Miracle-dz/UniFAR-FTUs huggingface dataset:
CPVT-associated calmodulin variants N53I and A102V dysregulate Ca2+ signalling via different mechanisms

ABSTRACT Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited condition that can cause fatal cardiac arrhythmia. Human mutations in the Ca2+ sensor calmodulin (CaM) have been associated with CPVT susceptibility, suggesting that CaM dysfunction is a key driver of the disease. However, the detailed molecular mechanism remains unclear. Focusing on the interaction with the cardiac ryanodine receptor (RyR2), we determined the effect of CPVT-associated variants N53I and A102V on the structural characteristics of CaM and on Ca2+ fluxes in live cells. We provide novel data showing that interaction of both Ca2+/CaM-N53I and Ca2+/CaM-A102V with the RyR2 binding domain is decreased. Ca2+/CaM–RyR23583-3603 high-resolution crystal structures highlight subtle conformational changes for the N53I variant, with A102V being similar to wild type (WT). We show that co-expression of CaM-N53I or CaM-A102V with RyR2 in HEK293 cells significantly increased the duration of Ca2+ events; CaM-A102V exhibited a lower frequency of Ca2+ oscillations. In addition, we show that CaMKIIδ (also known as CAMK2D) phosphorylation activity is increased for A102V, compared to CaM-WT. This paper provides novel insight into the molecular mechanisms of CPVT-associated CaM variants and will facilitate the development of strategies for future therapies.
The Use of Genotypic Information for the Genetic Improvement of 'Pinus radiata'

The invention of high-throughput genotyping technologies, in particular the single nucleotide polymorphism (SNP) chip, has prompted a revolution in the field of genetics. With the potential of genotyping literally hundreds of thousands of molecular markers at an affordable price, the once distant prospect of establishing an individuals genetic value without need of its pedigree has now become a reality. This thesis is primarily concerned with the use of genotypic data for ’genomic selection’ a novel and computationally intensive method of selection that uses all available genotypic data to estimate an individuals genetic potential. The efficiency of this method is considered within the broader context of the genetic improvement of Pinus radiata. We begin by introducing the reader to a basic application of SNP markers in an analysis of population structure and linkage disequilibrium (LD) for three of the five native Pinus radiata populations located on the west coast of California. We show that although these populations are geographically distinct, estimates of genetic distance derived from marker genotypes suggest that all three once belonged to the same population. Levels of LD are shown to be orders of magnitude higher within genes than outside the genes. We extend the use of SNP markers to the Bayesian estimation of quantitative trait loci (QTL) effects and breeding values. By adopting a ’best case scenario’ approach, we demonstrate that the detection and estimation of more than 10 individual QTL effects remains a virtually impossible task, even in highly heritable traits and whilst assuming complete LD between markers and QTL. In contrast, we show through simulation that at moderate to high heritabilities genomic estimated breeding values (GEBVs) can be estimated with very high accuracy (r > 0.70) even for traits with up to 1,000 QTL. We show that further increases in the accuracy of selection can be made through the use of clones in families, especially at lower heritabilities and for traits with large numbers of QTL effects. The importance of statistical methodology in the analysis of genotypic data is assessed by comparing a non-linear Bayesian method called Bayes-A, with traditional best linear unbiased prediction (BLUP). It is shown that whilst Bayes-A is superior in the estimation
Impact of abiotic factors on population dynamics of Bactrocera dorsalis Hendel and Bactrocera zonata (Saunders) at different ecological zones in NW Plains of India

In India, fruit flies have been identified as one of the ten most serious problems of agriculture because of their polyphagous nature and the huge economic loss it causes to the fruits and vegetables (2.5 to 100%). Study was carried to determine the population dynamics of fruit flies (Bactrocera dorsalis and Bactrocera zonata) and establish the correlation with abiotic factors in guava and citrus fruits crops in two agro ecological zones of North West India. Fruit flies population was recorded by installation of pheromone traps in different fruit crop ecosystems during the fruiting season of this zone. The data of trap catches of both the locations was correlated with the significantly influencing abiotic parameters. The peak fruit fly incidence varied between 31st to 34th standard weeks in guava ecosystem at both the locations. In citrus ecosystem, the incidence was highest during 35th and 39th standard weeks coinciding with the ripening of the fruits. At both the locations, trap catches of guava ecosystem were positively correlated with all the weather parameters, while under citrus ecosystem minimum temperature and rainfall showed negative correlation, but relative humidity was positively correlated. Information may be utilized in targeting suitable pest management techniques for respective zones.
Granzyme-Producing CD4 T Cells in Cancer and Autoimmune Disease

CD4 T cells play important roles in promoting protective immunity and autoimmune disease. A great deal of attention has been given to the differentiation and function of subsets of cytokine-producing CD4 T cells (i.e., Th1, Th2, and Th17 cells) in these settings. However, others have also observed the accumulation of granzyme-producing CD4 T cells in tumors and in autoimmune patients that are distinct from their cytokine-producing counterparts. Despite the relatively large numbers of granzyme-producing cells in diseased tissues, their roles in driving disease have remained enigmatic. This review will focus on the phenotype(s) and roles of granzyme-producing CD4 T cells in cancer and autoimmunity. We will also examine how granzyme-producing cells interact with current therapeutics and speculate how they may be targeted during disease.
Knowledge Sharing sebagai Sumber Inovasi dan Keunggulan Bersaing pada Usaha Mikro Kecil dan Menengah (UMKM) Sektor Batik

Small and medium batik sector are significantly contribution to econo mic development and the culturalÂ heritage,Â but development are still many prob lems, especiallyÂ theÂ empowermentÂ ofÂ internalÂ Â assetsÂ soÂ itÂ hasÂ anÂ impactÂ onÂ the development of innovation capability ann competitive advantage. Â This study aims to examine the effect of knowledge sharingÂ processÂ Â to innovation capability and competitiveÂ advantageÂ Â atÂ Â Â smallÂ andÂ mediumÂ batikÂ sectorÂ inÂ CentralÂ Â Java. Sampling methods using purposive sampling and dataÂ analysis using the Partial LeastÂ SquareÂ (PLS). Â TheÂ researchÂ Â resultsÂ Â Â Â Â Â thatÂ Â Â knowledgeÂ donataingÂ Â and knowledge collecting are significantly effect on innovation capability. Knowledge donating, knowledge collecting and innovation capabilityÂ areÂ significantly effect on theÂ competitive advantage. Â Keywords : Knowledge collecting , Knowledge donating, Innovation capability
When Collaborating in Constructive Task With Spouse: Attachment Orientation Predicts Exploratory Behavior Among Older Couples

In order to examine the function of the attachment system in later life, this study investigated the relationships between attachment orientation and exploratory behavior in a collaborative constructive activity with one’s spouse among older adults. In total, 49 older couples completed a collaborative constructive task, and their behaviors were videotaped. Each participant’s exploratory behavior (i.e., engagement, enjoyment, and distress) was coded by independent raters. The results revealed older adults highly engaged in the collaborative activity. In addition, based on the actor-partner interdependence model, the results indicated that attachment avoidance positively predicted the individuals’ enjoyment as well as their partners’ distress during the collaborative activity. The current findings extend the literature regarding the effects of attachment on exploration from early adulthood to later life, from the workplace to family life, and from individual’s own behavior to collaborative situation.
Linguistic Traces of Subjectivity and Dissent. A Discursive Analysis of Inclusive Language in Argentina

In Argentina, the so-called “inclusive language” aims at avoiding the bias for a particular sex or gender and objects to a grammatical binary system (feminine – masculine). Although in most Spanish-speaking countries, inclusive language has been limited to the realms of activism, gender studies and a certain type of public administration, in Argentina, its use has been extended to different social spheres, mostly urban. Considering such context, this work aims to investigate the inclusive language in Spanish and characterize its most relevant resources in a series of public texts that circulated in Argentina between 2018 and 2020. On the one hand, its origin is explained, differentiating it from non-sexist language and the different theoretical positions around inclusive language are exposed. On the other hand, from the Dialogical Approach to Argumentation and Polyphony, this paper proposes to address inclusive language resources as subjectivity and polyphony marks which evidence certain aspects of the discourse of patriarchy, with respect to which there is dissent; therefore, inclusive language resources show viewpoints that were once silenced and rejected. For this, a corpus of various speeches is addressed, made up of outdoor urban inscriptions, flyers (advertisements), audiovisual informative speeches and digital press, written in inclusive language, between 2018 and 2020. Throughout the paper it is warns that the inclusive language marks, such as –e and x, are traces of the “heterogeneity shown marked” that object to grammatical binarism and convey comments by the subject about their own enunciation, alluding to the image of previous sexist and patriarchal discourses with whom they disagree. The analysis reveals that the words or expressions in which inclusive language resources are employed (-e and x) work as traces of harassed identities and manifest comments by the speaker on their own enunciation. This way, this research shows that gender inclusive language holds conflict linguistic marks which point to historically denied dissidence forms, linked to gender identity and the assertion of collective rights. Finally, this article aims at, on the one hand, contributing to the description of Argentinean Spanish, and on the other, promoting reflection in favor of linguistic education. Undoubtedly, opening instances of debate on the subject can have an impact on the deepening of linguistic reflection and the training of speakers who contribute to forging a more egalitarian society, one which is inclusive and respectful of differences.
Managing warehousing in an agile supply chain environment: an F-AIS algorithm based approach

In recent years, application of the agile concept in the manufacturing sector has been researched extensively to reduce the varying effect of customer demands. However, most of the research work is focused on the shop floor of different manufacturing processes, while issues concerning the control of warehouse scheduling in a supply chain have been neglected so far. Realising this in the present research an attempt has been made to address the scheduling aspect of a warehouse in an agile supply chain environment. To resolve the warehouse problem in this paper, the authors have proposed a new Fuzzy incorporated Artificial Immune System Algorithm (F-AIS). This algorithm encapsulates the salient features of a fuzzy logic controller and immune system. The proposed algorithm has been compared with genetic algorithm (GA), simulated annealing (SA) and artificial immune system (AIS) algorithm to reveal the efficacy of the proposed F-AIS algorithm.
Severe disturbance overflows the stabilizing buffer of variable biotic interactions

Recent studies have uncovered that biotic interaction strength varies over time in real ecosystems intrinsically and/or responding to anthropogenic disturbances. Little is known, however, about whether such interaction variability strengthens or weakens community resistance against disturbances. Here, we examine how the change in interaction strength after pesticide application mediates disturbance impacts on a freshwater community using outdoor mesocosms. We show that the change in interaction strength buffered the disturbance impact but amplified it once the disturbance severity exceeded a certain threshold. Importantly, we also show that interactions fluctuating more temporally under no disturbances were more changeable in response to pesticide applications. Our findings suggest that a severe disturbance may have a surprise impact on a biological community amplified by their own interaction variability, but the possibility still remains that we can predict the consequences of the disturbance by measuring the interaction variability before the disturbance occurs.
On the channel length dependence of negative bias temperature instability in nano-CMOS technology

The channel length dependence of NBTI degradation in a 65 nm CMOS technology is studied. Although it is generally observed that the NBTI degradation increases with the channel length decreasing, the role of the generated interface traps and the oxide positive charges in the NBTI channel length dependence is not clear yet. In this work, it is shown that the NBTI degradation of the B(boron) LDD devices have stronger channel length dependence as compared with the BF2 LDD devices. The channel length dependence of the oxide trapped charges density (ΔNot) and the interface trap density (ΔNit) are quantitatively estimated. Although both of the ΔNot and the ΔNit increase with the decreasing channel length, it is shown that the local ΔNit is significantly enhanced at the gate edge in B LDD devices. On the other hand, the ΔNot shows weaker channel length dependence in both B and BF2 LDD devices, as compared with the ΔNit in B LDD devices. These results imply that the enhanced NBTI degradation must be taking into consideration in the future device scaling.
CordNet: Toward a Distributed Behavior Model for Emergency Response Coordination

Existing studies of coordination theory in human networks have looked at coordination problems requiring stable working relationships with no environmental uncertainties. With emergency response management demanding distributed coordination in volatile situations, the designs of existing models are useful as a building block, yet flawed for application. We hypothesize that changes to interconnectedness of nodes in the network may have implications on the potential to coordinate. To test our hypotheses, we investigate survey data from state law enforcement, state emergency services, and local law enforcement by performing agency-based (macro) and cross-agency (micro) analysis to identify attributes of each network and coordination.
Altered Functional Connectivity of Insular Subregions in Type 2 Diabetes Mellitus

Diabetes-related brain damage can lead to cognitive decline and increase the risk of depression, but the neuropathological mechanism of this phenomenon remains unclear. Different insular subregions have obvious functional heterogeneity, which is related to many aspects of type 2 diabetes mellitus (T2DM)-related brain damage. However, little is known about changes in functional connectivity (FC) in insular subregions in patients with T2DM. Therefore, we aimed to investigate FC between different insular subregions and clinical/cognitive variables in patients with T2DM. Fifty-seven patients with T2DM and 55 healthy controls (HCs) underwent a neuropsychological assessment and resting-state FC examination. We defined three insular subregions, including the bilateral dorsal anterior insula (dAI), bilateral ventral anterior insula (vAI), and bilateral posterior insula (PI). We examined differences in FC between insular subregions and the whole brain in patients with T2DM compared with HCs. A correlation analysis was performed to examine the relationship between FC and clinical/cognitive variables. Compared with HCs, patients with T2DM showed significantly decreased FC between the dAI and the right inferior frontal gyrus, right superior/middle temporal gyrus, right hippocampus, and right precentral gyrus. FC between the vAI and the right supramarginal gyrus, as well as the PI and the right precentral/postcentral gyrus, was reduced in the T2DM group compared with the control group. In the T2DM group, we showed a significant negative correlation between glycated hemoglobin concentration and FC in the dAI and right hippocampus (r = −0.428, P = 0.001) after Bonferroni correction. We conclude that different insular subregions present distinct FC patterns with functional regions and that abnormal FC in these insular subregions may affect cognitive, emotional, and sensorimotor functions in patients with T2DM.
Elevated Post K‐Pg Export Productivity in the Gulf of Mexico and Caribbean

The global heterogeneity in export productivity after the Cretaceous‐Paleogene (K‐Pg) mass extinction is well documented, with some sites showing no change on geologic timescales, some demonstrating sustained decline, and a few showing a somewhat surprising increase. However, observational data come from sites so widespread that a key outstanding question is the geographic scale of changes in export productivity, and whether similar environments (e.g., open ocean gyres) responded similarly or whether heterogeneity is unrelated to environment. To address this, we developed three new Ba/Ti export productivity records from sites in the Gulf of Mexico and Caribbean which, combined with published data from a fourth site in the Chicxulub Crater itself, allow us to reconstruct regional changes in post K‐Pg export productivity for the first time. We find that, on a regional scale, export productivity change was homogenous, with all four sites showing a ∼300 Kyr period of elevated export production just after the boundary, followed by a longer period of decline. Interestingly, this interval of elevated export production appears to coincide with the post K‐Pg global micrite layer, which is thought to at least partially have been produced by blooms of carbonate‐producing cyanobacteria and other picophytoplankton. Global comparison of sites shows that elevated export productivity appears to have been most common in oligotrophic gyres, which suggests that changing plankton ecology evidenced by the micrite layer altered the biological pump, leading to a temporary increase in export production in these settings.
Biological Models of the Lower Human Airways—Challenges and Special Requirements of Human 3D Barrier Models for Biomedical Research

In our review, we want to summarize the current status of the development of airway models and their application in biomedical research. We start with the very well characterized models composed of cell lines and end with the use of organoids. An important aspect is the function of the mucus as a component of the barrier, especially for infection research. Finally, we will explain the need for a nondestructive characterization of the barrier models using TEER measurements and live cell imaging. Here, organ-on-a-chip technology offers a great opportunity for the culture of complex airway models.
Design and emotion

Excellence in design is about more than the final product itself. It is about creating positive, rich and meaningful user experiences. Consumers are ever mindful that the products we surround ourselves with and engage with during our daily tasks need to satisfy needs beyond the functional. While design is a key contributing factor at the point of purchase, the bond that emerges between the consumer and the product becomes the differentiator for long-term success, or failure, as is so often the case. As consumers of meaning, not matter, we construct our aggregate identities through engagements with the products we fill our lives with, objects that hold particular meaning (e.g. symbols of our achievements and indicators of our social lives), and this bespoke collection of frequently mass-manufactured objects (products) has a significant impact on the experiential fabric of our daily lives. The relationship between design and emotion represents a contemporary dualism, the significance of which is only beginning to be understood, in terms of its role in shaping the social, economic and environmental implications of design, production and consumption. For the new product developer, it becomes critical that products are developed in such a way that their technology, appearance and use resonate and respond to consumer needs, aspirations and lifestyle choices. If products do not meet these needs, then barriers develop that become obstacles to the product’s success – desire rapidly mutates into disappointment and replacement motives promptly manifest. Eliciting user needs is not as straightforward as measuring what is measurable. Users often say one thing, do another and often feel something else. We need to be mindful that design is culturally located in that the consumers’values may not apply to another population, and therefore the research presented in this collection is transferrable though not necessarily generalisable, but equally could be valuable. Much debate focuses on the degree to which design can influence, or author, the emotional experience mediated by products, due in large part to the deeply idiosyncratic, random nature of each individual user – their memories, experiences and values – regardless of their firm location within a prescribed demographic profile – people are people and things change. For designers, the emotional and ephemeral nature of consumers’ needs have been acknowledged for some time. With this special issue, it is our intention that we broaden the research in this area to include the engineering design community, mobilising an expansive, critical set of propositions. This special issue is dedicated to highlighting the increasing awareness and value of emotions within the designing process, for both the product developer and the consumer. Based on thorough and strict peer reviews, a total of six papers were selected for publication from 16 submissions. These papers represent a snapshot of cutting edge research, disseminating recent developments in the field of design education, design research and new product development.