542 research outputs found
Charm cross section and fragmentation fractions in pp collisions with ALICE (12'+3')
No full textIn this contribution, the latest , and the first , and baryon measurements performed with the ALICE detector at midrapidity in proton--proton collisions at TeV and TeV at the LHC are presented. Recent measurements of baryon-to-meson cross-section ratios at midrapidity show significantly higher results than in and ep collisions, suggesting that the fragmentation of charm is not universal across different collision systems. Thus, measurements of charm-baryon production are crucial to study the charm-quark hadronisation in pp collisions and the possible difference with respect to and ep collisions.
In addition, the baryon-production measurements were essential for the measurement of the c production cross section performed by ALICE at midrapidity in pp collisions and also presented in this contribution.
Furthermore, the new preliminary measurement of the / ratio in in p--Pb collisions will be discussed. The measurement of charm baryons in proton--nucleus collisions provides important information about Cold Nuclear Matter (CNM) effects. It also helps to understand how the possible presence of collective effects could modify the production of heavy-flavour hadrons and to interpret the similarities observed among pp, proton--nucleus and nucleus--nucleus systems
A Strategy Oriented Framework for Food and Beverage E-Supply Chain Management
No full textSeveral authors have emphasized the importance of analysing the impact of e-business, e-commerce and online-shopping on supply chain and operations management; however, it seems that to date no one has suggested a comprehensive framework that could help identify and support supply chain design decisions for companies about to enter the online-business in the consumer goods retail trade, encompassing the business drivers at a strategic level. This paper aims to bridge the gap between theoretical taxonomies or abstract models and the concrete supply chain design problems encountered by logistics managers who need to take their Food & Beverage retail company into the internet business while also preserving a consistent alignment with their current company strategy. Some insights on this area are presented along with a field study approach and a proposal of a 6-phase framework to jointly manage all the relevant strategic and functional aspects of supply networks
Does Smartphone Use Affect a Subsequent Swimming Training Session? Preliminary Results in Amateur Triathletes
No full textTo date, the literature has failed to individuate a clear motivation for the performance decrement after a mental fatigue-inducing task. This study aimed to evaluate biomechanical and perceptual variables during a swimming training session in different mental fatigue states. Seven amateur triathletes watched a documentary, utilized a smartphone, or performed an AX-CPT for 45 min randomly on three different days. After, they performed a 15-min warm-up followed by 6 x 200 m at constant pre-set speed plus one 200 m at maximal effort. The mental fatigue status was assessed by the visual analog scale (VAS) and short-Stroop task results before, post-mental task, and post-swimming session. The biomechanical and motor coordination variables during swimming were assessed using five IMU sensors and video analysis. The heart rate and rate of perceived exertion were monitored during the task. No differences in biomechanical and perceptual variables were found between and within conditions. Higher mental fatigue was found only in the AX-CPT condition at post task by VAS. In this preliminary study, no changes in swimming biomechanics were highlighted by mental fatigue, but the warm-up performed may have counteracted its negative effects. Further studies are recommended
PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment
No full text: Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts and covalently PARylates TRF1 in S-phase modifying its DNA affinity. Therefore, genetic and pharmacological inhibition of PARP1 impairs the dynamic association of TRF1 and the bromodeoxyuridine incorporation at replicating telomeres. Inhibition of PARP1 also affects the recruitment of WRN and BLM helicases in TRF1 containing complexes during S-phase, triggering replication-dependent DNA-damage and telomere fragility. This work unveils an unprecedented role for PARP1 as a "surveillant" of telomere replication, which orchestrates protein dynamics at proceeding replication fork
A novel G-Quadruplex structure within Apolipoprotein E promoter: a new promising target in cancer and dementia fight?
No full textHuman Apolipoprotein E (APOE) is a crucial lipid transport glycoprotein involved in various biological processes, including lipid metabolism, immune response, and neurodegeneration. Elevated APOE levels are linked to poor prognosis in several cancers and increased risk of Alzheimer\u27s disease (AD). Therefore, modulating APOE expression presents a promising therapeutic strategy for both cancer and AD.
Considering the pivotal role of G-quadruplex (G4) structures in medicinal chemistry as modulators of gene expression, here we present a newly discovered G-quadruplex (G4) structure within the ApoE gene promoter. Bioinformatic analysis identified 21 potential G4-forming sequences in the ApoE promoter, with the more proximal to the transcription start site, pApoE, showing the highest G-score. Biophysical studies confirmed the folding of pApoE into a stable parallel G4 under physiological conditions, supported by circular dichroism, NMR spectroscopy, UV-melting, and quantitative PCR stop assay. Moreover, the ability to modulate pApoE-G4 folding was demonstrated using G4-stabilizing ligands (HPHAM, Braco19, and PDS), which increased the thermal stability of pApoE-G4. In contrast, peptide nucleic acid conjugates synthesized to disrupt G4 formation, effectively hybridizing with pApoE sequences, confirming the potential to unfold G4 structures. Overall, our findings provide a mainstay for future therapeutic approaches targeting ApoE-G4s to regulate APOE expression, offering potential advancements in cancer and AD treatment
BRC-1 co-localizes with pro-CO factors.
No full text(A) BRC-1::HA co-localizes with pro-CO factor COSA-1 in late prophase I. MP/LP = mid-/late pachynema, LP/DP = late pachynema/diplonema. Scale bar, 5 μm. (B) BRC-1::HA co-localizes with ZHP-3 and (C) GFP::MSH-5 in late pachytene nuclei. Scale bar, 5 μm. Bottom: Analysis of embryonic viability and segregation of male progeny shows full functionality of GFP::msh-5 and OLLAS::cosa-1 tagged lines. Embryos scored: WT (1311), GFP::msh-5 (1191), OLLAS::cosa-1 (1098), msh-5 (971), cosa-1 (927). (D) Partial projections of nuclei under super-resolution structured illumination microscopy: different examples show BRC-1::HA localization in the region surrounding the COSA-1-labeled CO site. BRC-1::HA forms a nodule-like structure together with SYP-1. (E) Insets showing magnified details from nuclei in (D).</p
Mechanism of BRCA1-BARD1 function in DNA end resection and DNA protection
No full textDNA double-strand break (DSB) repair by homologous recombination is initiated by DNA end resection, a process involving the controlled degradation of the 5'-terminated strands at DSB sites1,2. The breast cancer suppressor BRCA1-BARD1 not only promotes resection and homologous recombination, but it also protects DNA upon replication stress1,3-9. BRCA1-BARD1 counteracts the anti-resection and pro-non-homologous end-joining factor 53BP1, but whether it functions in resection directly has been unclear10-16. Using purified recombinant proteins, we show here that BRCA1-BARD1 directly promotes long-range DNA end resection pathways catalysed by the EXO1 or DNA2 nucleases. In the DNA2-dependent pathway, BRCA1-BARD1 stimulates DNA unwinding by the Werner or Bloom helicase. Together with MRE11-RAD50-NBS1 and phosphorylated CtIP, BRCA1-BARD1 forms the BRCA1-C complex17,18, which stimulates resection synergistically to an even greater extent. A mutation in phosphorylated CtIP (S327A), which disrupts its binding to the BRCT repeats of BRCA1 and hence the integrity of the BRCA1-C complex19-21, inhibits resection, showing that BRCA1-C is a functionally integrated ensemble. Whereas BRCA1-BARD1 stimulates resection in DSB repair, it paradoxically also protects replication forks from unscheduled degradation upon stress, which involves a homologous recombination-independent function of the recombinase RAD51 (refs. 4-6,8). We show that in the presence of RAD51, BRCA1-BARD1 instead inhibits DNA degradation. On the basis of our data, the presence and local concentration of RAD51 might determine the balance between the pronuclease and the DNA protection functions of BRCA1-BARD1 in various physiological contexts.The Swiss National Science Foundation (grant nos. 310030_207588 and 310030_205199) and the European Research Council (grant no. 101018257) support the research in the Cejka laboratory. M.R.D.S. is a recipient of the EMBO Postdoctoral Fellowship (grant no. ALTF-710-2021). Work in the Huertas laboratory was supported by grant no. PID2022-136791NB-I00 funded by grant no. MICIU/AEI/10.13039/501100011033/FEDER/UE. This work is supported by Agence Nationale de la Recherche (grant no. ANR-21-CE44-0009) and by IDRIS (grant no. AD010314343R1) to R.G. Research in the Noordermeer laboratory is funded by the European Union through the MSCA doctoral network Replifate and by Oncode Institute. We thank the Sung laboratory for communicating data before publication.Peer reviewe
A Novel G‑Quadruplex Structure within Apolipoprotein E Promoter: A New Promising Target in Cancer and Dementia Fight?
No full textIntegrating Enterprise Resource Planning (ERP) Systems to Symbiotic Simulation
No full textSymbiotic simulation is inspired by symbiosis in biology and is defined as a
close association between a simulation system and a physical system, which is
usually beneficial to at least one of them. Many applications have been
proposed in recent years to implement symbiotic simulation to physical
systems. However, little research has been carried out on implementing
computer-based information systems to symbiotic simulation.
In this research, symbiotic simulation is developed with the integration of
Enterprise Resource Planning (ERP) systems. On the one hand, simulation
models benefit from the relevant manufacturing data which are provided by
ERP systems. On the other hand, ERP systems and physical systems benefit
from the feedback offered by simulation models.
A tube manufacturing shop floor has been selected as a case to demonstrate
how the symbiotic simulation can be practically implemented. In this case
example, a simulation model has been built using Anylogic 6 to mutually interact
with a SAP R/3 system. Experimentation has also been carried out to evaluate
the extent to which the symbiotic simulation can effectively address
uncertainties in manufacturing environments and ultimately control the ERP
system and the tube manufacturing shop floor
Chromosome end protection by RAP1-mediated inhibition of DNA-PK [Elektronisk resurs]
No full textDuring classical non-homologous end joining (cNHEJ), DNA-dependent protein kinase (DNA-PK) encapsulates free DNA ends, forming a recruitment platform for downstream end-joining factors including ligase 4 (LIG4)1. DNA-PK can also bind telomeres and regulate their resection2, 3-4, but does not initiate cNHEJ at this position. How the end-joining process is regulated in this context-specific manner is currently unclear. Here we show that the shelterin components TRF2 and RAP1 form a complex with DNA-PK that directly represses its end-joining function at telomeres. Biochemical experiments and cryo-electron microscopy reveal that when bound to TRF2, RAP1 establishes a network of interactions with KU and DNA that prevents DNA-PK from recruiting LIG4. In mouse and human cells, RAP1 is redundant with the Apollo nuclease in repressing cNHEJ at chromosome ends, demonstrating that the inhibition of DNA-PK prevents telomere fusions in parallel with overhang-dependent mechanisms. Our experiments show that the end-joining function of DNA-PK is directly and specifically repressed at telomeres, establishing a molecular mechanism for how individual linear chromosomes are maintained in mammalian cells.</p
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