Sou\u27wester: Volume 2, Number 4-December 25, 1938

https://digitalmaine.com/souwester/1002/thumbnail.jp

Sou\u27wester: Volume 2, Number 3-November 24, 1938

https://digitalmaine.com/souwester/1001/thumbnail.jp

Direct spectroscopic evidence for mixed-valence Tl in the low carrier-density superconductor Pb1-xTIxTe

Upon doping with Tl the narrow band-gap semiconductor PbTe exhibits anomalously high-temperature superconductivity despite a very low carrier-density as well as signatures of the Kondo effect despite an absence of magnetic moments. These phenomena have been explained by invoking 2e fluctuations of the valence of the Tl dopants, but a direct measurement of the mixed valency implied by such a mechanism has not been reported to date. In this work we present the unambiguous observation of multiple valences of Tl in Tl-doped PbTe via photoemission spectroscopy measurements. It is shown via a quantitative analysis that the suppression of the carrier density in compositions exhibiting superconductivity and Kondo-like behavior can be accounted for by mixed valency, thus arguing against a self-compensation scenario proposed elsewhere for this material and strengthening the case for valence fluctuation models. In addition to the identification of Tl+ and Tl3+ a possible third intermediate local charge-density is suggested by full fits to the data, the origins of which are also discussed but remain unclear

FOXD3 Regulates VISTA Expression in Melanoma.

Immune checkpoint inhibitors have improved patient survival in melanoma, but the innate resistance of many patients necessitates the investigation of alternative immune targets. Many immune checkpoint proteins lack proper characterization, including V-domain Ig suppressor of T cell activation (VISTA). VISTA expression on immune cells can suppress T cell activity; however, few studies have investigated its expression and regulation in cancer cells. In this study, we observe that VISTA is expressed in melanoma patient samples and cell lines. Tumor cell-specific expression of VISTA promotes tumor onset in vivo, associated with increased intratumoral T regulatory cells, and enhanced PDL-1 expression on tumor-infiltrating macrophages. VISTA transcript levels are regulated by the stemness factor Forkhead box D3 (FOXD3). BRAF inhibition upregulates FOXD3 and reduces VISTA expression. Overall, this study demonstrates melanoma cell expression of VISTA and its regulation by FOXD3, contributing to the rationale for therapeutic strategies that combine targeted inhibitors with immune checkpoint blockade

Analytic Inversion of Emission Lines of Arbitrary Optical Depth for the Structure of Supernova Ejecta

We derive a method for inverting emission line profiles formed in supernova ejecta. The derivation assumes spherical symmetry and homologous expansion (i.e., $v(r) \propto r$), is analytic, and even takes account of occultation by a pseudo-photosphere. Previous inversion methods have been developed which are restricted to optically thin lines, but the particular case of homologous expansion permits an analytic result for lines of {\it arbitrary} optical depth. In fact, we show that the quantity that is generically retrieved is the run of line intensity $I_\lambda$ with radius in the ejecta. This result is quite general, and so could be applied to resonance lines, recombination lines, etc. As a specific example, we show how to derive the run of (Sobolev) optical depth $\tau_\lambda$ with radius in the case of a pure resonance scattering emission line.Comment: 6 pages, no figures, to appear in Astrophysical Journal Letters, requires aaspp4.sty to late

Investigating Mitochondrial Fission, Fusion, and Biogenesis in Pathology of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. Due to our fragmented understanding of AMD’s pathologic mechanisms, there remains no FDA-approved treatment for the dry form of AMD. Studies from the Ferrington laboratory at the University of Minnesota and other groups report evidence of mitochondrial damage and dysfunction in RPE from AMD donors. Under normal conditions, the RPE maintains a healthy pool of mitochondria through dynamic processes such as mitochondrial Fission, Fusion, Biogenesis, and Mitophagy. In this poster, we investigated protein abundance levels of key proteins involved in mitochondrial Fission, Fusion, and Biogenesis. Our results indicate statically significant differences in abundance levels of proteins involved in Fission as well as Biogenesis between AMD and No AMD donors.This research was supported by the Undergraduate Research Opportunities Program (UROP).Shaaeli, Adam A; Fisher, Cody R; Ebeling, Mara C; Ferrington, Deborah A. (2021). Investigating Mitochondrial Fission, Fusion, and Biogenesis in Pathology of Age-Related Macular Degeneration. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/223232

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs)

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.Peer reviewe

Fluctuating selection models and Mcdonald-Kreitman type analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates

Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for Comparative Characterization of Complex Mixture Drugs

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.As the second of a 3-part series of articles in this issue concerning the development of a mathematical model for comparative characterization of complex mixture drugs using crofelemer (CF) as a model compound, this work focuses on the evaluation of the chemical stability profile of CF. CF is a biopolymer containing a mixture of proanthocyanidin oligomers which are primarily composed of gallocatechin with a small contribution from catechin. CF extracted from drug product was subjected to molecular weight–based fractionation and thiolysis. Temperature stress and metal-catalyzed oxidation were selected for accelerated and forced degradation studies. Stressed CF samples were size fractionated, thiolyzed, and analyzed with a combination of negative-ion electrospray ionization mass spectrometry (ESI-MS) and reversed-phase-HPLC with UV absorption and fluorescence detection. We further analyzed the chemical stability data sets for various CF samples generated from reversed-phase-HPLC-UV and ESI-MS using data-mining and machine learning approaches. In particular, calculations based on mutual information of over 800,000 data points in the ESI-MS analytical data set revealed specific CF cleavage and degradation products that were differentially generated under specific storage/degradation conditions, which were not initially identified using traditional analysis of the ESI-MS results