Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased importin-β-dependent nuclear import of the actin modulating protein CapG promotes cell invasion

CapG (gCap39) is a ubiquitous gelsolin-family actin modulating protein involved in cell signalling, receptor-mediated membrane ruffling, phagocytosis and motility. CapG is the only gelsolin-related actin binding protein that localizes constitutively to both nucleus and cytoplasm. Structurally related proteins like severin and fragmin are cytoplasmic because they contain a nuclear export sequence that is absent in CapG. Increased CapG expression has been reported in some cancers but a causal role for CapG in tumour development, including invasion and metastasis, has not been explored. We show that moderate expression of green fluorescent protein-tagged CapG (CapG-EGFP) in epithelial cells induces invasion into collagen type I and precultured chick heart fragments. Nuclear export sequence-tagged CapG-EGFP fails to induce invasion, whereas point mutations in the nuclear export sequence permitting nuclear re-entry restore cellular invasion. Nuclear import of CapG is energy-dependent and requires the cytosolic receptor importin β but not importin α. Nuclear CapG does not possess intrinsic transactivation activity but suppresses VP16 transactivation of a luciferase reporter gene in a dose-dependent manner. Furthermore, invasion requires signalling through the Ras-phosphoinositide 3-kinase pathway and Cdc42 or RhoA, but not Rac1. We show for the first time active nuclear import of an actin binding protein, and our findings point to a role for nuclear CapG in eliciting invasion, possibly through interfering with the cellular transcription machinery.
Precise Brightfield Localization Alignment for Fourier Ptychographic Microscopy

Fourier ptychographic microscopy (FPM) is a recently developed microscope technology that overcomes the resolution limit of a low numerical aperture objective lens by employing angular varying illuminations. Combining the concepts of ptychography, synthetic aperture, and phase retrieval, FPM achieves high-resolution, wide-field, and quantitative phase imaging at the same time. In typical FPM systems, the angular varying illuminations are achieved with LED arrays whose positional misalignments bring significant errors in the reconstruction procedure. In previous studies, several LED array alignment methods are developed, which iteratively recover the positional misalignment parameters during the reconstruction. These methods consume additional calculations in FPM reconstruction and may not be practical in other microscopy system. In this work, we represent a preprocessing LED array alignment method by accurately localizing the brightfield area on the sample plane. By applying particle swarm optimization method and random sample consensus method, the global misalignment parameters can be estimated with high accuracy and speed. Both numerical simulations and actual system experiments are carried out to evaluate the effectiveness of our method and the results show that the reconstruction quality of high-resolution images is significantly improved by using our method.
Homotopic connectivity in drug-naïve, first-episode, early-onset schizophrenia.

BACKGROUND The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy - a measure of interhemispheric connection - and its relevance to clinical symptoms in first-episode drug-naïve early-onset schizophrenia (EOS) patients. METHODS Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naïve EOS patients (age: 14.5 ± 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 ± 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC). RESULTS Early-onset schizophrenia patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients. CONCLUSIONS Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status.
mVisualizer: Easily Accessible Data Exploration for Clinicians

In medical research and clinical work, having direct access to a large knowledge base of information about patients is very useful. Software for information visualisation can help the user browse, analyse and learn from such knowledge, thus providing new insights and accelerating research. However, when introducing new software to clinicians, who may have limited computer knowledge, adoption can be hindered by the complexity of the applications and the time investments necessary to learn them. By involving clinicians directly in the design process, we have developed mVisualizer, an application that provides a hands-on workspace to visualise and explore patient data. mVisualizer was designed for accessibility and simplicity, and to encourage users to explore the data in order to make discoveries and pose new questions relevant for knowledge gathering and research. The user-centered approach helped ensure that mVisualizer is understandable and easy to learn for clinicians. The application is in use by clinicians today, and its use has led to new discoveries and theories that will be the subject of future medical research. This leads to the conclusion that information visualisation software for exploring patient data can help clinicians and researchers by making the data more accessible, which stimulates research and learning.
AGRICULTURAL INTENSIFICATION IN SUB-SAHARAN AFRICA

This paper focuses on extracts from a recent comparative analysis of livestock and land use surveys across a range of agro-climatic conditions in sub-Saharan Africa, based on information from systematic low level aerial reconnaissance and complementary ground studies in Mali, Niger, Nigeria, Sudan and Tchad, between 1980 and 1993. Results indicate a highly significant relationship between livestock biomass and the intensity of land use, and suggest that cultivation and human habitation are the best predictors of livestock distribution. These findings are consistent with expectations of the Boserup hypothesis, and are indicative of the `autonomous intensification' of agricultural production associated with the growth of human population, through closer interaction between livestock and arable farmers. The autonomous control of tsetse and trypanosomiasis is a further consequence of the environmental impact of human population growth, which has favoured the southward dispersal and year-round presence of cattle in the Nigerian sub-humid zone. This in turn has created circumstances which have favoured the spread of animal traction and livestock fattening, which are themselves indicative of the intensification process.
Learning Document-Level Semantic Properties from Free-Text Annotations

This paper presents a new method for inferring the semantic properties of documents by leveraging free-text keyphrase annotations. Such annotations are becoming increasingly abundant due to the recent dramatic growth in semi-structured, user-generated online content. One especially relevant domain is product reviews, which are often annotated by their authors with pros/cons keyphrases such as "a real bargain" or "good value. " These annotations are representative of the underlying semantic properties; however, unlike expert annotations, they are noisy: lay authors may use different labels to denote the same property, and some labels may be missing. To learn using such noisy annotations, we find a hidden paraphrase structure which clusters the keyphrases. The paraphrase structure is linked with a latent topic model of the review texts, enabling the system to predict the properties of unannotated documents and to effectively aggregate the semantic properties of multiple reviews. Our approach is implemented as a hierarchical Bayesian model with joint inference. We find that joint inference increases the robustness of the keyphrase clustering and encourages the latent topics to correlate with semantically meaningful properties. Multiple evaluations demonstrate that our model substantially outperforms alternative approaches for summarizing single and multiple documents into a set of semantically salient keyphrases.
Borderline Personality Disorder

The term ‘Borderline Personality Disorder’ (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity. In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral ‘strategy’ which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic ‘deficit’-oriented models, which may have profound implications for therapeutic approaches.
Survey on Privacy Permission Management Approaches for Android OS Applications

Smart phones have been becoming popular and mobile users are increasingly relying on them to store and handle personal information. The intake of smart phone devices for email writing, online bank transactions growing with growth of the smartphone market and accessing other forms of sensitive content has lead to the emergence of a new and ever changing threat. However, recent studies also reveal the disturbing fact that users personal information is put at risk by smart phone applications. Existing mobile privacy approaches are having limitations in their performance in handling these privacyviolating smart phone applications. Android OS(Operating System) supports the third party software development mostly. However, many of these applications accesses private or sensitive data totally negligent which immediately leads to serious privacy concerns. To reduce this problem, the current Android permission rules are much too coarse and incomprehensible from the average users perspective. Mobile users does not understands the meaning of the permissions, so he or she must either accept all of them or waive the application. Privacy Permission Management for Android OS has becomes very important security issue as, the user has only two options when they install new applications – accept the permissions and allow the install, or reject all the terms and exit without installation. So here is the need to design system in the manner which provides security to user’s personal information leak and misuse of it should be prevented. This paper provides the study of different approaches of privacy permission management and the outline of all the studied papers.
Perturbation of the morphology of the trans-Golgi network following Brefeldin A treatment: redistribution of a TGN-specific integral membrane protein, TGN38

Brefeldin A (BFA) has a dramatic effect on the morphology of the Golgi apparatus and induces a rapid redistribution of Golgi proteins into the ER (Lippincott-Schwartz, J., L. C. Yuan, J. S. Bonifacino, and R. D. Klausner. 1989. Cell. 56:801-813). To date, no evidence that BFA affects the morphology of the trans-Golgi network (TGN) has been presented. We describe the results of experiments, using a polyclonal antiserum to a TGN specific integral membrane protein (TGN38) (Luzio, J.P., B. Brake, G. Banting, K. E. Howell, P. Braghetta, and K. K. Stanley. 1990. Biochem. J. 270:97-102), which demonstrate that incubation of cells with BFA does induce morphological changes to the TGN. However, rather than redistributing to the ER, the majority of the TGN collapses around the microtubule organizing center (MTOC). The effect of BFA upon the TGN is (a) independent of protein synthesis, (b) fully reversible (c) microtubule dependent (as shown in nocodazole- treated cells), and (d) relies upon the hydrolysis of GTP (as shown by performing experiments in the presence of GTP gamma S). ATP depletion reduces the ability of BFA to induce a redistribution of Golgi proteins into the ER; however, it has no effect upon the BFA-induced relocalizations of the TGN. These data confirm that the TGN is an organelle which is independent of the Golgi, and suggest a dynamic interaction between the TGN and microtubules which is centered around the MTOC.
Increased dispersion of atrial repolarization in Brugada syndrome.

AIMS Patients with Brugada syndrome (BS) often experience atrial fibrillation (AF) and atrial vulnerability, as measured by increased atrial conduction time. To date, however, dispersion of atrial repolarization has not been reported in these patients. METHODS AND RESULTS Monophasic action potentials (MAPs) recorded from four sites of the right atrium were analysed in 11 patients (10 men, 1 woman; mean age, 40 ± 9 years) with BS and in 10 controls (8 men, 2 women; mean age, 35 ± 8 years). None of these patients had a history of AF. Monophasic action potentials were recorded during right atrial pacing at a drive cycle length of 600 ms after continuous pacing. Dispersion of MAP duration (D-MAPD90) was defined as the difference between the maximum and minimum MAP duration measured at 90% repolarization (MAPD90). Inducibility of AF and repetitive atrial firing were also determined. The MAPD90 did not differ significantly between the BS and control groups (245 ± 42 vs. 228 ± 24 ms, P = ns), but D-MAPD90 was significantly higher in the BS group (69.1 ± 35.0 vs. 41.4 ± 10.3 ms, P < 0.05). Atrial fibrillation was induced in six BS patients and repetitive atrial firing in four, but neither was induced in any of the control subjects. CONCLUSION The significantly increased dispersion of MAPD90 observed in patients with BS suggests that the heterogeneity of atrial repolarization may contribute to the development of atrial fibrillation in patients with BS.
A framework for case-based fuzzy multicriteria decision support for tropical cyclone forecasting

Case-based reasoning and multicriteria decision making have common grounds: they are both problem solving methodologies; both involve the selection, ranking and aggregation of best alternatives and provide tools for evaluating the alternatives in respect to multiple attributes or criteria. Each of the two methodologies has its own strengths and weaknesses. By integrating the two methodologies, we can take advantage of their strengths and complement each other's weaknesses. This paper proposes a multi-stage framework for intelligent decision support that integrates case-based reasoning and fuzzy multicriteria decision making techniques. We illustrated the proposed approach in the context of tropical cyclone prediction. We describe a prototype intelligent decision support system, which helps the forecaster in retrieving best-fitted solutions in terms of both usefulness and similarity to the current observed case.
Optimal initial insulin dosage for managing steroid-induced hyperglycemia in hospitalized COVID-19 patients: A retrospective single-center study

Objectives: To determine the optimal initial insulin dosage for controlling hyperglycemia in COVID-19 patients receiving steroids, an area with limited data. Methods: We retrospectively analyzed 156 COVID-19 patients with steroid-induced hyperglycemia treated with insulin. Patients were categorized by their total daily dose of subcutaneous insulin therapy when starting dexamethasone ⩾6 mg/day or equivalent dose of glucocorticoid: Group A (⩽0.29 units/kg), Group B (0.3–0.49 units/kg), Group C (0.5–0.69 units/kg), and Group B (⩾0.7 units/kg). Treatment failure was defined as mean blood glucose level > 280 mg/dL for two consecutive days after initiating insulin or any blood glucose ⩾ 400 mg/dL. Results: The mean age was 64 ± 14 years, with 50% male, and a mean body mass index of 26.9 ± 6.9 kg/m2. Most had preexisting type 2 diabetes (62%). Mean admission blood glucose and HbA1c were 233 ± 112 mg/dL and 7.8 ± 2.3%, respectively. Group A had the lowest HbA1c (6.7 ± 1.2%), while group D had the highest (9.8 ± 2.5%). Median daily dexamethasone dosage or equivalent was 36 (IQR 16.72) mg, with no significant differences in among groups. Group A had the lowest treatment failure rate. There were no significant differences in treatment failure rate between Groups B, C, and D. Additionally, there were no statistically significant differences in mean BG across the groups: Group A 232 ± 42 mg/dL, Group B 247 ± 57 mg/dL, Group C 247 ± 61 mg/dL, and Group D 227 ± 67 mg/dL (p = 0.2). Group D had a significantly higher rate of level 1 hypoglycemia (p = 0.008), while no differences in clinically significant hypoglycemia (level 2 or 3) were observed between groups. Conclusions: Among patients requiring TDD ⩾ 0.3 units/kg/day, there was no significant difference in treatment failure rate between Groups B, C, and D. Group D had the highest rate of level 1 hypoglycemia. This initial insulin dosage for hospitalized COVID-19 patients on high-dose steroid therapy should be personalized.
Pregnanolone Glutamate, a Novel Use-Dependent NMDA Receptor Inhibitor, Exerts Antidepressant-Like Properties in Animal Models

A number of studies demonstrated a rapid onset of an antidepressant effect of non-competitive N-methyl-d-aspartic acid receptor (NMDAR) antagonists. Nonetheless, its therapeutic potential is rather limited, due to a high coincidence of negative side-effects. Therefore, the challenge seems to be in the development of NMDAR antagonists displaying antidepressant properties, and at the same time maintaining regular physiological function of the NMDAR. Previous results demonstrated that naturally occurring neurosteroid 3α5β-pregnanolone sulfate shows pronounced inhibitory action by a use-dependent mechanism on the tonically active NMDAR. The aim of the present experiments is to find out whether the treatment with pregnanolone 3αC derivatives affects behavioral response to chronic and acute stress in an animal model of depression. Adult male mice were used throughout the study. Repeated social defeat and forced swimming tests were used as animal models of depression. The effect of the drugs on the locomotor/exploratory activity in the open-field test was also tested together with an effect on anxiety in the elevated plus maze. Results showed that pregnanolone glutamate (PG) did not induce hyperlocomotion, whereas both dizocilpine and ketamine significantly increased spontaneous locomotor activity in the open field. In the elevated plus maze, PG displayed anxiolytic-like properties. In forced swimming, PG prolonged time to the first floating. Acute treatment of PG disinhibited suppressed locomotor activity in the repeatedly defeated group-housed mice. Aggressive behavior of isolated mice was reduced after the chronic 30-day administration of PG. PG showed antidepressant-like and anxiolytic-like properties in the used tests, with minimal side-effects. Since PG combines GABAA receptor potentiation and use-dependent NMDAR inhibition, synthetic derivatives of neuroactive steroids present a promising strategy for the treatment of mood disorders. Highlights: - 3α5β-pregnanolone glutamate (PG) is a use-dependent antagonist of NMDA receptors. - We demonstrated that PG did not induce significant hyperlocomotion. - We showed that PG displayed anxiolytic-like and antidepressant-like properties.
Genome-Wide Identification of PYL/RCAR ABA Receptors and Functional Analysis of LbPYL10 in Heat Tolerance in Goji (Lycium barbarum)

The characterization of the PYL/RCAR ABA receptors in a great deal of plant species has dramatically advanced the study of ABA functions involved in key physiological processes. However, the genes in this family are still unclear in Lycium (Goji) plants, one of the well–known economically, medicinally, and ecologically valuable fruit crops. In the present work, 12 homologs of Arabidopsis PYL/RCAR ABA receptors were first identified and characterized from Lycium (L.) barbarum (LbPYLs). The quantitative real–time PCR (qRT–PCR) analysis showed that these genes had clear tissue–specific expression patterns, and most of them were transcribed in the root with the largest amount. Among the three subfamilies, while the Group I and Group III members were down–regulated by extraneous ABA, the Group II members were up–regulated. At 42 °C, most transcripts showed a rapid and violent up–regulation response to higher temperature, especially members of Group II. One of the genes in the Group II members, LbPYL10, was further functionally validated by virus–induced gene silencing (VIGS) technology. LbPYL10 positively regulates heat stress tolerance in L. barbarum by alleviating chlorophyll degradation, thus maintaining chlorophyll stability. Integrating the endogenous ABA level increase following heat stress, it may be concluded that LbPYL–mediated ABA signaling plays a vital role in the thermotolerance of L. barbarum plants. Our results highlight the strong potential of LbPYL genes in breeding genetically modified L. barbarum crops that acclimate to climate change.
Accelerating Procedures of the Value Iteration Algorithm for Discounted Markov Decision Processes, Based on a One-Step Lookahead Analysis

Accelerating procedures for solving discounted Markov decision processes problems are developed based on a one-step lookahead analysis of the value iteration algorithm. We apply the criteria of minimum difference and minimum variance to obtain good adaptive relaxation factors that speed up the convergence of the algorithm. Several problems including Howard's automobile replacement are tested and a preliminary numerical evaluation reveals considerable reductions in computation time when compared to existing value iteration schemes.