Intrinsic Preferences Research Articles

Modulating the Competition between Different Atoms to Form Halogen Bonds.

I and Br atoms are placed on opposite ends of a n-butyl group, with each allowed to form a halogen bond (XB) with NH3. DFT calculations show that the intrinsic preference of the nucleophile for the heavier I over Br can be reversed by the proper placement of substituents on the alkyl chain. A similar reversal occurs for NH2 and OH groups on the alkyl chain, where substituents make the O a better electron donor than N in an XB to an electrophilic ICCH. The highly mobile π-electron cloud of an aromatic ring makes such reversals much more difficult when the pair of competing atoms are placed on, or within, such a ring.

The inelastic demand for affirmative action

We study the role of financial incentives in driving support for affirmative action (AA) in a series of online experiments. Participants act as employers deciding whether to use AA in hiring. We implement three treatments to disentangle AA preferences stemming from perceived gender differences in productivity, perceived effects of AA on productivity, or other costs of AA for employers. Around 1/3 of employers consistently implement AA, and we do not find any significant difference across treatments, despite successfully altering beliefs about productivity differences. Our results suggest that AA choice reflects a more intrinsic and inelastic preference for advancing female candidates.

Comments to the Editor on “The Willingness to Pay for Diversification”

Mahmoud [ Mahmoud O (2022) The willingness to pay for diversification. Management Sci. 68(8):6235–6249] presents experimental evidence showing that people have an intrinsic preference for diversification that is driven by risk aversion and loss aversion, with risk-averse and loss-averse individuals being more willing to pay for diversification. We document numerous discrepancies between the results reported in the paper and the results calculated from the experimental data. In particular, the data show that risk-averse individuals are actually less willing to pay for diversification, whereas the effect of loss aversion is nonmonotonic and not statistically significant. We thus show that the data do not support the paper’s claim of a preference for diversification driven by risk aversion and loss aversion. This paper was accepted by Tomasz Piskorski, finance. Funding: The authors gratefully acknowledge financial support from the OP Group Research Foundation [Grants 20220057 and 20220089]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.01581 .

Diffusing protein binders to intrinsically disordered proteins.

Proteins which bind intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) with high affinity and specificity could have considerable utility for therapeutic and diagnostic applications. However, a general methodology for targeting IDPs/IDRs has yet to be developed. Here, we show that starting only from the target sequence of the input, and freely sampling both target and binding protein conformation, RFdiffusion can generate binders to IDPs and IDRs in a wide range of conformations. We use this approach to generate binders to the IDPs Amylin, C-peptide and VP48 in a range of conformations with Kds in the 3 -100nM range. The Amylin binder inhibits amyloid fibril formation and dissociates existing fibers, and enables enrichment of amylin for mass spectrometry-based detection. For the IDRs G3bp1, common gamma chain (IL2RG) and prion, we diffused binders to beta strand conformations of the targets, obtaining 10 to 100 nM affinity. The IL2RG binder colocalizes with the receptor in cells, enabling new approaches to modulating IL2 signaling. Our approach should be widely useful for creating binders to flexible IDPs/IDRs spanning a wide range of intrinsic conformational preferences.

Optimizing bioremediation techniques for soil decontamination in a linguistic intuitionistic fuzzy framework

Bioremediation techniques, which harness the metabolic activities of microorganisms, offer sustainable and environmentally friendly approaches to contaminated soil remediation. These methods involve the introduction of specialized microbial consortiums to facilitate the degradation of pollutants, contribute to soil restoration, and mitigate environmental hazards. When selecting the most effective bioremediation technique for soil decontamination, precise and dependable decision-making methods are critical. This research endeavors to tackle the aforementioned concern by utilizing the tool of aggregation operators in the framework of the Linguistic Intuitionistic Fuzzy (LIF) environment. Linguistic Intuitionistic Fuzzy Sets (LIFSs) provide a robust framework for representing and managing uncertainties associated with linguistic expressions and intuitionistic assessments. Aggregation operators enrich the decision-making process by efficiently handling the intrinsic uncertainties, preferences, and priorities of MADM problems; as a consequence, the decisions produced are more reliable and precise. In this research, we utilize this concept to devise innovative aggregation operators, namely the linguistic intuitionistic fuzzy Dombi weighted averaging operator (LIFDWA) and the linguistic intuitionistic fuzzy Dombi weighted geometric operator (LIFDWG). We also demonstrate the critical structural properties of these operators. Additionally, we formulate novel score and accuracy functions for multiple attribute decision-making (MADM) problems within LIF knowledge. Furthermore, we develop an algorithm to confront the complexities associated with ambiguous data in solving decision-making problems in the LIF Dombi aggregation environment. To underscore the efficacy and superiority of our proposed methodologies, we adeptly apply these techniques to address the MADM problem concerning the optimal selection of a bioremediation technique for soil decontamination. Moreover, we present a comparative evaluation to delineate the authenticity and practical applicability of the recently introduced approaches relative to previously formulated techniques.

Endless loop tachycardia among patients with devices having advanced preventive algorithms: A case series and brief review.

Endless loop tachycardia (ELT) is the commonest pacemaker mediated tachycardia (PMT) encountered among patients with cardiac implantable electronic devices (CIEDs). Despite being enabled with various preventive algorithms, we encountered several cases having recurrent, long, and symptomatic ELT. We retrospectively analyzed consecutive device checkups at device clinic at a single center of eastern India between January 2019 to March 2023. There were 20 cases of confirmed and sustained ELT among 4520 device checks. Although mostly benign, in two cases ELT led to clinical worsening in patients having left ventricular (LV) systolic dysfunction. Even with good ventricular function, ELT resulted in improper atrioventricular (AV) synchrony leading to disabling symptom in one case. The differentiation of ELT from sinus tachycardia and atrial tachycardia (AT) was not always easy. Magnet application is certainly useful to differentiate. The situations that provoked ELT in this study were-long AV delays, VIP (ventricular intrinsic preferences)/MVP (managed ventricular pacing), atrial non-capture, atrial under/over sensing, premature ventricular contractions (PVCs)/couplets, premature atrial contractions (PAC) and slower ventriculo-atrial (VA) conduction. Rate responsive shortening of post-ventricular atrial refractory period (PVARP) also promoted its occurrence and hindered troubleshooting. When ELT occurred despite post-PVC extension of PVARP, lowering the atrial sensitivity, switching to bipolar sensing and manual setting of longer PVARP after measuring VA conduction time were useful. "Rate responsive PVARP" had to be turned off in a few cases to prevent ELT. On the contrary, an over aggressive prolongation of PVARP led to repetitive non-reentrant ventriculo-atrial synchrony (RNRVAS) in two cases. Checking VA conduction during implantation and noninvasive program stimulation (NIPS) during follow up were useful to check the tendency for ELT. Clinically significant ELT is rare but not uncommon among devices having in-built preventive algorithms. Manual adjustments are often useful to troubleshoot the same.

A Multi-Method Study Examining the Role of Swiping on Dating Apps: Mate Value Preferences, Sexual Satisfaction, and Need Satisfaction with Matches in Emerging Adults.

Intrinsic (i.e., personality traits) and extrinsic mate value (i.e., resources, physical attractiveness) preferences play a crucial role in (online) relationship formation. The role of mate values in dating applications was unclear and was addressed in a multi-method study. A first content analytical study examined the prevalence of mate values (MVs) on Tinder profiles (Study 1) and two subsequent cross-sectional studies explored the relationships between dating app use, various swiping behaviors, sexual satisfaction (Studies 2-3), need satisfaction with matches (Study 3), having a committed relationship versus casual sex motivation for using dating apps and users' gender. The content analysis of 307 Tinder profiles indicated that resources and physical attractiveness were most salient in biographies and pictures, respectively. The first cross-sectional study (nfullsample = 325, ndating app users = 133) revealed no significant relationships between dating app frequency/swiping frequency, intrinsic and extrinsic MV preferences, and sexual satisfaction. The second cross-sectional study (n = 323) showed no significant relationships between picture-based or biography-based swiping, intrinsic and extrinsic MV preferences, and need satisfaction with matches. Gender differences emerged in the presentation of MVs on Tinder (Study 1) and general MV preferences (Study 2-3), but not in the relationships between different types of dating app use/swiping and MV preferences (Study 2-3). A committed relationship and a casual sex motivation played a role in the relationships between different types of swiping behaviors and MV preferences, and between MV preferences, and sexual satisfaction/need satisfaction with matches.

KATP channel mutation disrupts hippocampal network activity and nocturnal gamma shifts.

ATP-sensitive potassium (KATP) channels couple cell metabolism to cellular electrical activity. Humans affected by severe activating mutations in KATP channels suffer from developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). While the aetiology of diabetes in DEND syndrome is well understood, the pathophysiology of the neurological symptoms remains unclear. We hypothesised that impaired activity of parvalbumin-positive interneurons (PV-INs) may result in seizures and cognitive problems. We found, by performing electrophysiological experiments, that expressing the DEND mutation Kir6.2-V59M selectively in mouse PV-INs reduced intrinsic gamma frequency preference and short-term depression as well as disturbed cognition-associated gamma oscillations and hippocampal sharp waves. Furthermore, the risk of seizures was increased and the day-night shift in gamma activity disrupted. Blocking KATP channels with tolbutamide partially rescued the network oscillations. The non-reversible part may, to some extent, result from observed altered PV-IN dendritic branching and PV-IN arrangement within CA1. In summary, PV-INs play a key role in DEND syndrome, and this provides a framework for establishing treatment options.

Effects of the Japanese medical office system on innovation creation among medical doctors: A survey of cardiologists in acute care settings

ABSTRACT In the Japanese medical office system, medical doctors are dispatched from university medical offices to affiliated hospitals. In the present study, the effects of Japan’s unique medical office system on innovation creation among medical doctors were examined. A questionnaire survey was administered to 150 cardiologists between 7 and 30 June 2023; results showed that 109 (73.0%) participants were affiliated with the medical office system and 41 (27.0%) were not. From the literature, the following categories of elements of creativity were extracted: personality, cognitive processes, competence/intelligence, motivation, work environment/management, social networks and entrepreneurial orientation. Analysis of these categories identified five types of factors influencing creativity: knowledge-seeking attitude, challenging work environment, intrinsic motivation promotion, diversity preference and self-help. Linear regression analysis showed that creativity increased with age (beta, 0.274 [95% confidence interval, 0.084–0.464]; p = 0.005) but was unaffected by all other factors. Thus, the study found that the medical office system did not have a negative impact on the creativity (i.e. innovation creation) of individual medical doctors; however, this system may delay the age at which these doctors can demonstrate their creativity.

Molecular Basis for Chemoselectivity Control in Oxidations of Internal Aryl-Alkenes Catalyzed by Laboratory Evolved P450s.

P450 enzymes naturally perform selective hydroxylations and epoxidations of unfunctionalized hydrocarbon substrates, among other reactions. The adaptation of P450 enzymes to a particular oxidative reaction involving alkenes is of great interest for the design of new synthetically useful biocatalysts. However, the mechanism that these enzymes utilize to precisely modulate the chemoselectivity and distinguishing between competing alkene double bond epoxidations and allylic C-H hydroxylations is sometimes not clear, which hampers the rational design of specific biocatalysts. In a previous work, a P450 from Labrenzia aggregata (P450LA1) was engineered in the laboratory using directed evolution to catalyze the direct oxidation of trans-β-methylstyrene to phenylacetone. The final variant, KS, was able to overcome the intrinsic preference for alkene epoxidation to directly generate a ketone product via the formation of a highly reactive carbocation intermediate. Here, additional library screening along this evolutionary lineage permitted to serendipitously detect a mutation that overcomes epoxidation and carbonyl formation by exhibiting a large selectivity of 94 % towards allylic C-H hydroxylation. A multiscalar computational methodology was applied to reveal the molecular basis towards this hydroxylation preference. Enzyme modelling suggests that introduction of a bulky substitution dramatically changes the accessible conformations of the substrate in the active site, thus modifying the enzymatic selectivity towards terminal hydroxylation and avoiding the competing epoxidation pathway, which is sterically hindered.

Frequent winners explain apparent skewness preferences in experience-based decisions

Do people's attitudes toward the (a)symmetry of an outcome distribution affect their choices? Financial investors seek return distributions with frequent small returns but few large ones, consistent with leading models of choice in economics and finance that assume right-skewed preferences. In contrast, many experiments in which decision-makers learn about choice options through experience find the opposite choice tendency, in favor of left-skewed options. To reconcile these seemingly contradicting findings, the present work investigates the effect of skewness on choices in experience-based decisions. Across seven studies, we show that apparent preferences for left-skewed outcome distributions are a consequence of those distributions having a higher value in most direct outcome comparisons, a "frequent-winner effect." By manipulating which option is the frequent winner, we show that choice tendencies for frequent winners can be obtained even with identical outcome distributions. Moreover, systematic choice tendencies in favor of right- or left-skewed options can be obtained by manipulating which option is experienced as the frequent winner. We also find evidence for an intrinsic preference for right-skewed outcome distributions. The frequent-winner phenomenon is robust to variations in outcome distributions and experimental paradigms. These findings are confirmed by computational analyses in which a reinforcement-learning model capturing frequent winning and intrinsic skewness preferences provides the best account of the data. Our work reconciles conflicting findings of aggregated behavior in financial markets and experiments and highlights the need for theories of decision-making sensitive to joint outcome distributions of the available options.

Direct and indirect effects of mother's spatial ability on child's spatial ability: What role does the home environment play?

Individual differences in spatial thinking are predictive of children's math and science achievement and later entry into Science, Technology, Engineering, and Mathematics (STEM) disciplines. Little is known about whether parent characteristics predict individual differences in children's spatial thinking. This study aims to understand whether, and to what extent, mother's intrinsic (i.e., mental rotation) and extrinsic (i.e., spatial scaling) spatial ability directly and indirectly, via the variation in home spatial environment, predicts children's intrinsic and extrinsic spatial ability. A total of 165 mothers and their 4-6-year-old children were recruited to participate in a remote video session with an experimenter. Mothers were administered a forced-choice Intrinsic Spatial Toy Preference Task gauging their preference for highly spatial versus less spatial toys and asked questions with the Home Intrinsic Spatial Environmental Questionnaire about the frequency with which they engage their child in spatial activities at home. Mothers completed a Mental Rotations Test and a Spatial Scaling Task adapted for adults. Children were administered the Picture Rotation Task, the Spatial Scaling Task, and the Peabody Picture Vocabulary Test. Structural equation modeling was used to examine direct and indirect, via home spatial environment and toy choices, influences of mother spatial ability on child spatial ability. Contrary to our predictions, we did not find direct, nor indirect, relations between mother and child spatial ability. These findings suggest that researchers should consider alternative conceptualizations of the early home spatial environment beyond the frequency of spatial play in the home. RESEARCH HIGHLIGHTS: The identification of factors that predict individual differences in children's spatial ability is important in order to maximize STEM learning outcomes. Data collection was conducted remotely rather than in traditional preschool or laboratory settings. Contrary to our pre-registered hypotheses, no significant relations between mother spatial ability, the early home spatial environment, and children's development of spatial skills were found. Future research should consider examining the amount of spatial language used in the home or the quality of parent-child interactions during spatial play as potential explanations for individual differences in children's spatial ability.

Dynamic and Static Representation Learning Network for Recommendation.

Existing review-based recommendation methods learn a latent representation of user and item from user-generated reviews by a static strategy, which are unable to capture the dynamic evolution of users' interests and the dynamic attraction of items. Here, we propose a dynamic and static representation learning network (DSRLN) to improve the rating prediction accuracy by exploring fine-grained representations of users and items. Specifically, we built DSRLN with a dynamic representation extractor to model the dynamic evolution of users' interests by exploring the inner relations of an interaction sequence, and with a static representation extractor to model the users' intrinsic preferences by learning the semantic coherence and feature strength information from reviews. To identify the different influences of dynamic and static features for different users, a personalized adaptive fusion module was designed using a weighted attention mechanism. Extensive experiments on five real-world datasets from Amazon demonstrated the superiority of the proposed model, and the additional ablation studies verified the effectiveness of the components designed in the DSRLN model.

Intrinsic conformational preference in the monomeric protein governs amyloid polymorphism.

The inherent stochasticity associated with the hierarchical self-assembly of either native-like or partially-unfolded protein monomers leads to the formation of transient, morphologically-diverse prefibrillar species resulting in structurally-distinct polymorphic protein aggregates. High-resolution structural characterization of mature aggregates has revealed heterogeneous supramolecular packing of protofibrils within amyloid polymorphs. However, little is known about whether initial monomeric protein conformers engender polymorphism at the onset of aggregation. Here, we show that intrinsic conformational preference in aggregation-competent monomeric ovalbumin, an archetypal serpin, dictates fibrillar polymorphism by modulating aggregation pathways. Using fluorescence, FT-IR, and vibrational Raman spectroscopy coupled with dynamic light scattering and electron microscopy, we demonstrate that conformationally-diverse amyloidogenic monomers, formed via an interplay of electrostatic and hydrophobic interactions before the commencement of aggregation, play a crucial role in promoting amyloid polymorphism. Moreover, the monomeric conformational fingerprints, accrued at the onset of aggregation, persist and propagate during the formation of polymorphic amyloids. Our results delineate essential conformational characteristics of the monomeric protein preceding aggregation, which will have broad implications in the mechanistic understanding of amyloid strain diversity observed in disease-related proteins.

Loss of fluorine during crosslinking by the biarylitide P450Blt proceeds due to restricted peptide orientation.

The biarylitide crosslinking enzyme P450Blt can perform crosslinking between m-F-Tyr-3 and His-5 residues within peptide substrates with concomitant and specific loss of fluorine. Our investigations suggest that a small intrinsic preference for coupling ipso to fluorine is magnified by the binding of the peptide in a specific orientation that enforces the loss of fluorine during peptide crosslinking, likely via a two-step reaction mechanism involving the non-enzyme catalysed reductive elimination of fluoride.

DNA conformational dynamics in the context-dependent non-CG CHH methylation by plant methyltransferase DRM2

DNA methylation provides an important epigenetic mechanism that critically regulates gene expression, genome imprinting, and retrotransposon silencing. In plants, DNA methylation is prevalent not only in a CG dinucleotide context, but also in non-CG contexts, namely CHG and CHH (H = C, T, or A) methylation. It has been established that plant non-CG DNA methylation is highly context dependent, with the +1- and +2-flanking sequences enriched with A/T nucleotides. How DNA sequence, conformation, and dynamics influence non-CG methylation remains elusive. Here, we report structural and biochemical characterizations of the intrinsic substrate preference of DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), a plant DNA methyltransferase responsible for establishing all cytosine methylation and maintaining CHH methylation. Among nine CHH motifs, the DRM2 methyltransferase (MTase) domain shows marked substrate preference toward CWW (W = A or T) motifs, correlating well with their relative abundance in planta. Furthermore, we report the crystal structure of DRM2 MTase in complex with a DNA duplex containing a flexible TpA base step at the +1/+2-flanking sites of the target nucleotide. Comparative structural analysis of the DRM2-DNA complexes provides a mechanism by which flanking nucleotide composition impacts DRM2-mediated DNA methylation. Furthermore, the flexibility of the TpA step gives rise to two alternative DNA conformations, resulting in different interactions with DRM2 and consequently temperature-dependent shift of the substrate preference of DRM2. Together, this study provides insights into how the interplay between the conformational dynamics of DNA and temperature as an environmental factor contributes to the context-dependent CHH methylation by DRM2.

What drives solo and team startups at European universities? The interactive role of entrepreneurial climate, gender, and entrepreneurship course participation

ABSTRACT Student entrepreneurship can take the form of solo or team efforts. While a positive and supportive university context is likely to increase entrepreneurial activities in general, it is unclear whether this effect is equally strong on both forms of entrepreneurship and for all types of students. Focusing on students embedded in universities, we study the entrepreneurial climate of universities and its combined effects with gender and entrepreneurship education on solo and team entrepreneurship. Drawing from organizational theory and team formation literature, we hypothesize that a positive entrepreneurial climate stimulates both, solo and team entrepreneurship. Yet, we argue that this effect is contingent on individuals’ intrinsic preferences for independence or growth which may differ by gender and entrepreneurship course participation. We test our hypotheses by means of a multilevel and longitudinal research design, using a large international dataset on student entrepreneurs (GUESSS). We find that a positive entrepreneurial climate indeed fosters solo and team startups of students, with gender and entrepreneurship education having an interactive effect. Our results suggest that a positive climate leads to more solo startups of women and more team startups of men. We contribute to a better understanding of student entrepreneurship and, specifically, the formation of solo and team startups. Our results elucidate the hitherto overlooked person-context dynamics and help explain why a supportive university context can unintentionally widen the gender gap in team startups.

Intrinsic Information Preferences and Skewness

We examine whether people have an intrinsic preference for negatively skewed or positively skewed information structures and how these preferences relate to intrinsic preferences for informativeness. The results from lab experiments show a strong intrinsic preference for positively skewed information and suggest that providing such information can improve information uptake. Evidence from field studies in decision- and ego-relevant contexts replicates these findings. We discuss our findings through the lens of existing theories and the potential trade-offs in information provision policies. (JEL C91, C93, D12, D82, D83)

A multi-method investigation of motive dispositions: affiliative and antagonistic dispositions in psychopathy

Purpose To replicate and extend research on psychopathy and intrinsic interpersonal preferences under the broader umbrella of affiliation, intimacy and antagonism, this paper aims to examine motivational correlates of psychopathy in a nonclinical sample (N = 125). Design/methodology/approach We used a multimethod design, including self-reports, a behavioral task and a physiological assessment of motive dispositions (automatic affective reactions to stimuli of interpersonal transactions measured with facial electromyography). Findings Results showed that self-reported psychopathy was negatively associated with self-reported intimacy motive. In the same vein, via the social discounting task, this paper found a negative association between psychopathy and a tendency to share hypothetical monetary amounts with very close others. Finally, regarding fEMG findings, multilevel analyses revealed that although individuals with low levels of psychopathy reacted more positively to affiliative stimuli, individuals with high levels of psychopathy reacted equally positively to both affiliative and antagonistic stimuli, and these results were robust across psychopathy measures. Results remained mostly unchanged on the subscale level. Originality/value These findings highlight the contribution of multimethod assessments in capturing nuances of motivation. Implicit physiological measures might be particularly sensitive in capturing motive dispositions in relation to psychopathy. Identifying mechanisms that foster positive connections between psychopathic traits and nonprosocial tendencies may be theoretically and clinically informative, with implications for forensic and penal practices.

Higher mitochondrial oxidative capacity is the primary molecular differentiator in muscle of rats with high and low intrinsic cardiorespiratory fitness

ObjectiveCardiorespiratory fitness (CRF) is tightly linked with health and longevity and is implicated in metabolic flexibility and substrate metabolism. The high capacity runner (HCR) and low capacity runner (LCR) rat lines are a genetically heterogeneous rat model selected and bred for CRF that reflect CRF in humans by exhibiting differences in nutrient handling. This study aims to differentiate the intrinsic substrate preference of the HCR compared to LCR rats to better understand the intersection of mitochondrial respiration and intrinsic CRF. MethodsWe performed bulk skeletal muscle RNA-Sequencing on male and female HCR and LCR rats and assessed the effect of rat line on mitochondrial gene expression pathways using the MitoCarta3.0 database. In a separate cohort of rats, mitochondria were isolated from skeletal and cardiac muscle and maximal oxidation rates were measured using an Oroboros O2k when provided either pyruvate or fatty acid substrates. ResultsThe expression of mitochondrial genes are significantly upregulated in HCR skeletal muscle in both male and female rats. In respirometry experiments, fatty acid oxidative capacities were greater in HCR compared to LCR, and male compared to female rats, as a function of both mitochondrial quality and mitochondrial density. This effect was greater in the skeletal muscle than in the heart. Pyruvate oxidation did not differ significantly between lines. ConclusionsThe capacity for increased fatty acid oxidation in the HCR rat is a result of selection for running capacity and is likely a key contributor to the healthy metabolic phenotype of individuals with high CRF.