ENDF-6 compatible evaluation of neutron induced reaction cross sections for 182,183,184,186W

An ENDF-6 compatible evaluation for neutron induced reactions in the resonance region has been completed for 182,183,184,186W. The parameters are the result of an analysis of experimental data available in the literature together with a parameter adjustment on transmission and capture data obtained at the time-of-flight facility GELINA. Complete evaluated data files in ENDF-6 format have been produced by joining the evaluations in the resonance region with corresponding files from the JEFF-32T1 and ENDF/B-VII.1 library. The evaluated files have been processed with the latest updates of NJOY.99 to test their format and application consistency as well as to produce a continuous-energy data library in ACE format for use in Monte Carlo codes. The evaluated files will be implemented in the next release of the JEFF-3 library which is maintained by the Nuclear Energy Agency of the OECD. The evaluated files will be implemented in the next release of the JEFF-3 library which is maintained by the Nuclear Energy Agency of the OECD.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Evaluation of neutron induced reaction cross sections in the resolved and unresolved resonance region at EC-JRC-IRMM

Recent efforts made at the EC-JRC-IRMM to produce evaluated cross section data files for neutron induced reactions are described as well as the methodology applied in both the resolved and unresolved resonance. For the resolved resonance region the paper focuses on a recent evaluation of isotopes present in natural cadmium. For the unresolved resonance region results for gold are presented.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Development of neutron resonance densitometry at the GELINA TOF facility

Neutrons can be used as a tool to study properties of materials and objects. An evolving activity in this field concerns the existence of resonances in neutron induced reaction cross sections. These resonance structures are the basis of two analytical methods which have been developed at the EC-JRC-IRMM: Neutron Resonance Capture Analysis (NRCA) and Neutron Resonance Transmission Analysis (NRTA). They have been applied to determine the elemental composition of archaeological objects and to characterize nuclear reference materials. A combination of NRTA and NRCA together with Prompt Gamma Neutron Analysis, referred to as Neutron Resonance Densitometry (NRD), is being studied as a non-destructive method to characterize particle-like debris of melted fuel that is formed in severe nuclear accidents such as the one which occurred at the Fukushima Daiichi nuclear power plants. This study is part of a collaboration between JAEA and EC-JRC-IRMM. In this contribution the basic principles of NRTA and NRCA are explained based on the experience in the use of these methods at the time-of-flight facility GELINA of the EC-JRC-IRMM. Specific problems related to the analysis of samples resulting from melted fuel are discussed. The programme to study and solve these problems is described and results of a first measurement campaign at GELINA are given.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Oncostatin-M inhibits luteinizing hormone stimulated Leydig cell progenitor formation in vitro

Background: The initial steps of stem Leydig cell differentiation into steroid producing progenitor cells are thought to take place independent of luteinizing hormone (LH), under the influence of locally produced factors such as leukaemia inhibitory factor (LIF), platelet derived growth factor A and stem cell factor. For the formation of a normal sized Leydig cell population in the adult testis, the presence of LH appears to be essential. Oncostatin M (OSM) is a multifunctional cytokine and member of the interleukin (IL)-6 family that also includes other cytokines such as LIF. In the rat OSM is highly expressed in the late fetal and neonatal testis, and may thus be a candidate factor involved in Leydig cell progenitor formation. Methods: Interstitial cells were isolated from 13-day-old rat testes and cultured for 1, 3 or 8 days in the presence of different doses of OSM ( range: 0.01 to 10 ng/ml) alone or in combination with LH ( 1 ng/ml). The effects of OSM and LH on cell proliferation were determined by incubating the cultures with [3H] thymidine or bromodeoxyuridine ( BrdU). Developing progenitor cells were identified histochemically by the presence of the marker enzyme 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Results: OSM, when added at a dose of 10 ng/ml, caused a nearly 2-fold increase in the percentage of Leydig cell progenitors after 8 days of culture. Immunohistochemical double labelling experiments with 3beta-HSD and BrdU antibodies showed that this increase was the result of differentiation of stem Leydig cells/precursor cells and not caused by proliferation of progenitor cells themselves. The addition of LH to the cultures consistently resulted in an increase in progenitor formation throughout the culture period. Surprisingly, when OSM and LH were added together, the LH induced rise in progenitor cells was significantly inhibited after 3 and 8 days of culture. Conclusion: Taken together, the results of the present study suggest that locally produced OSM may not only play a role in the regulation of Sertoli cell proliferation and the initiation of spermatogenesis but may also play a role in the regulation of Leydig cell progenitor formation by keeping the augmenting effects of LH on this process in abeyance

Spermatogonial stem cell sensitivity to capsaicin: An in vitro study

Background: Conflicting reports have been published on the sensitivity of spermatogenesis to capsaicin (CAP), the pungent ingredient of hot chili peppers. Here, the effect of CAP on germ cell survival was investigated by using two testis germ cell lines as a model. As CAP is a potent agonist of the transient receptor potential vanilloid receptor 1 (TRPV1) and no information was available of its expression in germ cells, we also studied the presence of TRPV1 in the cultured cells and in germ cells in situ. Methods: The rat spermatogonial stem cell lines Gc-5spg and Gc-6spg were used to study the effects of different concentrations of CAP during 24 and 48 h. The response to CAP was first monitored by phase-contrast microscopy. As germ cells appear to undergo apoptosis in the presence of CAP, the activation of caspase 3 was studied using an anti activated caspase 3 antibody or by quantifying the amount of cells with DNA fragmentation using flow cytometry. Immunolocalization was done with an anti-TRPV1 antibody either with the use of confocal microscopy to follow live cell labeling (germ cells) or on Bouin fixed paraffin embedded testicular tissues. The expression of TRPV1 by the cell lines and germ cells was confirmed by Western blots. Results: Initial morphological observations indicated that CAP at concentrations ranging from 150 uM to 250 uM and after 24 and 48 h of exposure, had deleterious apoptotic-like effects on both cell lines: A large population of the CAP treated cell cultures showed signs of DNA fragmentation and caspase 3 activation. Quantification of the effect demonstrated a significant effect of CAP with doses of 150 uM in the Gc-5spg cell line and 200 uM in the Gc-6spg cell line, after 24 h of exposure. The effect was dose and time dependent in both cell lines. TRPV1, the receptor for CAP, was found to be expressed by the spermatogonial stem cells in vitro and also by premeiotic germ cells in situ. Conclusion: CAP adversely affects spermatogonial survival in vitro by inducing apoptosis to those cells and TRPV-1, a CAP receptor, may be involved in this effect as this receptor is expressed by mitotic germ cells

Association between growth differentiation factor-15 (GDF-15) serum levels, anorexia and low muscle mass among cancer patients

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity

Hepatic lipogenesis marked by GCKR‐modulated triglycerides increases serum FGF21 in children/teens with obesity

Aims: Fibroblast growth factor 21 (FGF21) decreases hepatic lipogenesis in animal models, and FGF21 analogues decrease serum triglycerides (TG) in adults in phase-2 trials. On the other hand, serum FGF21 is associated with higher TG in observational studies of people with obesity, raising a sort of paradox. We tested the hypothesis that FGF21 is induced by TG in youth with obesity, as a compensatory mechanism. Materials and Methods: We recruited 159 children/adolescents with obesity (80 males, 12.7 ± 2.1 years). Besides serum FGF21 and lipid dosages, we genotyped the Pro446Leu variant at glucokinase regulator (GCKR) as a known marker of genetically increased hepatic de novo lipogenesis, and we used it as an instrumental variable to establish a cause-and-effect relationship between FGF21 and TG, according to a Mendelian randomization analysis. Results: The Pro446Leu variant increased circulating TG (β = +0.35, p < 0.001), which was positively associated with circulating FGF21 (β = +0.42, p < 0.001). The Pro446Leu variant increased FGF-21 (β = +0.14, p = 0.031) with the expected slope (β-coefficient) in case of association entirely mediated by TG: 0.35 (slope between Pro446Ala and TG) × 0.42 (slope between TG and FGF21) = 0.14. Conclusions: Hepatic lipogenesis, marked by GCKR-modulated triglycerides, is significantly associated with increased serum FGF-21 in children/adolescents with obesity

Retrospective Correlation between First Drug Treatment Duration and Survival Outcomes in Sequential Treatment with Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer: A Real-World Subgroup Analysis

Background: Patients with refractory metastatic colorectal cancer (mCRC) rarely receive third-line or further treatment. In this context, regorafenib (R) and trifluridine/tipiracil (T) are two important novel therapeutic choices with statistically significant increases in overall survival (OS), progression-free survival (PFS), and disease control, with different toxicity profiles. This study is a subgroup analysis of our larger retrospective study, already published, whose objective was to assess the outcomes of patients when R and T were given sequentially. Patients and Methods: The study involved thirteen Italian cancer centers on a 10-year retrospective observation (2012-2022). In this subgroup analysis, we focused our attention on the correlation between the first drug treatment duration (&lt;3 months, 3 to &lt;6 months and &gt;= 6 months) and survival outcomes in patients who had received the sequence regorafenib-to-trifluridine/tipiracil, or vice versa. Results: The initial study included 866 patients with mCRC who received sequential T/R, or R/T, or T or R alone. This analysis is focused on evaluating the impact of the duration of the first treatment in the sequence on clinical outcomes (OS, PFS) and includes 146 and 116 patients of the T/R and R/T sequences, respectively. Based on the duration of the first drug treatment, subgroups for the T/R sequence included 27 patients (18.4%) who received T for &lt;3 months, 86 (58.9%) treated for 3 to &lt;6 months, and 33 (22.6%) treated for &gt;= 6 months; in the reverse sequence (R as the first drug), subgroups included 18 patients (15.5%) who received their first treatment for &lt;3 months, 62 (53.4%) treated for 3 to &lt;6 months, and 35 (31.0%) treated for &gt;= 6 months. In patients who received their first drug treatment for a period of 3 to &lt;6 months, the R/T sequence had a significantly longer median OS (13.7 vs. 10.8 months, p = 0.0069) and a longer median PFS (10.8 vs. 8.5 months, p = 0.0003) than the T/R group. There were no statistically significant differences between groups with first drug treatment durations of &lt;3 months and &gt;= 6 months. Conclusions: Our analysis seems to suggest that the administration of R for a period of 3 to &lt;6 months before that of T can prolong both OS and PFS, as compared to the opposite sequence