Observation of a Nuclear Recoil Peak at the 100 eV Scale Induced by Neutron Capture.

Coherent elastic neutrino-nucleus scattering and low-mass dark matter detectors rely crucially on the understanding of their response to nuclear recoils. We report the first observation of a nuclear recoil peak at around 112 eV induced by neutron capture. The measurement was performed with a CaWO_{4} cryogenic detector from the NUCLEUS experiment exposed to a ^{252}Cf source placed in a compact moderator. We identify the expected peak structure from the single-γ de-excitation of ^{183}W with 3σ and its origin by neutron capture with 6σ significance. This result demonstrates a new method for precise, in situ, and nonintrusive calibration of low-threshold experiments.

Non-viral chimeric antigen receptor (CAR) T cells going viral.

Chimeric antigen receptor (CAR) T cell therapy has made significant strides in the treatment of B-cell malignancies, but its application in treating solid tumors still poses significant challenges. Particularly, the widespread use of viral vectors to deliver CAR transgenes into T cells comes with limitations, including high costs and regulatory restrictions, which hinder the translation of novel genetic engineering concepts into clinical applications. Non-viral methods, such as transposon/transposase and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems, offer promising alternatives for stable transgene insertion in CAR-T cells. These methods offer the potential to increase accessibility and efficiency in the development and delivery of CAR-T cell therapies. The main challenge in using non-viral methods, however, is their low knock-in efficiency, which leads to low transgene expression levels. In this review, we discuss recent developments in non-viral approaches for CAR-T cell production, the manufacturing requirements for clinical-grade production of non-viral CAR-T cells, and the adjustments needed in quality control for proper characterization of genomic features and evaluation of potential genotoxicity.

Characterization of a kg-scale archaeological lead-based PbWO4 cryogenic detector for the RES-NOVA experiment.

Core-collapse Supernovae (SNe) are one of the most energetic events in the Universe, during which almost all the star's binding energy is released in the form of neutrinos. These particles are direct probes of the processes occurring in the stellar core and provide unique insights into the gravitational collapse. RES-NOVA will revolutionize how we detect neutrinos from astrophysical sources, by deploying the first ton-scale array of cryogenic detectors made from archaeological lead. Pb offers the highest neutrino interaction cross-section via coherent elastic neutrino-nucleus scattering (CEνNS). Such process will enable RES-NOVA to be equally sensitive to all neutrino flavours. For the first time, we propose the use archaeological Pb as sensitive target material in order to achieve an ultra-low background level in the region of interest (O(1 keV)). All these features make possible the deployment of the first cm-scale neutrino telescope for the investigation of astrophysical sources. In this contribution, we will characterize the radiopurity level and the performance of a small-scale proof-of-principle detector of RES-NOVA, consisting in a PbWO4 crystal made from archaeological-Pb operated as cryogenic detector.

Towards an automated data cleaning with deep learning in CRESST.

The CRESST experiment employs cryogenic calorimeters for the sensitive measurement of nuclear recoils induced by dark matter particles. The recorded signals need to undergo a careful cleaning process to avoid wrongly reconstructed recoil energies caused by pile-up and read-out artefacts. We frame this process as a time series classification task and propose to automate it with neural networks. With a data set of over one million labeled records from 68 detectors, recorded between 2013 and 2019 by CRESST, we test the capability of four commonly used neural network architectures to learn the data cleaning task. Our best performing model achieves a balanced accuracy of 0.932 on our test set. We show on an exemplary detector that about half of the wrongly predicted events are in fact wrongly labeled events, and a large share of the remaining ones have a context-dependent ground truth. We furthermore evaluate the recall and selectivity of our classifiers with simulated data. The results confirm that the trained classifiers are well suited for the data cleaning task.

Secular equilibrium assessment in a CaWO4 target crystal from the dark matter experiment CRESST using Bayesian likelihood normalisation.

CRESST is a leading direct detection sub-GeVc-2 dark matter experiment. During its second phase, cryogenic bolometers were used to detect nuclear recoils off the CaWO4 target crystal nuclei. The previously established electromagnetic background model relies on Secular Equilibrium (SE) assumptions. In this work, a validation of SE is attempted by comparing two likelihood-based normalisation results using a recently developed spectral template normalisation method based on Bayesian likelihood. Albeit we find deviations from SE in some cases we conclude that these deviations are artefacts of the fit and that the assumptions of SE is physically meaningful.

Thermal neutron-induced γ-ray background in 124Sn.

The thermal neutron-induced gamma-ray background in 124Sn is investigated in connection with neutrinoless double beta decay (0νßß) studies in 124Sn. For this purpose, a 99.26% enriched 124Sn sample was irradiated with a thermal neutron fluence of 3×1015/cm2 in the Dhruva reactor at the Bhabha Atomic Research Centre, Mumbai. The gamma ray spectra of the irradiated sample were measured in a low background counting setup to study both long-lived and short-lived activities. The present data give an independent measurement of the half-life of 125Sn*(32+) and 125Sn(112-) as 10.01(8) min and 9.63(2) d, respectively. The impact of the observed high-energy gamma rays and the residual activity due to 125Sb, on the background in the region of interest around the Qßß value of 124Sn (~2.291 MeV) is discussed.

Study of the effect of external noise pickups on the performance of a cryogenic bolometer.

This paper reports the detailed noise characterization, investigation of various noise sources, and its mitigation to improve the performance of a cryogenic bolometer detector for the TIN.TIN experiment. The noise spectrum has been measured for a sapphire bolometer test setup with an indigenously developed neutron transmutation doped Ge sensor in the cryogen free dilution refrigerator system at Mumbai. The effect of external noise, arising either from ground loops in the system or from the diagnostic and control electronics of the cryostat, on the performance of the bolometer is assessed. A systematic comparison of the influence of different noise pickups on the bolometer resolution is also presented. The best-achieved resolution (σE) at 15 mK is ∼15 keV for heater pulses and appears to be mainly limited by the noise due to the pulse tube cryocooler.

Comparison of the effect of calcium(II) and manganese(II) ions on trypsin autolysis.

The effect of Mn2+ and Ca2+ ions on the rate of trypsin autolysis was studied at pH 7.0 and at 34.4-60.2 degrees C. For comparison, the kinetic constants of esterolytic activity of trypsin in the presence of the metal ion were determined at pH 7.4 and at 36 degrees and 40 degrees C. There was no significant difference in the rate of autolysis between Mn2+ and Ca2+ in the temperature range 34-47 degrees C, but at 56.8 degrees and 60.2 degrees autolysis was slightly more rapid in the presence of Mn2+. The Mn2+ or Ca2+ ion bound to trypsin is supposed to control the conformation and thereby the stability and the activity of the enzyme. The indirect effect of Mn2+ and Ca2+ is discussed on a structural basis of the enzyme molecule.

Differences in effect of Mn(II), Fe(III), Co(II), and Zn(II) ions on trypsinogen activation.

The influence of Mn2+, Fe3+, Co2+, and Zn2+ ions on the extent of trypsinogen activation has been determined for several ion concentrations at pH 7.4 and 36.4 degrees C. For the Mn2+ ion also the autocatalytic rate constants have been detected. The effect of Ca2+ has been reinvestigated for comparison purposes. The apparent dissociation constants of KMn2+ = 0.01 (M) and KCa2+ = 0.02 (M) have been found for the given metal ion-trypsinogen complexes. For Co2+ ion, however, only a slight effect and for Fe3+ and Zn2+ ions no significant effect could be detected on trypsinogen activation. The investigated ions are of empty, open, and completed d subshells of electrons and they are different also in their ionic size. The differences in effects of the ions are discussed on the basis of these factors.

Reduction of doxorubicin (adriamycin) bone marrow toxicity.

Doxorubicin (adriamycin), an antineoplastic antibiotic, is a potent suppressant of bone marrow. Previous studies on doxorubicin disposition indicated that its diversion from bone marrow in the first few minutes after administration should result in a marked decrease in total exposure to the drug (concentration X time) with a concomitant reduction in concentration-time-dependent toxicity. To test this hypothesis, the descending aorta of rabbits was occluded just proximal to the iliac bifurcation for 30 min to deprive bone marrow of blood flow. Both these rabbits and the control rabbits were given 5 mg/kg of doxorubicin intravenously, and the total white cell could in peripheral blood was monitored periodically for 15 days. The decrease in toxicity produced by the occlusion was quite evident by comparison of white cell counts and deaths in all groups. A possible mechanism of this effect was shown to be a decreased doxorubicin exposure of bone marrow tissue in the occluded animals as judged by relative doxorubicin concentration-time curves in rabbits with and without the aortic occlusion.