Miracle-dz/UniFAR-FTUs huggingface dataset:
The Story of the Little Blue Box: A Tribute to Siegfried Hünig

Abstract The tetracationic cyclophane, cyclobis(paraquat‐p‐phenylene), also known as the little blue box, constitutes a modular receptor that has facilitated the discovery of many host–guest complexes and mechanically interlocked molecules during the past 35 years. Its versatility in binding small π‐donors in its tetracationic state, as well as forming trisradical tricationic complexes with viologen radical cations in its doubly reduced bisradical dicationic state, renders it valuable for the construction of various stimuli‐responsive materials. Since the first reports in 1988, the little blue box has been featured in over 500 publications in the literature. All this research activity would not have been possible without the seminal contributions carried out by Siegfried Hünig, who not only pioneered the syntheses of viologen‐containing cyclophanes, but also revealed their rich redox chemistry in addition to their ability to undergo intramolecular π‐dimerization. This Review describes how his pioneering research led to the design and synthesis of the little blue box, and how this redox‐active host evolved into the key component of molecular shuttles, switches, and machines.
Multiple Nf1 Schwann cell populations reprogram the plexiform neurofibroma tumor microenvironment

To define alterations early in tumor formation, we studied nerve tumors in neurofibromatosis 1 (NF1), a tumor predisposition syndrome. Affected individuals develop neurofibromas, benign tumors driven by NF1 loss in Schwann cells (SCs). By comparing normal nerve cells to plexiform neurofibroma (PN) cells using single-cell and bulk RNA sequencing, we identified changes in 5 SC populations, including a de novo SC progenitor–like (SCP-like) population. Long after Nf1 loss, SC populations developed PN-specific expression of Dcn, Postn, and Cd74, with sustained expression of the injury response gene Postn and showed dramatic expansion of immune and stromal cell populations; in corresponding human PNs, the immune and stromal cells comprised 90% of cells. Comparisons between injury-related and tumor monocytes/macrophages support early monocyte recruitment and aberrant macrophage differentiation. Cross-species analysis verified each SC population and unique conserved patterns of predicted cell-cell communication in each SC population. This analysis identified PROS1-AXL, FGF-FGFR, and MIF-CD74 and its effector pathway NF-κB as deregulated in NF1 SC populations, including SCP-like cells predicted to influence other types of SCs, stromal cells, and/or immune cells in mouse and human. These findings highlight remarkable changes in multiple types of SCs and identify therapeutic targets for PN.
Nonlinear secret sharing immune against cheating

The paper investigates the design of secret sharing that is immune against cheating (as defined by the Tompa-Woll attack). We examine secret sharing with binary shares and secrets. Bounds on the probability of successful cheating are given for two cases. The first case relates to secret sharing based on bent functions and results in a non-perfect scheme. The second case considers perfect secret sharing built on highly nonlinear balanced Boolean functions.
Outcomes of Convalescent Plasma with Defined High versus Lower Neutralizing Antibody Titers against SARS-CoV-2 among Hospitalized Patients: CoronaVirus Inactivating Plasma (CoVIP) Study

In this study, in a high-risk population of patients admitted for COVID-19, we found an earlier time to hospital discharge among participants receiving CCP with nAb titers of >1:640 compared with participants receiving CCP with a lower nAb titer and no CCP-related AEs. The significance of our research is in identifying a dose response of CCP and clinical outcomes based on nAb titer. ABSTRACT COVID-19 convalescent plasma (CCP) was an early and widely adopted putative therapy for severe COVID-19. Results from randomized control trials and observational studies have failed to demonstrate a clear therapeutic role for CCP for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Underlying these inconclusive findings is a broad heterogeneity in the concentrations of neutralizing antibodies (nAbs) between different CCP donors. We conducted this study to evaluate the effectiveness and safety of nAb titer-defined CCP in adults admitted to an academic referral hospital. Patients positive by a SARS-CoV-2 nucleic acid amplification test and with symptoms for <10 days were eligible. Participants received either CCP with nAb titers of >1:640 (high-titer group) or ≥1:160 to 1:640 (standard-titer group) in addition to standard of care treatments. The primary clinical outcome was time to hospital discharge, with mortality and respiratory support evaluated as secondary outcomes. Adverse events were contrasted by CCP titer. Between 28 August and 4 December 2020, 316 participants were screened, and 55 received CCP, with 14 and 41 receiving high- versus standard-titer CCP, respectively. Time to hospital discharge was shorter among participants receiving high- versus standard-titer CCP, accounting for death as a competing event (hazard ratio, 1.94; 95% confidence interval [CI], 1.05 to 3.58; Gray’s P = 0.02). Severe adverse events (SAEs) (≥grade 3) occurred in 4 (29%) and 23 (56%) of participants receiving the high versus standard titer, respectively, by day 28 (risk ratio, 0.51; 95% CI, 0.21 to 1.22; Fisher’s P = 0.12). There were no observed treatment-related AEs. (This study has been registered at ClinicalTrials.gov under registration no. NCT04524507). IMPORTANCE In this study, in a high-risk population of patients admitted for COVID-19, we found an earlier time to hospital discharge among participants receiving CCP with nAb titers of >1:640 compared with participants receiving CCP with a lower nAb titer and no CCP-related AEs. The significance of our research is in identifying a dose response of CCP and clinical outcomes based on nAb titer. Although limited by a small study size, these findings support further study of high-nAb-titer CCP defined as >1:640 in the treatment of COVID-19.
CRISPRactivation-SMS, a message for PAM sequence independent gene up-regulation in Escherichia coli

Abstract Governance of the endogenous gene regulatory network enables the navigation of cells towards beneficial traits for recombinant protein production. CRISPRactivation and interference provides the basis for gene expression modulation but is primarily applied in eukaryotes. Particularly the lack of wide-ranging prokaryotic CRISPRa studies might be attributed to intrinsic limitations of bacterial activators and Cas9 proteins. While bacterial activators need accurate spatial orientation and distancing towards the target promoter to be functional, Cas9-based CRISPR tools only bind sites adjacent to NGG PAM sequences. These circumstances hampered Cas9-guided activators from mediating the up-regulation of endogenous genes at precise positions in bacteria. We could overcome this limitation by combining the PAM independent Cas9 variant SpRY and a CRISPRa construct using phage protein MCP fused to transcriptional activator SoxS. This CRISPRa construct, referred to as SMS, was compared with previously reported CRISPRa constructs and showed up-regulation of a reporter gene library independent of its PAM sequence in Escherichia coli. We also demonstrated down-regulation and multi-gene expression control with SMS at non-NGG PAM sites. Furthermore, we successfully applied SMS to up-regulate endogenous genes, and transgenes at non-NGG PAM sites, which was impossible with the previous CRISPRa construct.
Dynamic changes in perfectionism dimensions and psychological distress among adolescents assessed before and during the COVID-19 pandemic.

This prospective longitudinal study evaluated changes in psychological distress among adolescents, pre-pandemic to intra-pandemic, the extent to which within-person and between-person differences in trait multidimensional perfectionism were associated with such changes, and the role of stress in explaining associations between perfectionism and psychological distress. Adolescents (N = 187; 80% female; 78% White, 7% Asian Canadian, 2% Indigenous Peoples in Canada, 2% Black or African Canadian, 2% Latin Canadian, or 9% Other; Mage = 17.96 years) completed online surveys assessing perfectionism (i.e., self-oriented perfectionism and socially prescribed perfectionism), depression, anxiety, and stress pre-pandemic (i.e., March 12, 2020 or earlier) and during Ontario, Canada's first (i.e., March 13, 2020 to July 24, 2020) and second (December 26, 2020 to February 7, 2021) government-mandated lockdowns. Between-person differences and within-person changes in multidimensional trait perfectionism were associated with increases in psychological distress and perceived stress. Perceived stress served as an intermediary pathway linking multidimensional trait perfectionism to psychological distress during the pandemic.
The Luminous Type Ic Supernova 1992ar at z = 0.145

We present spectroscopic and photometric observations of SN 1992ar, the most distant supernova (SN) in the Calán/Tololo Survey. We compare its spectrum with those of nearby Type Ia and Ic SNe and conclude that the latter type is a better match to SN 1992ar. Using K-corrections based on the spectra of well-observed Type Ic and Ia SNe, we compute different possible rest-frame light curves of SN 1992ar and compare them with those of representative SNe of each type observed in the nearby universe. From the photometry and the spectra, we are able to conclude that SN 1992ar cannot be matched by any known example of a Type Ia SN. Even though the data set collected is fairly complete (one spectrum and 10 photometric points), it is not possible to decide whether SN 1992ar was a fast Type Ic SN, like SN 1994I, or a slow one, like SN 1983V. The absolute V magnitudes at maximum implied by each of these possibilities are -19.2 and -20.2, respectively. The latter would make SN 1992ar one of the brightest SNe on record. SN 1992ar, hence, illustrates the problem of contamination faced by the high-z Type Ia SNe samples whose luminosity distances are used to determine the cosmological parameters of the universe. We present observational criteria to distinguish the two SN types when the Si II 6355 Å line is redshifted out of the sensitivity range of typical CCD detectors and discuss the effect that these luminous Type Ic SNe would have on the measured cosmological parameters, if not removed from the high-z Type Ia SN samples.
Flavor Sensing in Utero and Emerging Discriminative Behaviors in the Human Fetus

The diet of pregnant women exposes fetuses to a variety of flavors consisting of compound sensations involving smell, taste, and chemesthesis. The effects of such prenatal flavor exposure on chemosensory development have so far been measured only postnatally in human infants. Here, we report the first direct evidence of human fetal responsiveness to flavors transferred via maternal consumption of a single-dose capsule by measuring frame-by-frame fetal facial movements. Pregnant women and their fetuses based in the northeast of England were involved in this study from 32 to 36 weeks’ gestation. Fetuses exposed to carrot flavor (n = 35) showed “lip-corner puller” and “laughter-face gestalt” more frequently, whereas fetuses exposed to kale flavor (n = 34) showed more “upper-lip raiser,” “lower-lip depressor,” “lip stretch,” “lip presser,” and “cry-face gestalt” in comparison with the carrot group and a control group not exposed to any flavors (n = 30). The complexity of facial gestalts increased from 32 to 36 weeks in the kale condition, but not in the carrot condition. Findings of this study have important implications for understanding the earliest evidence for fetal abilities to sense and discriminate different flavors.
Pain‐autonomic measures reveal nociceptive sensitization in complex regional pain syndrome

Allodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism‐based treatment strategies.
Elementary Differential Geometry

The link between the physical world and its visualization is geometry. This easy-to-read, generously illustrated textbook presents an elementary introduction to differential geometry with emphasis on geometric results. Avoiding formalism as much as possible, the author harnesses basic mathematical skills in analysis and linear algebra to solve interesting geometric problems, which prepare students for more advanced study in mathematics and other scientific fields such as physics and computer science. The wide range of topics includes curve theory, a detailed study of surfaces, curvature, variation of area and minimal surfaces, geodesics, spherical and hyperbolic geometry, the divergence theorem, triangulations, and the Gauss–Bonnet theorem. The section on cartography demonstrates the concrete importance of elementary differential geometry in applications. Clearly developed arguments and proofs, colour illustrations, and over 100 exercises and solutions make this book ideal for courses and self-study. The only prerequisites are one year of undergraduate calculus and linear algebra.
ASYMPTOTIC DISTRIBUTION OF NUMBER OF DISTINCT OBSERVATIONS AMONG A SAMPLE FROM MIXTURE OF DIRICHLET PROCESSES

Let X 1 ; X 2 ; (cid:1) (cid:1) (cid:1) ; X n be a sample of size n from a random discrete distribution P on the real line R . If we consider i and j are equivalent in case of X i = X j , this equivalence relation give a random partition of N n = f 1 ; 2 ; (cid:1) (cid:1) (cid:1) ; n g . In the case where P is given by a mixture of Dirichlet processes, we discuss the convergence in distribution of the number K n of distinct components of the random partition of N n .
Neonatal hyperoxia in mice triggers long-term cognitive deficits via impairments in cerebrovascular function and neurogenesis

Preterm birth is the leading cause of death in children under 5 years of age. Premature infants who receive life-saving oxygen therapy often develop bronchopulmonary dysplasia (BPD), a chronic lung disease. Infants with BPD are at a high risk of abnormal neurodevelopment, including motor and cognitive difficulties. While neural progenitor cells (NPCs) are crucial for proper brain development, it is unclear whether they play a role in BPD-associated neurodevelopmental deficits. Here, we show that hyperoxia-induced experimental BPD in newborn mice led to lifelong impairments in cerebrovascular structure and function as well as impairments in NPC self-renewal and neurogenesis. A neurosphere assay utilizing nonhuman primate preterm baboon NPCs confirmed impairment in NPC function. Moreover, gene expression profiling revealed that genes involved in cell proliferation, angiogenesis, vascular autoregulation, neuronal formation, and neurotransmission were dysregulated following neonatal hyperoxia. These impairments were associated with motor and cognitive decline in aging hyperoxia-exposed mice, reminiscent of deficits observed in patients with BPD. Together, our findings establish a relationship between BPD and abnormal neurodevelopmental outcomes and identify molecular and cellular players of neonatal brain injury that persist throughout adulthood that may be targeted for early intervention to aid this vulnerable patient population.
Genital mycobacteriosis caused by Mycobacterium marinum detected in two captive sharks by peptide nucleic acid–fluorescence in situ hybridization

Abstract Mycobacterium marinum is a prevalent nontuberculous mycobacterium (NTM)‐infecting teleosts. Conversely, little is known about mycobacteriosis in elasmobranchs, and M. marinum infection has never been reported from the subclass. This study investigated the histopathological characteristics and localization of this mycobacterium through molecular analysis of two captive sharks, a scalloped hammerhead Sphyrna lewini and a Japanese bullhead shark Heterodontus japonicus, exhibited in the same aquarium tank. We detected genital mycobacteriosis caused by M. marinum infection using molecular analyses, including polymerase chain reaction (PCR) and DNA sequencing targeting the 60 kDa heat‐shock protein gene (hsp65), and peptide nucleic acid–fluorescence in situ hybridization (PNA‐FISH) targeting the 16S rRNA gene. Both sharks showed granulomas in connective tissues of the gonads without central necrosis or surrounding fibrous capsules, which is unlike the typical mycobacterial granulomas seen in teleosts. This study reveals that elasmobranchs can be aquatic hosts of M. marinum. Because M. marinum is a representative waterborne NTM and a potential zoonotic agent, cautious and intensive research is needed to overcome a lack of data on the relationship between NTM and the aquatic environment in association with this subclass of Chondrichthyes.
Estimation Under Stochastic Differential Equations

Stochastic approaches are used in modern financial analysis to explore the underlying dynamics of securities like stocks and options. Statistical modeling and inferences within this aspect is an important concern because pricing errors could lead to serious economic losses. In this thesis, statistical estimation motivated by real applications are developed for inferences under stochastic diffusion processes using tensor method and kernel smooth method. We consider in Chapter 2 parameter estimation for multi-factor stochastic processes defined by stochastic differential equations. The class of processes considered are multivariate diffusion which are popular processes in modeling the dynamics of financial assets. We quantify the bias and variance by developing theoretical expansions for a large class of estimators which includes as special cases estimators based on the maximum likelihood, approximate likelihood and discretizations. We apply the proposed methods to evaluate bias in estimated contingent claims. We also provide simulation results for a set of popular multi-factor processes to confirm our theory. Our Chapter 3 is dedicated to improve the estimation of the market volatility, specifically the VIX index introduced by Chicago Board Option Exchange (CBOE). This index provides a way to measure the 30-day expected volatility of the S & P 500 index. Among a few ways to estimate it, the CBOE and the Goldman Sachs had developed an estimator based on the concept of fair value of future variance. In realizing the discretization error, truncation error, and the approximation error in their estimator, as well as the possible option pricing errors involved, we propose a new method that combines the CBOE method and the kernel smoothing method. We derive the weak convergence property of our estimator. Simulation is run to justify the improvement.
Ethylene response factor ERF.D7 activates Auxin response factor 2 paralogs to regulate tomato fruit ripening.

Despite the obligatory role of ethylene in climacteric fruit ripening and the identification of 77 ethylene response factors (ERFs) in the tomato (Solanum lycopersicum) genome, the role of few ERFs has been validated in the ripening process. Here, using a comprehensive morpho-physiological, molecular and biochemical approach, we demonstrate the regulatory role of Ethylene Response Factor D7 (SlERF.D7) in tomato fruit ripening. SlERF.D7 expression positively responded to exogenous ethylene and auxin treatments, most likely in a Ripening Inhibitor (RIN)-independent manner. SlERF.D7 overexpression promoted ripening, and its silencing had the opposite effect. Alterations in its expression modulated ethylene production, pigment accumulation, and fruit firmness. Consistently, genes involved in ethylene biosynthesis and signalling, lycopene biosynthesis, and cell wall loosening were upregulated in the overexpression lines and downregulated in RNAi lines. These transgenic lines also accumulated altered levels of IAA at late-breaker stages. A positive association between Auxin Response Factor 2 (ARF2) paralog's transcripts and SlERF.D7 mRNA levels and that SlARF2A and SlARF2B are direct targets of SlERF.D7 underpinned the perturbed auxin-ethylene crosstalk for the altered ripening program observed in the transgenic fruits. Overall, this study uncovers that SlERF.D7 positively regulates SlARF2A/B abundance to amalgamate auxin and ethylene signalling pathways for controlling tomato fruit ripening.
Population genetic models for the spatial spread of adaptive variants: A review in light of SARS-CoV-2 evolution

Theoretical population genetics has long studied the arrival and geographic spread of adaptive variants through the analysis of mathematical models of dispersal and natural selection. These models take on a renewed interest in the context of the COVID-19 pandemic, especially given the consequences that novel adaptive variants have had on the course of the pandemic as they have spread through global populations. Here, we review theoretical models for the spatial spread of adaptive variants and identify areas to be improved in future work, toward a better understanding of variants of concern in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) evolution and other contemporary applications. As we describe, characteristics of pandemics such as COVID-19—such as the impact of long-distance travel patterns and the overdispersion of lineages due to superspreading events—suggest new directions for improving upon existing population genetic models.
Carbohydrate utilization by the gut microbiome determines host health responsiveness to whole grain type and processing methods

ABSTRACT Little is known about how interactions among grain processing, grain type, and carbohydrate utilization (CU) by the microbiome influence the health benefits of whole grains. Therefore, two whole grains – brown rice and whole wheat – and two processing methods – boiling (porridge) and extrusion – were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high but not low CU microbiome also gained more weight and fat over time and were less glucose tolerant when consuming extruded grain diets. In high CU microbiome mice, the exacerbated negative health outcomes associated with extrusion were related to altered abundances of Lachnospiraceae and Ruminococcaceae as well as elevated sugar degradation and colonic acetate production. The amplicon sequence variants (ASVs) associated with extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. In conclusion, mice harboring both high and low CU microbiomes responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health. Abbreviations: CU- carbohydrate utilization; SCFA- short-chain fatty acids; GF- germ-free; HMA, human-microbiome associated; ipGTT- intraperitoneal glucose tolerance test; HOMA-IR- Homeostatic Model Assessment for Insulin Resistance; AUC- area under the glycemia curve; ASV- amplicon sequence variant; lf- low-fat; wd- Western diet; wd_wwp- Western diet containing whole wheat porridge; wd_wwe- Western diet containing whole wheat extrudate; wd_bre- Western diet containing brown rice extrudate; wd_extr- Western diet containing either whole wheat or brown rice extrudate.