Empirically testing <i>Tonnetz</i>, voice-leading, and spectral models of perceived triadic distance

We compare three contrasting models of the perceived distance between root-position major and minor chords and test them against new empirical data. The models include a recent psychoacoustic model called spectral pitch class distance, and two well-established music theoretical models – Tonnetz distance and voice-leading distance. To allow a principled challenge, in the context of these data, of the assumptions behind each of the models, we compare them with a simple “benchmark” model that simply counts the number of common tones between chords. Spectral pitch class and Tonnetz have the highest correlations with the experimental data and each other, and perform significantly better than the benchmark. The voice-leading model performs worse than the benchmark. We suggest that spectral pitch class distance provides a psychoacoustic explanation for perceived harmonic distance and its music theory representation, the Tonnetz. Scores and MIDI files of the stimuli, the experimental data, and the computational models are available in the online supplement

Characterisation of AMS H35 HV-CMOS monolithic active pixel sensor prototypes for HEP applications

Monolithic active pixel sensors produced in High Voltage CMOS (HV-CMOS) technology are being considered for High Energy Physics applications due to the ease of production and the reduced costs. Such technology is especially appealing when large areas to be covered and material budget are concerned. This is the case of the outermost pixel layers of the future ATLAS tracking detector for the HL-LHC. For experiments at hadron colliders, radiation hardness is a key requirement which is not fulfilled by standard CMOS sensor designs that collect charge by diffusion. This issue has been addressed by depleted active pixel sensors in which electronics are embedded into a large deep implantation ensuring uniform charge collection by drift. Very first small prototypes of hybrid depleted active pixel sensors have already shown a radiation hardness compatible with the ATLAS requirements. Nevertheless, to compete with the present hybrid solutions a further reduction in costs achievable by a fully monolithic design is desirable. The H35DEMO is a large electrode full reticle demonstrator chip produced in AMS 350 nm HV-CMOS technology by the collaboration of Karlsruher Institut f\"ur Technologie (KIT), Institut de F\'isica d'Altes Energies (IFAE), University of Liverpool and University of Geneva. It includes two large monolithic pixel matrices which can be operated standalone. One of these two matrices has been characterised at beam test before and after irradiation with protons and neutrons. Results demonstrated the feasibility of producing radiation hard large area fully monolithic pixel sensors in HV-CMOS technology. H35DEMO chips with a substrate resistivity of 200$\Omega$ cm irradiated with neutrons showed a radiation hardness up to a fluence of $10^{15}$n$_{eq}$cm$^{-2}$ with a hit efficiency of about 99% and a noise occupancy lower than $10^{-6}$ hits in a LHC bunch crossing of 25ns at 150V

Spatial and Temporal Trends in Travel for COVID-19 Vaccinations

Highlights : Disparities in distances people traveled for vaccinations by demographics exist. Males and White people traveled longer distances for vaccination appointments. Travel distances of over 10 miles for vaccination likely required motorized transportation. Introduction: Understanding spatial and temporal trends in travel for COVID-19 vaccinations by key demographic characteristics (i.e., gender, race, age) is important for ensuring equitable access to and increasing distribution efficiency of vaccines and other health services. The aim of this study is to examine trends in travel distance for COVID-19 vaccinations over the course of the vaccination rollout in North Carolina. Methods: Data were collected using electronic medical records of individuals who had first- or single-dose COVID-19 vaccination appointments through UNC Health between December 15, 2020, and August 31, 2021 (N = 204,718). Travel distances to appointments were calculated using the Euclidean distance from individuals’ home ZIP code centroids to clinic addresses. Descriptive statistics and multivariable regression models with individuals’ home ZIP codes incorporated as fixed effects were used to examine differences in travel distances by gender, race, and age. Results: Males and White individuals traveled significantly farther for vaccination appointments throughout the vaccination rollout. On average, females traveled 14. 4 miles, 3.5% shorter distances than males; Black individuals traveled 13.6 miles, 10.0% shorter distances than White individuals; and people aged 65 and older traveled 14.5 miles, 2.6% longer distances than younger people living in the same ZIP code. Conclusions: Controlling for socioeconomic status and spatial proximity to vaccination clinics at the ZIP code level, males and White individuals traveled longer distances for vaccination appointments, demonstrating more ability to travel for vaccinations. Results indicate a need to consider differential ability to travel to vaccinations by key demographic characteristics in COVID-19 vaccination programs and future mass health service delivery efforts

New label-free methods for protein relative quantification applied to the investigation of an animal model of Huntington Disease

Spectral Counts approaches (SpCs) are largely employed for the comparison of protein expression profiles in label-free (LF) differential proteomics applications. Similarly, to other comparative methods, also SpCs based approaches require a normalization procedure before Fold Changes (FC) calculation. Here, we propose new Complexity Based Normalization (CBN) methods that introduced a variable adjustment factor (f), related to the complexity of the sample, both in terms of total number of identified proteins (CBN(P)) and as total number of spectral counts (CBN(S)). Both these new methods were compared with the Normalized Spectral Abundance Factor (NSAF) and the Spectral Counts log Ratio (Rsc), by using standard protein mixtures. Finally, to test the robustness and the effectiveness of the CBNs methods, they were employed for the comparative analysis of cortical protein extract from zQ175 mouse brains, model of Huntington Disease (HD), and control animals (raw data available via ProteomeXchange with identifier PXD017471). LF data were also validated by western blot and MRM based experiments. On standard mixtures, both CBN methods showed an excellent behavior in terms of reproducibility and coefficients of variation (CVs) in comparison to the other SpCs approaches. Overall, the CBN(P) method was demonstrated to be the most reliable and sensitive in detecting small differences in protein amounts when applied to biological samples

Management of imatinib-resistant CML patients

Imatinib has had marked impact on outcomes in chronic myelogenous leukemia (CML) patients for all stages of the disease and is endorsed by international treatment guidelines as the first line option. Although imatinib is highly effective and well tolerated, the development of resistance represents a clinical challenge. Since the most frequently identified mechanism of acquired imatinib resistance is bcr-abl kinase domain point mutations, periodic hematologic, cytogenetic, and molecular monitoring is critical throughout imatinib therapy. Once cytogenetic remission is achieved, residual disease can be monitored by bcr-abl transcript levels as assayed by reverse transcription polymerase chain reaction (RT-PCR). Detection of bcr-abl mutants prior to and during imatinib therapy can aid in risk stratification as well as in determining therapeutic strategies. Thus, mutation screening is indicated in patients lacking or losing hematologic response. Moreover, search for mutations should also be performed when a 3-log reduction of bcr-abl transcripts is not achieved or there is a reproducible increase of transcript levels. In patients harboring mutations which confer imatinib resistance, novel second line tyrosine kinase inhibitors have demonstrated encouraging efficacy with low toxicity. Only the T315I bcr-abl mutant has proved totally resistant to all clinically available bcr-abl inhibitors. Strategies to further increase the rates of complete molecular remissions represent the next frontier in the targeted therapy of CML patients

New label-free methods for protein relative quantification applied to the investigation of an animal model of Huntington Disease

Spectral Counts approaches (SpCs) are largely employed for the comparison of protein expression profiles in label-free (LF) differential proteomics applications. Similarly, to other comparative methods, also SpCs based approaches require a normalization procedure before Fold Changes (FC) calculation. Here, we propose new Complexity Based Normalization (CBN) methods that introduced a variable adjustment factor (f), related to the complexity of the sample, both in terms of total number of identified proteins (CBN(P)) and as total number of spectral counts (CBN(S)). Both these new methods were compared with the Normalized Spectral Abundance Factor (NSAF) and the Spectral Counts log Ratio (Rsc), by using standard protein mixtures. Finally, to test the robustness and the effectiveness of the CBNs methods, they were employed for the comparative analysis of cortical protein extract from zQ175 mouse brains, model of Huntington Disease (HD), and control animals (raw data available via ProteomeXchange with identifier PXD017471). LF data were also validated by western blot and MRM based experiments. On standard mixtures, both CBN methods showed an excellent behavior in terms of reproducibility and coefficients of variation (CVs) in comparison to the other SpCs approaches. Overall, the CBN(P) method was demonstrated to be the most reliable and sensitive in detecting small differences in protein amounts when applied to biological samples

What antarctic plants can tell us about climate changes: Temperature as a driver for metabolic reprogramming

Global warming is strongly affecting the maritime Antarctica climate and the consequent melting of perennial snow and ice covers resulted in increased colonization by plants. Colobanthus quitensis is a vascular plant highly adapted to the harsh environmental conditions of Antarctic Peninsula and understanding how the plant is responding to global warming is a new challenging target for modern cell physiology. To this aim, we performed differential proteomic analysis on C. quitensis plants grown in natural conditions compared to plants grown for one year inside open top chambers (OTCs) which determine an increase of about 4 °C at midday, mimicking the effect of global warming. A thorough analysis of the up and downregulated proteins highlighted an extensive metabolism reprogramming leading to enhanced photoprotection and oxidative stress control as well as reduced content of cell wall components. Overall, OTCs growth seems to be advantageous for C. quitensis plants which could benefit from a better CO2 diffusion into the mesophyll and a reduced ROS‐mediated photodamage

Thermal conductivity of the Toda lattice with conservative noise

We study the thermal conductivity of the one dimensional Toda lattice perturbed by a stochastic dynamics preserving energy and momentum. The strength of the stochastic noise is controlled by a parameter $\gamma$. We show that heat transport is anomalous, and that the thermal conductivity diverges with the length $n$ of the chain according to $\kappa(n) \sim n^\alpha$, with $0 < \alpha \leq 1/2$. In particular, the ballistic heat conduction of the unperturbed Toda chain is destroyed. Besides, the exponent $\alpha$ of the divergence depends on $\gamma$

Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia

During the last few years many Checkpoint kinase 1/2 (Chk1/Chk2) inhibitors have been developed for the treatment of different type of cancers. In this study we evaluated the efficacy of the Chk 1/2 inhibitor prexasertib mesylate monohydrate in B-/T- cell progenitor acute lymphoblastic leukemia (ALL) as single agent and in combination with other drugs. The prexasertib reduced the cell viability in a dose and time dependent manner in all the treated cell lines. The cytotoxic activity was confirmed by the increment of apoptotic cells (Annexin V/Propidium Iodide staining), by the increase of \u3b3H2A.X protein expression and by the activation of different apoptotic markers (Parp-1 and pro-Caspase3 cleavage). Furthermore, the inhibition of Chk1 changed the cell cycle profile. In order to evaluate the chemo-sensitizer activity of the compound, different cell lines were treated for 24 and 48 hours with prexasertib in combination with other drugs (imatinib, dasatinib and clofarabine). The results from cell line models were strengthened in primary leukemic blasts isolated from peripheral blood of adult acute lymphoblastic leukemia patients. In this study we highlighted the mechanism of action and the effectiveness of prexasertib as single agent or in combination with other conventional drugs like imatinib, dasatinib and clofarabine in the treatment of B-/T-ALL