Future paradigms for precision oncology

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Distributive congruence lattices of congruence-permutable algebras

We prove that every distributive algebraic lattice with at most $\aleph_1$ compact elements is isomorphic to the normal subgroup lattice of some group and to the submodule lattice of some right module. The $\aleph_1$ bound is optimal, as we find a distributive algebraic lattice $D$ with $\aleph_2$ compact elements that is not isomorphic to the congruence lattice of any algebra with almost permutable congruences (hence neither of any group nor of any module), thus solving negatively a problem of E. T. Schmidt from 1969. Furthermore, $D$ may be taken as the congruence lattice of the free bounded lattice on $\aleph_2$ generators in any non-distributive lattice variety. Some of our results are obtained via a functorial approach of the semilattice-valued "distances" used by B. Jonsson in his proof of Whitman's embedding Theorem. In particular, the semilattice of compact elements of $D$ is not the range of any distance satisfying the V-condition of type $3/2$. On the other hand, every distributive join-semilattice with zero is the range of a distance satisfying the V-condition of type 2. This can be done via a functorial construction

Sonic Hedgehog and Triiodothyronine Pathway Interact in Mouse Embryonic Neural Stem Cells

Neural stem cells are fundamental to development of the central nervous system (CNS)—as well as its plasticity and regeneration—and represent a potential tool for neuro transplantation therapy and research. This study is focused on examination of the proliferation dynamic and fate of embryonic neural stem cells (eNSCs) under differentiating conditions. In this work, we analyzed eNSCs differentiating alone and in the presence of sonic hedgehog (SHH) or triiodothyronine (T3) which play an important role in the development of the CNS. We found that inhibition of the SHH pathway and activation of the T3 pathway increased cellular health and survival of differentiating eNSCs. In addition, T3 was able to increase the expression of the gene for the receptor smoothened (Smo), which is part of the SHH signaling cascade, while SHH increased the expression of the T3 receptor beta gene (Thrb). This might be the reason why the combination of SHH and T3 increased the expression of the thyroxine 5-deiodinase type III gene (Dio3), which inhibits T3 activity, which in turn affects cellular health and proliferation activity of eNSCs

Gamma irradiation of ATLAS18 ITk strip sensors affected by static charge

Construction of the new all-silicon Inner Tracker (ITk), developed by the ATLAS collaboration to be able to track charged particles produced at the High-Luminosity LHC, started in 2021 and is expected to continue until 2028. The ITk detector will include ~18,000 highly segmented and radiation hard n+-in-p silicon strip sensors, which are being manufactured by Hamamatsu Photonics. Upon their delivery, the ATLAS ITk strip sensor collaboration performs detailed measurements of sensors to monitor quality of all fabricated pieces. QC electrical tests include current-voltage (IV) and capacitance-voltage (CV) tests, full strip tests, and a measurement of the long-term stability of the sensor leakage current. While most sensors demonstrate excellent performance during QC testing, we have nevertheless observed that a number of sensors from several production batches failed the electrical tests. Accumulated data indicates a strong correlation between observed electrical test failures and high electrostatic charge measured on the sensor surface during initial reception tests. This electrostatic charge enhances the risk of "Local trapped charge" events during manufacturing, shipping, and handling procedures, resulting in failed electrical QC tests. To mitigate the above-described issues, the QC testing institutes modified the sensor handling procedures and introduced sensor recovery techniques. Despite the implementation of various recovery techniques, it is still possible that some affected sensors will not be identified by the sensor QC testing, or that "Local trapped charge" events could occur in later manipulation stages of the sensor. In the presented study, we have investigated whether the total ionizing dose (TID) expected in the real experiment can effectively resolve early breakdown or low interstrip isolation caused by the electrostatic charge. Selected charge-affected sensors were irradiated with gamma rays from the 60Co source for a number of TID values. The results of this study indicate that the negative effects of the electrostatic charge on the critical sensors characteristics disappear after a very small amount of an accumulated TID, which actually corresponds to one or two days in the experiment. This finding gives us confidence in mitigating the issue of electrostatic charge during the operation of the ITk strip sensors in the real experiment

Effect of irradiation and annealing performed with bias voltage applied across the coupling capacitors on the interstrip resistance of ATLAS ITk silicon strip sensors

The powering configuration of the silicon strip modules developed for the new Inner Tracker of the ATLAS experiment includes a voltage of up to 0.5 V across the coupling capacitor of each individual strip. However, this voltage is usually not applied in the sensor irradiation studies due to the significant technical and logistical complications. To study the effect of an irradiation and a subsequent beneficial annealing on the strip sensors in real experimental conditions, four prototype ATLAS17LS miniature sensors were irradiated by $^{60}$Co source and annealed, both with and without the bias voltage of 0.5 V applied across the coupling capacitors. The values of interstrip resistance measured on irradiated samples before and after annealing indicate that increase of radiation damage caused by the applied voltage can be compensated by the presence of this voltage during annealing

Effect of irradiation and annealing performed with bias voltage applied across the coupling capacitors on the interstrip resistance of ATLAS ITk strip silicon sensors

In order to cope with the occupancy and radiation doses expected at the High-Luminosity LHC, the ATLAS experiment will replace its Inner Detector with an all-silicon Inner Tracker (ITk), containing pixel and strip subsystems. The strip detector will be built from modules, consisting of one or two n+-in-p silicon sensors, PCB hybrids accommodating the front-end electronics, and powerboard providing high voltage, low voltage, and monitoring electronics. The aluminium strips of the silicon sensors developed for the ITk project are AC-coupled with n-type implants in a p-type float-zone silicon bulk. The module powering configuration includes a voltage of up to 0.5 V across the sensor coupling capacitor. However, this voltage is usually not applied in the sensor irradiation studies due to the significant technical and logistical complications. To study the effect of an irradiation and a subsequent beneficial annealing on the ITk strip sensors in real experimental conditions, four prototype ATLAS17LS miniature sensors were irradiated by Co60 source and annealed for 80 minutes at 60°C, both with and without the bias voltage of 0.5 V applied across the coupling capacitors. The values of interstrip resistance measured on irradiated samples before and after annealing indicate that increase of radiation damage caused by the applied voltage can be compensated by the presence of this voltage during annealing

Analysis of the Quality Assurance results from the initial part of production of the ATLAS18 ITk strip sensors

The production of strip sensors for the ATLAS Inner Tracker (ITk) started in 2021. Since then, a Quality Assurance (QA) program has been carried out continuously, by using specific test structures, in parallel to the Quality Control (QC) inspection of the sensors. The QA program consists of monitoring sensor-specific characteristics and the technological process variability, before and after the irradiation with gammas, neutrons, and protons. After two years, half of the full production volume has been reached and we present an analysis of the parameters measured as part of the QA process. The main devices used for QA purposes are miniature strip sensors, monitor diodes, and the ATLAS test chip, which contains several test structures. Such devices are tested by several sites across the collaboration depending on the type of samples (non-irradiated components or irradiated with protons, neutrons, or gammas). The parameters extracted from the tests are then uploaded to a database and analyzed by Python scripts. These parameters are mainly examined through histograms and time-evolution plots to obtain parameter distributions, production trends, and meaningful parameter-to-parameter correlations. The purpose of this analysis is to identify possible deviations in the fabrication or the sensor quality, changes in the behavior of the test equipment at different test sites, or possible variability in the irradiation processes. The conclusions extracted from the QA program have allowed test optimization, establishment of control limits for the parameters, and a better understanding of device properties and fabrication trends. In addition, any abnormal results prompt immediate feedback to the vendor

Identification and Recovery of ATLAS18 Strip Sensors with High Surface Static Charge

The new all-silicon Inner Tracker (ITk) is being constructed by the ATLAS collaboration to track charged particles produced at the High-Luminosity LHC. The outer portion of the ITk detector will include nearly 18,000 highly segmented and radiation hard silicon strip sensors (ATLAS18 design). Throughout the production of 22,000 sensors, the strip sensors are subjected to a comprehensive suite of mechanical and electrical tests as part of the Quality Control (QC) program. In a large fraction of the batches delivered to date, high surface electrostatic charge has been measured on both the sensors and the plastic sheets which sheathe the sensors for shipping and handling rigidity. Aggregate data from across QC sites indicate a correlation between observed electrical failures and the sensor/plastic sheet charge build up. To mitigate these issues, the QC testing sites introduced recovery techniques involving UV light or flows of ionizing gas. Significant modifications to sensor handling procedures were made to prevent subsequent build up of static charge. This publication details a precise description of the issue, a variety of sensor recovery techniques, and trend analyses of sensors initially failing electrical tests (IV, strip scan, etc.)