Ulrich bundles on some threefold scrolls over F_e

We investigate the existence of Ulrich vector bundles on suitable 3-fold scrolls Xe over Hirzebruch surfaces Fe, for any e⩾0, which arise as tautological embedding of projectivization of very-ample vector bundles on Fe which are uniform in the sense of Brosius and Aprodu--Brinzanescu (cf. [8] and [3], respectively, in Bibliography). We explicitely describe components of moduli spaces of rank r⩾1 Ulrich vector bundles whose general point is a slope-stable, indecomposable vector bundle. We moreover determine the dimension of such components as well as we prove that they are generically smooth. As a direct consequence of these facts, we also compute the Ulrich complexity of any such Xe and give an effective proof of the fact that such Xe's turn out to be geometrically Ulrich wild

KDM3B inhibitors disrupt the oncogenic activity of PAX3-FOXO1 in fusion-positive rhabdomyosarcoma

fusion-positive rhabdomyosarcoma (FP-RMS) is an aggressive pediatric sarcoma driven primarily by the PAX3-FOXO1 fusion oncogene, for which therapies targeting PAX3-FOXO1 are lacking. here, we screen 62,643 compounds using an engineered cell line that monitors PAX3-FOXO1 transcriptional activity identifying a hitherto uncharacterized compound, P3FI-63. RNA-seq, ATAC-seq, and docking analyses implicate histone lysine demethylases (KDMs) as its targets. enzymatic assays confirm the inhibition of multiple KDMs with the highest selectivity for KDM3B. structural similarity search of P3FI-63 identifies P3FI-90 with improved solubility and potency. biophysical binding of P3FI-90 to KDM3B is demonstrated using NMR and SPR. P3FI-90 suppresses the growth of FP-RMS in vitro and in vivo through downregulating PAX3-FOXO1 activity, and combined knockdown of KDM3B and KDM1A phenocopies P3FI-90 effects. thus, we report KDM inhibitors P3FI-63 and P3FI-90 with the highest specificity for KDM3B. their potent suppression of PAX3-FOXO1 activity indicates a possible therapeutic approach for FP-RMS and other transcriptionally addicted cancers.there is lack of therapies targeting the PAX3-FOXO1 fusion oncogene in fusion-positive rhabdomyosarcoma (FP-RMS). here, the authors identify and characterise an inhibitor with highest inhibition of histone lysine demethylase 3B that suppresses PAX3-FOXO1 activity in FP-RMS

Search for pair production of squarks or gluinos decaying via sleptons or weak bosons in final states with two same-sign or three leptons with the ATLAS detector

A search for pair production of squarks or gluinos decaying via sleptons or weak bosons is reported. The search targets a final state with exactly two leptons with same-sign electric charge or at least three leptons without any charge requirement. The analysed data set corresponds to an integrated luminosity of 139fb−1 of proton-proton collisions collected at a centre-of-mass energy of 13TeV with the ATLAS detector at the LHC. Multiple signal regions are defined, targeting several SUSY simplified models yielding the desired f inal states. A single control region is used to constrain the normalisation of the WZ +jets background. No significant excess of events over the Standard Model expectation is observed. The results are interpreted in the context of several supersymmetric models featuring R-parity conservation or R-parity violation, yielding exclusion limits surpassing those from previous searches. In models considering gluino (squark) pair production, gluino (squark) masses up to 2.2 (1.7) TeV are excluded at 95% confidence leve

Photocatalytic degradation of organic pollutants - Nile Blue, Methylene Blue, and Bentazon Herbicide - using NiO-ZnO nanocomposite

Water pollution poses a significant threat to both human health and ecosystem integrity. Chemical pollutants such as dyes and pesticides affect the water quality and endanger aquatic life. Among the methods for water purification from organic pollutants, photodegradation is certainly a valid technique to decrease such contaminants. In this work, pristine NiO, ZnO, and NiO-ZnO photocatalysts were synthesized by the homogeneous co-precipitation method. X-ray diffraction confirms the formation of a photocatalyst consisting of ZnO (Hexagonal) and NiO (Cubic) structures. The crystalline size was calculated by the Scherrer formula, which is 19 nm for the NiO-ZnO photocatalyst. The band gap measurements of the prepared samples were obtained using the Tauc Plot, equation which is 2.93 eV, 3.35 eV and 2.63 eV for NiO, ZnO, and NiO-ZnO photocatalysts, respectively. The photocatalytic performance of NiO-ZnO nanocomposite was evaluated through the degradation of Methylene Blue and Nile Blue dyes under sunlight, and Bentazon herbicide under a UV light. Photocatalyst degradation efficiency was 95% and 97% for Methylene Blue and Nile Blue in 220 min under sunlight while a degradation of 70% for Bentazon after 100 min under UV light source was found

Business network paradoxes: A literature review and co-evolutionary perspective

How can studying paradoxes in business networks help understand the networks' adaptation and survival? IMP identifies three central paradoxes influencing business networks: i) Development of Relationships vs. Inability to Change, ii) Controlling vs. Effectiveness, and iii) Stability vs. Change. Studying them seems critical to knowing how interdependent participants in business networks adapt to one another. To do that, we use a co-evolutionary lens to review 41 articles dealing with business network paradoxes from an IMP perspective. Results of the Reflexive Thematic Analysis underline that salient tensions mainly originate from weak coordinating norms, resource misallocation, the relationship of newness and aging, and Machiavellian behaviour. As the main value of our work, we then advance that embracing a co-evolutionary perspective can help shed novel light on these paradoxes by contrasting the factors that make the tensions salient with those able to overcome them. Specifically, we identify moral behaviour, structuration of the network, network capability development, and co-adaptation as four main factors that mitigate the paradoxes and help networks' adaptation and survival. Accordingly, we advocate a co-evolutionary conceptual framework regarding paradoxes and outline five co-evolutionary claims as implications for research and practice

Hearing dysfunction heralds an increase in non-motor burden and a worse quality of life in Parkinson’s disease: new insights from non-motor spectrum

background: sensorial non-motor symptoms (NMSs) in parkinson's disease (PD) still lack appropriate investigation in clinical practice. this study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). methods: We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. demographic and clinical data were collected. patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed non-motor symptoms scale (NMSS) and parkinson's disease questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. Results: 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. conclusion: this study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL

Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART

Introduction Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIV RNA and cell-associated (CA) HIV DNA and RNA. Both CA-DNA and CA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population. Methods Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CA-RNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested. Results CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CA-RNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-alpha was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ T-lymphocytes were not predictive of the CA-RNA in this cross-sectional study. Conclusions Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation