Influence of notch sensitivity and crack initiation site on low cycle fatigue life of notched components under multiaxial non-proportional loading

A series of strain controlled multiaxial low cycle fatigue (LCF) tests under proportional and non-proportional loading conditions have been conducted on notched specimens. Cylindrical bars of Al 6061 aluminum alloy and AISI 316L stainless steel with four values of stress concentration factors referred to the net section Kt,n were employed. The experimental results evidenced a reduction of fatigue life due to non-proportional loading. Furthermore, the crack initiation site has been detected to be moved from the notch tip in the case of steel for high values of notch radius under nonproportional loading. Stress concentration factor evaluated in the elastic field Kt,n has been included in the Itoh-Sakane parameter to evaluate the fatigue life, returning a general underestimation of fatigue life especially for high values of Kt,n. Material notch sensitivity and crack initiation position have been taken into account to further modify the model, improving the original results and showing a better assessment

Optimización de empaques aplicando lineamientos de diseño para el ensamble validado en los contextos de empaque, transporte y desempaque

Experimental tests were conducted on additive manufactured Ti-6Al-4V titanium alloy to investigate the mechanical and crack properties under multiaxial cyclic loading. Selective Laser Sintering technique (SLS) was employed to fabricate four types of cylindrical hollow specimens. The typology of each specimen is defined by the orientation of the layers and by the application of a stress-relieving heat treatment after the production process. Stress-strain cyclic curves of the materials were obtained to investigate the material cyclic plastic behavior, that resulted independent of specimen variety. Strain-controlled multiaxial low cycle fatigue tests under proportional and non-proportional loading paths were carried out on the specimens. Not heat-treated specimens exhibited a higher low cycle fatigue resistance both for proportional and non-proportional loading. Drastic initial softening was detected in the majority of the tests. Additional hardening was detected in part of non-proportional tests, which is atypical for this alloy. The mutual influence of applied load and microstructural characteristics on fatigue life are finally discussed

Influence of Notch Sensitivity and Crack Initiation Site on Low Cycle Fatigue Life of Notched Components under Multiaxial Non-proportional Loading

A series of strain-controlled multiaxial low cycle fatigue (LCF) tests under proportional and non-proportional loading conditions have been conducted on notched specimens. Cylindrical bars of Al 6061 aluminum alloy and AISI 316L stainless steel with four values of stress concentration factors referred to the net section Kt,n were employed. The experimental results evidenced a reduction of fatigue life due to non-proportional loading. Furthermore, the crack initiation site has been detected to be moved from the notch tip in the case of steel for high values of notch radius under non-proportional loading. Stress concentration factor evaluated in the elastic field Kt,n has been included in the Itoh-Sakane parameter to evaluate the fatigue life, returning a general underestimation of fatigue life especially for high values of Kt,n. Material notch sensitivity and crack initiation position have been taken into account to further modify the model, improving the original results and showing a better assessment

Massive binary black holes from Population II and III stars

Population III stars, born from the primordial gas in the Universe, lose a negligible fraction of their mass via stellar winds and possibly follow a top-heavy mass function. Hence, they have often been regarded as the ideal progenitors of massive black holes (BHs), even above the pair instability mass gap. Here, we evolve a large set of Population III binary stars (metallicity $Z=10^{-11}$) with our population-synthesis code SEVN, and compare them with Population II binary stars ($Z=10^{-4}$). In our models, the lower edge of the pair-instability mass gap corresponds to a BH mass of $\approx{86}$ ($\approx{91}$) M$_\odot$ for single Population III (II) stars. Overall, we find only mild differences between the properties of binary BHs (BBHs) born from Population III and II stars, especially if we adopt the same initial mass function and initial orbital properties. Most BBH mergers born from Population III and II stars have primary BH mass below the pair-instability gap, and the maximum secondary BH mass is $< 50$ M$_\odot$. Only up to $\approx{3.3}$% ($\approx{0.09}$%) BBH mergers from Population III (II) progenitors have primary mass above the gap. Unlike metal-rich binary stars, the main formation channel of BBH mergers from Population III and II stars involves only stable mass transfer episodes in our fiducial model.Comment: 15 pages, 17 figures, comments are welcom

Compact object mergers: exploring uncertainties from stellar and binary evolution with SEVN

Population-synthesis codes are an unique tool to explore the parameter space of massive binary star evolution and binary compact object (BCO) formation. Most population-synthesis codes are based on the same stellar evolution model, limiting our ability to explore the main uncertainties. Our code SEVN overcomes this issue by interpolating the main stellar properties from a set of pre-computed evolutionary tracks. With SEVN, we evolved $1.2\times10^9$ binaries in the metallicity range $0.0001\leq Z \leq 0.03$, exploring a number of models for electron-capture, core-collapse and pair-instability supernovae, different assumptions for common envelope, stability of mass transfer, quasi-homogeneous evolution and stellar tides. We find that stellar evolution has a dramatic impact on the formation of single and binary compact objects. Just by slightly changing the overshooting parameter ($\lambda_{\rm ov}=0.4,0.5$) and the pair-instability model, the maximum mass of a black hole can vary from $\approx{60}$ to $\approx{100}\ \mathrm{M}_\odot$. Furthermore, the formation channels of BCOs and the merger efficiency we obtain with SEVN show significant differences with respect to the results of other population-synthesis codes, even when the same binary-evolution parameters are used. For example, the main traditional formation channel of BCOs is strongly suppressed in our models: at high metallicity ($Z\gtrsim{0.01}$) only $<20$% of the merging binary black holes and binary neutron stars form via this channel, while other authors found fractions $>70$%. The local BCO merger rate density of our fiducial models is consistent with the most recent estimates by the LIGO--Virgo--KAGRA collaboration.Comment: Submitted to MNRAS, comments welcome! The SEVN code is available at https://gitlab.com/sevncodes/sevn.git. All the data underlying this article are available in Zenodo at the link https://doi.org/10.5281/zenodo.7260771. All the Jupyter notebooks used to produce the plots in the paper are available in the gitlab repository https://gitlab.com/iogiul/iorio22_plot.gi

Probing dark matter with star clusters: a dark matter core in the ultra-faint dwarf Eridanus II

We present a new technique to probe the central dark matter (DM) density profile of galaxies that harnesses both the survival and observed properties of star clusters. As a first application, we apply our method to the `ultra-faint' dwarf Eridanus II (Eri II) that has a lone star cluster ~45 pc from its centre. Using a grid of collisional $N$-body simulations, incorporating the effects of stellar evolution, external tides and dynamical friction, we show that a DM core for Eri II naturally reproduces the size and the projected position of its star cluster. By contrast, a dense cusped galaxy requires the cluster to lie implausibly far from the centre of Eri II (>1 kpc), with a high inclination orbit that must be observed at a particular orbital phase. Our results, therefore, favour a dark matter core. This implies that either a cold DM cusp was `heated up' at the centre of Eri II by bursty star formation, or we are seeing an evidence for physics beyond cold DM.Comment: Minor changes to match the version in press in MNRA

Targeting CD205 with the antibody drug conjugate MEN1309/OBT076 is an active new therapeutic strategy in lymphoma models

Antibody drug conjugates represent an important class of anti-cancer drugs in both solid tumors and hematological cancers. Here, we report preclinical data on the anti-tumor activity of the first-in-class antibody drug conjugate MEN1309/OBT076 targeting CD205. The study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination and validation experiments on in vivo models. CD205 was first shown frequently expressed in lymphomas, leukemias and multiple myeloma by immunohistochemistry on tissue microarrays. Anti-tumor activity of MEN1309/OBT076 as single agent was then shown across 42 B-cell lymphoma cell lines with a median IC50 of 200 pM and induction of apoptosis in 25/42 (59.5%) of the cases. The activity appeared highly correlated with its target expression. After in vivo validation as the single agent, the antibody drug conjugate synergized with the BCL2 inhibitor venetoclax, and the anti-CD20 monoclonal antibody rituximab. The first-in-class antibody drug targeting CD205, MEN1309/OBT076, demonstrated strong pre-clinical anti-tumor activity in lymphoma, warranting further investigations as a single agent and in combination

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P &lt; 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P &lt; 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223