Robotic-inspired approach to multi-domain membrane receptor conformation space: theory and SARS-CoV-2 spike protein case study -
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+The spike protein of SARS-CoV-2 is a highly flexible membrane receptor that triggers the translocation of the virus into cells by attaching to the human receptors. Like other type I membrane receptors, this protein has several extracellular domains connected by flexible hinges. The presence of these hinges results in high flexibility, which consequently results in challenges in defining the conformation of the protein. Here, We developed a new method to define the conformational space based on a few variables inspired by the robotic field's methods to determine a robotic arm's forward kinematics. Using newly performed atomistic molecular dynamics (MD) simulations and publicly available data, we found that the Denavit-Hartenberg (DH) parameters can reliably show the changes in the local conformation. Furthermore, the rotational and translational components of the homogenous transformation matrix constructed based on the DH parameters can identify the changes in the global conformation of the spike and also differentiate between the conformation with a similar position of the spike head, which other types of parameters, such as spherical coordinates, fail to distinguish between such conformations. Finally, the new method will be beneficial for looking at the conformational heterogeneity in all other type I membrane receptors.
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ViRNN: A Deep Learning Model for Viral Host Prediction -
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+Viral outbreaks are on the rise in the world, with the current outbreak of COVID-19 being among one of the worst thus far. Many of these outbreaks were the result of zoonotic transfer between species, and thus understanding and predicting the host of a virus is very important. With the rise of sequencing technologies it is becoming increasingly easy to sequence the full genomes of viruses, databases of publicly available viral genomes are widely available. We utilize a convolutional and recurrent neural network architecture (ViRNN) to predict the hosts for the Coronaviridae family (Coronaviruses) amongst the eleven most common hosts of this family. Our architecture performed with an overall accuracy of 90.55% on our test dataset, with a micro-average AUC-PR of 0.97. Performance was variable per host. ViRNN outperformed previously published methods like k-nearest neighbors and support vector machines, as well as previously published deep learning based methods. Saliency maps based on integrated gradients revealed a number of proteins in the viral genome that may be important interactions determining viral infection in hosts. Overall, this method provides an adaptable classifier capable of predicting host species from viral genomic sequence with high accuracy.
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Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2 -
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+The Covid-19 pandemic showcases a coevolutionary race between the human immune system and SARS-CoV-2, mirroring the Red Queen hypothesis of evolutionary biology. The immune system generates neutralizing antibodies targeting the SARS-CoV-2 spike protein's receptor binding domain (RBD), crucial for host cell invasion, while the virus evolves to evade antibody recognition. Here, we establish a synthetic coevolution system combining high-throughput screening of antibody and RBD variant libraries with protein mutagenesis, surface display, and deep sequencing. Additionally, we train a protein language machine learning model that predicts antibody escape to RBD variants. Synthetic coevolution reveals antagonistic and compensatory mutational trajectories of neutralizing antibodies and SARS-CoV-2 variants, enhancing the understanding of this evolutionary conflict.
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Emotional distress and affective knowledge representation one year after the Covid-19 outbreak -
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+This study examines whether the detrimental effects of the COVID-19 pandemic on the affectivity of the population extend one year after the outbreak. In an online-mobile session, participants completed surveys (i.e. demographic characteristics, positive-negative affectivity, interoceptive awareness) and a similarity judgment task of triplets of emotional concepts, from which we derived 2D maps of their affective knowledge representation. Compared with pre-pandemic data derived from a comparable population, we report three main findings. First, we observed enhanced negative affectivity during the pandemic, but no changes in positive affectivity levels. Second, increased self-reported interoceptive awareness compared to pre-pandemic data, with greater attention to bodily sensations and adaptive aspects of interoceptive sensitivity. Furthermore, female participants reported higher scores than males on the questionnaire subscales of Emotional Awareness and Attention Regulation. Third, the effect of pandemic-related conditions is also apparent in the mental organization of emotional concepts, especially for female participants (i.e., reduced coherence in the organization of the concepts along the arousal dimension and more misclassification of concepts based on arousal) and participants who did not perform physical activity (a collapse of the arousal dimension). Some of the effects of the pandemic, thus, persist about a year after the outbreak. These results advise providing programs of psychological and emotional assistance throughout the pandemic beyond the outbreak, and that age-dependent gender differences should be accounted for to define tailored interventions. Physical activity might relieve pandemic-related stressors, so it should be promoted during particularly stressful periods for the population.
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Nanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles -
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+The SARS-CoV-2 viral infection transforms host cells and produces special organelles in many ways, and we focus on the replication organelle where the replication of viral genomic RNA (vgRNA) occurs. To date, the precise cellular localization of key RNA molecules and replication intermediates has been elusive in electron microscopy studies. We use super-resolution fluorescence microscopy and specific labeling to reveal the nanoscopic organization of replication organelles that contain vgRNA clusters along with viral double-stranded RNA (dsRNA) clusters and the replication enzyme, encapsulated by membranes derived from the host endoplasmic reticulum (ER). We show that the replication organelles are organized differently at early and late stages of infection. Surprisingly, vgRNA accumulates into distinct globular clusters in the cytoplasmic perinuclear region, which grow and accommodate more vgRNA molecules as infection time increases. The localization of ER labels and nsp3 (a component of the double-membrane vesicle, DMV) at the periphery of the vgRNA clusters suggests that replication organelles are enclosed by DMVs at early infection stages which then merge into vesicle packets as infection progresses. Precise co-imaging of the nanoscale cellular organization of vgRNA, dsRNA, and viral proteins in replication organelles of SARS-CoV-2 may inform therapeutic approaches that target viral replication and associated processes.
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A mechanism that transduces lysosomal damage signals to stress granule formation for cell survival -
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+Lysosomal damage poses a significant threat to cell survival. Our previous work has reported that lysosomal damage induces stress granule (SG) formation. However, the importance of SG formation in determining cell fate and the precise mechanisms through which lysosomal damage triggers SG formation remains unclear. Here, we show that SG formation is initiated via a novel calcium-dependent pathway and plays a protective role in promoting cell survival in response to lysosomal damage. Mechanistically, we demonstrate that during lysosomal damage, ALIX, a calcium-activated protein, transduces lysosomal damage signals by sensing calcium leakage to induce SG formation by controlling the phosphorylation of eIF2. ALIX modulates eIF2 phosphorylation by regulating the association between PKR and its activator PACT, with galectin-3 exerting a negative effect on this process. We also found this regulatory event of SG formation occur on damaged lysosomes. Collectively, these investigations reveal novel insights into the precise regulation of SG formation triggered by lysosomal damage, and shed light on the interaction between damaged lysosomes and SGs. Importantly, SG formation is significant for promoting cell survival in the physiological context of lysosomal damage inflicted by SARS-CoV-2 ORF3a, adenovirus infection, Malaria hemozoin, proteopathic tau as well as environmental hazard silica.
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Aversive personality and COVID-19: A first review and meta-analysis -
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+The Coronavirus Disease 2019 (COVID-19) has strongly affected individuals and societies worldwide. In this review and meta-analysis, we investigated how aversive personality traits—i.e., relatively stable antisocial personality characteristics—related to how individuals perceived, evaluated, and responded to the COVID-19 pandemic. Across 34 studies with overall 26,780 participants, we found that people with higher scores in aversive personality traits were less likely to perceive guidelines and restrictions to curb the spread of the virus as protective (p̂ = -.11), to engage in health behaviors related to COVID-19 (p̂ = -.16), and to engage in non-health related prosocial behavior related to COVID-19 (p̂ = -.14). We found no consistent relation between aversive personality and negative affect regarding the pandemic. The results thus indicate the importance of aversive personality traits in understanding individual differences with regard to COVID-19.
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Information about herd immunity through vaccination and empathy promote COVID-19 vaccination intentions -
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+Objective: An effective vaccine against COVID-19 is a desired solution to curb the spread of the disease. However, vaccine hesitancy might hinder high uptake rates and thus undermine efforts to eliminate COVID-19 once an effective vaccine became available. The present contribution addresses this issue by examining two ways of increasing the intention to get vaccinated against COVID-19. Methods: Two pre-registered online studies were conducted (N = 2,315 participants from the UK) in which knowledge about and beliefs in herd immunity through vaccination, as well as empathy for those most vulnerable to the virus, were either measured (Study 1) or manipulated (Study 2). As a dependent variable, individuals’ self-reported vaccination intention once a vaccine against COVID-19 became available was assessed. Results: In Study 1 (N = 310), the intention to get vaccinated against COVID-19 was correlated with knowledge about and belief in herd immunity (r = .58, p < .001), as well as with empathy for those most vulnerable to the virus (r = .26, p < .001). In Study 2 (N = 2,005), information about herd immunity (Cohen’s d = 0.13, p = .003) and empathy (Cohen’s d = 0.22, p < .001) independently promoted vaccination intention. Conclusions: The motivation to get vaccinated against COVID-19 was related to and could be causally promoted by both mere information about herd immunity and by empathy. As such, the present research provides a better understanding of the intention to get vaccinated against COVID-19.
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The emotional path to action: Empathy promotes physical distancing and wearing of face masks during the COVID-19 pandemic -
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+The COVID-19 pandemic presents a major challenge to societies all over the globe. To curb the spread of the disease, two measures implemented in many countries are minimizing close contact between people (“physical distancing”) and wearing face masks. In the present research, we tested the idea that physical distancing and wearing face masks can be the result of a genuine prosocial emotion—empathy for those most vulnerable to the virus. In four pre-registered studies (total N = 3,718, Western population), we show that (i) empathy is indeed a basic motivation for physical distancing and wearing face masks, and (ii) inducing empathy for those most vulnerable to the virus promotes the motivation to adhere to these measures (whereas providing mere information about its importance is not). In sum, the present research provides a better understanding of the promoting factors underlying the willingness to follow two important measures during the COVID-19 pandemic.
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Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: Implications to alternative conformations and their statistical structural analyses -
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+The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition.
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+Broad-spectrum therapeutics capable of inhibiting SARS-CoV-2, its variants, and related coronaviruses hold promise in curbing the spread of COVID-19 and averting future pandemics. Here, we employed a multidisciplinary approach that included molecular dynamics simulation (MDS) and artificial intelligence (AI)-based docking predictions to identify potent inhibitors that target a conserved region within the SARS-CoV-2 spike protein that mediates membrane fusion by undergoing large-scale mechanical rearrangements. In silico binding screens honed in on this region, leading to the discovery of FDA-approved drugs and novel molecules predicted to disrupt spike protein conformational changes. These compounds significantly inhibited SARS-CoV-2 infection and blocked the entry of spike protein-bearing pseudotyped , {beta}, {gamma}, {delta} variants as well as SARS-CoV and MERS-CoV in cultured human ACE2-expressing cells. The optimized lead compound significantly inhibited SARS-CoV2 infection in mice when administered orally.
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Enhanced mucosal B- and T-cell responses against SARS-CoV-2 after heterologous intramuscular mRNA prime/intranasal protein boost vaccination with a combination adjuvant. -
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+Current COVID-19 mRNA vaccines delivered intramuscularly (IM) induce effective systemic immunity, but with suboptimal immunity at mucosal sites, limiting their ability to impart sterilizing immunity. There is strong interest in rerouting immune responses induced in the periphery by parenteral vaccination to the portal entry site of respiratory viruses, such as SARS-CoV-2, by mucosal vaccination. We previously demonstrated the combination adjuvant, NE/IVT, consisting of a nanoemulsion (NE) and an RNA-based RIG-I agonist (IVT) induces potent systemic and mucosal immune responses in protein-based SARS-CoV-2 vaccines administered intranasally (IN). Herein, we demonstrate priming IM with mRNA followed by heterologous IN boosting with NE/IVT adjuvanted recombinant antigen induces strong mucosal and systemic antibody responses and enhances antigen-specific T cell responses in mucosa-draining lymph nodes compared to IM/IM and IN/IN prime/boost regimens. While all regimens induced cross-neutralizing antibodies against divergent variants and sterilizing immunity in the lungs of challenged mice, mucosal vaccination, either as homologous prime/boost or heterologous IN boost after IM mRNA prime was required to impart sterilizing immunity in the upper respiratory tract. Our data demonstrate the benefit of hybrid regimens whereby strong immune responses primed via IM vaccination are rerouted by IN vaccination to mucosal sites to provide optimal protection to SARS-CoV-2.
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Development and Application of Decontamination Methods for the Re-Use of Laboratory Grade Plastic Pipette Tips -
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+During the SARS-CoV-2 pandemic, a need for methods to decontaminate and reuse personal protective equipment (PPE) and medical plastics became a priority. In this investigation we aimed to develop a contamination evaluation protocol for laboratory pipette tips, after decontamination. Decontamination methods tested in this study included cleaning with a common laboratory detergent (2.5% Alconox(R) solution followed with steam decontamination), exposure of ozone vapor at 250 and 14400 PPM * minute, and exposure to cold atmospheric plasma (CAP). All tips (control and experimental groups) were introduced to the methods described, while tips exposed to DNA extracts of Aeromonas hydrophila (ATCC-23211) were assessed for experimental groups. Decontamination was determined by turnover ratio and log reduction in detectable genomic material on the contaminated products using real-time quantitative PCR (qPCR) assay. Our results showed, cleaning tips with lab detergents along with steam decontamination removed genetic material, resulting in the highest log reduction, compared with ozone or CAP treatments. Detergent/washing methods showed the highest turnover ratio (95.9 %) and log reduction (5.943). However, the excessive residue (post- cleaning) on the plastic, within inner filters, and tip boxes suggested that washing with lab detergents was not favorable for reuse. Ozone vapor at 14400 PPM * minutes showed the second highest turnover ratio (98.4 %) and log reduction (4.511). CAP exposure with tips inverted (the tip end exposed closer to the plasma flame) for 1 minute showed a turnover ratio of (68.3 %) and log reduction (4.002). Relatively, lower turnover ratio and log reduction of CAP could be attributed to development/optimization of treatment conditions, including increases in exposure time and relative to tip positioning.
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Human long noncoding RNA, VILMIR, is induced by major respiratory viral infections and modulates the host interferon response -
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+Long noncoding RNAs (lncRNAs) are a newer class of noncoding transcripts identified as key regulators of biological processes. Here we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic datasets. Using bulk RNA-sequencing (RNA-seq) analysis, we identified a previously uncharacterized lncRNA, named virus inducible lncRNA modulator of interferon response (VILMIR), that was consistently upregulated after in vitro influenza infection across multiple human epithelial cell lines and influenza A virus subtypes. VILMIR was also upregulated after SARS-CoV-2 and RSV infections in vitro. We experimentally confirmed the response of VILMIR to influenza infection and interferon-beta (IFN-{beta}) treatment in the A549 human epithelial cell line and found the expression of VILMIR was robustly induced by IFN-{beta} treatment in a dose and time-specific manner. Single cell RNA-seq analysis of bronchoalveolar lavage fluid (BALF) samples from COVID-19 patients uncovered that VILMIR was upregulated across various cell types including at least five immune cells. The upregulation of VILMIR in immune cells was further confirmed in the human T cell and monocyte cell lines, SUP-T1 and THP-1, after IFN-{beta} treatment. Finally, we found that knockdown of VILMIR expression reduced the magnitude of host transcriptional responses to IFN-{beta} treatment in A549 cells. Together, our results show that VILMIR is a novel interferon-stimulated gene (ISG) that regulates the host interferon response and may be a potential therapeutic target for human respiratory viral infections upon further mechanistic investigation.
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Inference of epidemic dynamics in the COVID-19 era and beyond -
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+The COVID-19 pandemic demonstrated the key role that epidemiology and modelling play in analysing infectious threats and supporting decision making in real-time. Motivated by the unprecedented volume and breadth of data generated during the pandemic, we review new analytic opportunities and methodological developments available to address questions that emerge during a major modern epidemic. Following the broad chronology of insights required - from understanding initial dynamics to retrospective evaluation of interventions, we describe the theoretical foundations of each approach and the underlying intuition. Through a series of case studies, we illustrate real life applications, and discuss implications for future work.
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Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD) - Conditions: Post-Acute Sequelae of COVID-19 Interventions: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program Sponsors: University of Minnesota Recruiting
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Valacyclovir Plus Celecoxib for Post-Acute Sequelae of SARS-CoV-2 - Conditions: Long COVID; PASC Post Acute Sequelae of COVID 19 Interventions: Drug: Valacyclovir celecoxib dose 1; Drug: Valacyclovir celecoxib dose 2; Drug: Placebo Sponsors: Bateman Horne Center Recruiting
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From PubMed
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Quantitating SARS-CoV-2 Neutralizing Antibodies from Human Dried Blood Spots - CONCLUSION: SARS-CoV-2 neutralizing titers can be derived with confidence from DBS eluates, thereby opening the door to the use of these biospecimens for the analysis of vulnerable populations and normally hard to reach communities.
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Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection - CONCLUSION: Both LNP-Trap and LNP-Trim formulations were able to safely and effectively inhibit SARS-CoV-2 pseudoviral infection in airway epithelial cells. These studies provide proof-of-principle for a localized treatment approach for SARS-CoV-2 in the upper airway.
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Transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus - Tinnitus is a disturbing condition defined as the occurrence of acoustic hallucinations with no actual sound. Although the mechanisms underlying tinnitus have been explored extensively, the pathophysiology of the disease is not completely understood. Moreover, genes and potential treatment targets related to auditory hallucinations remain unknown. In this study, we examined transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus in rats by performing RNA…
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Acceptance, safety, and immunogenicity of a booster dose of inactivated SARS-CoV-2 vaccine in patients with primary biliary cholangitis - Inactivated coronavirus disease 2019 (COVID-19) vaccines showed impaired immunogenicity in some autoimmune diseases, but it remains unclear in primary biliary cholangitis (PBC). This study aimed to explore the antibody response to the inactivated COVID-19 vaccine in individuals with PBC, as well as to evaluate coverage, safety, and attitudes toward the COVID-19 vaccine among them. Two cohorts of patients with PBC were enrolled in this study. One cohort was arranged to evaluate the immunogenicity…
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Vgamma9Vdelta2 T-cells are potent inhibitors of SARS-CoV-2 replication and represent effector phenotypes in COVID-19 patients - Vγ9Vδ2 T-cells play a key role in the innate immune response to viral infections through butyrophilin (BTN)-3A. Here, we reported that blood Vγ9Vδ2 T-cells decreased in clinically mild COVID-19 compared to healthy volunteers (HV), and was maintained up to 28-days and in the recovery period. Terminally differentiated Vγ9Vδ2 T-cells tend to be enriched on the day of diagnosis, 28-days after and during the recovery period. These cells showed cytotoxic and inflammatory activities following…
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Isolation, characterization and SARS-CoV-2 3CL protease inhibitory activity of a new methylsulfinyl-butanyl derivative from Raphani Semen - A new compound named raphanised A (1), along with two known methylsulfinyl -butanyl derivatives (2-3) and seven known indole derivatives (4-10), were isolated from the Raphani Semen. Among the indole derivatives, 5 was identified as a new natural product, and 4, 6, 7, 8, 9, 10 were isolated from the genus of Raphanus for the first time. Their structures were elucidated based on the NMR and HR-EI-MS analysis. Additionally, the inhibitory activity of methylsulfinyl-butanyl derivatives 1-3 on SARS…
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CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation - CONCLUSIONS: Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells…
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Comparative evaluation of tocilizumab and itolizumab for treatment of severe COVID-19 in India: a retrospective cohort study - CONCLUSIONS: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.
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Synthesis and pharmacodynamic evaluation of Dihydropteridone derivatives against PDCoV in vivo and in vitro - Porcine Delta Coronavirus (PDCoV) infection can induce serious dehydration, diarrhea and even death of piglets, which has caused huge losses to the breeding industry. PDCoV has been reported to have the potential for cross species transmission, and even reports of infecting humans have emerged. At present, there are still no effective prevention and control measures for PDCoV. In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these…
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New conjugates based on N4-hydroxycytidine with more potent antiviral efficacy in vitro than EIDD-2801 against SARS-CoV-2 and other human coronaviruses - The spread of COVID-19 continues due to genetic variation in SARS-CoV-2. Highly mutated variants of SARS-CoV-2 have an increased transmissibility and immune evasion. Due to the emergence of various new variants of the virus, there is an urgent need to develop broadly effective specific drugs for therapeutic strategies for the prevention and treatment of COVID-19. Molnupiravir (EIDD-2801, MK-4482), is an orally bioavailable ribonucleoside analogue of β-D-N4-hydroxycytidine (NHC), has demonstrated…
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Biological responses in Danio rerio by the disinfectant SDBS in SARS-CoV-2 pandemic - The use of disinfectants, such as Sodium Dodecylbenzene Sulfonic acid salt (SDBS), has grown since the SARS-CoV-2 pandemic, with environmentally unknown consequences. The present study analyzed SDBS effects in the fish species Danio rerio, using a combination of biomarkers. Our data reported that larvae had their total locomotor activity increased when exposed to 1mg/L of SDBS, but this parameter was decreased in fish exposed to 5mg/L. A significant increment of erratic movements was reported in…
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Preclinical evaluation of the SARS-CoV-2 M(pro) inhibitor RAY1216 shows improved pharmacokinetics compared with nirmatrelvir - Although vaccines are available for SARS-CoV-2, antiviral drugs such as nirmatrelvir are still needed, particularly for individuals in whom vaccines are less effective, such as the immunocompromised, to prevent severe COVID-19. Here we report an α-ketoamide-based peptidomimetic inhibitor of the SARS-CoV-2 main protease (M^(pro)), designated RAY1216. Enzyme inhibition kinetic analysis shows that RAY1216 has an inhibition constant of 8.4 nM and suggests that it dissociates about 12 times slower…
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A new DNA aptamer which binds to SARS-CoV-2 spike protein and reduces pro-inflammatory response - COVID-19 caused by SARS-CoV-2 spread rapidly around the world, endangering the health of people globally. The SARS-CoV-2 spike protein initiates entry into target cells by binding to human angiotensin-converting enzyme 2 (ACE2). In this study, we developed DNA aptamers that specifically bind to the SARS-CoV-2 spike protein, thereby inhibiting its binding to ACE2. DNA aptamers are small nucleic acid fragments with random structures that selectively bind to various target molecules. We identified…
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Protective mucosal SARS-CoV-2 antibodies in the majority of the general population in the Netherlands - Antibodies to SARS-CoV-2 at mucosal surfaces of the respiratory tract are understood to contribute to protection against SARS-CoV-2 infection. We aimed to describe the prevalence, levels and functionality of mucosal antibodies in the general Dutch population. Nasal samples were collected from 778 randomly selected participants, 1-90 years of age, nested within the nationwide prospective SARS-CoV-2 PIENTER corona serosurvey in the Netherlands. Spike-specific IgG was detected in nasal samples of…
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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has decreased the efficacy of SARS-CoV-2 vaccines in containing coronavirus disease 2019 (COVID-19) over time, and booster vaccination strategies are urgently necessitated to achieve sufficient protection. Intranasal immunization can improve mucosal immunity, offering protection against the infection and sustaining the spread of SARS-CoV-2. In this study, an intranasal booster of the RBD-HR vaccine after two…
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From Patent Search
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How Chinese Students Experience America - COVID, guns, anti-Asian violence, and diplomatic relations have complicated the ambitions of the some three hundred thousand college students who come to the U.S. each year. - link
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The Hottest Restaurant in France Is an All-You-Can-Eat Buffet - Les Grands Buffets features a seven-tiered lobster tower, a chocolate fountain, and only what it considers traditional French food. Gourmands are willing to wait months for a table. - link
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So You Think You’ve Been Gaslit - What happens when a niche clinical concept becomes a ubiquitous cultural diagnosis. - link
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The Brazilian Special-Forces Unit Fighting to Save the Amazon - As miners ravage Yanomami lands, combat-trained environmentalists work to root them out. - link
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What Have Fourteen Years of Conservative Rule Done to Britain? - Living standards have fallen. The country is exhausted by constant drama. But the U.K. can’t move on from the Tories without facing up to the damage that has occurred. - link
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From Vox
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How did the cost of food delivery get so high? -
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+Food delivery apps have recently added new fees in response to minimum pay rules in New York City and Seattle. | Getty Images/iStockphoto
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+As delivery discourse rages, don’t forget the middlemen: apps like UberEats, DoorDash, and Grubhub.
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+No one is happy about the delivery apps. Not the customers, who feel gouged by an avalanche of fees. Not restaurants, who feel gut-punched by the commission apps take from them. Certainly not delivery workers, who have long been rewarded with a pittance for doing a job that, in a city like New York, has a higher injury rate than that of construction workers.
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+Amid this dogpile of disgruntlement, the merry-go-round of debating the value of food deliverykeepsspinning. After all, some people, especially those with disabilities, rely on such services — but then, it is difficult work, and everyone ought to tip well. Another faction argues that this isn’t fair, because it’s already so unaffordable. The delivery apps themselves recede somewhat into the background, as if their existence is a given. They’re merely fulfilling a demand in the market, naturally taking a cut for themselves — two plus two equals four. Our desire to consume is seen as the problem, the having-cake-and-eating-it-too mentality of expecting affordable convenience.
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+But we should give credit where it’s due. Delivery apps have expended a lot of effort (and money) making the case that we — restaurants, workers, and consumers — desperately need them. Unhappy about the state of things now? You’ll really be pulling your hair out if you try to force the apps to change. In New York City and Seattle, new minimum pay laws for delivery workers recently went into effect. Immediately, additional “regulatory” fees were charged to customers, and restaurants and delivery workers complained that orders dropped, with Uber claiming in a blog post that they had dipped by 30 percent. Neither city’s minimum wage laws have forced delivery apps to tack on new fees, but both DoorDash and Uber Eats have introduced them nonetheless. The message is clear: If you try to mediate how the apps operate, things will just get worse.
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+An Uber spokesperson told Vox that there were “consequences to bad regulations and we made these consequences clear in repeated testimony that both cities chose to disregard.” A DoorDash spokesperson wrote that its platform “has to work for everyone who uses it — Dashers, merchants, and customers alike — which is why we’ve opposed these extreme new rules.” They continued that the new laws “require platforms like DoorDash to pay well above the local minimum wages, not including additional pay for mileage and tips. Just as we warned, the increased costs created by these regulations have led to an alarming drop in work for Dashers and lost revenue for small businesses.” Grubhub did not reply to a request for comment.
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+Some headlineshave already declared app-delivery regulations a failure; the Seattle City Council is considering gutting the law while the ink is still drying. At the crisis point of consumers fed up with the cost of food delivery, companies like DoorDash, Uber Eats, and Grubhub — the three biggest in the US — are insisting on their irreplaceable value to the restaurants, consumers, and workers who have long complained about them.
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+Kimberly Wolfe, a delivery app driver in Seattle who fought for the wage law with an advocacy group called Working Washington, isn’t buying it. “These guys are doing what I call a corporate tantrum,” she tells Vox. “They’re just cutting off their nose to spite their face.”
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+What apps take from restaurants and customers
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+To be sure, delivery apps are convenient. For this ease of use, customers are painfully up-charged. Menu prices are almost always more expensive than ordering directly from restaurants. Then there are the line-item fees that appear on the receipt. There’s the delivery fee, but also the frustratingly generic “service fee” that could cover anything from keeping the apps’ servers up to paying their drivers. DoorDash charges a 15 percent service fee that starts at a $3 minimum. Uber Eats charges an unspecified service fee that depends on basket size. Browsing Grubhub in Seattle, I loaded a sample $62 food order and was levied a $14 service fee. Then add the taxes and tip. For the privilege of having a meal delivered to your home — something pizza and Chinese restaurants have done for at least half a century — you might find yourself paying nearly double the cost of just the food.
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+For restaurants, there’s a price as well. For the privilege of being found in the apps’ centralized hubs, apps can swipe as much as 30 percent of an order’s subtotal from restaurants, even collecting a commission on pickup orders. That’s if diners choose them over the influx of ghost kitchens and promoted partners.
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+Much attention has been paid to the fact that delivery apps aren’t profitable, or were on a long road to becoming profitable — but that’s in large part because they chose to invest aggressively in growth over being in the black at the end of the year. Last year, DoorDash’s profit margin was nearly 49 percent. Even after deducting a bunch of its biggest expenses, including driver pay, Uber’s delivery segment pocketed $1.5 billion, an increase of 173 percent from 2022.
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+Out of $8.6 billion in revenue in 2023, DoorDash spent almost $2 billion on sales and marketing, and another billion on R&D. It also spent $750 million last year buying back its own stock, a move often used by corporations to boost stock value. Uber has also long poured money into sales and marketing, which includes things like promotions and discounts, as well as R&D, in order to grow. This year, the company is preparing to shell out a cool $7 billion on stock buybacks.
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+What (little) apps provide to delivery workers
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+While customers find themselves paying $9-plus service fees on a delivery order, the worker handing you the food might only get a few dollars, all while paying for their own vehicle and fuel.
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+Wolfe recalls how paltry some of the payouts were before the Seattle wage law, when she would see $2 to $3 for an order before tips. In May 2022, Working Washington aggregated data from over 400 delivery jobs in the Seattle area and found that restaurant delivery workers were making on average $8.71 per hour after deducting basic expenses such as gas, which was far below the city’s 2022 minimum hourly wage of $17.27. During a Working Washington protest at City Hall in 2022, paper bags with receipts showing how much a worker had made on a delivery order were put on display.
+
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+“There were quite a few that were negative,” says Wolfe. “Once you figured expenses and all that, you were basically paying them to deliver.”
+
+
+A 2022 study from NYC’s Department of Consumer and Worker Protection (DCWP) found that, after expenses, food delivery workers in the city were making an average of $11.12 per hour — again, sub-minimum wages. Crucially, customer tips made up about half of a delivery driver’s total earnings before expenses. (Data from Solo, which makes software for app-based gig workers, shows that tips make up a similar proportion of pay in Seattle.) A more recent report on the adopted minimum pay projected that drivers’ annual earnings after expenses (and accounting for the common practice of working for multiple apps) would rise from $11,970 in 2021 to $32,500 by 2025. Yet this calculation relies on a key assumption: that customers would keep tipping about the same amount as before the wage law.
+
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+It’s hard to imagine that tipping rates in Seattle and NYC would stay the same given that the apps have added friction to the process. On both DoorDash and Uber Eats in these two cities, the tipping prompt now comes up after delivery, not at checkout, when diners are less likely to engage with the app. On GrubHub, the option to tip at checkout is still available, but many NYC-area restaurants on the platform now show lower default tipping options that max out at 12 percent. (Of course, a customer can still input a custom amount.)
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+It has also likely gone down because deliveries have gone down. Some workers in NYC report that the apps are now locking them out, restricting the number of hours they work. Justice for App Workers, a coalition of rideshare and delivery workers, held a rally in front of New York’s city hall on March 27 to demand that the city address the lockouts. Food delivery workers are saying that they’re “unable to work for hours and days on end,” according to a statement released by the group. Bimal Ghale, a delivery worker in New York who is part of the Justice for App Workers group, told Vox through an interpreter that he used to work five to six hours at a time. “After the minimum wage started, I would be on the apps and after two hours it would lock me out,” he says. “The apps claim the area isn’t busy.” But Ghale is still delivering in the same neighborhoods he did before the new pay law, and the DCWP has also stated that orders have “remained steady.”
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+An Uber spokesperson said that the city had known workers’ access to apps would become limited due to the new hourly pay rule. “Since the rule went into effect, nearly 6,000 couriers have lost access to the platform, nearly 20,000 people are on the waitlist to work on the app,” the spokesperson said.
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+Since last December, when the pay rule went into effect in NYC, at least 500 complaints have been lodged with the DCWP alleging that apps aren’t following it. A DCWP spokesperson told Vox that the department was monitoring compliance.
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+In Seattle, DoorDash has slapped a $4.99 regulatory fee on all orders, and in NYC it charges an extra $1.99. It’s unclear how these meaningfully differ from the catchall service fee, a portion of which can also cover worker pay — except that the labeling points the finger at the law for higher prices. DoorDash’s regulatory response fees are meant to cover the costs of new regulations. The DCWP estimates that if apps passed on only half of their labor costs to consumers, instead of all of it, they would still pocket $232 million a year in revenue. It’s not a given that the apps have to charge us more to pay their workers better.
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+Apps cry that their hands are tied
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+Not long after the pay law went into effect, DoorDash published a blog claiming that Seattle businesses had already lost over $1 million in revenue and that workers were making less because orders on the platform had dropped. Grubhub’s write-up on the law’s adverse effects claims that tips are down 26 percent, with no mention of the fact that many of its Seattle-area merchants now show a lower range of tipping options — a tactic the company has used before.
+
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+None of these tactics are new. Just look at what happened in California after the passage of a ballot initiative called Proposition 22 a few years ago, which allowed app-based gig work companies like Uber and DoorDash to classify their workers as independent contractors, saving them a lot of money. In exchange, they agreed to pay 120 percent of the minimum wage for every hour of trip time — as in, time spent logged on the app, waiting for a ride or for an order to appear, would not count. App companies spent hundreds of millions of dollars backing Prop 22, even threatening to pull out of California if it failed to pass. They also warned that, without Prop 22, prices would go up for customers. A month after the successful vote, delivery apps announced fee increases anyway.
+
+
+The math doesn’t add up. On the one hand, delivery apps play up the fact that they’re just intermediaries helping facilitate the sale or delivery of a product — they’re not employers, who would be on the hook for far greater payroll taxes and other employment costs than what apps currently pay. On the other hand, they command a steep price from restaurants and customers for matchmaking, of which the workers only see a narrow slice. The apps don’t make the food taste better, or deliver faster, and it’s obviously not cheaper. So who, exactly, benefits from their existence? What do they really add to the tangle of relationships we call the economy? If app companies leave cities like Seattle and New York to avoid having to pay higher labor costs, who would lose?
+
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+Wolfe doesn’t seem worried. Her thinking is that if they can’t run a competent business, perhaps they shouldn’t be in business. “Don’t let the door hit you,” she says. “Because you want capitalism — baby, that’s capitalism.”
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+
Pig kidney transplants are cool. They shouldn’t be necessary. -
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+Melissa Mattola-Kiatos, RN, removes the pig kidney from its box to prepare for transplantation as part of Mass General’s historic pig kidney transplant surgery on March 16, 2024. | Massachusetts General Hospital
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+We eat pigs. Do we need them to process our urine too?
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+No one tells you, when you donate your kidney, that from that point on you’re a Kidney Guy.
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+When kidney things happen in the news, everyone you know will text you. When a friend of a friend is diagnosed with kidney failure, as about 136,000 Americans were in 2021, you’ll hear about it. When acquaintances are thinking about donating, you’ll get a call.
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+It’s been nearly eight years since I donated mine in 2016, and my Kidney Guy status has not faded.
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+
+The flurry of kidney texts started anew at the end of March when researchers at Massachusetts General Hospital in Boston announced that they had transplanted a kidney from a genetically engineered pig into a living human for the first time.
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+They weren’t the first to try something like this. In 2021, researchers at NYU conducted the first pig kidney (or “pigney”) donation to a brain-dead patient, finding that the transplant took and the kidney was producing urine, the way kidneys should. They also used a genetically engineered pig to reduce the odds that the human immune system would reject the organ. In 2023, the NYU team repeated the experiment and found that a pigney could last for over two months.
+
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+But the Mass General researchers went a step further when they transplanted a pigney into Rick Slayman, a 62-year-old Weymouth, Massachusetts, man who was very much alive. He luckily remains alive as of this writing and is producing urine through the piece of pork that some doctors put in him.
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+This is unquestionably good news for Slayman, and while routine pig kidney transplants are still a few years off, it’s obviously good for people with kidney failure to have more options.
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+We shouldn’t let the news distract us, however, from an uncomfortable fact: Humans could, if we wanted to, end the kidney shortage right now without any assistance from our porcine friends.
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+Why pigneys are a game changer
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+The Mass General announcement is big news for one simple reason: Not enough humans are donating their kidneys.
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+While some 135,972 Americans were diagnosed in 2021 with end-stage renal disease, a condition that you need either dialysis or a transplant to survive, only 25,549 transplants took place that year. The remaining 110,000 people needed to rely on dialysis.
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+Dialysis is a miraculous technology, but compared to transplants, it’s awful. Over 60 percent of patients who started traditional dialysis in 2017 were dead by 2022. Of patients diagnosed with kidney failure in 2017 who subsequently got a transplant from a living donor, only 13 percent were dead five years later.
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+Life on dialysis is also dreadful to experience. It usually requires thrice-weekly four-hour sessions sitting by a machine, having your blood processed. You can’t travel for any real length of time, since you have to be close to the machine. More critically, even part-time work is difficult because dialysis is physically extremely draining.
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+Pigneys are exciting because they represent the possibility of a world where dialysis is a relic, like iron lungs for polio.
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+There’s still a ways to go before this future is realized. Technically, pigneys aren’t even in the clinical trial stage — to date, experiments have been allowed under “compassionate use” rules, and those participating have either been already dead or without any other option for survival. Researchers will need years to conduct formal trials and evaluate the approach for safety and complications.
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+But these early indications are promising, and logistically, it would be feasible.
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+We can easily have farms breed 68,000 pigs a year, each giving its kidneys to two deserving human recipients as soon as they’re diagnosed with kidney failure. The US has 75 million pigs alive now for meat production; a few dozen thousand more for transplantation is a drop in the bucket.
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+ Irfan Khan / Los Angeles Times via Getty Images
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+Dialysis is a miraculous technology, but compared to transplants, it’s awful.
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+We shouldn’t need pigneys
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+
+But there’s something sad to me about the pigney moment, too.
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+Partly this is because I’m an animal lover who thinks there’s something wrong with killing pigs, which are intelligent animals capable of tasks like playing video games, for meat.
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+And while I argue there’s obviously less wrong with killing them to harvest lifesaving organs, it seems like a necessary evil at best. Maybe we’ll take one kidney each from the pigs and then send them off to live on a beautiful farm, but I have my doubts.
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+The bigger issue is that we should not have to rely on pigs at all.
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+There are more than enough human beings walking around with spare kidneys who could donate them to strangers in need. They simply choose not to.
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+Getting 136,000 human kidneys for transplant every year in the US is very possible.
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+We can make up part of the gap by collecting more organs from deceased patients. Organ procurement organizations, which distribute organs from dead people, have been very conservative about which organs they’ll use; federal agencies are now investigating them for fraud. There are likely thousands more organs we could be recovering every year by reforming these groups — but not enough to wipe out the kidney backlog.
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+We can’t rely on dead people, or pigs, to close the kidney gap in the near term. We need living people.
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+We could do more to encourage donations. Going through a nephrectomy is real work, and it deserves compensation. Many kidney donors have rallied behind a proposal to give a $10,000-a-year tax credit for every donor for five years, to make up for lost wages and other costs incurred due to donating. This would go a long way toward filling the shortage
+
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+But that kind of policy change will take time as well.
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+In the meantime, we could eliminate the backlog, this year, if a tiny share of adult Americans agreed to donate their kidney to someone who needs one. Not everyone is eligible, but far more than most people think are. Maybe a friend of yours could. Maybe a family member. Maybe you.
+
The voices Oppenheimer left out -
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+Passersby walk near a poster for ‘Oppenheimer’ in Roppongi, as the film debuts in Japan eight months post worldwide launch on March 30, 2024. | Marcin Nowak/Anadolu/Getty Images
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+The film’s Japan premiere renews critiques about what the movie omitted.
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+The Oscar-winning film centers heavily on J. Robert Oppenheimer and follows the physicist’s journey in developing the atomic bomb for the United States. It does not directly show the fallout of the bombs in Hiroshima and Nagasaki, and it also does not feature any Japanese perspectives in the form of major characters or testimonials.
+
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+While some Japanese viewers noted that the film is from Oppenheimer’s point of view and that the lack of these voices is in line with that, others argued that its focus on his perspective helped glorify his actions and downplay their consequences.
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+“From Hiroshima’s standpoint, the horror of nuclear weapons was not sufficiently depicted,” former Hiroshima Mayor Takashi Hiraoka said during a premiere event for the film.
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+These reactions echoed similar pushback the film received in the US — reinvigorating questions about whose stories get told, and whether the ones that Hollywood chooses to focus on offer a limited understanding of the world and gloss over major harms.
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+On Friday, the film premiered with content warnings for viewers, which noted that it could spur recollections about the damage and trauma the bombs caused in Hiroshima and Nagasaki in 1945. Those bombs killed an estimated 140,000 people in Hiroshima and 74,000 in Nagasaki, maimed and wounded tens of thousands of others, and caused higher rates of cancer survivors.
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+According to several news reports, the Barbenheimer controversy and the nature of the film’s subject matter have added attention to its release in Japan. Hiraoka, the former mayor of Hiroshima, is among those who have commented on the film, along with multiple surviving victims of the atomic bombs, known as “hibakusha.” “Is this really a movie that people in Hiroshima can bear to watch?” Kyoko Heya, the head of Hiroshima’s international film festival, previously asked. According to Variety, the film placed third at the box office in its opening weekend.
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+Some Japanese people who saw the film questioned both the lack of Japanese perspectives as well as the tone of the movie, which they saw as lauding both Oppenheimer and his work on the Manhattan Project.
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+“The sense of excitement among people celebrating the experiment and the dropping of the atomic bomb. I felt incredibly disgusted,” Erika Abiko, an anti-nuclear activist, told the BBC.
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+“Of course this is an amazing film which deserves to win the Academy Awards,” Kawai, another viewer in Hiroshima, told Reuters. “But the film also depicts the atomic bomb in a way that seems to praise it, and, as a person with roots in Hiroshima, I found it difficult to watch.”
+
+Director Christopher Nolan has responded to such critiques in the past, noting that the film is intended to capture Oppenheimer’s perspective, so it doesn’t go beyond that. “To depart from [his experience] would betray the terms of the storytelling,” Nolan has said. “He learned about the bombings of Hiroshima and Nagasaki on the radio — the same as the rest of the world.”
+
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+Certain Japanese moviegoers agreed with this sentiment, stating that the film’s emphasis on Oppenheimer and exclusion of other experiences made sense. Others noted that it still served as an important cautionary tale despite failing to fully capture what took place in Hiroshima and Nagasaki.
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+“This was really a film about Oppenheimer the man, and the way he wrestled with his conscience, so in that sense, I think it was right not to broaden it out too much to show the aftermath,” Mei Kawashima, a Hiroshima resident, told the Guardian.
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+Broadly, though, many Japanese viewers expressed discomfort with Oppenheimer’s storytelling and felt the portrayal was incomplete. “The film was only about the side that dropped the A-bomb,” Tsuyuko Iwanai, a Nagasaki resident, told NPR. “I wish they had included the side it was dropped on.”
+
+
+These reactions build on a conversation about missing voices
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+
+At its core, the Oppenheimer discourse is about which characters get humanized in major films — and who gets to narrate these stories.
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+“I was uncomfy watching yet another movie about tortured white male genius when the victims of the atrocities glossed over by the script — Japanese people, interned Japanese Americans, and Native Americans — had no voice,” Li Lai, a Taiwanese American media critic, wrote last July.
+
+
+The exclusion of Japanese people in the film has been a major point of contention, as has the erasure of stories of Native Americans and Hispanic Americans who lived near New Mexico sites where significant bomb testing took place.
+
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+Both Native and Hispanic communities in the region were displaced by the construction of Los Alamos, and residents who lived close to test sites have experienced disproportionately high rates of cancer and infant deaths in the decades since.
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+By leaving these voices out of the movie, critics say Oppenheimer fails to fully grapple with the impact of the titular character’s actions — and the violence that followed.
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+The film’s premiere in Japan has forced a confrontation of some of these concerns. There’s been debate, too, about whether Oppenheimer could have shown more of the trauma from the bombings, or if that approach would have been harmful and effectively gawking at the suffering.
+
+
+Naoko Wake, a Michigan State University historian who has interviewed survivors of the bombings, notes that thoughtfully including such images could be vital for awareness when there has been so little understanding of Japanese civilians’ perspective.
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+“I ask my students every time I teach this subject, ‘Have you ever been exposed to any of the images outside of the mushroom clouds?’ They say that they have never seen images from ground zero or any effects of radiation exposure,” Wake told Vox. She points to a scene of Oppenheimer turning away from photos he’s being shown from the bombings as a potential moment in which the film could have allowed viewers to bear witness as well.
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+Beyond videos or photos of the violence, no Japanese characters were included to express or convey the effects of these weapons, either. It’s possible to envision a scene of a radio broadcast featuring interviews with Japanese people describing their experience with the horrors of the bombs, for example.
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+Notably, this pushback matters because it raises questions about whose perspective gets to be the definitive one in storytelling — including on such high-profile platforms.
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+“Hollywood is a powerful tool for white perspectives,” Ponipate Rokolekutu, a professor of race and resistance studies at San Francisco State University, told KQED. “They don’t want other histories to be known.”
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From The Hindu: Sports
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Umpire Marais Erasmus admits to making ‘massive error’ in 2019 ODI World Cup final - England won their maiden ODI World Cup title by edging New Zealand on the now-scrapped boundary countback rule after both teams were tied following a Super Over.
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Reminiscence and Vincent Van Gogh please -
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India, Australia and England cricket boards in talks to revive Champions League T20 - The last edition of the CLT20 was held in India in 2014 with Chennai Super Kings winning the title after defeating Kolkata Knight Riders in the final at Bengaluru
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All India Football Federation suspends member for alleged physical assault of two women players - Sports Minister Anurag Thakur had asked the AIFF to take “quick” and “strong legal action” against the official
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Twenty20 World Cup | Ben Stokes pulls out; says it’s his sacrifice to remain an all-rounder - Ben Stokes has informed the England & Wales Cricket Board (ECB) about his decision, two months ahead of the showpiece that will be held in the USA and West Indies.
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From The Hindu: National News
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TRAI seeks more inputs for I&B Ministry’s National Broadcasting Policy - The National Broadcasting Policy is likely to expand the policy ambit of the subject beyond linear broadcasting to OTT streaming
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Road over the Sengipatti vehicular underpass on national highway reopened to two-way traffic - Some of the facia panels on the southern side of the flyover near the Sengipatti bus stop collapsed on June 20 last year and the stretch was closed for vehicular traffic
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KCR should be named as main accused in phone tapping case: BJP - Mr. Rao said that the phone tapping investigation should be done from June 2, 2014 onwards including ‘vote for note’ case under which the present CM Revanth Reddy was sent to jail
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Vijay Deverakonda on ‘Family Star’: We have gone all out to give people an entertainer - Actor Vijay Deverakonda discusses his new film ‘Family Star’, opens up on what has mellowed him in recent times, learnings from ‘Liger’ and the business of cinema
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Two companies of CAPF personnel arrive in Perambalur for poll duty -
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From BBC: Europe
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Child held after pupil shot dead at Finnish school - Police say a shooting north of Helsinki leaves one child dead and a suspect aged 12 in custody.
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Deepest Ukraine drone attack into Russia injures 12 - Tatarstan region authorities say drones hit the town of Yelabuga and an oil refinery in Nizhnekamsk.
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French toddler’s remains found but death a mystery - Emile Soleil disappeared in a tiny Alpine village nine months ago. How he died remains unclear.
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Investigation links ‘Havana Syndrome’ to Russia - Media reports further fuel the view that US diplomats may have been targeted with sonic weapons.
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Barrage of Russian attacks aims to cut Ukraine’s lights - Russia has launched a wave of additional strikes across the country targeting the energy supply.
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From Ars Technica
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Daily Telescope: A shiny cluster of stars in a nearby galaxy - This cluster is about 2 billion years old. - link
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Trash from the International Space Station may have hit a house in Florida - NASA collected the item to confirm whether it came from the International Space Station. - link
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OpenAI drops login requirements for ChatGPT’s free version - ChatGPT 3.5 still falls far short of GPT-4, and other models surpassed it long ago. - link
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Microsoft splits up the Teams and Office apps worldwide, following EU split - Changes may save a bit of money for people who want Office apps without Teams. - link
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Discord starts down the dangerous road of ads this week - Discord’s first real foray into ads seems minimally intrusive. - link
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From Jokes Subreddit
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Scotsman, Englishman, and an Irishman walk into a bar -
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+Sitting in a bar the Scotsman says, “As good as this bar is, I still prefer the pubs back home. In Glasgow, there’s a wee place. The landlord goes out of his way for the locals. When you buy four drinks, he’ll buy the fifth drink.” “Well,” said the Englishman, “At my local in London , the barman will buy you your third drink after you buy the first two.” “Ahhh, dat’s nothin’,” said the Irishman, “back home in my favorite pub, the moment you set foot in the place, they’ll buy you a drink, then another, all the drinks you like, actually. Then, when you’ve had enough drinks, they’ll take you upstairs and see that you gets laid, all on the house!” The Englishman and Scotsman were suspicious of the claims. The Irishman swore every word was true. Then the Englishman asked, “Did this actually happen to you?” “Not to me, personally, no,” admitted the Irishman, “but it did happen to me sister quite a few times.”
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+Jack goes to his buddy Bob and says … “I’m sleeping with the priest’s wife. Can you hold him in church for an hour after mass for me?” The friend doesn’t like it but being a buddy, he agrees. After mass, Bob starts talking to the priest, asking him all sorts of stupid questions, just to keep him occupied. Finally the priest gets annoyed and asks him what he’s really up to. Bob feeling guilty, finally confesses to the priest… “My friend is sleeping with your wife right now, so he asked me to keep you occupied.” The priest smiles, puts a brotherly hand on Bob’s shoulder and says… “You better hurry home now. My wife died a year ago”.
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+One day, a man bought a lie detecting robot that would slap anyone who lies. He’s sitting in his living room when his son walks in the front door. The Dad asks, “Where ya been, son?” Son: “I went to watch the new kung fu panda movie.” The robot comes and slaps the son. Dad:“Son, the robot slaps anyone who lies, now tell me the truth.” Son:“dad, I actually went to watch an R rated film, I’m sorry,” Dad:“Is this how we raised you, son, watching filth in your age, I have never done anything like this in your age,” The robot comes and slaps the dad. Seeing this, the mom walks in and says “ha what did you expect? he’s your son after all” The robot comes and slaps the mom
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+Bob goes to confession and says, “Bless me father for I have sinned. On Friday I went golfing and I used the “F” word." The priest replies, “Tell me about it, my son”.
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+Bob says, “I was on the first tee, and I shanked a shot wide left”. The priest responds, “Oh, you must have said it then”. “No,” Bob says,” because the ball went into the woods, hit a tree, and bounced back right into the middle of the fairway.”
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+The priest says, “And then what happened?” Bob went on, “I hit my second shot, and the ball went wide right”. The priest asks again, “So you said it then?” Bob replies, “No, because my shot hit the ball washer machine on the next hole, popped up, and wound up right in the low rough”.
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+The rapidly becoming exasperated priest asks loudly, “Oh, so did you say it then?” “No, because I took my wedge and hit it, and it wound up on the green, about six inches from the cup.” Bob replied.
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+The priest shouts, “Oh, lord! You missed that fucking put, didn’t you!”
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+/cdn.vox-cdn.com/uploads/chorus_asset/file/25366406/GettyImages_1212888001.jpg)
Irfan Khan / Los Angeles Times via Getty Images
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