julilili42/papers huggingface dataset:
Witnessing nonclassicality through large deviations in quantum optics
2020-04-27

Nonclassical correlations in quantum optics as resources for quantum computation are important in the quest for highly specialized quantum devices. Here, we put forward a methodology to witness nonclassicality of the output field from a generic quantum optical setup via the statistics of time-integrated photocurrents. Specifically, exploiting the thermodynamics of quantum trajectories, we express a known nonclassicality witness for bosonic fields fully in terms of the source master equation, thus bypassing the explicit calculation of the output light state.
Observing inter-professional videos: impact of collaboration between physicians and psychologists on attitude and knowledge acquisition
2020-04-27

Abstract Background Inter-professional collaboration (IPC) is an important prerequisite for successful patient care. Even though inter-professional education (IPE) is increasingly common in undergraduate medical education, few IPE approaches explicitly address the IPC among medical students and students of psychology. IPE videos can be used to give learners the opportunity to gather relevant knowledge from different professional perspectives. So far it has been unclear whether it is enough when the topic of the video itself is inter-professional or if it is necessary for experts from different professions explicitly to appear in the video. Methods In an online experiment, medical students watched one of two videos about Parkinson’s disease (PD) and the care of PD patients. The information was either provided by protagonists from only one profession (i.e., physicians; mono-professional condition) or provided by protagonists from two different professions (i.e., physicians and a psychologist; inter-professional condition). Attitude toward inter-professional interaction and learning, evaluation of the entertaining and illustrative character of the video, attitude toward physicians and psychologists, importance of IPC, evaluation of psychological treatment support, and knowledge acquisition served as dependent variables. Results The analysis was based on 140 participants (74 in the mono-, 66 in the inter-professional condition). We found that the inter-professional video was perceived to be more entertaining than the mono-professional video (t (138) = -2.227; p = 0.028; d = 0.38). The inter-professional video was also considered to be more illustrative (t (138) = -6.269; p &lt; 0.001; d = 1.06). Moreover, participants improved their attitude toward physicians by watching the video ( F (1, 138) = 4.860, p &lt; 0.001, η 2 p = 0.11), but they did not change their attitude toward psychologists ( p = 0.146). Participants who watched the inter-professional video considered IPC to be more important than participants who watched the mono-professional video (t (138) = -7.954; p &lt; 0.001; d = 1.354). Finally, the inter-professional video led to better performance in the knowledge test (t (138) = -2.285; p = 0.024; d = 0.04). Conclusions Inter-professional videos showing explicitly the appearance of experts from different professions come along with several advantages. We discuss the implications of their application in educational practice. Trial registration The study was pre-registered on the pre-registration platform AsPredicted (aspredicted.org) before we began data collection (registration number: #33143).
Polycationic gold nanorods as multipurposein vitromicrotubule markers
2020-04-27

Abstract Gold nanoparticles are intriguing because of their unique size- and shape-dependent chemical, electronic and optical properties. Various microscopy and biomedical applications are based on the particles’ biocompatibility, surface functionalizability, light absorption, and plasmon resonances. Gold nanorods (AuNRs) are particularly promising for various sensor applications due to their tip-enhanced plasmonic fields. For biomolecule attachment, AuNRs are often stabilized with amphiphilic molecules and functionalized with antibodies or biotin-binding proteins. However, by their intrinsic size such molecules block the most sensitive near-field region of the AuNRs. Here, we used short cationic thiols to covalently functionalize the gold surface. We show that the functionalization layer is thin and that these polycationic AuNRs bind in vitro to negatively charged microtubule filaments. Furthermore, we can plasmonically stimulate light emission from the AuNRs and, therefore, use them as bleach- and blinkfree microtubule markers. We confirmed colocalization by transmission electron microscopy or the combination of interference reflection and single-molecule fluorescence microscopy of fluorescently-labeled or plasmonic photoluminescent versions of the AuNRs. We expect that polycationic AuNRs may be applicable to in vivo systems and other negatively charged molecules like DNA. In the long-term, microtubule-bound AuNRs can be used as ultrasensitive single-molecule sensors for molecular machines that interact with microtubules.
NAMPT/SIRT2–mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells
2020-04-27

Abstract Background: Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins (SIRTs). SIRTs regulate functions of histones and none-histone proteins. The role of NAMPT/SIRTs pathway in the regulation of maintenance and differentiation of human induced pluripotent stem (iPS) cells is not fully elucidated. Methods: We evaluated the effects of specific inhibitors of NAMPT-, or SIRT2 on the pluripotency, proliferation, survival and hematopoietic differentiation of human iPS cells. We also studied the molecular mechanism downstream of NAMPT/SIRTs in iPS cells. Results: We demonstrated that NAMPT is indispensable for the maintenance, survival and hematopoietic differentiation of induced pluripotent stem (iPS) cells. We found that inhibition of NAMPT or SIRT2 in iPS cells induces p53 protein by promoting its lysine acetylation. This leads to activation of the p53 target, p21, with subsequent cell cycle arrest and induction of apoptosis in iPS cells. NAMPT and SIRT2 inhibition also affects hematopoietic differentiation of iPS cells in an embryoid body (EB)-based cell culture system. Conclusions: Our data demonstrate the essential role of the NAMPT/SIRT2/p53/p21 signaling axis in the maintenance and hematopoietic differentiation of iPS cells.
Immune Landscape in Burkitt Lymphoma reveals M2-macrophage polarization and Correlation between PD-L1 expression and Non-Canonical EBV latency program
2020-04-27

Abstract BACKGROUND : The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. METHODS : In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis. RESULTS : Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway. CONCLUSION : In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.
Degradation, Bone Regeneration and Tissue Response of an Innovative Volume Stable Magnesium-Supported GBR/GTR Barrier Membrane
2020-04-28

Introduction: Bioresorbable collagenous barrier membranes are used to prevent premature soft tissue ingrowth and to allow bone regeneration. For volume stable indications, only non-absorbable synthetic materials are available. This study investigates a new bioresorbable hydrofluoric acid (HF)-treated magnesium (Mg) mesh in a native collagen membrane for volume stable situations. Materials and Methods: HF-treated and untreated Mg were compared in direct and indirect cytocompatibility assays. In vivo, 18 New Zealand White Rabbits received each four 8 mm calvarial defects and were divided into four groups: (a) HF-treated Mg mesh/collagen membrane, (b) untreated Mg mesh/collagen membrane (c) collagen membrane and (d) sham operation. After 6, 12 and 18 weeks, Mg degradation and bone regeneration was measured using radiological and histological methods. Results: In vitro, HF-treated Mg showed higher cytocompatibility. Histopathologically, HF-Mg prevented gas cavities and was degraded by mononuclear cells via phagocytosis up to 12 weeks. Untreated Mg showed partially significant more gas cavities and a fibrous tissue reaction. Bone regeneration was not significantly different between all groups. Discussion and Conclusions: HF-Mg meshes embedded in native collagen membranes represent a volume stable and biocompatible alternative to the non-absorbable synthetic materials. HF-Mg shows less corrosion and is degraded by phagocytosis. However, the application of membranes did not result in higher bone regeneration.
Effect of Caloric Restriction on the in vivo Functional Properties of Aging Microglia
2020-04-28

Throughout the lifespan, microglia, the primary innate immune cells of the brain, fulfill a plethora of homeostatic as well as active immune defense functions, and their aging-induced dysfunctionality is now considered as a key trigger of aging-related brain disorders. Recent evidence suggests that both organism's sex and age critically impact the functional state of microglia but <i>in vivo</i> determinants of such state(s) remain unclear. Therefore, we analyzed <i>in vivo</i> the sex-specific functional states of microglia in young adult, middle aged and old wild type mice by means of multicolor two-photon imaging, using the microglial Ca<sup>2 +</sup> signaling and directed process motility as main readouts. Our data revealed the sex-specific differences in microglial Ca<sup>2 +</sup> signaling at all ages tested, beginning with young adults. Furthermore, for both sexes it showed that during the lifespan the functional state of microglia changes at least twice. Already at middle age the cells are found in the reactive or immune alerted state, characterized by heightened Ca<sup>2 +</sup> signaling but normal process motility whereas old mice harbor senescent microglia with decreased Ca<sup>2 +</sup> signaling, and faster but disorganized directed movement of microglial processes. The 6-12 months long caloric restriction (70% of <i>ad libitum</i> food intake) counteracted these aging-induced changes shifting many but not all functional properties of microglia toward a younger phenotype. The improvement of Ca<sup>2 +</sup> signaling was more pronounced in males. Importantly, even short-term (6-week-long) caloric restriction beginning at old age strongly improved microglial process motility and induced a significant albeit weaker improvement of microglial Ca<sup>2 +</sup> signaling. Together, these data provide first sex-specific <i>in vivo</i> characterization of functional properties of microglia along the lifespan and identify caloric restriction as a potent, cost-effective, and clinically relevant tool for rejuvenation of microglia.
Highest reported visual acuity after electronic retinal implantation
2020-04-28

Abstract Purpose To report the highest attained visual acuity with an electronic retinal implant for the treatment of advanced retinal degeneration following a novel intensive period of visual training. Methods A case study as part of the prospective, international, multi‐centre, interventional clinical trial (ClinicalTrials.gov NCT02720640 and NCT01024803) of patients with the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for advanced retinal degeneration. A patient with subretinal device implanted into worse‐seeing eye with no useful perception of light vision secondary to USH2A retinal degeneration underwent intensive period of visual training. Results The device remains functional with no safety concerns at 3 years postsurgical implantation, and following visual training, the patient achieved the highest visual acuity so far with an electronic retinal device, with real, digitally unenhanced, reading vision of 0.04 decimal (equivalent to 1.39 LogMAR and 20/500 or 6/150 Snellen). In addition, perception as well as partial identification of obstacles and evaluation of distances was possible in both daylight and night‐time settings. Conclusions Retinal implants are currently the only available therapy option for advanced retinal degeneration. Visual rehabilitation postimplantation has potential to maximize visual percepts. The novel concept of intensive visual training presented herein shows what is achievable with electronic retinal implants and has implications for other therapeutic options, such as optogenetics, that aim to stimulate remaining inner retinal cells in advanced retinal degeneration.
Recent advances in influenza vaccines
2020-04-28

<ns4:p>Seasonal influenza remains a major public health problem, responsible for hundreds of thousands of deaths every year, mostly of elderly people. Despite the wide availability of vaccines, there are multiple problems decreasing the effectiveness of vaccination programs. These include viral variability and hence the requirement to match strains by estimating which will become prevalent each season, problems associated with vaccine and adjuvant production, and the route of administration as well as the perceived lower vaccine efficiency in older adults. Clinical protection is still suboptimal for all of these reasons, and vaccine uptake remains too low in most countries. Efforts to improve the effectiveness of influenza vaccines include developing universal vaccines independent of the circulating strains in any particular season and stimulating cellular as well as humoral responses, especially in the elderly. This commentary assesses progress over the last 3 years towards achieving these aims. Since the beginning of 2020, an unprecedented international academic and industrial effort to develop effective vaccines against the new coronavirus SARS-CoV-2 has diverted attention away from influenza, but many of the lessons learned for the one will synergize with the other to mutual advantage. And, unlike the SARS-1 epidemic and, we hope, the SARS-CoV-2 pandemic, influenza will not be eliminated and thus efforts to improve influenza vaccines will remain of crucial importance.</ns4:p>
Development of directed and random exploration in children
2020-04-28

Are young children just random explorers who learn serendipitously? Or are even young children guided by uncertainty-directed sampling, seeking to explore in a systematic fashion? We study how children between the ages of 4 and 9 search in an explore-exploit task with spatially-correlated rewards, where exhaustive exploration is infeasible and not all options can be experienced. By combining behavioral data with a computational model that decomposes search into similarity-based generalization, uncertainty-directed exploration, and random exploration, we map out developmental trajectories of generalization and exploration. The behavioral data show strong developmental differences in children’s capability to exploit environmental structure, with performance and adaptiveness of sampling decisions increasing with age. Through model-based analyses, we disentangle different forms of exploration, finding signatures of both uncertainty-directed and random exploration. The amount of random exploration strongly decreases as children get older, supporting the notion of a developmental “cooling off” process that modulates the randomness in sampling. However, even at the youngest age range, children do not solely rely on random exploration. Even as random exploration begins to taper off, children are actively seeking out options with high uncertainty in a goal-directed fashion, and using inductive inferences to generalize their experience to novel options. Our findings provide critical insights into the behavioral and computational principles underlying the developmental trajectory of learning and exploration.
Normative Observational Nerve Ultrasound Values in School-Age Children and Adolescents and Their Application to Hereditary Neuropathies
2020-04-28

<b>Backgrounds:</b> We have aimed to establish nerve ultrasound reference data in 8 to 17-year-old children and adolescents and to compare those data to younger children, adults, and age-matched children with polyneuropathies. <b>Methods:</b> High-resolution ultrasounds of the nerves were performed in 117 healthy children and adolescents at 20 predefined landmarks in the neck and the extremities of both sides. Mean values, side-to-side differences and intraneural ratios, as well as upper limits have been calculated. In a second step, a comparison between 25 children and adolescents of the same age range with proven hereditary and acquired neuropathies and lysosomal storage diseases has been carried out. <b>Results:</b> Nerve growth correlates significantly with age and reaches adult values at the age of around 15 years. The influence of body mass index and gender is negligible at most segments. By the use of age-specific upper limits, nerve enlargement could be seen in distinct types of neuropathies, particularly in demyelinating hereditary and inflammatory types, which is comparable to findings in adults, but also in rare lysosomal storage diseases. <b>Conclusion:</b> Nerve size correlates with age during childhood and reaches a climax in younger adults. Age-matched reference data are inevitable to differ between hypertrophic and non-hypertrophic nerve damage, e.g., in neuropathies.
Do single-sex schools help Australians major in STEMM at university?
2020-04-28

Single-sex schooling is believed to benefit students’ academic&#13;\\nachievement and girls’ engagement in science, technology,&#13;\\nengineering, mathematics, and medicine (STEMM). The latter is&#13;\\nassumed because single-sex environments are meant to neutralise&#13;\\ngender stereotypes. Little is known, however, about longer term&#13;\\neffects of such schooling. Therefore, we consider whether&#13;\\ngraduating from a single-sex school increases the uptake of&#13;\\nuniversity majors in physical or life sciences. Using data from the&#13;\\n2003 cohort of the Longitudinal Survey of Australian Youth and&#13;\\nmultinomial logistic regressions, we find that girls who graduated&#13;\\nfrom single-sex schools did not major in physical sciences at&#13;\\nuniversity at rates higher than their peers from coeducational&#13;\\nschools. Likewise, there are no differences in the take up of life&#13;\\nscience majors, irrespective of gender or type of school. By&#13;\\ncontrast, fewer boys who graduated from single-sex schools went&#13;\\non to study physical sciences at university. We discuss the&#13;\\nimplications of these findings.
Are Pathogenic Germline Variants in Metastatic Melanoma Associated with Resistance to Combined Immunotherapy?
2020-04-28

Background: Combined immunotherapy has significantly improved survival of patients with advanced melanoma, but there are still patients that do not benefit from it. Early biomarkers that indicate potential resistance would be highly relevant for these patients. Methods: We comprehensively analyzed tumor and blood samples from patients with advanced melanoma, treated with combined immunotherapy and performed descriptive and survival analysis. Results: Fifty-nine patients with a median follow-up of 13 months (inter quartile range (IQR) 11–15) were included. Interestingly, nine patients were found to have pathogenic or likely pathogenic (P/LP) germline variants in one of these genes: BRCA2, POLE, WRN, FANCI, CDKN2A, BAP1, PALB2 and RAD54B. Most of them are involved in DNA repair mechanisms. Patients with P/LP germline variants had a significantly shorter progression-free survival (PFS) and melanoma specific survival (MSS) compared to patients without P/LP germline variants (HR = 2.16; 95% CI: 1.01–4.64; p = 0.048 and HR = 3.21; 95% CI: 1.31–7.87; p = 0.011, respectively). None of the patients with a P/LP germline variant responded to combined immunotherapy. In the multivariate Cox-regression analysis, presence of a P/LP germline variant, S100B and lactate dehydrogenase (LDH) remained independently significant factors for MSS (p = 0.036; p = 0.044 and p = 0.001, respectively). Conclusions: The presence of P/LP germline variants was associated with resistance to combined immunotherapy in our cohort. As genes involved in DNA repair mechanisms are also involved in lymphocyte development and T-cell differentiation, a P/LP germline variant in these genes may preclude an antitumor immune response.
Uncovering the Late Pleistocene LSA of Mpumalanga Province, South Africa: Early Results from Iron Pig Rock Shelter
2020-04-28

Abstract South Africa is one of the best-studied regions in terms of Stone Age research in the last few decades. Considerable progress has been made, especially for the Middle Stone Age ( MSA ). Recently the late Pleistocene Later Stone Age ( LSA ) has come back into focus. However, there are still large understudied areas such as northeastern South Africa. Here we present the first data from an archaeological site containing late Pleistocene occupations associated with the Robberg techno-complex in this region. Iron Pig rock shelter provides a well-dated sequence spanning from &gt;16000 cal BP to &lt;9000 cal BP. A lithic analysis of the Robberg occupations of the lowermost layers 5 and 6 provided here implies gradual temporal shifts in technology indicating short-term changing traditions. A comparative review of other LSA sites in the wider region suggests considerable research gaps and the necessity of intensified work in this area.
ONX 0914 Lacks Selectivity for the Cardiac Immunoproteasome in CoxsackievirusB3 Myocarditis of NMRI Mice and Promotes Virus-Mediated Tissue Damage
2020-04-28

Inhibition of proteasome function by small molecules is highly efficacious in cancer treatment. Other than non-selective proteasome inhibitors, immunoproteasome-specific inhibitors allow for specific targeting of the proteasome in immune cells and the profound anti-inflammatory potential of such compounds revealed implications for inflammatory scenarios. For pathogen-triggered inflammation, however, the efficacy of immunoproteasome inhibitors is controversial. In this study, we investigated how ONX 0914, an immunoproteasome-selective inhibitor, influences CoxsackievirusB3 infection in NMRI mice, resulting in the development of acute and chronic myocarditis, which is accompanied by formation of the immunoproteasome in heart tissue. In groups in which ONX 0914 treatment was initiated once viral cytotoxicity had emerged in the heart, ONX 0914 had no anti-inflammatory effect in the acute or chronic stages. ONX 0914 treatment initiated prior to infection, however, increased viral cytotoxicity in cardiomyocytes, promoting infiltration of myeloid immune cells into the heart. At this stage, ONX 0914 completely inhibited the β5 subunit of the standard cardiac proteasome and less efficiently blocked its immunoproteasome counterpart LMP7. In conclusion, ONX 0914 unselectively perturbs cardiac proteasome function in viral myocarditis of NMRI mice, reduces the capacity of the host to control the viral burden and promotes cardiac inflammation.