Expression of CD80 and CD86 costimulatory molecules are potential markers for better survival in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>B7 Costimulatory signal is essential to trigger T-cell activation upon the recognition of tumor antigens. This study examined the expression of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules along with HLA-DR and the presence of infiltrating lymphocytes and dendritic cells to assess their significance in patients with nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Expression of CD80, CD86, HLA-DR, S-100 protein and the presence of infiltrating lymphocytes and follicular dendritic reticulum cells were immunohistochemically examined on the paraffin-embedded tissue blocks from newly diagnosed NPC patients (n = 50). The results were correlated with clinical outcome of patients.</p> <p>Results</p> <p>CD80 and CD86 were each expressed in 10 of 50 cases in which they co-expressed in 9 cases. Univariate analysis revealed that patients with CD80/CD86 expression had significantly better overall survival than those without it (P = 0.017), but after adjustment for stage, nodal status, and treatment, the expression of CD80/CD86 did not significantly correlate with overall survival. Expression of HLA-DR and the presence of infiltrating lymphocytes and dendritic cells did not appear to have impact on the survival of patients.</p> <p>Conclusion</p> <p>Expression of CD80 and CD86 costimulatory molecules appears to be a marker of better survival in patient with NPC.</p

Integral Human Pose Regression

State-of-the-art human pose estimation methods are based on heat map representation. In spite of the good performance, the representation has a few issues in nature, such as not differentiable and quantization error. This work shows that a simple integral operation relates and unifies the heat map representation and joint regression, thus avoiding the above issues. It is differentiable, efficient, and compatible with any heat map based methods. Its effectiveness is convincingly validated via comprehensive ablation experiments under various settings, specifically on 3D pose estimation, for the first time

Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia

Objective: Familial glucocorticoid deficiency type I (FGD1) is a rare form of primary adrenal insufficiency resulting from recessive mutations in the ACTH receptor (MC2R, MC2R). Individuals with this condition typically present in infancy or childhood with signs and symptoms of cortisol insufficiency, but disturbances in the renin-angiotensin system, aldosterone synthesis or sodium homeostasis are not a well-documented association of FGD1. As ACTH stimulation has been shown to stimulate aldosterone release in normal controls, and other causes of hyponatraemia can occur in children with cortisol deficiency, we investigated whether MC2R changes might be identified in children with primary adrenal failure who were being treated for mineralocorticoid insufficiency. Design: Mutational analysis of MC2R by direct sequencing. Patients: Children (n = 22) who had been diagnosed with salt-losing forms of adrenal hypoplasia (19 isolated cases, 3 familial), and who were negative for mutations in DAX1 (NR0B1) and SF1 (NR5A1). Results: MC2R mutations were found in three individuals or kindred (I: homozygous S74I; II: novel compound heterozygous R146H/560delT; III: novel homozygous 579-581delTGT). These changes represent severely disruptive loss-of-function mutations in this G-protein coupled receptor, including the first reported homozygous frameshift mutation. The apparent disturbances in sodium homeostasis were mild, manifest at times of stress (e.g. infection, salt-restriction, heat), and likely resolved with time. Conclusions: MC2R mutations should be considered in children who have primary adrenal failure with apparent mild disturbances in renin-sodium homeostasis. These children may have been misdiagnosed as having salt-losing adrenal hypoplasia. Making this diagnosis has important implications for treatment, counselling and long-term prognosi

ENIGMA: Efficient Learning-based Inference Guiding Machine

ENIGMA is a learning-based method for guiding given clause selection in saturation-based theorem provers. Clauses from many proof searches are classified as positive and negative based on their participation in the proofs. An efficient classification model is trained on this data, using fast feature-based characterization of the clauses . The learned model is then tightly linked with the core prover and used as a basis of a new parameterized evaluation heuristic that provides fast ranking of all generated clauses. The approach is evaluated on the E prover and the CASC 2016 AIM benchmark, showing a large increase of E's performance.Comment: Submitted to LPAR 201

Study on antioxidant activity of Echinacea purpurea L. extracts and its impact on cell viability

This study investigates the antioxidant activity of Echinacea Purpurea L. (EP) extracts and its impact on cell viability. The polysaccharides content of EP was 159.8 ± 12.4 mg/g dry weight (DW), with extracts obtained by applying 55% ethanol at 55°C containing 11.0 ±1.0 mg gallic acid equivalent/g DW of total phenolic compound. Trolox equivalent antioxidant capacity, 0.1 mg/mL of EP extracts exhibited only 30% when compared to the ascorbic acid at the same concentration. Reducing power of extractsincreased linearly with its concentration and the concentration at 2.0 mg/mL reached about 65% of ascorbic acid at 0.3 mg/mL. The chelating capacity of ferrous iron (Fe2+) was 70% as good as that of thesynthetic metal chelater EDTA when added to 5.0 mg/mL of EP extracts. The DPPH scavenging capacity showed 85.1% at 0.5 mg/mL of extracts and with half-effective doses (ED50) was measured at 0.23mg/mL. The superoxide anions scavenging capacity of EP extracts was nearly equivalent to ascorbic acid (91.1% vs 93.0%) at the same concentration of 1.6 mg/mL and ED50 was 0.32 and 0.13 mg/mL, respectively. Microculture tetrazolium assays showed extracts had 92% cell viability at 1.6 mg/mL forchicken’s peripheral blood mononuclear cells (PBMCs) and 84% for RAW 264.7 macrophages, neither reaching the IC50 level. In summary, the EP extracts had antioxidant activity similar to that of ascorbic acid, but have no serious effect on inhibiting chicken’s PBMCs viability

Parity Doubling and the S Parameter Below the Conformal Window

We describe a lattice simulation of the masses and decay constants of the lowest-lying vector and axial resonances, and the electroweak S parameter, in an SU(3) gauge theory with $N_f = 2$ and 6 fermions in the fundamental representation. The spectrum becomes more parity doubled and the S parameter per electroweak doublet decreases when $N_f$ is increased from 2 to 6, motivating study of these trends as $N_f$ is increased further, toward the critical value for transition from confinement to infrared conformality.Comment: 4 pages, 5 figures; to be submitted to PR

Modeling and analysis of energy distribution networks using switched differential systems

It is a pleasure to dedicate this contribution to Prof. Arjan van der Schaft on the occasion of his 60th birthday. We study the dynamics of energy distribution networks consisting of switching power converters and multiple (dis-)connectable modules. We use parsimonious models that deal effectively with the variant complexity of the network and the inherent switching phenomena induced by power converters. We also present the solution to instability problems caused by devices with negative impedance characteristics such as constant power loads. Elements of the behavioral system theory such as linear differential behaviors and quadratic differential forms are crucial in our analysis

Towards atomically precise manipulation of 2D nanostructures in the electron microscope

Despite decades of research, the ultimate goal of nanotechnology—top-down manipulation of individual atoms—has been directly achieved with only one technique: scanning probe microscopy. In this review, we demonstrate that scanning transmission electron microscopy (STEM) is emerging as an alternative method for the direct assembly of nanostructures, with possible applications in plasmonics, quantum technologies, and materials science. Atomically precise manipulation with STEM relies on recent advances in instrumentation that have enabled non-destructive atomicresolution imaging at lower electron energies. While momentum transfer from highly energetic electrons often leads to atom ejection, interesting dynamics can be induced when the transferable kinetic energies are comparable to bond strengths in the material. Operating in this regime, very recent experiments have revealed the potential for single-atom manipulation using the Ångströmsized electron beam. To truly enable control, however, it is vital to understand the relevant atomicscale phenomena through accurate dynamical simulations. Although excellent agreement between experiment and theory for the specific case of atomic displacements from graphene has been recently achieved using density functional theory molecular dynamics, in many other cases quantitative accuracy remains a challenge. We provide a comprehensive reanalysis of available experimental data on beam-driven dynamics in light of the state-of-the-art in simulations, and identify important targets for improvement. Overall, the modern electron microscope has great potential to become an atom-scale fabrication platform, especially for covalently bonded 2D nanostructures. We review the developments that have made this possible, argue that graphene is an ideal starting material, and assess the main challenges moving forward

Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.

BackgroundM2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages.MethodsMycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm2. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.ResultsThe ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm3) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).ConclusionsDietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC