines scope for future research and suggests inclusion of other service sectors, geographical locations and performance indicators to attain a better understanding of the constructs examined.

Practical implications

The paper outlines implications for policy makers concerned with healthcare. Providers of health services ought to develop a proactive customer-oriented approach so as to deliver value through service innovations. Integrating customer co-production processes may further augment the overall quality of care.

Originality/value

Empirical studies integrating the resource-oriented view of innovation along with firms’ co-production and collaborative mechanisms are majorly lacking. The study bridges this gap and suggests ways to bring innovation in health services, a pivotal need for health institutions of an emerging economy like India.
The effect of royal family members on the board on firm performance in Saudi Arabia
Authors: AL Nasser Zahra
Published: August 2019

Purpose

The purpose of this paper is to empirically examine the effect of royal family members on firm performance of publicly listed companies in Saudi Arabia.

Design/methodology/approach

Using 491 firm-year observations of non-financial publicly listed firms in Saudi Arabia’s stock market between 2009 and 2013, the study employs, besides others, the advanced econometric technique GMM-system estimator. This allows the dynamic nature and control of the endogeneity problem to be accounted for in corporate governance and firm performance.

Findings

The main result is that the attendance of royal family members at board meetings negatively influences firm performance but does not have an influence on firm value. The results also show that firms with many independent royal family members on the board of directors have better firm performance and firm value. In addition, firms with a high number of royal family members presenting on the board have better firm performance.

Research limitations/implications

This study offers guidance to assist the further investigation of the SA Royal Family’s BoD membership either in SA or in other monarchy countries. It is interesting to compare these results in order to further understand the different effects that the Royal Family’s BoD membership have in such countries. This study’s results suggest that independent members of SA’s Royal Family on the BoD have some influence on firm performance in both the short and long term. Thus, policymakers should encourage the members of SA’s Royal Family to become more involved in firms’ BoDs.

Practical implications

This study offers guidance for further investigation of royal family members in the region or in other monarchy countries. It will be interesting to compare these results. The study suggests that royal family members on the board have a partial influence on firm performance, especially the independent ones. Thus, the policymakers should encourage more involvement of independent royal family members on the board.

Social implications

Foreign and minority investors, who invest in SA’s publicly listed firms, should note that when independent members of SA’s Royal Family are on the BoD their investment will benefit from the reduced risks and uncertainty.

Originality/value

To the best of the author’s knowledge, this is the first study undertaken to investigate empirically the influence a royal family’s presence on the board of directors has on firm performance. This study is based on both theories, namely the agency theory and resource dependence theory.
Behind the cloak of competence: brain injury and mental capacity legislation
Authors: Moore Sophie , Wotus Rebecca , Norman Alyson , Holloway Mark , Dean Jackie
Published: August 2019

Purpose

Brain Injury Case Managers (BICMs) work closely with individuals with Acquired Brain Injury (ABI), assessing needs, structuring rehabilitation interventions and providing support, and have significant experience of clients with impairments to decision making. The purpose of this paper is to explore the application of the Mental Capacity Act (MCA) and its guidance when applied to ABI survivors. This research aimed to: first, highlight potential conflicts or tensions that application of the MCA might pose, and second, identify approaches to mitigate the problems of the MCA and capacity assessments with ABI survivors. It is hoped that this will support improvements in the services offered.

Design/methodology/approach

Using a mixed method approach, 93 BICMs responded to an online questionnaire about decision making following ABI. Of these, 12 BICMs agreed to take part in a follow-up semi-structured telephone interview.

Findings

The data revealed four main themes: disagreements with other professionals, hidden disabilities, vulnerability in the community and implementation of the MCA and capacity assessments.

Practical implications

The findings highlight the need for changes to the way mental capacity assessments are conducted and the need for training for professionals in the hidden effects of ABI.

Originality/value

Limited research exists on potential limitations of the application of the MCA for individuals with an ABI. This paper provides much needed research on the difficulties surrounding mental capacity and ABI.