Piezoresistive Membrane Surface Stress Sensors for Characterization of Breath Samples of Head and Neck Cancer Patients

For many diseases, where a particular organ is affected, chemical by-products can be found in the patient’s exhaled breath. Breath analysis is often done using gas chromatography and mass spectrometry, but interpretation of results is difficult and time-consuming. We performed characterization of patients’ exhaled breath samples by an electronic nose technique based on an array of nanomechanical membrane sensors. Each membrane is coated with a different thin polymer layer. By pumping the exhaled breath into a measurement chamber, volatile organic compounds present in patients’ breath diffuse into the polymer layers and deform the membranes by changes in surface stress. The bending of the membranes is measured piezoresistively and the signals are converted into voltages. The sensor deflection pattern allows one to characterize the condition of the patient. In a clinical pilot study, we investigated breath samples from head and neck cancer patients and healthy control persons. Evaluation using principal component analysis (PCA) allowed a clear distinction between the two groups. As head and neck cancer can be completely removed by surgery, the breath of cured patients was investigated after surgery again and the results were similar to those of the healthy control group, indicating that surgery was successful

TRINITY IV: Predictions for Supermassive Black Holes at z≳7z \gtrsim 7

We present predictions for the high-redshift halo-galaxy-supermassive black hole (SMBH) connection from the TRINITY model. Constrained by a comprehensive compilation of galaxy ($0\leq z \leq 10$) and SMBH datasets ($0\leq z \leq 6.5$), TRINITY finds: 1) The number of SMBHs with $M_\bullet > 10^9 M_\odot$ in the observable Universe increases by six orders of magnitude from $z\sim10$ to $z\sim2$, and by another factor of $\sim 3$ from $z\sim2$ to $z=0$; 2) The $M_\bullet > 10^9/10^{10} M_\odot$ SMBHs at $z\sim 6$ live in haloes with $\sim (2-3)/(3-5) \times 10^{12} M_\odot$; 3) the new JWST AGNs at $7\lesssim z \lesssim 11$ are broadly consistent with the median SMBH mass-galaxy mass relation for AGNs from TRINITY; 4) Seeds from runaway mergers in nuclear star clusters are viable progenitors for the SMBHs in GN-z11 ($z=10.6$) and CEERS_1019 ($z=8.7$); 5) $z=6-10$ quasar luminosity functions from wide area surveys by, e.g., Roman and Euclid, will reduce uncertainties in the $z=6-10$ SMBH mass-galaxy mass relation by up to $\sim 0.5$ dex.Comment: 15 pages, 12 figures, submitted to MNRAS. Questions and comments are welcome

Limits on Supernova-Associated Fe 60/Al 26 Nucleosynthesis Ratios from Accelerator Mass Spectrometry Measurements of Deep-Sea Sediments

We searched for the presence of Al26 in deep-sea sediments as a signature of supernova influx. Our data show an exponential dependence of Al26 with the sample age that is fully compatible with radioactive decay of terrigenic Al26. The same set of samples demonstrated a clear supernova Fe60 signal between 1.7 and 3.2 Myr ago. Combining our Al26 data with the recently reported Fe60 data results in a lower limit of 0.18-0.08+0.15 for the local interstellar Fe60/Al26 isotope ratio. It compares to most of the ratios deduced from nucleosynthesis models and is within the range of the observed average galactic Fe60/Al26 flux ratio of (0.15±0.05).This work was funded in part by the Austrian Science Fund (FWF), Projects No. P20434 and No. I428 (EUROCORES project EuroGENESIS, subproject CoDustMas), by BMBF Project No. 05K2016, DAAD (56266169), and by the University of Vienna

Impaired aldehyde dehydrogenase 1 subfamily member 2A-dependent retinoic acid signaling is related with a mesenchymal-like phenotype and an unfavorable prognosis of head and neck squamous cell carcinoma

Background: An inverse correlation between expression of the aldehyde dehydrogenase 1 subfamily A2 (ALDH1A2) and gene promoter methylation has been identified as a common feature of oropharyngeal squamous cell carcinoma (OPSCC). Moreover, low ALDH1A2 expression was associated with an unfavorable prognosis of OPSCC patients, however the causal link between reduced ALDH1A2 function and treatment failure has not been addressed so far. Methods: Serial sections from tissue microarrays of patients with primary OPSCC (n = 101) were stained by immunohistochemistry for key regulators of retinoic acid (RA) signaling, including ALDH1A2. Survival with respect to these regulators was investigated by univariate Kaplan-Meier analysis and multivariate Cox regression proportional hazard models. The impact of ALDH1A2-RAR signaling on tumor-relevant processes was addressed in established tumor cell lines and in an orthotopic mouse xenograft model. Results: Immunohistochemical analysis showed an improved prognosis of ALDH1A2high OPSCC only in the presence of CRABP2, an intracellular RA transporter. Moreover, an ALDH1A2highCRABP2high staining pattern served as an independent predictor for progression-free (HR: 0.395, p = 0.007) and overall survival (HR: 0.303, p = 0.002), suggesting a critical impact of RA metabolism and signaling on clinical outcome. Functionally, ALDH1A2 expression and activity in tumor cell lines were related to RA levels. While administration of retinoids inhibited clonogenic growth and proliferation, the pharmacological inhibition of ALDH1A2-RAR signaling resulted in loss of cell-cell adhesion and a mesenchymal-like phenotype. Xenograft tumors derived from FaDu cells with stable silencing of ALDH1A2 and primary tumors from OPSCC patients with low ALDH1A2 expression exhibited a mesenchymal-like phenotype characterized by vimentin expression. Conclusions: This study has unraveled a critical role of ALDH1A2-RAR signaling in the pathogenesis of head and neck cancer and our data implicate that patients with ALDH1A2low tumors might benefit from adjuvant treatment with retinoids

The physical constraints on a new LoBAL QSO at z=4.82

Very few low-ionization broad absorption line (LoBAL) QSOs have been found at high redshifts to date. One high-redshift LoBAL QSO, J0122+1216, was recently discovered at the Lijiang 2.4-m Telescope with an initial redshift determination of 4.76. Aiming to investigate its physical properties, we carried out follow-up observations in the optical and near-IR spectroscopy. Near-IR spectra from UKIRT and P200 confirms that it is a LoBAL, with a new redshift determination of $4.82\pm0.01$ based on the \mgii~ emission-line. The new \mgii~ redshift determination reveals strong blueshifts and asymmetry of the high-ionization emission lines. We estimated a black hole mass of $\sim 2.3\times 10^9 M_\odot$ and Eddington ratio of $\sim 1.0$ according to the empirical \mgii-based single-epoch relation and bolometric correction factor. It is possible that strong outflows are the result of an extreme quasar environment driven by the high Eddington ratio. A lower limit on the outflowing kinetic power ($>0.9\% L_{Edd}$) was derived from both emission and absorption lines, indicating these outflows play a significant role in the feedback process to regulate the growth of its black hole as well as host galaxy evolution.Comment: 12 pages, 10 figures. Accepted for publication in The Astrophysical Journa

Longest Increasing Subsequence under Persistent Comparison Errors

We study the problem of computing a longest increasing subsequence in a sequence $S$ of $n$ distinct elements in the presence of persistent comparison errors. In this model, every comparison between two elements can return the wrong result with some fixed (small) probability $p$, and comparisons cannot be repeated. Computing the longest increasing subsequence exactly is impossible in this model, therefore, the objective is to identify a subsequence that (i) is indeed increasing and (ii) has a length that approximates the length of the longest increasing subsequence. We present asymptotically tight upper and lower bounds on both the approximation factor and the running time. In particular, we present an algorithm that computes an $O(\log n)$-approximation in time $O(n\log n)$, with high probability. This approximation relies on the fact that that we can approximately sort $n$ elements in $O(n\log n)$ time such that the maximum dislocation of an element is at most $O(\log n)$. For the lower bounds, we prove that (i) there is a set of sequences, such that on a sequence picked randomly from this set every algorithm must return an $\Omega(\log n)$-approximation with high probability, and (ii) any $O(\log n)$-approximation algorithm for longest increasing subsequence requires $\Omega(n \log n)$ comparisons, even in the absence of errors

Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors

Summary Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to dystrophin-expressing myofibers upon transplantation in vivo. Notably, a subset of transplanted iMPCs maintain Pax7 expression and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7+ cells and require Pax7 itself for maintenance. Finally, we show that myogenic progenitor cell lines can be established from muscle tissue following small-molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple cell types