Observation of high-energy neutrinos from the Galactic plane.

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, is unknown. Because of deflection by interstellar magnetic fields, cosmic rays produced within the Milky Way arrive at Earth from random directions. However, cosmic rays interact with matter near their sources and during propagation, which produces high-energy neutrinos.

Modulation of the functional interfaces between retroviral intasomes and the human nucleosome.

Infection by retroviruses as HIV-1 requires the stable integration of their genome into the host cells. This process needs the formation of integrase (IN)-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes within cell chromatin. To provide new tools to analyze this association and select drugs, we applied the AlphaLISA technology to the complex formed between the prototype foamy virus (PFV) intasome and nucleosome reconstituted on 601 Widom sequence.

Simulation of Tetrahedral Profiled Carbon Rovings for Concrete Reinforcements.

Textile reinforcements are increasingly establishing their position in the construction industry due to their high tensile properties and corrosion resistance for concrete applications. In contrast to ribbed monolithic steel bars with a defined form-fit effect, the conventional carbon rovings' bond force is transmitted primarily by an adhesive bond (material fit) between the textile surface and the surrounding concrete matrix. As a result, relatively large bonding lengths are required to transmit bond forces, resulting in inefficient material utilization.

Synthesis and biological evaluation of DIDS analogues as efficient inhibitors of RAD51 involved in homologous recombination.

RAD51 is a pivotal protein of the homologous recombination DNA repair pathway, and is overexpressed in some cancer cells, disrupting then the efficiency of cancer-treatments. The development of RAD51 inhibitors appears as a promising solution to restore these cancer cells sensitization to radio- or chemotherapy. From a small molecule identified as a modulator of RAD51, the 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), two series of analogues with small or bulky substituents on the aromatic parts of the stilbene moiety were prepared for a structure-activity relationship study.

Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication.

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale ν_{μ} Disappearance at IceCube.

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{μτ}. The best-fit value is consistent with no NSI at a p value of 25.

An Assist for Cognitive Diagnostics in Soccer: Two Valid Tasks Measuring Inhibition and Cognitive Flexibility in a Soccer-Specific Setting With a Soccer-Specific Motor Response.

In professional soccer, players, coaches, and researchers alike recognize the importance of cognitive skills. Research addressing the relevance of cognitive skills has been based on the cognitive component skills approach (i.e.

Search for Relativistic Magnetic Monopoles with Eight Years of IceCube Data.

We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.

Inhibiting homologous recombination by targeting RAD51 protein.

Homologous recombination (HR) is involved in repairing DNA double-strand breaks (DSB), the most harmful for the cell. Regulating HR is essential for maintaining genomic stability. In many forms of cancer, overactivation of HR increases tumor resistance to DNA-damaging treatments.

, and Models for Monitoring SARS-CoV-2 Spike/Human ACE2 Complex, Viral Entry and Cell Fusion.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Productive SARS-CoV-2 infection relies on viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). Indeed, viral entry into cells is mostly mediated by the early interaction between the viral spike protein S and its ACE2 receptor.

Systemic Glycosaminoglycan Clearance by HARE/Stabilin-2 Activates Intracellular Signaling.

Scavenger receptors perform essential functions, critical to maintaining mammalian physiologic homeostasis by continuously clearing vast numbers of biomolecules from blood, interstitial fluid and lymph. Stabilin-2 (Stab2) and the Hyaluronic Acid Receptor for Endocytosis (HARE), a proteolytic isoform of Stab2, are important scavenger receptors responsible for the specific binding and internalization (leading to degradation) of 22 discrete molecules, macromolecular complexes and cell types. One-third of these ligands are glycosaminoglycans (GAGs).

Averted Transfers in Rural Emergency Departments Using Telemedicine: Rates and Costs Across Six Networks.

This analysis identified the rate of transfers and averted transfers and their associated costs across multiple emergency department telemedicine (teleED) networks. This study is a prospective cohort analysis in six teleED networks operating in 65 hospitals in 11 states across the United States. Each submitted uniform data on all teleED encounters for a 26-month period to a data co-ordinating center.

Rational Engineering of the Substrate Specificity of a Thermostable D-Hydantoinase (Dihydropyrimidinase).

D-hydantoinases catalyze an enantioselective opening of 5- and 6-membered cyclic structures and therefore can be used for the production of optically pure precursors for biomedical applications. The thermostable D-hydantoinase from ATCC 31783 is a manganese-dependent enzyme and exhibits low activity towards bulky hydantoin derivatives. Homology modeling with a known 3D structure (PDB code: 1K1D) allowed us to identify the amino acids to be mutated at the substrate binding site and in its immediate vicinity to modulate the substrate specificity.

Self-regenerating giant hyaluronan polymer brushes.

Tailoring interfaces with polymer brushes is a commonly used strategy to create functional materials for numerous applications. Existing methods are limited in brush thickness, the ability to generate high-density brushes of biopolymers, and the potential for regeneration. Here we introduce a scheme to synthesize ultra-thick regenerating hyaluronan polymer brushes using hyaluronan synthase.

Tele-emergency behavioural health in rural and underserved areas.

Introduction: Challenges accessing behavioural health services in rural and underserved areas are compounded by severe shortages of behavioural health specialists, and difficulties placing patients. Tele-emergency (tele-ED) behavioural health is a promising solution for enhancing access to specialists and assisting in patient placement. This paper describes two tele-ED behavioural health models in the Midwest delivering mental- and substance use disorder services to rural and underserved adult populations.

Mobilising cross-sector collaborations to improve population health in US rural communities: a qualitative study.

Objectives: This study examines types and forms of cross-sector collaborations employed by rural communities to address community health issues and identifies factors facilitating or inhibiting such collaborations.

Setting: We conducted case studies of four rural communities in the US state of Iowa that have demonstrated progress in creating healthier communities.

Participants: Key informants from local public health departments, hospitals and other health-promoting organisations and groups participated in this study.

Interactions of the Rad51 inhibitor DIDS with human and bovine serum albumins: Optical spectroscopy and isothermal calorimetry approaches.

Rad51 is a key protein in DNA repair by homologous recombination and an important target for development of drugs in cancer therapy. 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) has been used in clinic during the past 30 years as an inhibitor of anion transporters and channels. Recently DIDS has been demonstrated to affect Rad51-mediated homologous pairing and strand exchange, key processes in homologous recombination.

Discovery of the Liver Hyaluronan Receptor for Endocytosis (HARE) and Its Progressive Emergence as the Multi-Ligand Scavenger Receptor Stabilin-2.

Since the discovery of a novel liver hyaluronan (HA) clearance receptor in 1981 by Laurent, Fraser and coworkers, 22 different ligands cleared by the renamed receptor (the Hyaluronan Receptor for Endocytosis (HARE); Stabilin-2 (Stab2)) were discovered over 37 years. Ligands fall into three groups: (1) 11 anionic polymers, (2) seven cleaved or modified proteins and (3) four types of cells. Seven synthetic ligands, not found normally in serum or tissues, likely mimic natural molecules cleared by the receptor.

Paediatric tele-emergency care: A study of two delivery models.

Introduction: Tele-emergency models have been utilized for decades, with growing evidence of their effectiveness. Due to the variety of tele-emergency department (tele-ED) models used in practice, however, it is challenging to build standardized metrics for ongoing evaluation. This study describes two tele-ED programs, one specialized and one general, that provide care to paediatric populations.

Bonded thin film lithium niobate modulator on a silicon photonics platform exceeding 100 GHz 3-dB electrical modulation bandwidth.

We demonstrate an ultra-high-bandwidth Mach-Zehnder electro-optic modulator (EOM), based on foundry-fabricated silicon (Si) photonics, made using conventional lithography and wafer-scale fabrication, oxide-bonded at 200C to a lithium niobate (LN) thin film. Our design integrates silicon photonics light input/output and optical components, such as directional couplers and low-radius bends. No etching or patterning of the thin film LN is required.

Assessment of DNA-PKcs kinase activity by quantum dot-based microarray.

Therapeutic efficacy against cancer is often based on a variety of DNA lesions, including DNA double-strand breaks (DSBs) which are repaired by homologous recombination and non-homologous end joining (NHEJ) pathways. In the past decade, the functions of the DNA repair proteins have been described as a potential mechanism of resistance in tumor cells. Therefore, the DNA repair proteins have become targets to improve the efficacy of anticancer therapy.