Broad Family Research Articles

An interpersonal form of faith

AbstractAn athlete has faith in her unathletic partner to run a marathon, a teacher has faith in her currently poor‐performing students to improve in the future, and your friend has faith in you to succeed in the difficult project that you have been pursuing, even, and especially, when your chance of failing is non‐trivial. This paper develops and defends a relational view of interpersonal faith by considering four interesting phenomena: first, in virtue of placing faith in someone, we stand in solidarity with that person; second, interpersonal faith is called for during moments of difficulty, but it can seem inappropriate during moments of ease; third, one's faith in others can feel unwelcomed, and can be rejected; and fourth, when interpersonal faith is frustrated, disappointment, rather than resentment, is warranted. I propose that when the faithor (e.g., your friend) places faith in the faithee (e.g., you) to φ, the faithor does something close to inviting the faithee to (re)commit to φ‐ing. This invitation‐like move, once properly taken up by the faithee, puts both sides of the faith in a new kind of normative relationship that is in the same broad family as a promissory relationship, albeit with a different normative profile.

LEA_4 motifs function alone and in conjunction with synergistic cosolutes to protect a labile enzyme during desiccation.

Organisms from all kingdoms of life depend on Late Embryogenesis Abundant (LEA) proteins to survive desiccation. LEA proteins are divided into broad families distinguished by the presence of family-specific motif sequences. The LEA_4 family, characterized by 11-residue motifs, plays a crucial role in the desiccation tolerance of numerous species. However, the role of these motifs in the function of LEA_4 proteins is unclear, with some studies finding that they recapitulate the function of full-length LEA_4 proteins in vivo, and other studies finding the opposite result. In this study, we characterize the ability of LEA_4 motifs to protect a desiccation-sensitive enzyme, citrate synthase (CS), from loss of function during desiccation. We show here that LEA_4 motifs not only prevent the loss of function of CS during desiccation but also that they can do so more robustly via synergistically interactions with cosolutes. Our analysis further suggests that cosolutes induce synergy with LEA_4 motifs in a manner that correlates with transfer free energy. This research advances our understanding of LEA_4 proteins by demonstrating that during desiccation their motifs can protect specific clients to varying degrees and that their protective capacity is modulated by their chemical environment. Our findings extend beyond the realm of desiccation tolerance, offering insights into the interplay between IDPs and cosolutes. By investigating the function of LEA_4 motifs, we highlight broader strategies for understanding protein stability and function.

Practical realization of chiral nonlinearity for strong topological protection

Nonlinear topology has been much less inquired compared to its linear counterpart. Existing advances have focused on nonlinearities of limited magnitudes and fairly homogeneous types. As such, the realizations have rarely been concerned with the requirements for nonlinearity. Here we explore nonlinear topological protection by determining nonlinear rules and demonstrate their relevance in real-world experiments. We take advantage of chiral symmetry and identify the condition for its continuation in general nonlinear environments. Applying it to one-dimensional topological lattices, we show possible evolution paths for zero-energy edge states that preserve topologically nontrivial phases regardless of the specifics of the chiral nonlinearities. Based on an acoustic prototype design with non-local nonlinearities, we theoretically, numerically, and experimentally implement the nonlinear topological edge states that persist in all nonlinear degrees and directions without any frequency shift. Our findings unveil a broad family of nonlinearities compatible with topological non-triviality, establishing a solid ground for future drilling in the emergent field of nonlinear topology.

A Japanese family of hereditary diffuse gastric cancer with a germline pathogenic variant of CTNN1A detected via comprehensive genome profiling.

CTNNA1 codes α-1 catenin, a molecule that functions in intercellular adhesion in combination with E-cadherin (coded by CDH1). A germline pathogenic variant (GPV) of CTNNA1 increases the risk of hereditary diffuse gastric cancer (HDGC); however, this GPV has not been reported in Japan. A 35-year-old Japanese man with an advanced gastric cancer underwent comprehensive genome profiling (CGP), which led to the detection of a CTNNA1 GPV (p.Q662*). His gastric cancer tissues demonstrated a loss of α-1 catenin expression. His mother with a history of gastric signet-ring cell carcinoma had undergone genetic counseling 2years ago, because of her broad family history of young-onset gastric cancer. Then, she had undergone germline multigene panel testing (MGPT) that included CDH1 but not CTNNA1, and no GPV had been detected. Here, Japanese precision cancer medicine revealed a GPV of a gene rarely associated with HDGC, that could not be detected by common MGPTs.

Relative Performance of Frequentist and Bayesian Methods for Incorporating External Controls: A Case Study with Patient Level Data from the DapaHF Trial

Some populations, such as rare diseases, cannot be studied in randomized clinical trials due to feasibility or ethical considerations. One way to address this is to incorporate external data to augment what is learned in the trial about a standard of care control arm. Statistically, there are two broad families of approaches for incorporating external controls for comparisons, propensity score-based methods (PSM) and Bayesian dynamic borrowing (BDB) methods. We evaluate these methods in terms of bias and precision with patient-level data from a large cardiovascular trial. We consider a hybrid trial setting, where external data augments a concurrently randomized control arm, and a single-arm trial using external data as a formal comparator. We evaluate performance with and without systemic biases between the trial and the external controls. The performance of PSM depends on the extent to which covariates are associated with the outcome. The performance of BDB depends on the choice of modelling parameters. Overall, there is a precision-bias trade-off in the use of external data. In practice, it is appropriate that the observed treatment effect needs to not just achieve statistical significance, but also qualitatively overwhelm the possibility that the observed treatment effect is driven by systematic differences between data sources.

Toward germanate ceramics Li2AGeO4:Nd3+ (A = Zn, Mg) emitting near‐infrared radiation

AbstractGermanate ceramics Li2ZnGeO4:Nd3+ and Li2MgGeO4:Nd3+ have been studied for near‐infrared (IR) luminescence applications. The phase identification showed that both ceramic compounds crystallized in a monoclinic lattice, characteristic of a broad family of germanate olivines. Near‐IR luminescence spectra have been analyzed for Li2AGeO4:Nd3+ (A = Zn, Mg) under different excitation wavelengths. Near‐IR emission bands observed in the second biological window correspond to the ceramic host as well as 4F3/2 → 4I11/2 and 4F3/2 → 4I13/2 transitions of Nd3+ ions, respectively. Based on luminescence spectra and their decays, several spectroscopic parameters for un‐doped and Nd3+‐doped ceramic samples were determined. The experimental results for germanate olivines containing Nd3+ ions suggest that ceramic host gives important contribution to near‐IR luminescence at second biological window.

Identification and Characterization of Two Aryl Sulfotransferases from Deep-Sea Marine Fungi and Their Implications in the Sulfation of Secondary Metabolites.

Sulfation plays a critical role in the biosynthesis of small molecules, regulatory mechanisms such as hormone signaling, and detoxification processes (phase II enzymes). The sulfation reaction is catalyzed by a broad family of enzymes known as sulfotransferases (SULTs), which have been extensively studied in animals due to their medical importance, but also in plant key processes. Despite the identification of some sulfated metabolites in fungi, the mechanisms underlying fungal sulfation remain largely unknown. To address this knowledge gap, we conducted a comprehensive search of available genomes, resulting in the identification of 174 putative SULT genes in the Ascomycota phylum. Phylogenetic analysis and structural modeling revealed that these SULTs belong to the aryl sulfotransferase family, and they are divided into two potential distinct clusters of PAPS-dependent SULTs within the fungal kingdom. SULT genes from two marine fungi isolated from deep-sea hydrothermal vents, Hortaea werneckii UBOCC-A-208029 (HwSULT) and Aspergillus sydowii UBOCC-A-108050 SULT (AsSULT), were selected as representatives of each cluster. Recombinant proteins were expressed in Escherichia coli and biochemically characterized. HwSULT demonstrated high and versatile activity, while AsSULT appeared more substrate-specific. Here, HwSULT was used to sulfate the mycotoxin zearalenone, enhancing its cytotoxicity toward healthy feline intestinal cells.

(Invited) EIS Measurements in Ionic Liquids: Monitoring of the Electrodeposition of a Thin Metal Layer

Ionic liquids are increasingly used in a variety of applications, including electrolytes for electrochemical devices, solvents for the electroplating of thin metal layers, and corrosion inhibitors. Ionic liquids are a broad family of solvents whose physicochemical properties (viscosity, conductivity, etc.) depend on the nature of the anion and cation that form them. Some are protic with a labile proton, others are non-protic. Electrodeposition of metal in a protic ionic liquid such as ethylammonium nitrate (EAN) can be carried out at ambient temperature whereas higher temperatures are frequently performed in a non-protic ionic liquid. In addition, the electrodeposition of several elements is simple, yielding to an alloy whose composition and morphology are determined by the electroplating conditions. In this presentation, we will show how Electrochemical Impedance Spectroscopy (EIS) which is an efficient technique for characterizing the solid-liquid interface and investigating the electrodeposition mechanisms, can help for working in these media.In a first part, we will look at the electrodeposition of Nickel, Cobalt and their mixtures in EAN, a pure protic ionic liquid, and discuss EIS results. In a second part, we will take advantage of the low vapor pressure of ILs, and we will discuss how we can characterize a material reactivity by performing electrochemical measurements in a 3 - 5 µL drop of ionic liquid.

The Impact of HLA-A29 Homozygosity and of the Second HLA-A Allele on Susceptibility and Severity of Birdshot Chorioretinitis.

HLA-A29 is the main susceptibility factor for birdshot chorioretinitis (BSCR). Our study assessed the impact of the second HLA-A allele alongside HLA-A29 on BSCR severity and susceptibility, focusing on HLA-A29 homozygous patients and those with alleles from the HLA-Aw19 group. We included 120 additional cases to our previous analysis of 286 patients with BSCR, all HLA-A29 positive. Patients were categorized based on the second allele being also HLA-A29 (A29/nonA29 vs. A29/A29) or belonging to the HLA-Aw19 family, including A29, A30, A31, and A33 (A29/nonAw19 vs. A29/Aw19). HLA-A32 was analyzed separately (A29/nonA32 vs. A29/A32). The prevalence of these groups among patients with BSCR was compared with their frequencies in a sample of 151,997 French subjects. Disease severity was approximated by assessing disease onset and visual function at the last visit and was compared between patient groups. When comparing the HLA-A29-positive patients with BSCR to HLA-A29-positive French subjects, we found an overrepresentation of HLA-A29 for the second HLA-A allele (χ² = 4.34; P = 0.037; odds ratio, 1.57; confidence interval, 1.01-2.44). Within the HLA-Aw19 broad antigen family, HLA-A32 was found to be under-represented (χ² = 6.15; P = 0.013; odds ratio, 0.40; confidence interval, 0.19-0.85). The nature of the second HLA-A allele did not impact disease severity. Homozygosity for HLA-A29 increased the risk of developing BSCR without affecting disease severity. The under-representation of HLA-A32 in patients with BSCR suggests a potential protective role.

Enzymatic removal of the sulfa drugs sulfamethoxazole and sulfamerazine from synthetic wastewater by soybean peroxidase.

Sulfa drugs are a broad family of antibiotics widely used in the treatment of a range of infections. They have been found in surface and groundwater, as well as in sewage and effluent (treated sewage and sludge) of municipal or industrial wastewater treatment plants in concentrations of ng/L to >g/L. The continued presence of these so-called emerging contaminants (ECs) and their metabolites can cause adverse ecological effects, including bacterial resistance, even at very low concentrations. In this study, the first aim was to explore the feasibility of oxidation processes catalyzed by soybean peroxidase as an eco-friendly and economically advantageous alternative method for the conversion of the sulfonamides, sulfamethoxazole, and sulfamerazine. Optimum conditions were determined for 0.2 and 0.1 mM of the respective substrates. Optimum pHs were 1.6 and 3.6, respectively. Optimum molar peroxide ratios were 3.0 and 2.5 for the respective substrates. Enzyme activities of 4 and 2 U/mL showed 83 and 76% removal. With the redox mediator hydroxybenzotriazole, optimum pH was 3.6 for both substrates, optimum peroxide ratios were 1.5 and 1.25, and the optimum enzyme requirement decreased 40-fold. A time course study was conducted under optimal mediated conditions to determine the initial first-order rate constant and half-life of each substrate, from which half-lives were 0.0804 and 0.0608 min, normalized for substrate concentration. These two values were among the lowest when compared to 25 other compounds studied with the same enzyme. Finally, the oligomerization products of enzymatic treatment were characterized by mass spectrometry and showed the formation of oxidative dimers and azo compounds.

Self-organized efficient transmission in dynamic networks

Effective protocols are needed to ensure successful transmission of signals, messages, or parcels through a network of intermediaries. Existing studies often overlook real-world constraints such as limited resources. We investigate the design of efficient and robust transmission strategies in dynamic networks subject to dissipation and resource limited node activity, as in wireless sensor networks. We find that dissipation and randomness can enhance transmission efficiency and network resilience. For a broad family of protocols, a self-organized dynamics assures global connectivity, even in the limit of low density of links, where random networks fail.

Dwarfism-related skeletal dysplasia in Italy. Multi-analytic study of 8th century CE human remains from Azzio (Varese) and biocultural implications of a pathology

Skeletal dysplasias are a broad family of genetic disorders, often challenging to diagnose even in clinical literature without molecular analysis. Some cases of possible skeletal dysplasia have also been identified in osteoarchaeological samples, although achieving a definitive diagnosis is fraught with difficulties. This paper presents the analysis of the osteological remains of AZ-III-3, discovered in the archaeological context of the Church of Sant’Antonio and Eusebio in Azzio (Varese province, Italy). The study aims to demonstrate that even with limited skeletal elements, a diagnosis can be hypothesised using macroscopic morphometric and radio diagnostic techniques. These methods, compared with clinical and paleopathological literature, have allowed for the identification of a rare Italian case of dwarfism-related skeletal dysplasia. This contribution seeks to address the biocultural presence of individuals affected by these skeletal dysplasias, listing and discussing all published Italian cases, including that of AZ-III-3, whose chronological framework was established through both archaeological context analysis and 14C dating.

Factors associated with caregiver strain among mothers and fathers of children with advanced cancer.

To characterize caregiver experiences in the context of advanced pediatric cancer by identifying individual (i.e., demographic factors, stress) and family context factors (i.e., family roles, social support) associated with caregiver strain. Families of children (ages 5-25) with advanced cancer (i.e., physician-estimated prognosis < 60%, relapsed/refractory disease) were recruited from a large children's hospital. Mothers (n = 55; 87% White) and fathers (n = 30; 83% White) reported on their caregiver strain, cancer-specific stress, general stress, social support, division of 7 family roles (e.g., medical care of ill child, household chores), and their satisfaction with each role. Parents reported moderate caregiver strain, cancer-specific stress, and general stress, and high social support and satisfaction with family roles. Fathers reported family roles were shared equally, whereas mothers reported either sharing roles or completing them independently. When accounting for income and partnership status, greater caregiver strain for mothers was associated with greater general stress, greater satisfaction with family roles, and lower social support. For fathers, greater caregiver strain was associated only with greater cancer-specific stress. In the context of advanced pediatric cancer, fathers may experience caregiver strain as cancer-specific stress increases, whereas mothers' strain may depend on broader family and social factors. Psychosocial providers should address general and cancer-specific stress within families, and provide resources for enhancing mothers' social support. Additional research is needed with larger, more diverse samples to inform future intervention approaches.

Tutorial on machine learning for acoustics

Acoustic data provide scientific and engineering insights in fields ranging from biology and communications to ocean and Earth science. We survey the recent advances and transformative potential of machine learning (ML), including deep learning, in the field of acoustics. ML is a broad family of techniques, which are often based in statistics, for automatically detecting and utilizing patterns in data. We have ML examples from ocean acoustics, room acoustics, and personalized spatial audio. For room acoustics, we take room impulse responses (RIR) generation as an example application. For personalized spatial audio, we take head-related transfer function (HRTF) up-sampling as examples. The tutorial will conclude with a set of Jupiter notebook examples on GitHub demonstrating ML benefits.

Tail variance and confidence of using tail conditional expectation: analytical representation, capital adequacy, and asymptotics

Abstract In this paper, we explore the applications of Tail Variance (TV) as a measure of tail riskiness and the confidence level of using Tail Conditional Expectation (TCE)-based risk capital. While TCE measures the expected loss of a risk that exceeds a certain threshold, TV measures the variability of risk along its tails. We first derive analytical formulas of TV and TCE for a large variety of probability distributions. These formulas are useful instruments for relevant research works on tail risk measures. We then propose a distribution-free approach utilizing TV to estimate the lower bounds of the confidence level of using TCE-based risk capital. In doing so, we introduce sharpened conditional probability inequalities, which halve the bounds of conventional Markov and Cantelli inequalities. Such an approach is easy to implement. We further investigate the characterization of tail risks by TV through an exploration of TV’s asymptotics. A distribution-free limit formula is derived for the asymptotics of TV. To further investigate the asymptotic properties, we consider two broad distribution families defined on tails, namely, the polynomial-tailed distributions and the exponential-tailed distributions. The two distribution families are found to exhibit an asymptotic equivalence between TV and the reciprocal square of the hazard rate. We also establish asymptotic relationships between TCE and VaR for the two families. Our asymptotic analysis contributes to the existing research by unifying the asymptotic expressions and the convergence rate of TV for Student-t distributions, exponential distributions, and normal distributions, which complements the discussion on the convergence rate of univariate cases in [28]. To show the usefulness of our results, we present two case studies based on real data from the industry. We first show how to use conditional inequalities to assess the confidence of using TCE-based risk capital for different types of insurance businesses. Then, for financial data, we provide alternative evidence for the relationship between the data frequency and the tail categorization by the asymptotics of TV.

Bounds on the number of squares in recurrence sequences

We investigate the number of squares in a very broad family of binary recurrence sequences with u0=1. We show that there are at most two distinct squares in such sequences (the best possible result), except under very special conditions where we prove there are at most three such squares.

Iridium-Catalyzed C-H Borylations: Regioselective Functionalizations of Calix[4]arene Macrocycles.

We report iridium-catalyzed C-H borylations for the regioselective synthesis of distally disubstituted calix[4]arene macrocycles. The atom- and step-economical method led to a broad family of calix[4]arenes in good yields and functional group tolerance. The synthetic utility of the C-H borylation protocol was finally illustrated with several late-stage modifications for the synthesis of elaborate calix[4]arenes frameworks, otherwise challenging to achieve with commonly employed procedures.

DeepAFT: A nonlinear accelerated failure time model with artificial neural network.

The Cox regression model or accelerated failure time regression models are often used for describing the relationship between survival outcomes and potential explanatory variables. These models assume the studied covariates are connected to the survival time or its distribution or their transformations through a function of a linear regression form. In this article, we propose nonparametric, nonlinear algorithms (deepAFT methods) based on deep artificial neural networks to model survival outcome data in the broad distribution family of accelerated failure time models. The proposed methods predict survival outcomes directly and tackle the problem of censoring via an imputation algorithm as well as re-weighting and transformation techniques based on the inverse probabilities of censoring. Through extensive simulation studies, we confirm that the proposed deepAFT methods achieve accurate predictions. They outperform the existing regression models in prediction accuracy, while being flexible and robust in modeling covariate effects of various nonlinear forms. Their prediction performance is comparable to other established deep learning methods such as deepSurv and random survival forest methods. Even though the direct output is the expected survival time, the proposed AFT methods also provide predictions for distributional functions such as the cumulative hazard and survival functions without additional learning efforts. For situations where the popular Cox regression model may not be appropriate, the deepAFT methods provide useful and effective alternatives, as shown in simulations, and demonstrated in applications to a lymphoma clinical trial study.

Imidazopyridine Family: Versatile and Promising Heterocyclic Skeletons for Different Applications.

In recent years, there has been increasing attention focused on various products belonging to the imidazopyridine family; this class of heterocyclic compounds shows unique chemical structure, versatile optical properties, and diverse biological attributes. The broad family of imidazopyridines encompasses different heterocycles, each with its own specific properties and distinct characteristics, making all of them promising for various application fields. In general, this useful category of aromatic heterocycles holds significant promise across various research domains, spanning from material science to pharmaceuticals. The various cores belonging to the imidazopyridine family exhibit unique properties, such as serving as emitters in imaging, ligands for transition metals, showing reversible electrochemical properties, and demonstrating biological activity. Recently, numerous noteworthy advancements have emerged in different technological fields, including optoelectronic devices, sensors, energy conversion, medical applications, and shining emitters for imaging and microscopy. This review intends to provide a state-of-the-art overview of this framework from 1955 to the present day, unveiling different aspects of various applications. This extensive literature survey may guide chemists and researchers in the quest for novel imidazopyridine compounds with enhanced properties and efficiency in different uses.

Intramolecular Disulfide Bridges in Voltage-Dependent Anion Channel 2 (VDAC2) Protein from Rattus norvegicus Revealed by High-Resolution Mass Spectrometry.

Voltage-Dependent Anion Channel isoforms (VDAC1, VDAC2, and VDAC3) are relevant components of the outer mitochondrial membrane (OMM) and play a crucial role in regulation of metabolism and in survival pathways. As major players in the regulation of cellular metabolism and apoptosis, VDACs can be considered at the crossroads between two broad families of pathologies, namely, cancer and neurodegeneration, the former being associated with elevated glycolytic rate and suppression of apoptosis in cancer cells, the latter characterized by mitochondrial dysfunction and increased cell death. Recently, we reported the characterization of the oxidation pattern of methionine and cysteines in rat and human VDACs showing that each cysteine in these proteins is present with a preferred oxidation state, ranging from the reduced to the trioxidized form, and such an oxidation state is remarkably conserved between rat and human VDACs. However, the presence and localization of disulfide bonds in VDACs, a key point for their structural characterization, have so far remained undetermined. Herein we have investigated by nanoUHPLC/High-Resolution nanoESI-MS/MS the position of intramolecular disulfide bonds in rat VDAC2 (rVDAC2), a protein that contains 11 cysteines. To this purpose, extraction, purification, and enzymatic digestions were carried out at slightly acidic or neutral pH in order to minimize disulfide bond interchange. The presence of six disulfide bridges was unequivocally determined, including a disulfide bridge linking the two adjacent cysteines 4 and 5, a disulfide bridge linking cysteines 9 and 14, and the alternative disulfide bridges between cysteines 48, 77, and 104. A disulfide bond, which is very resistant to reduction, between cysteines 134 and 139 was also detected. In addition to the previous findings, these results significantly extend the characterization of the oxidation state of cysteines in rVDAC2 and show that it is highly complex and presents unusual features. Data are available via ProteomeXchange with the identifier PXD044041.