Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver macrophages and sinusoidal endothelial cells execute vaccine-elicited capture of invasive bacteria

Vaccination has substantially reduced the morbidity and mortality of bacterial diseases, but mechanisms of vaccine-elicited pathogen clearance remain largely undefined. We report that vaccine-elicited immunity against invasive bacteria mainly operates in the liver. In contrast to the current paradigm that migrating phagocytes execute vaccine-elicited immunity against blood-borne pathogens, we found that invasive bacteria are captured and killed in the liver of vaccinated host via various immune mechanisms that depend on the protective potency of the vaccine. Vaccines with relatively lower degrees of protection only activated liver-resident macrophage Kupffer cells (KCs) by inducing pathogen-binding immunoglobulin M (IgM) or low amounts of IgG. IgG-coated pathogens were directly captured by KCs via multiple IgG receptors FcγRs, whereas IgM-opsonized bacteria were indirectly bound to KCs via complement receptors of immunoglobulin superfamily (CRIg) and complement receptor 3 (CR3) after complement C3 activation at the bacterial surface. Conversely, the more potent vaccines engaged both KCs and liver sinusoidal endothelial cells by inducing higher titers of functional IgG antibodies. Endothelial cells (ECs) captured densely IgG-opsonized pathogens by the low-affinity IgG receptor FcγRIIB in a “zipper-like” manner and achieved bacterial killing predominantly in the extracellular milieu via an undefined mechanism. KC- and endothelial cell–based capture of antibody-opsonized bacteria also occurred in FcγR-humanized mice. These vaccine protection mechanisms in the liver not only provide a comprehensive explanation for vaccine-/antibody-boosted immunity against invasive bacteria but also may serve as in vivo functional readouts of vaccine efficacy. The liver is the major immune organ for vaccine-elicited protection against invasive bacteria. Editor’s summary Two types of vaccine against Streptococcus pneumoniae (PCV13 and PPV23) are available, and both have common antigens but different efficacies. Using studies in mice, Wang et al. show that the greater efficacy of PCV13 associates with increased capture of circulating pathogens by hepatic endothelial cells, which is promoted by IgG-FcγRIIB interaction. In contrast, PPV23 only activates Kupffer cells via IgM-induced complement activation without invoking capture by endothelial cells. Similar findings are also shown for vaccines against Neisseria meningitidis and Klebsiella pneumoniae, suggesting that these findings could have broad implications for vaccine development. —Catherine Charneski
Inhibition of RIP1 improves immune reconstitution and reduces GVHD mortality while preserving graft-versus-leukemia effects

Graft-versus-host disease (GVHD) remains the major cause of morbidity and nonrelapse mortality (NRM) after hematopoietic cell transplantation (HCT). Inflammatory cytokines mediate damage to key GVHD targets such as intestinal stem cells (ISCs) and also activate receptor interacting protein kinase 1 (RIP1; RIPK1), a critical regulator of apoptosis and necroptosis. We therefore investigated the role of RIP1 in acute GVHD using samples from HCT patients, modeling GVHD damage in vitro with both human and mouse gastrointestinal (GI) organoids, and blocking RIP1 activation in vivo using several well-characterized mouse HCT models. Increased phospho-RIP1 expression in GI biopsies from patients with acute GVHD correlated with tissue damage and predicted NRM. Both the genetic inactivation of RIP1 and the RIP1 inhibitor GNE684 prevented GVHD-induced apoptosis of ISCs in vivo and in vitro. Daily administration of GNE684 for 14 days reduced inflammatory infiltrates in three GVHD target organs (intestine, liver, and spleen) in mice. Unexpectedly, GNE684 administration also reversed the marked loss of regulatory T cells in the intestines and liver during GVHD and reduced splenic T cell exhaustion, thus improving immune reconstitution. Pharmacological and genetic inhibition of RIP1 improved long-term survival without compromising the graft-versus-leukemia (GVL) effect in lymphocytic and myeloid leukemia mouse models. Thus, RIP1inhibition may represent a nonimmunosuppressive treatment for GVHD. RIP1 inhibition is not immunosuppressive and prevents the apoptosis of intestinal stem cells to reduce GVHD severity while preserving GVL effects. Editor’s summary Allogeneic hematopoietic cell transplantation (HCT) is performed for patients with leukemia to induce graft-versus-leukemia (GVL) effects. However, the GVL effect is closely tied to development of graft-versus-host disease (GVHD), and GVHD treatments can limit GVL effects. Here, Prado-Acosta and colleagues studied the role of receptor interacting protein kinase 1 (RIP1) in acute GVHD, finding that increased phospho-RIP1 was associated with worsened intestinal damage and increased nonrelapse mortality in patients undergoing allogeneic HCT. In mice undergoing HCT, genetic knockout or pharmacological inhibition of RIP1 was associated with decreased intestinal damage and improved survival. RIP1 inhibition also improved immune reconstitution in mice undergoing allogeneic HCT and did not inhibit GVL effects in leukemic mice, suggesting that RIP1 inhibition may be a nonimmunosuppressive treatment for GVHD. —Melissa L. Norton
Effectiveness of Neuropediatric Inpatient Rehabilitation

Abstract Aim Inpatient rehabilitation plays an important role in treating neurological diseases in children and adolescents. However, there is a lack of current research concerning this matter. This retrospective study aims to analyze the effectiveness of neuropediatric inpatient rehabilitation, to identify influencing factors, and to examine the importance of inpatient rehabilitation programs. Methods We reviewed medical records of patients, diagnosed with cerebral palsy, traumatic brain injury (TBI), or stroke who had an inpatient rehabilitation at the Department of Neuropediatrics of St. Mauritius Therapieklinik in Meerbusch from 2012 to 2019. The patients received several units of different therapies such as motor and cognitive rehabilitation or speech therapy per day, depending on their individual needs and aims. Rehabilitation outcome was assessed by comparing Gross Motor Function Measure-88 and Pediatric Evaluation of Disability Inventory admission and discharge scores. Influences of sex, age, length of stay (LOS), and admission score were analyzed. Results A total of 738 patients with a mean age of 9.2 (± 5.1) years and a mean LOS of 53.8 (± 33.7) days were included; 38.5% were female. Patients, regardless of their diagnosis, sex, or age, demonstrated highly significant and meaningful improvements of self-care, mobility, and social function during inpatient rehabilitation. Especially, the group of patients with TBI and stroke could approximate their skills substantially to the ones of healthy peers. A longer LOS correlated significantly with greater improvement of skills. Interpretation This is a current study, supporting the effectiveness of neuropediatric inpatient rehabilitation and affirming its value in treating neurological diseases in children and adolescents.
Optimization and far-field characteristic of metal/dielectric coated circular semiconductor nano-lasers

Metal/dielectric coated semiconductor lasers with sub-wavelength dimensions have shown promising applications in photonics integrated circuits and on-chip optical interconnects. In this study, we optimize the structure of circular InAlGaAs/InP nanocavities by employing the finite-difference time-domain (FDTD) numerical simulation method. It was found that, the quality factors of monopole modes in a cavity with radius of 250 nm can be over 1000 after structure optimization. Furthermore, the far-field characteristics of resonant modes in the cavities with different radius were studied. For the monopole modes, the divergent angle of far-field distribution decreases along with the increase of longitudinal order. Meanwhile, the cavity radius has a significant effect on the far-field distribution for monopole modes. For the dipole modes, the far-field distribution concentrates on a small angle range which is much better than that of monopole modes, and the effect of cavity radius on the far-field distribution is small. The research results of this study provide valuable insights for the design and fabrication of efficient and high-performance nano-lasers.
The impact of entrepreneurial education, mindset, and creativity on entrepreneurial intention: mediating role of entrepreneurial self-efficacy of students in Indonesia

Entrepreneurship is the process of identifying opportunities, taking risks, and creating and managing business ventures. With the continued development of business in Indonesia, it will encourage economic growth in Indonesia and is expected to reduce the number of unemployed. Therefore, it is very important for every educational institution to continue to encourage students to increase their interest in entrepreneurship. The purpose of this study was to determine the direct effect of entrepreneurship education, entrepreneurial mindset, and creativity on entrepreneurial intentions with an indirect role in entrepreneurial self-efficacy. This research study takes a quantitative approach, in which the data obtained from the survey is statistically evaluated using SmartPLS. Researchers took a sample of 105 samples from students throughout Indonesia who had participated in entrepreneurship learning or training as research objects using a purposive sampling method. The results of this study indicate that there is a positive and significant direct relationship between entrepreneurship education and entrepreneurial intention, entrepreneurial mindset and entrepreneurial intention, creativity and entrepreneurial intention, entrepreneurship education and entrepreneurial self- efficacy, entrepreneurial mindset and entrepreneurial self- efficacy, creativity and efficacy entrepreneurial self, as well as entrepreneurial selfefficacy and entrepreneurial intention. In addition, the results of the study show that entrepreneurial self-efficacy partially mediates the relationship between the variables of entrepreneurship education, entrepreneurial mindset, and creativity on entrepreneurial intentions.
The Role of a Green Economy in Revitalising Shrinking Cities: Comparative Case Studies in France and Mexico

Abstract This paper aims to research different strategies for developing the green economy in shrinking cities. Considering urban shrinkage and the green economy as two extended concepts, a French town in post-Fordist transition and a Mexican post-mining town are selected as the most diverse/similar systems to indicate different strategies for sustainable development in shrinking cities. Embedded into different national backgrounds, including urban dynamics and support schemes for the green economy, the selected cases share the objectives of greening and regrowing strategies relying on other sectors of the green economy. The methodology applied is qualitative, including fieldwork, semi-structured interview techniques, carried out in person or remotely, and questionnaires. Findings show some positive results regarding sustainability and ecological transition in the French case, while regrowth trends were reached in the Mexican case. However, the analysis leads to uncertain scenarios for positive long-term impacts, especially due to uncertainty around future supporting policies for territorial cohesion and sustainability at national and regional levels.
Suitability of Watershed Models to Predict Distributed Hydrologic Response in the Awramba Watershed in Lake Tana Basin

Planning effective landscape interventions is an important tool to fight against land degradation and requires knowledge on spatial distribution of runoff. The objective of this paper was to test models that predict temporal and spatial distribution of runoff. The selected models were parameter‐efficient semi‐distributed watershed model (PED‐WM), Hydrologiska Byrans Vattenbalansavdelning integrated hydrological modeling system (HBV‐IHMS), and Soil and Water Assessment Tool (SWAT). We choose 7‐km2 Awramba watershed in the Lake Tana basin with detailed hydrological information for testing these models. Discharge at the outlet, rainfall, and distributed information on infiltration rates, water table, and extent of the saturated area were collected from 2013 to 2015. The maximum saturated area was 6·5% of the watershed. Infiltration rates exceeded rainfall intensities 91% of the time. Hence, saturation excess runoff was the main runoff mechanism. Models were calibrated for the rainy seasons in 2013 and 2014 and validated for 2015. For daily flow validation, the PED‐WM model (Nash–Sutcliff efficiency, NSE = 0·61) outperformed HBV‐IHMS (NSE = 0·51) and SWAT (NSE = 0·48). Performance on monthly time step was similar. Difference in model behavior depended on runoff mechanism. In PED‐WM, saturation excess is the main direct runoff process and could predict the maximum extent of the saturated area closely at 6·9%. HBV‐IHMS model runoff simulation depended on soil moisture status and evapotranspiration, and hence was able to simulate saturation excess flow but not the extent of the saturated area. SWAT, where infiltration excess is the main runoff mechanism, could only predict the monthly discharges well. This study shows that prevailing runoff mechanisms and distribution of runoff source areas should be used for proper model selection. Copyright © 2016 John Wiley & Sons, Ltd.
Intricacies of the Multifaceted Triad-Complexity, Accuracy, and Fluency: A Review of Studies on Measures of Oral Production

Complexity, accuracy, and fluency (CAF) as measures of language proficiency have been used extensively in assessing second language production in English language studies related to task-based language teaching. The present review adds the following critical elements to the existing body of literature: (i) Provides synthesis and critical analysis of various measures of CAF used in empirical studies and reveals the variation with which the three constructs have been used; (ii) Lays down the most appropriate CAF measures for beginners, intermediates and advanced learners for a valid and robust assessment of oral production in English as a second and foreign language.
Duration as a contrast enhancer in a Northern German dialect

This study investigates durational differences of the fricatives /ç/ and / ∫ / in three minimal pairs, elicited in isolation and in carrier phrases, in German. Data was collected from five groups of speakers in Berlin and – as a contrast - from a group of high school students in a northern German small town. Both, Berlin and the small town near Hamburg belong to the lower German dialect area, however, speakers from these two areas differ with regard to the acoustic realization of these two fricatives. Berlin speakers in general have a stronger tendency to merge [ç] and [ ∫ ] to various degrees while speakers from the north keep these two sounds quite separate on various acoustic dimensions. In this study, we are investigating the duration of these two contrasting fricatives in these two German varieties. Berlin speakers across five different speaker groups show similar durational patterns in the carrier phrase condition while the northern speakers have a greater durational difference, showing that the contrast is also preserved in [ ∫ ] being longer than [ç] when normalized for word duration. We attribute the durational differences between the Berlin speakers and the northern German speakers as a prosodic guise of contrast enhancement between these two fricatives.
The Eastern Ghats Belt, India, in the context of supercontinent assembly

Abstract The Eastern Ghats Belt (India) bears testimony to the assembly and dispersal of both the Columbia and Rodinia supercontinents, and possibly the formation of East Gondwana. The belt itself is a collage of different lithotectonic and isotopic domains, and therefore the petrological evolution of each domain is to be considered separately prior to the formation of the belt. In this paper, we present an updated review on the petrological and tectonic evolution of the different domains along with geochronological constraints. We develop tectonic models to show how different lithotectonic domains fit into supercontinent cycles in the Proterozoic period.
The Loss of Territorial Efficiency: An Ecological Analysis of Land-Use Changes in Western Mediterranean Agriculture (Vallès County, Catalonia, 1853-2004)

scale experiments that could be used more often than they actually are to develop the foundations of a disturbance ecology. [. ] Man becomes very powerful by using external energy to move materials, especially along the horizontal plane. Horizontal transport destroys the mosaic of patches that could each have its own independent development. [. ] Man creates systems to control and amplify fl ows of external energy that become more and more O The Loss of Landscape Efficiency: An Ecological Analysis of Land-Use Changes in Western Mediterranean Agriculture (Valles County, Catalonia, 1853-2004)*
Mediating Role of Employee Engagement in the Relationship between Perceived Supervisor Support and Job Satisfaction

The objective of this study is to see how perceived supervisor supports influence job satisfaction by investigating the mediating result of employee engagement. The study was conducted on 100 faculty members working at different management institutions situated in Delhi NCR. Partial Least Square-Structural Equation Modeling (PLS-SEM) and Mediation model proposed by Hayes (2008) were utilized to scrutinize the collected information. SOBEL test was assessed to investigate the mediating relationship. The analysis divulges positive relation subsists between both perceived supervisor support and job satisfaction. Further, the results designate that perceived supervisor support has a high positive significant association with employee engagement that is also significantly positively related to job satisfaction. Additionally, employee engagement plays a mediating role between perceived supervisor support and job satisfaction. An inference of this research helps institution's management to check supervisory support to engage their faculty members and fulfilling their overall job satisfaction.
Molecular Disambiguation of Heart Rate Control by the Nucleus Ambiguus

The nucleus ambiguus (nAmb) provides parasympathetic control of cardiorespiratory functions as well as motor control of the upper airways and striated esophagus. A subset of nAmb neurons innervates the heart through the vagus nerve to control cardiac function at rest and during key autonomic reflexes such as the mammalian diving reflex. These cardiovagal nAmb neurons may be molecularly and anatomically distinct, but how they differ from other nAmb neurons in the adult brain remains unclear. We therefore classified adult mouse nAmb neurons based on their genome-wide expression profiles, innervation of cardiac ganglia, and ability to control HR. Our integrated analysis of single-nucleus RNA-sequencing data predicted multiple molecular subtypes of nAmb neurons. Mapping the axon projections of one nAmb neuron subtype, Npy2r-expressing nAmb neurons, showed that they innervate cardiac ganglia. Optogenetically stimulating all nAmb vagal efferent neurons dramatically slowed HR to a similar extent as selectively stimulating Npy2r+ nAmb neurons, but not other subtypes of nAmb neurons. Finally, we trained mice to perform voluntary underwater diving, which we use to show Npy2r+ nAmb neurons are activated by the diving response, consistent with a cardiovagal function for this nAmb subtype. These results together reveal the molecular organization of nAmb neurons and its control of heart rate.
VPS13B is localized at the cis-trans Golgi complex interface and is a functional partner of FAM177A1

Mutations in VPS13B, a member of a protein family implicated in bulk lipid transport between adjacent membranes, cause Cohen syndrome. VPS13B is known to be concentrated in the Golgi complex, but its precise location within this organelle and thus the site(s) where it achieves lipid transport remains unclear. Here we show that VPS13B is localized at the interface between cis and trans Golgi sub-compartments and that Golgi complex re-formation after Brefeldin A (BFA) induced disruption is delayed in VPS13B KO cells. This delay is phenocopied by loss of FAM177A1, a Golgi complex protein of unknown function reported to be a VPS13B interactor and whose mutations also result in a developmental disorder. In zebrafish, the vps13b orthologue, not previously annotated in this organism, genetically interacts with fam177a1. Collectively, these findings raise the possibility that bulk lipid transport by VPS13B may play a role in expanding Golgi membranes and that VPS13B may be assisted in this function by FAM177A1.
Active membrane deformations of a minimal synthetic cell

Biological cells exhibit the remarkable ability to adapt their shape in response to their environment, a phenomenon that hinges on the intricate interplay between their deformable membrane and the underlying activity of their cytoskeleton. Yet, the precise physical mechanisms of this coupling remain mostly elusive. Here, we introduce a synthetic cell model, comprised of an active cytoskeletal network of microtubules, crosslinkers and molecular motors encapsulated inside giant vesicles. Remarkably, these active vesicles exhibit large shape fluctuations and life-like morphing abilities. Active forces from the encapsulated cytoskeleton give rise to large-scale traveling membrane deformations. Quantitative analysis of membrane and microtubule fluctuations shows how the intricate coupling of confinement, membrane material properties and cytoskeletal forces yields fluctuation spectra whose characteristic scales in space and time are distinctly different from passive vesicles. We demonstrate how activity leads to uneven probability fluxes between fluctuation modes and hence sets the temporal scale of membrane fluctuations. Using simulations and theoretical modelling, we extend the classical approach to membrane fluctuations to active cytoskeleton-driven vesicles, highlighting the effect of correlated activity on the dynamics of membrane deformations and paving the way for quantitative descriptions of the shape-morphing ability typical of living systems.
EFEMP1 contributes to light-dependent ocular growth in zebrafish

Myopia (short-sightedness) is the most common ocular disorder. It generally develops after over-exposure to aberrant visual environments, disrupting emmetropization mechanisms that should match eye growth with optical power. A pre-screening of strongly associated myopia-risk genes identified through human genome-wide association studies implicates efemp1 in myopia development, but how this gene impacts ocular growth remains unclear. Here, we modify efemp1 expression specifically in the retina of zebrafish. We found that under normal lighting, efemp1 mutants developed axial myopia, enlarged eyes, reduced spatial vision and altered retinal function. However, under myopia-inducing dark-rearing, compared to control fish, mutants remained emmetropic and showed changes in retinal function. Efemp1 modification changed the expression of efemp1, egr1, tgfb1a, vegfab and rbp3 genes in the eye, and changes the inner retinal distributions of myopia-associated EFEMP1, TIMP2 and MMP2 proteins. Efemp1 modification also impacted dark-rearing-induced responses of vegfab and wnt2b genes and above-mentioned myopia-associated proteins. Together, we provided robust evidence that light-dependent ocular growth is regulated by efemp1. Summary This study shows that retina-specific modification of efemp1 expression in zebrafish results in myopic eye, and impacts responses to myopia-inducing dark-rearing in eye growth, retinal function, and myopia-associated molecular expression and distribution, implicating light-dependent regulation of efemp1 in ocular development.