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This integrated analysis evaluates the efficacy and safety of voclosporin, a novel calcineurin inhibitor, at 23.7 mg twice daily in combination with mycophenolate mofetil (MMF) and oral glucocorticoids in lupus nephritis (LN) using pooled data from two large phase II and phase III clinical trials. The purpose was to expand the pool of patients for safety analyses and to increase power for efficacy analyses in patient subpopulations. Aurinia Urinary Protein Reduction in Active Lupus with Voclosporin (AURA‐LV) (phase II) and Aurinia Renal Response in Active Lupus With Voclosporin (AURORA 1) (phase III) were randomized, placebo‐controlled, double‐blind trials with similar designs and end points comparing voclosporin to control in combination with MMF and oral glucocorticoids for the treatment of LN. The primary efficacy outcome of the integrated analysis was complete renal response (CRR) at approximately one year (Week 48 data from AURA‐LV and Week 52 from AURORA 1). Safety was assessed throughout the trials. Overall, 534 patients (268 voclosporin; 266 control) were included in the integrated analysis. Significantly more patients achieved a CRR at one year in the voclosporin group than in the control group (43.7% vs. 23.3%; OR 2.76; 95% CI 1.88, 4.05 P< 0.0001). The incidence of adverse events (AEs) was similar (91.4% voclosporin; 87.2% control). Most AEs were mild to moderate in severity; the most commonly reported AEs were classified as infections and infestations (62.2% voclosporin; 54.9% control) and gastrointestinal disorders (45.3% voclosporin; 35.3% placebo). No new or unexpected safety signals were detected. This integrated analysis demonstrates the efficacy and safety of voclosporin in the treatment of LN across the diverse racial and ethnic groups studied.

The grain refinement, microstructure, morphology and fraction of interdendritic phases and micro-segregation in superalloy K4169 solidified with a low voltage pulsed magnetic field were investigated. The experimental results showed that the as-cast grains were well refined from ~ 7 to ~ 2 mm under the action of pulsed magnetic field. Some blocky Laves phases and MC phases were observed in the interdendritic region. The fractions of these two phases were both increased under pulsed magnetic field without little change in morphologies. The element contents in dendrite arms and interdendritic region were measured. The results indicated the micro-segregation of solute elements Ti, Nb, Mo, Al, Fe, Cr was in general a little severer when the pulsed magnetic field was applied. The increase of interdendritic phases and the segregation of solute elements were caused by the destruction of solute boundary layer and forced convection in front of the solidification interface by the pulsed magnetic field.

Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis.

A multi-biomarker disease activity (MBDA) score has been validated as an objective measure of disease activity in rheumatoid arthritis (RA) and shown to track response to treatment with several disease-modifying anti-rheumatic drugs (DMARDs). The objective of this study was to evaluate the ability of the MBDA score to track response to treatment with rituximab. Data were used from 57 RA patients from three cohorts treated with rituximab 1000 mg and methylprednisolone 100 mg at days 1 and 15. The MBDA score was assessed in serum samples obtained at baseline and 6 months. Spearman’s rank correlation coefficients were calculated for baseline values, 6-month values, and change from baseline to 6 months (∆), between MBDA score and the following measures: disease activity score assessing 28 joints (DAS28) using erythrocyte sedimentation rate (ESR) or high-sensitivity C-reactive protein (hsCRP), ESR, (hs)CRP, swollen and tender joint counts assessing 28 joints (SJC28, TJC28), patient visual analogue scale for general health (VAS-GH), health assessment questionnaire (HAQ), and radiographic progression over 12 months using Sharp/van der Heijde score (SHS), as well as six bone turnover markers. Additionally, multivariable linear regression analyses were performed using these measures as dependent variable and the MBDA score as independent variable, with adjustment for relevant confounders. The association between ∆MBDA score and European League Against Rheumatism (EULAR) response at 6 months was assessed with adjustment for relevant confounders. At baseline, the median MBDA score and DAS28-ESR were 54.0 (IQR 44.3–70.0) and 6.3 (IQR 5.4–7.1), respectively. MBDA scores correlated significantly with DAS28-ESR, DAS28-hsCRP, ESR and (hs)CRP at baseline and 6 months. ∆MBDA score correlated significantly with changes in these measures. ∆MBDA score was associated with EULAR good or moderate response (adjusted OR = 0.89, 95% CI = 0.81–0.98, p= 0.02). Neither baseline MBDA score nor ΔMBDA score correlated statistically significantly with ∆SHS (n= 11) or change in bone turnover markers (n= 23), although ∆SHS ≥ 5 was observed in 5 (56%) of nine patients with high MBDA scores. We have shown, for the first time, that the MBDA score tracked disease activity in RA patients treated with rituximab and that change in MBDA score reflected the degree of treatment response.

Variations in mitochondrial genome have been found to be associated with hearing loss. Of these, the mitochondrial 12S rRNA and tRNASer(UCN)are the hot-spots for pathogenic variants associated with deafness. To understand the putative role of mitochondrial DNA (mtDNA) variants in hearing loss, we recently screened the variants in mitochondrial genomes in patients with deafness from the Hangzhou area of Zhejiang Province, People’s Republic of China (PRC). In this study, we describe a maternally-inherited Han Chinese family with high penetrance of hearing loss, notably, the penetrance of hearing loss in this family were 80.0 and 40.0%, when the aminoglycoside was included or excluded. Three matrilineal relatives in this pedigree exhibited different levels of hearing loss with different age at onset. In addition, sequence analysis of the complete mitochondrial genome showed the presence of the well-known C1494T pathogenic variant in the 12S rRNAgene and the G7444A pathogenic variant in the COI/ tRNASer(UCN). The C1494T anomaly had been reported to be a pathogenic mutation associated with aminoglycoside-induced and nonsyndromic hearing loss (AINHL), while the G7444A was considered as a secondary mutation associated with deafness. However, the lack of functional variants in GJB2and TRMUgenes suggested that nuclear modified genes may not play important roles in deafness expression. Thus, the combination of G7444A and C1494T pathogenic variants in the mitochondrial genome may account for the high penetrance of hearing loss in this Chinese family.

Epithelial–mesenchymal transition (EMT) is regarded as a crucial contributing factor to cancer progression. Diverse factors have been identified as potent EMT inducers in ovarian cancer. However, molecular mechanism sustaining EMT of ovarian cancer cells remains elusive. Here we show that the presence of SOS1/EPS8/ABI1 complex is critical for sustained EMT traits of ovarian cancer cells. Consistent with the role of SOS1/EPS8/ABI1 complex as a Rac1-specific guanine nucleotide exchange factor, depleting Rac1 results in the loss of most of mesenchymal traits in mesenchymal-like ovarian cancer cells, whereas expressing constitutively active Rac1 leads to EMT in epithelial-like ovarian cancer cells. With the aid of clinically tested inhibitors targeting various EMT-associated signaling pathways, we show that only combined treatment of mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) and Src inhibitors can abolish constitutively active Rac1-led EMT and mesenchymal traits displayed by mesenchymal-like ovarian cancer cells. Further experiments also reveal that EMT can be induced in epithelial-like ovarian cancer cells by co-expressing constitutively active MEK1 and Src rather than either alone. As the activities of Erk and Src are higher in ovarian cancer cells with constitutively active Rac1, we conclude that Rac1 sustains ovarian cancer cell EMT through simultaneous activation of MEK1/2 and Src signaling pathways. Importantly, we demonstrate that combined use of MEK1/2 and Src inhibitors effectively suppresses development of intraperitoneal xenografts and prolongs the survival of ovarian cancer-bearing mice. This study suggests that cocktail of MEK1/2 and Src inhibitors represents an effective therapeutic strategy against ovarian cancer progression.

Compared with fossil fuels reforming to hydrogen, electrolytic water to hydrogen is highly energy-intensive. It is still a big challenge to decrease the cost of electrolytic water to hydrogen. Herein, we investigate the electrocatalytic activity of uniform bimetal zeolite imidazole framework (CuxCoy-ZIFs, x: y = 1:3, 1:1, 3:1 mol ratio) nanododecahedrons. Bimetal CuxCoy-ZIFs show an obviously higher oxygen evolution reaction (OER) activity than ZIF-67, which is mainly attributed to the synergistic effect of Co and Cu. The Cu doping accelerates electron transfer and optimizes the electron structure of Co. In addition, the in-situgenerated hydroxides/oxides (Co(OH)2, Cu(OH)2Co3O4, Cu2O) during electrocatalytic reaction may be the main active sites are for ZIF-67 and CuxCoy-ZIF. Meanwhile, density functional theory calculations demonstrate that H+and OH−adsorptions on Cu1Co1-ZIF are more favorable thermodynamically than that on ZIF-67. Furthermore, when OER is substituted by glycerol oxidation reaction (GOR), the anodic GOR current increases by 8.9 times than OER current. Compared with OER-based electrolyzer, the cell voltage of GOR-based electrolyzer has decreased by 18.81%, and its Faradaic efficiency rises to 94.4%. The innovative system can efficiently produce hydrogen at an ultra-low electric energy consumption and a high conversion of energy.

Acquired resistance to chemotherapy remains a major stumbling block in cancer treatment. Chronic inflammation has a crucial role in induction of chemoresistance and results, in part, from the induction and expansion of inflammatory cells that include myeloid-derived suppressor cells (MDSCs) and IL-13+Th2 cells. The mechanisms that lead to induction of activated MDSCs and IL-13+Th2 cells have not yet been identified. Here we demonstrated that doxorubicin (DOX) treatment of 4T1 breast tumor-bearing mice led to the induction of IL-13R+miR-126a+MDSCs (DOX-MDSC). DOX-MDSC promote breast tumor lung metastasis through MDSC miR-126a+exosomal-mediated induction of IL-13+Th2 cells and tumor angiogenesis. The induction of DOX-MDSC is regulated in a paracrine manner. DOX treatment not only increases interleukin (IL)-33 released from breast tumor cells, which is crucial for the induction of IL-13+Th2 cells, but it also participates in the induction of IL-13 receptors and miR-126a expressed on/in the MDSCs. IL-13 released from IL-13+Th2 cells then promotes the production of DOX-MDSC and MDSC miR-126a+exosomes via MDSC IL-13R. MDSC miR-126a+exosomes further induce IL13+Th2 cells in a positive feed-back loop manner. We also showed that MDSC miR-126a rescues DOX-induced MDSC death in a S100A8/A9-dependent manner and promotes tumor angiogenesis. Our findings provide insight into the MDSC exosomal-mediated chemoresistance mechanism, which will be useful for the design of inhibitors targeting the blocking of induction of miR-126a+MDSCs.

The WASF3gene is overexpressed in high-grade breast cancer and promotes invasion and metastasis, but does not affect proliferation. The HER2/ERBB2/NEUgene is also frequently overexpressed in breast cancer, and has been shown to promote invasion and metastasis in these tumors. Here, we show that WASF3 is present in the HER2 immunocomplex and suppression of WASF3 function leads to suppression of invasion even in the presence of HER2 expression. Overexpression of both HER2and WASF3in non-metastatic MCF7 breast cancer cells promotes invasion and metastasis more significantly than either gene alone. HER2 forms homodimers as well as heterodimers with other HER family members and we now show that the ability of WASF3 to promote invasion is highly dependent on the HER2/HER3 heterodimer. The engagement of WASF3 with the HER2/HER3 complex facilitates its phospho-activation and transcriptional upregulation, which is facilitated by HER2/HER3 activation of JAK/STAT signaling. In breast cancer cells overexpressing HER2, therefore, WASF3 is specifically required to facilitate the invasion/metastasis response. Targeting WASF3, therefore, could be a potential therapeutic approach to suppress metastasis of HER2-overexpressing breast tumors.

Steroid sex hormones can induce prostate carcinogenesis, and are thought to contribute to the development of prostate cancer during aging. However, the mechanism for hormone-induced prostate carcinogenesis remains elusive. Here, we report that activating transcription factor 3 (ATF3)—a broad stress sensor—suppressed hormone-induced prostate carcinogenesis in mice. Although implantation of testosterone and estradiol (T+E2) pellets for 2 months in wild-type mice rarely induced prostatic intraepithelial neoplasia (PIN) in dorsal prostates (one out of eight mice), the loss of ATF3led to the appearance of not only PIN but also invasive lesions in almost all examined animals. The enhanced carcinogenic effects of hormones on ATF3-deficient prostates did not appear to be caused by a change in estrogen signaling, but were more likely a consequence of elevated androgen signaling that stimulated differentiation of prostatic basal cells into transformation-preferable luminal cells. Indeed, we found that hormone-induced lesions in ATF3-knockout mice often contained cells with both basal and luminal characteristics, such as p63+cells (a basal-cell marker) showing luminal-like morphology, or cells double-stained with basal (CK5+) and luminal (CK8+) markers. Consistent with these findings, low ATF3expression was found to be a poor prognostic marker for prostate cancer in a cohort of 245 patients. Our results thus support that ATF3 is a tumor suppressor in prostate cancer.

AAA domain containing 3A (ATAD3A) is an integral mitochondrial membrane protein with unknown function, although we now show that high-level expression is associated with poor survival in breast cancer patients. Using a mass spectrometry approach we have demonstrated that ATAD3A interacts with the WASF3 metastasis-promoting protein. Knockdown of ATAD3Aleads to decreased WASF3 protein levels in breast and colon cancer cells. Silencing ATAD3Aalso results in loss of both cell anchorage-independent growth and invasion and suppression of tumor growth and metastasis in vivousing immuno-compromised mice. HSP70 is responsible for stabilizing WASF3 in the cytoplasm, but inactivation of HSP70 does not lead to the loss of WASF3 stability at the mitochondrial membrane, where presumably it is protected through its interaction with ATAD3A. In response to endoplasmic reticulum (ER) stress, increases in the GRP78 protein level leads to increased WASF3 protein levels. We also show that ATAD3A was present in a WASF3-GRP78 complex, and suppression of GRP78 led to destabilization of WASF3 at the mitochondrial membrane, which was ATAD3A dependent. Furthermore, ATAD3A-mediated suppression of CDH1/E-cadherin occurs through its regulation of GRP78-mediated WASF3 stability. Proteolysis experiments using isolated mitochondria demonstrates the presence of the N-terminal end of WASF3 within the mitochondria, which is the interaction site with the N-terminal end of ATAD3A. It appears, therefore, that stabilization of WASF3 function occurs through its interaction with ATAD3A and GRP78, which may provide a bridge between the ER and mitochondria, allowing communication between the two organelles. These findings also suggest that pharmacologic inhibition of ATAD3A could be an effective therapeutic strategy to treat human cancer.

Reactive bulk rubber (EOR-g-MA) and reactive core-shell rubber (ABS-g-MA) are selected as toughening agents to toughen PA6 nanocomposites. The two blends are designed with 20 wt-% rubber phase and 3 wt-% organoclay. X-ray diffraction, transmission electron microscopy and scanning electron microscopy were used to evaluate the degree of exfoliation of organoclays and morphology of the nanocomposites. The organoclay platelets are well exfoliated in the nanocomposites. At the same time, the size of the elastomer particles and interfacial adhesion between polyamide 6 and elastomers are dramatically affected by the existence of organoclay. ABS-g-MA is found to promote the toughness efficiency of PA6 than does EOR-g-MA, which reveals higher impact strength and elongation at break. However, tensile strength and Young's modulus of PA6 blends based on EOR-g-MA elastomer are higher than those based on ABS-g-MA elastomer.

This paper presents a stochastic analysis of a tapered column subjected to gravity as well as horizontal and vertical earthquake accelerations. The normal mode approach is used. The approach considers the effect of both nonuniformity in column configuration and axial loading on mode shapes and natural frequencies. The earthquake accelerations are modeled as nonstationary Gaussian random processes with either white or nonwhite power spectra. This allows the statistical moments of column responses to be solved from a set of first order ordinary differential equations derived from the theory of Markov process. Both time histories of responses and spatial distribution of maximum responses along the elevation of the column are presented. Exact analytical sequences can be applied to handle problems of nonuniform columns.

Two series of U doped zirconolite–sphene composite materials were prepared by solid state reaction method: CaZr(1-m)UmTi2O7-(1-m) Ca(1-x)UxAl2xTi(1-2x)SiO5(m?=?7x) and Ca(1-n)U6nZr(1-5n)Al2nTi(2-2n)O7-(1-5n) Ca(1-y)UyAl2yTi(1-2y)SiO5(n?=?5y/6). The effects of U content on the phase structure of the composite materials were mainly investigated. The results show that the optimal synthesis temperature of the composite material is ~1230°C. In comparison with the incorporation of U in the Zr site of zirconolite, U incorporation in the Ca site of zirconolite using Al as charge compensating ions was not very efficient. Hydrothermal stability of the U doped zirconolite–sphene composite material was examined by modified product consistency test method at 90°C in deionised water (pH 7). The normalised U leach rate is fairly constant in a low value below 10-5g m-2day-1after 28 days.

A Gulf of Mexico performance evaluation and comparison of coastal circulation and wave models was executed through harmonic analyses of tidal simulations, hindcasts of Hurricane Ike (2008) and Rita (2005), and a benchmarking study. Three unstructured coastal circulation models (ADCIRC, FVCOM, and SELFE) validated with similar skill on a new common Gulf scale mesh (ULLR) with identical frictional parameterization and forcing for the tidal validation and hurricane hindcasts. Coupled circulation and wave models, SWAN+ADCIRC and WWMII+SELFE, along with FVCOM loosely coupled with SWAN, also validated with similar skill. NOAA's official operational forecast storm surge model (SLOSH) was implemented on local and Gulf scale meshes with the same wind stress and pressure forcing used by the unstructured models for hindcasts of Ike and Rita. SLOSH's local meshes failed to capture regional processes such as Ike's forerunner and the results from the Gulf scale mesh further suggest shortcomings may be due to a combination of poor mesh resolution, missing internal physics such as tides and nonlinear advection, and SLOSH's internal frictional parameterization. In addition, these models were benchmarked to assess and compare execution speed and scalability for a prototypical operational simulation. It was apparent that a higher number of computational cores are needed for the unstructured models to meet similar operational implementation requirements to SLOSH, and that some of them could benefit from improved parallelization and faster execution speed. ADCIRC, FVCOM, and SELFE perform similarly for tides and storm surgeSLOSH did not simulate storm surge as accurately as unstructured modelsSLOSH is computationally less costly than the unstructured models.

Tribological properties of ceramic cutting tool materials in contact with wood based materials were studied in this paper by examining how Al2O3-ceramics and Si3N4-ceramics behave in dry sliding experiment in contact with wood-based materials and by comparing their behavior with tungsten carbide material at the same time. It had been found that the ceramics exhibited much better tribological properties than tungsten carbide material, and Si3N4-ceramic performed better than Al2O3-ceramics. The Al2O3-ceramics with an addition of ZrO2 had better tribological performance than the common Al2O3-ceramics in contact with wood-based materials. The tungsten carbide had better tribological performance than ceramics in tribological contact with wood flour/PE material. A well-marked difference occurred in various cutting materials/MDF frictional pair, but the differences in various cutting materials/PB frictional pair were insignificant. An increase of the normal force didn’t result in any significant decrease of the friction coefficient. An addition of ZrO2 in the Al2O3-ceramics could inhabit corrosive wear.

Aminopeptidases play essential roles in protein maturation, activation, and stability as well as in the degradation and regulation of hormonal and nonhormonal peptides that can serve as important enzyme targets for drug design. This review will focus on an effective inhibitor of aminopeptidases, bestatin, including work to find better inhibitors in the past three decades that has sought to optimize bestatin and prospective developments in bestatin optimization in the future.

This paper describes the successful development of a middle-range six-degrees-of-freedom stage, using the features of a flexible structure. The system includes two parts: a middle-range positioning X—Ystage and a four-degrees-of-freedom stage. The flexible structure of the four-degrees-of-freedom stage is built from two kinds of flexible bodies: circular hinges and a new two-degrees-of-freedom flexible body. The four-degrees-of-freedom stage was designed to compensate movement errors including linear displacement, pitch, and roll errors. The linear displacement reaches 20 mm along the X-axis, 20 mm along the Y-axis, and 5 μm along the Z-axis. The rotation angle around the X-axis (θx), Y-axis (θy), and Z-axis (θz) were all 10 arcsec. A novel six-degrees-of-freedom measuring system was also designed. Precision feedback control is demonstrated in a series of experiments performed using the proposed measurement system.

AbstractThe extent and factors influencing sorption of plutonium (Pu) in shale media have been studied in batch-type experiments. The equilibrium time and isotherm of Pu sorption have been firstly determined. The effect of shale grain size, aqueous pH, water/solid ratio, co-existing ions (cations and anions) and temperature were studied as the factors likely to influence Pu sorption. The experimental variables included the following: grain sizes in five ranges, 0.12 to 0.15 mm, 0.15 to 0.18 mm, 0.18 to 0.25 mm, 0.25 to 0.38 mm, and 0.38 to 0.83 mm; solution pH values of 4, 6, 8, and 10; water/solid ratios of 10:0.25, 10:0.5, 10:0.75, and 10:1; temperatures of 20 °C, 40 °C, and 60 °C); and selected co-existing conventional cations including Na+, Fe+, Al3+, Ca2+, and K+and anions including SO42-, CO32-, NO3-, and Cl-in each case in solutions of the same total ionic strength. The experimental results demonstrate that the equilibrium time of Pu sorption is 9 d, that the sorption behavior of Pu in the solution is well described by the Freundlich sorption isotherm (Cs=kCeqN), and that Pu is strongly sorbed on shale media. The extent of Pu sorption increased with decreasing grain size, apparently in response to the increase in specific surface area and total pore volume. The results also show that Pu sorption increases with increasing solution pH and with increasing water/solid ratio. The influence of co-existing anions on Pu sorption was much stronger, under the same conditions, than that of the cations; this was attributed to Pu complexation in solution, i.e., the complexing apparently weakened the sorption of Pu on shale particles in the solution. Finally, the influence of varying temperature on Pu sorption is found to be less important than that of other factors, but should never be ignored.

Recent studies have suggested that the dys-regulated progressive immune responses in some inflammatory conditions can lead to significantly increased osteoclasts (OC) frequency and activity associated with active bone destruction; termed inflammation-induced bone loss. Among the inflammatory infiltrates, monocytes/macrophages (Mo/MQ), T and B cells, have been well studied and documented as central players in osteoimmunological interactions (osteoimmunology: is an interdisciplinary field linking the immune and skeletal systems). We and others investigated the role(s) of dendritic cells (DC) during inflammation-induced osteoclastogenesis and bone loss. In addition to their innate effector functions, DC are potent professional antigen-presenting cells (APC) involved in triggering and orchestrating adaptive immunity, thereby implicated as potential osteo-immune players. Herein, bone remodeling and DCs biology including their development and functions are reviewed along with the contribution of DC at the crossroad of the osteo-immune interface during the process of inflammation-induced osteoclastogenesis. Furthermore, we provide a summary of recent progress, and discuss a proposed alternative mechanism underlying inflammation-induced bone loss. Understanding the cellular and molecular mechanisms regulating DCs roles in inflammation-induced osteoclastogenesis and bone loss might benefit future treatment approaches, especially if targeting DC can be translated into therapeutic strategies to ameliorate both tissue inflammation and bone destruction during disease progression associated with inflammatory bone diseases.

ObjectiveTo evaluate the efficacy and safety of intraarticular infliximab compared with intraarticular methylprednisolone in patients with gonarthritis.MethodsIn 23 patients with recurrent gonarthritis despite previous intraarticular corticosteroid therapy, a total of 41 intraarticular injections 20 infliximab and 21 methylprednisolone were performed in 28 knees. Initial therapy was randomly assigned, and crossover therapy was eligible within 3 months. The clinical effect was assessed during 6 months of followup. The primary outcome was eventfree survival, defined as the time after treatment until local retreatment was performed andor nonimprovement of the knee joint score. Adverse effects were recorded during followup.ResultsAll patients treated with intraarticular infliximab had an insufficient response. In contrast, 8 of the 21 intraarticular methylprednisolone injections were effective P 0.004. Between groups, no differences in the patients age, disease duration, number of diseasemodifying antirheumatic drugs, or previous intraarticular methylprednisolone were observed. Reported adverse effects were not related to therapy.ConclusionTreatment with intraarticular infliximab injection was not effective in patients with a chronically inflamed knee joint. Intraarticular injection with methylprednisolone was superior despite previous intraarticular corticosteroid therapy. Further investigation is needed to provide these patients with a better alternative.

In this paper, it presents a useful dual-axial five-degrees-of-freedom measuring system with five degrees of freedom (DoFs) for the simultaneous measurement of five-DoF motion errors of a nano-stage. The system integrates a miniature fibre-coupled laser interferometer with specially designed optical paths and quadrant detectors, capable of measuring five-DoF motion errors. It presents a new precision five-DoF measuring system which has been developed and implemented for the simultaneous measurement of five-DoF motion errors (two linear positions, as well as pitch, roll, and yaw) of a nano-stage. In this paper, the five-DoF laser interferometer was produced by designing the optical path from the one-DoF laser interferometer. The system employs two three-DoF interferometers to detect two position errors and three angular errors of the nano-stage. The experimental set-ups and measuring procedure and a systematic calculated method for the error verification are presented as well. The resolution of measuring the angular errors component is about 0.06″.

Acute thyroid abscess is rare, however this report describes the case of a 71-year-old male with an acute thyroid abscess resulting from oesophageal perforation who was successfully treated with antibiotic (cefotaxime sodium), neck exploration and a right subtotal thyroidectomy. The patient reported ingesting a fish bone and, although this had been dislodged, he experienced continuing pharyngalgia and fever. An anterior neck swelling with tenderness and erythema was noted at the level of the right thyroid. At operation, the recurrent laryngeal nerve was identified and preserved, and a large part of the right thyroid was excised. During the 5-year follow-up period, deglutition function and thyroid function tests remained normal. This result indicates that early administration of antibiotic, and surgical treatment of the infection source and affected thyroid tissue are critical for a successful outcome and the prevention of severe complications.

Immunoglobulin-secreting cells comprise both short-lived proliferating plasmablasts and long-lived nonproliferating plasma cells. To determine the phenotype and functional activity of Ig-secreting cells in human lymphoid tissue, we used a tonsillar organ culture model. A significant proportion of IgA and IgG secretion was shown to be mediated by long-lived, nonproliferating plasma cells that coexpressed high levels of CD27 and CD38. The presence of such cells was further corroborated by the finding of enhanced expression in the CD19+B-cell population of XBP-1, IRF-4, and particularly Blimp-1 genes involved in the differentiation of plasma cells. Intact tissue seemed to be necessary for optimal functional activity of plasma cells. A strong correlation was found between concentrations of interleukin-6 and IgA or IgG, but not IgM, in culture supernatants suggesting a role for interleukin-6 in the survival of long-lived plasma cells. Taken together, the present study demonstrates that human lymphoid tissue harbors a population of nonproliferating plasma cells that are dependent on an intact microenvironment for ongoing Ig secretion.

The aim of the present study is to obtain the epidemiological data on post-partum thyroiditis (PPT) firstly in Chinese women, and to try to evaluate whether excessive intake of iodine in post-partum women imposes any danger of occurring PPT. Sixty hundred and ten pregnant women were involved in the cohort just before delivery. Four hundred and eighty-eight (80%) of them accepted taking part in follow-ups more than 6 months post-partum. A blood sample was taken from participants before delivery and every 3 months post-partum for testing of serum TSH, thyroid autoantibodies. Free T3(FT3), free T4(FT4) and TSH receptor antibody (TRAb) were detected if TSH was abnormal. The iodine nutrition was evaluated according to the mean level of the fasting urinary iodine excretions at different times during the studying period, and participants were subgrouped into 3 categories with low, adequate and high iodine intake. For those participants who had thyroid dysfunction within 6 months post-partum, the follow-up persisted for 1 yr. Of 488 preg- nant women, PPT developed in 11.9% (58/488). Given overt and subclinical PPT, the prevalence was 7.17% (no.=35) and 4.71% (no.=23), respectively. There was a strong association between the presence of thyroid peroxidase antibody (TPOAb) at delivery and the risk of developing PPT [RR=6.76, 95% (CI) 4.42–10.34]. Overt cases had much higher titers of TPOAb than subclinical patients (all p<0.05). The median urinary iodine (MUI) of patients with PPT was significantly higher than that of healthy women (231.93 vs 199.88 μg/l p=0.00153). Both the prevalence of PPT and positive TPOAb rise with the increment of iodine intakes. Pregnant women with high iodine intake had more risk of developing PPT when compared with those with low iodine intake (RR=2.92, 95%CI 1.31–6.50). We concluded that positive TPOAb was of value for predicting the occurrence and severity of PPT, and a high iodine intake was a risk factor triggering PPT.

The selective oxidation of methane with oxygen to C1 oxygenates (methanol and formaldehyde) is an important process. However, the precise reaction mechanism in a gaseous chain reaction has not been clarified. Methane activation and the selectivity of C1 oxygenates (CH3OH, CH2O) in a gaseous selective oxidation of CH4−O2−NO2 have been examined under atmospheric pressure with both theoretical and experimental approaches. Theoretically calculated transition barrier of hydrogen abstraction from CH4 of the reaction CH4 + NO2 → CH3 + HNO2 was lower than that of the reaction with O2, i.e., CH4 + O2 → CH3 + O2H. This decrease of the transition barrier was experimentally verified by the linear enhancement of CH4 conversion with NO2 concentration in CH4−O2−NO2. The experimental varied results of selectivity of C1 oxygenates on various reaction conditions (NO2 concentration, CH4/O2 ratio, space velocity) showed the appropriateness of the consideration on the selectivity with the calculated values of transition barriers and rate constants of the selected reaction routes from CH3O to CH3OH and CH2O. After considering the transition barriers and rate constants of each elemental reaction route, we attained ca. 7% yield of C1 oxygenates.

RAD26, the yeast homologue of human CSB, has an essential role in transcription-coupled repair (TCR). We have mapped the requisite of Rad26 for nucleotide excision repair (NER) within the different regions of the yeast Saccharomyces cerevisiae MFA2 gene at nucleotide resolution. Our results show that Rad26 is dispensable for enhanced NER in both the MFA2 upstream promoter, except in the TATA box region, and for enhanced NER in both strands of the active gene at a site close to the transcription termination region. As expected, it is not needed for repair of regions downstream of where transcription terminates. However, it is required for TCR in the transcription initiation and elongation regions. Our data support the hypothesis that Rad26 is required for the interchange between holo-TFIIH and a putative repairosome containing core TFIIH and other NER proteins. Close to the end of transcription, hotspots for the repair of CPDs in both the transcribed strand and the non-transcribed strand occur. This enhanced repair is independent of Rad26. Hence, TFIIH may take a form favourable for forming a repairosome without Rad26 assistance; here the organisation of the DNA during the termination of transcription may facilitate access of a repair complex to enable enhanced repair of both strands.

Single phase zirconolite (CaZrTi2O7) was synthesised by a novel method using acid corrosion to treat zirconolite–diopside mixture powders (2CaZrTi2O7–Mg2Si2O6). The mixture powders were prepared by solid state reaction method at 1200°C for 2 h. Single phase zirconolite powders were obtained by acid corrosion method with 5% hydrofluoric acid on the zirconolite–diopside Synroc mixture powders and washed with 10% acetic acid.

Polyelectrolyte behavior of the inner part of poly(methacrylic acid) shell and microscopic properties of the interface between the hydrophobic core and the hydrophilic shell in polystyrene-block-poly(methacrylic acid) micelles were studied by UV−vis spectroscopy and by the steady-state and time-resolved fluorometry using two fluorescent probes, 5-(N-octadecanoyl)aminofluorescein (OAF) and 5-(N-dodecanoyl)aminofluorescein (DAF). Two almost identical copolymer samples of polystyrene-block-poly(methacrylic acid), PS-PMA and PS-DPA-PMA, were used in the study, except that the latter was fluorescently tagged between blocks by a pending p-vinyl-9,10-diphenylanthracene group (DPA), which allows also for studying the OAF binding in the interfacial region by means of nonradiative energy transfer from DPA to fluorescein head-groups of either OAF or DAF. Pronounced shifts in pKa of both OAF and DAF, which were observed after binding to polymeric micelles, are explained by a competition of two effects. The first effect is caused by the association processes of amphiphilic probes in the bulk aqueous solution, and the second one is due to an additional energy that is needed for the proton dissociation from the fluorescein −OH group in the anionic polyelectrolyte shell and for the consequent proton transfer into the bulk (the latter is similar to that described by Fromherz et al.).

A reaction model for the conversion of methane to C1-oxygenates (methanol and formaldehyde) with NOx (x = 1, 2) has been proposed theoretically using the ab initio molecular orbital method. The geometric and electronic structures for all the present molecules have been calculated by means of the MP2 (frozen core)/6-311++G(2d,p) level of theory. On the basis of the optimized structures, the single point calculations of the energies are carried out at the CCSD(T) level with the same basis sets. Through the theoretical analysis of the simplified CH4−NOx system instead of the experimental CH4−O2−NO system, we found the possible reaction path leading to C1-oxygenates within all the barriers of less than 40 kcal/mol via CH3O at 800 K. NO2 has a higher activity for the hydrogen abstraction from methane than NO and O2, though the calculated rate constants at 800 K indicate that this reaction is the rate-determining step in the conversion of methane to C1-oxygenates. It is also found that increasing the concentration of NO promotes the yield of formaldehyde with the decreasing formation of methanol, which is consistent with recent experimental results in the CH4−O2−NO system.

Two separate human liver aldehyde dehydrogenases exist which show differences in substrate specificity, cation inhibition or activation, and molecular weight. In this paper we report a common absence of enzyme 2 in Chinese which may be taken to indicate a gene deletion coding for this enzyme. The possible implication of this gene deletion among Chinese is discussed.

Human alcohol dehydrogenase ADH2 and ADH3 were investigated in liver and stomach specimens of Chinese and Indians from West Malaysia. Eight-nine percent of the Chinese carry the atypical ADH2 type, a proportion very similar to that reported in Japanese. However, among 43 Indian specimens there was not a single case of atypical ADH2. In Indians, the gene frequency of ADH31 is 0.64 and of ADH32 0.36, similar to the frequencies in Caucasians, whereas in Chinese, the gene frequency for ADH31 and ADH32 is 0.91 and 0.09, respectively. We also report some unusual enzymatic characteristics in the course of our study.

Partitioning of pyrene between poly(tert-butylacrylate)-block-poly(2-vinylpyridine) and polystyrene-block-poly-(methacrylic acid) micelles and aqueous solvent has been studied by fluorometric techniques. The partition coefficient was evaluated on the basis of the steady-state fluorescence spectra and the time-resolved fluorescence decays from a series of solutions with decreasing copolymer concentrations, and the obtained values were compared. The agreement is very good. In the accompanying paper, the release kinetics of pyrene from micelles upon a sudden and prodigious dilution of micellar solution by the aqueous solvent was studied by time-dependent measurements of the steady-state fluorescence intensity. Simultaneous mathematical treatment of dilution curves in the absence and presence of water-soluble quencher based on the model of diffusion from a sphere allows the diffusion coefficient of pyrene in micellar cores to be evaluated. The assumption that micelles do not reorganize upon the shock dilution is tested by an independent experiment.

The kinetics of the release of pyrene from poly(tert-butyl acrylate)-block-poly(2-vinylpyridine) polyelectrolyte micelles into aqueous media was studied by two independent experimental fluorometric techniques. Mathematical treatment of the time-dependent fluorescence intensities based on a model of diffusion from a sphere allowed the evaluation of the diffusion coefficient of pyrene in the dense poly(tert-butyl acrylate) micellar core. Assumptions necessary for mathematical treatment of experimental curves were tested and their validity was proved. Fluorometric measurements suggest that a considerable fraction of pyrene is solubilized also in poly(2-vinylpyridine) micellar shells.

Digital Elevation Models are considered in relation to their use in a parallel computing environment. In particular, the problem of approximating terrain surface through a Triangulated Irregular Network (TIN) is analysed. A parallel algorithm is presented that builds a TIN based on Delaunay triangulation, by selecting a sparse subset of points from a dense regular grid of sampled data. An implementation of the algorithm on a CM-2 is described and experimental results are shown.