Intelligent Methods for Test and Reliability Amrouch, H.; Anders, J.; Becker, S. ...
2022 Design, Automation & Test in Europe Conference & Exhibition (DATE),
2022-March-14
Conference Proceeding
Test methods that can keep up with the ongoing increase in complexity of semiconductor products and their underlying technologies are an essential prerequisite for maintaining quality and safety of ...our daily lives and for continued success of our economies and societies. There is a huge potential how test methods can benefit from recent breakthroughs in domains such as artificial intelligence, data analytics, virtual/augmented reality, and security. The Graduate School on "Intelligent Methods for Semiconductor Test and Reliability" (GS-IMTR) at the University of Stuttgart is a large-scale, radically interdisciplinary effort to address the scientific-technological challenges in this domain. It is funded by Advantest, one of the world leaders in automatic test equipment. In this paper, we describe the overall philosophy of the Graduate School and the specific scientific questions targeted by its ten projects.
Context.
Type Ia supernovae (SNe Ia) are widely used to measure the expansion of the Universe. Improving distance measurements of SNe Ia is one technique to better constrain the acceleration of ...expansion and determine its physical nature.
Aims.
This document develops a new SNe Ia spectral energy distribution (SED) model, called the SUpernova Generator And Reconstructor (SUGAR), which improves the spectral description of SNe Ia, and consequently could improve the distance measurements.
Methods.
This model was constructed from SNe Ia spectral properties and spectrophotometric data from the Nearby Supernova Factory collaboration. In a first step, a principal component analysis-like method was used on spectral features measured at maximum light, which allowed us to extract the intrinsic properties of SNe Ia. Next, the intrinsic properties were used to extract the average extinction curve. Third, an interpolation using Gaussian processes facilitated using data taken at different epochs during the lifetime of an SN Ia and then projecting the data on a fixed time grid. Finally, the three steps were combined to build the SED model as a function of time and wavelength. This is the SUGAR model.
Results.
The main advancement in SUGAR is the addition of two additional parameters to characterize SNe Ia variability. The first is tied to the properties of SNe Ia ejecta velocity and the second correlates with their calcium lines. The addition of these parameters, as well as the high quality of the Nearby Supernova Factory data, makes SUGAR an accurate and efficient model for describing the spectra of normal SNe Ia as they brighten and fade.
Conclusions.
The performance of this model makes it an excellent SED model for experiments like the Zwicky Transient Facility, the Large Synoptic Survey Telescope, or the Wide Field Infrared Survey Telescope.
We present an analysis of 507 spectra of 173 stripped-envelope (SE) supernovae (SNe) discovered by the untargeted Palomar Transient Factory (PTF) and intermediate PTF (iPTF) surveys. Our sample ...contains 55 Type IIb SNe (SNe IIb), 45 Type Ib SNe (SNe Ib), 56 Type Ic SNe (SNe Ic), and 17 Type Ib/c SNe (SNe Ib/c). We have compared the SE SN subtypes via measurements of the pseudo-equivalent widths (pEWs) and velocities of the He I λλ5876, 7065 and O I λ7774 absorption lines. Consistent with previous work, we find that SNe Ic show higher pEWs and velocities in O I λ7774 compared to SNe IIb and Ib. The pEWs of the He I λλ5876, 7065 lines are similar in SNe Ib and IIb after maximum light. The He I λλ5876, 7065 velocities at maximum light are higher in SNe Ib compared to SNe IIb. We identify an anticorrelation between the He I λ7065 pEW and O I λ7774 velocity among SNe IIb and Ib. This can be interpreted as a continuum in the amount of He present at the time of explosion. It has been suggested that SNe Ib and Ic have similar amounts of He, and that lower mixing could be responsible for hiding He in SNe Ic. However, our data contradict this mixing hypothesis. The observed difference in the expansion rate of the ejecta around maximum light of SNe Ic (Vm = √2Ek/Mej ≈ 15 000 km s−1Vm=2Ek/Mej≈15 000 km s−1${V_{\rm{m}}} = \sqrt {2{E_{\rm{k}}}/{M_{{\rm{ej}}} \approx 1{\rm{5 \, 000 \, km }} \, {{\rm{s}}^{ - 1}}$) and SNe Ib (Vm ≈ 9000 km s−1) would imply an average He mass difference of ∼1.4 M⊙, if the other explosion parameters are assumed to be unchanged between the SE SN subtypes. We conclude that SNe Ic do not hide He but lose He due to envelope stripping.
Preclinical data suggest that dual blockade of the insulin-like growth factor-1 receptor (IGF-1R) and HER3 pathways has superior activity to IGF-1R blockade alone in pancreatic ductal adenocarcinoma ...(PDAC). We tested whether istiratumab, an IGF-1R- and ErbB3-bispecific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with metastatic PDAC selected for high IGF-1 serum levels.
CARRIE was an international, randomized, double-blind, placebo-controlled phase II study for patients with previously untreated metastatic PDAC. In part 1, 10 patients were evaluated for pharmacokinetics and safety. In part 2, patients with high free serum IGF-1 levels were randomized 1 : 1 to receive either istiratumab 2.8 g intravenously (i.v.) every 2 weeks or placebo combined with gemcitabine/nab-paclitaxel at approved dose schedule. The co-primary endpoints were progression-free survival (PFS) in patients with high IGF-1 levels and PFS in patients with both high serum IGF-1 levels and heregulin (HRG)+ tumors. Key secondary endpoints were overall survival (OS), objective response rate (ORR) by RECIST v.1.1, and adverse events (AEs) rate.
A total of 317 patients were screened, with 88 patients randomized in part 2 (experimental arm n = 43; control n = 45). In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively hazard ratio (HR) = 1.88, P = 0.027. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42). Median OS and ORR for the overall population were similar between two arms. No significant difference in serious or grade ≥3 AEs was observed, although low-grade AEs leading to early discontinuation were higher in the experimental (39.5%) versus control arm (24.4%).
Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. High serum IGF-1 levels did not appear to be an adverse prognostic factor when compared with non-biomarker-selected historic controls.
ClinicalTrials.gov: NCT02399137; EUDRA CT: 2014-004572-34.
•Dual targeting of IGF-1R and ErbB3 ineffective in metastatic pancreatic cancer.•Elevated serum IGF-1 levels not clearly prognostic.•Integral biomarker for patient selection feasible in this patient population.
With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate ...whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer.
We did a multicentre, open-label, randomised, controlled trial (PET-Plan; ARO-2009-09) in 24 centres in Austria, Germany, and Switzerland. Previously untreated patients (aged older than 18 years) with inoperable locally advanced non-small-cell lung cancer suitable for chemoradiotherapy and an Eastern Cooperative Oncology Group performance status of less than 3 were included. Undergoing 18F-fluorodeoxyglucose (18F-FDG) PET and CT for treatment planning, patients were randomly assigned (1:1) using a random number generator and block sizes between four and six to target volume delineation informed by 18F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone (18F-FDG PET-based target group). Randomisation was stratified by centre and Union for International Cancer Control stage. In both groups, dose-escalated radiotherapy (60–74 Gy, 2 Gy per fraction) was planned to the respective target volumes and applied with concurrent platinum-based chemotherapy. The primary endpoint was time to locoregional progression from randomisation with the objective to test non-inferiority of 18F-FDG PET-based planning with a prespecified hazard ratio (HR) margin of 1·25. The per-protocol set was included in the primary analysis. The safety set included all patients receiving any study-specific treatment. Patients and study staff were not masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT00697333.
From May 13, 2009, to Dec 5, 2016, 205 of 311 recruited patients were randomly assigned to the conventional target group (n=99) or the 18F-FDG PET-based target group (n=106; the intention-to-treat set), and 172 patients were treated per protocol (84 patients in the conventional target group and 88 in the 18F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9–54), the risk of locoregional progression in the 18F-FDG PET-based target group was non-inferior to, and in fact lower than, that in the conventional target group in the per-protocol set (14% 95% CI 5–21 vs 29% 17–38 at 1 year; HR 0·57 95% CI 0·30–1·06). The risk of locoregional progression in the 18F-FDG PET-based target group was also non-inferior to that in the conventional target group in the intention-to-treat set (17% 95% CI 9–24 vs 30% 20–39 at 1 year; HR 0·64 95% CI 0·37–1·10). The most common acute grade 3 or worse toxicity was oesophagitis or dysphagia (16 16% of 99 patients in the conventional target group vs 17 16% of 105 patients in the 18F-FDG PET-based target group); the most common late toxicities were lung-related (12 12% vs 11 10%). 20 deaths potentially related to study treatment were reported (seven vs 13).
18F-FDG PET-based planning could potentially improve local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours.
German Cancer Aid (Deutsche Krebshilfe).
Summary Background Preoperative chemoradiotherapy with infusional fluorouracil, total mesorectal excision surgery, and postoperative chemotherapy with fluorouracil was established by the German ...CAO/ARO/AIO-94 trial as a standard combined modality treatment for locally advanced rectal cancer. Here we compare the previously established regimen with an investigational regimen in which oxaliplatin was added to both preoperative chemoradiotherapy and postoperative chemotherapy. Methods In this multicentre, open-label, randomised, phase 3 study we randomly assigned patients with rectal adenocarcinoma, clinically staged as cT3–4 or any node-positive disease, to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (1000 mg/m2 on days 1–5 and 29–33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m2 on days 1–5 and 29); or to an investigational group receiving preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (250 mg/m2 on days 1–14 and 22–35) and oxaliplatin (50 mg/m2 on days 1, 8, 22, and 29), followed by surgery and eight cycles of oxaliplatin (100 mg/m2 on days 1 and 15), leucovorin (400 mg/m2 on days 1 and 15), and infusional fluorouracil (2400 mg/m2 on days 1–2 and 15–16). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1–3 vs cT4), and clinical N category (cN0 vs cN1–2) without masking. The primary endpoint was disease-free survival, defined as the time between randomisation and non-radical surgery of the primary tumour (R2 resection), locoregional recurrence after R0/1 resection, metastatic disease or progression, or death from any cause, whichever occurred first. Survival and cumulative incidence of recurrence analyses followed the intention-to-treat principle; toxicity analyses included all patients treated. Enrolment of patients in this trial is completed and follow-up is ongoing. This study is registered with ClinicalTrials.gov , number NCT00349076. Findings Of the 1265 patients initially enrolled, 1236 were assessable (613 in the investigational group and 623 in the control group). With a median follow-up of 50 months (IQR 38–61), disease-free survival at 3 years was 75·9% (95% CI 72·4–79·5) in the investigational group and 71·2% (95% CI 67·6–74·9) in the control group (hazard ratio HR 0·79, 95% CI 0·64–0·98; p=0·03). Preoperative grade 3–4 toxic effects occurred in 144 (24%) of 607 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 128 (20%) of 625 patients who actually received fluorouracil chemoradiotherapy. Of 445 patients who actually received adjuvant fluorouracil and leucovorin and oxaliplatin, 158 (36%) had grade 3–4 toxic effects, as did 170 (36%) of 470 patients who actually received adjuvant fluorouracil. Late grade 3–4 adverse events in patients who received protocol-specified preoperative and postoperative treatment occurred in 112 (25%) of 445 patients in the investigational group, and in 100 (21%) of 470 patients in the control group. Interpretation Adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy (at the doses and intensities used in this trial) significantly improved disease-free survival of patients with clinically staged cT3–4 or cN1–2 rectal cancer compared with our former fluorouracil-based combined modality regimen (based on CAO/ARO/AIO-94). The regimen established by CAO/ARO/AIO-04 can be deemed a new treatment option for patients with locally advanced rectal cancer. Funding German Cancer Aid (Deutsche Krebshilfe).
Context. Observations of type Ia supernovae (SNe Ia) can be used to derive accurate cosmological distances through empirical standardization techniques. Despite this success neither the progenitors ...of SNe Ia nor the explosion process are fully understood. The U-band region has been less well observed for nearby SNe, due to technical challenges, but is the most readily accessible band for high-redshift SNe. Aims. Using spectrophotometry from the Nearby Supernova Factory, we study the origin and extent of U-band spectroscopic variations in SNe Ia and explore consequences for their standardization and the potential for providing new insights into the explosion process. Methods. We divide the U-band spectrum into four wavelength regions λ(uNi), λ(uTi), λ(uSi) and λ(uCa). Two of these span the Ca H&K λλ 3934, 3969 complex. We employ spectral synthesis using SYNAPPS to associate the two bluer regions with Ni/Co and Ti. Results. The flux of the uTi feature is an extremely sensitive temperature/luminosity indicator, standardizing the SN peak luminosity to 0.116 ± 0.011 mag root mean square (RMS). A traditional SALT2.4 fit on the same sample yields a 0.135 mag RMS. Standardization using uTi also reduces the difference in corrected magnitude between SNe originating from different host galaxy environments. Early U-band spectra can be used to probe the Ni+Co distribution in the ejecta, thus offering a rare window into the source of light curve power. The uCa flux further improves standardization, yielding a 0.086 ± 0.010 mag RMS without the need to include an additional intrinsic dispersion to reach χ2∕dof ~ 1. This reduction in RMS is partially driven by an improved standardization of Shallow Silicon and 91T-like SNe.
SN Ia cosmology depends on the ability to fit and standardize observations of supernova magnitudes with an empirical model. We present here a series of new models of SN Ia spectral time series that ...capture a greater amount of supernova diversity than is possible with the models that are currently customary. These are entitled SuperNova Empirical MOdels (SNEMO; https://snfactory.lbl.gov/snemo). The models are constructed using spectrophotometric time series from 172 individual supernovae from the Nearby Supernova Factory, comprising more than 2000 spectra. Using the available observations, Gaussian processes are used to predict a full spectral time series for each supernova. A matrix is constructed from the spectral time series of all the supernovae, and Expectation Maximization Factor Analysis is used to calculate the principal components of the data. K-fold cross-validation then determines the selection of model parameters and accounts for color variation in the data. Based on this process, the final models are trained on supernovae that have been dereddened using the Fitzpatrick and Massa extinction relation. Three final models are presented here: SNEMO2, a two-component model for comparison with current Type Ia models; SNEMO7, a seven-component model chosen for standardizing supernova magnitudes, which results in a total dispersion of 0.100 mag for a validation set of supernovae, of which 0.087 mag is unexplained (a total dispersion of 0.113 mag with an unexplained dispersion of 0.097 mag is found for the total set of training and validation supernovae); and SNEMO15, a comprehensive 15-component model that maximizes the amount of spectral time-series behavior captured.
In this paper, we present new experimental measurements of the turbulent transport of salt across an interface between two layers of fluid of equal depth but different salinities. The fluid is ...confined to a cylindrical annulus with a vertical axis. The outer cylinder is stationary and the inner cylinder rotates to produce a turbulent flow field consisting of an approximately irrotational mean azimuthal flow, with narrow boundary layers on the inner and outer cylinders. We focus on the limit of high-Richardson-number flow, defined as Ri = gΔρH/(ρ0u2rms), where ρ0 is a reference density, Δρ is the time-dependent difference of the layers' mean densities, urms is the root mean square of the turbulent velocity fluctuations and H is the layer depth. The mean flow has Reynolds number of the order of 104−105, and the turbulent fluctuations in the azimuthal and radial directions have root-mean-square speed of order 10% of the mean azimuthal flow. Measurements based on our experimental system show that when the Richardson number is in the range 7 < Ri < 200, the interface between the two layers remains sharp, each layer remains well mixed, and the vertical flux of salt between the layers, Fs ~(1.15 ± 0.15)Ri−1 (H/ΔR)urmsΔS, where ΔS is the spatially-averaged time-dependent salinity difference between the layers and in general (H/ΔR) is a dimensionless function of the tank aspect ratio, here taken to be unity, with ΔR being the gap width of the annulus. The salt transport appears to be caused by turbulent eddies scouring and sharpening the interface and implies a constant rate of conversion of the turbulent kinetic energy to potential energy, independent of the density contrast between the layers. For smaller values of Ri, the flow regime changes qualitatively, with eddies penetrating the interface, causing fluid in the two layers to co-mingle and rapidly homogenize.
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