Short-term Adaptation Research Articles

Supplemental Material for The Impact of Unemployment on Cognitive, Affective, and Eudaimonic Well-Being Facets: Investigating Immediate Effects and Short-Term Adaptation

Supplemental Material for The Impact of Unemployment on Cognitive, Affective, and Eudaimonic Well-Being Facets: Investigating Immediate Effects and Short-Term Adaptation

Impact of roadside burning on genetic diversity in ahigh-biomass invasive grass.

The invasive grass–fire cycle is a widely documented feedback phenomenon in which invasive grasses increase vegetation flammability and fire frequency, resulting in further invasion and compounded effects on fire regimes. Few studies have examined the role of short‐term adaptation in driving the invasive grass–fire cycle, despite invasive species often thriving after introduction to new environments. We used a replicated (nine locations), paired sampling design (burn vs unburnt sites) to test the hypothesis that roadside burning increases genetic diversity and thus adaptive potential in the invasive, high‐biomass grass Cenchrus ciliaris. Between four and five samples per site (n = 93) were genotyped using the DArTseq platform, and we filtered the data to produce panels of 15,965 neutral and 5030 non‐neutral single nucleotide polymorphism (SNP) markers. Using fastSTRUCTURE, we detected three distinct genetic clusters with extremely high F ST values among them (0.94–0.97) suggesting three different cultivars. We found high rates of asexual reproduction, possibly related to clonality or apomixis common in this species. At three locations, burnt and unburnt sites were genetically different, but genetic structure was not consistently related to fire management across the study region. Burning was associated with high genetic diversity and sexual reproduction in one genetic cluster, but with low genetic diversity and clonality in another. Individual SNPs were associated with longitude and genetic clustering, but not with recent fire management. Overall, we found limited evidence that roadside burning consistently increased genetic diversity and adaptive potential in C. ciliaris; evolutionary and breeding history more strongly shaped genetic structure. Roadside burning could therefore continue to be used for managing biomass in this species, with continued monitoring. Our study provides a framework for detecting fire‐related changes on a genetic level–a process that could be used as an early warning system to detect the invasive grass–fire cycle in future.

REMOTE EMPLOYMENT: A SHORT-TERM STRATEGY FOR ADAPTING TO THE CRISIS OR THE NEW REALITY OF HUMAN RESOURCE MANAGEMENT

The purpose of the article is to explore the use of remote employment as a short-term adaptation strategy for the enterprise in times of crisis and as a long-term strategy for human resource management in the future. The subject of the study is new strategies in human resource management, which began to be widely used during the COVID-19 pandemic. The main focus of the article is on remote employment. Its spread is studied, on the one hand, as an opportunity for companies to adapt to crisis phenomena in the short term, on the other hand, as a long-term strategy in human resource management, which will become a new reality in the management process. Methodology. This article uses a comprehensive approach using the component method and multivariate correlation to analyze the results of public opinion surveys on the introduction of remote employment as a human resource management strategy in an unstable environment and to examine the likelihood of digitalization of labor. Results. An analytical assessment of sociological research on the introduction of remote employment as a strategy for human resource management in conditions of instability was carried out and trends were identified, the main ones for different countries. The probability of digitalization of labor and the use of remote employment for workers with different educational and qualification levels and different professional groups were investigated. The effectiveness of the introduction of new flexible forms of employment and adaptation to remote employment in enterprises was analyzed. It has been proven that the effectiveness and sustainability of the positive results achieved can be maintained with the clear planning of work processes in the enterprise. The practical implications of this study are the optimization of a set of human resource management strategies and remote employment in particular, as well as a radical revision of the format of the work organization. This study was performed as part of the research work of the Department of Finance and Economics of Borys Hrinchenko Kyiv University (№ 0118U001561) on the topic: "Development of the economy of Kyiv in terms of European integration".

The heavier the arm, the higher the action: the effects of forearm-weight changes on reach-to-grasp movements.

Usually, our bodily movements are performed against gravity. Most studies using a force field have focused on adaptation processes to force applied in the horizontal plane, which is novel to us, but not to force in the gravitational direction. The present study investigated the immediate effects (aftereffects) of a force toward the gravitational direction on the kinematics of reach-to-grasp movements as well as short-term adaptation to the force, simply by adding a weight to participants' forearm. Healthy young adults performed blocks of 10 reach-to-grasp movements under three weight conditions; as the weights were changed between blocks, the participants experienced weight changes ranging from - 200 to + 200g. We obtained three main results; first, the height of movement trajectory (trajectory height) was remarkably higher immediately after the forearm weight changed to lighter than after the weight changed to heavier, suggesting that participants planed the trajectory height with the same muscle efforts as in the previous trial. Second, the trajectory height at the end of the block became higher only in 200g condition, indicating that the participants could not achieve same trajectory height as that without any weight load, at least in ten trials of adaptation period to the 200g weight load. Third, the coordination between reach and grasp components was preserved immediately after forearm-weight changes. These findings may contribute to further understand how we perform adaptive reach-to-grasp movements with frequent weight changes that are inevitable in everyday life.

Mitochondrial and metabolic remodelling in human skin fibroblasts in response to glucose availability.

Cell culture conditions highly influence cell metabolism in vitro. This is relevant for preclinical assays, for which fibroblasts are an interesting cell model, with applications in regenerative medicine, diagnostics and therapeutic development for personalized medicine, and the validation of ingredients for cosmetics. Given these cells' short lifespan in culture, we aimed to identify the best cell culture conditions and promising markers to study mitochondrial health and stress in normal human dermal fibroblasts (NHDF). We tested the effect of reducing glucose concentration in the cell medium from high glucose (HGm) to a more physiological level [low glucose medium (LGm)], or its complete removal and replacement by galactose [medium that forces oxidative phosphorylation (OXPHOSm)], always in the presence of glutamine and pyruvate. We have demonstrated that only with OXPHOSm was it possible to observe the selective inhibition of mitochondrial adenosine triphosphate (ATP) production. This reliance on mitochondrial ATP was accompanied by changes in oxygen consumption rate and extracellular acidification rate, oxidation of citric acid cycle substrates, fatty acids, lactate, and other substrates, increased mitochondrial network extension and polarization, the increased protein content of voltage-dependent anion channel (VDAC) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha and changes in several key transcripts related to energy metabolism. LGm did not promote significant metabolic changes in NHDF, although mitochondrial network extension and VDAC protein content were increased compared to HGm-cultured cells. Our results indicate that short-term adaptation to OXPHOSm is ideal for studying mitochondrial health and stress in NHDF.

Exploring smallholder farmers’ climate adaptation decision-making in mountainous areas of Central Vietnam: implications for extension services

ABSTRACT Purpose To explore smallholder farmers’ decision-making for climate adaptation in the mountainous areas of Central Vietnam, in order to target extension efforts. Design/Methodology/Approach The study focussed on Thừa Thiên-Huế province, utilising commune meetings, key informant interviews and a survey of 302 households as data collection methods. Findings Smallholder farmers in the study region are undertaking short-term, reactionary adaption. In particular, ethnic minority farmers are not following a full range of steps in their decision-making, instead moving from the identification of climate impacts to implementing (other farmers’) actions at scale. Practical implications Short term adaptation and reliance on other farmers suggests that bonding social capital in the study sites is favourable but development of bridging and linking social capital through a greater network of agricultural advisory services could improve farmers’ perceptions of climate risk and subsequent adaptation strategies. Theoretical implications The study adds to the literature on farmers’ decision-making for climate adaptation. Specifically, it provides insight regarding extension programme design, based on data of farmers’ adaptation decision-making. Originality/value Much has been written on farmers’ adaptation to climate change. This paper focuses explicitly on the steps of that decision-making for the purpose of targeting extension programmes to support sustainable development.

Адаптация сердечно- сосудистой и эндокринной систем младших школьников к когнитивной нагрузке при выполнении теста на ноутбуке

Adaptation of children’s body to cognitive activity is an important issue for developmental physiology. The purpose of this study was to assess the nature of short-term adaptation of the cardiovascular and endocrine systems of primary school children to cognitive load when performing a test on a laptop. Materials and methods. Using spectral and temporal analysis of heart rate variability, electrocardiography, bipolar rheoencephalography, tonometry, and enzyme immunoassay to determine cortisol concentrations in saliva, we examined 32 primary school children (10–11 years old) performing a cognitive task (Anfimov’s tables) on a laptop. The cardiovascular system parameters were assessed before and during the test, the saliva was collected before and after the cognitive load. Results. In primary school children, the process of short-term adaptation of the cardiovascular and autonomic nervous systems to cognitive load was going favourably, without straining the regulation mechanisms, and was accompanied by an increase in sympathetic influences and heart rate, a decrease in the RR interval, and an increase in the tone of medium and small vessels in the occipital regions of the brain without changes in the indicators characterizing blood flow intensity. Two types of reaction of the endocrine system to cognitive load were revealed: 1) an increase in cortisol concentration in the saliva, observed in 40 % of children; 2) a decrease in the level of cortisol, characteristic of the majority of the examined schoolchildren. The obtained results showed that short-term adaptation of heart rate and haemodynamic parameters to cognitive load in primary school children is a problem-free process. A distinctive feature of children of this age is the manifestation of a proactive response of the endocrine system to the effects of environmental factors, which manifested itself in an increase in the level of the stress hormone cortisol before cognitive load.

Dietary and agricultural adaptations to drought among smallholder farmers in South Africa: A qualitative study

Building resilience to environmental change is an integral part of long-term climate adaptation planning and local policy. There is an increased understanding of the impact of climate change on global crop production however, little focus has been given to local adaptation pathways and rural smallholder community responses, especially regarding food security. It is becoming increasingly evident that local level decision-making plays a vital role in reducing vulnerability to environmental change. This research aimed to qualitatively investigate coping and adaptive strategies adopted by smallholder farming households to respond to the impacts of drought in rural KwaZulu-Natal, South Africa. Focus group discussions (n = 7) consisting of 5–9 participants and individual interviews (n = 9) using pre-tested topic guides, involving a total of 57 adults were conducted in rural areas of drought-affected districts: Msinga, Richmond and Umbumbulu of KwaZulu-Natal, in July 2018. The data were analysed using thematic analysis in NVivo 12. Thematic analysis identified three principal themes: 1. Perceived effects of droughts on the local food system and diets; 2. Current coping strategies; and 3. Enablers for successful adaptation. All sites reported a change in food consumption habits, with the majority perceiving drought to be the main driver behind a shift from vegetable-based to starch-based diets and decreased animal source food consumption. Only short-term coping strategies were implemented across the study sites. However, knowledge of long-term adaptation strategies existed but was unattainable to most respondents. Recommendations of perceived context-specific long-term adaptation strategies that could be used at a local scale were communicated by the respondents. However, they would need external help to actualize them. A need exists to support smallholder communities’ short-term response methods to drought to achieve more holistic resilience and successful adaptation. Short-term adaptation strategies, if implemented alone, often have significant trade-offs with longer-term adaptation and building resilience. This study highlights the need for targeted, contextualised policy solutions to improve smallholder productivity during drought through a strategic combination of both short- and longer-term adaptation measures, i.e. short-term adaptation should be guided by a long-term adaptation strategy. Proper planning, including the use of climate scenarios combined with information on nutritional status, is needed to develop context-specific and transformative adaptation strategies. These strategies should aim to strengthen resilience at a local level and should be included as policy recommendations.

Shaping Individualized Impedance Landscapes for Gait Training via Reinforcement Learning

Assist-as-needed (AAN) control aims at promoting therapeutic outcomes in robot-assisted rehabilitation by encouraging patients' active participation. Impedance control is used by most AAN controllers to create a compliant force field around a target motion to ensure tracking accuracy while allowing moderate kinematic errors. However, since the parameters governing the shape of the force field are often tuned manually or adapted online based on simplistic assumptions about subjects' learning abilities, the effectiveness of conventional AAN controllers may be limited. In this work, we propose a novel adaptive AAN controller that is capable of autonomously reshaping the force field in a phase-dependent manner according to each individual's motor abilities and task requirements. The proposed controller consists of a modified Policy Improvement with Path Integral algorithm, a model-free, sampling-based reinforcement learning method that learns a subject-specific impedance landscape in real-time, and a hierarchical policy parameter evaluation structure that embeds the AAN paradigm by specifying performance-driven learning goals. The adaptability of the proposed control strategy to subjects' motor responses and its ability to promote short-term motor adaptations are experimentally validated through treadmill training sessions with able-bodied subjects who learned altered gait patterns with the assistance of a powered ankle-foot orthosis.

Beyond motion extrapolation: vestibular contribution to head-rotation-induced flash-lag effects.

The perceived position of a flash aligned with a moving object usually lags behind that object. This illusion is well known as the flash-lag effect. Interestingly, head rotation alone can also induce a flash-lag effect. To date, the underlying mechanism for the head-rotation-induced flash-lag effect remains unclear. Using a virtual reality approach, we examined the contribution of vestibular signal processing in producing the effect. We found that vestibular, rather than kinesthetic, signal processing is critical for this type of flash-lag effect to occur. When head rotation induced a stationary reference stimulus in space to move on the retina, we observed a flash-lead effect relative to the reference (or a flash-lag effect relative to the head). Moreover, after a short-term adaptation training on a novel association between head rotation and retinal motion, the direction of the flash-lag effect was consistent with the newly trained association. These findings disagree with a previous account extended from the influential motion extrapolation hypothesis. Rather, they support a cross-modal bias hypothesis that the visual-vestibular associations developed from multisensory experiences may generate biasing visual signals in the associated direction with the vestibular signals, which help produce the head-rotation-induced flash-lag effects. Our findings may provide new insight into other multisensory integration phenomena.

Brief Stimuli Cast a Persistent Long-Term Trace in Visual Cortex.

Visual processing is strongly influenced by recent stimulus history, a phenomenon termed adaptation. Prominent theories cast adaptation as a consequence of optimized encoding of visual information by exploiting the temporal statistics of the world. However, this would require the visual system to track the history of individual briefly experienced events, within a stream of visual input, to build up statistical representations over longer timescales. Here, using an openly available dataset from the Allen Brain Observatory, we show that neurons in the early visual cortex of the mouse indeed maintain long-term traces of individual past stimuli that persist despite the presentation of several intervening stimuli, leading to long-term and stimulus-specific adaptation over dozens of seconds. Long-term adaptation was selectively expressed in cortical, but not in thalamic, neurons, which only showed short-term adaptation. Early visual cortex thus maintains concurrent stimulus-specific memory traces of past input, enabling the visual system to build up a statistical representation of the world to optimize the encoding of new information in a changing environment.SIGNIFICANCE STATEMENT In the natural world, previous sensory input is predictive of current input over multisecond timescales. The visual system could exploit these predictabilities by adapting current visual processing to the long-term history of visual input. However, it is unclear whether the visual system can track the history of individual briefly experienced images, within a stream of input, to build up statistical representations over such long timescales. Here, we show that neurons in early visual cortex of the mouse brain exhibit remarkably long-term adaptation to brief stimuli, persisting over dozens of seconds, and despite the presentation of several intervening stimuli. The visual cortex thus maintains long-term traces of individual briefly experienced past images, enabling the formation of statistical representations over extended timescales.

Short-Term Adaptations in Skeletal Muscle Mitochondrial Oxidative Capacity and Metabolic Pathways to Breaking up Sedentary Behaviors in Overweight or Obese Adults.

Breaking up sedentary behavior with short-frequent bouts of physical activity (PA) differentially influences metabolic health compared with the performance of a single-continuous bout of PA matched for total active time. However, the underlying mechanisms are unknown. We compared skeletal muscle mitochondrial respiration (high-resolution respirometry) and molecular adaptations (RNA sequencing) following 4-day exposure to breaks vs. energy-matched single-continuous PA bout in inactive adults with overweight/obesity. Participants (9M/10F, 32.2 ± 6.4 years, 30.3 ± 3.0 kg/m2) completed three 4-day interventions of a randomized cross-over study: SED, sedentary control; MICRO, 5 min brisk walking each hour for 9 h; ONE: 45 min/d continuous brisk walking bout. Fasted muscle biopsies were collected on day 5. Mitochondrial coupling in the presence of lipid-associated substrates was higher after ONE (4.8 ± 2.5) compared to MICRO (3.1 ± 1.1, p = 0.02) and SED (2.3 ± 1.0, p = 0.001). Respiratory rates did not differ across groups with carbohydrate-associated substrates. In pathways associated with muscle contraction transcription signaling, ONE and MICRO similarly enhanced Oxidative Phosphorylation and Sirtuin Signaling expression (p < 0.0001, for both). However, ONE (p < 0.001, for all), but not MICRO, had greater pathway enrichment, including Ca++, mTOR, AMPK, and HIF1α signaling, than SED. Although breaking up sedentary behavior triggered skeletal muscle molecular adaptations favoring oxidative capacity, it did not improve mitochondrial function over the short term.

Resting-State Functional Connectivity in the Dorsal Attention Network Relates to Behavioral Performance in Spatial Attention Tasks and May Show Task-Related Adaptation.

Between-subject variability in cognitive performance has been related to inter-individual differences in functional brain networks. Targeting the dorsal attention network (DAN) we questioned (i) whether resting-state functional connectivity (FC) within the DAN can predict individual performance in spatial attention tasks and (ii) whether there is short-term adaptation of DAN-FC in response to task engagement. Twenty-seven participants first underwent resting-state fMRI (PRE run), they subsequently performed different tasks of spatial attention [including visual search (VS)] and immediately afterwards received another rs-fMRI (POST run). Intra- and inter-hemispheric FC between core hubs of the DAN, bilateral intraparietal sulcus (IPS) and frontal eye field (FEF), was analyzed and compared between PRE and POST. Furthermore, we investigated rs-fMRI-behavior correlations between the DAN-FC in PRE/POST and task performance parameters. The absolute DAN-FC did not change from PRE to POST. However, different significant rs-fMRI-behavior correlations were revealed for intra-/inter-hemispheric connections in the PRE and POST run. The stronger the FC between left FEF and IPS before task engagement, the better was the learning effect (improvement of reaction times) in VS (r = 0.521, p = 0.024). And the faster the VS (mean RT), the stronger was the FC between right FEF and IPS after task engagement (r = −0.502, p = 0.032). To conclude, DAN-FC relates to the individual performance in spatial attention tasks supporting the view of functional brain networks as priors for cognitive ability. Despite a high inter- and intra-individual stability of DAN-FC, the change of FC-behavior correlations after task performance possibly indicates task-related adaptation of the DAN, underlining that behavioral experiences may shape intrinsic brain activity. However, spontaneous state fluctuations of the DAN-FC over time cannot be fully ruled out as an alternative explanation.

Subgenome dominance and its evolutionary implications in crop domestication and breeding.

Polyploidization or whole-genome duplication (WGD) is a well-known speciation and adaptation mechanism in angiosperms, while subgenome dominance is a crucial phenomenon in allopolyploids, established following polyploidization. The dominant subgenomes contribute more to genome evolution and homoeolog expression bias, both of which confer advantages for short-term phenotypic adaptation and long-term domestication. In this review, we firstly summarize the probable mechanistic basis for subgenome dominance, including the effects of genetic [transposon, genetic incompatibility, and homoeologous exchange (HE)], epigenetic (DNA methylation and histone modification), and developmental and environmental factors on this evolutionary process. We then move to Brassica rapa, a typical allopolyploid with subgenome dominance. Polyploidization provides the B. rapa genome not only with the genomic plasticity for adapting to changeable environments, but also an abundant genetic basis for morphological variation, making it a representative species for subgenome dominance studies. According to the ‘two-step theory’, B. rapa experienced genome fractionation twice during WGD, in which most of the genes responding to the environmental cues and phytohormones were over-retained, enhancing subgenome dominance and consequent adaption. More than this, the pangenome of 18 B. rapa accessions with different morphotypes recently constructed provides further evidence to reveal the impacts of polyploidization and subgenome dominance on intraspecific diversification in B. rapa. Above and beyond the fundamental understanding of WGD and subgenome dominance in B. rapa and other plants, however, it remains elusive why subgenome dominance has tissue- and spatiotemporal-specific features and could shuffle between homoeologous regions of different subgenomes by environments in allopolyploids. We lastly propose acceleration of the combined application of resynthesized allopolyploids, omics technology, and genome editing tools to deepen mechanistic investigations of subgenome dominance, both genetic and epigenetic, in a variety of species and environments. We believe that the implications of genomic and genetic basis of a variety of ecologically, evolutionarily, and agriculturally interesting traits coupled with subgenome dominance will be uncovered and aid in making new discoveries and crop breeding.

Systematic derivation of customized development sprints for an agile development of wind turbines

To account for the increasing volatility and uncertainty of external requirements, mechanical and plant engineering companies are facing growing demands for increased flexibility and adaptability within product development. The wind turbine industry in particular, which is characterized by low unit numbers, long development time and high development costs, is especially affected by this trend. Companies are forced to implement processes that allow for short-term adaptation to changing requirements. Plan-driven approaches typically presume that requirements are defined in the early stages of product development and remain static throughout the process. Companies are increasingly resorting to agile approaches, which rely on an incremental and highly iterative development process divided into short sprints. However, the main challenge for them is moving from plan-driven to agile due to the lack of a comprehensive method of incorporating and transforming their current development activities into an agile approach. This allows for the configuration of agile sprints on a short-term, results-oriented basis from process modules identified in the current development. A five step method for this purpose is being presented. The five steps are as follows: (1) Process analysis to record the status as-is; (2) Identification of recurring process modules throughout the development process; (3) Identification of development objects that are used or generated by the process modules; (4) Bottom-up classification and consolidation of these development objects; (5) Configuration of development sprints as a sequence of process modules linked via development objects. The respective steps were validated in cooperation with a company from the wind turbine industry.

Generating cropping schemes from FADN data at the farm and territorial scale

The paper presents an innovative approach to cropping scheme classification based on fad n data with two main goals. First, the identification at the regional level (NUTS 2) of land use patterns common to similar farms defined ‘group cropping scheme'. Second, the farm-level construction of farm cropping schemes, which expand the observed crop mix and identify suitable variation ranges considering the farm production context. The schemes are based on the observed behaviour of homogeneous farms and capture their common structural characteristics regarding land use.The schemes can be used at the territorial scale to analyse landuse trends and patterns over time. At the farm level, the method is designed to analyse short-term adaptations and is suitable to be used, together with other data, in mathematical programming models to run policy analysis exercises. At this latter scale, crop substitution within a scheme allows the set of eligible crops to be expanded while remaining linked to the observed behaviour on a spatial basis.The paper applies the methodology to identify and quantify the cropping schemes using FADN data on Italian farms specialising in annual field crops. An algorithm implemented in gams automates the process. Results confirm the validity of the method and open a field of research for future applications.

Adaptive Feedback Control in Human Reaching Adaptation to Force Fields.

Sensorimotor adaptation is a central function of the nervous system, as it allows humans and other animals to flexibly anticipate their interaction with the environment. In the context of human reaching adaptation to force fields, studies have traditionally separated feedforward (FF) and feedback (FB) processes involved in the improvement of behavior. Here, we review computational models of FF adaptation to force fields and discuss them in light of recent evidence highlighting a clear involvement of feedback control. Instead of a model in which FF and FB mechanisms adapt in parallel, we discuss how online adaptation in the feedback control system can explain both trial-by-trial adaptation and improvements in online motor corrections. Importantly, this computational model combines sensorimotor control and short-term adaptation in a single framework, offering novel perspectives for our understanding of human reaching adaptation and control.

Short-Term Adaptation of Dairy Cattle Production Parameters to Individualized Changes in Dietary Top Dress.

Simple Summary“Short-Term Adaptation of Dairy Cattle Production Parameters to Individualized Changes in Dietary Top Dress” focuses on feeding dairy cattle varying amounts of top dressed corn grain, soybean meal, or grass hay in order to obtain data on individual cow responses to be utilized for future development of individualized dairy precision feeding models. Precision feeding systems aimed at feeding dairy cattle individually to increase feed efficiency could contribute to profitability of dairies. The information provided in this study includes considerations of how we should design such systems.Immediate and short-term changes in diet composition can support individualized, real-time interventions in precision dairy production systems, and might increase feed efficiency (FE) of dairy cattle in the short-term. The objective of this study was to determine immediate and short-term effects of changes in diet composition on production parameters of dairy cattle fed varying amounts of top dressed commodities. A 4 × 4 replicated Latin square design was used to evaluate responses of twenty-four Holstein cows fed either no top dress (Control) or increasing amounts of: corn grain (CG), soybean meal (SBM), or chopped mixed grass hay (GH) top dressed on a total mixed ration (TMR) over four, 9-day periods. Throughout each period, top dressed commodities were incrementally increased, providing 0% to 20% of calculated net energy of lactation (NEL) intake. Measured production responses were analyzed for each 9-d period using a mixed-effects model considering two different time ranges. Samples collected from d 3 and 4 and from d 7 and 8 of each period were averaged and used to reflect “immediate” vs. “short-term” responses, respectively. In the immediate response time frame, control fed cows had lower milk yield, milk fat yield, and milk true protein yield than CG and SBM supplemented animals but similar responses to GH supplemented animals. Milk fat and protein percentages were not affected by top dress type in the immediate term. In the short-term response time-frame, GH supplemented animals had lower DMI and milk fat yield than all other groups. Control and GH supplemented cows had lower milk yield than CG and SBM fed cows. In the immediate response time frame, FE of SBM supplemented cows was superior to other groups. In the short-term time frame, FE of GH and SBM groups was improved over the control group. Results suggest that lactating dairy cows show rapid performance responses to small (<20% NEL) changes in dietary composition, which may be leveraged within automated precision feeding systems to optimize efficiency of production. Before this potential can be realized, further research is needed to examine integration of such strategies into automatic feeding systems and downstream impacts on individual animal FE and farm profitability.

Abstract P256: Pan-ErbB inhibition enhances activity of KRASG12C inhibitors in preclinical models of KRASG12C mutant cancers

Abstract Sotorasib (AMG 510) is the first KRAS inhibitor to be FDA-approved for the treatment of KRASG12C mutant lung adenocarcinomas which comprise ~42% of KRAS mutations in lung adenocarcinomas. Preclinical studies have shown that within hours of KRASG12C inhibition, synthesis of new KRASG12C protein and increased KRAS signaling was observed, leading to enhanced tumor cell growth and survival. This appeared to be due, at least in part, to a feeback loop leading to activation of EGFR signaling but the role of other ErbB family members including ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4) has not been fully evaluated. We hypothesize that short-term adaptation to KRAS inhibition is driven by multiple ErbB family members, and that the combination of pan-ErbB inhibitors with KRASG12C inhibitors could enhance KRASG12C inhibitor activity and prolong survival in preclinical models harboring KRASG12C mutations to a greater extent than more specific EGFR inhibitors. To investigate the role of different ErbB family members in this feedback signaling, we evaluated the impact of an EGFR specific inhibitor, erlotinib, an EGFR/HER2 inhibitor, afatinib, or pan-ErbB inhibitor (EGFR/HER2/3/4), poziotinib on anti-tumor activity of KRASG12C inhibitors in KRASG12C mutant NSCLC cell lines. We initially tested the different inhibitors in combination with sotorasib and adagrasib (MRTX849) and calculated the BLISS index (BI) for each drug pair matrix, using SynergyFinder. We found that when combined with either sotorasib or adagrasib, poziotinib had a synergistic effect (BI&amp;gt;10) in H23 (BI: 17, p=0.01), HCC44 (BI: 11, p=0.04), and H1792 (BI: 13, p=0.01) and an additive effect (BI= -10–10) in H2122 (BI: 2.8). Afatinib and erlotinib were additive in H23 (BI: 9.2 &amp; 9.4), HCC44 (BI:8.8 &amp; 7.9), H2122 (BI: -4.5 &amp; -3.3) and H1792 (BI: 6.6 &amp; 3.3). Poziotinib yielded a higher BI across all four cell lines compared to afatinib (p&amp;lt;0.0001) or erlotinib (p=0.0004). To determine if poziotinib prevented upregulation of ErbB-signaling after treatment with KRASG12C inhibitors, we treated KRASG12C mutant cell lines (NSCLC: H23 and Bladder Cancer: UM-UC-3) with KRASG12C inhibitors, sotorasib or adagrasib, for four hours and found by Western blotting that phosphorylated EGFR, HER2, HER3, and HER4 were increased after treatment. The addition of 10 nM poziotinib prevented the upregulation of phosphorylated EGFR, HER2, HER3, and HER4 in both cell lines. Together these data demonstrate that inhibition of EGFR, HER2, HER3, and HER4 signaling by the pan-ErbB inhibitor poziotinib resulted in greater synergy with KRASG12C inhibitors than EGFR or EGFR/HER2 inhibitors and highlight the potential importance of HER3 and HER4, in addition to EGFR and HER2, in feedback signaling after KRAS G12C inhibition. Additional studies of pan-ErbB and ErbB-specific inhibitors with KRASG12C inhibitors are warranted to determine tolerability and optimal dosing to prolong survival in KRAS mutant cancers. Citation Format: Jacqulyne P. Robichaux, Ana Galan-Cobo, Ried T. Powell, Kelly A. Gale, Jun He, Fahao Zhang, Monique B. Nilsson, Xiang Zhang, Mary M. Sobieski, Nghi Nguyen, Stephan C. Clifford, John V. Heymach. Pan-ErbB inhibition enhances activity of KRASG12C inhibitors in preclinical models of KRASG12C mutant cancers [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P256.

Peculiarities of foreign economic activity management of enterprises

Introduction. The paper is devoted to the problems of research of features and modern mechanisms of economic regulation of foreign economic activity of enterprises in Ukraine. The purpose of the paper is to improve the scientific and methodological basis for stimulating the development of foreign economic activity of enterprises and substantiation of the theoretical foundations of foreign economic activity of enterprises in order to further their development in the today's globalized world. Results. It is determined that one of the problems of foreign economic activity of enterprises is the problem of inefficient management system, lack of strategic and marketing approaches to enterprise management, and enterprises more often use the technique of short-term adaptation. An enterprise focused on the development of foreign economic activity should develop approaches to improve international marketing, especially in terms of making effective management decisions based on the processing of a significant amount of information data and assessing the factors of the international market environment. The main condition for the adaptation of enterprises to the rapidly changing external environment may be the formation of a system of strategic planning, which provides a more rational use of limited resources, promotes consistent development and implementation of management decisions, focuses on sustainable development in market conditions. The management staff should clearly formulate the principles of strategic research in order to intensify foreign trade in industrial enterprises, and most importantly – formed a marketing strategy for foreign trade. The main means of increasing the potential of foreign economic activity of enterprises are the formation of such economic conditions that would allow due to modernization of production to increase domestic production and services, introduce innovative technologies. Conclusion. In order to improve the foreign economic activity of Ukrainian enterprises, it is proposed to implement a policy aimed at increasing merchandise exports by introducing innovative developments to improve the quality of domestic products, which must meet international norms and standards necessary to create a sufficient level of competitiveness in domestic markets.