Miracle-dz/UniFAR-FTUs huggingface dataset:
Kaehler surfaces and parabolic polystability

A complex ruled surface admits an iterated blow-up encoded by a parabolic structure with rational weights. Under a condition of parabolic stability, one can construct a Kähler metric of constant scalar curvature on the blow-up according to [18]. We present a generalization of this construction to the case of parabolically polystable ruled surfaces. Thus we can produce numerous examples of Kähler surfaces of constant scalar curvature with circle or toric symmetry.
Keyframe-based tracking for rotoscoping and animation

We describe a new approach to rotoscoping --- the process of tracking contours in a video sequence --- that combines computer vision with user interaction. In order to track contours in video, the user specifies curves in two or more frames; these curves are used as keyframes by a computer-vision-based tracking algorithm. The user may interactively refine the curves and then restart the tracking algorithm. Combining computer vision with user interaction allows our system to track any sequence with significantly less effort than interpolation-based systems --- and with better reliability than "pure" computer vision systems. Our tracking algorithm is cast as a spacetime optimization problem that solves for time-varying curve shapes based on an input video sequence and user-specified constraints. We demonstrate our system with several rotoscoped examples. Additionally, we show how these rotoscoped contours can be used to help create cartoon animation by attaching user-drawn strokes to the tracked contours.
Automatic Structural Parcellation of Mouse Brain MRI Using Multi-Atlas Label Fusion

Multi-atlas segmentation propagation has evolved quickly in recent years, becoming a state-of-the-art methodology for automatic parcellation of structural images. However, few studies have applied these methods to preclinical research. In this study, we present a fully automatic framework for mouse brain MRI structural parcellation using multi-atlas segmentation propagation. The framework adopts the similarity and truth estimation for propagated segmentations (STEPS) algorithm, which utilises a locally normalised cross correlation similarity metric for atlas selection and an extended simultaneous truth and performance level estimation (STAPLE) framework for multi-label fusion. The segmentation accuracy of the multi-atlas framework was evaluated using publicly available mouse brain atlas databases with pre-segmented manually labelled anatomical structures as the gold standard, and optimised parameters were obtained for the STEPS algorithm in the label fusion to achieve the best segmentation accuracy. We showed that our multi-atlas framework resulted in significantly higher segmentation accuracy compared to single-atlas based segmentation, as well as to the original STAPLE framework.
Information Security: Facilitating User Precautions Vis-à-Vis Enforcement Against Attackers

We compare alternative information security policies—facilitating enduser precautions and enforcement against attackers. The context is mass and targeted attacks, taking account of strategic interactions between end users and attackers. For both mass and targeted attacks, facilitating end-user precautions reduces the expected loss of end users. However, the impact of enforcement on expected loss depends on the balance between deterrence and slackening of end-user precautions. Facilitating end-user precautions is more effective than enforcement against attackers when the cost of precautions and the cost of attacks are lower. With targeted attacks, facilitating end-user precautions is more effective for users with relatively high valuation of information security, while enforcement against attackers is more effective for users with relatively low valuation of security.
Molecular epidemiology of respiratory syncytial virus in Kilifi district, Kenya

Respiratory syncytial virus (RSV) causes significant burden of disease during infancy and childhood. This study examined the genetic relatedness of RSV positive samples from child inpatients and outpatients and a birth cohort from a rural coastal district of Kenya and also the distribution of strains between these three groups. Clinical samples were collected over a 4‐year period in Kilifi District, Kenya from community and hospital surveillance. Three hundred ninety seven of 1,044 nasal specimens from children (under 5 years old) attending Kilifi District Hospital, and from community‐monitored infants, were positive for RSV by multiplex RT‐PCR. Of these, 376 samples were analysed further by restriction fragment length polymorphisms (RFLP) of the nucleocapsid (N) and attachment (G) protein genes. The G gene was sequenced for 109 samples and phylogenetic analysis carried out. The group A samples from Kilifi fell into two clusters based on G gene sequences, while only one group B cluster was observed. One RSV‐B sample from 2003 demonstrated the presence of a 60‐nucleotide duplication within the G gene, clustering with similar isolates from Buenos Aries from 1999. All had similar sequences to isolates from the UK, USA, Spain, or Uruguay. The Kilifi District samples showed greater than 97% homology to isolates from South Africa and Mozambique and 91–94% homology to isolates from The Gambia. Samples from different sources, clearly differing in disease severity, did not differ in genotype characteristics, suggesting that disease causing variants are a general reflection of infections within this community. J. Med. Virol. 74:344–354, 2004. © 2004 Wiley‐Liss, Inc.
Designing and Testing of Novel Taxanes to Probe the Highly Complex Mechanisms by Which Taxanes Bind to Microtubules and Cause Cytotoxicity to Cancer Cells

Our previous work identified an intermediate binding site for taxanes in the microtubule nanopore. The goal of this study was to test derivatives of paclitaxel designed to bind to this intermediate site differentially depending on the isotype of β-tubulin. Since β-tubulin isotypes have tissue-dependent expression—specifically, the βIII isotype is very abundant in aggressive tumors and much less common in normal tissues—this is expected to lead to tubulin targeted drugs that are more efficacious and have less side effects. Seven derivatives of paclitaxel were designed and four of these were amenable for synthesis in sufficient purity and yield for further testing in breast cancer model cell lines. None of the derivatives studied were superior to currently used taxanes, however computer simulations provided insights into the activity of the derivatives. Our results suggest that neither binding to the intermediate binding site nor the final binding site is sufficient to explain the activities of the derivative taxanes studied. These findings highlight the need to iteratively improve on the design of taxanes based on their activity in model systems. Knowledge gained on the ability of the engineered drugs to bind to targets and bring about activity in a predictable manner is a step towards personalizing therapies.
Effects of Glucagon-Like Peptide-1 in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction After Successful Reperfusion

Background—Glucose-insulin-potassium infusions are beneficial in uncomplicated patients with acute myocardial infarction (AMI) but are of unproven efficacy in AMI with left ventricular (LV) dysfunction because of volume requirements associated with glucose infusion. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties that stimulate glucose uptake without the requirements for concomitant glucose infusion. Methods and Results—We investigated the safety and efficacy of a 72-hour infusion of GLP-1 (1.5 pmol/kg per minute) added to background therapy in 10 patients with AMI and LV ejection fraction (EF) <40% after successful primary angioplasty compared with 11 control patients. Echocardiograms were obtained after reperfusion and after the completion of the GLP-1 infusion. Baseline demographics and background therapy were similar, and both groups had severe LV dysfunction at baseline (LVEF=29±2%). GLP-1 significantly improved LVEF (from 29±2% to 39±2%, P <0.01), global wall motion score indexes (1.94±0.11→1.63±0.09, P <0.01), and regional wall motion score indexes (2.53±0.08→2.02±0.11, P <0.01) compared with control subjects. The benefits of GLP-1 were independent of AMI location or history of diabetes. GLP-1 was well tolerated, with only transient gastrointestinal effects. Conclusions—When added to standard therapy, GLP-1 infusion improved regional and global LV function in patients with AMI and severe systolic dysfunction after successful primary angioplasty.
MSH6 haploinsufficiency at relapse contributes to the development of thiopurine resistance in pediatric B-lymphoblastic leukemia

Survival of children with relapsed acute lymphoblastic leukemia is poor, and understanding mechanisms underlying resistance is essential to developing new therapy. Relapse-specific heterozygous deletions in MSH6, a crucial part of DNA mismatch repair, are frequently detected. Our aim was to determine whether MSH6 deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance, or if it leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents. We knocked down MSH6 in mismatch repair proficient cell lines (697 and UOCB1) and showed significant increases in IC50s to 6-thioguanine and 6-mercaptopurine (697: 26- and 9-fold; UOCB1: 5- and 8-fold) in vitro, as well as increased resistance to 6-mercaptopurine treatment in vivo. No shift in IC50 was observed in deficient cells (Reh and RS4;11). 697 MSH6 knockdown resulted in increased DNA thioguanine nucleotide levels compared to non-targeted cells (3070 vs. 1722 fmol/μg DNA) with no difference observed in mismatch repair deficient cells. Loss of MSH6 did not give rise to microsatellite instability in cell lines or clinical samples, nor did it significantly increase mutation rate, but rather resulted in a defect in cell cycle arrest upon thiopurine exposure. MSH6 knockdown cells showed minimal activation of checkpoint regulator CHK1, γH2AX (DNA damage marker) and p53 levels upon treatment with thiopurines, consistent with intrinsic chemoresistance due to failure to recognize thioguanine nucleotide mismatching and initiate mismatch repair. Aberrant MSH6 adds to the list of alterations/mutations associated with acquired resistance to purine analogs emphasizing the importance of thiopurine therapy.
Inflammasome-Independent NLRP3 Restriction of a Protective Early Neutrophil Response to Pulmonary Tularemia

Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft challenge, more mature myeloid cells are elicited and are protective. In addition, inflammasome-dependent IL-1β and IL-18 are important for protection. As Nlrp3 appears dispensable for resistance to infection with Francisella novicida, we considered its role during infection with the virulent Type A strain SchuS4 and the attenuated Type B live vaccine strain LVS. Here we show that both in vitro macrophage and in vivo IL-1β and IL-18 responses to Ft LVS and SchuS4 involve both the Aim2 and Nlrp3 inflammasomes. However, following lethal infection with Francisella, IL-1r-, Caspase-1/11-, Asc- and Aim2-deficient mice exhibited increased susceptibility as expected, while Nlrp3-deficient mice were more resistant. Despite reduced levels of IL-1β and IL-18, in the absence of Nlrp3, Ft infected mice have dramatically reduced lung pathology, diminished recruitment and death of immature myeloid cells, and reduced bacterial burden in comparison to wildtype and inflammasome-deficient mice. Further, increased numbers of mature neutrophil appear in the lung early during lethal Ft infection in Nlrp3-deficient mice. Finally, Ft infection induces myeloid and lung stromal cell death that in part requires Nlrp3, is necrotic/necroptotic in nature, and drives host mortality. Thus, Nlrp3 mediates an inflammasome-independent process that restricts the appearance of protective mature neutrophils and promotes lethal necrotic lung pathology.
Hepatoprotective Evaluation of Trapa natans against Drug-induced Hepatotoxicity of Antitubercular Agents in Rats

Background: Medicinal herbs are significantly effective against a variety of liver disorders and Trapa natans was traditionally used for the treatment of anti-inflammatory, pain disorder, and various types of hepatic ailment. Objective: The purpose of this study was to evaluate the hepatoprotective activity of T. natans fruit peel extract against antitubercular drugs (isoniazid + rifampicin [INH + RIF])-induced hepatotoxicity in rats. Materials and Methods: Liver toxicity was induced by INH + RIF at a dose level of 50 mg/kg each, intraperitoneally. for 15 days. Fifty percent ethanolic extract of T. natans (TNE) at a dose of 200 and 400 mg/kg was administered orally once daily for 15 days. The hepatoprotective activity was assessed using various biochemical parameters such as aspartate transaminase, alanine transaminase, alkaline phosphate, lactate dehydrogenase, albumin, cholesterol, and bilirubin. Furthermore, in vivo antioxidant activities and histopathological investigation were performed to assess hepatoprotective activity. Results: Obtained results demonstrated that the level of liver marker enzymes and antioxidant parameters were significantly altered by INH + RIF treatment. Treatment with T. natans peel extract causes significant (P < 0.01 to P < 0.001) reduction in liver injury & normalized all altered liver marker enzymes. In addition, TNE significantly normalized the activity of antioxidant enzymes, namely, lipid peroxidation (P < 0.01 to P < 0.001), reduced glutathione (P < 0.05 to P < 0.001), superoxide dismutase (P < 0.05 to P < 0.001), and catalase (P < 0.01 to P < 0.001) in the liver tissue of INH + RIF-treated groups. Histological observations of the liver tissues correlated with the biochemical observations. Conclusion: These findings powerfully support that the protective effect of T. natans fruit peel extract against liver injury which may be attributed to its hepatoprotective activity due to normalizes the altered liver marker enzymes and antioxidant defense status and thereby contributed to its antihepatotoxic potential. Abbreviations used: INH: Isoniazid; RIF: Rifampicin; DIH: Drug-induced hepatotoxicity; CMC: Carboxy methyl cellulose; ALT: Alanine transaminase; ALP: Alkaline phosphate; CHL: Total cholesterol; ALB: Albumin; LDH: Lactate dehydrogenase; LPO: Lipid peroxidation; CAT: Catalase; GSH: Reduced glutathione; SOD: Superoxide dismutase; TNE: Trapa natans extract.
Self-Criticism: A Measure of Uncompassionate Behaviors Toward the Self, Based on the Negative Components of the Self-Compassion Scale

Background: The use of the Self-Compassion Scale (SCS) as a single measure has been pointed out as problematic by many authors and its originally proposed structure has repeatedly been called into question. The negative facets of this construct are more strongly related to psychopathology than the positive indicators. The aim of this study was to evaluate and compare the different structures proposed for the SCS, including a new measure based only on the negative factors, and to assess the psychometric features of the more plausible solution. Method: The study employed a cross-sectional and cross-cultural design. A sample of Brazilian (n = 406) and Spanish (n = 416) primary care professionals completed the SCS, and other questionnaires to measure psychological health-related variables. The SCS factor structure was estimated using confirmatory factor analysis by the maximum likelihood method. Internal consistency was assessed by squaring the correlation between the latent true variable and the observed variables. The relationships between the SCS and other constructs were analyzed using Spearman's rs. Results: The structure with the best fit was comprised of the three negative first-order factors of “self-judgment”, “isolation” and “over-identification”, and one negative second-order factor, which has been named “self-criticism” [CFI = 0.92; RMSEA = 0.06 (90% CI = 0.05–0.07); SRMR = 0.05]. This solution was supported by both samples, presented partial metric invariance [CFI = 0.91; RMSEA = 0.06 (90% CI = 0.05–0.06); SRMR = 0.06], and showed significant correlations with other health-related psychological constructs. Reliability was adequate for all the dimensions (R ≥ 0.70). Conclusions: The original structure proposed for the SCS was not supported by the data. Self-criticism, comprising only the negative SCS factors, might be a measure of uncompassionate behaviors toward the self, with good psychometric properties and practical implications from a clinical point of view, reaching a stable structure and overcoming possible methodological artifacts.
Effective Connectivity Reveals Right-Hemisphere Dominance in Audiospatial Perception: Implications for Models of Spatial Neglect

Detecting the location of salient sounds in the environment rests on the brain's ability to use differences in sounds arriving at both ears. Functional neuroimaging studies in humans indicate that the left and right auditory hemispaces are coded asymmetrically, with a rightward attentional bias that reflects spatial attention in vision. Neuropsychological observations in patients with spatial neglect have led to the formulation of two competing models: the orientation bias and right-hemisphere dominance models. The orientation bias model posits a symmetrical mapping between one side of the sensorium and the contralateral hemisphere, with mutual inhibition of the ipsilateral hemisphere. The right-hemisphere dominance model introduces a functional asymmetry in the brain's coding of space: the left hemisphere represents the right side, whereas the right hemisphere represents both sides of the sensorium. We used Dynamic Causal Modeling of effective connectivity and Bayesian model comparison to adjudicate between these alternative network architectures, based on human electroencephalographic data acquired during an auditory location oddball paradigm. Our results support a hemispheric asymmetry in a frontoparietal network that conforms to the right-hemisphere dominance model. We show that, within this frontoparietal network, forward connectivity increases selectively in the hemisphere contralateral to the side of sensory stimulation. We interpret this finding in light of hierarchical predictive coding as a selective increase in attentional gain, which is mediated by feedforward connections that carry precision-weighted prediction errors during perceptual inference. This finding supports the disconnection hypothesis of unilateral neglect and has implications for theories of its etiology.
A Multi-Project Model of Key Factors Affecting Organizational Benefits from Enterprise Systems

This paper develops a long-term, multi-project model of factors affecting organizational benefits from enterprise systems (ES), then reports a preliminary test of the model. In the shorter-term half of the model, it is hypothesized that once a system has gone live, two factors, namely functional fit and overcoming organizational inertia, drive organizational benefits flowing from each major ES improvement project. The importance of these factors may vary from project to project. In the long-term half of the model, it is hypothesized that four additional factors, namely integration, process optimization, improved access to information, and on-going major ES business improvement projects, drive organizational benefits from ES over the long term. Preliminary tests of the model were conducted using data from 126 customer presentations from SAP's 2003 and 2005 Sapphire U.S. conferences. All six factors were found to be important in explaining variance in organizational benefits from enterprise systems from the perspective of senior management.
Respecting and fulfilling the right of post-primary pupils to consent to participate in trials and evaluative research: a discussion paper

ABSTRACT This paper provides an introduction to issues surrounding the participation rights of young people in research and the implications of their growing involvement in research as well as providing a discourse on the ethical implications related to consent. The unique contribution of this paper is that it considers children’s rights in respect to the increasing opportunities for young people to take part in evaluation research. The aim of this paper, therefore, is to acknowledge the growing involvement for young people in research and the implications of ensuring that their rights of participation are respected. Secondly, we will consider the children’s rights legislation and our obligations as researchers to implement this. Finally, we will explore consent as an issue in its own right as well as the practicalities of accessing participants. This paper will postulate that any research about young people should involve and prioritize at all stages of the research process; including participation in decision-making. We conclude by identifying five key principles, which we believe can help to facilitate the fulfilment of post-primary pupils’ ability to consent to participate in trials and evaluative research.
The effect of functional hearing loss and age on long- and short-term visuospatial memory: evidence from the UK biobank resource

The UK Biobank offers cross-sectional epidemiological data collected on >500,000 individuals in the UK between 40 and 70 years of age. Using the UK Biobank data, the aim of this study was to investigate the effects of functional hearing loss and hearing aid usage on visuospatial memory function. This selection of variables resulted in a sub-sample of 138,098 participants after discarding extreme values. A digit triplets functional hearing test was used to divide the participants into three groups: poor, insufficient and normal hearers. We found negative relationships between functional hearing loss and both visuospatial working memory (i.e., a card pair matching task) and visuospatial, episodic long-term memory (i.e., a prospective memory task), with the strongest association for episodic long-term memory. The use of hearing aids showed a small positive effect for working memory performance for the poor hearers, but did not have any influence on episodic long-term memory. Age also showed strong main effects for both memory tasks and interacted with gender and education for the long-term memory task. Broader theoretical implications based on a memory systems approach will be discussed and compared to theoretical alternatives.