Miracle-dz/UniFAR-FTUs huggingface dataset:
Shortest paths with side sensors

We present a complete characterization of shortest paths to a goal position for a vehicle with unicycle kinematics and a limited range sensor, constantly keeping a given landmark in sight. Previous work on this subject studied the optimal paths in case of a frontal, symmetrically limited Field-Of-View (FOV). In this paper we provide a generalization to the case of arbitrary FOVs, including the case that the direction of motion is not an axis of symmetry for the FOV, and even that it is not contained in the FOV. The provided solution is of particular relevance to applications using side-scanning, such as e.g. in underwater sonar-based surveying and navigation.
Ketone body 3‐hydroxybutyrate mimics calorie restriction via the Nrf2 activator, fumarate, in the retina

Calorie restriction (CR) being the most robust dietary intervention provides various health benefits. D‐3‐hydroxybutyrate (3HB), a major physiological ketone, has been proposed as an important endogenous molecule for CR. To investigate the role of 3HB in CR, we investigated potential shared mechanisms underlying increased retinal 3HB induced by CR and exogenously applied 3HB without CR to protect against ischemic retinal degeneration. The repeated elevation of retinal 3HB, with or without CR, suppressed retinal degeneration. Metabolomic analysis showed that the antioxidant pentose phosphate pathway and its limiting enzyme, glucose‐6‐phosphate dehydrogenase (G6PD), were concomitantly preserved. Importantly, the upregulation of nuclear factor erythroid 2 p45‐related factor 2 (Nrf2), a regulator of G6PD, and elevation of the tricarboxylic acid cycle's Nrf2 activator, fumarate, were also shared. Together, our findings suggest that CR provides retinal antioxidative defense by 3HB through the antioxidant Nrf2 pathway via modification of a tricarboxylic acid cycle intermediate during 3HB metabolism.
A Cost-Effectiveness Analysis of Alternative At-Home or In-Laboratory Technologies for the Diagnosis of Obstructive Sleep Apnea Syndrome

Background . Obstructive sleep apnea syndrome (OSAS) is a common disorder that affects 2% to 9% of the population. Health care policy makers have noted increased referrals for sleep studies. Objective . In this article, the authors conduct a cost-effectiveness analysis to determine the optimal technology for the diagnosis of OSAS using polysomnography (PSG) or partial sleep monitoring (PSM). Design . The target population was a hypothetical cohort of patients suspected of having OSAS. A 2-level decision tree was formulated that reflects all possible steps of OSAS diagnosis and therapy. The method represents a comprehensive strategy to determine which of the 2 systems—PSG or PSM—has cost advantages. The financial and operational aspects of OSAS diagnosis and therapy were analyzed. A sensitivity analysis was performed over all uncertain parameters (i.e., diagnostic agreement, data loss, and referral to therapy). Results . Unattended at-home sleep monitoring was the most expensive method. The combination of 1:2 PSG and attended PSM strategy was the optimal strategy with respect to financing and operations. Compared to the PSG-only strategy, this combination may lead to a 10% reduction of the annual expenditure. Conclusion . This study provides proof of concept (under a wide range of sensitivity assumptions) that the cost of sleep study techniques can be modeled. It rejects the assumption that at-home portable sleep monitoring is cost advantageous. The combination of PSG and attended PSM OSAS is the most cost-effective approach to sleep evaluation.
Epstein–Barr Virus‐Related Post‐Transplant Lymphoproliferative Disorders: Pathogenetic Insights for Targeted Therapy

Post‐transplant lymphoproliferative disorder (PTLD) is a spectrum of major, life‐threatening lymphoproliferative diseases occurring in the post‐transplant setting. The majority of PTLD is of B‐cell origin and is associated with several risk factors, the most significant being Epstein‐Barr virus (EBV) infection. EBV's in vitro transforming abilities, distinctive latency, clonality within the malignant cells and response to targeted therapies implicate a critical role in the biology of PTLD. This minireview focuses on EBV‐related PTLD pathogenesis, in particular the interplay between aspects of the EBV life cycle and latency with nonviral factors resulting in the wide spectrum of histology and clinical presentations encountered in PTLD. With the increased prevalence of transplantation a rise in the incidence of PTLD may be expected. Therefore the importance of laboratory and animal models in the understanding of PTLD and the development of novel therapeutic approaches is discussed.
Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide excision repair complex

Significance Impairment of global genome nucleotide excision repair (NER) leads to extreme sun sensitivity and predisposition to cancers. The xeroderma pigmentosum C (XPC) complex senses diverse environmentally induced DNA lesions from predominantly normal DNA, and initiates NER by recruiting downstream factors. Using unique fluorescent approaches, this study unveils previously unresolved DNA dynamics during lesion recognition by radiation-sensitive 4 (Rad4; yeast XPC ortholog) and demonstrates that Rad4 nonspecifically deforms (“twists”) the DNA before specifically recognizing (“opening”) target lesions. These results mark the first observation, to our knowledge, of DNA distortional dynamics that reflect a nonspecific search/interrogation process by a DNA repair protein that relies entirely on DNA deformability to recognize its lesions, and provides keys to understanding the protein’s ability to search rapidly and yet also reliably recognize diverse lesions. DNA damage repair starts with the recognition of damaged sites from predominantly normal DNA. In eukaryotes, diverse DNA lesions from environmental sources are recognized by the xeroderma pigmentosum C (XPC) nucleotide excision repair complex. Studies of Rad4 (radiation-sensitive 4; yeast XPC ortholog) showed that Rad4 “opens” up damaged DNA by inserting a β-hairpin into the duplex and flipping out two damage-containing nucleotide pairs. However, this DNA lesion “opening” is slow (˜5–10 ms) compared with typical submillisecond residence times per base pair site reported for various DNA-binding proteins during 1D diffusion on DNA. To address the mystery as to how Rad4 pauses to recognize lesions during diffusional search, we examine conformational dynamics along the lesion recognition trajectory using temperature-jump spectroscopy. Besides identifying the ˜10-ms step as the rate-limiting bottleneck towards opening specific DNA site, we uncover an earlier ˜100- to 500-μs step that we assign to nonspecific deformation (unwinding/“twisting”) of DNA by Rad4. The β-hairpin is not required to unwind or to overcome the bottleneck but is essential for full nucleotide-flipping. We propose that Rad4 recognizes lesions in a step-wise “twist-open” mechanism, in which preliminary twisting represents Rad4 interconverting between search and interrogation modes. Through such conformational switches compatible with rapid diffusion on DNA, Rad4 may stall preferentially at a lesion site, offering time to open DNA. This study represents the first direct observation, to our knowledge, of dynamical DNA distortions during search/interrogation beyond base pair breathing. Submillisecond interrogation with preferential stalling at cognate sites may be common to various DNA-binding proteins.
Mechanistic elucidation of the mycofactocin-biosynthetic radical S-adenosylmethionine protein, MftC

Ribosomally synthesized and posttranslationally modified peptide (RiPP) pathways produce a diverse array of natural products. A subset of these pathways depends on radical S-adenosylmethionine proteins to modify the RiPP-produced peptide. Mycofactocin biosynthesis is one example of an S-adenosylmethionine protein-dependent RiPP pathway. Recently, it has been shown that MftC catalyzes the oxidative decarboxylation of the C-terminal tyrosine (Tyr-30) on the mycofactocin precursor peptide MftA; however, this product has not been verified by techniques other than MS. Herein, we provide a more detailed study of MftC catalysis and report a revised mechanism for MftC chemistry. We show that MftC catalyzes the formation of two isomeric products. Using a combination of MS, isotope labeling, and 1H and 13C NMR techniques, we established that the major product, MftA*, is a tyramine-valine-cross-linked peptide formed by MftC through two S-adenosylmethionine-dependent turnovers. In addition, we show that the hydroxyl group on MftA Tyr-30 is required for MftC catalysis. Furthermore, we show that a substitution in the penultimate MftA Val-29 position causes the accumulation of an MftA** minor product. The 1H NMR spectrum indicates that this minor product contains an αβ-unsaturated bond that likely arises from an aborted intermediate of MftA* synthesis. The finding that MftA* is the major product formed during MftC catalysis could have implications for the further elucidation of mycofactocin biosynthesis.
Spectrophotometric determination of low levels arsenic species in beverages after ion-pairing vortex-assisted cloud-point extraction with acridine red

ABSTRACT A new, low-cost, micellar-sensitive and selective spectrophotometric method was developed for the determination of inorganic arsenic (As) species in beverage samples. Vortex-assisted cloud-point extraction (VA-CPE) was used for the efficient pre-concentration of As(V) in the selected samples. The method is based on selective and sensitive ion-pairing of As(V) with acridine red (ARH+) in the presence of pyrogallol and sequential extraction into the micellar phase of Triton X-45 at pH 6.0. Under the optimised conditions, the calibration curve was highly linear in the range of 0.8–280 µg l−1 for As(V). The limits of detection and quantification of the method were 0.25 and 0.83 µg l−1, respectively. The method was successfully applied to the determination of trace As in the pre-treated and digested samples under microwave and ultrasonic power. As(V) and total As levels in the samples were spectrophotometrically determined after pre-concentration with VA-CPE at 494 nm before and after oxidation with acidic KMnO4. The As(III) levels were calculated from the difference between As(V) and total As levels. The accuracy of the method was demonstrated by analysis of two certified reference materials (CRMs) where the measured values for As were statistically within the 95% confidence limit for the certified values.
Cosmological constraints from the 100-deg2 weak-lensing survey

We present a cosmic shear analysis of the 100-deg 2 weak-lensing survey, combining data from the CFHTLS-Wide, RCS, VIRMOS-DESCART and GaBoDS surveys. Spanning ∼100 deg 2 , with a median source redshift ∼0.78, this combined survey allows us to place tight joint constraints on the matter density parameter Ω m , and the amplitude of the matter power spectrum σ 8 , finding σ 8 (Ω m /0.24) 0.59 = 0.84 ±0.05. Tables of the measured shear correlation function and the calculated covariance matrix for each survey are included as supplementary material to the online version of this article. The accuracy of our results is a marked improvement on previous work owing to three important differences in our analysis; we correctly account for sample variance errors by including a non-Gaussian contribution estimated from numerical simulations; we correct the measured shear for a calibration bias as estimated from simulated data; we model the redshift distribution, n(z), of each survey from the largest deep photometric redshift catalogue currently available from the CFHTLS-Deep. This catalogue is randomly sampled to reproduce the magnitude distribution of each survey with the resulting survey-dependent n(z) parametrized using two different models. While our results are consistent for the n(z) models tested, we find that our cosmological parameter constraints depend weakly (at the 5 per cent level) on the inclusion or exclusion of galaxies with low-confidence photometric redshift estimates (z > 1.5). These high-redshift galaxies are relatively few in number but contribute a significant weak-lensing signal. It will therefore be important for future weak-lensing surveys to obtain near-infrared data to reliably determine the number of high-redshift galaxies in cosmic shear analyses.
Biotic stoichiometric controls on the deep ocean N:P ratio

Abstract. We re-examine what controls the deep ocean N:P ratio in the light of recent findings that the C:N:P stoichiometry of phytoplankton varies with growth rate, nutrient and light limitation, species and phylum, and that N2-fixation may be limited by Fe, temperature and/or light in large parts of the world ocean. In particular, we assess whether a systematic change in phytoplankton stoichiometry can alter the deep ocean N:P ratio. To do this we adapt recent models to include non-Redfieldian stoichiometry of phytoplankton and restriction of N2-fixers to a fraction of the surface ocean. We show that a systematic change in phytoplankton C:N:P can alter the concentrations of NO3 and PO4 in the deep ocean but cannot greatly alter their ratio, unless it also alters the N:P threshold for N2-fixation. This occurs if competitive dynamics set the N:P threshold for N2-fixation, in which case it remains close to the N:P requirement of non-fixers (rather than that of N2-fixers) and consequently so does the deep ocean N:P ratio. Then, even if N2-fixers are restricted to a fraction of the surface ocean, they reach higher densities there, minimising variations in deep ocean N:P. Theoretical limits on the N:P requirements of phytoplankton suggest that whilst the deep ocean has been well oxygenated (i.e. since the Neoproterozoic, with the possible exception of Oceanic Anoxic Events), its N:P ratio is unlikely to have varied by more than a factor of two in either direction. Within these bounds, evolutionary changes in phytoplankton composition, and increased phosphorus weathering due to the biological colonisation of the land surface, are predicted to have driven long-term changes in ocean composition.
OspE-Related, OspF-Related, and Elp Lipoproteins Are Immunogenic in Baboons Experimentally Infected with Borrelia burgdorferi and in Human Lyme Disease Patients

ABSTRACT Presently, the rhesus macaque is the only nonhuman primate animal model utilized for the study of Lyme disease. While this animal model closely mimics human disease, rhesus macaques can harbor the herpes B virus, which is often lethal to humans; macaques also do not express the full complement of immunoglobulin G (IgG) subclasses found in humans. Conversely, baboons contain the full complement of IgG subclasses and do not harbor the herpes B virus. For these reasons, baboons have been increasingly utilized as the basis for models of infectious diseases and studies assessing the safety and immunogenicity of new vaccines. Here we analyzed the capability of baboons to become infected with Borrelia burgdorferi, the agent of Lyme disease. Combined culture and PCR analyses of tick- and syringe-infected animals indicated that baboons are a sufficient host for B. burgdorferi. Analysis of the antibody responses in infected baboons over a 48-week period revealed that antibodies are generated early during infection against many borrelial antigens, including the various OspE, OspF, and Elp paralogs that are encoded on the ubiquitous 32-kb circular plasmids (cp32s). By using the baboon sera generated by experimental infection it was determined that a combination of two cp32-encoded lipoproteins, OspE and ElpB1, resulted in highly specific and sensitive detection of B. burgdorferi infection. An expanded analysis, which included 39 different human Lyme disease patients, revealed that a combination of the OspE and ElpB1 lipoproteins could be the basis for a new serodiagnostic assay for Lyme disease. Importantly, this novel serodiagnostic test would be useful independent of prior OspA vaccination status.
Reading Books and Watching Films as a Protective Factor against Suicidal Ideation

Reading books and watching films were investigated as protective factors for serious suicidal ideation (SSI) in young people with low perceived social belonging. Cross-sectional and longitudinal (12-month) analyses were performed using data from a representative European sample of 3256 students from the “Saving and Empowering Young Lives in Europe” study. Low social belonging was associated to SSI. However, reading books and watching films moderated this association, especially for those with lowest levels of belonging. This was true both at baseline and at 12 months of follow-up analyses. These media may act as sources of social support or mental health literacy and thus reduce the suicide risk constituted by low sense of belonging.
Detection of a novel Cys628STOP mutation of the myosin VIIA gene in Usher syndrome type Ib.

A Spanish family with three Usher I syndrome-affected members was linked to markers located on chromosome 11q. A search for mutations on the myosin VIIA gene revealed a novel mutation (Cys628STOP) on exon 16 segregating with the disorder in a homozygous state. This nonsense mutation could be responsible for the disease since it leads to a truncated protein that presumably has no function.
Interleukin-1 gene locus polymorphisms are associated with risk to breast cancer in Croatian population

Breast cancer has a complex genetic susceptibility. Innate and adaptive immunity can additionally increase the genetic risk to breast cancer development. We typed polymorphisms in the genes of the interleukin(IL)-1 and IL-17 proinflammatory cytokines in a case-control study in Caucasian population from Croatia. We compared the allelic and genotypic frequencies between patients (n=194), healthy women (n=188) and general population (n=531). The risk for breast cancer has been significantly different at both allelic and genotypic levels for two polymorphisms: the IL1B gene single nucleotide polymorphism (SNP) at -511 (G>A; rs16944) and the IL1 Receptor antagonist gene (IL1RN) variable number of tandem repeats (VNTR). The major allele (G) of the IL1B rs16944 SNP was associated with susceptibility to breast cancer (P<0.01) in general population with odds ratio (OR) of 1.42 and 95 % confidence interval (CI) at 1.09–1.85. The IL1RN VNTR allele 3 (5 repeats) was correlated with predisposition to disease (P<0.01, OR: 9.71, 95 % CI: 1.34–198.51) in women. At the genotype level, G/G homozygosity at IL1B rs16944 was significantly associated with predisposition to disease (P<0.02, OR: 1.68, 95 % CI: 1.10–2.57), whereas the heterozygosity (G/A) was correlated with protection to disease (P<0.01, OR: 0.57, 95 % CI: 0.37–0.89) in women. The IL1RN VNTR genotype 1/3 was significantly associated with susceptibility to breast cancer (P<0.01, OR: 10.01, 95 % CI: 1.37–207.55). Genotypic differences were also significantly different in comparison with general population for IL1B SNP (P<0.001) and IL1RN VNTR (P<0.01). These results corroborate a premise that inflammatory factors play a role in pathogenesis to breast cancer.
How Phenotype and Developmental Stage Affect the Genes We Find: GABRA2 and Impulsivity

Context: The detection and replication of genes involved in psychiatric outcome has been notoriously difficult. Phenotypic measurement has been offered as one explanation, although most of this discussion has focused on problems with binary diagnoses. Objective: This article focuses on two additional components of phenotypic measurement that deserve further consideration in evaluating genetic associations: (1) the measure used to reflect the outcome of interest, and (2) the developmental stage of the study population. We focus our discussion of these issues around the construct of impulsivity and externalizing disorders, and the association of these measures with a specific gene, GABRA2. Design, Setting, and Participants: Data were analyzed from the Collaborative Study on the Genetics of Alcoholism Phase IV assessment of adolescents and young adults (ages 12–26; N = 2,128). Main Outcome Measures: Alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder symptoms were measured by psychiatric interview; Achenbach youth/adult self-report externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity scale; NEO extraversion and consciousness. Results: GABRA2 was associated with subclinical levels of externalizing behavior as measured by the Achenbach in both the adolescent and young adult samples. Contrary to previous associations in adult samples, it was not associated with clinical-level DSM symptom counts of any externalizing disorders in these younger samples. There was also association with sensation-seeking and extraversion, but only in the adolescent sample. There was no association with the Barratt impulsivity scale or conscientiousness. Conclusions: Our results suggest that the pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. The findings support the heterogeneous nature of impulsivity and demonstrate that both the measure used to assess a construct of interest and the age of the participants can have profound implications for the detection of genetic associations.
Improvement of Defibrillation Efficacy with Preshock Synchronized Pacing

Introduction: We previously demonstrated that wavefront synchronization by spatiotemporal excitable gap pacing (Sync P) is effective at facilitating spontaneous termination of ventricular fibrillation (VF). Therefore, we hypothesized that a spatiotemporally controlled defibrillation (STCD) strategy using defibrillation shocks preceded by Sync P can improve defibrillation efficacy.
Risk of Mesothelioma and Occupational Exposure to Asbestos and Man-Made Vitreous Fibers: Evidence From Two Case-Control Studies in Montreal, Canada

Objective: To examine the effects of exposure to occupational asbestos and man-made vitreous fibers (MMVF) across a wide range of occupations on risk of mesothelioma. Methodology: Two population-based case–control studies (1979–1986 and 1996–2001) provided 35 histologically confirmed mesothelioma cases and 1965 controls. A detailed job history was obtained to evaluate occupational exposure to many agents, including asbestos and MMVF. Results: The mesothelioma odds ratio for exposure to any asbestos type was 3.7 (95% confidence interval = 1.7 to 7.8). The subset exposed to amphibole fibers experienced an odds ratio = 7.0 (95% confidence interval = 2.7 to 18.5). Effects of MMVF could not be disentangled from those of asbestos. Discussion: In workers with exposure levels lower than in most historical cohort studies and across a wide range of industries, a strong association was found between asbestos, especially when it was amphibole, and mesothelioma.