bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lubricity Problems and Solutions for a Methanol Fueled Gas Turbine
Authors: Bond Robert E. , Loth John L. , Guiler Richard W. , Clark Nigel N. , Heydorn Edward C. 
Published: November 2021

Abstract
The Liquid Phase Methanol (LPMEOH™) process, which was developed by Air Products and Chemicals Inc. and sponsored by the United States Department of Energy, uses a slurry bubble column reactor to convert synthesis gas to methanol. In 1998, LPMOH™ “as produced” (about 98% purity) was used at West Virginia University to fuel a small (235 Hp) gas turbine. The objective was to demonstrate the viability of LPMEOH™ as a gas turbine fuel, identify and operational problems and obtain exhaust gas emissions samples using the WVU Mobile Emissions Laboratory. During these tests, the fuel system gear pump and rpm controller failed due to the lack of lubricity of the methanol fuel. To remedy this problem, a pint (over an order of magnitude larger than the recommended amount) of a commercially available fuel additive was dissolved in half a barrel of methanol, and the fuel controller/pump was replaced. The next series of runs produced a similar failure. This prompted the WVU team to search for a suitable methanol additive, which can provide lubricity equal or better than that of jet fuel. To minimize the amount and thus cost of such an additive, it was essential to accurately measure lubricity of methanol/additive solutions, at various concentration levels. Conventional lubricity measuring tests are based on measuring wear. When used with methanol, the data were erratic due to a changing wear pattern. To get repeatable steady data, a new lubricity test apparatus was developed, based on comparing friction coefficients, at a typical bearing design load. After many modifications this apparatus provided satisfactory and consistent results. A few percent castor oil or less than one percent of Two Cycle Blue, a racing fuel additive, produced a methanol lubricity in excess of that of jet fuel.
Experimental Study of Multiphase Flow in Cold Box Core Process
Authors: Bakhtiyarov Sayavur I. , Overfelt Ruel A. 
Published: November 2021

Abstract
The results of experimental study of pressure variations inside core box during resin bonded sand filling process are reported. The test core specimens were produced using Laempe® Test Specimen Curing Machine L 1. A special pressure measurement system was designed and built with safety and portability requirements of the foundry environment. Special experiments were conducted to establish the effect of sand deposition on vent permeability.
Uneven spatial sampling distorts reconstructions of Phanerozoic seawater temperature
Authors: Jones Lewis A. , Eichenseer Kilian 
Published: November 2021

Abstract
Paleotemperature proxy records are widely used to reconstruct the global climate throughout the Phanerozoic and to test macroevolutionary hypotheses. However, the spatial distribution of these records varies through time. This is problematic because heat is unevenly distributed across Earth's surface. Consequently, heterogeneous spatial sampling of proxy data has the potential to bias reconstructed temperature curves. We evaluated the spatiotemporal evolution of sampling using a compilation of Phanerozoic δ18O data. We tested the influence of variable spatial coverage on global estimates of paleotemperature by sampling a steep “modern-type” latitudinal temperature gradient and a flattened “Eocene-type” gradient, based on the spatial distribution of δ18O samples. We show that global paleotemperature is overestimated in ∼70% of Phanerozoic stages. Perceived climatic trends for some intervals might be artifactually induced by shifts in paleolatitudinal sampling, with equatorward shifts in sampling concurring with warming trends, and poleward shifts concurring with cooling trends. Yet, the magnitude of some climatic perturbations might also be underestimated. For example, the observed Ordovician cooling trend may be underestimated due to an equatorward shift in sampling. Our findings suggest that while proxy records are vital for reconstructing Earth's paleotemperature in deep time, consideration of the spatial nature of these data is crucial to improving these reconstructions.
Advances in systemic therapy for non-small cell lung cancer
Authors: Miller Meagan , Hanna Nasser 
Published: November 2021

ABSTRACTLung cancer remains a leading cause of cancer related mortality worldwide. Despite numerous advances in treatments over the past decade, non-small cell lung cancer (NSCLC) remains an incurable disease for most patients. The optimal treatment for all patients with locally advanced, but surgically resectable, NSCLC contains at least chemoradiation. Trimodality treatment with surgical resection has been a subject of debate for decades. For patients with unresectable or inoperable locally advanced disease, the incorporation of immunotherapy consolidation after chemoradiation has defined a new standard of care. For decades, the standard of care treatment for advanced stage NSCLC included only cytotoxic chemotherapy. However, with the introduction of targeted therapies and immunotherapy, the landscape of treatment has rapidly evolved. This review discusses the integration of these innovative therapies in the management of patients with newly diagnosed NSCLC.
48 Immune environment correlates with NSCLC and CRC patient survival
Authors: Miller Dannah , Nguyen Huong , Hieber Kate , Caldwell Charles , Gianani Roberto 
Published: November 2021

BackgroundImmune cells within the tumor microenvironment (TME) play a vital role in regulating tumor progression. Therefore, immunotherapies that stimulate anti-tumor responses are of great interest for the treatment of various cancers. PD-L1 expression on immune cells is positively correlated with increased patient survival. Our hypothesis is that non-small cell lung carcinoma (NSCLC) and colorectal cancer (CRC) patients with high immune infiltration and greater amounts of anti-tumor immune cells within the tumor compartment have an increased time of survival compared to cancers with immune excluded or immune desert environments.MethodsOne NSCLC and one CRC tumor microarray (TMA) containing primary tumors, metastases, and normal tissue were stained via multiplex immunofluorescence (mIF) for 6 different immune markers: CD3, CD8, CD56, CD68, CD163, and PD-L1. This multiplex panel was designed to evaluate the immune cell population as well as tumor and immune cell PD-L1 status to aid in research for immunotherapies, specifically anti-PD-L1 therapies. The stained TMAs were analyzed utilizing Flagship Biosciences’ proprietary image analysis platform. Machine learning algorithms stratified cells as belonging to the tumoral or stromal space based on their cellular features. Core level expression data was pulled and represented on a whole-cohort basis. All staining and image analysis outputs were reviewed by a board-certified, MD pathologist. Kaplan-meier curves were generated based on survival data in relation to the levels of immune cells present within the tumor cores as well as the percentage of immune cells infiltrating into the tumor.ResultsThere is a clear correlation between patient survival and the presence or absence of various types of immune cells, including helper T cells, cytotoxic T cells, M1 macrophages, M2, macrophages, NK cells, as well as PDL1 expression on tumor and immune cells. Specifically, the increased presence of anti-tumor immune cells as well as increased expression of PD-L1 on immune cells within the tumor compartment correlates with an increase in patient survival.ConclusionsData generated through Flagship Biosciences’ image analysis platform showed a strong relationship between immune cell presence and localization and NSCLC and CRC patient survival. Altering the immune cells within the tumor to an anti-tumor immune environment could increase patient survival times. Combining immune checkpoint inhibitors with current FDA approved therapies for NSCLC and CRC are of interest to further extend patient survival. Further, utilizing Flagship Biosciences’ image analysis software to understand cancer immune microenvironments should be further utilized to aid in diagnosis and treatment decisions.
64 A cloning and expression system of the neoantigen-specific TCRs from tumor-infiltrating lymphocytes by single-cell sequencing of paired TCRα and TCRβ chains
Authors: Kobayashi Yukari , Nagaoka Koji , Kubo Kaori , Nishie Toshikazu , Okamoto Sachiko , Enoki Tatsuji , Mineno Junichi , Sato Yasuyoshi , Takahashi Shunji , Nakajima Jun , Kakimi Kazuhiro 
Published: November 2021

BackgroundT-cells that target tumor neoantigens arising from cancer mutations are the primary mediators of cancer immunotherapies. Identifying neoantigens and T-cells that recognize them is essential for T-cell-based immunotherapy. However, neoantigen-reactive Tumor-infiltrating lymphocytes (TILs) are highly differentiated or exhausted with a limited proliferative capacity; it is challenging to expand them for a sufficient number to probe their specificity. Therefore, we developed a novel cloning and expression system to examine TCRs discovered by single-cell sequencing of TILs for their neoantigen-specificity.MethodsTILs of lung cancer and sarcoma were analyzed. Surgically removed tumors were divided into several pieces. They were enzymatically digested to prepare fresh tumor digest (FTD) and cryopreserved. They were used to generate TIL cultures and perform WES and RNA-Seq to identify tumor-specific mutations. MHCflurry was used to predict the binding affinity of potential epitopes arising from these mutations to HLA class I. Peptides that were predicted to bind to patients‘ own MHC class I molecules strongly were then synthesized. Single TILs isolated with the ICELL8® cx system (Takara Bio) were dispensed into a nanowell TCR chip containing preprinted barcodes. Barcoded cDNAs were PCR-amplified in-chip, pooled off-chip, and used as a template in the TCR-specific PCR or for the whole transcriptome library generation of 5’ ends of all transcripts. Based on single-cell transcriptome data and TCR profiles of TILs, we predict and prioritize neoantigen-specific TCRs and cloned them into siTCR® retrovirus vectors. These TCRs were transduced into SUP-T1-based reporter cells in which ZsGreen fluorescent protein expression is controlled by AP-1 and NFAT binding sites. TCR-expressing reporter cells were cocultured with patient autologous APCs pulsed with a pool of candidate neoantigen peptides. ZsGreen expression indicates that TCRs match their cognate neoantigens.ResultsIn a lung cancer patient, we set up 18 TIL cultures and obtained 12 TILs. TILs were cocultured with FTD; IFN-γ production was measured by ELISA to evaluate their reactivity to the autologous tumor. NGS identified 197 somatic mutations, 4 fusion genes, and 8 highly expressed cancer-testis antigens. Among them, 339 candidate peptides were synthesized and screened. In addition, we cloned 3 pairs of TCRαβ chains from most expanded TIL cultures and 4 TCRs from ex vivo TILs with exhausted phenotype. Two reporter cells that express TCRs from exhausted TILs responded to the same neoantigen peptide.ConclusionsGenerating TCR expressing cell lines facilitated the identifying neoantigens and their cognate TCR sequences from patients.Ethics ApprovalG3545
281 Measuring immune checkpoint inhibitor efficacy using primary patient-derived 3D spheroids
Authors: Appleton Kathryn , Lassahn Katy , Elrod Ashley , DesRochers Tessa 
Published: November 2021

BackgroundCancerous cells can utilize immune checkpoints to escape T-cell-mediated cytotoxicity. Agents that target PD-1, PD-L1 and CTLA4 are collectively deemed immune checkpoint inhibitors (ICIs), and many have been approved for treatment of non-small cell lung cancer (NSCLC) and melanoma. Unfortunately, many patients do not respond to these therapies and often experience disease progression. Immunohistochemistry assays to predict response to ICIs have been inconsistent in their readouts and often patients with low expression levels respond to ICIs. Understanding the determinants of ICI response in individual patients is critical for improving the clinical success of this drug class. Using patient-derived spheroids from NSCLC and melanoma primary tissue, we developed a multi-plexed assay for detecting ICI efficacy.MethodsNine NSCLC and 11 melanoma primary tumor samples were dissociated to single cells, classified for immune checkpoint expression and cell content by flow cytometry, and seeded for spheroid formation. Spheroids were treated with pembrolizumab, nivolumab, atezolizumab, ipilimumab or durvalumab across a range of concentrations and monitored for cytotoxicity at 24-hours and viability at 72-hours by multiplexing CellTox™ Green Cytotoxicity Assay and CellTiter-Glo® 3D Cell Viability Assay. IFNγ and granzyme B secretion was assessed using Luminex technology. ICI response was evaluated by determining the concentration-response relationship for all three read-outs.ResultsIncreased IFNγ and granzyme B were detected for every ICI in one or more patient samples. ICI-induced IFNγ secretion inversely correlated with PD-1+ immune cells. Durvalumab was significantly more cytotoxic for both NSCLC and melanoma spheroids compared to the other ICIs and significantly reduced spheroid viability with mean spheroid survival decreasing to 19.5% for NSCLC and 58.2% for melanoma. We evaluated if there was an association between durvalumab response and cell composition and found that percent spheroid survival significantly correlated with CD8+ T-cells for both NSCLC (r=-0.7920, p=0.0191) and melanoma (r=-0.6918, p=0.0390). Furthermore, CD8+ T-cells correlated with durvalumab-induced granzyme B secretion for NSCLC (r=-0.7645, p=0.0271) and melanoma (r=-0.7419, p=0.0221).ConclusionsIn this study we show ICI-specific increases in immune-related analytes in a concentration-dependent manner for NSCLC and melanoma patient-derived spheroids. We detected spheroid cytotoxicity following short term ICI treatment which closely mirrored decreased spheroid viability at a later timepoint. Finally, we can decipher response mechanisms as exemplified by durvalumab-induced granzyme B secretion correlating with the presence of CD8+ T-cells which results in reduced spheroid viability for both tested cancer indications.
315 Application of the SITC immunotherapy resistance taskforce definitions of anti-PD-1 resistance to studies evaluating patients with advanced melanoma
Authors: Shui Irene , Scherrer Emilie , Frederickson Andrew , Druyts Eric , Tawbi Hussein 
Published: November 2021

BackgroundUntil the recent 2020 publication by the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Taskforce, there was little consensus on defining primary and secondary resistance to anti-programmed cell death protein 1 monotherapy. Our objective was to characterize the clinical outcomes reported in peer-reviewed literature when categorized according to the SITC definitions.MethodsA systematic literature review (SLR) was conducted in Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, and Cochrane Central Register of Controlled Trials (September 2015 - September 2020). Data were extracted on the proportion of patients with progressive disease (PD), and SITC criteria were applied to define resistance (table 1).ResultsThirty six studies were included, yielding 55 patient cohorts with data on PD; 42 cohorts reported PD specifically by best overall response, while 13 cohorts provided another definition of response. Response evaluation criteria in solid tumors (RECIST) 1.1 was most commonly used (37 cohorts), followed by immune-RECIST (7 cohorts). Twenty four cohorts reporting PD also had data on length of drug exposure, 13 on duration of response, 22 on utilization of a confirmatory scan, and 1 on whether progression occurred within 12 weeks of the last dose of therapy; no studies reported on all 4 criteria. We were able to partially apply SITC criteria for primary resistance to 42 of 55 cohorts and the proportion of patients with primary resistance ranged from 25% to 81%. Only a few studies had data on secondary resistance, but none provided enough granularity to fully categorize secondary resistance by SITC.Abstract 315 Table 1SITC definitions of primary and secondary resistance in advanced diseaseConclusionsThe majority of studies in this SLR did not report complete criteria to apply the SITC definitions; however, partial categorization of primary resistance was possible. The patient characteristics and outcomes reported varied, thus the data assessed were heterogeneous. Future studies should consider utilizing the SITC consensus definitions to harmonize how resistance is classified and facilitate meaningful context for clinical activity.
Noninvasive Prototype for Type 2 Diabetes Detection
Authors: Castillo García Javier Ferney , Ortiz Jesús Hamilton , Ibrahim Khalaf Osamah , Valencia Hernández Adrián David , Rodríguez Timaná Luis Carlos 
Published: November 2021

The present work demonstrates the design and implementation of a human-safe, portable, noninvasive device capable of predicting type 2 diabetes, using electrical bioimpedance and biometric features to train an artificial learning machine using an active learning algorithm based on population selection. In addition, there is an API with a graphical interface that allows the prediction and storage of data when the characteristics of the person are sent. The results obtained show an accuracy higher than 90% with statistical significance (

p

< 0.05). The Kappa coefficient values were higher than 0.9, showing that the device has a good predictive capacity which would allow the screening process of type 2 diabetes. This development contributes to preventive medicine and makes it possible to determine at a low cost, comfortably, without medical preparation, and in less than 2 minutes whether a person has type 2 diabetes.
Transnational Isolates: Portuguese Colonial Race Science and the Foreign World
Authors: Roque Ricardo 
Published: November 2021

Abstract
This article examines scientific transnationalism as an art of engagement with, and avoidance of, the threats and promises of what was foreign to the nation. Portuguese racial anthropologists experienced a tension between remaining imperial-nationalistic in character, and internationalist in their activities simultaneously. They struggled to exclude foreigners from colonial field sites; they aimed at nativist authority based on total control of colonial data. Yet, they eagerly sought connections with foreign experts to capitalize provincial scientific authority within Portugal’s colonies. The essay conceptualizes this mode of transnationalism as also a kind of isolationism, an inward oriented form of engaging with foreign sciences and scientists as ambivalently powerful and threatening strangers.
The Chapters on Women in Two Adab Encyclopaedias from the Mamluk Period
Authors: López Bernal Desirée 
Published: November 2021

Abstract
This paper is a study of the chapters devoted to women in general and to female figures (female singers) in two encyclopaedic adab works of the Mamluk period, al-Nuwayrī’s Nihāyat al-arab and al-Ibshīhī’s al-Mustaṭraf fī kulli fann al-mustaẓraf. We will analyse the content of these chapters, their focus, the materials from which they are constructed and their objectives within the ensemble of the works. We will also look at the moral and intellectual qualities that configure the portrayal of women in these books, in common with others of adab prose. The final aim of all this is to obtain results to add to those that already exist, with a view to defining the female character types in this literature, the topics that make women visible in it and their relationship with male characters in the stories.
Canonization, Satire, and Criticism of Avot in Midrash Yelammedenu from the Genizah
Authors: Rosenfeld Eliyahu 
Published: November 2021

Abstract
In this article, I present a midrashic reference to one mishnah of tractate Avot that would appear to undermine its canonical status. A close reading of the midrash, will show that it makes use of various satirical tools, including exaggeration and ridicule, which appear to be aimed at a mocking of the mishnah. However, further reading of the midrash in light of a more comprehensive look at tractate Avot will show that contrary to this initial impression, the use of satire may not be directed at undermining the canonical status of Avot but rather at strengthening it. According to this reading, the satire is directed at internal criticism that the midrash identifies in the heart of the mishnaic text, with the result that Avot’s status is restored.
The Flash Flood Guidance System Implementation Worldwide: A Successful Multidecadal Research-to-Operations Effort
Authors: Georgakakos Konstantine P. , Modrick Theresa M. , Shamir Eylon , Campbell Rochelle , Cheng Zhengyang , Jubach Robert , Sperfslage Jason A. , Spencer Cristopher R. , Banks Randall 
Published: November 2021

Abstract
At the beginning of the twenty-first century a research-to-operations program was initiated to design and develop operational systems to support local forecasters in their challenging task to provide advance warning for flash floods worldwide. Twenty-some years later, the Flash Flood Guidance System with global coverage provides real-time assessment and guidance products to more than 60 countries, serving nearly 3 billion people. The implementation domains cover a wide range of hydroclimatological, geomorphological, and land-use regimes worldwide. This flexible and evolving system combines meteorology and hydrology data and concepts as well as supports product utility for flash flood disaster mitigation on very large scales with high spatial and temporal resolution. Through quality control procedures, it integrates remotely sensed data of land surface precipitation and of land surface properties from geostationary and polar-orbiting satellite platforms, reflectivity data from a variety of weather radar systems, and asynchronous precipitation data from ground-based automated precipitation gauges in order to produce assessments and short-term forecasts that support forecasters and disaster managers in real time. For each region, it also integrates mesoscale meteorological model forecasts with land surface model response to produce longer-term guidance products. It contains components and interfaces that allow real-time forecaster adjustments to products based on local last-minute field information and relevant forecaster experience. Assessments of utility for flash flood warning operations by national forecasting agencies worldwide are positive. The article exemplifies the process of realization and evolution of the Flash Flood Guidance System (FFGS) from research in interdisciplinary fields to operations in diverse environments, and discusses lessons learned.