Initial Studies Research Articles

Harnessing Dialogue as a Social Technology for Systems Change in Development Institutions

Across global development discourse and practice can be seen a growing a recognition that deep transformation of social, economic and ecological systems cannot be achieved through new policies, data or technology alone. The capabilities needed for 21st century leadership and governance relate to the ability to create new conditions, relationships and pathways for social and moral imagination to flourish. Drawing from an in-depth case study of several interlinked initiatives of the United Nations Development Programme to build such capabilities among development practitioners, this conceptual paper elaborates the continued need for, and pathways and barriers to institutionalizing, more dialogic- and process-based approaches to systems transformation in mainstream development processes. It posits that a reconceptualization of dialogue within multilateral and government-led systems transformation frameworks in particular can help valorize the seeds of development impact that reside in the sites where culture, relationships and shared consciousness are built. Further learning is needed, however, to understand and address barriers that lie in normative perceptions, organizational culture, and accountability frameworks of these institutions, which impede the rhetorical interest in inclusive and transformative dialogue from translating to more process- and relationship-centric ways of working. As a contribution to this learning, the paper considers how conceptual frames that give weight and visibility to the role of social containers in systems change processes, with dialogue as a core technology for container-building, canhelp advance more transformative development paradigms and praxis that tend to the reciprocal relationships between inner change and societal change.

Research on the Interaction Mechanism of Multi-Fracture Propagation in Hydraulic Fracturing

During the hydraulic-fracturing process, stress interference occurs among multiple wells and fractures, potentially affecting the trajectory of hydraulic fracture propagation. Previous studies have largely overlooked the influence of proppant support stresses on the trajectories of fracture propagation. This paper establishes a mathematical model, grounded in the boundary element method, designed to compute the propagation of multiple fractures, considering both proppant support on the fracture surface and dynamic perturbations within the local stress field. The findings of this research reveal that the stress field induced by hydraulic fracturing exhibits dynamic evolution characteristics, necessitating a comprehensive study of the fracture initiation and extension across the entire fracturing time domain. The effect of the residual fracture width under proppant action on the in situ stress field cannot be ignored. During simultaneous fracturing, hydraulic fractures are inclined to propagate in the direction of the maximum horizontal principal stress, particularly as the in situ differential stress escalates. Staggered fracturing between wells has been proven to be more effective than head-to-head fracturing. Simply increasing the well spacing cannot solve the problem of inter-well fracture interference. In zipper fracturing, adjusting the fracturing sequence can inhibit the fracture intersections between wells, thereby controlling the trajectory of fracture propagation. The aforementioned research has considerable significance in guiding the control of fracture morphology during hydraulic-fracturing processes.

Study on Microscopic Characteristics and Rock Mechanical Properties of Tight Sandstone after Acidification–Supercritical CO2 Composite Action: Case Study from Xujiahe Formation, China

Acidified CO2 fracturing is a viable method for increasing production in deep, tight sandstone reservoirs. However, the potential mechanism of changes in pore structure and mechanical properties of sandstone under acidified CO2 supercritical composite is not clear. Understanding this mechanism is important for the study of crack initiation and extension in tight sandstone reservoirs. This study utilizes sandstone samples from the Xujiahe Formation reservoir in Rongchang District as experimental specimens. The primary focus is to analyze the changes in pore structure and mechanical properties of these samples after acidification–supercritical CO2 composite action. Nuclear magnetic resonance (NMR) and uniaxial compression tests are employed as the main investigative techniques. The results show that there was a physicochemical synergy between the acidification–supercritical CO2 composite effect; the crack initial stress, damage stress, and peak stress of the sandstone after 16 MPa supercritical CO2 acidification treatment were reduced by 20%, 49.5%, and 49.8%, respectively; the crack volumetric strain accelerated and the sandstone evolved from brittle to ductile damage; and the larger pore space and microcracks of the sandstone increased significantly after the treatment, which can be attributed to the gradual dissolution of intergranular cement leading to the formation of new pores connected to the existing pore network. The change mechanism of sandstone after acidification–supercritical CO2 compound treatment is also proposed.

Thermal creep properties of virgin and irradiated cladding tubes made of Ti-stabilised DIN 1.4970 (15-15Ti) austenitic stainless steel

ABSTRACT This paper presents assessments performed on a large database of virgin material and irradiated material thermal creep data from uniaxial and pressurised DIN 1.4970 Ti-stabilised austenitic stainless steel i.e. EN X10NiCrMoTiB15–15 or ‘15-15Ti’ cladding tubes. The data base incorporates multi-heat data from uniaxial and bi-axial (internal pressure) creep tests conducted during the fast reactor R&D program of the DeBeNe (Deutschland-Belgium-Netherlands) consortium between the 1960s to the late 1980s together with more recent data, for example, from the European projects MATTER and PATRICIA and the EERA JPNM pilot project TASTE. The data comprises of a virgin material data base and a data base with irradiated creep data. The virgin material data comprises of time-to-rupture and time-to-0.2% creep strain in a temperature range of 600–800°C and covers a large range of stresses. The irradiated data base has less data and does not cover all material heats tested for the virgin material properties. The irradiation conditions are also different depending on the test reactor specifics and the irradiation campaign targets. The attained ‘irradiation damage’ in displacements per atom (DPA) for the irradiated materials range from 0.1 up to 38.1. Un-irradiated ‘reference material’ models for tensile strength and creep strength are constructed from the current-state of the art literature data and more recent results from the Sandvik 24% cold worked 1515–Ti cladding tube currently used as the main material batch studied at SCK CEN. The tensile strength model is used throughout the paper for normalizing creep strengths by the tensile properties, needed when applying the Wilshire (WE) creep model. Time factors (TF), stress factors (SF) and temperature ratio factors (TRF) are calculated for different material states for describing the impact of heat treatments, (virgin and irradiated) and irradiation conditions. This initial study targets to give estimates for the thermal creep properties of cladding tubes with a cold work range of 16–24% in a non-annealed state, as it is the preferred option for future designs according to the state-of-the art knowledge base. However, the main bulk of the available data on irradiated material is on claddings with a cold work range of 0-16% with and without annealing and at various levels of irradiation damage, thus leading to the need for estimation by interpolation and extrapolation assuming that irradiation damage levels and trends, e.g. time reduction factors found on a lower cold worked material can also be applied on materials with higher cold work levels. The results of the assessments clearly show relative strength differences between chosen material heats and heat treatments and has enabled constructing simple multilinear models for estimating the life of irradiated material. The models show that low creep test temperatures (and irradiation temperatures), low stress levels, low levels of cold work and high irradiation doses are increasing the detrimental difference between the specific material condition and the reference material. Also, it was found that the general level of life reduction (time factor TF and stress factor SF) for irradiation damaged material failure, in relation to the reference material failure, roughly coincides the corresponding values of time to 0.2% creep strain for virgin material. The estimated ‘failure creep temperature limits’ for 30 000 hours of service are studied and compared for both virgin and irradiated materials at a reference stress level of 1/3 of the tensile strength (at temperature).

A Study of Sustainable Initiatives taken by H&M with respect to Pune City

This study aims to analyze the sustainable initiatives undertaken by H&M within its outlets located in Pune City, India. As sustainability becomes an increasingly critical aspect of corporate operations, the fashion industry has been under scrutiny for its environmental and social impact. H&M, as a global fashion retailer, has been proactive in implementing various sustainability measures to address these concerns.

François Gros: from antibiotics to messenger RNA.

François Gros was a prominent French Molecular Biologist who made a major contribution to the discovery of messenger RNA in 1961. He pursued outstanding research on bacterial mRNA and its translation into proteins followed by pioneering work on muscle differentiation. I was lucky to be among his graduate students and owe much of my success in science to him. In this short text I will describe how the initial post-war studies of François guided him to discover the existence of short-lived RNA in bacteria, the messenger RNA containing the information for protein synthesis. I will also recount the influence he had on his students and their carrier in science.

Unraveling the molecular mechanisms governing axillary meristem initiation in plants.

Axillary meristems (AMs) located in the leaf axils determine the number of shoots or tillers eventually formed, thus contributing significantly to the plant architecture and crop yields. The study of AM initiation is unavoidable and beneficial for crop productivity. Shoot branching is an undoubted determinant of plant architecture and thus greatly impacts crop yield due to the panicle-bearing traits of tillers. The emergence of the AM is essential for the incipient bud formation, and then the bud is dormant or outgrowth immediately to form a branch or tiller. While numerous reviews have focused on plant branching and tillering development networks, fewer specifically address AM initiation and its regulatory mechanisms. This review synthesizes the significant advancements in the genetic and hormonal factors governing AM initiation, with a primary focus on studies conducted in Arabidopsis (Arabidopsis thaliana L.) and rice (Oryza sativa L.). In particular, by elaborating on critical genes like LATERAL SUPPRESSOR (LAS), which specifically regulates AM initiation and the networks in which they are involved, we attempt to unify the cascades through which they are positioned. We concentrate on clarifying the precise mutual regulation between shoot apical meristem (SAM) and AM-related factors. Additionally, we examine challenges in elucidating AM formation mechanisms alongside opportunities provided by emerging omics approaches to identify AM-specific genes. By expanding our comprehension of the genetic and hormonal regulation of AM development, we can develop strategies to optimize crop production and address global food challenges effectively.

Abstract 3382: Unveiling gastric premalignancy: A comprehensive study of tumor initiation and evolution using organoid models

Abstract Tumor initiation and evolution is still a poorly characterized process. Organoid models recapitulate three-dimensional tissue structure, differentiation, and disease pathogenesis. These models can help to better characterize pre-neoplastic processes and tumor evolution, with implications for early cancer detection and personalized therapeutic strategies for patients with gastric cancer (GC). In our research, we performed whole exome sequencing (WES) on 24 GC patient tumors, uncovering distinct mutation frequencies in well-known tumor suppressor genes -APC, TP53, and ARID1A (18.75%, 37.5%, 43.75%, respectively) -compared to The Cancer Genome Atlas (TCGA) PanCancer Altas Cohort (n=440) (13.48%, 50.56%, 22.47% respectively). To gain a deeper understanding of how these mutated genes promote gastric premalignancy, we generated multiple isogenic gastric organoid lines with mutant APC (AT-dmut) or ARID1A (ArT-dmut) on a TP53 mutant background as well as TP53 mutant-only lines (T-mut) using our established CRISPR/Cas9 genome-editing platform and two HLA patient-derived normal gastric organoid lines (HL-PDOs). After confirmation of functional gene knockouts, we focused on elucidating carcinogenic changes via a two-pronged approach: (1) a comparative analysis of growth and morphology between these mutant organoid models and the parental normal gastric organoids and (2) an in-depth examination of mutational and transcriptional changes in our edited AT-mut, ArT-mut and T-mut organoid models. We cultured each edited organoid line for up to 350 days and collected histological and molecular data at multiple time points. Preliminary analysis shows an increased growth rate of all edited cell lines compared to parental normal lines. The ArT-mut and AT-mut cell lines exhibit distinct morphological and 3D structural alterations, while T-mut cell lines do not. We expect to find additional mutation gains in these cells’ lines compared to the parental normal gastric organoids that promote gastric phenotype with the greatest gain of alternations at the 350-day timepoint. These additional mutations and transcriptional changes will help us gain insights into the pathways altered in gastric cancer initiation and early progression that may be specific to HLAs. Our overall goal is to enhance our understanding of the molecular mechanisms underlying gastric premalignancy among HLAs, ultimately contributing to advancements in early detection and tailored therapeutic interventions for HLA patients with GC and advancing cancer health equity. Citation Format: Alexa Morales Arana, Nicole B. Halmai, Hongyong Zhang, Paul Lott, Ana Estrada, University of California Minority Patient-DerivedXenograft Development and Trial (UCaMP) Center, Luis Carvajal-Carmona. Unveiling gastric premalignancy: A comprehensive study of tumor initiation and evolution using organoid models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3382.

Aufbau Suppressed Coupled Cluster Theory for Electronically Excited States.

We introduce an approach to improve single-reference coupled cluster theory in settings where the Aufbau determinant is absent from or plays only a small role in the true wave function. Using a de-excitation operator that can be efficiently hidden within a similarity transform, we create a coupled cluster wave function in which de-excitations work to suppress the Aufbau determinant and produce wave functions dominated by other determinants. Thanks to an invertible and fully exponential form, the approach is systematically improvable, size consistent, size extensive, and, interestingly, size intensive in a granular way that should make the adoption of some ground state techniques, such as local correlation, relatively straightforward. In this initial study, we apply the general formalism to create a state-specific method for orbital-relaxed, singly excited states. We find that this approach matches the accuracy of similar-cost equation-of-motion methods in valence excitations while offering improved accuracy for charge transfer states. We also find the approach to be more accurate than excited-state-specific perturbation theory in both types of states.

A Comparative Analysis of Student Perceptions of Recommendations for Engagement in Design Processes

Abstract Engineering designers are tasked with complex problems necessitating the use and development of various supports for navigating complexity. Prescriptive design process models are one such tool. However, little research has explored how engineering designers perceive these models' recommendations for engagement in design work. In this exploratory study, we analyzed data from individual semi-structured interviews with 18 mechanical engineering students to identify participant perceptions of design process models. As many design process model visualizations lack explicit attention to some social and contextual dimensions, we sought to compare perceptions among two models drawn from engineering texts and one model that was developed with the intent to emphasize social and contextual dimensions. We identified perceptions of the recommendations from the design process models related to starting and moving through a design process, gathering information, prototyping, evaluating or testing, and what they should consider. Participant perceptions across the three process models suggest different design process models make perceptions of certain recommendations more salient than others. However, participant perceptions also varied for the same process model. We suggest several implications for design education and training based on participant perceptions of the process models, particularly the importance of leveraging multiple design process models. The comprehensive descriptions of participant perceptions provide a foundation for further investigations bridging designers' perceptions to intent, behavior, and, ultimately, design outcomes.

Wage Dispersion and Team Performance: A Review of 25 Years of Research on Professional Sports

Since initial studies in the late 1990s, researchers have examined the relationship between wage dispersion and team performance in professional sports. While no definitive consensus has emerged across the sports studied, it is still useful to consider where this literature stands after 25 years of research given its clear importance not just for professional sports, but also for economic decision-making in general. This review of the relevant literature organizes discussion of: (1) the theoretical foundations underlying the wage dispersion–team performance empirical studies, (2) the favorable conditions found in professional sports that provide a unique “laboratory” for researching this topic, (3) conclusions from the empirical literature about the relationship in focus and the different factors in those studies which likely contribute to the varied conclusions, and (4) promising avenues for furthering this line of research in the near future.

Study of Fatigue Crack Initiation and the Propagation Mechanism Induced by Pores in a Powder Metallurgy Nickel-Based FGH96 Superalloy.

Thermally induced pores (TIPs) are generally the source of fatigue crack initiation in the powder metallurgy (PM) Ni-based FGH96 superalloy. The effect of TIPs on fatigue crack initiation on the surface of the FGH96 superalloy was detected using scanning electron microscopy (SEM). The cause of fatigue crack deflection was studied using electron backscatter diffraction (EBSD) analysis. The results indicated that there are two states of TIPs including isolated TIPs and clustered TIPs located at the grain boundary. The investigation of crack initiation and propagation around TIPs was conducted in detail through the comprehensive integration of experimental findings and computational results. For cracks initiated by isolated TIPs, the maximum equivalent size and the ratio of the vertical-parallel axis to the loading direction of the TIPs reveal a linear relationship, and both of them determine crack initiation. Regarding clustered TIPs, the constituent pores of the clustered TIPs will compete to initiate cracks based on the experimental results, and the largest pore will be more likely to initiate cracking. Moreover, the results showed that fatigue crack propagation can be hindered by hard-orientation grains and twins with a low Schmid factor (SF). Large-angle crack deflection due to twins with a low SF can significantly increase crack length and resistance to crack propagation.

Associations of radiologic characteristics of the neonatal hypothalamus with early life adiposity gain.

The mediobasal hypothalamus (MBH) is a key brain area for regulation of energy balance. Previous neuroimaging studies suggest that T2-based signal properties indicative of cellular inflammatory response (gliosis) are present in adults and children with obesity, and predicts greater adiposity gain in children at risk of obesity. The current study aimed to extend this concept to the early life period by considering if, in full-term healthy neonates (up to n = 35), MRI evidence of MBH gliosis is associated with changes in early life (neonatal to six months) body fat percentage measured by DXA. In this initial study, neonatal T2 signal in the MBH was positively associated with six-month changes in body fat percentage. This finding supports the notion that underlying processes in the MBH may play a role in early life growth and, by extension, childhood obesity risk.

Data driven modeling of heavy-duty joint system for DEMO manipulators: An initial study from MPD joint simulation

This study investigates the subspace modeling method in developing surrogate model of a heavy-duty joint system in a muti-purpose deployer. The joint system is constructed in the Matlab SIMULINK Simscape environment, which includes the multibody dynamics with friction models, meshing loss models and viscous models. The input and output data generated in simulation are used to develop the subspace model. The result shows the subspace modeling method can accurately identify the system order and linear part of dynamics in this joint system. The nonlinearity contributed by the gear friction, meshing and viscosity can't be neglected in the surrogate model. Further model augmentation technics are needed to improve the capability of subspace modeling method applying in nonlinear system.

Factors Affecting Reproducibility of Change in Glucose During Exercise: Results From the Type 1 Diabetes and EXercise Initiative.

To evaluate factors affecting within-participant reproducibility in glycemic response to different forms of exercise. Structured exercise sessions ~30 minutes in length from the Type 1 Diabetes Exercise Initiative (T1DEXI) study were used to assess within-participant glycemic variability during and after exercise. The effect of several pre-exercise factors on the within-participant glycemic variability was evaluated. Data from 476 adults with type 1 diabetes were analyzed. A participant's change in glucose during exercise was reproducible within 15 mg/dL of the participant's other exercise sessions only 32% of the time. Participants who exercised with lower and more consistent glucose level, insulin on board (IOB), and carbohydrate intake at exercise start had less variability in glycemic change during exercise. Participants with lower mean glucose (P < .001), lower glucose coefficient of variation (CV) (P < .001), and lower % time <70 mg/dL (P = .005) on sedentary days had less variable 24-hour post-exercise mean glucose. Reproducibility of change in glucose during exercise was low in this cohort of adults with T1D, but more consistency in pre-exercise glucose levels, IOB, and carbohydrates may increase this reproducibility. Mean glucose variability in the 24 hours after exercise is influenced more by the participant's overall glycemic control than other modifiable factors.

Precise Mass Measurement of OGLE-2013-BLG-0132/MOA-2013-BLG-148: A Saturn-mass Planet Orbiting an M Dwarf

We revisit the planetary microlensing event OGLE-2013-BLG-0132/MOA-2013-BLG-148 using Keck adaptive optics imaging in 2013 with NIRC2 and in 2020, 7.4 yr after the event, with OSIRIS. The 2020 observations yield a source and lens separation of 56.91 ± 0.29 mas, which provides us with a precise measurement of the heliocentric proper motion of the event μ rel,hel = 7.695 ± 0.039 mas yr−1. We measured the magnitude of the lens in the K band as K lens = 18.69 ± 0.04. Using these constraints, we refit the microlensing light curve and undertake a full reanalysis of the event parameters including the microlensing parallax π E and the distance to the source D S . We confirm the results obtained in the initial study by Mróz et al. and improve significantly upon the accuracy of the physical parameters. The system is an M dwarf of 0.495 ± 0.054 M ⊙ orbited by a cold, Saturn-mass planet of 0.26 ± 0.028 M Jup at projected separation r ⊥ = 3.14 ± 0.28 au. This work confirms that the planetary system is at a distance of 3.48 ± 0.36 kpc, which places it in the Galactic disk and not the Galactic bulge.

A Biotinylated cpFIT-PNA Platform for the Facile Detection of Drug Resistance to Artemisinin in Plasmodium falciparum.

The evolution of drug resistance to many antimalarial drugs in the lethal strain of malaria (Plasmodium falciparum) has been a great concern over the past 50 years. Among these drugs, artemisinin has become less effective for treating malaria. Indeed, several P. falciparum variants have become resistant to this drug, as elucidated by specific mutations in the pfK13 gene. This study presents the development of a diagnostic kit for the detection of a common point mutation in the pfK13 gene of P. falciparum, namely, the C580Y point mutation. FIT-PNAs (forced-intercalation peptide nucleic acid) are DNA mimics that serve as RNA sensors that fluoresce upon hybridization to their complementary RNA. Herein, FIT-PNAs were designed to sense the C580Y single nucleotide polymorphism (SNP) and were conjugated to biotin in order to bind these molecules to streptavidin-coated plates. Initial studies with synthetic RNA were conducted to optimize the sensing system. In addition, cyclopentane-modified PNA monomers (cpPNAs) were introduced to improve FIT-PNA sensing. Lastly, total RNA was isolated from red blood cells infected with P. falciparum (WT strain - NF54-WT or mutant strain - NF54-C580Y). Streptavidin plates loaded with either FIT-PNA or cpFIT-PNA were incubated with the total RNA. A significant difference in fluorescence for mutant vs WT total RNA was found only for the cpFIT-PNA probe. In summary, this study paves the way for a simple diagnostic kit for monitoring artemisinin drug resistance that may be easily adapted to malaria endemic regions.

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging.

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.

Abstract IA017: A liquid biopsy fingerprint of disease via nanoengineering

Abstract Serum biomarkers are often insufficiently sensitive or specific to facilitate cancer screening or diagnostic testing. In many cancers, including high-grade serous carcinoma (HGSC), biomarkers fail to detect early-stage cancer detection or to substantially impact mortality rates. We developed a perception-based sensing method that captures a biomarker-agnostic ‘disease fingerprint’ of HGSC using serum. Instead of measuring individual biomarkers, the method collects large data sets of molecular binding interactions to a diverse array of moderately-selective sensors, which were used to train machine learning algorithms. In an initial study using serum from 264 patients, we built a prediction model of nanosensor responses that reliably identified HGSC substantially better than CA125. We believe that the improvement of such a method, using larger nanosensor arrays, more sophisticated AI algorithms, and larger patient cohorts, could improve the detection of HGSC and facilitate biomarker discovery efforts. Citation Format: Daniel A. Heller, Mijin Kim, Lakshmi Ramanathan, Kara Long Roche. A liquid biopsy fingerprint of disease via nanoengineering [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr IA017.

Intranasal Ion-Triggered In Situ Delivery System of Virus-like Particles: Development Using the Quality by Design Approach.

The rapid growth in the prevalence of infectious diseases requires timely action from drug developers. In recent years, the COVID-19 pandemic has demonstrated the unpreparedness of the population for such emergencies. The introduction of modern methods of Design of Experiments (DoE) is required to accelerate the process of drug development and bring a drug to market. The main objective of this study was to develop an ion-triggered in situ system for intranasal delivery of VLP using a Quality by Design approach. Based on a literature review and initial studies, the key QTPP, CQA, CPP, and CMA were identified to develop a novel delivery system for virus-like particles. As a result of the studies on the quality attributes of the developed delivery system, an ion-triggered in situ gel meeting all the specified parameters was obtained using the Quality by Design method.