Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroimaging of Aggressive and Violent Behaviour in Children and Adolescents

In recent years, a number of functional and structural neuroimaging studies have investigated the neural bases of aggressive and violent behaviour in children and adolescents. Most functional neuroimaging studies have persued the hypothesis that pathological aggression is a consequence of deficits in the neural circuits involved in emotion processing. There is converging evidence for abnormal neural responses to emotional stimuli in youths with a propensity towards aggressive behaviour. In addition, recent neuroimaging work has suggested that aggressive behaviour is also associated with abnormalities in neural processes that subserve both the inhibitory control of behaviour and the flexible adaptation of behaviour in accord with reinforcement information. Structural neuroimaging studies in children and adolescents with conduct problems are still scarce, but point to deficits in brain structures in volved in the processing of social information and in the regulation of social and goal-directed behaviour. The indisputable progress that this research field has made in recent years notwithstanding, the overall picture is still rather patchy and there are inconsistencies between studies that await clarification. Despite this, we attempt to provide an integrated view on the neural abnormalities that may contribute to various forms of juvenile aggression and violence, and discuss research strategies that may help to provide a more profound understanding of these important issues in the future.
FUSION-Guided Hypothesis Development Leads to the Identification of N6,N6-Dimethyladenosine, a Marine-Derived AKT Pathway Inhibitor

Chemicals found in nature have evolved over geological time scales to productively interact with biological molecules, and thus represent an effective resource for pharmaceutical development. Marine-derived bacteria are rich sources of chemically diverse, bioactive secondary metabolites, but harnessing this diversity for biomedical benefit is limited by challenges associated with natural product purification and determination of biochemical mechanism. Using Functional Signature Ontology (FUSION), we report the parallel isolation and characterization of a marine-derived natural product, N6,N6-dimethyladenosine, that robustly inhibits AKT signaling in a variety of non-small cell lung cancer cell lines. Upon validation of the elucidated structure by comparison with a commercially available sample, experiments were initiated to understand the small molecule’s breadth of effect in a biological setting. One such experiment, a reverse phase protein array (RPPA) analysis of >50 kinases, indicated a specific cellular response to treatment. In all, leveraging the FUSION platform allowed for the rapid generation and validation of a biological mechanism of action hypothesis for an unknown natural product and permitted accelerated purification of the bioactive component from a chemically complex fraction.
Prokaryotic cDNA Subtraction: A Method to Rapidly Identify Functional Gene Biomarkers

Abstract : Perchlorate contamination of groundwater and surface water has been detected in at least 36 states and represents a public health concern. Bacteria capable of reducing perchlorate to chloride are ubiquitous in the environment, making biological perchlorate reduction an attractive treatment approach. For biological treatment to be successful, perchlorate-reducing bacteria (PRB) must not only be present, but they must also synthesize the enzymes that catalyze perchlorate reduction. The synthesis of specific enzymes, termed gene expression, is often regulated by each cell in response to environmental conditions (e.g., influent water characteristics). Changes in the composition or activity of the microbial community can lead to declines in perchlorate removal and ultimately, if left unchecked, failure of the treatment process. Molecular biology tools (MBT) can be used to determine how the composition and activity of microbial communities change in response to operational parameters and to gain insight into the causes of process upsets. While many studies have sought to quantify particular groups of bacteria by targeting their 16S rRNA genes, this approach is not ideal for PRB because they are phylogenetically diverse. MBT that target functional genes (e.g., genes that encode biodegradation enzymes), might prove more useful for determining the capabilities of the bacterial communities and for predicting process performance. Functional genes can be interrogated at the level of deoxyribonucleic acid (DNA) to determine functional potential or at the level of ribonucleic acid (RNA) to determine functional activity.
Accounting conservatism in Europe

This study investigates how the degree of accounting conservatism in the financial statements of European companies evolves over time during period 1996-2005. This study concludes that the financial statement information of European companies shows a certain degree of balance sheet conservatism and earnings conservatism during period 1991-2005; this degree of balance sheet conservatism and earnings conservatism evolves over time. The research findings do not indicate that the introduction of IFRS has reduced the differences in the degree of balance sheet conservatism and earnings conservatism between European companies reporting according to IFRS. Finally, the research findings indicate that IAS/IFRS based accounting standards have their own characteristics; this cause that the degree of accounting conservatism in financial statements differ importantly per accounting regulation.
Capturing Absorptive Capacity: Concepts, Determinants, Measurement Modes and Role in Open Innovation

Abstract Absorptive capacity (ACAP) enables firm to adjust to a rapidly changing environment and achieve sustained competitive advantage. This study contributes to the existing body of knowledge on ACAP by providing a comprehensive literature review of the various conceptual attributes of the construct, its determinants, outcomes, and positive and negative consequences of using its input-oriented, output-oriented, and perceptive measurement modes. Proposals for constructing ACAP based on the Community Innovation Survey (CIS) empirically illustrate for the conceptual part of the paper. Additionally, combining concepts of absorptive capacity and open innovation (which is still rare in the literature) provides a new perspective on the role of absorptive capacity in opening up the innovation process. This advances the understanding of both inter-related proposals. The article also identifies key problems and formulates future research directions to improve the multi-level characteristics of absorptive capacity.
Crucial Contributions by T Lymphocytes (Effector, Regulatory, and Checkpoint Inhibitor) and Cytokines (TH1, TH2, and TH17) to a Pathological Complete Response Induced by Neoadjuvant Chemotherapy in Women with Breast Cancer

The tumour microenvironment consists of malignant cells, stroma, and immune cells. Prominent tumour-infiltrating lymphocytes (TILs) in breast cancer are associated with a good prognosis and are predictors of a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC). The contribution of different T effector/regulatory cells and cytokines to tumour cell death with NAC requires further characterisation and was investigated in this study. Breast tumours from 33 women with large and locally advanced breast cancers undergoing NAC were immunohistochemically (intratumoural, stromal) assessed for T cell subsets and cytokine expression using labelled antibodies, employing established semiquantitative methods. Prominent levels of TILs and CD4+, CD8+, and CTLA-4+ (stromal) T cells and CD8+ : FOXP3+ ratios were associated with a significant pCR; no association was seen with FOXP3+, CTLA-4+ (intratumoural), and PD-1+ T cells. NAC significantly reduced CD4+, FOXP3+, CTLA-4+ (stromal) (concurrently blood FOXP3+, CTLA-4+ Tregs), and PD-1+ T cells; no reduction was seen with CD8+ and CTLA-4+ (intratumoural) T cells. High post-NAC tumour levels of FOXP3+ T cells, IL-10, and IL-17 were associated with a failed pCR. Our study has characterised further the contribution of T effector/regulatory cells and cytokines to tumour cell death with NAC.
Second-Order Optimal Array Receivers for Synchronization of BPSK, MSK, and GMSK Signals Corrupted by Noncircular Interferences

The synchronization and/or time acquisition problem in the presence of interferences has been strongly studied these last two decades, mainly to mitigate the multiple access interferences from other users in DS/CDMA systems. Among the available receivers, only some scarce receivers may also be used in other contexts such as F/TDMA systems. However, these receivers assume implicitly or explicitly circular (or proper) interferences and become suboptimal for noncircular (or improper) interferences. Such interferences are characteristic in particular of radio communication networks using either rectilinear (or monodimensional) modulations such as BPSK modulation or modulation becoming quasirectilinear after a preprocessing such as MSK, GMSK, or OQAM modulations. For this reason, the purpose of this paper is to introduce and to analyze the performance of second-optimal array receivers for synchronization and/or time acquisition of BPSK, MSK, and GMSK signals corrupted by noncircular interferences. For given performances and in the presence of rectilinear signal and interferences, the proposed receiver allows a reduction of the number of sensors by a factor at least equal to two.
Experiences in Process-Oriented Reorganisation through Reference Modelling in Public Administrations - The Case Study Regio at KomM

During the last years the optimisation of business processes has gained more and more importance in the context of modernising public administrations. In line with the concept of electronic government (eGovernment) citizens demand not only an improved design of internet sites, but also the creation of real added value to administrational services. In dimensions of benefits (from the citizen’s point of view) and in dimensions of cost reduction (from the administrations’ point of view) the added value can be generated by providing fully transactional online citizen services. The establishment of such services should be supported by reorganising the underlying business processes in terms of process organisation and enabling ICT. Approximately 13,000 German municipalities mainly have to deal with the same spectrum of tasks. The administration processes that are necessary to fulfil those tasks share strong structural analogies. Within process oriented reorganisation projects, reference models can contribute to cost reduction in the phase of to-be modelling. Aim of this paper is to present experiences in applying reference modelling within the process oriented reorganisation project Regio@KomM in public administrations. The reorganisation of the process of issuing a general debit note authorisation exemplifies the practical applicability and the value potential of reference modelling in public administrations.
Prediction of Propagation Path Loss for Stratospheric Platforms Mobile Communications in Urban Site LOS/NLOS Environment

Recently, there are of great interests on employing stratospheric platform as a new means of providing IMT-2000. One important issue that has not been much investigated is the propagation characteristic of its link. This paper aims at evaluating the impact of elevation and azimuth angles variation to the propagation mechanism in urban environment for mobile communication link. In order to examine the propagation loss experienced by this system in urban area, we developed the building block model and the ray tracing tool for simulation. We then apply the ray tracing tool with respect to the angle variations. As a result, propagation loss as a function of elevation and azimuth angles is obtained. We compared the result with a physical-statistical model for verification. Finally, link budget analysis and estimation to the required transmitted power at several transmission rates for the application of IMT-2000 is observed. Different scenario, which means different azimuth angles clearly show the critical limitations for mobile communication using a concept of stratospheric platform.
Predictors of long-term compliance with continuous positive airway pressure

Background There are very few data on objectively assessed long-term compliance with continuous positive airway pressure (CPAP). No single factor has been consistently identified as predictive of continued CPAP use. Methods Adherence to and associations with objective CPAP use were examined in 639 of 3900 patients in whom CPAP treatment was started between 1994 and 2005. Kaplan–Meier survival analyses were used to estimate the proportion of patients still on CPAP. Cox regression models were used to explore the effects of covariates on continued use of CPAP. Results The median (IQR) follow-up time after initiating CPAP therapy was 3.9 (1.5–6.9) years and the average use of CPAP was 6.2 (4.5–7.3) h/night. The percentage of patients adherent to CPAP after 5 and 10 years was 81% and 70%, respectively. Multivariate analysis, including gender, age, neck circumference, Epworth Sleepiness Score, oxygen desaturation index (ODI) and research study participation, indicated that ODI was the only clinical variable independently associated with long-term adherence to CPAP (HR per 1 event=0.97, p<0.001, 95% CI 0.96 to 0.98). ODI categories were significantly associated with the risk for stopping CPAP in multivariate analysis (using ODI group 0–15/h as reference, HR for ODI group >15–30/h=0.68, p=0.100, 95% CI 0.43 to 1.08; for ODI group >30–60/h=0.37, p<0.001, 95% CI 0.22 to 0.60; and for ODI group >60/h=0.17, p=0.001, 95% CI 0.06 to 0.48). Conclusions The majority of patients with sleep-disordered breathing are using CPAP in the long term and the severity of sleep-disordered breathing rather than sleepiness determines long-term adherence to CPAP therapy.
Leveraging biological replicates to improve analysis in ChIP-seq experiments

ChIP-seq experiments identify genome-wide profiles of DNA-binding molecules including transcription factors, enzymes and epigenetic marks. Biological replicates are critical for reliable site discovery and are required for the deposition of data in the ENCODE and modENCODE projects. While early reports suggested two replicates were sufficient, the widespread application of the technique has led to emerging consensus that the technique is noisy and that increasing replication may be worthwhile. Additional biological replicates also allow for quantitative assessment of differences between conditions. To date it has remained controversial about how to confirm peak identification and to determine signal strength across biological replicates, particularly when the number of replicates is greater than two. Using objective metrics, we evaluate the consistency of biological replicates in ChIP-seq experiments with more than two replicates. We compare several approaches for binding site determination, including two popular but disparate peak callers, CisGenome and MACS2. Here we propose read coverage as a quantitative measurement of signal strength for estimating sample concordance. Determining binding based on genomic features, such as promoters, is also examined. We find that increasing the number of biological replicates increases the reliability of peak identification. Critically, binding sites with strong biological evidence may be missed if researchers rely on only two biological replicates. When more than two replicates are performed, a simple majority rule (>50% of samples identify a peak) identifies peaks more reliably in all biological replicates than the absolute concordance of peak identification between any two replicates, further demonstrating the utility of increasing replicate numbers in ChIP-seq experiments.
The Costs of Being Private: Evidence from the Loan Market

Using a new data set of U.K. syndicated loans, we document a significant loan cost disadvantage incurred by privately-held ﬁrms. For identification, we use the distance of a firm’s headquarters to London’s capital markets as a plausibly exogenous variation in corporate structure (i.e. public/private) choice. We analyze the channels of the loan cost disadvantage of being private by documenting the importance of: the higher costs of information production, the lower bargaining power, the differences in ownership structure, and the differences in secondary market trading. Interestingly, we find no evidence that lenders price expected future performance into the loan spread differential.
Quantifying International Capital Mobility in the 1980s

The Feldstein-Horioka finding, that national saving and investment have been highly correlated in the past, has not been primarily due to econometric problems such as endogenous fiscal policy; it has held up equally well when instrumental variables are used. But the inflow of capital to the United States has been so large in recent years that an updating of the sample period to 1987 produces a coefficient on national saving that is lower than in past studies. This decline in the degree of crowding out of investment can be attributed to the increased degree of financial market integration in the 1980s. Capital controls and other bathers to the movement of capital across national borders remained for such countries as the United Kingdom and Japan as recently as 1979, and France and Italy as recently as 1986. But a new data set of forward exchange rates for 25 countries shows that a continuing worldwide trend of integration of financial markets in the 1980s had all but eliminated short-term interest differentials for major industrialized countries by 1988. It is only the country premium that has been eliminated however, this means that only covered interest differentials are small. Nominal and real exchange rate variability remain, and indeed were larger in the 1980s than in the 1970s. The result is that a currency premium remains, consisting of an exchange risk premium plus expected real currency depreciation. The popular null hypothesis that expected real depreciation is constant at zero is tested, and rejected, with a 119-year sample. (Post-1973 data sets do not allow enough observations to provide a useful test of this null hypothesis.) The existence of expected real depreciation means that, even if interest rates are equalized internationally when expressed in a common currency, large differentials in j interest rates remain. Investors have no incentive to arbitrage away such differentials. Because there is no force tying the domestic real interest rate to the world real interest rate, it follows that there is no reason to expect any country's shortfalls of national saving to be completely financed by borrowing from abroad.
The tomato fer gene encoding a bHLH protein controls iron-uptake responses in roots

Iron deficiency is among the most common nutritional disorders in plants. To cope with low iron supply, plants with the exception of the Gramineae increase the solubility and uptake of iron by inducing physiological and developmental alterations including iron reduction, soil acidification, Fe(II) transport and root-hair proliferation (strategy I). The chlorotic tomato fer mutant fails to activate the strategy I. It was shown previously that the fer gene is required in the root. Here, we show that fer plants exhibit root developmental phenotypes after low and sufficient iron nutrition indicating that FER acts irrespective of iron supply. Mutant fer roots displayed lower Leirt1 expression than wild-type roots. We isolated the fer gene by map-based cloning and demonstrate that it encodes a protein containing a basic helix–loop–helix domain. fer is expressed in a cell-specific pattern at the root tip independently from iron supply. Our results suggest that FER may control root physiology and development at a transcriptional level in response to iron supply and thus may be the first identified regulator for iron nutrition in plants.
Postnatal Loss of Neuronal and Glial Neurofascins Differentially Affects Node of Ranvier Maintenance and Myelinated Axon Function

Intricate molecular interactions between neurons and glial cells underlie the creation of unique domains that are essential for saltatory conduction of action potentials by myelinated axons. Previously, the cell surface adhesion molecule Neurofascin (Nfasc) has been shown to have a dual-role in the establishment of axonal domains from both the glial and neuronal interface. While the neuron-specific isoform of Neurofascin (NF186) is indispensable for clustering of voltage-gated sodium channels at nodes of Ranvier; the glial-specific isoform of Neurofascin (NF155) is required for myelinating glial cells to organize the paranodal domain. Although many studies have addressed the individual roles of NF155 and NF186 in assembling paranodes and nodes, respectively; critical questions about their roles in the maintenance and long-term health of the myelinated axons remain, which we aimed to address in these studies. Here using spatiotemporal ablation of Neurofascin in neurons alone or together with myelinating glia, we report that loss of NF186 individually from postnatal mice leads to progressive nodal destabilization and axonal degeneration. While individual ablation of paranodal NF155 does not disrupt nodes of Ranvier; loss of NF186 combined with NF155 causes more accelerated nodal destabilization than loss of NF186 alone, providing strong evidence regarding a supporting role for paranodes in nodal maintenance. In both cases of NF186 loss, myelinating axons show ultrastructural changes and degeneration. Our studies reveal that long-term maintenance of nodes and ultimately the health of axons is correlated with the stability of NF186 within the nodal complex and the presence of auxiliary paranodes.
Tsv-N1: A Novel DNA Algal Virus that Infects Tetraselmis striata

Numbering in excess of 10 million per milliliter of water, it is now undisputed that aquatic viruses are one of the major factors shaping the ecology and evolution of Earth’s microbial world. Nonetheless, environmental viral diversity and roles remain poorly understood. Here we report the first thorough characterization of a virus (designated TsV) that infects the coastal marine microalga Tetraselmis striata. Unlike previously known microalgae-infecting viruses, TsV is a small (60 nm) DNA virus, with a 31 kb genome. From a range of eight different strains belonging to the Chlamydomonadaceae family, TsV was only able to infect T. striata. Gene expression dynamics revealed an up-regulation of viral transcripts already 1 h post-infection (p.i.). First clear signs of infection were observed 24 h p.i. , with the appearance of viral factories inside the nucleus. TsV assembly was exclusively nuclear. TsV-N1 genome revealed very different from previously known algae viruses (Phycodnaviridae). Putative function and/or homology could be resolved for only 9 of the 33 ORFs encoded. Among those was a surprising DNA polymerase type Delta (only found in Eukaryotes), and two genes with closest homology to genes from human parasites of the urogenital tract. These results support the idea that the diversity of microalgae viruses goes far beyond the Phycodnaviridae family and leave the door open for future studies on implications of microalgae viruses for human health.