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RPS3, a universal core component of the 40S ribosomal subunit, interacts with mRNA at the entry channel. Whether RPS3 mRNA-binding contributes to specific mRNA translation and ribosome specialization in mammalian cells is unknown. Here we mutated RPS3 mRNA-contacting residues R116, R146 and K148 and report their impact on cellular and viral translation. R116D weakened cap-proximal initiation and promoted leaky scanning, while R146D had the opposite effect. Additionally, R146D and K148D displayed contrasting effects on start-codon fidelity. Translatome analysis uncovered common differentially translated genes of which the downregulated set bears long 5’UTR and weak AUG context, suggesting a stabilizing role during scanning and AUG selection. We identified an RPS3-dependent regulatory sequence (RPS3RS) in the sub-genomic 5’UTR of SARS-CoV-2 consisting of a CUG initiation codon and a downstream element that is also the viral transcription regulatory sequence (TRS). Furthermore, RPS3 mRNA-binding residues are essential for SARS-CoV-2 NSP1-mediated inhibition of host translation and for its ribosomal binding. Intriguingly, NSP1-induced mRNA degradation was also reduced in R116D cells, indicating that mRNA decay occurs in the ribosome context. Thus, RPS3 mRNA-binding residues have multiple translation regulatory functions and are exploited by SARS-CoV-2 in various ways to influence host and viral mRNA translation and stability.

Increasing evidence suggests that ribosome composition and modifications contribute to translation control. Whether direct mRNA binding by ribosomal proteins regulates the translation of specific mRNA and contributes to ribosome specialization has been poorly investigated. Here, we used CRISPR–Cas9 to mutate the RPS26 C-terminus (RPS26dC) predicted to bind AUG upstream nucleotides at the exit channel. RPS26 binding to positions −10 to −16 of short 5′ untranslated region (5′UTR) mRNAs exerts positive and negative effects on translation directed by Kozak and Translation Initiator of Short 5′UTR (TISU), respectively. Consistent with that, shortening the 5′UTR from 16 to 10 nt diminished Kozak and enhanced TISU-driven translation. As TISU is resistant and Kozak is sensitive to energy stress, we examined stress responses and found that the RPS26dC mutation confers resistance to glucose starvation and mTOR inhibition. Furthermore, the basal mTOR activity is reduced while AMP-activated protein kinase is activated in RPS26dC cells, mirroring energy-deprived wild-type (WT) cells. Likewise, the translatome of RPS26dC cells is correlated to glucose-starved WT cells. Our findings uncover the central roles of RPS26 C-terminal RNA binding in energy metabolism, in the translation of mRNAs bearing specific features and in the translation tolerance of TISU genes to energy stress.

The imagined universe of the people of Late Antiquity was heavily populated by gods. Even the broader philosophical trends and monotheistic foundation of Judaism and Christianity had failed to entirely diminish their power. How then did Jews and Christians cope with such a backdrop presence of “other gods”? Earlier research suggested that Jewish attitudes, which found their way into early Christian sources as well, fluctuate between accommodation and rejection. Following analysis of Jewish and Christian Late Antique literary traditions dealing with gods, and more specifically, goddesses, this article aims to demonstrate that such “fluctuation” resulted – in addition to the extreme positions – in a variety of middle of the road strategies. These strategies point to a keen harmonizing impulse to absorb—via domestication—motifs with mythic religious vitality from the broader cultural repository.

We suggest that individuals with obsessive-compulsive disorder (OCD) experience difficulty accessing their internal states, including their feelings, emotions, preferences, and motivations. Instead, they rely on proxies to inform them of these states—that is, discernible substitutes in the form of fixed rules and rituals, observable behavior, and indexes. The Seeking Proxies for Internal States (SPIS) model of OCD proposes that compulsions, obsessions, indecision, and doubt result from seeking and using such proxies. The SPIS model not only accounts for these OCD symptoms but also sheds new light on normal processes of action control, metacognition, decision-making, and introspection.

The past decade has witnessed the creation of a new international tax regime. The original international tax regime was created a century ago by the League of Nations. Until the 1980s, it functioned reasonably well and prevented most instances of double taxation and double non-taxation by allocating cross-border income between home and host jurisdictions based on a compromise reached in 1923. However, since the advent of globalization in the 1980s and digitalization in the 1990s, the original international tax regime ceased to function as intended. The main problems were the increased mobility of capital related to increased intangibility and digitalization, together with a relaxation of capital controls and increased tax competition. These developments posed a problem for countries that wished to leave their borders open to reap the benefits of globalization and to engage in tax competition to attract investment. The outcome was a significant fall in tax revenues that threatened the social safety net of the modern welfare state. The trilemma of open borders, tax competition, and satisfying voters’ demand for social insurance culminated in the financial crisis of 2008–09, where many countries were forced to implement austerity measures at the same time that parliamentary hearings, leaks, and media reports revealed that rich individuals and large corporations were paying very little tax on cross-border income. The results over the past decade have been the creation of a new international tax regime designed to curb both tax evasion by the rich and tax competition among countries seeking to attract business activity within their borders by granting various preferential tax provisions to multinational enterprises. The key question going forward is how the new international tax regime will deal with international (in)equity, i.e. the economic digital divide. In what follows, I will first discuss the decline of the original international tax regime from 1980 to 2009, then the creation of the new international tax regime from 2010 on, and finally the implications of the new international tax regime for the economic digital divide.

Multistage sequential decision-making scenarios are commonly seen in the healthcare diagnosis process. In this paper, an active learning-based method is developed to actively collect only the necessary patient data in a sequential manner. There are two novelties in the proposed method. First, unlike the existing ordinal logistic regression model which only models a single stage, we estimate the parameters for all stages together. Second, it is assumed that the coefficients for common features in different stages are kept consistent. The effectiveness of the proposed method is validated in both a simulation study and a real case study. Compared with the baseline method where the data is modeled individually and independently, the proposed method improves the estimation efficiency by 62\%-1838\%. For both simulation and testing cohorts, the proposed method is more effective, stable, interpretable, and computationally efficient on parameter estimation. The proposed method can be easily extended to a variety of scenarios where decision-making can be done sequentially with only necessary information.

This study investigated whether students’ academic motivation during the Hyflex learning modality have a significant relationship with parental autonomy support, parental involvement, and academic achievement and the level of parental autonomy support, parental involvement, Academic Achievement among college Student Motivation during HyFlex Learning Modality. A sample of 100 college students of National University- Baliwag participated to complete a series of questionnaires, Pearson Correlation was used to attain the relationship bet ween the variables that was used. The result of the study found that the college students’ Parental Autonomy Support, Parental Involvement, and their Academic Achievement, when combined, significantly predicts the dependent variable level of Academic Motivation during Hyflex Learning Modality (F [3, 96] = 4.744, p = .004). This implies that the null hypothesis (Ho) is rejected; thus, there is a significant relationship between the parental autonomy support, parental involvement, academic achievement of college students and their academic motivation during Hyflex learning modality when taken as a whole. The implies that among parents, providing better emotional and mental support, on top of the material supports could affect positively the academic achievements of college students. Based on these results, parents would benefit by considering different approach that suits the educational needs of the college students by providing autonomous support and becoming more physically and emotionally involved.

HYPOTHESIS: Computed tomography (CT) density measurement can be used to objectively distinguish otosclerosis from normal bone and to determine histologic grades of otosclerosis. BACKGROUND: Otosclerosis can be seen on CT as subtle radiolucent areas. An objective radiologic measurement that corresponds to known otosclerosis pathology may improve diagnostic accuracy, and could be used as a radiologic biomarker for otosclerosis grade. METHODS: A blinded, randomized evaluation of both histologic grade on histopathology slides and CT density measurement was performed on 78 human temporal bone specimens (31 with otosclerosis and 47 controls) that had undergone high-resolution multi-detector CT prior to histologic processing. Assessments were performed at 11 regions of interest (ROIs) in the otic capsule for each specimen. RESULTS: The CT density measurement mean (Hounsfield Units) ± standard deviation for all ROIs (#1-#9) was 2245 ± 854 for grade 0 (no otosclerosis, n=711), 1896 ±317 for grade 1 (inactive otosclerosis, n=109), and 1632 ±255 for grades 2 and 3 combined (mixed/active otosclerosis, n=35). There was a strong inverse correlation of CT density to histologic grade at ROIs #1–5 (ANOVA, p

This article focuses on the changing cultural, social, and ideological characteristics of the central Sephardi Rabban Yochanan Ben-Zakai synagogue in Jerusalem, as a lens reflecting social and ideological processes of the local Sephardi community during the first half of the twentieth century. These included the community's attempts to consolidate its cultural uniqueness and civic identity vis-à-vis the surrounding and evolving spirits—within the Jewish community and outside it; its struggles with the local Ashkenazi community over historical and legal hegemony; its changing and evolving attitude toward the Ottoman and British Empires; and its gradual yet distinct adoption of the Jewish national framework. The article is based on an in-depth study of the archives of the Sephardi Commission (Va'ad Ha'eda HaSepharadit) in Jerusalem, as well as literary and scholarly sources and the local Jewish press of the time.

Programmed ribosomal frameshifting (PRF) is a key mechanism that viruses use to generate essential proteins for replication, and as a means of regulating gene expression. PRF generally involves recoding signals or frameshift stimulators to elevate the occurrence of frameshifting at shift-prone 'slippery' sequences. Given its essential role in viral replication, targeting PRF was envisioned as an attractive tool to block viral infection. However, in contrast to controlled-PRF mechanisms, recent studies have shown that ribosomes of many human cancer cell types are prone to frameshifting upon amino acid shortage; thus, these cells are deemed to be sloppy. The resulting products of a sloppy frameshift at the 'hungry' codons are aberrant proteins the degradation and display of which at the cell surface can trigger T cell activation. In this review, we address recent discoveries in ribosomal frameshifting and their functional consequences for the proteome in human cancer cells.

We present a randomized algorithm for generating standard set-valued tableaux by extending the Green-Nijenhuis-Wilf hook walk algorithm. In the case of asymptotically rank two partitions, we use this algorithm to give a fully polynomial almost uniform sampler (FPAUS) for standard set-valued tableaux. This FPAUS is then used to construct a fully polynomial randomized approximation scheme (FPRAS) for counting the number of standard set-valued tableaux for such shapes. We also construct a FPAUS and FPRAS for standard set-valued tableaux when either the size of the partition or the difference between the maximum value and the size of the partition is fixed. Our methods build on the work of Jerrum-Valiant-Vazirani and provide a framework for constructing FPAUS's and FPRAS's for other counting problems in algebraic combinatorics., 20 pages

We studied and found that the populations of two gastropod species in the inter-tidal zone of the Red Sea at Eilat demonstrate a predominantly dextral chirality of their shells. We identified lateralization sinistral/dextral shell torsion for 675 live Tenguella granulata (left = 114, 16.9%; right = 561, 83.1%) and 405 Clanculus pharaonius (left = 102, 25.2%; right = 303, 74.8%). In both cases, we found differences between sinistral and dextral shell torsions for Tenguella granulata and Clanculus pharaonius. The ecological and evolutionary consequences of individuals with sinistral chirality are unclear, but there are indications that it is a directional rather than stochastic process.

A watchman path is a path such that a direct line of sight exists between each point in some region and some point along the path. Here, we study the online watchman path problem outside a convex polygon, i.e., in $\mathbb{R}^2\setminus \Omega$, where $\Omega$ is a convex polygon that is not known in advance. We present an algorithm for the exploration of the region outside the polygon. We prove that the presented algorithms guarantees a $\approx 22.77$ competitive ratio compared to the optimal offline watchman path.

OBJECTIVE Mounting evidence indicates the detrimental impact of posttraumatic stress following childbirth (PTS-FC). Nevertheless, research on preventive strategies is scarce. We recently reported that ultrasound visual biofeedback during second stage of labor was associated with immediate beneficial medical outcomes (increased pushing efficacy, decreased perineal tearing), as well as greater feelings of maternal connectedness toward her newborn immediately postlabor. The current study assessed the potential longer-term psychological benefits of these outcomes in buffering risk for PTS-FC. The study follows up the previously reported sample to examine the longitudinal clinical effect of the visual biofeedback intervention on symptoms of acute stress at 2 days postpartum and subsequent symptoms of PTS-FC at 1 month postpartum. METHOD A sample of 26 nulliparous women received visual biofeedback and was compared to a group of women receiving standard obstetrical coaching. Maternal feelings of connectedness and acute stress symptoms were assessed 2 days postpartum and PTS-FC was assessed 1 month postpartum. RESULTS Double-mediation analyses revealed a significant indirect relation between visual biofeedback and decreased PTS-FC symptoms 1 month postpartum. The relation was significantly mediated by increased feelings of maternal connectedness immediately postpartum, which in turn was associated with decreased symptoms of acute stress 2 days postpartum. CONCLUSIONS These results suggest that the visual biofeedback intervention during childbirth may decrease risk for PTS-FC. Importantly, findings suggest the preventive potential of fostering feelings of maternal connectedness toward her newborn to reduce symptoms of PTS-FC. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Accumulating evidence identifies non-genetic mechanisms substantially contributing to drug resistance in cancer patients. Preclinical and clinical data implicate the transcriptional co-activators YAP1 and its paralog TAZ in resistance to multiple targeted therapies, highlighting the strong need for therapeutic strategies overcoming YAP1/TAZ-mediated resistance across tumor entities. Here, we show particularly high YAP1/TAZ activity in MITFlow/AXLhigh melanomas characterized by resistance to MAPK pathway inhibition and broad receptor tyrosine kinase activity. To uncover genetic dependencies of melanoma cells with high YAP1/TAZ activity, we used a genome-wide CRISPR/Cas9 functional screen and identified SLC35B2, the 3′-phosphoadenosine-5′-phosphosulfate transporter of the Golgi apparatus, as an essential gene for YAP1/TAZ-driven drug resistance. SLC35B2 expression correlates with tumor progression, and its loss decreases heparan sulfate expression, reduces receptor tyrosine kinase activity, and sensitizes resistant melanoma cells to BRAF inhibition in vitro and in vivo. Thus, targeting heparan sulfation via SLC35B2 represents a novel approach for breaking receptor tyrosine kinase-mediated resistance to MAPK pathway inhibitors.

The introduction of the minimum tax in Pillar II of the Organization for Economic Cooperation and Development (OECD)/G20/Inclusive Forum(IF) framework was generally seen as a response to the US Tax Cuts and Jobs Act (TCJA) of 2017. The TCJA included both a minimum tax on outbound income (the Global Intangible Low-Taxed Income, or ‘GILTI’) and a minimum tax on inbound income (the Base Erosion Anti-Avoidance Tax, or ‘BEAT’). These were seen as the precursors to the Income Inclusion Rule (IIR) and the Under Tax Payments Rule (UTPR). Thus, unlike Pillar I which was perceived as a device to impose more tax on the US digital giants, Pillar II was seen as more consistent with US tax policy. This story is true to some extent, but the relationship between the US and Pillar II is more complicated. Pillar II was the culmination of years of efforts to implement the single tax principle (STP), which has its origins in the 1920s but was not the guiding principle of US tax policy for a long period before the TCJA. Moreover, the TCJA does not fully implement Pillar II, and it is unclear whether the US can in fact do so. In this article, the authors first discuss the relationship between the TCJA and Pillar II, then the possible US responses to Pillar II, and finally what would happen if the US does not implement Pillar II. In general, if Pillar II is not implemented in the US, the tax consequences are likely to be increased double taxation as well as a shift in revenues from the US to foreign jurisdictions. GloBE, pillar 2, TCJA

This recommendation document follows the mission of the World Association of Perinatal Medicine (WAPM) in collaboration with the Perinatal Medicine Foundation (PMF). We aim to bring together groups and individuals throughout the world for standardization to implement the ultrasound evaluation in labor ward and improve the clinical management of labor. Ultrasound in labor can be performed using a transabdominal or a transperineal approach depending upon which parameters are being assessed. During transabdominal imaging, fetal anatomy, presentation, liquor volume, and placental localization can be determined. The transperineal images depict images of the fetal head in which calculations to determine a proposed fetal head station can be made.

To describe the DISCO protocol (Dilation, Steroid injection, and post-operative Cough Exercise); a novel treatment for posterior glottic stenosis (PGS). Restoring glottic mobility in PGS is a major challenge. In orthopedic and plastic surgery, post-operative physical therapy is associated with improved motion range and flexibility; yet, this principle was never applied to laryngeal surgery.A retrospective cohort of PGS adult patients, treated by the DISCO protocol during 2018-2020. DISCO involves the following: scar release, glottic dilation, and steroid injection, followed by post-operative cough as glottic physical therapy. Maximal glottic opening angle (MGOA), relative glottic opening area (RGOA), and relative glottic insufficiency area (RGIA) were calculated before and post-operatively.Seventeen patients were included; PGS etiology was post-intubation (n = 10), post-irradiation (n = 3), both (n = 1) and joint sclerosis (n = 3). Six patients also had additional airway disorders. Sixteen patients were tracheostomy-dependent. 2 (12%), 8 (47%) and 7 (41%) patients had type II, III and IV stenosis, respectively. Surgery included scar release, dilation and steroid injection alone in 7 patients; and additional unilateral sub-mucosal arytenoidectomy in 10. The mean follow-up was 17.5 months. There were no major complications. Successful outcomes (e.g., decannulation or permanent capping) were achieved in 14 (82%) patients with some restoration of joint movement. None had a persistent voice or swallowing complaints. Both MGOA and RGOA increased in all patients (p 0.001). RGIA remained unchanged (p = 0.878).The DISCO protocol is a novel, effective and safe approach for PGS correction that can be easily applied. It can restore vocal fold mobility and may expand the glottic airway without causing glottic insufficiency.4 Laryngoscope, 2022.

BNT162b2 messenger RNA (mRNA) COVID-19 vaccine administered during pregnancy was found to produce a strong maternal immunoglobulin (IgG) response which crosses the placenta to the newborn. Our aim was to evaluate maternal and neonatal SARS-CoV-2 IgG antibody levels at birth, following a COVID-19 booster vaccine during the third trimester.A prospective cohort study including women admitted to delivery ward at least 7 days after their BNT162b2 (Pfizer/BioNTech) booster vaccination without a prior clinical COVID-19 infection. SARS-CoV-2 IgG antibodies levels were measured in maternal blood upon admission to delivery and in the umbilical blood within 30 min following delivery. The correlation between antibody titers, feto-maternal characteristics, maternal side effects following vaccination, and time interval from vaccination to delivery were analyzed.Between September to November 2021, high antibody levels were measured in all 102 women and 93 neonatal blood samples, at a mean ± standard deviation duration of 7.0 ± 2.9 weeks after the third vaccine. We found positive correlation between maternal and neonatal antibodies (r = 0.73, 95% confidence interval [CI] 0.61 to 0.81, p 0.001), with neonatal titers approximately 1.4 times higher compared to maternal titers. In the multivariable analysis maternal antibody levels dropped by -7.2% (95% CI -12.0 to -2.3%, p = 0.005) for each week that passed since the receipt of the third vaccine dose. In contrary, systemic side effects after the third vaccine were associated with higher maternal antibody levels of 52.0% (95% CI 4.7 to 120.8%, p = 0.028). Also, for each 1 unit increase in maternal body mass index, maternal antibody levels increased by 3.6% (95% CI 0.4 to 6.9%, p = 0.025).BNT162b2 mRNA COVID-19 booster dose during the third trimester of pregnancy was associated with strong maternal and neonatal responses as reflected by maternal and neonatal SARS-CoV-2 IgG antibody levels measured at birth. These findings support the administration of the COVID-19 booster to pregnant women to restore maternal and neonatal protection during the ongoing pandemic.

In this study, sixteen unique staphylococcal enterotoxin B (SEB)-reactive nanobodies (nbs), including ten monovalent and six bivalent nbs, were developed. All characterized nbs were highly specific for SEB and did not cross-react with other staphylococcal enterotoxins (SE). Several formats of highly sensitive enzyme-linked immunosorbent assays (ELISAs) were established using SEB nbs and a polyclonal antibody (pAb). The lowest limit of detection (LOD) reached 50 pg/mL in PBS. When applied to an ELISA to detect SEB-spiked milk (a commonly contaminated foodstuff), a LOD as low as 190 pg/mL was obtained. The sensitivity of ELISA was found to increase concurrently with the valency of nbs used in the assay. In addition, a wide range of thermal tolerance was observed among the sixteen nbs, with a subset of nbs, SEB-5, SEB-9, and SEB-62, retaining activity even after exposure to 95 °C for 10 min, whereas the conventional monoclonal and polyclonal antibodies exhibited heat-labile properties. Several nbs demonstrated a long shelf-life, with one nb (SEB-9) retaining 93% of its activity after two weeks of storage at room temperature. In addition to their usage in toxin detection, eleven out of fifteen nbs were capable of neutralizing SEB’s super-antigenic activity, demonstrated by their inhibition on IL-2 expression in an ex vivo human PBMC assay. Compared to monoclonal and polyclonal antibodies, the nbs are relatively small, thermally stable, and easy to produce, making them useful in applications for sensitive, specific, and cost-effective detection and management of SEB contamination in food products.

Background: Cancer immunotherapy is implemented by identifying antigens that are presented on the cell surface of cancer cells and illicit T-cell response (Schumacher and Schreiber, Science 348:69–74, 2015; Waldman et al., Nat Rev Immunol 20:651–668, 2020; Zhang et al., Front Immunol 12:672,356, 2021b). Classical candidates of such antigens are the peptides resulting from genetic alterations and are named "neoantigen" (Schumacher and Schreiber, Science 348:69–74, 2015). Neoantigens have been widely catalogued across several human cancer types (Tan et al., Database (Oxford) 2020;2020b; Vigneron et al., Cancer Immun 13:15, 2013; Yi et al., iScience 24:103,107, 2021; Zhang et al., BMC Bioinformatics 22:40, 2021a). Recently, a new class of inducible antigens has been identified, namely Substitutants, that are produced as a result of aberrant protein translation (Pataskar et al., Nature 603:721–727, 2022).Main: Catalogues of Substitutant expression across human cancer types, their specificity and association to gene expression signatures remain elusive for the scientific community's access. As a solution, we present ABPEPserver, an online database and analytical platform that can visualize a large-scale tumour proteomics analysis of Substitutant expression across eight tumour types sourced from the CPTAC database (Edwards et al., J Proteome Res 14:2707–2713, 2015). Functionally, ABPEPserver offers the analysis of gene-association signatures of Substitutant peptides, a comparison of enrichment between tumour and tumour-adjacent normal tissues, and a list of peptides that serve as candidates for immunotherapy design. ABPEPserver will significantly enhance the exploration of aberrant protein production in human cancer, as exemplified in a case study.Conclusion: ABPEPserver is designed on an R SHINY platform to catalogue Substitutant peptides in human cancer. The application is available athttps://rhpc.nki.nl/sites/shiny/ABPEP/. The code is available under GNU General public license from GitHub (https://github.com/jasminesmn/ABPEPserver).

There has been a worldwide substantial increase in accidental opioid-overdose deaths. The aim of this review, along with preliminary results from our pilot study, is to highlight the use of pharmacogenetics as a tool to predict causes of accidental opioid-overdose death. For this review, a systematic literature search of PubMed® between the time period of January 2000 to March 2023 was carried out. We included study cohorts, case–controls, or case reports that investigated the frequency of genetic variants in opioid-related post-mortem samples and the association between these variants and opioid plasma concentrations. A total of 18 studies were included in our systematic review. The systematic review provides evidence of the use of CYP2D6, and to a lower extent, CYP2B6 and CYP3A4/5 genotyping in identifying unexpectedly high or low opioid and metabolite blood concentrations from post-mortem samples. Our own pilot study provides support for an enrichment of the CYP2B6*4-allele in our methadone-overdose sample (n = 41) compared to the anticipated frequency in the general population. The results from our systematic review and the pilot study highlight the potential of pharmacogenetics in determining vulnerability to overdose of opioids.

Only two types of Standard Model particles are able to propagate the $480\,$meters separating the ATLAS interaction point and FASER: neutrinos and muons. Furthermore, muons are copiously produced in proton collisions. We propose to use FASER$\nu$ as a muon fixed target experiment in order to search for new bosonic degrees of freedom coupled predominantly to muons. These muon force carriers are particularly interesting in light of the recent measurement of the muon anomalous magnetic moment. Using a novel analysis technique, we show that even in the current LHC run, FASER$\nu$ could potentially probe previously unexplored parts of the parameter space. In the high-luminosity phase of the LHC, we find that the improved sensitivity of FASER$\nu2$ will probe unexplored parameter space and may be competitive with dedicated search proposals., Comment: 13 pages + appendices, 11 figures

We prove a short, root-system uniform, combinatorial classification of Levi-spherical Schubert varieties for any generalized flag variety $G/B$ of finite Lie type. We apply this to the study of multiplicity-free decompositions of a Demazure module into irreducible representations of a Levi subgroup., 11 pages

Purpose: Morgagni hernias account for less than 5% of congenital diaphragmatic hernias. They are characteristically retrosternal and bilateral, with right-sided predominance. An association between Trisomy 21 and diaphragmatic hernias resembling Morgagni hernia has been reported, but the effect of cardiac surgery on its formation has not been investigated. The purpose of this study was to determine whether there is a higher incidence of anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery. Methods: We compared the prevalence of anterior diaphragmatic hernias in 92 patients with Trisomy 21 who underwent cardiac surgery with its prevalence in two control groups - children without Trisomy 21 who underwent cardiac surgery, and children with Trisomy 21 who did not undergo cardiac surgery, 100 patients in each. All available CXRs of all children underwent revision for the presence of an anterior diaphragmatic hernia by a pediatric radiologist. Results: Within the study group, four cases of an anterior diaphragmatic hernia were detected, all upon presentation to the emergency room due to breathing difficulties. No cases of an anterior diaphragmatic hernia were found in the two control groups (P = 0.0094) Conclusions: A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed. In light of our findings, the surgical technique has been modified in patients with DS in our medical center.

The complex functions of neuronal synapses depend on their tightly interconnected protein network, and their dysregulation is implicated in the pathogenesis of autism spectrum disorders and schizophrenia. However, it remains unclear how synaptic molecular networks are altered biochemically in these disorders. Here, we applied multiplexed imaging to probe the effects of RNAi knockdown of 16 autism- and schizophrenia-associated genes on the simultaneous joint distribution of ten synaptic proteins, observing several protein composition phenotypes associated with these risk genes. We applied Bayesian network analysis to infer hierarchical dependencies amongst eight excitatory synaptic proteins, yielding predictive relationships that can only be accessed with single-synapse, multiprotein measurements performed simultaneously in situ. Finally, we found that central features of the network are affected similarly across several distinct gene knockdowns. These results offer insight into the convergent molecular etiology of these widespread disorders and provide a general framework to probe subcellular molecular networks.

Theoretical analyses indicate that aggressive signals should positively correlate with the signallers' willingness and abilities to fight. Few experimental studies, however, have tested this prediction. In two experiments employing distinct, ecologically realistic protocols, we quantified the association between aggressive signals and fighting in fruit fly genotypes and found high positive genetic correlations between threat and fighting ( r G = 0.80 and 0.74). Our results add to the growing body of experimental work indicating that aggressive signals have relatively high informational value.