Do We Still Need Non-Maximum Suppression? Accurate Confidence Estimates and Implicit Duplication Modeling with IoU-Aware Calibration

Object detectors are at the heart of many semi- and fully autonomous decision systems and are poised to become even more indispensable. They are, however, still lacking in accessibility and can sometimes produce unreliable predictions. Especially concerning in this regard are the -- essentially hand-crafted -- non-maximum suppression algorithms that lead to an obfuscated prediction process and biased confidence estimates. We show that we can eliminate classic NMS-style post-processing by using IoU-aware calibration. IoU-aware calibration is a conditional Beta calibration; this makes it parallelizable with no hyper-parameters. Instead of arbitrary cutoffs or discounts, it implicitly accounts for the likelihood of each detection being a duplicate and adjusts the confidence score accordingly, resulting in empirically based precision estimates for each detection. Our extensive experiments on diverse detection architectures show that the proposed IoU-aware calibration can successfully model duplicate detections and improve calibration. Compared to the standard sequential NMS and calibration approach, our joint modeling can deliver performance gains over the best NMS-based alternative while producing consistently better-calibrated confidence predictions with less complexity. The \hyperlink{https://github.com/Blueblue4/IoU-AwareCalibration}{code} for all our experiments is publicly available

Determinants of vessel contrast in BMI-adapted low dose CT coronary angiography with prospective ECG-triggering

We evaluated the determinants of vessel contrast in prospectively ECG-triggered CT coronary angiography (CTCA). Seventy patients underwent low-dose CTCA using Body Mass Index (BMI)-adapted tube parameters and a fixed contrast material bolus. Contrast to noise ratio (CNR) was calculated from contrast (between coronaries and perivascular tissue) and image noise (standard deviation of aortic attenuation). Cardiac output (CO) was calculated from gated 99mTc-tetrofosmin-SPECT. Mean radiation dose was 2.13±0.69mSv. Image noise was not affected by BMI (r=0.1, P=0.36), while CNR was inversely related to body surface area (BSA) (r=−0.5, P<0.001) and CO (r=−0.45, P<0.001). After successfully overcoming the impact of BMI on image noise by adapting tube parameters, CNR mainly depends on coronary vessel contrast. The latter reflects the dilution of the contrast material by blood volume and CO, which are both correlated to BSA. Therefore, BSA adapted contrast administration may help to compensate for this effec

Deregulated Syk inhibits differentiation and induces growth factor–independent proliferation of pre–B cells

The nonreceptor protein spleen tyrosine kinase (Syk) is a key mediator of signal transduction in a variety of cell types, including B lymphocytes. We show that deregulated Syk activity allows growth factor–independent proliferation and transforms bone marrow–derived pre–B cells that are then able to induce leukemia in mice. Syk-transformed pre–B cells show a characteristic pattern of tyrosine phosphorylation, increased c-Myc expression, and defective differentiation. Treatment of Syk-transformed pre–B cells with a novel Syk-specific inhibitor (R406) reduces tyrosine phosphorylation and c-Myc expression. In addition, R406 treatment removes the developmental block and allows the differentiation of the Syk-transformed pre–B cells into immature B cells. Because R406 treatment also prevents the proliferation of c-Myc–transformed pre–B cells, our data indicate that endogenous Syk kinase activity may be required for the survival of pre–B cells transformed by other oncogenes. Collectively, our data suggest that Syk is a protooncogene involved in the transformation of lymphocytes, thus making Syk a potential target for the treatment of leukemia

Addressing Modern Diagnostic Pathology for Patient-Derived Soft Tissue Sarcosphere Models in the Era of Functional Precision Oncology

Responses to therapy often cannot be exclusively predicted by molecular markers, thus evidencing a critical need to develop tools for better patient selection based on relations between tumor phenotype and genotype. Patient-derived cell models could help to better refine patient stratification procedures and lead to improved clinical management. So far, such ex vivo cell models have been used for addressing basic research questions and in preclinical studies. As they now enter the era of functional precision oncology, it is of utmost importance that they meet quality standards to fully represent the molecular and phenotypical architecture of patients' tumors. Well-characterized ex vivo models are imperative for rare cancer types with high patient heterogeneity and unknown driver mutations. Soft tissue sarcomas account for a very rare, heterogeneous group of malignancies that are challenging from a diagnostic standpoint and difficult to treat in a metastatic setting because of chemotherapy resistance and a lack of targeted treatment options. Functional drug screening in patient-derived cancer cell models is a more recent approach for discovering novel therapeutic candidate drugs. However, because of the rarity and heterogeneity of soft tissue sarcomas, the number of well-established and characterized sarcoma cell models is extremely limited. Within our hospital-based platform we establish high-fidelity patient-derived ex vivo cancer models from solid tumors for enabling functional precision oncology and addressing research questions to overcome this problem. We here present 5 novel, well-characterized, complex-karyotype ex vivo soft tissue sarcosphere models, which are effective tools to study molecular pathogenesis and identify the novel drug sensitivities of these genetically complex diseases. We addressed the quality standards that should be generally considered for the characterization of such ex vivo models. More broadly, we suggest a scalable platform to provide high-fidelity ex vivo models to the scientific community and enable functional precision oncology

Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma.

Defects in homologous recombination repair (HRR) in tumors correlate with poor prognosis and metastases development. Determining HRR deficiency (HRD) is of major clinical relevance as it is associated with therapeutic vulnerabilities and remains poorly investigated in sarcoma. Here, we show that specific sarcoma entities exhibit high levels of genomic instability signatures and molecular alterations in HRR genes, while harboring a complex pattern of chromosomal instability. Furthermore, sarcomas carrying HRDness traits exhibit a distinct SARC-HRD transcriptional signature that predicts PARP inhibitor sensitivity in patient-derived sarcoma cells. Concomitantly, HRD$^{high}$ sarcoma cells lack RAD51 nuclear foci formation upon DNA damage, further evidencing defects in HRR. We further identify the WEE1 kinase as a therapeutic vulnerability for sarcomas with HRDness and demonstrate the clinical benefit of combining DNA damaging agents and inhibitors of DNA repair pathways ex vivo and in the clinic. In summary, we provide a personalized oncological approach to treat sarcoma patients successfully

Discovery of a parsec-scale bipolar nebula around MWC 349A

We report the discovery of a bipolar nebula around the peculiar emission-line star MWC 349A using archival Spitzer Space Telescope 24 um data. The nebula extends over several arcminutes (up to 5 pc) and has the same orientation and geometry as the well-known subarcsecond-scale (~400 times smaller) bipolar radio nebula associated with this star. We discuss the physical relationship between MWC 349A and the nearby B0 III star MWC 349B and propose that both stars were members of a hierarchical triple system, which was ejected from the core of the Cyg OB2 association several Myr ago and recently was dissolved into a binary system (now MWC 349A) and a single unbound star (MWC 349B). Our proposal implies that MWC 349A is an evolved massive star (likely a luminous blue variable) in a binary system with a low-mass star. A possible origin of the bipolar nebula around MWC 349A is discussed.Comment: 9 pages, 6 figures, accepted for publication in A&

Excitation of local magnetic moments by tunnelling electrons

The advent of milli-kelvin scanning tunneling microscopes (STM) with inbuilt magnetic fields has opened access to the study of magnetic phenomena with atomic resolution at surfaces. In the case of single atoms adsorbed on a surface, the existence of different magnetic energy levels localized on the adsorbate is due to the breaking of the rotational invariance of the adsorbate spin by the interaction with its environment, leading to energy terms in the meV range. These structures were revealed by STM experiments in IBM Almaden in the early 2000's for atomic adsorbates on CuN surfaces. The experiments consisted in the study of the changes in conductance caused by inelastic tunnelling of electrons (IETS, Inelastic Electron Tunnelling Spectroscopy). Manganese and Iron adatoms were shown to have different magnetic anisotropies induced by the substrate. More experiments by other groups followed up, showing that magnetic excitations could be detected in a variety of systems: e.g. complex organic molecules showed that their magnetic anistropy was dependent on the molecular environment, piles of magnetic molecules showed that they interact via intermolecular exchange interaction, spin waves were excited on ferromagnetic surfaces and in Mn chains, and magnetic impurities have been analyzed on semiconductors. These experiments brought up some intriguing questions: the efficiency of magnetic excitations was very high, the excitations could or could not involve spin flip of the exciting electron and singular-like behavior was sometimes found at the excitation thresholds. These facts called for extended theoretical analysis; perturbation theories, sudden-approximation approaches and a strong coupling scheme successfully explained most of the magnetic inelastic processes. In addition, many-body approaches were also used to decipher the interplay between inelasComment: Review article to appear in Progress of Surface Scienc