Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipopolysaccharide- and Lipoteichoic Acid-Induced Tolerance and Cross-Tolerance: Distinct Alterations in IL-1 Receptor-Associated Kinase1

Human Toll-like receptor (TLR) 4 and TLR2 receptors recognize LPS or lipoteichoic acid (LTA), respectively. Prolonged exposure of human macrophages/monocytes to bacterial LPS induces a state of adaptation/tolerance to subsequent LPS challenge. Inflammatory gene expressions such as IL-1β and TNF-α are selectively repressed, while certain anti-inflammatory genes such as secretory IL-1R antagonist are still induced in LPS-adapted/tolerant cells. In this report, we demonstrate that LPS-tolerized human promonocytic THP-1 cells develop cross-tolerance and no longer respond to LTA-induced IL-1β/TNF-α production, indicating that disruption of common intracellular signaling is responsible for the decreased IL-1β/TNF-α production. We observe that down-regulation of IL-1R-associated kinase (IRAK) protein level and kinase activity closely correlates with the development of cross-tolerance. IRAK protein levels and kinase activities in LPS-tolerized cells remain low and hyporesponsive to subsequent LPS or LTA challenges. We also demonstrate that THP-1 cells with prolonged LTA treatment develop LTA tolerance and do not express IL-1β/TNF-α upon further LTA challenge. Strikingly, cells tolerized with LTA are only refractory to subsequent LTA challenge and can still respond to LPS stimulation. Correspondingly, stimulation of TLR2 by LTA, although activating IRAK, does not cause IRAK degradation. IRAK from LTA-tolerized cells can be subsequently activated and degraded by further LPS challenge, but not LTA treatment. Our studies reveal that LTA-induced tolerance is distinct compared with that of LPS tolerance, and is likely due to disruption of unique TLR2 signaling components upstream of MyD88/IRAK.
Acceptance and Intake of Gel and Liquid Sucrose Compositions by the Argentine Ant (Hymenoptera: Formicidae)

Abstract Liquids and gels are common delivery forms used in commercial ant baits, but the relative effectiveness of each is unknown. We compared the feeding responses of the Argentine ant, Linepithema humile (Mayr), to liquid and gel compositions of sucrose. In choice assays, more workers were counted on gel than liquid; however, substantially more liquid was consumed. Because workers could stand on the gel, more workers could feed simultaneously on the gel. The feeding bouts of individual workers, however, were much less efficient at extracting sucrose in gel form. Workers fed eightfold longer on the gel, yet removed fivefold less sucrose than workers feeding on liquid. This potential bias should be considered during attraction and palatability studies that use physically different bait compositions. When the toxicant fipronil was added to the compositions, a greater proportion of the colony died after workers had fed on liquid than gel baits. This finding suggests that liquid formulations may provide more effective control of Argentine ants due to the greater speed and abundance in which it is ingested.
Heredity and age-related macular degeneration. Observations in monozygotic twins.

OBJECTIVE To determine the concordance of age-related macular degenerative changes in monozygotic twins. PATIENTS Between 1984 and 1993, we examined a total of nine pairs of monozygotic twins with substantial age-related macular degenerative changes in at least one member of the pair, ranging from extensive large drusen to advanced atrophic and/or disciform scarring. Eight pairs were female and one pair was male. Ages ranged from 62 to 88 years. Monozygosity was confirmed by genetic testing in each of the seven twin pairs on whom it was performed. RESULTS In eight of the nine twin pairs, the fundus appearance and the incidence of visual impairment were similar. In the ninth pair, one twin had advanced exudative age-related macular degeneration with vision loss in one eye, while the other had large, confluent drusen and good visual function in both eyes. Environmental factor, including diet, geographic background, and medical history, were essentially similar in the twin pairs. CONCLUSION Although selection factors and similar environmental influences might impact our findings, the markedly similar incidence of macular degenerative changes in these monozygotic twins suggests that a substantial genetic component may exist in a potentially large proportion of patients with age-related macular degeneration. Further studies are warranted to define this hereditary influence.
A survey of Black hole attack detection in Manet

MANET is an infrastructure less, dynamic, decentralised network. Any node can join the network and leave the network at any point of time. Due to its simplicity and flexibility, it is widely used in military communication, emergency communication, academic purpose and mobile conferencing. In MANET there no infrastructure hence each node acts as a host and router. They are connected to each other by Peer-to-peer network. Decentralised means there is nothing like client and server. Each and every node is acted like a client and a server. Due to the dynamic nature of mobile Ad-HOC network it is more vulnerable to attack. Since any node can join or leave the network without any permission the security issues are more challenging than other type of network. One of the major security problems in ad hoc networks called the black hole problem. It occurs when a malicious node referred as black hole joins the network. The black hole conducts its malicious behavior during the process of route discovery. For any received RREQ, the black hole claims having route and propagates a faked RREP. The source node responds to these faked RREPs and sends its data through the received routes once the data is received by the black hole; it is dropped instead of being sent to the desired destination. This paper discusses some of the techniques put forwarded by researchers to detect and prevent Black hole attack in MANET using AODV protocol and based on their flaws a new methodology also have been proposed.
SEP-225289 Serotonin and Dopamine Transporter Occupancy: A PET Study

SEP-225289 is a novel compound that, based on in vitro potencies for transporter function, potentially inhibits reuptake at dopamine, norepinephrine, and serotonin transporters. An open-label PET study was conducted during the development of SEP-225289 to investigate its dopamine and serotonin transporter occupancy. Methods: Different single doses of SEP-225289 were administered to healthy volunteers in 3 cohorts: 8 mg (n = 7), 12 mg (n = 5), and 16 mg (n = 7). PET was performed before and approximately 24 h after oral administration of SEP-225289, to assess occupancy at trough levels. Dopamine and serotonin transporter occupancies were estimated from PET using 11C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (11C-PE2I) and 11C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine (11C-DASB), respectively. Plasma concentration of SEP-225289 was assessed before ligand injection, and subjects were monitored for adverse events. Results: Average dopamine and serotonin transporter occupancies increased with increasing doses of SEP-225289. Mean dopamine and serotonin transporter occupancies were 33% ± 11% and 2% ± 13%, respectively, for 8 mg; 44% ± 4% and 9% ± 10%, respectively, for 12 mg; and 49% ± 7% and 14% ± 15%, respectively, for 16 mg. On the basis of the relationship between occupancy and plasma concentration, dopamine transporter IC50 (the plasma concentration of drug at 50% occupancy) was determined (4.5 ng/mL) and maximum dopamine transporter occupancy was extrapolated (85%); however, low serotonin transporter occupancy prevented similar serotonin transporter calculations. No serious adverse events were reported. Conclusion: At the doses evaluated, occupancy of the dopamine transporter was significantly higher than that of the serotonin transporter, despite similar in vitro potencies, confirming that, in addition to in vitro assays, PET occupancy studies can be instrumental to the drug development process by informing early decisions about indication, dose, and therapeutic potential.
Darunavir: a nonpeptidic protease inhibitor for antiretroviral-naive and treatment-experienced adults with HIV infection

Introduction: Darunavir, a nonpeptidic inhibitor of the HIV-1 protease with potent activity against resistant virus, was initially approved by the FDA (2006) and the EMA (2007) for the treatment of antiretroviral-experienced adults, and later for naive adults. Darunavir/ritonavir (600/100 mg twice daily, ideally given with two other active antiretrovirals) demonstrated superior efficacy compared to lopinavir/ritonavir and other protease inhibitors in highly experienced patients. Darunavir/ritonavir (800/100 mg once daily) was demonstrated to be safe and effective for the treatment of naive patients and those with limited darunavir resistance-associated mutations (RAMs). Because darunavir must be coadministered with ritonavir, cytochrome P450 drug–drug interactions can be problematic. Areas covered: The chemistry, pharmacokinetics, pharmacodynamics, efficacy and safety of darunavir are reviewed in this paper. A PubMed search was conducted using the search terms ‘randomized’, ‘darunavir’ and ‘efficacy’. Review articles and studies that primarily focused on other drugs were excluded. Expert opinion: Because darunavir exhibits efficacy against virus with significant protease inhibitor resistance mutations, it is critically important in the treatment of experienced patients, although viral suppression rates may be lower in those with a high baseline viral load or a greater number of cumulative darunavir RAMs. Darunavir/ritonavir is efficacious and well tolerated as a once-daily regimen in naive patients.
Encoding bird's trajectory using Recurrent Neural Networks

Recurrent Neural Networks (RNNs) are currently state of art tools for processing and classifying data sequences. This work aims to exploit these capabilities in Long-Short Term Memory (LSTM) networks which are a powerful variant of RNNs for encoding the birds' trajectory data into state vectors. These vectors should encapsulate the contextual information about the immediate trajectory coordinates. Therefore, they can generate new trajectory points based on their state and the latest output. However, probabilistic behavior of birds, effects of environment and noisy nature of measurements pose challenges for training and testing of the LSTM network models. This study solely focuses on the effects of spatial context and their significance in subsequent outputs to achieve compact representation of the traversed trajectory. Therefore, trajectory coordinates of birds were used as input to LSTM networks to learn spatial path features encoded in hidden vectors of the network. In the end, t-SNE method is used to visualize the state vectors in lower dimensional space embeddings and It was observed that these vectors contained contextual information about the traversed path.
Innate immunity and neuroinflammation in the CNS: The role of microglia in Toll‐like receptor‐mediated neuronal injury

Microglia are key players of the immune response in the central nervous system (CNS) and, being the resident innate immune cells, they are responsible for the early control of infections and for the recruitment of cells of the adaptive immune system required for pathogen clearance. The innate and adaptive immune responses triggered by microglia include the release of proinflammatory mediators. Although an efficient immune response is required for the defense against invading pathogens, an inflammatory response in the CNS may also lead to tissue injury and neurodegeneration. Engagement of Toll‐like receptors (TLRs), a major family of pattern recognition receptors that mediate innate immunity but also link with the adaptive immune response, provides an important mechanism by which microglia are able to sense both pathogen‐ and host‐derived ligands within the CNS. Although there is an increasing body of evidence that TLR signaling mediates beneficial effects in the CNS, it has become clear that TLR‐induced activation of microglia and the release of proinflammatory molecules are responsible for neurotoxic processes in the course of various CNS diseases. Thus, the functional outcome of TLR‐induced activation of microglia in the CNS depends on a subtle balance between protective and harmful effects. This review focuses on the neurodegenerative effects of TLR signaling in the CNS. © 2009 Wiley‐Liss, Inc.
M.SpyI, a DNA Methyltransferase Encoded on a mefA Chimeric Element, Modifies the Genome of Streptococcus pyogenes

ABSTRACT While screening the clonality of Streptococcus pyogenes isolates from an outbreak of erythromycin-resistant pharyngitis in Pittsburgh, PA, we found a correlation between the presence of the chimeric element Φ10394. 4 (carrying the macrolide efflux gene, mefA) and genomic DNA being resistant to cleavage by SmaI restriction endonuclease. A search of the open reading frames in Φ10394. 4 identified a putative type II restriction-modification (R-M) cassette containing a cytosine methyltransferase gene (spyIM). Heterologous expression of the cloned spyIM gene, as well as allelic-replacement experiments, showed that the action of this methyltransferase (M.SpyI) was responsible for the inhibition of SmaI digestion of genomic DNA in the Φ10394. 4-containing isolates. Analysis of the methylation patterns of streptococcal genomic DNA from spyIM-positive strains, a spyIM deletion mutant, and a spyIM-negative strain determined that M.SpyI specifically recognized and methylated the DNA sequence to generate 5′-CmCNGG. To our knowledge, this is the first methyltransferase gene from S. pyogenes to be cloned and to have its activity characterized. These results reveal why pulsed field gel electrophoresis analysis of SmaI-digested genomic DNA cannot be used to analyze the clonality of some streptococci containing Φ10394. 4 and may explain the inability of previous epidemiological studies to use SmaI to analyze DNAs from macrolide-resistant streptococci. The presence of the SpyI R-M cassette in Φ10394. 4 could impart a selective advantage to host strain survival and may provide another explanation for the observed increase in macrolide-resistant streptococci.
Latent Infection with Herpes Simplex Virus Is Associated with Ongoing CD8+ T-Cell Stimulation by Parenchymal Cells within Sensory Ganglia

ABSTRACT CD8+ T-cell persistence can be seen in ganglia harboring latent herpes simplex virus (HSV) infection. While there is some evidence that these cells suppress virus reactivation, this view remains controversial. Given that maintenance of latency by CD8+ T cells would necessitate ongoing exposure to antigen within this site, we sought evidence for such chronic stimulation. Initial experiments showed infiltration by activated but not naïve CD8+ T cells into ganglia harboring latent HSV infection. While such infiltration was independent of T-cell specificity, once recruited, only virus-specific T cells expressed high levels of preformed granzyme B, a marker of ongoing activation. Moreover, bone marrow replacement chimeras showed that these elevated granzyme levels were totally dependent on presentation by parenchymal cells within the ganglia. Overall, this study argues that activated CD8+ T cells are nonspecifically recruited into latently infected ganglia, and in this site they are exposed to ongoing antigen stimulation, most likely by infected neuronal cells.
Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity

A hallmark of polyglutamine diseases, including Huntington disease (HD), is the formation of β-sheet-rich aggregates, called amyloid, of causative proteins with expanded polyglutamines. However, it has remained unclear whether the polyglutamine amyloid is a direct cause or simply a secondary manifestation of the pathology. Here we show that huntingtin-exon1 (thtt) with expanded polyglutamines remarkably misfolds into distinct amyloid conformations under different temperatures, such as 4 °C and 37 °C. The 4 °C amyloid has loop/turn structures together with mostly β-sheets, including exposed polyglutamines, whereas the 37 °C amyloid has more extended and buried β-sheets. By developing a method to efficiently introduce amyloid into mammalian cells, we found that the formation of the 4 °C amyloid led to substantial toxicity, whereas the toxic effects of the 37 °C amyloid were very small. Importantly, thtt amyloids in different brain regions of HD mice also had distinct conformations. The thermolabile thtt amyloid with loop/turn structures in the striatum showed higher toxicity, whereas the rigid thtt amyloid with more extended β-sheets in the hippocampus and cerebellum had only mild toxic effects. These studies show that the thtt protein with expanded polyglutamines can misfold into distinct amyloid conformations and, depending on the conformations, the amyloids can be either toxic or nontoxic. Thus, the amyloid conformation of thtt may be a critical determinant of cytotoxicity in HD.
Interleukins 2 and 12 activate natural killer cytolytic responses of peripheral blood mononuclear cells from patients with head and neck squamous cell carcinoma.

OBJECTIVES To examine the capacity of interleukin-2 (IL-2) and interleukin-12 (IL-12) to modulate the cytolytic activity of peripheral blood mononuclear cells against squamous cell carcinoma, and to determine whether peripheral blood mononuclear cells from healthy donors respond differently to IL-12 than do peripheral blood mononuclear cells from patients with head and neck squamous cell carcinoma. DESIGN Case-comparison study of a consecutive sample of patients with head and neck squamous cell carcinoma who were scheduled to undergo surgical excision. PARTICIPANTS The study included 10 patients with stage III or IV carcinoma matched with 10 volunteer blood donors. INTERVENTION Isolated peripheral blood mononuclear cells from patients and volunteers were treated with IL-2, 10 U/mL and 100 U/mL; IL-12, 1 U/mL or 10 U/mL; or a combination of IL-2 and IL-12. RESULTS The combination of IL-2 and IL-12 consistently produced the greatest activation cytolysis than either cytokine alone at all concentrations tested. This increased activity against a squamous cell carcinoma cell line was seen in lymphocytes from volunteers and patients. CONCLUSION Our findings suggest a new treatment regimen for the patient with head and neck cancer that uses immunomodulation with a combination of cytokines.
Comparative Structure‐Function Analysis of VEGFR‐1 and VEGFR‐2

Abstract: Activation of vascular endothelial growth factor receptor‐1 and ‐2 (VEGFR‐1 and VEGFR‐2) plays a critical role in vasculogenesis and angiogenesis. However, the mechanism by which activation of VEGFRs elicits these cellular events is not fully understood. We recently constructed chimeric receptors containing the extracellular domain of human CSF‐1R/c‐fms fused with the entire transmembrane and cytoplasmic domains of murine VEGFR‐1 and VEGFR‐2. Selective activation of chimeric VEGFR‐2, but not chimeric VEGFR‐1, stimulated endothelial cell growth, migration, and differentiation. Stimulation of cells coexpressing chimeric VEGFR‐1 and VEGFR‐2 suppressed VEGFR‐2‐mediated endothelial cell growth. Site‐directed mutagenesis demonstrated that tyrosines 799 and 1173 are required for VEGFR‐2‐mediated endothelial cell growth and activation of PI3 kinase. Further site‐directed mutagenesis demonstrated that tyrosine 1212, located in the carboxyl tail of VEGFR‐2, is required for the ligand‐dependent autophosphorylation of the receptor and its ability to activate signaling proteins. Collectively, our results suggest that activation of VEGFR‐1 and VEGFR‐2 differentially regulates endothelial cell function and angiogenesis. Second, activation of VEGFR‐2 is associated with many endothelial cell functions, including cell proliferation, migration, and differentiation. Third, activation of PI3 kinase by VEGFR‐2 regulates endothelial cell proliferation.
t(11;14)‐positive mantle cell lymphomas exhibit complex karyotypes and share similarities with B‐cell chronic lymphocytic leukemia

Until now, few data on additional chromosomal aberrations in t(11;14)‐positive mantle cell lymphomas (MCLs) have been published. We analyzed 39 t(11;14)‐positive MCLs by either comparative genomic hybridization (CGH; n = 8), fluorescence in situ hybridization (FISH) with a set of DNA probes detecting the most frequent aberrations in B‐cell neoplasms (n = 12), or both techniques (n = 19). The t(11;14) was present in all cases. In 37 of 39 cases, chromosomal imbalances were found. In 27 cases, complex karyotypes, i.e., ≥ 3 aberrations, were identified. The most frequent aberrations were losses of 13q14–21 or 13q32–34 (27 cases), 9p21 (16 cases), and 11q22–23 (12 cases) and gains of 3q26–29 (19 cases), 8q22–24 (11 cases), and 18q21–22 (9 cases). In 26% of cases (7 of 27) analyzed by CGH, a total of 10 high‐level DNA amplifications were identified. Although in comparison with B‐cell chronic lymphopcytic leukemia (B‐CLL) MCL is characterized by a much higher complexity of chromosomal aberrations, there are striking similarities: 13q14 deletions were identified in more than 50% of both MCL and B‐CLL cases. In contrast, in our CGH database containing 293 B‐cell lymphomas, this aberration was found in only 11% of other nodal lymphomas. Even more strikingly, 11q deletions, which are present in 20%–30 % of MCL and B‐CLL, were found very rarely in other nodal B‐cell lymphomas (CGH: 1 of 208 cases; FISH: 1 of 69 cases). These data show that MCL is characterized by specific secondary aberrations and that there may be similarities in the pathogenesis of MCL and B‐CLL. Genes Chromosomes Cancer 27:285–294, 2000. © 2000 Wiley‐Liss, Inc.
Allergen immunotherapy: an updated review of safety

Purpose of review Allergen immunotherapy is the only modality that can modify the immune response upon exposure to aeroallergens and venom allergens. This review will update the allergist on recent studies evaluating safety of sublingual and subcutaneous allergen immunotherapy. Recent findings Multiple clinical trials and retrospective studies have been published evaluating overall safety of these therapies. The risk of systemic reactions with subcutaneous immunotherapy remains quite low, but near-fatal and fatal anaphylaxis does occur, requiring physicians to be aware of potential risks for such events. Sublingual immunotherapy has a high incidence of local site application reactions, but severe anaphylactic events are very uncommon. Summary Subcutaneous immunotherapy and sublingual immunotherapy are beneficial in treating allergic rhinitis and venom hypersensitivity but should be administered only by physicians familiar with potential risk factors and able to manage treatment-related local and systemic allergic reactions.
"Open Learner Models: Future Research Directions" Special Issue of the IJAIED (Part 2)

A read/write method using a non-contact system and used between a storage substrate and a read/write unit, the method including a storage substrate providing a memory at a card or other substrates, and a read/write unit, the storage substrate providing a coil for power supply, a coil for receiving data to be recorded in a memory, a coil for outputting toward the read/write unit the data recorded in the memory, and a coil for receiving a mode command, the read/write unit providing coils corresponding to four coils at the storage substrate, so that the respective corresponding coils at the storage substrate are insertably positioned in the magnetic flux generated by each coil at the read/write unit, whereby the read/write unit writes data in the memory at the storage substrate, or the data stored in the memory at the storage substrate is read by the read/write unit.