Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane

Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG(4) to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.X111313sciescopu

The Impact of Improving Suicide Death Classification in South Korea: A Comparison with Japan and Hong Kong

Introduction The suicide rate of South Korea has increased dramatically during the past decades, as opposed to steadily decreasing trends in Japan and Hong Kong. Although the recent increase of suicide in South Korea may be related to changing socioeconomic conditions and other contextual factors, it may also reflect, in part, a reduction of misidentified suicide cases due to improving classification of manner of death. Method We compared the annual proportional change of suicide, undetermined death, and accidental death from South Korea with those of Japan and Hong Kong from 1992 to 2011; a greater proportional change of the manner-of-death categories during the period is indicative of a relatively less stable registration and hence a greater potential for misclassification bias on reported suicide trends. Subgroup analyses stratifying the deaths by methods were also conducted. To estimate the impact, the age-standardized rates of these three death categories in each site were calculated. Results We found that, during the 20-year observation period, the proportional change of suicide, undetermined death, and accidental death in South Korea was significantly greater than Japan and Hong Kong. Similar observations were made in subgroup analyses. While death rates of the three manners in Japan and Hong Kong generally moved in a parallel fashion, the increase of suicide in South Korea occurred concomitantly with a significant reduction of its accidental death rate. 43% of the increase in suicides could be attributed to the decrease in accidental deaths, while 57% of the increase could be due to fundamental causes. Conclusion Our data suggest that, during the mid-1990s and after, the increasing burden of suicide in South Korea initially was masked, in part, by misclassification. Thus, the later apparently rapid increase of suicides reflected steadily improving classification of manner of death, as well as a more fundamental increase in the suicide rate.published_or_final_versio

Dynamics and transport near quantum-critical points

The physics of non-zero temperature dynamics and transport near quantum-critical points is discussed by a detailed study of the O(N)-symmetric, relativistic, quantum field theory of a N-component scalar field in $d$ spatial dimensions. A great deal of insight is gained from a simple, exact solution of the long-time dynamics for the N=1 d=1 case: this model describes the critical point of the Ising chain in a transverse field, and the dynamics in all the distinct, limiting, physical regions of its finite temperature phase diagram is obtained. The N=3, d=1 model describes insulating, gapped, spin chain compounds: the exact, low temperature value of the spin diffusivity is computed, and compared with NMR experiments. The N=3, d=2,3 models describe Heisenberg antiferromagnets with collinear N\'{e}el correlations, and experimental realizations of quantum-critical behavior in these systems are discussed. Finally, the N=2, d=2 model describes the superfluid-insulator transition in lattice boson systems: the frequency and temperature dependence of the the conductivity at the quantum-critical coupling is described and implications for experiments in two-dimensional thin films and inversion layers are noted.Comment: Lectures presented at the NATO Advanced Study Institute on "Dynamical properties of unconventional magnetic systems", Geilo, Norway, April 2-12, 1997, edited by A. Skjeltorp and D. Sherrington, Kluwer Academic, to be published. 46 page

Prediction of Inflammatory Breast Cancer Survival Outcomes Using Computed Tomography-Based Texture Analysis

Background: Although inflammatory breast cancer (IBC) has poor overall survival (OS), there is little information about using imaging features for predicting the prognosis. Computed tomography (CT)-based texture analysis, a non-invasive technique to quantify tumor heterogeneity, could be a potentially useful imaging biomarker. The aim of the article was to investigate the usefulness of chest CT-based texture analysis to predict OS in IBC patients. Methods: Of the 3,130 patients with primary breast cancers between 2006 and 2016, 104 patients (3.3%) with IBC were identified. Among them, 98 patients who underwent pre-treatment contrast-enhanced chest CT scans, got treatment in our institution, and had a follow-up period of more than 2 years were finally included for CT-based texture analysis. Texture analysis was performed on CT images of 98 patients, using commercially available software by two breast radiologists. Histogram-based textural features, such as quantification of variation in CT attenuation (mean, standard deviation, mean of positive pixels [MPP], entropy, skewness, and kurtosis), were recorded. To dichotomize textural features for survival analysis, receiver operating characteristic curve analysis was used to determine cutoff points. Clinicopathologic variables, such as age, node stage, metastasis stage at the time of diagnosis, hormonal receptor positivity, human epidermal growth factor receptor 2 positivity, and molecular subtype, were assessed. A Cox proportional hazards model was used to determine the association of textural features and clinicopathologic variables with OS. Results: During a mean follow-up period of 47.9 months, 41 of 98 patients (41.8%) died, with a median OS of 20.0 months. The textural features of lower mean attenuation, standard deviation, MPP, and entropy on CT images were significantly associated with worse OS, as was the M1 stage among clinicopathologic variables (all P-values < 0.05). In multivariate analysis, lower mean attenuation (hazard ratio [HR], 3.26; P = 0.003), lower MPP (HR, 3.03; P = 0.002), and lower entropy (HR, 2.70; P = 0.009) on chest CT images were significant factors independent from the M1 stage for predicting worse OS. Conclusions: Lower mean attenuation, MPP, and entropy on chest CT images predicted worse OS in patients with IBC, suggesting that CT-based texture analysis provides additional predictors for OS

A colanic acid operon deletion mutation enhances induction of early antibody responses by live attenuated salmonella vaccine strains

Colanic acid (CA) is a common exopolysaccharide produced by many genera in the Enterobacteriaceae. It is critical for biofilm formation on HEp-2 cells and on chicken intestinal tissue by Salmonella. In this study, we generated different CA synthesis gene mutants and evaluated the immune responses induced by these mutants. One of these mutations, Δ(wza-wcaM)8, which deleted the whole operon for CA synthesis, was introduced into two Salmonella vaccine strains attenuated by auxotrophic traits or by the regulated delayed attenuation strategy (RDAS). The mice immunized with the auxotrophic Salmonella vaccine strain with the deletion mutation Δ(wza-wcaM)8 developed higher vaginal IgA titers against the heterologous protective antigen and higher levels of antigen-specific IgA secretion cells in lungs. In Salmonella vaccine strains with RDAS, the strain with the Δ(wza-wcaM)8 mutation resulted in higher levels of protective antigen production during in vitro growth. Mice immunized with this strain developed higher serum IgG and mucosal IgA antibody responses at 2 weeks. This strain also resulted in better gamma interferon (IFN-γ) responses than the strain without this deletion at doses of 10(8) and 10(9) CFU. Thus, the mutation Δ(wza-wcaM)8 will be included in various recombinant attenuated Salmonella vaccine (RASV) strains with RDAS derived from Salmonella enterica serovar Paratyphi A and Salmonella enterica serovar Typhi to induce protective immunity against bacterial pathogens

Imaging the Phase Transformation in Single Particles of the Lithium Titanate Anode for Lithium-Ion Batteries

Lithium uptake and release in lithium titanate (LTO) anode materials during a discharge and charge cycle is one of the fundamental processes of a lithium-ion battery (LIB), still not fully understood at the microscopic level. During the discharge cycle, LTO undergoes a phase transformation between Li4Ti5O12 and Li7Ti5O12 states within a cubic crystal lattice. To reveal the details of the microscopic mechanism, it is necessary to track the sequence of phase transformations at different discharge/charge states under operating conditions. Here, we use in situ Bragg coherent diffraction imaging (BCDI) and in situ X-ray diffraction (XRD) experiments to examine the lithium insertion-induced materials phase transformation within a single LTO particle and a bulk battery analogue, respectively. BCDI analysis from (111) Bragg peak shows the two-phase transformation manifesting as a distinct image phase modulation within a single LTO nanoparticle occurring in the middle of the discharge region then subsiding toward the end of the discharge cycle. We observe the biggest phase variation at the two-phase stage, indicating the formation of phase domains of 200 nm in size during the discharge process. We also observe a lattice contraction of >0.2% in a single LTO nanoparticle at the (400) Bragg peak measurement, larger than that in the corresponding bulk material. Our observation of this phase transformation at a single-particle level has implications for the understanding of the microscopic/mesoscale picture of the phase transformation in anode and cathode LIBs materials

Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing

The cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) is a cell-cycle checkpoint effector and inducer of senescence, regulated by p53. Yet, evidence suggests that p21 could also be oncogenic, through a mechanism that has so far remained obscure. We report that a subset of atypical cancerous cells strongly expressing p21 showed proliferation features. This occurred predominantly in p53-mutant human cancers, suggesting p53-independent upregulation of p21 selectively in more aggressive tumour cells. Multifaceted phenotypic and genomic analyses of p21-inducible, p53-null, cancerous and near-normal cellular models showed that after an initial senescence-like phase, a subpopulation of p21-expressing proliferating cells emerged, featuring increased genomic instability, aggressiveness and chemoresistance. Mechanistically, sustained p21 accumulation inhibited mainly the CRL4–CDT2 ubiquitin ligase, leading to deregulated origin licensing and replication stress. Collectively, our data reveal the tumour-promoting ability of p21 through deregulation of DNA replication licensing machinery—an unorthodox role to be considered in cancer treatment, since p21 responds to various stimuli including some chemotherapy drugs

Structural Explanation of the Dielectric Enhancement of Barium Titanate Nanoparticles Grown under Hydrothermal Conditions

When synthesized under certain conditions, barium titanate (BaTiO3, BTO) nanoparticles are found to have the non-thermodynamic cubic structure at room temperature. These particles also have a several-fold enhanced dielectric constant, sometimes exceeding 6000, and are widely used in thin-layer capacitors. A hydrothermal approach is used to synthesize BTO nanocrystals, which are characterized by a range of methods, including X-ray Rietveld refinement and the Williamson–Hall approach, revealing the presence of significant inhomogeneous strain associated with the cubic phase. However, X-ray pair distribution function measurements clearly show the local structure is lower symmetry than cubic. This apparent inconsistency is resolved by examining 3D Bragg coherent diffraction images of selected nanocrystals, which show the existence of ≈50 nm-sized domains, which are interpreted as tetragonal twins, and yet cause the average crystalline structure to appear cubic. The ability of these twin boundaries to migrate under the influence of electric fields explains the dielectric anomaly for the nanocrystalline phase

Behavior of strain stripe networks in barium titanate nanocrystals on crossing its ferroelectric phase transition

Nanoscale strain networks are reported in BaTiO3 (BTO) crystals of 300 nm size using Bragg coherent diffractive imaging. BTO nanocrystals with clear facets were chosen to identify the crystallographic directions, allowing the strain field direction and periodicity to be studied in detail. Stripes of strain were observed, which were both stable and preserved in tetragonal and cubic phases at elevated temperatures, above the tetragonal-to-cubic phase transition. A finite element analysis approach was used to simulate the domain structures inside a BTO crystal and to understand the origins of the strain stripes as piezoelectric blocks. A 180° domain model gives a better qualitative match to the experimental images

A rapid screening tool for psychological distress in children 3--6years old: results of a validation study.

International audienceABSTRACT: BACKGROUND: The mental health needs of young children in humanitarian contexts often remain unaddressed. The lack of a validated, rapid and simple tool for screening combined with few mental health professionals able to accurately diagnose and provide appropriate care mean that young children remain without care. Here, we present the results of the principle cross-cultural validation of the "Psychological Screening for Young Children aged 3 to 6" (PSYCAa3-6). The PSYCa 3--6 is a simple scale for children 3 to 6 years old administered by non-specialists, to screen young children in crises and thereby refer them to care if needed. METHODS: This study was conducted in Maradi, Niger. The scale was translated into Hausa, using corroboration of independent translations. A cross-cultural validation was implemented using quantitative and qualitative methods. A random sample of 580 mothers or caregivers of children 3 to 6 years old were included. The tool was psychometrically examined and diagnostic properties were assessed comparing the PSYCa 3--6 against a clinical interview as the gold standard. RESULTS: The PSYCa 3--6 Hausa version demonstrated good concurrent validity, as scores correlated with the gold standard and the Clinical Global Impression Severity Scale (CGI-S) [rho = 0.41, p-value = 0.00]. A reduction procedure was used to reduce the scale from 40 to 22 items. The test-retest reliability of the PSYCa 3--6 was found to be high (ICC 0.81, CI95% [0.68; 0.89]). In our sample, although not the purpose of this study, approximately 54 of 580 children required subsequent follow-up with a psychologist. CONCLUSIONS: To our knowledge, this is the first validation of a screening scale for children 3 to 6 years old with a cross-cultural validation component, for use in humanitarian contexts. The Hausa version of the PSYCa 3--6 is a reliable and a valuable screening tool for psychological distress. Further studies to replicate our findings and additional validations of the PSYCa 3--6 in other populations may help improve the delivery of mental health care to children