bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of different weed management strategies including non‐chemical tools and cinmethylin for control of multiple herbicide‐resistant Alopecurus myosuroides
Authors: Klauk Benjamin , Petersen Jan 
Published: June 2023

AbstractThe development of resistance in Alopecurus myosuroides populations to different herbicide active ingredients in Europe exacerbates efforts toward its chemical control. In Europe, cinmethylin provides an additional mode of action for the control of A. myosuroides. The objective of this study was to evaluate three resistance weed management (RWM) strategies, including cinmethylin and other pre‐emergence herbicides, for the control of multiple herbicide–resistant A. myosuroides. The RWM strategies used in this study differed in the extent of preventive cultural practices (tillage, crop rotation, sowing date and stale seedbed). Two field trials were conducted at sites with ACCase‐ and ALS‐resistant A. myosuroides biotypes in Germany between 2017 and 2020. Cinmethylin was included in the herbicide regime for A. myosuroides control. The combination of initial inversion tillage, delayed sowing, crop rotation diversification, and stale seedbed reduced the density of A. myosuroides bup to 90% compared to a strategy with pre‐emergence herbicides used as main components in control. At both sites, the amount of viable A. myosuroides seeds in the soil seed bank was reduced by over 90% after a 3‐year trial period in plots with initial inversion tillage. Molecular analyses revealed that the omission of ACCase and ALS inhibitors did not reduce the proportion of resistant A. myosuroides biotypes. Long‐term control of resistant A. myosuroides must be based on a combination of cultural practices that reduce the soil seed bank and suppress the occurrence of A. myosuroides and the use of still‐effective active ingredients for preventing the renewed entry of seeds into the soil.
Molecular detection of Rickettsia spp. in wild ungulates and their ticks in Mediterranean areas of southwestern Spain
Authors: Remesar Susana , Cano‐Terriza David , Morrondo Patrocinio , Jiménez‐Ruiz Saúl , López Ceferino M. , Jiménez‐Martín Débora , Díaz Pablo , Paniagua Jorge , García‐Bocanegra Ignacio 
Published: June 2023

AbstractWildlife is an important reservoir of zoonotic pathogens. The objective of the present study was to assess the importance of wild ungulates in the epidemiology of Rickettsia spp. Ticks and spleen samples were collected from 262 red deer (Cervus elaphus) and 83 wild boar (Sus scrofa) hunted in southwestern Spain over a 5‐year period. DNA was extracted from tick pools (n = 191) and spleens (n = 345), and two nested PCR assays targeting the rOmpA and rOmpB genes were used to detect Rickettsia DNA. Five tick species were identified (Hyalomma lusitanicum, Dermacentor marginatus, Ixodes ricinus, Rhipicephalus bursa and Haemaphysalis sulcata). Rickettsia DNA was detected in 31 (16.2%) tick pools and two red deer spleen samples (0.8%). Four validated Rickettsia species (R. slovaca, R. monacensis, R. helvetica and R. raoultii), one uncultivated species (Candidatus R. rioja) and two uncharacterized Rickettsia spp. were detected in ticks. R. helvetica and R. slovaca were also detected in spleen samples from red deer. The overall prevalence in ungulate spleen samples was lower than in tick pools suggesting that these ungulates do not play a major role in the transmission of Rickettsia spp. However, their importance as spreaders of positive ticks cannot be ruled out. The results present a challenge for the veterinary and public health communities since most of the Rickettsia spp. detected are pathogenic. Furthermore, the new Rickettsia species could be potential pathogens. For these reasons, identifying Rickettsia species present in ticks and wildlife is of particular interest to clarify their sylvatic cycle and establish appropriate control measures.
Functional Modeling Supports System Representation
Authors: Murphy Alexander R. , Banks Henry D. , Nagel Robert L. , Linsey Julie S. 
Published: June 2023

Abstract
Understanding how engineers formulate and evolve mental models holds the potential to inform the development of materials that benefit systems thinking. A first step toward realizing this benefit is measuring and assessing change in mental models following educational interventions. In this work, engineering students’ mental models are elicited from common household products before and after learning functional modeling and are compared to the mental models of students who do not learn functional modeling. Results show statistically significant improvements in mental model representations on two of the three given systems after the functional modeling intervention, whereas no significant differences were found for students who did not learn function. Furthermore, results show statistical improvements in the identification of system components common to three systems and higher mental model scores for participants with prior experience disassembling the product. Taken together, these results suggest that functional modeling likely supports the ability to communicate knowledge, retrieve knowledge, and/or interpret existing mental models of engineered systems providing a foundation for systems understanding and communication. As we improve our understanding of how students form, change, and communicate their mental models of engineered systems, educators can shape curricula to facilitate the skills necessary for the comprehensive systems understanding that is important for professional engineers and designers.
Surrogate-Based Time-Dependent Reliability Analysis for a Digital Twin
Authors: Hu Weifei , Yan Jiquan , Zhao Feng , Jiang Chen , Liu Hongwei , Cho Hyunkyoo , Lee Ikjin 
Published: June 2023

Abstract
A mature digital twin (DT) is supposed to enable engineers to accurately evaluate the real-time reliability of a complex engineering system. However, in practical engineering problems, reliability analysis (RA) often involves nonlinear, implicit, and computationally expensive relationships between the performance and uncertain parameters, which makes it very challenging to conduct time-dependent reliability analysis (TRA) instantly and accurately for a DT. This article proposes a new surrogate-based time-dependent reliability analysis (STRA) method for a DT, specifically making the following three contributions: (i) the number of discrete time nodes used to convert the stochastic processes into a series of random variables in the expansion optimal linear estimation process is dynamically selected, leading to a good tradeoff between the accurate representation of stochastic processes and fast reliability evaluation; (ii) based on Voronoi partition sampling and a modified leave-one-out cross-validation procedure, multiple sensitive subdomains in each iteration are selected simultaneously to guide adaptive sampling at the insufficiently fitted vicinity of the limit state function, which helps accurately calculate the probability of failure and reduce the number of design-of-experiment (DoE) samples; and (iii) an improved weighted expected feasibility function is proposed considering the importance of each sample and the sensitivity of the subdomain to which it belongs, which further improves the sampling efficiency. The proposed STRA method is applied to the TRA of a numerical model, a corroded beam structure, and a cutterhead of a tunnel boring machine to demonstrate its effectiveness for realistic DT applications.
Middle Miocene fire activity and C4 vegetation expansion in the Barstow Formation, California, USA
Authors: Loughney Katharine M. , Harkness Anna , Badgley Catherine 
Published: June 2023

Abstract
C4 grassland ecosystems expanded across North America between ca. 8 and 3 Ma. Studies of ungulate enamel and environmental indicators from the middle Miocene Barstow Formation of southern California (USA) have demonstrated the presence of C4 vegetation prior to the late Miocene expansion of C4 grasslands. Fire promotes the growth of modern C4 grasslands and may have contributed to the Miocene expansion of C4 vegetation. We analyzed the concentration and accumulation rate (CHAR) of microscopic charred particles from sediment samples spanning the Barstow Formation in order to investigate the relationship between fire activity, canopy cover, and the presence of C4 vegetation. Concentration and CHAR were low throughout the formation then increased dramatically at 13.5 Ma. Enriched values of δ13C from soil organic matter and phytolith counts indicate the presence of C4 grasses and seasonally dry, open-canopy habitats at this time. The spike in concentration coincides with climatic cooling and drying in southern California after the Miocene Climatic Optimum. Increased fire activity may have contributed to habitat opening from forest to woodland and promoted the spread of C4 plants. This is the first charcoal record of fire activity from the middle Miocene of southwestern North America.
Late Quaternary paleoceanography of Vestnesa Ridge, Fram Strait: Ostracode species as a potential indicator of cold seep activity
Authors: Chu Rachel Wai Ching , Yasuhara Moriaki , Riise Karoline Myrvang , Asahi Hirofumi , Huang Huai-Hsuan May , Cotton Laura J. , Hong Yuanyuan , Rasmussen Tine L. 
Published: June 2023

Abstract
Past intensity of methane release from deep-ocean methane hydrates continues to be challenging to reconstruct reliably. Here, we used fossil ostracode fauna paired with foraminiferal δ13C values in a marine sediment core from Vestnesa Ridge, western Svalbard margin, to reconstruct methane seepage activity during the late Quaternary and to examine faunal response to deglacial climatic changes. Benthic foraminiferal δ13C values indicate methane seepage activity was relatively strong during marine isotope stage 2, corresponding to a high percentage of the ostracode Rosaliella svalbardensis in the assemblage. In contrast, this species was absent under conditions of no or very strong seepage of methane. Faunal changes in other taxa were more related to global climate changes regardless of the seepage activity. This result indicates that Rosaliella svalbardensis is a potential new useful proxy for past methane release.
On aether terms in a space-time with a compact extra dimension
Authors: Furtado J. , Mariz T. , Nascimento J. R. , Petrov A. Yu. 
Published: June 2023

AbstractIn this paper, we explicitly calculate the aether-like corrections for the electromagnetic field in the case when the space-time involves an extra compact spatial dimension besides of usual four dimensions. Our methodology is based on an explicit summation over the Kaluza–Klein tower of fields which turns out to be no more difficult than the finite-temperature calculations. We found some new terms which can be treated as certain five-dimensional generalizations of the aether-like terms $$\kappa ^{mnpq}F_{mn}F_{pq}$$

κ

mnpq

F

mn

F

pq

and $$\bar{\psi }c^{mn}\gamma _m\partial _n \psi $$

ψ

¯

c

mn

γ
m

∂
n

ψ

which in four dimensions are treated as important ingredients of the Lorentz-breaking extension of the standard model. We have shown that these new terms become to dominate in the limit where the extra dimension is very small, allowing us to suggest that there will be essential modifications of quantum corrections if our space indeed has a small extra spatial dimension. Moreover, we have shown that in the CPT-even case we have extra new particles as a consequence of the extra dimension.
Probing time orientability of spacetime
Authors: Lemos N. A. , Müller D. , Rebouças M. J. 
Published: June 2023

AbstractIn general relativity, cosmology and quantum field theory, spacetime is assumed to be an orientable manifold endowed with a Lorentz metric that makes it spatially and temporally orientable. The question as to whether the laws of physics require these orientability assumptions is ultimately of observational or experimental nature, or the answer might come from a fundamental theory of physics. The possibility that spacetime is time non-orientable lacks investigation, and so should not be dismissed straightaway. In this paper, we argue that it is possible to locally access a putative time non-orientability of Minkowski empty spacetime by physical effects involving quantum vacuum electromagnetic fluctuations. We set ourselves to study the influence of time non-orientability on the stochastic motions of a charged particle subject to these electromagnetic fluctuations in Minkowski spacetime equipped with a time non-orientable topology and with its time orientable counterpart. To this end, we introduce and derive analytic expressions for a statistical time orientability indicator. Then we show that it is possible to pinpoint the time non-orientable topology through an inversion pattern displayed by the corresponding orientability indicator, which is absent when the underlying manifold is time orientable.
Extent and significance of the Upper Ordovician felsic volcanism in the Pyrenees and Mouthoumet Massifs, SW Europe
Authors: Casas Josep Maria , Sánchez-García Teresa , Díez-Montes Alejandro , Clariana Pilar , Margalef Aina , Valverde-Vaquero Pablo , Beranoaguirre Aratz , Román-Alpiste Manuel J. , Pujol-Solà Núria , Álvaro J. Javier 
Published: June 2023

Abstract
New geochronological (U–Pb isotope dilution thermal ionization mass spectrometry), geochemical and isotopic data from Upper Ordovician felsic volcanic rocks recorded in the Pyrenees and Mouthoumet massifs, SW Europe, suggest that this volcanic activity is more widely represented than previously accepted, and allows a better refinement of the age span involved in the Sardic Unconformity. This Sandbian volcanism represents the final pulse of the Sardic tectonothermal event, starting with the Floian–Darriwilian emplacement of voluminous plutonic rocks and the contemporaneous erosion of the uplifted pre–Upper Ordovician basement, and followed by a tholeiitic volcanism contemporaneous with extensional features and the opening of (half-)grabens finally sealed by Hirnantian glaciomarine deposits. The Sardic-related lithospheric extension may be linked to thermal doming originated by a superplume activity that caused, in turn, an extensive crustal melting responsible for the onset of the felsic (calc-alkaline-dominated), Floian–Darriwilian intrusive and Sandbian extrusive magmatism along the northern margin of Gondwana.
Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC) Unveils New Actionable Genomic Aberrations in PACC
Authors: Florou Vaia , Elliott Andrew , Bailey Matthew H. , Stone David , Affolter Kajsa , Soares Heloisa P. , Nevala-Plagemann Chris , Scaife Courtney , Walker Phillip , Korn W. Michael , Lou Emil , Shroff Rachna T. , Hosein Peter J. , Garrido-Laguna Ignacio 
Published: June 2023

Abstract

Purpose:
Pure pancreatic acinar cell carcinomas (PACC) are rare malignancies with no established treatment. PACC demonstrates significant genetic intertumoral heterogeneity with multiple pathways involved, suggesting using targeted cancer therapeutics to treat this disease. We aggregated one of the largest datasets of pure PACC to examine the genomic variability and explore patient-specific therapeutic targets.

Experimental Design:
PACC specimens (n = 51) underwent next-generation sequencing of DNA (n = 29) or whole exome (n = 22) and RNA (whole transcriptome, n = 29) at a commercial laboratory. We performed comparative analyses of a genomic cohort of pancreatic ductal adenocarcinomas (PDAC; n = 4,205). In parallel, we conducted a retrospective review of patients with PACC treated at Huntsman Cancer Institute (HCI).

Results:
The real-world dataset included samples from 51 patients with PACC. We found key molecular differences between pure PACC and PDAC, highlighting the unique characteristics of pure PACC. Major differences in PACC include lower MAPK signaling and less stromal cell abundance compared with PDAC. Pure PACC showed genomic loss-of-heterozygosity to largely coincide with mutations in BRCA1, BRCA2, and PALB2. Of the 7 patients treated at HCI, one had a tumor that harbored a BRAF-V600E mutation. Leveraging precision oncology, this patient is being treated with encorafenib plus binimetinib, achieving an exceptionally durable and ongoing complete response of more than 3 years.

Conclusions:
There are major differences between PACC and PDAC, including downregulation of the MAPK signaling pathway, and less stromal cell abundance. In addition, genomic characterization of pure PACC revealed frequent targetable alterations, which can guide patient treatment.
Preclinical Characterization and Phase I Trial Results of INBRX-109, A Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma
Authors: Subbiah Vivek , Chawla Sant P. , Conley Anthony P. , Wilky Breelyn A. , Tolcher Anthony , Lakhani Nehal J. , Berz David , Andrianov Vasily , Crago William , Holcomb Monica , Hussain Abrahim , Veldstra Carson , Kalabus James , O’Neill Brianne , Senne Lane , Rowell Emily , Heidt Analeah B. , Willis Katelyn M. , Eckelman Brendan P. 
Published: June 2023

Abstract

Purpose:
Patients with unresectable/metastatic chondrosarcoma have poor prognoses; conventional chondrosarcoma is associated with a median progression-free survival (PFS) of &lt;4 months after first-line chemotherapy. No standard targeted therapies are available. We present the preclinical characterization of INBRX-109, a third-generation death receptor 5 (DR5) agonist, and clinical findings from a phase I trial of INBRX-109 in unresectable/metastatic chondrosarcoma (NCT03715933).

Patients and Methods:
INBRX-109 was first characterized preclinically as a DR5 agonist, with binding specificity and hepatotoxicity evaluated in vitro and antitumor activity evaluated both in vitro and in vivo. INBRX-109 (3 mg/kg every 3 weeks) was then evaluated in a phase I study of solid tumors, which included a cohort with any subtype of chondrosarcoma and a cohort with IDH1/IDH2-mutant conventional chondrosarcoma. The primary endpoint was safety. Efficacy was an exploratory endpoint, with measures including objective response, disease control rate, and PFS.

Results:
In preclinical studies, INBRX-109 led to antitumor activity in vitro and in patient-derived xenograft models, with minimal hepatotoxicity. In the phase I study, INBRX-109 was well tolerated and demonstrated antitumor activity in unresectable/metastatic chondrosarcoma. INBRX-109 led to a disease control rate of 87.1% [27/31; durable clinical benefit, 40.7% (11/27)], including two partial responses, and median PFS of 7.6 months. Most treatment-related adverse events, including liver-related events, were low grade (grade ≥3 events in chondrosarcoma cohorts, 5.7%).

Conclusions:
INBRX-109 demonstrated encouraging antitumor activity with a favorable safety profile in patients with unresectable/metastatic chondrosarcoma. A randomized, placebo-controlled, phase II trial (ChonDRAgon, NCT04950075) will further evaluate INBRX-109 in conventional chondrosarcoma.
Abstract A072: Unique mouse models of high-risk prostate cancer adequate for targeted interception
Authors: Levenson Anait S. 
Published: June 2023

Abstract
Metastasis-associate protein 1 (MTA1), a master transcriptional co-regulator and chromatin modifier, is strongly associated with clinically aggressive prostate cancer. The loss of MTA1 reduces the aggressiveness and metastatic potential of prostate cancer cells. Preclinical studies with subcutaneous and orthotopic MTA1 knockdown xenograft models have shown the tumor promoting role of MTA1 and associated survival pathways in prostate cancer. However, the exact role of MTA1 in the pathobiology of prostate cancer is unknown. We first generated a conditional mouse with human MTA1 transgene knocked into the mouse Rosa26 locus (R26MTA1; Cre+ ). By crossing a R26MTA1 mouse with a Pten “floxed” mouse, we have created unique high-risk high-grade PIN-prone R26MTA1; Ptenf/+; Cre+ mice and a high-risk R26MTA1; Ptenf/f; Cre+ cohort of mice with characteristics of a castrate-resistant neuroendocrine subtype suitable for early chemoprevention/interception and novel effective therapies, respectively. I will discuss the potent MTA1-targeted anticancer effects of natural stilbenes (resveratrol, pterostilbene, and Gnetin C) observed in the preclinical R26MTA1; Ptenf/+; Cre+ model mimicking high-risk premalignant tumors with overexpressed MTA1. Further, evidence will be provided on the role of MTA1 in castrate resistance and on the neuroendocrine features defining the potential of the R26MTA1; Ptenf/f; Cre+ model in discovering novel chemoimmunotherapies. Our studies demonstrate progress towards successful targeted interception strategies for prostate cancer with an implication for precision medicine. Supported by the NCI/NIH R15CA216070 Award.
Citation Format: Anait S. Levenson. Unique mouse models of high-risk prostate cancer adequate for targeted interception [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A072.
Abstract B006: Identifying the molecular signature of bi-potent prostate epithelial cells through scRNA-seq
Authors: Khawaja Hunain , Miranti Cynthia 
Published: June 2023

Abstract
Introduction: Recent studies have shown that cells undergoing oncogenic processes usurp normal developmental pathways to escape regulators of unsolicited growth. Basal to luminal differentiation in the prostate serves as another cellular process that can go awry, the dysregulation of which can enable oncogenesis in the prostate. Studies have found bi-potent cells in prostate epithelium and speculate those to be cells of origin in prostate cancer. Methods and Results: Through single-cell RNA sequencing we investigated basal to luminal differentiation of normal human prostate epithelial cells across timepoints Days 0, 4, 8, 12, 16, and 20 by stimulating with FGF-7 (20ng/mL) and R1881 (10nM) and explored the data to identify unique populations present in the differentiation process. Our results show spatial separation at various timepoints with distinct transcriptomics profile at Day 0, Day 16, and Day 20. As expected, populations present at Day 0 are also present across all timepoint, though enrichment of various distinct populations emerged throughout the differentiation process. Using trajectory analysis (Monocle3) and the Cell Surface Protein Atlas, we profiled surface proteins for each cluster at Day 0 and identified a set of unique surface markers (SLC3A, LYPD3, TACSTD2, DSC2) from undifferentiated basal cells that express both basal (TP63+, K14+) and luminal markers (K8+, K18+), potentially serving as a bi-potent prostate epithelial cells. Conclusion: Our data have identified unique populations present in our prostate differentiation model expressing both luminal and basal signatures which can be isolated using identified surface markers to investigate the role of bi-potent cells in prostate differentiation and oncogenesis.
Citation Format: Hunain Khawaja, Cynthia Miranti. Identifying the molecular signature of bi-potent prostate epithelial cells through scRNA-seq [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B006.