bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Broadness of Wave Spectrum on Significant Wave Height and Wave Power for Open Ocean Conditions of the Peru Basin
Authors: De La Torre Dennys , Luyo Jaime , Ortega Arturo 
Published: January 2024

Abstract
When estimating significant wave height and wave power, it is regularly assumed 4 for the spectral estimate factor. It means considering a narrowband wave spectrum. That approach is accurate enough when the spectral broadness parameter is near zero. Since the Peru Basin is an open ocean: swells and local wind waves can overlap; therefore, its wave spectrum should be considered broadband. This work aims to demonstrate that the wave spectrum in the Peru Basin has waves in a broad band of frequencies and also discuss how this characteristic affects estimating the significant wave height and wave power. The methodology comprises numerical methods, inferential statistics, and spectral analysis applied to ocean data. The paper's conclusions declare the Peru Basin wave spectrum as broadband. The estimated significant wave height for broadband wave spectrum is 7% lower than if the wave spectrum was considered narrowband. We propose 3.7 as the spectral estimate factor for calculating the significant wave height in the Peru Basin instead of the commonly used 4. The significant wave height error when assuming a narrowband wave spectrum slightly affects the spectral parametric wave power calculation, causing a maximum overestimation of 5%. Nevertheless, accurately estimating significant wave height is critical for diverse marine technologies.
Efficiency & Emissions Improvement Package for the 7FDL High-Power, Medium-Speed, Locomotive Diesel Engine
Authors: Hart Matthew , Gray Taylor , Brigden Jesse , Brumberg Justin , Grayson AJ , Shindledecker Alex 
Published: January 2024

Abstract
This paper summarizes the technical development of a performance improvement package for Wabtec Corporation’s 7FDL diesel engine. To support the engine and make it more productive for its owners, Wabtec Corporation has developed a modification package for the engine that will improve its performance, enabling either a significant efficiency improvement over the current 7FDL Tier 1+ diesel engine or producing lower emissions at the current efficiency. The redesign improvements also focused on maximizing base engine part reuse to deliver an improvement package at an effective cost point, as well as minimize tooling changes and maintenance retraining efforts for end-users.
The engine performance benefits were achieved through changes in the air handling system, fuel system, and control system. Changes to the air handling system include the optimization of intake valve closure and matched turbocharger. The fuel system was upgraded to a high-pressure common rail fuel system that allowed for increased in-cylinder air-fuel mixing optimization. This performance improvement package for the 7FDL engine was developed through the Lean Startup method of Minimum Viable Product. A series of low-cost experiments were conducted to slowly step into the benefits of changing fuel system and air handling components.
A Computational Analysis of Fuel Evaporation and Mixing in a Methanol Opposed-Piston Engine With a Passive Pre-Chamber
Authors: Menaca Rafael , Silva Mickael , Moreno-Cabezas Kevin , Vorraro Giovanni , Turner James W. G. , Im Hong G. 
Published: January 2024

Abstract
Opposed-piston two-stroke engines (OP2S) have demonstrated high thermodynamic efficiencies due to reduced heat losses and high volume-to-surface area ratios. This leads to remarkable advantages over four-stroke conventional diesel engines, as well as superior combustion characteristics. Therefore, combining this concept with renewable fuels and advanced technologies, such as pre-chamber, can be a route to high-efficiency, carbon-neutral powertrains. The narrow-throat KAUST pre-chamber was chosen for initial assessment, due to its advantage of being a drop-in concept, which lowers the technological barriers for deployment. Key engine design aspects contributing to methanol evaporation and mixture formation in a passive pre-chamber methanol OP2S engine were numerically investigated. CONVERGE™ was selected as the solver to explore the sensitivity of the evaporation and the mixture formation to the variation of injection direction, port swirl angle, and piston bowl shape. Previous studies of the port swirl angle in OP2S engines report that its design can lead to a concentration of hot residual gases around the cylinder axis in the main chamber. Specifically for methanol, these unscavenged residuals could thermally contribute to an increase in evaporation. However, the current study reveals that the sensitivity of methanol to evaporation and mixing are mainly related to the flow dynamics, while the effect of the remaining hot gases is secondary. Lastly, a modified piston was used to demonstrate the sensitivity of fuel evaporation and mixing due to flow patterns associated with the piston design.
Investigation of the Effect of Ammonia Addition on the Two-Stage Ignition Process of Dimethyl Ether Based on Chemical Kinetic Analysis
Authors: Ou Juan , Yang Ruomiao , Yan Yuchao , Liu Zhentao , Liu Jinlong 
Published: January 2024

Abstract
Ammonia (NH3) has garnered considerable attention in recent years as a promising carbon-free hydrogen carrier fuel for internal combustion engines. However, directly using pure ammonia in compression-ignition engines poses challenges. To facilitate NH3 ignition, high-activity fuels are often employed to ignite the premixed NH3/air mixture and initiate combustion. This study specifically focuses on the ignition process of binary mixtures of NH3 and dimethyl ether (DME), considering that DME is a carbon-neutral high-activity fuel. By conducting zero-dimensional reaction kinetics analysis, we compare the ignition processes of DME and NH3/DME mixtures. The results reveal that the addition of NH3 has minimal impact on the control mechanism of DME’s two-stage ignition process. DME still heavily relies on the proliferation of OH radicals in the low-temperature oxidation pathway, releasing heat during the reaction progression. As the temperature increases, the low-temperature oxidation branching pathways are gradually replaced by chain propagation pathways, resulting in a decrease in overall reaction activity. The reactivity and temperature rise rate of the reaction system is then controlled by the H2O2 loop mechanism prior to the thermal ignition. However, the presence of ammonia noticeably extends the ignition delay period of DME. Ammonia competes with OH radicals, essential for DME oxidation, thereby inhibiting DME ignition. Additionally, as the ignition reaction advances, the involvement of NH3 kinetics increases. For instance, nitrogen-containing species generated from NH3 oxidation, such as NO, NO2, and NH2, react with CH3OCH2 to form CH3OCHO, reducing the flux through the low-temperature oxidation pathway of DME. While ammonia reaction pathways also generate OH radicals, this comes at the expense of HO2 radicals and H radicals, ultimately leading to H2O2 production. Overall, these findings clearly demonstrate the substantial impact of ammonia addition on the ignition process of DME, emphasizing the necessity for further fundamental research to enhance our understanding of NH3/DME binary fuel ignition. Such insights are pivotal for improving the design and operation strategies of NH3/DME dual-fuel engines, thereby improving engine efficiency and reliability.
Experimental Study and Analysis of Ultra-Low Temperature Fuel Spray With a Heavy-Duty Injector Under Vaporizing Conditions
Authors: Zhao Zhihao , Zhang Anqi , Schmidt Henry , Atkinson William , Naber Jeffrey 
Published: January 2024

Abstract
Despite efficiency and emission benefits, the Gasoline Compression Ignition (GCI) technology faces a key technical risk of deteriorated cold start performance. This study aims to provide experimental dataset and analysis of fuel sprays under ultra-low temperature (as low as −40 °C) adapted for GCI applications. Both RON92 gasoline and ultra-low sulfur diesel (ULSD) were tested in this study to investigate the effects of fuel properties and ambient conditions on the spray vaporization and mixing processes. The experiments were conducted in a constant-volume combustion vessel with various fuel temperatures, injection pressures, ambient densities, and charge gas temperatures, captured by simultaneous Mie scattering and schlieren imaging. A novel fuel chilling setup was introduced to control the fuel reservoir temperature by circulating of liquid-nitrogen-cooled methanol. Vapor penetration, liquid penetration, and spray cone angle from a heavy-duty multi-hole injector were obtained through image processing. The results showed comparable vapor penetration between RON92 and ULSD even with different fuel temperatures and charge gas temperatures. However, RON92 and ULSD differs in terms of liquid penetration at different ambient charge gas temperatures due to their different volatility. RON92 gasoline started to present saturated liquid length at 700K, while ULSD needed a higher temperature at 900K. A semi-quantitative analysis was practiced using single component surrogates to highlight the fuel volatility effect.
Protecting the Achilles heel: three FolE_I-type GTP-cyclohydrolases needed for full growth of metal-resistant
Cupriavidus metallidurans
under a variety of conditions
Authors: Schulz Vladislava , Galea Diana , Herzberg Martin , Nies Dietrich H. 
Published: January 2024

ABSTRACT

In
Cupriavidus metallidurans
and other bacteria, biosynthesis of the essential biochemical cofactor tetrahydrofolate (THF) initiates from guanosine triphosphate (GTP). This step is catalyzed by FolE_I-type GTP cyclohydrolases, which are either zinc-dependent FolE_IA-type or metal-promiscuous FolE_IB-type enzymes. As THF is also essential for GTP biosynthesis, GTP and THF synthesis form a cooperative cycle, which may be influenced by the cellular homeostasis of zinc and other metal cations. Metal-resistant
C. metallidurans
harbors one FolE_IA-type and two FolE_IB-type enzymes. All three proteins were produced in
Escherichia coli
. FolE_IA was indeed zinc dependent and the two FolE_IB enzymes metal-promiscuous GTP cyclohydrolases
in vitro
, the latter, for example, functioning with iron, manganese, or cobalt. Single and double mutants of
C. metallidurans
with deletions in the
folE_I
genes were constructed to analyze the contribution of the individual FolE_I-type enzymes under various conditions. FolE_IA was required in the presence of cadmium, hydrogen peroxide, metal chelators, and under general metal starvation conditions. FolE_IB1 was important when zinc uptake was impaired in cells without the zinc importer ZupT (ZIP family) and in the presence of trimethoprim, an inhibitor of THF biosynthesis. FolE_IB2 was needed under conditions of low zinc and cobalt but high magnesium availability. Together, these data demonstrate that
C. metallidurans
requires all three enzymes to allow efficient growth under a variety of conditions.

IMPORTANCE

Tetrahydrofolate (THF) is an important cofactor in microbial biochemistry. This “Achilles heel” of metabolism has been exploited by anti-metabolites and antibiotics such as sulfonamide and trimethoprim. Since THF is essential for the synthesis of guanosine triphosphate (GTP) and THF biosynthesis starts from GTP, synthesis of both compounds forms a cooperative cycle. The first step of THF synthesis by GTP cyclohydrolases (FolEs) is metal dependent and catalyzed by zinc- or metal-promiscuous enzymes, so that the cooperative THF and GTP synthesis cycle may be influenced by the homeostasis of several metal cations, especially that of zinc. The metal-resistant bacterium
C. metallidurans
needs three FolEs to grow in environments with both high and low zinc and cadmium content. Consequently, bacterial metal homeostasis is required to guarantee THF biosynthesis.
CREATE’ing improvements in first-year students’ science efficacy via an online introductory course experience
Authors: Garzke Jessica , Steinwand Blaire J. 
Published: January 2024

ABSTRACT

With a primary objective to engage students in the process of science online, we transformed a long-standing laboratory course for first-year science students into a more accessible, immersive experience of current biological research using a narrow and focused set of primary literature and the Consider, Read, Elucidate a hypothesis, Analyze and interpret data, Think of the next Experiment (CREATE) pedagogy. The efficacy of the CREATE approach has been demonstrated in a diversity of higher education settings and courses. It is, however, not yet known if CREATE can be successfully implemented online with a large, diverse team of faculty untrained in the CREATE pedagogy. Here, we present the transformation of a large-enrollment, multi-section, multi-instructor course for first-year students in which the instructors follow different biological research questions but work together to reach shared goals and outcomes. We assessed students’ (i) science self-efficacy and (ii) epistemological beliefs about science throughout an academic year of instruction fully administered online as a result of ongoing threats posed by COVID-19. Our findings demonstrate that novice CREATE instructors with varying levels of teaching experience and ranks can achieve comparable outcomes and improvements in students’ science efficacy in the virtual classroom as a teaching team. This study extends the use of the CREATE pedagogy to large, team-taught, multi-section courses and shows its utility in the online teaching and learning environment.
The membrane-associated ubiquitin ligase MARCHF8 stabilizes the human papillomavirus oncoprotein E7 by degrading CUL1 and UBE2L3 in head and neck cancer
Authors: Khalil Mohamed I. , Yang Canchai , Vu Lexi , Chadha Smriti , Nabors Harrison , James Claire D. , Morgan Iain M. , Pyeon Dohun 
Published: January 2024

ABSTRACT

The human papillomavirus (HPV) oncoprotein E7 is a relatively short-lived protein required for HPV-driven cancer development and maintenance. E7 is degraded through ubiquitination mediated by cullin 1 (CUL1) and the ubiquitin-conjugating enzyme E2 L3 (UBE2L3). However, E7 proteins are maintained at high levels in most HPV-positive cancer cells. A previous proteomics study has shown that UBE2L3 and CUL1 protein levels are increased by the knockdown of the E3 ubiquitin ligase membrane-associated ring-CH-type finger 8 (MARCHF8). We have recently demonstrated that HPV16 upregulates MARCHF8 expression in HPV-positive keratinocytes and head and neck cancer (HPV+ HNC) cells. Here, we report that MARCHF8 stabilizes the HPV16 E7 protein by degrading the components of the S-phase kinase-associated protein 1-CUL1-F-box ubiquitin ligase complex in HPV+ HNC cells. We found that
MARCHF8
knockdown in HPV+ HNC cells drastically decreases the HPV16 E7 protein level while increasing the CUL1 and UBE2L3 protein levels. We further revealed that the MARCHF8 protein binds to and ubiquitinates CUL1 and UBE2L3 proteins and that MARCHF8 knockdown enhances the ubiquitination of the HPV16 E7 protein. Conversely, the overexpression of CUL1 and UBE2L3 in HPV+ HNC cells decreases HPV16 E7 protein levels and suppresses tumor growth
in vivo
. Our findings suggest that HPV-induced MARCHF8 prevents the degradation of the HPV16 E7 protein in HPV+ HNC cells by ubiquitinating and degrading CUL1 and UBE2L3 proteins.

IMPORTANCE

Since human papillomavirus (HPV) oncoprotein E7 is essential for virus replication; HPV has to maintain high levels of E7 expression in HPV-infected cells. However, HPV E7 can be efficiently ubiquitinated by a ubiquitin ligase and degraded by proteasomes in the host cell. Mechanistically, the E3 ubiquitin ligase complex cullin 1 (CUL1) and ubiquitin-conjugating enzyme E2 L3 (UBE2L3) components play an essential role in E7 ubiquitination and degradation. Here, we show that the membrane ubiquitin ligase membrane-associated ring-CH-type finger 8 (MARCHF8) induced by HPV16 E6 stabilizes the E7 protein by degrading CUL1 and UBE2L3 and blocking E7 degradation through proteasomes. MARCHF8 knockout restores CUL1 and UBE2L3 expression, decreasing E7 protein levels and inhibiting the proliferation of HPV-positive cancer cells. Additionally, overexpression of CUL1 or UBE2L3 decreases E7 protein levels and suppresses
in vivo
tumor growth. Our results suggest that HPV16 maintains high E7 protein levels in the host cell by inducing MARCHF8, which may be critical for cell proliferation and tumorigenesis.
Whole-exome sequencing reveals causative genetic variants for several overgrowth syndromes in molecularly negative Beckwith-Wiedemann spectrum
Authors: Higashimoto Ken , Sun Feifei , Imagawa Eri , Saida Ken , Miyake Noriko , Hara Satoshi , Yatsuki Hitomi , Kubiura-Ichimaru Musashi , Fujita Atsushi , Mizuguchi Takeshi , Matsumoto Naomichi , Soejima Hidenobu 
Published: January 2024

BackgroundBeckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by (epi)genetic alterations at 11p15. Because approximately 20% of patients test negative via molecular testing of peripheral blood leukocytes, the concept of Beckwith-Wiedemann spectrum (BWSp) was established to encompass a broader cohort with diverse and overlapping phenotypes. The prevalence of other overgrowth syndromes concealed within molecularly negative BWSp remains unexplored.MethodsWe conducted whole-exome sequencing (WES) on 69 singleton patients exhibiting molecularly negative BWSp. Variants were confirmed by Sanger sequencing or quantitative genomic PCR. We compared BWSp scores and clinical features between groups with classical BWS (cBWS), atypical BWS or isolated lateralised overgrowth (aBWS+ILO) and overgrowth syndromes identified via WES.ResultsTen patients, one classified as aBWS and nine as cBWS, showed causative gene variants for Simpson-Golabi-Behmel syndrome (five patients), Sotos syndrome (two), Imagawa-Matsumoto syndrome (one), glycosylphosphatidylinositol biosynthesis defect 11 (one) or 8q duplication/9p deletion (one). BWSp scores did not distinguish between cBWS and other overgrowth syndromes. Birth weight and height in other overgrowth syndromes were significantly larger than in aBWS+ILO and cBWS, with varying intergroup frequencies of clinical features.ConclusionMolecularly negative BWSp encapsulates other syndromes, and considering both WES and clinical features may facilitate accurate diagnosis.
Rigorous Assessment of Model Inference Accuracy using Language Cardinality
Authors: Clun Donato , Shin Donghwan , Filieri Antonio , Bianculli Domenico 
Published: January 2024

Models such as finite state automata are widely used to abstract the behavior of software systems by capturing the sequences of events observable during their execution. Nevertheless, models rarely exist in practice and, when they do, get easily outdated; moreover, manually building and maintaining models is costly and error-prone. As a result, a variety of model inference methods that automatically construct models from execution traces have been proposed to address these issues.
However, performing a systematic and reliable accuracy assessment of inferred models remains an open problem. Even when a reference model is given, most existing model accuracy assessment methods may return misleading and biased results. This is mainly due to their reliance on statistical estimators over a finite number of randomly generated traces, introducing avoidable uncertainty about the estimation and being sensitive to the parameters of the random trace generative process.
This article addresses this problem by developing a systematic approach based on analytic combinatorics that minimizes bias and uncertainty in model accuracy assessment by replacing statistical estimation with deterministic accuracy measures. We experimentally demonstrate the consistency and applicability of our approach by assessing the accuracy of models inferred by state-of-the-art inference tools against reference models from established specification mining benchmarks.
Abstract A009: Association between unstable diabetes mellitus and risk of pancreatic cancer
Authors: Ali Sitwat , Coory Michael , Donovan Peter , Na Renhua , Pandeya Nirmala , Pearson Sallie-Anne , Spilsbury Katrina , Stewart Louise , Thompson Bridie , Tuesley Karen , Waterhouse Mary , Webb Penelope , Jordan Susan , Neale Rachel 
Published: January 2024

Abstract
Worsening of hyperglycemia in people with pre-existing diabetes mellitus may be an indicator of undiagnosed pancreatic cancer. However, there is limited evidence from longitudinal studies regarding the association between deterioration of diabetes and pancreatic cancer in people with previously stable diabetes. The size of the association between deterioration of diabetes and pancreatic cancer, and how the association changes over time, needs further investigation. A population-based matched cohort study was conducted within Australian women with stable diabetes mellitus. Unstable diabetes, the exposure of interest, was defined as change in the type of antidiabetic medication or addition of another antidiabetic medication after at least 24 months of stable antidiabetic medication use. The date of exposure was defined as the index date. Each woman with unstable diabetes was matched to 4 women with stable diabetes by birth year (±1 year) at the index date. Flexible parametric survival models were used to estimate hazard ratios (HR) (overall and at different times) and 95% confidence intervals (CI), and absolute risk in both groups at different time points. We identified 134,954 women with unstable diabetes; these were matched to women who had not developed unstable diabetes at the index date. The mean age of the cohort was 68 years. Over a median follow-up period of 2.8 years, 1,315 pancreatic cancer cases were diagnosed. Overall, women who experienced deterioration in glycemic control had a 2.5-fold increased risk of developing pancreatic cancer (HR 2.55; 95% CI 2.29 – 2.85). The risk was very high during the initial few months [HRs at 3 months (5.76; 95% CI 4.72 – 7.04), 6 months (4.56; 95% CI 3.81 – 5.46), and 12 months (3.33; 95% CI 2.86 – 3.89)]. The risk then progressively declined with time. Worsening of glycemic control in those with previously stable diabetes may be an early clinical manifestation of pancreatic cancer. Further research is warranted to differentiate this pancreatic cancer-associated deterioration of glycemic control from other causes. The longer-term (3-7 years) weaker association between pancreatic cancer and deterioration of glycemic control suggests that poorly controlled hyperglycemia is a predisposing factor for pancreatic cancer.
Citation Format: Sitwat Ali, Michael Coory, Peter Donovan, Renhua Na, Nirmala Pandeya, Sallie-Anne Pearson, Katrina Spilsbury, Louise Stewart, Bridie Thompson, Karen Tuesley, Mary Waterhouse, Penelope Webb, Susan Jordan, Rachel Neale. Association between unstable diabetes mellitus and risk of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A009.