Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-time Cosmology with High Precision Spectroscopy and Astrometry

Breakthroughs in physics and astrophysics are often driven by technological advances, with the recent detection of gravitational waves being one such example. This white paper focuses upon how improved astrometric and spectroscopic measurements from a new generation of precise, accurate, and stable astronomical instrumentation can address two of the fundamental mysteries of our time -- dark energy and dark matter -- and probe the nature of spacetime. Instrumentation is now on the cusp of enabling new cosmological measurements based on redshifts (cosmic redshift drift) and extremely precise time-series measurements of accelerations, astrophysical source positions (astrometry), and angles (cosmic parallax). These allow tests of the fundamental framework of the universe (the Friedmann equations of general relativity and whether cosmic expansion is physically accelerating) and its contents (dark energy evolution and dark matter behavior), while also anchoring the cosmic distance scale ($H_0$).
Waiting times in Orwell and ATMR

The Orwell and ATMR basic access mechanisms are modelled in this paper. The full slots are either released or reused by the destination station. The traffic matrix is fully symmetric, and a station may send to itself, as well. The new approximate analytic model is based on a random polling model with the Markovian server routing. Its accuracy is proved by comparing to the simulations results.
The state of the Lieb--Thirring conjecture

Estimates on the bound states of a Hamiltonian are of importance in quantum mechanics. For a Schrödinger operator −∆ + V on L(R) with decaying potential V : R → R of particular interest are bounds on power series ∑ j≥1 |Ej |γ of the negative eigenvalues E1 ≤ E2 ≤ · · · < 0. Illuminating heuristics can be obtained by recalling the semiclassical approach, which dates back to the early days of quantum mechanics. Each volume (2π) in 2d-dimensional phase space is assumed to support one quantum state. Identifying the Hamiltonian with the classical Hamilton function p + V (x) one can thus hope to approximate ∑ j≥1 |Ej| by ∑
Vecchia Likelihood Approximation for Accurate and Fast Inference in Intractable Spatial Extremes Models

Max-stable processes are the most popular models for high-impact spatial extreme events, as they arise as the only possible limits of spatially-indexed block maxima. However, likelihood inference for such models suffers severely from the curse of dimensionality, since the likelihood function involves a combinatorially exploding number of terms. In this paper, we propose using the Vecchia approximation, which conveniently decomposes the full joint density into a linear number of low-dimensional conditional density terms based on well-chosen conditioning sets designed to improve and accelerate inference in high dimensions. Theoretical asymptotic relative efficiencies in the Gaussian setting and simulation experiments in the max-stable setting show significant efficiency gains and computational savings using the Vecchia likelihood approximation method compared to traditional composite likelihoods. Our application to extreme sea surface temperature data at more than a thousand sites across the entire Red Sea further demonstrates the superiority of the Vecchia likelihood approximation for fitting complex models with intractable likelihoods, delivering significantly better results than traditional composite likelihoods, and accurately capturing the extremal dependence structure at lower computational cost.
Long-term collaboration with strong friendship ties improves academic performance in remote and hybrid teaching modalities in high school physics

Collaboration among students is fundamental for knowledge building and competency development. Nonetheless, the effectiveness of student collaboration depends on the extent that these interactions take place under conditions that favor commitment, trust, and decision making among those who interact. The worldwide pandemic due to COVID-19 and the transition to emergency remote teaching have added new challenges for collaboration, mainly because now students? interactions are wholly mediated by information and communication technologies. This study first explores the effectiveness of different collaborative relationships over performance in physics from a sample of secondary students from two schools located in rural and urban areas in southern Chile (exploratory study). We used social network analysis to map academic hierarchies as in the nominations for proficient peers in physics (i.e., physics prestige), collaboration, and friendship ties. We define a strong association if two students who collaborate shared a friendship tie. Using ordinary least squares multiple linear regression models on physics grades, we found positive effects of collaboration over grades, particularly among students working with friends (strong ties). To test whether the effects of collaboration found in the first study were stable throughout two semesters, the following year we designed a quasiexperiment in four classes from the same urban school in the exploratory study. Here, students attended hybrid school sessions where research participants were either in the classroom or participated remotely. The teacher collected the same social networks described in the first study at the end of semester 1, and two times during semester 2. In addition, we followed the same procedures to identify strong and weak collaboration from the network data on each wave of data collection. After fitting ordinary least squares multiple linear regression models, we found that collaborative variables negatively associated with grades on activity 1 (semester 1), yet at the end of the year (activity 3 in semester 2) having strong working ties became positively associated with physics grades. Interestingly, the relationship of academic hierarchies measured in physics prestige with grades transitions from positive on semester 1 to null by the end of the year. These results contribute to the literature of collaboration in physics education and its effectiveness, by taking into account social relationships and the needed time for developing beneficial collective processes among students in the classroom. We discuss these results and their implications for instructional design and guidelines for constructive group-level processes.
Algebraic canonical quantization of lumped superconducting networks

We present a systematic canonical quantization procedure for lumped-element superconducting networks by using a redundant conﬁguration-space description. The algorithm is based on an original, explicit, and constructive implementation of the symplectic diagonalization of positive semideﬁnite Hamiltonian matrices, a particular instance of Williamson’s theorem [1]. With it, we derive canonically quantized discrete-variable descriptions of passive causal systems. We exemplify the algorithm with representative singular electrical networks, a nonreciprocal extension for the black-box quantization method, as well as an archetypal Landau quantization problem.
Artificial Intelligence Solution for Effective Treatment Planning for Glioblastoma Patients

Glioblastomas are the most common malignant brain tumors in adults. Approximately 200000 people die each year from Glioblastoma in the world. Glioblastoma patients have a median survival of 12 months with optimal therapy and about 4 months without treatment. Glioblastomas appear as heterogeneous necrotic masses with irregular peripheral enhancement, surrounded by vasogenic edema. The current standard of care includes surgical resection, radiotherapy and chemotherapy, which require accurate segmentation of brain tumor subregions. For effective treatment planning, it is vital to identify the methylation status of the promoter of Methylguanine Methyltransferase (MGMT), a positive prognostic factor for chemotherapy. However, current methods for brain tumor segmentation are tedious, subjective and not scalable, and current techniques to determine the methylation status of MGMT promoter involve surgically invasive procedures, which are expensive and time consuming. Hence there is a pressing need to develop automated tools to segment brain tumors and non-invasive methods to predict methylation status of MGMT promoter, to facilitate better treatment planning and improve survival rate. I created an integrated diagnostics solution powered by Artificial Intelligence to automatically segment brain tumor subregions and predict MGMT promoter methylation status, using brain MRI scans. My AI solution is proven on large datasets with performance exceeding current standards and field tested with data from teaching files of local neuroradiologists. With my solution, physicians can submit brain MRI images, and get segmentation and methylation predictions in minutes, and guide brain tumor patients with effective treatment planning and ultimately improve survival time.
Diversity among health care leaders in Canada: a cross-sectional study of perceived gender and race

Background: Diverse health care leadership teams may improve health care experiences and outcomes for patients. We sought to explore the race and gender of hospital and health ministry executives in Canada and compare their diversity with that of the populations they serve. Methods: This cross-sectional study included leaders of Canada’s largest hospitals and all provincial and territorial health ministries. We included individuals listed on institutional websites as part of the leadership team if a name and photo were available. Six reviewers coded and analyzed the perceived race and gender of leaders, in duplicate. We compared the proportion of racialized health care leaders with the race demographics of the general population from the 2016 Canadian Census. Results: We included 3056 leaders from 135 institutions, with reviewer concordance on gender for 3022 leaders and on race for 2946 leaders. Reviewers perceived 37 (47.4%) of 78 health ministry leaders as women, and fewer than 5 (< 7%) of 80 as racialized. In Alberta, Saskatchewan, Prince Edward Island and Nova Scotia, provinces with a centralized hospital executive team, reviewers coded 36 (50.0%) of 72 leaders as women and 5 (7.1%) of 70 as racialized. In British Columbia, New Brunswick and Newfoundland and Labrador, provinces with hospital leadership by region, reviewers perceived 120 (56.1%) of 214 leaders as women and 24 (11.5%) of 209 as racialized. In Manitoba, Ontario and Quebec, where leadership teams exist at each hospital, reviewers perceived 1326 (49.9%) of 2658 leaders as women and 243 (9.2%) of 2633 as racialized. We calculated the representation gap between racialized executives and the racialized population as 14.5% for British Columbia, 27.5% for Manitoba, 20.7% for Ontario, 12.4% for Quebec, 7.6% for New Brunswick, 7.3% for Prince Edward Island and 11.6% for Newfoundland and Labrador. Interpretation: In a study of more than 3000 health care leaders in Canada, gender parity was present, but racialized executives were substantially under-represented. This work should prompt health care institutions to increase racial diversity in leadership.
Filopodia-mediated basement membrane assembly at pre-invasive tumor boundaries

Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer, where the tumor is encapsulated by a basement membrane (BM). At the invasive phase, the BM barrier is compromised enabling tumor cells to escape into the surrounding stroma. The molecular mechanisms that establish and maintain an epithelial BM barrier in vivo are poorly understood. Myosin-X (MYO10) is a filopodia-inducing motor protein implicated in metastasis and poor clinical outcome in patients with invasive breast cancer (IBC). We compared MYO10 expression in patient-matched normal breast tissue and DCIS lesions and found elevated MYO10 expression in DCIS samples, suggesting that MYO10 might facilitate the transition from DCIS to IBC. Indeed, MYO10 promoted the formation of filopodia and cell invasion in vitro and positively regulated the dissemination of individual cancer cells from IBC lesions in vivo. However, MYO10-depleted DCIS xenografts were, unexpectedly, more invasive. In these xenografts, MYO10 depletion compromised BM formation around the lesions resulting in poorly defined tumor borders and increased cancer cell dispersal into the surrounding stroma. Moreover, MYO10-depleted tumors showed increased EMT-marker-positive cells, specifically at the tumor periphery. We also observed cancer spheroids undergoing rotational motion and recruiting BM components in a filopodia-dependent manner to generate a near-continuous extracellular matrix boundary. Taken together, our data identify a protective role for MYO10 in early-stage breast cancer, where MYO10-dependent tumor cell protrusions support BM assembly at the tumor-stroma interface to limit cancer progression, and a pro-invasive role that facilitates cancer cell dissemination at later stages. Highlights - Filopodia sculpt the tumor-proximal stroma in pre-invasive ductal carcinoma in situ (DCIS). - Filopodia-dependent basement membrane (BM) assembly limits invasive transition of DCIS-like tumors in vivo. - Loss of MYO10-dependent filopodia impairs BM assembly and induces an EMT-like phenotype at the tumor-stroma interface in vivo. - MYO10 filopodia are anti-invasive in DCIS but facilitate dissemination in invasive breast cancer.
CCL28 modulates neutrophil responses during infection with mucosal pathogens

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here we show that CCL28 promotes neutrophil accumulation to the gut of mice infected with Salmonella and to the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency were different between the two infections, as Ccl28-/- mice were highly susceptible to Salmonella gut infection, but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes that were largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not of Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.
Self-learning algorithm for denoising and advancing the integration of scRNA-seq datasets improves the identification of resilient and susceptible retinal ganglion cell types

The clustering of single cell RNA-sequencing (scRNA-seq) data enables the classification of cell types, and the development of integration algorithms has enabled the tracing of altered-from-baseline transcriptomes to their respective cell type origins. Here, we developed an algorithm that removes sources of noise from scRNA-seq datasets and improves the accuracy of their integration. We found that this improvement of integration is further increased by an algorithm we developed for auto-determination of optimal weight-assignment to anchors. As a proof-of-concept, we show that our algorithm determined the type-origin of the 17% of injured retinal ganglion cells (RGCs) that an existing integration algorithm could not identify. As we found that the majority of the originally unassigned cells belonged to only several out of 45 RGC types, a consequent change in the proportions of the surviving types resulted in a moderately different ranking of resiliency to injury. This updated standard for RGC type resilience ranking improved the understanding of RGC type biology and the ranking-dependent prediction of genes for therapeutic neuroprotective targeting. Additional bioinformatic analyses revealed single-gene cluster-markers for RGC types and contributed new insights into the global characteristics of RGC types and how axonal injury affects them, showing how the extent of variance between transcriptomes of RGC types increases differentially during maturation and after injury. We also show, for the first time, that specific global properties of the transcriptome can predict the resilience to injury of certain cell types. Furthermore, we developed a website for cluster-by-cluster comparison of gene expression between uninjured and injured RGC types. The publicly available R library package, CellTools, for denoising and improving the integration of scRNA-seq datasets, as well as for associating cell types with the global properties of the transcriptome, will assist scRNA-seq studies of developing, injured, or diseased cell types across biological fields.
Genomic landscape of the DHA1 family in the newly emerged pathogen Candida auris and mapping substrate repertoire of the prominent member CauMdr1

The last decade has witnessed the rise of extremely threatening healthcare-associated multidrug resistant non-albicans Candida (NAC) species, Candida auris. Thus, understanding the molecular basis of antifungal resistance has emerged as the single most important goal amongst the research community. Since besides target alterations, efflux mechanisms contribute maximally to antifungal resistance, it is imperative to investigate their contributions in this pathogen. Of note, within the Major Facilitator Superfamily (MFS) of efflux pumps, Drug/H+ antiporter family 1 (DHA1) has been established as a predominant contributor towards xenobiotic efflux. Our study provides a complete landscape of DHA1 transporters encoded in the genome of C. auris. This study identifies 14 DHA1 transporters encoded in the genome of the pathogen. We also construct deletion and heterologous overexpression strains for the most important DHA1 drug transporter, viz., CauMdr1 to map the spectrum of its substrates. While the knockout strain did not show any significant changes in the resistance patterns against the majority of the tested substrates, the ortholog when overexpressed in a minimal background S. cerevisiae strain, AD1-8u-, showed significant enhancement in the Minimum inhibitory concentrations (MICs) against a large panel of antifungal molecules. Altogether, the present study provides a comprehensive template for investigating the role of DHA1 members of C. auris in antifungal resistance mechanisms.
Actin-dependent recruitment of AGO2 to the zonula adherens

Adherens junctions are cadherin-based structures critical for cellular architecture. E-cadherin junctions in mature epithelial cell monolayers tether to an apical actomyosin ring to form the zonula adherens (ZA). We have previously shown that the adherens junction protein PLEKHA7 associates with and regulates the function of the core RNA interference (RNAi) component AGO2 specifically at the ZA. However, the mechanism mediating Ago2 recruitment to the ZA remained unexplored. Here, we reveal that this ZA-specific recruitment of AGO2 depends on both the structural and tensile integrity of the actomyosin cytoskeleton. We found that depletion of not only PLEKHA7, but also either of three PLEKHA7-interacting, LIM-domain family proteins, namely LMO7, LIMCH1, and PDLIM1, results in disruption of actomyosin organization and tension, as well as disruption of AGO2 junctional localization and of its miRNA-binding ability. We also show that AGO2 binds Myosin IIB and that PLEKHA7, LMO7, LIMCH1, and PDLIM1 all disrupt interaction of AGO2 with Myosin IIB at the ZA. These results demonstrate that recruitment of Ago2 to the ZA is sensitive to actomyosin perturbations, introducing the concept of a mechanosensitive RNAi machinery, with potential implications in tissue remodeling and in disease. Summary Recruitment and miRNA-binding activity of the key RNA interference (RNAi) component AGO2 to epithelial zonula adherens depends on apical actomyosin integrity and tension, revealing the existence of a mechanosensitive RNAi machinery at the zonula adherens. Significance Statement Previous work has shown that PLEKHA7 recruits core RNAi components, including AGO2, to regulate tumor-suppressing miRNAs specifically at the zonula adherens (ZA), through an unknown mechanism. Here, the authors show that three LIM domain-containing proteins, LMO7, LIMCH1, and PDLIM1, are also responsible for AGO2’s recruitment and miRNA activity at the ZA and that all four PLEKHA7, LMO7, LIMCH1, PDLIM1 mediate AGO2 recruitment to the ZA not due to their protein-protein interactions, but through stabilizing actomyosin structure and tension. These findings introduce a mechanosensitive RNAi machinery responsive to actomyosin perturbations, with potentially broad implications in regulation of cellular plasticity.
Insights into β-manno-oligosaccharide uptake and metabolism in Bifidobacterium adolescentis DSMZ 20083 from whole-genome microarray analysis

Aims To determine the ability of adult-associated B. adolescentis DSMZ 20083 to utilize dietary β-manno-oligosaccharides and understand the underlying molecular mechanism. Methods and Results In-vitro fermentation and TLC were used to determine the ability of B. adolescentis DSMZ 20083 to utilize β-manno-oligosaccharides from guar gum, locust bean gum, konjac and copra meal. Further, Whole-genome transcriptome analysis, q-RT-PCR and molecular docking were employed to reconstruct copra meal β-manno-oligosaccharides (CM-β-MOS) utilization pathway in B. adolescentis DSMZ 20083. B. adolescentis DSMZ 20083 grew appreciably (A600nm up to 0.8) on all tested β-manno-oligosaccharides but maximally on CM-β-MOS. Transcriptome analysis revealed differential up-regulation of three distinct gene clusters encoding, ABC transporter cassette (ESBP’s and permeases), MFS transporter, GH1 β-glucosidase and, GH32 β-fructofuranosidases. ABC and MFS possibly transported majorly DP≥2 and DP≥3 CM-β-MOS, respectively. Sugar absorption and utilization pathways; ABC transport system, pyruvate metabolism, glycolysis/gluconeogenesis, pentose, and glucouronate inter-conversions were also up-regulated. Conclusions B. adolescentis DSMZ 20083 possibly utilizes ABC & MFS transporters to internalise and GH1 β-glucosidase, and GH32 β-fructofuranosidase to deconstruct CM-β-MOS. Significance and Impact of the Study First study reporting possible molecular determinants used by B. adolescentis DSMZ 20083 to utilize β-manno-oligosaccharides and thus, can prove resourceful in precision microbiome modulation.