Miracle-dz/UniFAR-FTUs huggingface dataset:
Functionally linked amygdala and prefrontal cortical regions are innervated by both single and double projecting cholinergic neurons

Cholinergic cells have been proposed to project simultaneously to those cortical areas that are mutually interconnected with each other. We tested this hypothesis by investigating the cholinergic innervation of functionally linked cortical regions: the basal amygdala nucleus (BA) – dorsal part of the medial prefrontal cortex (dmPFC) and the basomedial amygdala nucleus (BMA) – ventral part of the mPFC (vmPFC). Using retrograde tracing, we found that basal forebrain cholinergic neurons projecting to the BA and BMA were in the ventral pallidum/substantia innominata (VP/SI) and horizontal limb of the diagonal band of Broca (HDB), respectively. Anterograde viral tracing confirmed that VP/SI cholinergic neurons preferentially targeted the BA and dmPFC. In contrast, HDB cholinergic cells innervated the BMA and vmPFC. We also demonstrated that a portion of cholinergic neurons projected both to the amygdala and mPFC. Furthermore, we revealed that the vesicular glutamate transporter type 3 (VGLUT3) was present typically in cholinergic boutons in the BA but not BMA, whereas their vesicular GABA transporter (VGAT) content could not be detected in adult mice. Our data thus revealed that cholinergic innervation of the dmPFC-BA and vmPFC-BMA originates from two distinct neuronal populations, which innervate interconnected target regions in a mutually exclusive manner. The dual innervation strategy, i.e., the existence of cholinergic cell populations with single as well as simultaneous projections to the amygdala and mPFC, provides the possibility for both synchronous and independent control of the operation in these cortical areas, a structural arrangement that may maximize computational support for functionally linked regions. Significance statement This study reveals the logic how basal forebrain cholinergic neurons innervate two functionally linked cortical regions, the dmPFC-BA and vmPFC-BMA, mutually interconnected circuits that have been shown to be involved in controlling opposing fear states and behavior. Our findings demonstrate that the VP/SI and HDB innervate dmPFC-BA and vmPFC-BMA networks, respectively. Cholinergic cells project primary either to the mPFC or to the amygdala, but there is a population of cholinergic neurons that sends axon collaterals to both areas. This structural organization allows for simultaneous and independent control of operation, maximizing computational support for cortical processing. The two types of cholinergic control of fear-related cortical areas can be a significant research target at various fear learning deficits, such as PTSD.
Developing Responsible Chatbots for Financial Services: A Pattern-Oriented Responsible AI Engineering Approach

The recent release of ChatGPT has gained huge attention and discussion worldwide, with responsible AI being a key topic of discussion. How can we ensure that AI systems, including ChatGPT, are developed and adopted in a responsible way? To tackle the responsible AI challenges, various ethical principles have been released by governments, organisations, and companies. However, those principles are very abstract and not practical enough. Further, significant efforts have been put on algorithm-level solutions that only address a narrow set of principles, such as fairness and privacy. To fill the gap, we adopt a pattern-oriented responsible AI engineering approach and build a Responsible AI Pattern Catalogue to operationalise responsible AI from a system perspective. In this article, we first summarise the major challenges in operationalising responsible AI at scale and introduce how we use the Responsible AI Pattern Catalogue to address those challenges. We then examine the risks at each stage of the chatbot development process and recommend pattern-driven mitigations to evaluate the the usefulness of the Responsible AI Pattern Catalogue in a real-world setting.
Isolation a Homogalacturonan from the Outer Seed Coat of Shaddock (Citrus grandis Osbeck)

An acidic mucilage was isolated from the outer-layer seed coat of shaddock (Citrus grandis Osbeck) by water extraction at room temperature, and purified by DE-52 anion-exchange chromatography using 0.26 – 0.37 M NaCl. This purified mucilage was almost entirely composed of galacturonic acid residues. Glycosyl-linkage analysis showed that the backbone was 1→4 linked. Fourier Transform Infrared Spectroscopic analysis and determination of the degree of methylation further revealed that the mucilage was a low-degree (11.94%) esterified homogalacturonan. Size exclusion chromatography showed that the major molecular weight distribution of 610.9 kDa.
Computer Algorithms Show Potential for Improving Dermatologists’ Accuracy to Diagnose Cutaneous Melanoma; Results of ISIC 2017

Background: Computer vision has promise in image-based cutaneous melanoma diagnosis but clinical utility is uncertain. Objective: To determine if computer algorithms from an international melanoma detection challenge can improve dermatologist melanoma diagnostic accuracy. Methods: Cross-sectional study using 150 dermoscopy images (50 melanomas, 50 nevi, 50 seborrheic keratoses) from the test dataset of a melanoma detection challenge, along with algorithm results from twenty-three teams. Eight dermatologists and nine dermatology residents classified dermoscopic lesion images in an online reader study and provided their confidence level. Results: The top-ranked computer algorithm had a ROC area of 0.87, which was higher than the dermatologists (0.74) and the residents (0.66) (p<0.001 for all comparisons). At the dermatologists’ overall sensitivity in classification of 76.0%, the algorithm had a superior specificity (85.0% vs. 72.6%, p=0.001). Imputation of computer algorithm classifications for
A Comparison of the Acute Effects of Percussion Massage Therapy and Static Stretching on Hamstring Elasticity

BACKGROUND: The effect of percussion massage on hamstring flexibility is unknown. This study aimed to investigate the acute effects of percussion massage on hamstring flexibility and to compare its effectiveness with static stretching. METHODS: Fifty-four healthy individuals aged 18-25 years with at least 15 degrees of active knee extension were included in the study. The study was conducted between February and May 2022. The participants were randomly divided into 3 groups in this cross-randomization study as percussion
CTCF is a DNA-tension-dependent barrier to cohesin-mediated DNA loop extrusion

In eukaryotes, genomic DNA is extruded into loops by cohesin1. By restraining this process, the DNA-binding protein CTCF generates topologically associating domains (TADs)2–4 that play key roles in gene regulation and recombination during development and disease1,5–8. How CTCF establishes TAD boundaries and to what extent these are permeable to cohesin is unknown9. To address these questions, we visualize interactions of single CTCF and cohesin molecules on DNA in vitro. We show that CTCF is sufficient to block diffusing cohesin, possibly reflecting how cohesive cohesin accumulates at TAD boundaries, as well as to block loop-extruding cohesin, reflecting how CTCF establishes TAD boundaries. CTCF functions asymmetrically, as predicted, but unexpectedly is dependent on DNA tension. Moreover, CTCF regulates cohesin’s loop extrusion activity by changing its direction and by inducing loop shrinkage. Our data indicate that CTCF is not, as previously assumed, simply a barrier to cohesin-mediated loop extrusion but is an active regulator of this process, where the permeability of TAD boundaries can be modulated by DNA tension. These results reveal mechanistic principles of how CTCF controls loop extrusion and genome architecture.
Stem Cell Repor ts

SUMMARY The direct conversion of human skin ﬁbroblasts to neurons has a low efﬁciency and unclear mechanism. Here, we show that the knock-down of PTBP2 signiﬁcantly enhanced the transdifferentiation induced by ASCL1 , MIR9/9*-124, and p53 shRNA (AMp) to generate mostly GABAergic neurons. Longitudinal RNA sequencing analyses identiﬁed the continuous induction of many RNA splicing regulators. Among these, the knockdown of RBFOX3 (NeuN), signiﬁcantly abrogated the transdifferentiation. Overexpression of RBFOX3 signiﬁcantly enhanced the conversion induced by AMp; the enhancement was occluded by PTBP2 knockdown. We found that PTBP2 attenuation signiﬁcantly favored neuron-speciﬁc alternative splicing (AS) of many genes involved in synaptic transmission, signal transduction,andaxonformation. RBFOX3 knockdownsigniﬁcantlyreversedtheeffect,while RBFOX3 overexpressionoccludedtheenhance-ment. The study reveals the critical role of neuron-speciﬁc AS in the direct conversion of human skin ﬁbroblasts to neurons by showing that PTBP2 attenuation enhances this mechanism in concert with RBFOX3.
The Monetary-Fiscal Policy Mix: Perspectives from the U.S.

This paper discusses the U.S. perspective on the monetary-fiscal policy mix, and the interactions between monetary and fiscal policy more broadly. It identifies three sets of issues that have been modeled in the theoretical literature: composition effects, the implications of fiscal solvency, and problems stemming from coordination failures and strategic interactions. Empirical work presented in the paper indicates that fiscal and monetary policy appear to have had effects on the composition of output, but solvency, coordination and strategic issues have been neither significant nor endemic. In addition, there is no evidence of a systematic Federal Reserve response to fiscal policy, beyond that which would be implied by the impact of fiscal policy on future GDP growth.
Shepherding precision gene editing with CRISPR-Cas9 variants and adenoviral vectors

Targeted chromosomal insertion of large genetic payloads in human cells leverages and broadens synthetic biology and genetic therapy efforts. Yet, obtaining large-scale gene knock-ins remains particularly challenging especially in hard-to-transfect stem and progenitor cells. Here, fully viral gene-deleted adenovector particles (AdVPs) are investigated as sources of optimized high-specificity CRISPR-Cas9 nucleases and donor DNA constructs tailored for targeted insertion of full-length dystrophin expression units (up to 14.8-kb) through homologous recombination (HR) and homology-mediated end joining (HMEJ). In muscle progenitor cells, donors prone to HMEJ yielded higher CRISPR-Cas9-dependent genome editing frequencies than HR donors, with values ranging between 6%-34%. In contrast, AdVP transduction of HR and HMEJ substrates in induced pluripotent stem cells (iPSCs) resulted in similar CRISPR-Cas9-dependent genome editing levels. Notably, when compared to regular iPSCs, in p53 knockdown iPSCs, CRISPR-Cas9-dependent genome editing frequencies increased up to 6.7-fold specifically when transducing HMEJ donor constructs. Finally, single DNA molecule analysis by molecular combing confirmed that AdVP-based genome editing achieves long-term complementation of DMD-causing mutations through the site-specific insertion of full-length dystrophin expression units. In conclusion, AdVPs are a robust and flexible platform for installing large genomic edits in human cells and p53 inhibition fosters HMEJ-based genome editing in iPSCs.
D ec 2 02 2 NATURAL DIFFERENTIABLE STRUCTURES ON STATISTICAL MODELS AND THE FISHER METRIC

In this paper I discuss the relation between the concept of the Fisher metric and the concept of differentiability of a family of probability measures. I compare the concepts of smooth statistical manifolds, differentiable families of measures, k-integrable parameterized measure models, diffeological statistical models, differentiable measures, which arise in Information Geometry, mathematical statistics and measure theory, and discuss some related problems. Dedicated to Professor Shun-ichi Amari on his 88th birthday.
Afﬁne transitions for involution Stanley symmetric functions

We deﬁne a new family of Stanley symmetric functions for afﬁne involutions and study the basic properties of these power series. After classifying the covering relations in the Bruhat order of the afﬁne symmetric group restricted to involutions, we prove an afﬁne transition formula for involution Stanley symmetric functions.
Cuticle supplementation and nitrogen recycling by a dual bacterial symbiosis in a family of xylophagous beetles (Coleoptera: Bostrichidae)

Many insects engage in stable nutritional symbioses with bacteria that supplement limiting essential nutrients to their host. While several plant sap-feeding Hemipteran lineages are known to be simultaneously associated with two or more endosymbionts with complementary biosynthetic pathways to synthesize amino acids or vitamins, such co-obligate symbioses have not been functionally characterized in other insect orders. Here, we report on the characterization of a dual co-obligate, bacteriome-localized symbiosis in a family of xylophagous beetles using comparative genomics, fluorescence microscopy, and phylogenetic analyses. Across the beetle family Bostrichidae, all investigated species harbored the Bacteroidota symbiont Shikimatogenerans bostrichidophilus that encodes the shikimate pathway to produce tyrosine precursors in its severely reduced genome, likely supplementing the beetles’ cuticle biosynthesis, sclerotisation, and melanisation. One clade of Bostrichid beetles additionally housed the co-obligate symbiont Bostrichicola ureolyticus that is inferred to complement the function of Shikimatogenerans by recycling urea and provisioning the essential amino acid lysine, thereby providing additional benefits on nitrogen-poor diets. Both symbionts represent ancient associations within the Bostrichidae that have subsequently experienced genome erosion and co-speciation with their hosts. While Bostrichicola was repeatedly lost, Shikimatogenerans has been retained throughout the family and exhibits a perfect pattern of co-speciation. Our results reveal that co-obligate symbioses with complementary metabolic capabilities occur beyond the well-known sap-feeding Hemiptera and highlight the importance of symbiont-mediated cuticle supplementation and nitrogen recycling for herbivorous beetles. Significance statement Nutritional symbioses evolved frequently in insects and contribute diverse metabolites to their hosts’ physiology. Associations with dual symbionts providing complementary nutrients evolved in multiple Hemiptera lineages, compensating eroded biosynthetic capabilities of primary symbionts. Bostrichidae, a family of xylophagous beetles, harbor consistently a Flavobacterial symbiont encoding exclusively the Shikimate pathway to synthesis precursors of tyrosine. However, in two families a second, closely Flavobacterial symbiont capable of recycling urea and synthesizing lysine was retained. Both symbionts exhibit high genomic syntheny and tight co-cladogenesis with the host phylogeny, indicating ancestral, ecological highly beneficial symbioses.
for Speciﬁcation, Resource Estimation, and Optimized Observer Generation for Runtime Veriﬁcation in Hardware and Software

R2U2 is a modular runtime veriﬁcation framework capable of monitoring sets of speciﬁcations in real time and in resource-constrained environments. Such environments demand that a runtime monitor be fast, easily integrat-able, accessible to domain experts, and have predictable resource requirements. Version 3.0 adds new features to R2U2 and its associated suite of tools that meet these needs including a new front-end compiler that accepts a custom speciﬁ-cation language, a GUI for resource estimation, and improvements to R2U2’s internal architecture.
CROWDFUNDING SUCCESS PREDICTION USING PROJECT TITLE IMAGE AND CONVOLUTIONAL NEURAL NETWORK

Prediction of crowdfunding success is a challenging problem that has great importance for project creators and platforms. Although meta features, e.g., number of updates or backers, are widely used for success prediction, they are limited to time period after project posting where project creators cannot adapt their profiles. Because of that, ability to predict campaign success in pre-posting phase would significantly improve chance for project success. According to the theory, mostly used methods in this situation are those based on text features, while methods based on the influence of image modality on project success are rare. Due to this, in this article we propose deep learning-based method for crowdfunding success prediction in pre-posting phase using project title image. Experimental results show that image modality could be used for campaign success prediction. Proposed method obtains results comparable to competing methods from literature, but using only one image per campaign and no derived features. It is also shown that deeper convolutional neural network achieves better prediction performance.
The Effects of Audit Market Concentration and Auditor Reputation on Audit Quality: Evidence from Government Auditors

We investigate how a high degree of audit market concentration and auditor reputation affect audit quality. Using audit adjustments to student loan loss provisions in government audits to construct a new measure for excessive audit conservatism, we show that an audit market monopoly leads to excessively conservative audit adjustments to the provisions and, thus, to lower audit quality. We also examine the effect of a positive shock to auditor reputation on audit quality. We find that before the increase to their reputation, monopolistic auditors require more conservative, yet not excessively conservative, adjustments than auditors in a competitive market. However, after the reputation increase, the adjustments become excessively conservative. This result suggests that the combination of enhanced audit market concentration and high auditor reputation leads to excessive auditor conservatism. Consistent with the excessive nature of the adjustments, we find no significant association between the adjustments and future student loan writeoffs. Additional analysis reveals that career concerns play a role in driving the excessive conservatism. Our study has implications for the ongoing debate regarding the impact of reduced competition in the audit market on audit quality and for the government.
Intraspecific variability in isotopic composition of a monomorphic seabird, the Common Tern (Sterna hirundo), at wintering grounds

ABSTRACT Understanding sex differences in foraging behaviour has important implications for breeding biology and population ecology. This requires the evaluation of segregation throughout the annual cycle, including the non-breeding period. We studied the diet and foraging strategies of the Common Tern (Sterna hirundo) at an intraspecific level by sampling birds during two consecutive non-breeding periods in Punta Rasa, Buenos Aires Province, Argentina. Blood samples were taken for sex determination and carbon and nitrogen stable isotope analysis. No isotopic difference was observed between years, but higher isotopic values occurred during late non-breeding period. Carbon and nitrogen isotopic values were similar between sexes; however, differences were observed in standard ellipse analyses, considered to represent isotopic niches. Even though the Bayesian ellipse areas overlapped, females showed wider isotopic niches throughout the non-breeding period. This could be related to different feeding strategies, foraging areas or migratory stopover sites at either intraspecific or individual levels. Diet contributions of different prey categories estimated through mixing model analyses suggested a higher contribution of estuarine fish than of marine pelagic species. These results highlight the importance of stable isotope analyses as a complementary methodology to traditional diet studies, particularly during the non-breeding period.
Greater levels of cardiorespiratory and muscular fitness are associated with low stress and high mental resources in normal but not overweight men

Background: The aim of the present study was to investigate how cardio respiratory (CRF) and muscular fitness (MF) together with leisure-time physical activity (LTPA) influence stress symptoms and mental resources among normal-weight and overweight men, because it is not known how body weight affects this association. Methods: In a cross-sectional study, 824 men (mean ± SD: age 25 ± 5 y, weight 81 ± 13 kg, BMI 25 ± 4 kg/m) underwent CRF and MF tests and completed LTPA and stress questionnaires. For the analysis, the subjects were divided into BMI groups (normal vs. overweight) and CRF / MF / LTPA (low, moderate, high) tertiles. Results: Normal-weight men with low CRF reported 12 % (p = 0.001) more stress symptoms (SS) compared to normal-weight men with moderate CRF, and 13 % (p = 0.004) more SS compared to normal-weight men with high CRF. Normal-weight men with low MF reported 13 % (p = 0.001) higher SS compared to normal-weight men with moderate MF and 16 % (p = 0.002) more SS compared to men with high MF. Among overweight men, there were no significant differences in SS or mental resources (MR) between the low, moderate and high CRF and MF tertiles. Overweight men with high CRF experienced 8 % (p = 0.039) more SS compared to normal-weight participants with high CRF when age, tobacco and alcohol use, MF and LTPA were considered as covariates (p = 0.014). Conclusion: Higher CRF and MF are associated with lower stress and higher mental resources in normal-weight men, but in overweight men, these relationships may differ.
OFFPRINT k-connectivity for conﬁned random networks

– k -connectivity is an important measure of network robustness and resilience to random faults and disruptions. We undertake both local and global approaches to k -connectivity and calculate closed-form analytic formulas for the probability that a conﬁned random network remains fully connected after the removal of k − 1 nodes. Our analysis reveals that k -connectivity is governed by microscopic details of the network domain such as sharp corners rather than the macroscopic total volume. Hence, our results can aid in the design of reliable networks, an important problem in, e
Observation and modelling of the Saint-Etienne-de-Tinée landslide using SAR interferometry

SAR interferometry has been shown to lead to accurate e surface displacements mapping. The study of the La Clapiere' landslide, located in Southern France on the left bank of the Tinee river, was carried out in order to demonstrate the capability of interferometry to monitor displacements of small spatial extension. In a first study, six different interferograms have been derived from ERS-1 SAR images acquired during the Commissioning Phase The coherence of the associated images was shown to remain significant over most of the surface of the landslide during the two weeks of the survey, The interferograms, generated on a massively parallel computer, clearly evidenced deformation fringes associated with the landslide. They were remarkably similar, and indicated steady-state displacements over at least 12 days The displacement field derived from the interferograms was modeled and shown to be characterized by a non-uniform displacement gradient from the top to the bottom. It also revealed a significantly faster motion of the western part of the landslide, The amplitude of the motion was shown to be in good agreement with ground measurements. Furthermore, the interferograms allowed us to evidence a small-scale instability which could not be observed with discrete ground measurements Finally, we present preliminary results obtained on the same site with images acquired during the second Tandem mission. It provided the opportunity to extend the study of the landslide, which displacements are too high to be observed with images acquired on the standard orbital cycles of 35 days.