Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small-cell lung cancer

RNA interference (RNAi) is a powerful gene-silencing platform for cancer treatment. Previously, we demonstrated that ribophorin II (RPN2), which is part of the N-oligosaccharyl transferase complex, regulates docetaxel sensitivity and tumor lethal phenotypes in breast cancer. However, the molecular functions and clinical relevance of RPN2 in non-small-cell lung cancer (NSCLC) remain unknown. Here, we examined RPN2 expression in tumor specimens from recurrent NSCLC patients after resection (n = 32 and = 177) and assessed the correlation between RPN2 expression and various clinical features. We also investigated whether RPN2 affects cancer malignancy in vitro and tumor growth and drug resistance in vivo. Our data show that RPN2 expression confers early and distant recurrence as well as poor survival in NSCLC patients. Furthermore, RPN2 silencing suppressed cell proliferation and invasiveness, and increased the sensitivity to chemotherapeutic drugs in vitro. Remarkably, we found that intrinsic apoptosis signaling is the mechanism of cell death involved with RPN2 knockdown. Strikingly, RPN2 silencing repressed tumorigenicity and sensitized the tumors to cisplatin treatment, which led to the longer survival of NSCLC-bearing mice. In conclusion, these data suggest that RPN2 is involved in the regulation of lethal cancer phenotypes and represents a promising new target for RNAi-based medicine against NSCLC.
Chirp parameter estimation using rank reduction

This paper considers the problem of estimating the bandwidth and the center frequency of a linear chirp signal from discrete-time noisy observations. The non-stationarity property of chirp signals implies that the signal has high rank and reduces the applicability of subspace based algorithms significantly. However, the special structure of the sample covariance matrix invites to use regular frequency estimation algorithms. We show how subspace type algorithms may be modified to provide accurate signal parameter estimates for linear chirp signals. The root-MUSIC algorithm is used as an example. Simulations compare the algorithm with a rank reduction method proposed by DiMonte and Arun (1990).
Convergent Effects of Acute Stress and Glucocorticoid Exposure upon MAO-A in Humans

Monoamine oxidase-A (MAO-A), a key brain enzyme which metabolizes monoamines, is implicated in the pathophysiology of stress-related illnesses, including major depressive disorder, addiction, and violent behavior. Chronic stressors and glucocorticoid-administration typically associate with elevated MAO-A levels/activity. However, the relationship of shorter stress or glucocorticoid exposures and MAO-A levels/activity is not well established. Our objectives are to assess effects of acute stress upon MAO-A VT, an index of MAO-A density, in human brain and acute glucocorticoid exposure upon MAO-A levels in human neuronal and glial cell lines. Twelve healthy, non-smoking participants aged 18–50 underwent [11C]harmine positron emission tomography to measure brain MAO-A VT on two different days: One under acute psychosocial stress (via Trier Social Stress and Montreal Imaging Stress Tasks) and one under a non-stress condition. MAO-A density (by Western blot) and activity (by [14C]-5-HT metabolism and liquid scintillation spectroscopy) were measured in human neuronal and glial cell lines after 4 h exposure to dexamethasone. We observed a significant reduction in whole-brain MAO-A binding as reflected by reductions in 10 of 11 brain regions. Acute dexamethasone exposure in neuronal and glial cells significantly decreased MAO-A activity and protein levels. We observed a highly consistent relationship between acute stressors and glucocorticoid administration and decreased MAO-A binding, activity and protein levels. Since MAO-A metabolizes monoamines, this phenomenon may explain why acute stressors benefit healthy animals even though chronic stress is associated with illness.
Recognizing rotated faces and Greebles: What properties drive the face inversion effect?

The fact that faces are strongly affected by picture-plane inversion has often been cited as evidence for face-specific mechanisms. It is unclear, however, whether this “face inversion effect” is driven by properties shared by faces or whether the effect is specific to faces as a category. To address this issue, we compared the recognition of faces and novel Greebles, which were specifically matched to faces along various stimulus dimensions. In two experiments, participants were required to name individual faces or Greebles following training at either single or multiple orientations. We found that performance systematically decreased with increasing misorientation from either the upright (Experiment 1) or nearest trained orientation (Experiment 2). Importantly, the magnitude of this orientation effect was similar for both faces and Greebles. Taken together, these results suggest that the face inversion effect may be a consequence of the visual homogeneity of the stimulus category, regardless of the category.
Differential Involvement of the P2Y1 and P2Y12 Receptors in Platelet Procoagulant Activity

Objective—In vivo, activated platelets contribute to the initiation of thrombin generation through the exposure of phosphatidylserine to form a procoagulant catalytic surface and through platelet-leukocyte interactions, which lead to the exposure of leukocyte tissue factor (TF). On the basis of observations that the platelet P2Y1 and P2Y12 receptors both contribute to thrombosis and thrombin formation in an in vivo model of TF-induced thromboembolism, we further characterized the role of these receptors in thrombin generation. Methods and Results—By using the selective P2 antagonists MRS2179 and AR-C69931MX, the P2Y12 receptor was found to be involved in thrombin-induced exposure of PS on isolated platelets and consequently in TF-induced thrombin formation in platelet-rich plasma. By contrast, the P2Y1 receptor was not involved in phosphatidylserine exposure nor in thrombin generation in platelet-rich plasma. In addition, both receptors were found to contribute to the interactions between platelets and leukocytes mediated by platelet P-selectin exposure, which result in TF exposure at the surface of leukocytes. Conclusions—Overall, these results point to a differential involvement of the 2 platelet ADP receptors in the generation of thrombin and provide further evidence for the relevance of molecules targeting these receptors as antithrombotic agents.
Impaired Autoimmune T Helper 17 Cell Responses Following DNA Vaccination against Rat Experimental Autoimmune Encephalomyelitis

Background We have previously shown that vaccination with DNA encoding the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)91–108 (pMOG) suppresses MOG91–108-induced rat Experimental Autoimmune Encephalomyelitis (EAE), a model for human Multiple Sclerosis (MS). The suppressive effect of pMOG is dependent on inclusion of CpG DNA in the plasmid backbone and is associated with early induction of Interferon (IFN)-β. Principal Findings In this study we examined the mechanisms underlying pMOG-induced protection. We found that in the DNA vaccinated cohort proinflammatory Interleukin (IL)-17 and IL-21 responses were dramatically reduced compared to in the control group, but that the expression of Foxp3 and Tumor Growth Factor (TGF)-β1, which are associated with regulatory T cells, was not enhanced. Moreover, genes associated with Type I IFNs were upregulated. To delineate the role of IFN-β in the protective mechanism we employed short interfering RNA (siRNA) to IFN-β in the DNA vaccine. SiRNA to IFN-β completely abrogated the protective effects of the vaccine, demonstrating that a local early elaboration of IFN-β is important for EAE protection. IL-17 responses comparable to those in control rats developed in rats injected with the IFN-β-silencing DNA vaccine. Conclusions We herein demonstrate that DNA vaccination protects from proinflammatory Th17 cell responses during induction of EAE. The mechanism involves IFN-β as IL-17 responses are rescued by silencing of IFN-β during DNA vaccination.
Comparative Study of Genome Divergence in Salmonids with Various Rates of Genetic Isolation

The aim of the study is a comparative investigation of changes that certain genome parts undergo during speciation. The research was focused on divergence of coding and noncoding sequences in different groups of salmonid fishes of the Salmonidae (Salmo, Parasalmo, Oncorhynchus, and Salvelinus genera) and the Coregonidae families under different levels of reproductive isolation. Two basic approaches were used: (1) PCR-RAPD with a 20–22 nt primer design with subsequent cloning and sequencing of the products and (2) a modified endonuclease restriction analysis. The restriction fragments were shown with sequencing to represent satellite DNA. Effects of speciation are found in repetitive sequences. The revelation of expressed sequences in the majority of the employed anonymous loci allows for assuming the adaptive selection during allopatric speciation in isolated char forms.
Personality Assessment in Gender Dysphoria: clinical observation in psychopathological evidence

Background: Gender Dysphoria is a condition of great distress and mental suffering associated with a strong identification with the opposite sex than biological birth. The literature shows that there is a historical account of the evolution of the disorder and that the different approaches to clinical reality, generate considerations that also depend on the use of study methods. Method: Twentytwo subjects, diagnosed with gender dysphoria, aged between 18 and 47 years, studied through clinical and content scales of MMPI-2 questionnaire, to highlight the presence psychopathological indices. Results: Findings in the descriptive analysis shows that the majority of patients do not present a prevalence of psychopatology, with the exception of Pa scale. In differential terms are highlighted scraps with male predominance in the Fear scale and female prevalence in the ASP scale. As regards the frequencies, there is female predominance in ANG and Pd scales. Conclusions: The study suggests some scientific elements related to clinical practice with Gender Dysphoria, which take into account the meant of questionnaire’s use for subject's personality study.
Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice.

The purpose of these studies was to examine the growth characteristics and metastatic behavior of freshly isolated human colorectal carcinomas implanted into athymic nude mice. Four tumor lines were derived from primary colorectal carcinomas, three lines from hepatic metastases, and one line from a metastasis to a mesenteric lymph node. Subsequent to implantation into the subcutis or the muscularis, tumor lines derived from metastases grew faster in the nude mice than did cells isolated from the primary neoplasms. Regardless of the source of the cells, however, little or no visceral organ metastasis was found. Subsequent to i.v. injection, experimental lung colonies could be produced by some of the cells, but there was no correlation between lung tumor colony formation and the origin of the human colorectal cells. The intrasplenic injection of colorectal carcinoma cells provided a useful procedure to identify human colorectal carcinoma cells with metastatic potential to liver. Extensive tumor burdens in the liver were observed as early as 30 days after injection with two of the three liver metastasis-derived tumor lines. No liver metastases were found after the intrasplenic injection of cells isolated from the lymph node-derived tumor line. Ninety days after the intrasplenic injection of cells from the four primary colorectal carcinomas, limited liver metastases were observed. We conclude that metastasis of human colorectal carcinomas can be studied in nude mice, and its outcome depends upon both the intrinsic metastatic capacity of the human tumor cells and the organ environment of implantation.
A Pathway-Dependent on ApoE, ApoAI, and ABCA1 Determines Formation of Buoyant High-Density Lipoprotein by Macrophage Foam Cells

Objective—ABCA1-dependent and ABCA1-independent pathways may operate in high-density lipoprotein formation by macrophages secreting apolipoprotein (apo) E. We examined the impact of ABCA1 on apoE-mediated efflux from cholesterol-enriched macrophages. Methods and Results—Without acceptors, wild-type, ABCA1−/−, and apoE−/− macrophages released 5.7%±0.3%, 1.8%±0.1%, and 2.3%±0.2% of their cholesterol, and the LXR agonist, TO-901317, enhanced efflux by 137%, 10%, and 20%. Although similar amounts of apoE were secreted from ABCA1−/− and wild-type cells, apoE from ABCA1−/− cells was only partially phospholipidated and floated at density >1.21g/mL, whereas apoE from wild-type cells floated at density of 1.09 to 1.17g/mL and paralleled the density of cholesterol. With apoAI, LXR stimulation increased efflux by 139% and 86% from wild-type and apoE−/− cells, resulting in a large difference in efflux (29.5%±0.2% versus 17.0%±0.5%). The density of apoE and cholesterol from wild-type cells did not change with apoAI, and most apoAI floated at density ≥1.17g/mL. In apoE−/− cells, apoAI and cholesterol floated at similar density, but the peak fraction only contained 4 &mgr;g cholesterol/mg protein versus 18 in WT cells. Conclusions—Macrophage apoE requires ABCA1 for formation of high-density lipoprotein. ApoAI facilitates association of apoE with more buoyant high-density lipoprotein, suggesting that apoE, plasma apoAI, and ABCA1 operate together to optimize mobilization of macrophage cholesterol, a process critical to limiting plaque development.
Dendritic Cells Induced by TLR4 or TLR3 in Human of Th1 Cytokines That Are Specifically Stimulation Blocks the Induction of a Subset IL-10 Released by Concomitant TLR2

Recognition of microbial products through TLRs triggers the expression of several cytokines that regulate innate and adaptive immunity. Signaling by various TLRs is not equivalent and leads to differential gene induction. This study analyzed the responses of human dendritic cells (DCs) and PBMCs stimulated with agonists of TLR2, TLR3, TLR4, TLR5, and TLR7, ﬁrst individually and then in combination. Several cytokines were equally induced by all TLR agonists, but four genes, IFN- (cid:1) , IFN- (cid:2) -inducible protein 10 (IP-10), IL-12p35, and IL-15, showed a very restricted pattern of induction. Thus, each TLR appears to possess a distinctive ability to activate DCs or PBMCs, suggesting that TLR-mediated responses cannot be simply cataloged as resembling either TLR2 (MyD88 dependent) or TLR4 (MyD88 independent) and that other signaling modalities may exist. The analysis of DC and PBMC activation by combinations of TLR agonists revealed that TLR2 agonists are able to block the induction of IP-10, IL-12p35, and IFN- (cid:2) , but not IL-15 and IFN- (cid:1) , by TLR3 and TLR4. TLR2 stimulation led to rapid release of IL-10 that is responsible for inhibition of IP-10 and IL-12p35 induction. Cross-talk between different TLRs may modify the primary responses of TLR to their agonist, adding a further level of complexity to the regulation of innate immunity. The Journal of Immunology, 2004, 173: 7548–7555.
Money ethic, moral conduct and work related attitudes: Field study from the public sector in Swaziland

Purpose This study investigates perception of ethical and moral conduct in the public sector in Swaziland, specifically, the relationship among: money ethic, attitude towards business ethics, corruption perception, turnover intention, job performance, job satisfaction, and the demographic profile of respondents. Methodology/Approach The study was a survey using self-administered questionnaires. Using stratified sampling technique in selected organisations, usable data was collected from 83 public sector employees in Swaziland. Findings Results indicated significant relationship among money ethic, attitude towards business ethics, turnover intention and job performance. The importance of money as a motivator was also demonstrated. Respondents hold that civil servants’ involvement in corruption is high and that bribery and corruption is widespread in Swaziland. Research limitations/implications The sample size was small and hence limits generalization of findings, but provides preliminary information for a larger study. The need to enrich future studies with in-depth follow-up interviews was noted. Practical implication The respondents’ perception of widespread corruption calls for a reinvigoration of government anti-graft efforts and the need to promote ethical consciousness in the country. Originality/value of paper This paper has demonstrated the importance of ethical awareness, the importance of money as a motivator and the state of corruption in another cultural setting – Swaziland.
Virtual Knowledge Communities for Distributed Knowledge Management: A Multi-Agent-Based Approach using JADE

Virtual communities are becoming increasingly popular, particularly on the internet, as a means for like-minded individuals to meet, share and gain access to the information they are most interested in quickly and efficiently, from other individuals they can learn to trust. The concept of a community of practice or a community of interest can be supported in a virtual community in order to bring the appropriate parties together, to share their knowledge with each other. In this project, the most general model for modelling distributed knowledge management is investigated, that involves extending the abstraction of an agent, such that it becomes an actor within a knowledge community. In this model, agents themselves, software or human, are the members of the virtual knowledge sharing communities. Agents can choose to join, leave, create and destroy communities, and can be member of many communities simultaneously. A Jade-based prototype design and implementation are used to show how such a system can operate and be useful in practice.
Domatic number of graph products

A partition of V (G), all of whose classes are dominating sets in G, is called a domatic partition of G. The maximum number of classes of a domatic partition of G is called the domatic number of G. The concept of a domatic number was introduced in [1]. More interesting results on domatically full graphs, domatically critical, domatically cocritical graphs and other domatic numbers can be found in [3], [4], [5], [6], [7]. We explore the bounds the domatic number of the cartesian product, the strong product and the corona of two graphs. The join of two graphs and its generalization also is studied. Motivation of this problem comes from [2], where the domatic number of the cartesian product of two paths was established.
Somatosensory system; touch : Physiology and Neuronal Correlates of Discriminative and Affective Touch

This essay is about the somatosensory system, which is divided into different kinds of touch. Described briefly are the proprioceptive touch, which is transported to the brain via A-alfa fibers and transmits information about e. g. limb position and movement. The cutaneous touch is the main focus and it is divided into discriminative touch and affective touch. The first corresponds to stimuli such as vibration and pressure and is transported via A-beta axons. The second, affective touch, corresponds to e.g. painful and pleasant stimuli which are transported to the brain via A-delta and C-fibers. The aim of the essay is to give an overview of the sense of touch, by doing a literature search, including a discussion of relevant neuronal correlates focusing particularly on affective touch. Moreover, the physiological aspects of touch will be presented. The sources that are used are review and original articles taken from databases such as ScienceDirect, and some articles send by the author. Some books have also been used to find more general knowledge. The conclusion for the essay is that touch is important for humans to function in everyday life. Additional, a specific receptor called C- tactile (CT) is identified to correspond to gentle touch and is suggested to have a vital role for humans in maintaining and forming social bounds. Moreover, discriminative touch is associated with activation in the primary and secondary somatosensory cortex, whereas affective touch seems to be associated with activity in the orbitofrontal cortex, cingulate cortex and the insula cortex, as well as the prefrontal cortex, which is suggested to be activated during interpersonal touch. Further, the sense touch needs to be more researched in order to understand its functions and benefits deeper.
LTP and LTD in the Visual Cortex Require the Activation of NOX2

Reactive oxygen species (ROS) are signaling factors involved in many intracellular transduction pathways. In the nervous system, ROS are thought to modulate various mechanisms of synaptic plasticity. One important source of ROS production in the brain is the NADPH oxidase complex. Stimulation of NMDA receptors activates NADPH oxidase, which provides selective oxidative responses accompanying the induction of synaptic changes. The activity of NADPH oxidase is known to be crucial for the induction of LTP in the hippocampus. However, the involvement of this complex in cortical synaptic plasticity is still unclear. Here we provide evidence that genetic ablation of NOX2 (the prototypical member of NADPH oxidase family of proteins) suppresses LTP and LTD in the primary visual cortex of the mouse. We also found that the involvement of NOX2 on LTP is partially age-dependent, as the activity of this complex is not critical for mechanisms of synaptic potentiation occurring in immature animals. Furthermore, we show that inhibition of NOX2 reduces the NMDA receptor function, suggesting a possible mechanism that could be the basis of the effects on synaptic plasticity.