Miracle-dz/UniFAR-FTUs huggingface dataset:
Active Surveillance for Scrapie by Third Eyelid Biopsy and Genetic Susceptibility Testing of Flocks of Sheep in Wyoming

ABSTRACT Control of scrapie, an ovine transmissible spongiform encephalopathy or prion disorder, has been hampered by the lack of conventional antemortem diagnostic tests. Currently, scrapie is diagnosed by postmortem examination of the brain and lymphoid tissues for PrPSc, the protein marker for this group of disorders. For live, asymptomatic sheep, diagnosis using tonsil or third-eyelid lymphoid tissue biopsy and PrPSc assay has been described. To evaluate the feasibility and efficacy of third-eyelid testing for identification of infected flocks and individual infected sheep, 690 sheep from 22 flocks were sampled by third-eyelid lymphoid tissue biopsy and immunohistochemistry. Sheep were further evaluated for relative genetic susceptibility and potential contact exposure to scrapie. Third-eyelid testing yielded suitable samples for 80% of the sheep tested, with a mean of 18.1 lymphoid follicles (germinal centers) per histologic section. Three hundred eleven of the sheep were sampled through passive surveillance programs, in which only sheep with potential contact with an infected sheep at a lambing event were tested, regardless of their scrapie susceptibility genotype. In addition, 141 genetically susceptible sheep with no record of contact with an infected animal at a lambing event were sampled through a targeted active surveillance program. Ten PrPSc-positive sheep were identified through the passive surveillance program, and an additional three PrPSc-positive sheep, including two from flocks with no history of scrapie, were identified through the active surveillance program. All PrPSc-positive sheep had the highly susceptible PrP genotype. Third-eyelid testing is a useful adjunct to flock monitoring programs, slaughter surveillance, and mandatory disease reporting in a comprehensive scrapie eradication and research program.
Is social entrepreneurship transformational leadership in action

As the title indicates we started with this question with a view to understand how research findings in these two fields of study, social entrepreneurship and transformational leadership, can help groom transformational leaders. It has been argued persuasively by leadership scholars that transformational leaders are essential to building sustainable organizations which consistently create wealth and contribute to the well-being of its employees. Even though the importance of transformational leadership in organizations is gaining more and more acceptance among both practitioners and scholars, most organizations still practice a transactional work style. These transactional work environments are not conducive for developing transformational leaders and therefore in this paper we suggest that letting aspiring leaders to get involved in social entrepreneurial ventures is an effective way to groom future transformational leaders. In this research we explored and uncovered the relationship between social entrepreneurship and transformational leadership for the following two purposes: First, to help social entrepreneurship researchers learn from the transformational leadership literature. Compared to social entrepreneurship research, the field of transformational leadership has reached a certain level of maturity so that social entrepreneurship researchers can borrow proven research methodologies and ideas from it. Secondly, we use this knowledge to develop strategies for instilling transformational leadership skills in students and practitioners aspiring to become transformational leaders. We have developed a framework to compare the conceptual basis of both social entrepreneurship and transformational leadership. We have also tried to explore the similarities between the processes of social-entrepreneuring and transformational-leading using this framework. Additionally, we have used the framework to study three of the most famous social entrepreneur turned transformational leaders of our time: Mother Teresa, Mahatma Gandhi and Wangari Maathai. We propose that helping people to experience social entrepreneuring is an effective way to instill transformational leadership skills.
Towards Model-Based Test automation for embedded systems using UML and UTP

Model-based methodologies such as the Model-Driven Development (MDD) and Model-Based Testing (MBT) are being explored, in the recent decade, for automation in embedded software engineering projects. In this context, the target of this paper is to demonstrate the adoption and applicability of the Unified Modeling Language (UML) and the UML Testing Profile (UTP) for deploying MBT in Resource-Constrained (RC)-Real-Time Embedded Systems (RTES). Though the UTP standard has been introduced several years ago, concrete approaches or tool support for generating the test artifacts based on the UTP is currently unavailable. This paper aims to close this gap and discusses a concise set of UTP artifacts in the context of MBT for RC-RTES. A detailed discussion on the test artifacts generation algorithm demonstrating the applicability of our approach in a real-life RC-RTES example is presented.
Visualizing lipid structure and raft domains in living cells with two-photon microscopy

The lateral organization of cellular membranes is formed by the clustering of specific lipids, such as cholesterol and sphingolipids, into highly condensed domains (termed lipid rafts). Hence such domains are distinct from the remaining membrane by their lipid structure (liquid-ordered vs. -disordered domains). Here, we directly visualize membrane lipid structure of living cells by using two-photon microscopy. In macrophages, liquid-ordered domains are particularly enriched on membrane protrusions (filopodia), adhesion points and cell–cell contacts and cover 10–15% of the cell surface at 37°C. By deconvoluting the images, we demonstrate the existence of phase separation in vivo. We compare the properties of microscopically visible domains (<1 μm2), with those of isolated detergent-resistant membranes and provide evidence that membrane coverage by lipid rafts and their fluidity are principally governed by cholesterol content, thereby providing strong support for the lipid raft hypothesis.
Neuropsychological and sensory gating deficits related to remote alcohol abuse history in schizophrenia

Recent evidence suggests that changes in brain structure associated with alcohol abuse are compounded in individuals dually diagnosed with alcohol abuse and schizophrenia. To investigate the separate, and possibly interacting, effects of these diagnoses, an event-related brain potential (ERP) measure of auditory information processing (P50 sensory gating paradigm) and neuropsychological measures were administered to healthy control participants with either (1a) no history of alcohol abuse/dependence, or (1b) a remote history of alcohol abuse/dependence, and patients with schizophrenia with either (2a) no history of alcohol abuse/dependence, or (2b) a remote history of alcohol abuse/dependence. Schizophrenia was associated with impaired P50 sensory gating and poorer performance across neuropsychological scores compared to measurements in healthy control participants. Those with a positive alcohol history had impaired gating ratios in contrast to those with a negative alcohol history. There were additive effects of schizophrenia diagnosis and alcohol history for P50 sensory gating and for neuropsychological scores: attention, working memory, and behavioral inhibition. For executive attention and general memory there was an interaction, suggesting that the combination of schizophrenia and history of alcohol abuse results in greater impairment than that predicted by the presence of either diagnosis alone. (JINS, 2006, 12, 34–44.)
Correlation of Left Ventricular Diastolic Function and Left Ventricular Geometry in Patients with Obstructive Sleep Apnoea Syndrome.

BACKGROUND The aim of this study is to evaluate the correlation of the left ventricular diastolic function and the left ventricular geometry in patients with obstructive sleep apnoea syndrome (OSAS) by echocardiography. METHODS The 181 patients diagnosed with OSAS were divided into the normal geometry group (NG), the concentric remodelling group (CR), the eccentric hypertrophy group (EH) and the concentric hypertrophy group (CH). Pearson correlation analysis and multiple linear regression analysis were performed toward the correlation of the left ventricular diastolic function and the left ventricular geometry. RESULTS The E peak in the EH and CH group was significantly reduced, with significant difference; the E/A, Em, Am and Em/Am was reduced in the order of the CR, EH and CH groups, while E/Em was increased, and the difference was significant. Pearson correlation analysis revealed that the Em/Am showed significant negative correlations with the left ventricular mass index (LVMI) [r = -0.419] and relative wall thickness (RWT) [r = -0.289], while the E/Em was significantly positively correlated with the LVMI (r = 0.638) and RWT [r = 0.328] (p < 0.001). Multiple linear regression analysis revealed that LVMI and RWT had influence on the Em/Am and E/Em (r2 = 0.402, r2 = 0.107, p < 0.001). The left ventricular diastolic dysfunction was the worst in the CH group. CONCLUSIONS There was correlation between the left ventricular diastolic dysfunction and the changes in cardiac geometry.
Segmentation using Sparse Shape Composition and minimally supervised method in liver surgery planning system

Liver surgery planning system plays an important role in achieving the optimized surgery plan in Living Donor Liver Transplantation (LDLT). Segmentation of liver is a very challenging component in liver surgery planning systems. Patient-specific shape prior is of great significance in improving the robustness of liver segmentation. However, complex liver shape variations among different patients are difficult to model, which affects the accurate segmentation in liver surgery planning. To address this problem, we incorporated the Sparse Shape Composition (SSC) in the computer assisted liver surgery planning system. The basic modules of the system consist of: (1) Segmentation module. The Sparse Shape Composition (SSC) model is employed to get a patient-specific liver shape prior and then the shape prior is combined with a minimally supervised method to segment the liver parenchyma, hepatic vessels and tumors simultaneously. (2) Approximation of liver segments. It divides the liver into several functionally independent segments. (3) Visualization module. The result of clinical experiment shows this system has a good performance in providing accurate and robust liver surgery planning.
AGD5 is a GTPase-activating protein at the trans-Golgi network.

ARF-GTPases are important proteins that control membrane trafficking events. Their activity is largely influenced by the interplay between guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which facilitate the activation or inactivation of ARF-GTPases, respectively. There are 15 predicted proteins that contain an ARF-GAP domain within the Arabidopsis thaliana genome, and these are classified as ARF-GAP domain (AGD) proteins. The function and subcellular distribution of AGDs, including the ability to activate ARF-GTPases in vivo, that remain largely uncharacterized to date. Here we show that AGD5 is localised to the trans-Golgi network (TGN), where it co-localises with ARF1, a crucial GTPase that is involved in membrane trafficking and which was previously shown to be distributed on Golgi and post-Golgi structures of unknown nature. Taking advantage of the in vivo AGD5-ARF1 interaction at the TGN, we show that mutation of an arginine residue that is critical for ARF-GAP activity of AGD5 leads to longer residence of ARF1 on the membranes, as expected if GTP hydrolysis on ARF1 was impaired due to a defective GAP. Our results establish the nature of the post-Golgi compartments in which ARF1 localises, as well as identifying the role of AGD5 in vivo as a TGN-localised GAP. Furthermore, in vitro experiments established the promiscuous interaction between AGD5 and the plasma membrane-localised ADP ribosylation factor B (ARFB), confirming that ARF-GAP specificity for ARF-GTPases within the cell environment may be spatially regulated.
Protection Against Late-Onset AIDS in Macaques Prophylactically Immunized with a Live Simian HIV Vaccine Was Dependent on Persistence of the Vaccine Virus1

This is a 5-year follow-up study on 12 macaques that were immunized orally with two live SHIV vaccines, six with V1 and six with V2. All 12 macaques became persistently infected after transient replication of the vaccine viruses; all were challenged vaginally 6 mo later with homologous pathogenic SHIVKU-1. Two of the V1 group developed full-blown AIDS without evidence of vaccine virus DNA in tissues. The data on the 10 vaccinated survivors showed that all 10 became infected with SHIVKU-1 and that DNA of both vaccine and SHIVKU-1 viruses were present 6 mo postchallenge, with minimal replication of SHIVKU-1. During the following 5 years, these animals remained persistently infected, but with only one of the two viruses. Six animals eliminated their vaccine virus after variable periods of time and four of these succumbed to reactivation of the challenge virus and AIDS. Five years after challenge, four latently infected animals, two with V2 and two with SHIVKU-1, were reinoculated with SHIVKU-1. This resulted in transient superinfection and the animals promptly returned to their prechallenge status. Immunosuppression of the four animals 1 year later with Abs to CD8+ lymphocytes resulted in transiently productive replication of their respective latent viruses, and upon recovery of CD8+ lymphocytes, they reverted to their latent virus status. The major finding was that of eight animals that eliminated the vaccine virus, six developed AIDS. The two others harboring SHIVKU-1 remain at risk for developing late-onset disease. The primary correlate against AIDS was persistence of the vaccine virus.
Neonatal macrophages express elevated levels of interleukin‐27 that oppose immune responses

Microbial infections are a major cause of infant mortality worldwide because of impaired immune defences in this population. The nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. Interleukin‐27 (IL‐27) is a heterodimeric cytokine of the IL‐12 family that is produced primarily by antigen‐presenting cells and is immunosuppressive toward a variety of immune cell types. We show that IL‐27 gene expression is elevated in cord blood‐derived macrophages relative to macrophages originating from healthy adults. We also evaluated the duration over which elevated IL‐27 gene expression may impact immune responses in mice. Age‐dependent analysis of IL‐27 gene expression indicated that levels of IL‐27 remained significantly elevated throughout infancy and then declined in adult mice. Flow cytometric analysis of intracellular cytokine‐stained splenocytes further confirmed these results. Interleukin‐27 may be induced during pregnancy to contribute to the immunosuppressive environment at the fetal–maternal interface because we demonstrate dose‐responsive gene expression to progesterone in macrophages. Neutralization of IL‐27 in neonatal macrophages improved the ability of these cells to limit bacterial replication. Moreover, neutralization of IL‐27 during incubation with the Mycobacterium bovis bacillus Calmette–Guérin vaccine augmented the level of interferon‐γ elicited from allogeneic CD4+ T lymphocytes. This suggests that blocking IL‐27 during vaccination and infection may improve immune responses in newborn and infant populations. Furthermore, mice will be a suitable model system to further address these possibilities.
Enhanced Effector and Memory CTL Responses Generated by Incorporation of Receptor Activator of NF-κB (RANK)/RANK Ligand Costimulatory Molecules into Dendritic Cell Immunogens Expressing a Human Tumor-Specific Antigen 12

The outcome of dendritic cell (DC) presentation of Ag to T cells via the TCR/MHC synapse is determined by second signaling through CD80/86 and, importantly, by ligation of costimulatory ligands and receptors located at the DC and T cell surfaces. Downstream signaling triggered by costimulatory molecule ligation results in reciprocal DC and T cell activation and survival, which predisposes to enhanced T cell-mediated immune responses. In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-κB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8+ T cell responses. We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-γ-secreting effector and memory T cells and E7-specific CTLs. These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens. Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival. These results have generic implications for improved tumor Ag-expressing DC vaccines, and specific implications for a DC-based vaccine approach for human papillomavirus 16-associated cervical carcinoma.
Clinical cues for detection of people with undiscovered depression in primary health care: a case–control study

Aim To identify clinical cues indicative of depression in medical records of cases in primary care with undetected depression. Background Depressive disorders are common; the lifetime risk for men and women is 27% and 45%, respectively. Despite effective treatment methods such as antidepressants and cognitive behavioural therapy, depression often remains undiscovered in primary care, with great implications both on the individual and societal level. Methods Clinical cues indicating depression were sought in medical records the year before an opportunistic screening for depression in primary care. In a previous study of 221 patients in the waiting room of a primary care centre during 10 randomly selected days, 45 (20%) showed signs of depression (MADRS-S ⩾ 12) and 60% of these were verified as having depressive disorders (Prime-MD). These 45 patients constitute the cases in the present study. Age- and gender-matched controls were selected among those who scored below the chosen cut-off level. Findings Seventeen (38%) of the 45 cases compared with eight (18%) of the 45 controls had one or more cues [odds ratio (OR) 2.81; 95% confidence interval (CI): 1.06–7.43]. Sleep disturbance showed the greatest difference between cases and controls (OR 4.53; 95% CI: 1.17–17.55). A significant relationship was found between severity of depression, frequency of cues and lower functional level. Cues were twice as common in patients with undetected depression and their functional level was lower. A two-stage procedure, screening and a structured diagnostic interview, is recommended when sleep disturbances and lowered function are present.
Assessing the transport of receptor-mediated drug-delivery devices across cellular monolayers

Receptor-mediated endocytosis (RME) has been extensively studied as a method for augmenting the transport of therapeutic devices across monolayers. These devices range from simple ligand-therapeutic conjugates to complex ligand-nanocarrier systems. However, characterizing the uptake of these carriers typically relies on their comparisons to the native therapeutic, which provides no understanding of the ligand or cellular performance. To better understand the potential of the RME pathway, a model for monolayer transport was designed based on the endocytosis cycle of transferrin, a ligand often used in RME drug-delivery devices. This model established the correlation between apical receptor concentration and transport capability. Experimental studies confirmed this relationship, demonstrating an upper transport limit independent of the applied dose. This contrasts with the dose-proportional pathways that native therapeutics rely on for transport. Thus, the direct comparison of these two transport mechanisms can produce misleading results that change with arbitrarily chosen doses. Furthermore, transport potential was hindered by repeated use of the RME cycle. Future studies should base the success of this technology not on the performance of the therapeutic itself, but on the capabilities of the cell. Using receptor-binding studies, we were able to demonstrate how these capabilities can be predicted and potentially adopted for high-throughput screening methods.
Leptin and lipid metabolism in chronic kidney failure

Objective. In the general population, leptin has been associated with atherosclerosis and has been shown to interfere with lipoprotein profiles. Patients with chronic renal failure are at increased risk of cardiovascular disease and display alterations in both lipoprotein and leptin levels. The aim of this study was to investigate the relationship between leptin and the lipoprotein profile in non‐dialyzed patients with chronic kidney disease (CKD). Material and methods. Leptin and lipid and lipoprotein concentrations were studied in 73 CKD patients and in 68 healthy controls in a cross‐sectional case‐control design. Results. The mean leptin levels were increased in the CKD patients (24.0 (SD 37.1) ng/mL) compared to those in controls (9.0 (SD 8.5) ng/mL) (p = 0.008). Also, the ratio between leptin levels and body mass index (leptin/BMI) was increased in CKD patients (mean 0.80 (SD 1.03)) compared to that in controls (0.31 (SD 0.24)) (p = 0.001). In linear regression analysis, leptin independently predicted total cholesterol and triglycerides in CKD patients (p = 0.010 and p = 0.001, respectively) and ratio between total and HDL cholesterol (Chol/HDL) in controls (p = 0.024). Furthermore, in CKD patients, the leptin/BMI predicted the variation in total cholesterol and triglycerides (p = 0.010 and p = 0.002, respectively). Conclusions. Leptin concentrations and leptin/BMI were elevated in CKD patients compared to those in controls. Leptin levels in both study groups, and leptin/BMI in the CKD group, were associated with atherogenic lipid profiles, which may contribute to the elevated cardiovascular risk that has been linked to hyperleptinaemia.