Miracle-dz/UniFAR-FTUs huggingface dataset:
The Antiinflammatory Endothelial Tyrosine Kinase Tie2 Interacts With a Novel Nuclear Factor-&kgr;B Inhibitor ABIN-2

Abstract— Tie2 is a receptor tyrosine kinase expressed predominantly in endothelial cells and is essential for blood vessel formation and maintenance. The receptor has potent antiinflammatory effects on endothelial cells, suppressing vascular endothelial growth factor– and tumor necrosis factor–induced expression of leukocyte adhesion molecules and procoagulant tissue factor and inhibiting vascular leakage. To delineate the signaling pathways utilized by Tie2, we performed yeast two-hybrid screening of a human endothelial cell cDNA library and identified a novel protein interacting with the intracellular domain of the receptor. This protein was found to be human A20 binding inhibitor of NF-&kgr;B activation-2, ABIN-2, an inhibitor of NF-&kgr;B–mediated inflammatory gene expression. Coexpression of Tie2 and ABIN-2 in CHO cells confirmed the interaction occurs in mammalian cells. In contrast, Tie1 did not interact with ABIN-2 in the yeast two-hybrid system or mammalian cells. Deletion analysis identified the Tie2 binding motif to be encompassed between residues 171 and 272 in ABIN-2. Interaction was dependent on Tie2 autophosphorylation but ABIN-2 was not tyrosine phosphorylated by Tie2. Furthermore, in endothelial cells the interaction was stimulated by the Tie2 ligand angiopoietin-1. Expression of ABIN-2 deletion mutants in endothelial cells suppressed the ability of angiopoietin-1 to inhibit phorbol ester–stimulated NF-&kgr;B–dependent reporter gene activity. These findings provide the first direct link between Tie2 and a key regulator of inflammatory responses in endothelial cells. Interaction between Tie2 and ABIN-2 may be important in the vascular protective antiinflammatory actions of Tie2.
Astigmatic Peripheral Defocus with Different Contact Lenses: Review and Meta-Analysis

ABSTRACT Purpose: To review the level of relative peripheral defocus measured with different devices with potential use for myopia retention. To present comparative data of the change in astigmatic peripheral refraction with different contact lenses evaluated in different studies conducted in the same laboratory following the same methodology in myopic human eyes Methods: A joint analysis of work, carried out at the same laboratory (CEORLab) in 137 myopic subjects with different types of contact lenses (CL), was performed to obtain the tangential (FT = M − J0), sagittal (FS = M + J0), and mean (M) power refractive errors (M and J0 are the refraction vector components). Orthokeratology, standard aspheric rigid gas-permeable (RGP), experimental RGP, experimental soft CL, and different multifocal soft CL were used to induce peripheral myopic defocus (236 peripheral refraction measures). Results: Compared with values obtained in naked eye condition (baseline), only three of the eight approaches tested show statistically significant peripheral myopic defocus induction (p < 0.001) in both temporal and nasal retina (orthokeratology, experimental RGP, and Proclear multifocal CL with Add: +3.00 D). Standard aspheric RGP also produced a significant increase in myopic defocus for the FT, of about −2.00 D. The experimental soft CL, designed to mimic the peripheral performance of the experimental RGP, induced a similar effect to the standard aspheric soft CL. Conclusion: Orthokeratology, multifocal soft CL, and custom-designed RGP CL were able to generate a significant relative peripheral myopia in myopic eyes. Conversely, standard and experimental soft CL were not able to induce significant peripheral myopic and astigmatic defocus values.
Cyclic Nucleotide-Gated Channel Activation Is Not Required for Activity-Dependent Labeling of Zebrafish Olfactory Receptor Neurons by Amino Acids

The olfactory epithelium of fish is heterogeneous both with respect to the types of receptor cells (ORNs) present and the families of odorant receptors expressed in these cells. As a consequence of this diversity, the transduction cascade(s) activated by odorants has yet to be unambiguously established. In the current study, electrophysiological and activity-dependent labeling techniques were used to assess the role of the cyclic nucleotide-gated channel in zebrafish olfactory transduction. Both amino acid and bile salt odorants elicited robust electrophysiological responses, however, activity-dependent labeling of ORNs could be stimulated only by the amino acid odorants. An adenylate cyclase (AC) activator (forskolin) and a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, IBMX) also elicited robust electrophysiological responses; generally larger than the responses elicited by either the amino acid or bile salt odorants. However, neither forskolin alone or a mixture of forskolin and IBMX stimulated activity-dependent labeling. Bathing the olfactory epithelium with forskolin, which presumably increased the intracellular concentration of cAMP, reduced the responses to bile salt odorants to a significantly greater extent than amino acid odorants. Collectively, these findings suggest that the transduction of amino acid input does not rely primarily on cyclic nucleotide-gated (CNG) channel activation and that CNG channel activation may be required for the transduction of bile salt input.
The mismatch between the health research and development (R&D) that is needed and the R&D that is undertaken: an overview of the problem, the causes, and solutions

One of the most pressing global health problems is that there is a mismatch between the health research and development (R&D) that is needed and that which is undertaken. The dependence of health R&D on market incentives in the for-profit private sector and the lack of coordination by public and philanthropic funders on global R&D priorities have resulted in a global health R&D landscape that neglects certain products and populations and is characterised, more generally, by a distribution that is not ‘needs-driven’. This article provides an overview of the mismatch, its causes, and solutions.
A chitinase-like protein in the lung and circulation of patients with severe asthma.

BACKGROUND The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3-like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated. METHODS We quantified serum YKL-40 levels in three cohorts of patients with asthma--one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin--as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated. RESULTS Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001) and with airway remodeling (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels. CONCLUSIONS YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.
Right trisegment portal vein embolization for biliary tract carcinoma: technique and clinical utility.

BACKGROUND Right portal vein embolization has become popular in preparation for right hepatic lobectomy. However, right trisegment portal vein embolization (R3PE) is not well established. METHODS We performed R3PE in 15 patients with biliary tract carcinoma and 1 patient with primary sclerosing cholangitis. We used 2 types of 5.5 F triple-lumen balloon catheters to embolize portal branches of the right trisegment (the left medial, the right anterior, and the right posterior segments). RESULTS R3PE was successful in all patients without any complications. The calculated volume of the right lobe significantly (P < .01) decreased from 650 +/- 161 cm3 before embolization to 585 +/- 143 cm3 after embolization; the volume of the left lateral segment significantly (P < .0005) increased from 240 +/- 58 cm3 to 361 +/- 66 cm3. The volume of the left medial segment was unchanged. The volume gain of the left lateral segment was larger in patients with R3PE than in those patients (n = 41) with right portal vein embolization (122 +/- 39 cm3 vs 66 +/- 35 cm3; P < .0001). Two of the 16 patients underwent only laparotomy because of peritoneal dissemination, and the remaining 14 patients underwent right hepatic trisegmentectomy with caudate lobectomy. In addition, portal vein resection was also performed in 5 patients, and pancreatoduodenectomy and right hemicolectomy was performed in 3 patients. One patient died of posthepatectomy liver failure 87 days after surgery, a mortality rate of 7.1% (1/14 patients). CONCLUSIONS R3PE is more useful than standard right portal vein embolization in preparation for right hepatic trisegmentectomy and has the potential to increase the safety of this high-risk surgery for patients with biliary tract carcinoma.
Cell adhesion on polytetrafluoroethylene modified by UV-irradiation in an ammonia atmosphere.

We report on the modification of polytetrafluoroethylene (PTFE) by exposure to the ultraviolet (UV) light of a Xe(2)*-excimer lamp at a wavelength of 172 nm in an ammonia atmosphere. Typical treatment times were up to 30 min. Subsequently, the samples were grafted with the amino acid alanine from an aqueous solution. The samples were characterized by means of optical transmission spectroscopy, laser-induced fluorescence and contact-angle measurements. We studied the adhesion of rat aortic smooth muscle cells (SMC) and mouse fibroblasts (3T3 cells) to the modified polymer samples using an in vitro technique, where the population density and spread of adhering cells is determined 24 h after seeding by image analysis. For both cell types the exposure of PTFE to UV-light in an ammonia atmosphere resulted in a significant increase in the number of adhering cells and in the size of their spreading area. The grafting with alanine enhanced this effect. Additional experiments with human endothelial cells (HEC) also demonstrated improved adhesion to modified PTFE. Thus, PTFE modified by our method appears to be a promising material for fabrication of artificial vascular prostheses and implants or for cultivation of skin substitutes.
Low-dose graphic-processing-unit based limited-angle CT reconstruction algorithm development for a home-designed dual modality micro-FT/CT system

Computed tomography (CT) has evolved into an indispensable imaging method in clinical routine for a long time. It gives us high resolution, high contrast and non-invasive tomographic images in a brief scan time. However, their high radiation dose is an important issue to be solved in CT system development. Iterative algorithms can give us better image quality than analytical types and reduce some artifact effectively. However, they are not only time consuming, but also need very large-scale memory size. In this study, we reduce our projection data to <;180-degree limited angle reconstruction, which was based on compressive sensing (CS) criteria and total variation (TV) minimization. This is a computer simulation study combined with CPU and graphic processing units (GPUs). We developed a 3D system matrix in which ray-tracing and circular redundancy technique were included. All CT image data were collected by our homemade micro-FT/CT dual modality system and reconstructed by model based post total-variation constrained algebraic reconstruction technique (ART-TV) algorithm, inner total-variation constrained expectation-maximization (TV-EM) and post total-variation constrained expectation-maximization (EM-TV) in transmission types. The reconstruction volume was 216 × 216 × 384 by 4 × 4 binning of the detector size. There is only 90-degree angular sampling range with 1 degree/projection. Some figures of merit (FOMs) such as rootmean-square error (RMSE), universal quality index (UQI) and coefficient of variation (CV) were used to evaluate image quality. Although now the total speed up ratio is about 1.3 × than CPU multi-threading but compare to our previous study, we push our reconstruction scale from simulated 16 ×16 × 16 and 32 × 34 detector size to the size of a realistic scan. Our study demonstrates that statistic reconstruction technique (SRT) with <; 180-degree limited angle reconstruction can produce low-dose CT images.
Inter-phyla studies on neuropeptides: the potential for broad-spectrum anthelmintic and/or endectocide discovery

Flatworm, nematode and arthropod parasites have proven their ability to develop resistance to currently available chemotherapeutics. The heavy reliance on chemotherapy and the ability of target species to develop resistance has prompted the search for novel drug targets. In view of its importance to parasite/pest survival, the neuromusculature of parasitic helminths and pest arthropod species remains an attractive target for the discovery of novel endectocide targets. Exploitation of the neuropeptidergic system in helminths and arthropods has been hampered by a limited understanding of the functional roles of individual peptides and the structure of endogenous targets, such as receptors. Basic research into these systems has the potential to facilitate target characterization and its offshoots (screen development and drug identification). Of particular interest to parasitologists is the fact that selected neuropeptide families are common to metazoan pest species (nematodes, platyhelminths and arthropods) and fulfil specific roles in the modulation of muscle function in each of the three phyla. This article reviews the inter-phyla activity of two peptide families, the FMRFamide-like peptides and allatostatins, on motor function in helminths and arthropods and discusses the potential of neuropeptide signalling as a target system that could uncover novel endectocidal agents.
How Can Local Governance Systems Strengthen Community Resilience? A Social-Ecological Systems Approach

At their core, donor-funded climate and disaster resilience programmes provide goods and services to help build assets and minimise the impact of shocks and stresses on people’s lives and livelihoods. Little is known, however, about the way local risk governance systems and the broader institutional arrangements, in which they are embedded, mediate people’s access to these services and therefore lead to improved resilience. Drawing on Social-Ecological Systems theory, we explore those characteristics of risk governance systems believed to be more favourable for building resilience at the community level in different developing country contexts. These include: diversity; polycentricism and connectivity; decentralisation and flexibility; participation and community engagement; and, learning and innovation. This review paper proposes a conceptual framework and assesses the evidence linking risk governance and access to the services needed to build resilient outcomes, drawing particularly on evidence from the Sahel and Horn of Africa. In doing so, we can start to understand where the entry points might be for strengthening resilience and the conditions needed for community-level initiatives to be brought to scale from the bottom up.
Labor Supply and Time Allocation in Remittance-Receiving Households: Evidence from Rural Pakistan

ix List of Abbreviations Used . x Acknowledgements . xi Chapter
Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI

Objective: To examine the neural basis of cognitive complaints in healthy older adults in the absence of memory impairment and to determine whether there are medial temporal lobe (MTL) gray matter (GM) changes as reported in Alzheimer disease (AD) and amnestic mild cognitive impairment (MCI). Methods: Participants were 40 euthymic individuals with cognitive complaints (CCs) who had normal neuropsychological test performance. The authors compared their structural brain MRI scans to those of 40 patients with amnestic MCI and 40 healthy controls (HCs) using voxel-based morphometry and hippocampal volume analysis. Results: The CC and MCI groups showed similar patterns of decreased GM relative to the HC group on whole brain analysis, with differences evident in the MTL, frontotemporal, and other neocortical regions. The degree of GM loss was associated with extent of both memory complaints and performance deficits. Manually segmented hippocampal volumes, adjusted for age and intracranial volume, were significantly reduced only in the MCI group, with the CC group showing an intermediate level. Conclusions: Cognitive complaints in older adults may indicate underlying neurodegenerative changes even when unaccompanied by deficits on formal testing. The cognitive complaint group may represent a pre–mild cognitive impairment stage and may provide an earlier therapeutic opportunity than mild cognitive impairment. MRI analysis approaches incorporating signal intensity may have greater sensitivity in early preclinical stages than volumetric methods.
T cell signal transducer and activator of transcription (STAT) 4 and 6 are affected by adalimumab therapy in rheumatoid arthritis.

OBJECTIVES TNF-alpha inhibition therapy affects the systemic immune response in rheumatoid arthritis by influencing T cell subtypes (Th1, Th2, Treg), but its effect on the intracellular signal transduction in T cells remains largely unexplored. Here we studied the activation of Th1-associated signalling molecule STAT4 and Th2-associated STAT6 in CD4+ T cells. METHODS Eight rheumatoid arthritis patients were studied before and after 12 weeks of adalimumab therapy and compared to 8 healthy individuals. Peripheral blood mononuclear cells (PBMC) were analysed flow cytometrically either directly after isolation or after 24 hours of anti-CD3/anti-CD28 stimulation, to determine spontaneous and IL-4/IL-12-induced STAT4 and STAT6 phosphorylation in CD4+ T cells. Cytokine production by stimulated PBMC was measured in the supernatant using a cytometric bead array. Non-parametric statistical tests were applied. RESULTS After adalimumab therapy, phospho-STAT6 increased, both in freshly isolated and anti-CD3/anti-CD28-stimulated CD4+ T cells. The STAT6 response to brief IL-4 stimulation did not change. In healthy individuals and adalimumab-treated patients, anti-CD3/anti-CD28 induced the phosphorylation of STAT4, but not in untreated patients. IFN-gamma production in untreated patients was significantly lower than in healthy individuals or adalimumab-treated patients. In contrast, the production of IL-4, IL-6 and IL-12 was not influenced. CONCLUSIONS Adalimumab therapy increases Th2-associated STAT6 phosphorylation and restores the activation-induced STAT4 phosphorylation to the levels in healthy individuals. This advocates against a pro-inflammatory effect of Th1-associated STAT4 and might provide an explanation for the influence of TNF inhibition therapy on the systemic T cell response in rheumatoid arthritis.
Lab-on-a-Chip Technology for Integrative Bioengineering

Recent progress of lab-on-a-chip technology is challenging for the development of nanobiotechnology and integrative bioengineering. In this work, several novel microfluidic devices for biotechnology and bioengineering, based on the synergetic integration of miniaturization technology to biology, chemistry, and medicine, are described. Currently, we focus on the development of a nanobiosensor, microfluidic device and lab-on-a-chip as a new platform for biological sample processing, separation, and detection, including optoelectrofluidic manipulation, hydrophoretic separation, magnetophoretic assay, and cell-based assay. The final application of these research activities covers several aspects of biomolecular diagnostics, micro total analysis system (μTAS), cell-based screening platform, nanobio device, etc.
Spray-Drying as a Method for Microparticulate Controlled Release Systems Preparation: Advantages and Limits. I. Water-Soluble Drugs

Spray-drying was used for the preparation of paracetamol/eudragit RS or RL or ethylcellulose microspheres to verify the possibility of their use in controlled-release solid-dosage forms formulation and try to determine advantages and limits of the technique of such use. Microspheres were first characterized by scanning electron microscopy, differential scanning calorimetry, x-ray diffractometry, and in vitro dissolution studies and then used for the preparation of tablets. During this step, the compressibility of the spray-dried powders was also evaluated. In vitro dissolution studies were performed also on the tablets and their release control was accessed. Although powders were unable to slow down drug release, tablets obtained from microsphere compression showed a good capability of controlling paracetamol release when eudragit RS or ethylcellulose was used, even at low polymer amounts.
Genetic rescue of an insular population of large mammals

Natural populations worldwide are increasingly fragmented by habitat loss. Isolation at small population size is thought to reduce individual and population fitness via inbreeding depression. However, little is known about the time-scale over which adverse genetic effects may develop in natural populations or the number and types of traits likely to be affected. The benefits of restoring gene flow to isolates are therefore also largely unknown. In contrast, the potential costs of migration (e.g. disease spread) are readily apparent. Management for ecological connectivity has therefore been controversial and sometimes avoided. Using pedigree and life-history data collected during 25 years of study, we evaluated genetic decline and rescue in a population of bighorn sheep founded by 12 individuals in 1922 and isolated at an average size of 42 animals for 10–12 generations. Immigration was restored experimentally, beginning in 1985. We detected marked improvements in reproduction, survival and five fitness-related traits among descendants of the 15 recent migrants. Trait values were increased by 23–257% in maximally outbred individuals. This is the first demonstration, to our knowledge, of increased male and female fitness attributable to outbreeding realized in a fully competitive natural setting. Our findings suggest that genetic principles deserve broader recognition as practical management tools with near-term consequences for large-mammal conservation.