Prediction of disease progression, treatment response and dropout in chronic obstructive pulmonary disease (COPD).

Drug development in chronic obstructive pulmonary disease (COPD) has been characterised by unacceptably high failure rates. In addition to the poor sensitivity in forced expiratory volume in one second (FEV1), numerous causes are known to contribute to this phenomenon, which can be clustered into drug-, disease- and design-related factors. Here we present a model-based approach to describe disease progression, treatment response and dropout in clinical trials with COPD patients

NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration

<p>Abstract</p> <p>Background</p> <p>Activation of microglia causes the production of proinflammatory factors and upregulation of NADPH oxidase (NOX) that form reactive oxygen species (ROS) that lead to neurodegeneration. Previously, we reported that 10 daily doses of ethanol treatment induced innate immune genes in brain. In the present study, we investigate the effects of chronic ethanol on activation of NOX and release of ROS, and their contribution to ethanol neurotoxicity.</p> <p>Methods</p> <p>Male C57BL/6 and NF-κB enhanced GFP mice were treated intragastrically with water or ethanol (5 g/kg, i.g., 25% ethanol w/v) daily for 10 days. The effects of chronic ethanol on cell death markers (activated caspase-3 and Fluoro-Jade B), microglial morphology, NOX, ROS and NF-κB were examined using real-time PCR, immunohistochemistry and hydroethidine histochemistry. Also, Fluoro-Jade B staining and NOX gp91^phoximmunohistochemistry were performed in the orbitofrontal cortex (OFC) of human postmortem alcoholic brain and human moderate drinking control brain.</p> <p>Results</p> <p>Ethanol treatment of C57BL/6 mice showed increased markers of neuronal death: activated caspase-3 and Fluoro-Jade B positive staining with Neu-N (a neuronal marker) labeling in cortex and dentate gyrus. The OFC of human post-mortem alcoholic brain also showed significantly more Fluoro-Jade B positive cells colocalized with Neu-N, a neuronal marker, compared to the OFC of human moderate drinking control brain, suggesting increased neuronal death in the OFC of human alcoholic brain. Iba1 and GFAP immunohistochemistry showed activated morphology of microglia and astrocytes in ethanol-treated mouse brain. Ethanol treatment increased NF-κB transcription and increased NOX gp91^phoxat 24 hr after the last ethanol treatment that remained elevated at 1 week. The OFC of human postmortem alcoholic brain also had significant increases in the number of gp91^phox+ immunoreactive (IR) cells that are colocalized with neuronal, microglial and astrocyte markers. In mouse brain ethanol increased gp91^phoxexpression coincided with increased production of O₂^-and O₂^-- derived oxidants. Diphenyleneiodonium (DPI), a NOX inhibitor, reduced markers of neurodegeneration, ROS and microglial activation.</p> <p>Conclusions</p> <p>Ethanol activation of microglia and astrocytes, induction of NOX and production of ROS contribute to chronic ethanol-induced neurotoxicity. NOX-ROS and NF-κB signaling pathways play important roles in chronic ethanol-induced neuroinflammation and neurodegeneration.</p

Coherent excitation transferring via dark state in light-harvesting process

We study the light absorption and energy transferring in a donor-acceptor system with a bionic structure. In the optimal case with uniform couplings, it is found that the quantum dynamics of this seemingly complicated system is reduced as a three-level system of $\Lambda$-type. With this observation, we show that the dark state based electromagnetically-induced transparency (EIT) effect could enhance the energy transfer efficiency, through a quantum interference effect suppressing the excited population of the donors. We estimate the optimal parameters of the system to achieve the maximum output power. The splitting behavior of maximum power may be used to explain the phenomenon that the photosynthesis systems mainly absorb two colors of light.Comment: 4 pages, 3 figure

Repeatability and Longitudinal Assessment of Foveal Cone Structure in Cngb3-associated Achromatopsia

PURPOSE: Congenital achromatopsia is an autosomal recessive disease causing substantial reduction or complete absence of cone function. Although believed to be a relatively stationary disorder, questions remain regarding the stability of cone structure over time. In this study, the authors sought to assess the repeatability of and examine longitudinal changes in measurements of central cone structure in patients with achromatopsia. METHODS: Forty-one subjects with CNGB3-associated achromatopsia were imaged over a period of between 6 and 26 months using optical coherence tomography and adaptive optics scanning light ophthalmoscopy. Outer nuclear layer (ONL) thickness, ellipsoid zone (EZ) disruption, and peak foveal cone density were assessed. RESULTS: ONL thickness increased slightly compared with baseline (0.184 μm/month, P = 0.02). The EZ grade remained unchanged for 34/41 subjects. Peak foveal cone density did not significantly change over time (mean change 1% per 6 months, P = 0.126). CONCLUSION: Foveal cone structure showed little or no change in this group of subjects with CNGB3-associated achromatopsia. Over the time scales investigated (6–26 months), achromatopsia seems to be a structurally stable condition, although longer-term follow-up is needed. These data will be useful in assessing foveal cone structure after therapeutic intervention

Osteogenesis evaluation of duck’s feet derived collagen/hydroxyapatite sponges immersed in dexamethasone

Background: The aim of this study was to investigate the osteogenesis effects of DC and DC/HAp sponge immersed in without and with dexamethasone. Methods: The experimental groups in this study were DC and DC/HAp sponge immersed in without dexamethasone (Dex(â )DC and Dex(â )-DC/HAp group) and with dexamethasone (Dex(+)-DC and Dex(+)-DC/HAp group). We characterized DC and DC/HAp sponge using compressive strength, scanning electron microscopy (SEM). Also, osteogenic differentiation of BMSCs on sponge (Dex(â )DC, Dex(â )-DC/HAp, Dex(+)-DC and Dex(+)-DC/HAp group) was assessed by SEM, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assay, alkaline phosphatase (ALP) activity assay and reverse transcription-PCR (RT-PCR). Results: In this study, we assessed osteogenic differentiation of BMSCs on Duckâ s feet-derived collagen (DC)/ HAp sponge immersed with dexamethasone Dex(+)-DC/HAp. These results showed that Dex(+)-DC/HAp group increased cell proliferation and osteogenic differentiation of BMSCs during 28 days. Conclusion: From these results, Dex(+)-DC/HAp can be envisioned as a potential biomaterial for bone regeneration applications.This work was supported by Technology Commercialization Support Program [grant number 814005-03-3-HD020], Ministry for Food, Agriculture, Forestry and Fisheries (MIFAFF).info:eu-repo/semantics/publishedVersio

Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia

PURPOSE: Congenital achromatopsia (ACHM) is an autosomal recessive disorder in which cone function is absent or severely reduced. Gene therapy in animal models of ACHM have shown restoration of cone function, though translation of these results to humans relies, in part, on the presence of viable cone photoreceptors at the time of treatment. Here, we characterized residual cone structure in subjects with CNGB3-associated ACHM. METHODS: High-resolution imaging (optical coherence tomography [OCT] and adaptive optics scanning light ophthalmoscopy [AOSLO]) was performed in 51 subjects with CNGB3-associated ACHM. Peak cone density and inter-cone spacing at the fovea was measured using split-detection AOSLO. Foveal outer nuclear layer thickness was measured in OCT images, and the integrity of the photoreceptor layer was assessed using a previously published OCT grading scheme RESULTS: Analyzable images of the foveal cones were obtained in 26 of 51 subjects, with nystagmus representing the major obstacle to obtaining high-quality images. Peak foveal cone density ranged from 7,273 to 53,554 cones/mm2, significantly lower than normal (range, 84,733–234,391 cones/mm2), with the remnant cones being either contiguously or sparsely arranged. Peak cone density was correlated with OCT integrity grade; however, there was overlap of the density ranges between OCT grades. CONCLUSIONS: The degree of residual foveal cone structure varies greatly among subjects with CNGB3-associated ACHM. Such measurements may be useful in estimating the therapeutic potential of a given retina, providing affected individuals and physicians with valuable information to more accurately assess the risk-benefit ratio as they consider enrolling in experimental gene therapy trials. (www.clinicaltrials.gov, NCT01846052.

Robotic Wireless Sensor Networks

In this chapter, we present a literature survey of an emerging, cutting-edge, and multi-disciplinary field of research at the intersection of Robotics and Wireless Sensor Networks (WSN) which we refer to as Robotic Wireless Sensor Networks (RWSN). We define a RWSN as an autonomous networked multi-robot system that aims to achieve certain sensing goals while meeting and maintaining certain communication performance requirements, through cooperative control, learning and adaptation. While both of the component areas, i.e., Robotics and WSN, are very well-known and well-explored, there exist a whole set of new opportunities and research directions at the intersection of these two fields which are relatively or even completely unexplored. One such example would be the use of a set of robotic routers to set up a temporary communication path between a sender and a receiver that uses the controlled mobility to the advantage of packet routing. We find that there exist only a limited number of articles to be directly categorized as RWSN related works whereas there exist a range of articles in the robotics and the WSN literature that are also relevant to this new field of research. To connect the dots, we first identify the core problems and research trends related to RWSN such as connectivity, localization, routing, and robust flow of information. Next, we classify the existing research on RWSN as well as the relevant state-of-the-arts from robotics and WSN community according to the problems and trends identified in the first step. Lastly, we analyze what is missing in the existing literature, and identify topics that require more research attention in the future

Molecular Dynamics Studies of the Nucleoprotein of Influenza A Virus: Role of the Protein Flexibility in RNA Binding

The influenza viruses contain a segmented, negative stranded RNA genome. Each RNA segment is covered by multiple copies of the nucleoprotein (NP). X-ray structures have shown that NP contains well-structured domains juxtaposed with regions of missing electron densities corresponding to loops. In this study, we tested if these flexible loops gated or promoted RNA binding and RNA-induced oligomerization of NP. We first performed molecular dynamics simulations of wt NP monomer and trimer in comparison with the R361A protein mutated in the RNA binding groove, using the H1N1 NP as the initial structure. Calculation of the root-mean-square fluctuations highlighted the presence of two flexible loops in NP trimer: loop 1 (73–90), loop 2 (200–214). In NP, loops 1 and 2 formed a 10–15 Å-wide pinch giving access to the RNA binding groove. Loop 1 was stabilized by interactions with K113 of the adjacent β-sheet 1 (91–112) that interacted with the RNA grove (linker 360–373) via multiple hydrophobic contacts. In R361A, a salt bridge formed between E80 of loop 1 and R208 of loop 2 driven by hydrophobic contacts between L79 and W207, due to a decreased flexibility of loop 2 and loop 1 unfolding. Thus, RNA could not access its binding groove in R361A; accordingly, R361A had a much lower affinity for RNA than NP. Disruption of the E80-R208 interaction in the triple mutant R361A-E80A-E81A increased its RNA binding affinity and restored its oligomerization back to wt levels in contrast with impaired levels of R361A. Our data suggest that the flexibility of loops 1 and 2 is required for RNA sampling and binding which likely involve conformational change(s) of the nucleoprotein

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC) and the possibility of predicting those at higher risk.</p> <p>Methods</p> <p>A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH), 262 patients with esophageal squamous cell dysplasia (ESCD), 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for <it>CYP2E1 </it>G1259C, <it>hOGG1 </it>C326G, <it>MTHFR </it>C677T, <it>MPO </it>G463A, and <it>ALDH2 </it>allele genes were identified in blood samples collected from all participants.</p> <p>Results</p> <p>The alleles <it>ALDH2 </it>and <it>MTHFR </it>C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the <it>ALDH </it>1*1 genotype, the <it>ALDH </it>2*2 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of <it>MTHFR </it>C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 2*2/1*2 of <it>ALDH </it>2 and TT/TC of <it>MTHFR </it>C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (OR_G) of the two combined genotypes was 1.83 (95%CI: 1.55-2.16), indicating a strong genetic association with the risk of carcinogenic progression in the esophagus.</p> <p>Conclusions</p> <p>The study demonstrated that the genotypes <it>ALDH2*2 </it>and <it>MTHFR </it>677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.</p