Dizajniranje i sinteza novih derivata tiofenkarbohidrazida, tienopirazola i tienopirimidina s antioksidativnim i antitumorskim djelovanjem

2-Amino-5-acetyl-4-methyl-thiophene-3-carboxylic acid ethyl ester (1) and 5-acetyl-2-amino-4-methylthiophene-3-carbohydrazide (2) were synthesized and used as starting materials for the synthesis of new series of 1-(5-amino-4-(3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3a), 1-(5-amino-4-(4-chloro-3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3b), 1-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) pyrazolidine-3,5-dione (4), (Z)-N\u27-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) formohydrazonic acid (5a), (Z)-ethyl-N\u27-(4-methyl-2-amino-5-acetylthiophene-3-carbonylformo hydrazonate (5b), 6-acetyl-3-amino-2,5-dimethylthieno2,3-dpyrimidin-4(3H)-one (8), 5-methyl-3-amino-2-mercapto-6-acetylthieno2,3-dpyrimidin-4(3H)-one (10) and 5-methyl-6-acetyl-2-thioxo-2,3-dihydrothieno2,3-dpyrimidin-4(1H)-one (12) as potential antioxidant and antitumor agents. Pharmacological results showed that compounds 6a, 6b, 8, 10 and 12 exhibited promising antitumor and antioxidant activity.Etilni ester 2-amino-5-acetil-4-metil-tiofen-3-karboksilne kiseline (1) i 5-acetil-2-amino-4-metiltiofen-3-karbohidrazid (2) sintetizirani su i upotrebljeni kao reaktanti u sintezi novih spojeva 1-(5-amino-4-(3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3a), 1-(5-amino-4-(4-klor-3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3b), 1-(4-metil-2-amino-5-acetiltiofen-3-karbonil) pirazolidin-3,5-diona (4), (Z)-N\u27-(4-metil-2-amino-5-acetiltiofen-3-karbonil) formohidrazonske kiseline (5a), (Z)-etil-N\u27-(4-metil-2-amino-5-acetiltiofen-3-karbonilformo hidrazonata (5b), 6-acetil-3-amino-2,5-dimetiltieno2,3-dpirimidin-4(3H)-one (8), 5-metil-3-amino-2-merkapto-6-acetiltieno2,3-dpirimidin-4(3H)-ona (10) i 5-metil-6-acetil-2-tiokso-2,3-dihidrotieno2,3-dpirimidin-4(1H)-ona (12) kao potencijalnih antioksidansa i citostatika. Farmakološka ispitivanja ukazuju na to da spojevi 6a, 6b, 8, 10 i 12 imaju značajno antitumorsko i antioksidativno djelovanje

Constraints in modeling the quasielastic response in inclusive lepton-nucleus scattering

We show that the quasielastic (QE) response calculated with the superscaling approach (SuSAv2) model, that relies on the scaling phenomenon observed in the analysis of (e,e′) data and on the relativistic mean-field theory, is very similar to that from a relativistic distorted-wave impulse approximation model when only the real part of the optical potentials is employed. The coincidence between the results from these two completely independent approaches, which satisfactorily agree with the inclusive data, reinforces the reliability of the quasielastic predictions stemming from both models and sets constraints for the QE response. We also study the low-energy and momentum-transfer region of the inclusive response by confronting the results of the relativistic mean-field model with those of the Hartree-Fock continuum random-phase approximation model, which accounts for nuclear long-range correlations. Finally, we present a comparison of our results with the recent Jefferson Laboratory (JLab) (e,e′) data for argon, titanium, and carbon, finding good agreement with the three data sets.Spanish Ministerio de Economia y Competitividad and European Regional Development Fund) FIS2017-88410-PJunta de Andalucia FQM 160, SOMM17/6105/UGRConsolider-Ingenio 2000 program CPAN (CSD2007-0042)Spanish Government (FPA2015-65035P and RTI2018-098868-B-I00

Summary of the NuSTEC Workshop on Neutrino-Nucleus Pion Production in the Resonance Region

The NuSTEC workshop held at the University of Pittsburgh in October 2019 brought theorists and experimentalists together to discuss the state of modeling and measurements related to pion production in neutrino-nucleus scattering in the kinematic region where pions are produced through both resonant and non-resonant mechanisms. Modeling of this region is of critical importance to the current and future accelerator- and atmospheric-based neutrino oscillation experiments. For the benefit of the community, links to the presentations are accompanied by annotations from the speakers highlighting significant points made during the presentations and resulting discussions

Vitamin-V: Virtual Environment and Tool-boxing for Trustworthy Development of RISC-V based Cloud Services

Vitamin-V is a 2023-2025 Horizon Europe project that aims to develop a complete RISC-V open-source software stack for cloud services with comparable performance to the cloud-dominant x86 counterpart and a powerful virtual execution environment for software development, validation, verification, and test that considers the relevant RISC-V ISA extensions for cloud deployment

Quantum gravity effects in Myers-Perry space-times

We study quantum gravity effects for Myers-Perry black holes assuming that the leading contributions arise from the renormalization group evolution of Newton's coupling. Provided that gravity weakens following the asymptotic safety conjecture, we find that quantum effects lift a degeneracy of higher-dimensional black holes, and dominate over kinematical ones induced by rotation, particularly for small black hole mass, large angular momentum, and higher space-time dimensionality. Quantum-corrected space-times display inner and outer horizons, and show the existence of a black hole of smallest mass in any dimension. Ultra-spinning solutions no longer persist. Thermodynamic properties including temperature, specific heat, the Komar integrals, and aspects of black hole mechanics are studied as well. Observing a softening of the ring singularity, we also discuss the validity of classical energy conditions

Equine post-breeding endometritis: A review

The deposition of semen, bacteria and debris in the uterus of the mare after breeding normally induces a self-limiting endometritis. The resultant fluid and inflammatory products are cleared by 48 hours post cover. Mares that are susceptible to persistent post-breeding endometritis (PPBEM) have impaired uterine defence and clearance mechanisms, making them unable to resolve this inflammation within the normal time. This persists beyond 48 hours post-breeding and causes persistent fluid accumulation within the uterus. Mares with PPBEM have an increased rate of embryonic loss and a lower overall pregnancy rate than those without the condition. To enhance conception rates, mares at high risk need optimal breeding management as well as early diagnosis, followed by the most appropriate treatment. This article reviews the pathogenesis, diagnosis and treatment of PPBEM and the management of affected mares

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(> MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of >= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

Second-line treatment with irinotecan plus cisplatin vs cisplatin of patients with advanced non-small-cell lung cancer pretreated with taxanes and gemcitabine: a multicenter randomised phase II study

The aim of this study was to compare the irinotecan/cisplatin regimen with cisplatin as second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) pretreated with a taxane/gemcitabine regimen. Patients (n=147) with stage IV NSCLC pretreated with a taxane/gemcitabine regimen were randomly assigned to receive either irinotecan (110 mg m−2, day 1 and 100 mg m−2, day 8) and cisplatin (80 mg m−2, day 8) (IC; n=74) or CDDP (80 mg m−2, day 1) (C; n=73) every 3 weeks. Patients treated with IC and C had a median survival of 7.8 and 8.8 months, respectively (P=0.933). The 1-year survival rate was 34.3% for IC-treated patients and 31.7% for C-treated patients. Cox's regression analysis revealed that response to treatment (hazard ratio (HR)=2.787; 95% confidence interval (CI): 1.1578–4.922) and performance status (HR=1.865; 95% CI: 1.199–2.872) was independent prognostic factors for survival. Overall response rate was 22.5% (95% CI: 12.8–32.2%) for IC-treated patients and 7.0% (95% CI: 1.15–13.6%) for C-treated patients (P=0.012); tumour growth control (partial remission (PR)+stable disease (SD)) was observed in 26 (38%) IC and 25 (36%) C patients (P=0.878). There was no difference in terms of quality of life between the two chemotherapy arms. The incidence of febrile neutropenia, grade 3 and 4 neutropenia and grade 3 and 4 diarrhoea was significantly higher in the IC- than the C-treated patients. Other toxicities were mild. There were no treatment-related deaths in either arm. The IC regimen did not confer a survival benefit compared with C as second-line treatment of patients with advanced NSCLC pretreated with a taxane/gemcitabine regimen, despite its better efficacy in terms of response rate

Effect of Outgoing Nucleon Wave Function on Reconstructed Neutrino Energy

International audienceThe main goal of accelerator-based neutrino experiments is the determination of the neutrino oscillation parameters, The oscillation probability depends on the ratio of the distance traveled by the neutrino to its energy, therefore the determination of the distribution of neutrino energies in a detector is crucial. The reconstructed neutrino energy is a kinematic variable which is determined by the energy and scattering angle of the final state lepton in charged current (CC) scattering off an atomic nucleus. The distribution of reconstructed energies around the true incoming energy depends on the nuclear model used to describe the $\nu$ -nucleus cross section. We show the effect of distortion of the outgoing nucleon wave function on these distributions