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OBJECTIVE: To detect the ectodysplasin A (EDA) gene mutation in patients with hypohidro-tic ectodermal dysplasia (HED), and to analyze the distribution pattern of missing permanent teeth and the systemic manifestation of HED patients with EDA gene mutation. METHODS: Twelve HED families were enrolled from clinic for genetic history collection, systemic physical examination and oral examination. Peripheral blood or saliva samples were collected from the probands and the family members to extract genomic DNA. PCR amplification and Sanger sequencing were utilized to detect the EDA gene variations, which were compared with the normal sequence (NM_001399.5). The functional impact of EDA gene variants was then evaluated by functional prediction of mutation, conservation analysis and protein structure prediction. The pathogenicity of each EDA gene variation was assessed according to the stan-dards and guidelines of the American College of Medical Genetics and Genomics (ACMG). The systemic phenotype and missing permanent tooth sites of HED patients with EDA gene mutations were summarized, and the missing rate of each tooth position was analyzed and compared. RESULTS: Eight out of twelve HED families were identified to carry EDA gene mutations, including: c.164T>C(p.Leu55Pro); c.457C>T (p.Arg153Cys); c.466C>T(p.Arg156Cys); c. 584G>A(p.Gly195Glu); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys). Among them, c.164T>C(p.Leu55Pro); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys) were novel mutations. The HED patients with EDA gene mutations in this study were all male. Our results showed that the average number of missing permanent teeth was 13.86±4.49, the average number of missing permanent teeth in the upper jaw was 13.14±5.76, the missing rate was 73.02%. And in the lower jaw, the average number of missing permanent teeth was 14.57±3.05, the missing rate was 80.95%. There was no significant difference in the number of missing teeth between the left and right sides of the permanent dentition (P>0.05). Specifi-cally, the maxillary lateral incisors, the maxillary second premolars and the mandibular lateral incisors were more likely to be missing, while the maxillary central incisors, the maxillary and mandibular first molars had higher possibility of persistence. CONCLUSION: This study detected novel EDA gene pathogenic variants and summarized the distribution pattern of missing permanent teeth of HED patients, thus enriched the variation and phenotype spectrum of EDA gene, and provided new clinical evidence for genetic diagnosis and prenatal consultation.

Using high-resolution angle-resolved photoemission spectroscopy, we systematically investigate the electronic structure of \ensuremath{\beta}-InSe, a van der Waals semiconductor with a direct band gap. Our measurements show a good agreement with ab initio calculations, which helps reveal the important impact of spin-orbit coupling on the electronic structure of \ensuremath{\beta}-InSe. Using surface potassium doping, we tune the chemical potential of the system and observe the unoccupied conduction band. The direct band gap is determined to be about 1.3 eV. Interestingly, we observe a global band shift when the sample is illuminated by a continuous-wave laser at 632.8 nm, which can be understood by an efficient surface photovoltaic effect. The surface photovoltaic can be tuned by in situ surface potassium doping. Our results not only provide important insights into the semiconducting properties of InSe, but also suggest a feasible method to study and engineer the surface photovoltaic effect in InSe-based devices.

Using high-resolution angle-resolved photoemission spectroscopy and ab initio calculation, we have studied the bulk and surface electronic structure of metallic rutile 5d transition metal oxide IrO2 that harbors both edge and corner sharing Ir-O octahedrons. We observe strong modulation of the band structure by spin-orbit coupling (SOC). The measured band structure is well reproduced by our ab initio calculation without band renormalization, suggesting the absence of the SOC-enhanced correlation effect in IrO2. In accordance with the calculation, we visualize two types of Dirac nodal lines (DNLs) protected by mirror symmetry and nonsymmorphic crystal symmetry, respectively. SOC gaps the first type of DNLs, which may contribute largely to the strong spin Hall effect. The second type of DNLs at the edges of Brillouin zone, however, remain intact against SOC. Our results not only provide important insights into the exotic transport properties of IrO2, but also shed light on the understanding of the role of SOC in the iridate family.

Summary GS-9190 is a NS5B non-nucleoside analogue with demonstrated effectiveness in a Phase 1 monotherapy study and in combination with other DAAs for treatment of chronic HCV infection. Here, the resistance profile of GS-9190 monotherapy in a Phase 1b study was investigated. Resistance analysis was performed by population sequencing and allele-specific PCR (AS-PCR) for Y448H with an assay cut-off of 0.5%. Phenotypic susceptibility analyses were performed on patient isolates as well as site-directed mutagenesis of mutations selected during monotherapy. No resistance-associated variants were observed in patients before or after receiving single doses of GS-9190 by population sequencing. In contrast, in patients who received GS-9190 for 8 days, mutations Y448H and Y452H in NS5B were observed by population sequencing in 21/36 (58%) and 2/36 (5.6%) patients, respectively, at Day 8 or Day 14. Among the remaining 15 patients who had no detectable Y448H at Day 8 or Day 14 by population sequencing, low frequencies of Y448H ranging from 1.3 to 9.7% were detected in 14 of 15 patients by AS-PCR. By AS-PCR, Y448H remained detectable at reduced frequency in the majority of patients analysed through 4–6 months of follow-up. Chimeric HCV replicons constructed with the NS5B sequence from patients with Y448H and Y448H + Y452H/Y demonstrated 27-fold and 78.5-fold reduced susceptibility to GS-9190. In conclusion, Y448H was rapidly selected in the majority of patients receiving multiple doses of GS-9190 as monotherapy, despite undetectable levels in pretreatment samples. Y448H confers reduced susceptibility to GS-9190 and other NNIs and persisted in most patients for months post-treatment.

Angle-resolved photoemission spectroscopy (ARPES) and torque magnetometry (TM) measurements have been carried out to study the electronic structures of a correlated topological insulator (TI) candidate YbB6. We observed clear surface states on the [001] surface centered at the Γ ¯ and M ¯ points of the surface Brillouin zone. Interestingly, the fermiology revealed by the quantum oscillation of TM measurements agrees excellently with ARPES measurements. Moreover, the band structures we observed suggest that the band inversion in YbB6 happens between the Yb5d and B2p bands, instead of the Yb5d and Yb4f bands as suggested by previous theoretical investigation, which will help settle the heavy debate regarding the topological nature of samarium/ytterbium hexaborides.

Two-dimensional materials have attracted considerable research attention recently due to their extraordinary physical and chemical properties. In this paper, we systematically investigate the electronic structure of ultrathin tetragonal CoSe films with different thicknesses that are isostructural to two-dimensional high-temperature superconductor FeSe using high-resolution angle-resolved photoemission spectroscopy, scanning tunneling microscopy, and ab initio calculation. Interestingly, the nonsymmorphic symmetry of the CoSe monolayer protects both exotic saddle band degeneracy and Dirac points, realizing two-dimensional Dirac fermions. Our temperature and film-thickness-dependent measurements reveal momentum-dependent electron-phonon coupling in CoSe films, which is enhanced with reduced film thickness. Moreover, the electronic states in the CoSe monolayer strongly couple to high-frequency phonons in the $\mathrm{SrTi}{\mathrm{O}}_{3}$ substrate, similar to the situation in the FeSe monolayer. Our results not only present a platform to investigate the electronic properties in close vicinity of the high-temperature superconductor FeSe monolayer, but also shed light on the understanding of the coupling between two-dimensional materials and substrates beneath.

The aim of the present study was to investigate the effects of vaccination with the hepatitis B vaccine (HBVac) in HB surface antibody (HBsAb)-negative pregnant mothers on the vertical transmission of HB virus (HBV) from father to infant. All the fathers tested positive for the serum HBV DNA and HB surface antigen (HBsAg) markers. The pregnant females were divided into an observation group or a control group depending on whether their serum was HBsAb-negative or positive. A total of 93 healthy individuals without HBV infection were included in a blank group, while 96 females who were serum HBV marker-negative or HB core antibody (HBcAb)-positive/(HBsAb)-negative were included in the observation group. The control group comprised 89 females who all tested positive for serum HBsAb, HB envelope antibodies and HBcAb. In the observation group, the positive rate of HBV DNA in the newborns was 7.29% (7/96), the positive rate of HBsAg was 3.13% (3/96) and the positive rate of HBsAb was 81.3% (78/96). In the control group, the positive rates of HBV DNA, HBsAg and HBsAb in the newborns were 4.49% (4/89), 2.25% (2/89) and 89.9% (80/89), respectively. No statistically significant differences were observed between the two groups. Therefore, the results of the present study indicate that HBVac treatment for HBsAb-negative pregnant females may have a positive role in blocking the vertical transmission of HBV from father to infant, as long as the vaccination is able to induce the production of a sufficient quantity of HBsAb. The HBVac exhibited no difference compared with pre-pregnancy HBsAb in blocking the vertical transmission of HBV from father to infant.

We examined the efficacy and safety of nucleoside analogues in preventing the vertical transmission of hepatitis B virus (HBV) from father to infant. We included 201 patients who visited the liver clinic of our hospital. The patients were positive for HBV surface antigen (HBsAg), HBeAg, anti-HBc, and HBV DNA; 189 patients (94%) had abnormal liver function. In all couples, the fathers were HBV DNA-negative and had normal liver function, and the mothers were anti-HB-positive before pregnancy. The control group comprised 188 couples who visited our hospital during the same time period. The fathers in the control group were positive for HBsAg, HBeAg, anti-HBc, and HBV DNA. The mothers were HBsAg-negative and anti-HBs-positive. No infants in the case group were HBsAg-positive and HBV DNA-positive, and all were anti-HBs-positive, indicating that father to infant HBV vertical transmission was prevented in the case group. In the control group, 147 of 188 newborns (78.2%) were anti-HBs-positive at birth, 28 (14.9%) were HBV DNA-positive, and 19 (10.1%) were HBsAg-positive. A significant difference was observed between the two groups. No statistically significant difference was observed in the gestational age, birth weight, birth length, 1-min and 8-min Apgar score, jaundice, other internal and surgical diseases, delivery mode, and other birth information between the neonates born to couples in the case and control groups; there were no fetal malformations and stillbirths in the two groups. Our results showed that administration of antiretroviral therapy to HBV DNA-positive fathers before pregnancy can cause a decrease in the viral load and prevent father to infant HBV vertical transmission. The use of antiviral nucleoside analogues before pregnancy was safe in fathers, and the fathers who wanted children could continue to use anti-viral therapy. The sample size in our study was small, and further studies with a large sample size and longer follow-up time are required for determining the use of nucleoside analogues from the point view of prenatal and postnatal care.

The effects of heat treatments on the microstructure and dry sliding friction and wear performance of Al–7·5Si–4Cu alloy were studied in this paper. The results indicated that after T6 treatment, the grains of the α-Al phase and eutectic structure were evenly distributed with increase in grain number, reduction in defects, and Si phase morphology tending round. In addition, A12Cu phase and AlMnFeSi phase precipitated interdependently in clumps or granular shape. Under lower load of 100 N, the wear loss of three alloys added slowly with increasing load, and the dominant wear mechanism was abrasive wear accompanied by slight adhesive wear. Especially, the alloy after water quenching plus aging treatment possessed the highest wear resistance. Under higher load of 300 N, the wear mechanism was delamination wear and abrasive wear for as cast alloy, serious adhesive wear and abrasive wear for alloy with water quenching plus aging treatment and abrasive wear accompanied by adhesive wear for alloy after T...

The effects of different mould sands and casting wall thicknesses on the properties and microstructures of multivariate Al–7·5Si–4Cu alloy, which was modified by Al–10Sr, RE and Al–5Ti–B master alloys, were investigated. The melt was poured into multistep moulds made from three mould sands (quartz, alumina and chromite) to produce specimens for mechanical property testing and metallography. The results demonstrated that the sample with chromite sand exhibited the best mechanical properties owing to its higher cooling rate. Tensile strength and elongation decreased monotonically with increasing wall thickness. No obvious trend of wall thickness on hardness of the alloy was found. When the cooling speed decreased, the grain refinement and transformation effect became weaker, the dendrite arm spacing (DAS) increased obviously and the properties and microstructures became poorer. A series of fitting models was established and used to predict properties of Al–7·5Si–4Cu alloy from the DAS.

This paper presents a planar notched antenna with a long meandered line for wireless USB dongle applications. The printed notched structure is used as additional resonators to generate multiple bands operation for covering GSM1800/1900/UMTS2100/LTE2300/2500 bands. In addition, with the help of the long meandered line via hole to ground, a lower resonant mode is sufficiently generated at around 770 MHz and forms a wider lower operating bandwidth (LTE700/GSM850/900). Briefly printed on a 0.8 mm thick FR4 dielectric substrate of size 20×70 mm² and electrically connected (via hole) to the ground plane of the USB dongle, the proposed antenna can provide a wide operating bandwidth (3:1 VSWR) of larger than 120 % centered at 2,000 MHz, allowing it to cover 698–960 and 1,710–2,690 MHz bands. The proposed antenna also can be attached to laptop computer by the USB interface. Detailed design considerations of the proposed antenna are described, and obtained experimental and simulation results are also presented and discussed in this paper.

The relationship of inhibitory quotient (IQ) with the virologic response to specific inhibitors of human hepatitis C virus (HCV) and the best method to correct for serum protein binding in calculating IQ have not been addressed. A common method is to determine a fold shift by comparing the EC(50) values determined in cell culture in the absence and presence of human serum (fold shift in EC(50) ), but this method has a number of disadvantages. In the present study, the fold shifts in drug concentrations between 100% human plasma (HP) and cell culture medium (CCM) were directly measured using a modified comparative equilibrium dialysis (CED) assay for three HCV protease inhibitors (PIs) and for a novel HCV inhibitor GS-9132. The fold shift values in drug concentration between the HP and CCM (CED ratio) were ∼1 for SCH-503034, VX-950 and GS-9132 and 13 for BILN-2061. These values were ∼3-10-fold lower than the fold shift values calculated from the EC(50) assay for all inhibitors except BILN-2061. Using the CED values, a consistent pharmacokinetic and pharmacodynamic relationship was observed for the four HCV inhibitors analysed. Specifically, an approximate 1 log(10) reduction in HCV RNA was achieved with an IQ close to 1, while 2-3 and greater log(10) reductions in HCV RNA were achieved with IQ values of 3-5 and greater, respectively. Thus, use of CED to define IQ provides a predictive and quantitative approach for the assessment of the in vivo potency of HCV PIs and GS-9132. This method provides a framework for the evaluation of other classes of drugs that are bound by serum proteins but require the presence of serum for in vitro evaluation.

The aim of this study was to compare the proteomics pattern of the kidneys from Cyld knockout mice with that from normal mouse kidneys and establish a preliminary understanding of the role of Cyld in the kidney. Proteins from the kidneys of knockout Cyld mice and wild-type mice were extracted, isobaric tags for relative and absolute quantitation (iTRAQ) was performed, and the proteomics patterns of the two groups were compared. The genotypes of the mice were verified by polymerase chain reaction. A total of 1748 proteins with a local false discovery rate of ≤5% were identified, among which 1437 proteins were reliably recognized and quantified. The expression of two dysregulated proteins was confirmed by Western blotting. Gene ontology and pathway analyses indicated that the proteins identified were involved in biological processes, cell components, and molecular functions, and participated in different pathways. Some of the proteins identified were relevant to renal function or kidney diseases. The difference between the proteomics profiles of kidneys from Cyld knockout mice and wild-type mice was prominent, which correlates to kidney dysfunction and the development of renal diseases.

The aim of this study was to examine the efficacy of combined immunization of hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine (HBVac) in blocking father-infant transmission of hepatitis B virus (HBV). Newborns positive at birth for blood HBV sur-face antigen (HBsAg) and/or HBV DNA were selected and immunized with HBIG combination HBVac. At 7 months, HBV markers and HBV DNA of each neonate were measured using electrochemiluminescence with the Cobas-e-411 Automatic Electrochemiluminescence Immuno-assay Analyzer and fluorescence quantitative polymerase chain reaction. Among all 7-month-old subjects, the negative conversion rates of HBV DNA and HBsAg were 48/61 (78.7%) and 19/41 (46.3%), respectively. Therefore, this study demonstrated that prompt combination injection of HBIG and HBVac can protect some of the HBV DNA- and/ or HBsAg-positive newborns from HBV.

The aim of the present study was to observe the efficacy and safety of nucleoside analogs in inhibiting father-to-infant vertical transmission of hepatitis B virus (HBV). Nucleoside analogs compete with HBV DNA polymerase substrate to inhibit DNA polymerase, thus preventing the replication of HBV DNA. A case group and control group were recruited for the study. Between March 2006 and March 2012 at the Liver Disease Center of Qinhuangdao Third Hospital, a total of 201 couples were recruited for the case group. In each case, the father tested positive the following HBV markers: Hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), antibodies against the hepatitis B core antigen (anti-HBc) and HBV DNA. In total, 189 male patients presented with abnormal liver function (94.0%; 189/201). Prior to pregnancy, all the males in the case group were required to test negative for HBV DNA and exhibit normal liver function, while the females were required to test positive for antibodies against HBsAg (anti-HBs). In total, 188 couples comprised the control group. The couples were recruited between March 2006 and March 2012 in the Prenatal Clinic of Qinhuangdao Women's and Children's Hospital. The fathers tested positive for HBsAg, HBeAg, anti-HBc and HBV DNA. With regard to the females, HBsAg tests were all negative and anti-HBs tests were positive. In the case group, there were no HBsAg-positive or HBV DNA-positive newborns, while anti-HBs tests were all positive; thus, the father-to-infant HBV vertical transmission was successfully inhibited. In the control group, 147/188 newborns tested positive for anti-HBs at birth, accounting for 78.2%. In addition, 28 newborns were positive for HBV DNA (14.9%), and 19 newborns tested positive for HBsAg (10.1%). Statistically significant differences were observed between the two groups with regard to these parameters. However, no statistically significant differences in gestational age, birth weight, birth height, 1- and 8-min Apgar scores, presence of jaundice, other internal and surgical diseases, delivery mode and other birth information were observed when comparing the case group with the control group. Furthermore, there were no fetal malformations or stillbirths in the two groups. In the HBV DNA-positive fathers prior to pregnancy, antiretroviral therapy resulted in a reduced virus load. Therefore, blocking father-to-infant HBV vertical transmission maximally was important. The use of antiviral nucleoside analogs prior to pregnancy was shown to be safe. When the benefits outweighed the risks, the fathers who wanted to have a child continued to use antiviral therapy. However, the sample size of the present study was small, and an increased number of cases and longer follow-up times are required. In addition, the use of nucleoside analogs requires further in-depth assessment from the point of view of prenatal and postnatal care.

Halo evolution of an Al-17.5Si alloy surface after treatment with increasing pulse numbers of a high-current pulsed electron beam (HCPEB) was investigated. A halo is a ring microstructure resembling a bull’s eye. SEM results indicate that the nanocrystallization of halo induced by HCPEB treatment leads to gradual diffusion of the Si phase. Multiple pulses numbers cause the Si phase to be significantly refined and uniformly distributed. In addition, nanosilicon particles with a grain size of 30~100 nm were formed after HCPEB treatment, as shown by TEM observation. XRD results indicate that Si diffraction peaks broadened after HCPEB treatment. The microhardness tests demonstrate that the microhardness at the midpoint from the halo edge to center decreased sharply from 9770.7 MPa at 5 pulses to 2664.14 MPa at 25 pulses. The relative wear resistance of a 15-pulse sample is effectively improved by a factor of 6.5, exhibiting optimal wear resistance.

A novel in-situ reaction system Al-Zr-O was developed. In-situ Al3Zr and Al 2 O 3 particulate reinforced A356 alloy matrix composites have been fabricated by direct melt reaction method. The results show that the maximum size of Al3Zr and Al 2 O 3 particulate synthesized in the system ZrOCl2-A356 is 1um and 3um respectively, and they are well distributed in the matrix. The investigation shows that Al3Zr crystal is in the shape of polyhedron and rectangle. There is a faceted growth phenomenon on Al3Zr crystal surface. It is firstly found that the Al3Zr crystal grows in the mechanism of twin. The twin plane is [Formula: see text], and the twinning direction is [Formula: see text]. The crystal morphology of in-situ[Formula: see text] particulate is rectangle or sphere. Furthermore. ( Al 3 Zr+Al 2 O 3) p / A356 composites have not only higher tensile strength at room temperature (376.2MPa) but also higher yield strength (319.4MPa) and higher tensile strength at elevated temperature (200°C) than that of A356 alloy.

Thinopyrum intermedium (2n = 6x = 42, JJJsJsSS) is potentially a useful source of resistance to wheat streak mosaic virus (WSMV) and its vector, the wheat curl mite (WCM). Five partial amphiploids, namely Zhong 1, Zhong 2, Zhong 3, Zhong 4, and Zhong 5, derived from Triticum aestivum × Thinopyrum intermedium crosses produced in China, were screened for WSMV and WCM resistance. Zhong 1 and Zhong 2 had high levels of resistance to WSMV and WCM. The other three partial amphiploids, Zhong 3, 4, and 5, were resistant to WSMV, but were susceptible to WCM. Genomic in situ hybridization (GISH) using a genomic DNA probe from Pseudoroegneria strigosa (SS, 2n = 14) demonstrated that two partial amphiploids, Zhong 1 and Zhong 2, have almost the identical 10 Th. intermedium chromosomes, including four Js, four J, and two S genome chromosomes. Both of them carry two pairs of J and a pair of Js genome chromosomes and two different translocations that were not observed in the other three Zhong lines. The partial amphiploids Zhong 3, 4, and 5 have another type of basic genomic composition, which is similar to a reconstituted alien genome consisting of four S and four Js genome chromosomes of Th. intermedium (Zhong 5 has two Js chromosomes plus two Js–W translocations) with six translocated chromosomes between S and Js or J genomes. All three lines carry a specific S–S–Js translocated chromosome, which might confer resistance to barley yellow dwarf virus (BYDV-PAV). The present study identified a specific Js2 chromosome present in all five of the Zhong lines, confirming that a Js chromosome carries WSMV resistance. Resistance to WCM may be linked with J or Js chromosomes. The discovery of high levels of resistance to both WSMV and WCM in Zhong 1 and Zhong 2 offers a useful source of resistance to both the virus and its vector for wheat breeding programs.Key words: GISH, genomic composition, J, Js and S genomes, Thinopyrum intermedium, partial amphiploid, WSMV, WCM resistance.

Tantalum pentoxide (Ta 2 O 5 ) thin film with an initial thickness of 10.5 nm was deposited onto p-type silicon substrate by chemical vapor deposition (CVD), and subsequently annealed in O 2 ambience at 500 to 800 °C for 30 min. It was found that with proper thermal treatment, we could reduce the leakage current down to 6.4×10 −8 A cm −2 at 3 V, although, the effective oxide thickness will also increase from 2.42 to 3.50 nm. Higher annealing temperatures will result in a rougher sample surface and higher leakage current due to Ta 2 O 5 crystallization. Before the crystallization of the Ta 2 O 5 film, the leakage current was dominated by the Poole–Frenkel emission mechanism. For the crystalline Ta 2 O 5 film, the conduction mechanism at low electric field was not obvious and could be affected by the formation of the grain boundary in the Ta 2 O 5 film.

The barrier properties of sputter-deposited tantalum carbide (TaC x ) and tungsten carbide (WC x ) for Cu metallization were investigated and compared. The incorporation of the C atom is shown to be effective in decorating local defects of the barrier layer and improving the thermal stability of the Cu/barrier/Si contact system. Owing to a higher melting point and better chemical inertness, with respect to Si substrate, the TaC x (600 A) film shows a better thermal stability (up to 650°C) than that of WC x (∼600°C) film based on material analyses, while the highest stable temperature as evaluated by the n + p-diode leakage measurement is found to be approximately 550°C for the TaC x and 500°C for the WC x barrier layer. The failure of the TaC x and WC x barriers is found to be mainly due to Cu diffusion through the localized defects of the barrier layers into the Si substrate. The interfacial reaction between the WC x layer and the Si substrate is found to play an additional role in the failure of the WC x film.

The activity of NF-κB/Rel transcription factors can inhibit the apoptosis induced by TNF, UV or cancer therapy drugs in a number of cell types, including human T lymphocytes. Furthermore, the NF-κB/Rel inducer, phorbol-12-myristate-13-acetate (PMA), has been reported to suppress the CD95-induced apoptosis of human T lymphocytes. To verify whether the survival-enhancing effect of PMA required NF-κB/Rel activity, we generated two Jurkat cell sublines (AL.7 and AL.8) transfected with a pCMV4-IκBα construct, and two (AL.3 and AL.5) with the void pCMV4 vector. Compared to wild type, AL.3 and AL.5 cells, the AL.7 and AL.8 sublines displayed markedly lower amounts of NF-κB/Rel nuclear complexes and a reduced expression of a κB-controlled CAT reporter gene after 1 and 4 h of incubation with PMA, respectively. All the five cell types displayed negligible levels of apoptosis when cultured with medium or PMA alone; when stimulated with the mAb CH-11, the AL.7 and AL.8 sublines displayed apoptotic responses only slightly ( 85% in wild type, AL.3 and AL.5 cells and by 4-fold higher than in control cells. We conclude that the inhibition of the CD95-induced apoptosis by PMA relies on both NF-κB/Rel-dependent and -independent mechanisms. The partial contribution of these nuclear factors to the suppression of apoptosis indicates that the NF-κB/Rel activity can influence the extent of the CD95-induced T cell death.

The dielectric constant and the leakage current density of (Ba, Sr)TiO/sub 3/ (BST) thin films deposited on various bottom electrode materials (Pt, Ir, IrO/sub 2//Ir, Ru, RuO/sub 2//Ru) before and after annealing in O/sub 2/ ambient were investigated. The improvement of crystallinity of BST films deposited on various bottom electrodes was observed after the postannealing process. The dielectric constant and leakage current of the films mere also strongly dependent on the postannealing conditions. BST thin film deposited on Ir bottom electrode at 500/spl deg/C, after 700/spl deg/C annealing in O/sub 2/ for 20 min, has the dielectric constant of 593, a loss tangent of 0.019 at 100 kHz, a leakage current density of 1.9/spl times/10/sup -8/ A/cm/sup 2/ at an electric field of 200 kV/cm with a delay time of 30 s, and a charge storage density of 53 fC//spl mu/m/sup 2/ at an applied field of 100 kV/cm. The BST films deposited on Ir with post-annealing can obtain better dielectric properties than on other bottom electrodes in our experiments. And Ru electrode is unstable because the interdiffusion of Ru and Ti occurs at the interface between the BST and Ru after postannealing. The ten year lifetime of time-dependent dielectric breakdown (TDDB) studies indicate that BST on Pt, Ir, IrO/sub 2//Ir, Ru, and RuO/sub 2//Ru have long lifetimes over ten gears on operation at the voltage bias of 2 V.

The dielectric constant and the leakage current of (Ba, Sr)TiO3 (BST) thin films deposited on Pt bottom electrodes before and after annealing in O2 and N2 ambients were investigated. The crystallinity was improved after post-deposition annealing. The refractive index, dielectric constant, and leakage current of the films were strongly dependent on the annealing conditions. The O2-annealed BST films have higher dielectric constant and lower leakage current than those annealed in N2 ambient.

The Mutatox test (the commercial name for a bioluminescent bacterial genotoxicity test), which has been proved to be a good alternative to the Ames test, was used in this study to test the genotoxicity of fatty acid derivatives and heated oils. This test allows either pure or complex compounds to be rapidly screened for genotoxicity. Five different column fractions isolated from autoxidized methyl linoleate or autoxidized methyl linolenate were not genotoxic with or without the activation by the S-9 (microsomal) fraction. Chlorinated fatty acids including chloroethyl caprate, laurate, palmitate, and linoleate were genotoxic in the presence of S-9 activation. When heated at 180 °C, after 32 h, soybean oil exhibited genotoxic activity with or without the S-9 activation. The addition of 1% cholesterol into the soybean oil increased the onset of the genotoxicity during heating. Keywords: Mutatox test; genotoxicity test; fatty acid hydroperoxides; chlorinated fatty acids

The ARGO-YBJ experiment is currently under construction at the Yangbajing Cosmic Ray Laboratory (4300 m a.s.l.).The detector consists of a central carpet, 74 × 78 m2, made of a single layer of Resistive Plate Counters (RPCs), and surrounded by a partially instrumented guard ring for a total instrumented area of about 6700 m2. The digital read-out, performed by means of pick-up electrodes 6.7 × 62 cm2 (strip), allows to measure the charged particle number of small size air showers. The technique of counting the number of fired strips on the ARGO carpet corresponds to operate in the 10÷500 TeV energy region where both direct and indirect measurements on the primary cosmic radiation have been performed. Many composition models have been proposed by different experiments. In this work we discuss the ability of the ARGO detector to discriminate among some models.

Thin films of (Ba,Sr)TiO3 on Pt/SiO2/Si substrates were deposited using rf magnetron sputtering at various substrate temperatures and O2/(Ar+O2) mixing ratios (OMR). The crystallinity of the films improved significantly as the OMR increased. The dielectric constant increased with increasing OMR and reached a maximum value at 50% OMR. The leakage current density decreased with increasing oxygen flow, but had a minimum value at 40% OMR. The results for the dielectric constant and the leakage current were interpreted in terms of polarization effect and loss theory. The film deposited at 450 °C and 50% OMR exhibited good surface morphology and had a dielectric constant of 375, a tangent loss of 0.074 at 100 kHz, a leakage current density of 7.35×10−9 A/cm2 at an electric field of 100 kV/cm with a delay time of 30 s, and a charge storage density of 49 fC/μm2 at an applied field of 150 kV/cm. The 10 yr lifetime of time-dependent dielectric breakdown studies indicate that a 50% OMR sample has a longer lifetime than the 0% OMR sample.

This work investigated the barrier properties of metalorganic chemical‐vapor‐deposited (CVD) tantalum nitride (TaN) and physical‐vapor‐deposited (PVD) TaN between Cu and Si. The CVD TaN film had a preferred orientation (200) with a grain size of around 60 nm, while the PVD TaN had a (111) preferred orientation with a grain size of around 20 nm, as determined by transmission electron microscopy (TEM) and x‐ray diffraction (XRD) analyses. Degradation study of the Cu/TaN/Si contact system was also performed by sheet resistance measurement, scanning electron microscopy (SEM), XRD, secondary ion mass spectroscopy (SIMS), and shallow junction diodes. These results indicated that the PVD TaN film can act as a better diffusion barrier than the CVD TaN film. The higher thermal stability of PVD TaN than CVD TaN can be accounted by their difference in microstructures. The failure mechanisms of both CVD TaN and PVD TaN films as diffusion barriers between Cu and Si were also discussed.

Low-resistivity tantalum nitride (TaN) films were deposited by low-pressure metal-organic chemical vapor deposition (MOCVD) using a new precursor tertbutylimidotrisdiethylamidotantalum. The surface morphology and the step coverage of TaN films were characterized by scanning electron microscopy. The film deposited at 450 °C had nearly 100% step coverage and the step coverage decreased to 25% for the films deposited at 650 °C. The carbon and oxygen concentrations are about 10 at.% in the CVD TaN films, as determined by Auger electron spectroscopy. From Rutherford backscattering spectroscopy and secondary ion mass spectroscopy analysis, TaN films were found to be effective diffusion barriers between aluminum and silicon up to 550 °C. The electrical measurements of diode-leakage current indicate that the Al/TaN Si structure remained stable up to 500 °C, after which Al started to diffuse through the TaN layer and resulted in a higher leakage current.

Wnts-related signaling pathways have been reported to play roles in the pathogenesis of stress-induced depression-like behaviors. However, there is relatively few direct evidence to indicate the effect of Wnt ligands on this process. Here, we investigated the role of Wnts in mediating chronic restraint stress (CRS)-induced depression-like behaviors. We found that CRS induced a significant decrease in the expression of Wnt2 and Wnt3 in the ventral hippocampus (VH) but not in the dorsal hippocampus. Knocking down Wnt2 or Wnt3 in the VH led to impaired Wnt/β-catenin signaling, neurogenesis deficits and depression-like behaviors. In contrast, overexpression of Wnt2 or Wnt3 reversed CRS-induced depression-like behaviors. Moreover, Wnt2 and Wnt3 activated cAMP response element-binding protein (CREB) and there was CREB-dependent positive feedback between Wnt2 and Wnt3. Finally, fluoxetine treatment increased Wnt2 and Wnt3 levels in the VH and knocking down Wnt2 or Wnt3 abolished the antidepressant effect of fluoxetine. Taken together, our study indicates essential roles for Wnt2 and Wnt3 in CRS-induced depression-like behaviors and antidepressant.

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of the adult T-cell leukemia, an aggressive and often fatal malignancy of activated human CD4 T cells. HTLV-I encodes an essential 40-kDa protein termed Tax that not only transactivates the long terminal repeat of this retrovirus but also induces an array of cellular genes. Tax-mediated transformation of T cells likely involves the deregulated expression of various cellular genes that normally regulate lymphocyte growth produced by altered activity of various endogenous host transcription factors. In particular, Tax is capable of modulating the expression or activity of various host transcription factors, including members of the NF-kappa B/Rel and CREB/ATF families, as well as the cellular factors HEB-1 and p67SRF. An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells. In this study, we demonstrate that HTLV-I Tax can physically associate with p100, the product of the Rel-related NF-kappa B2 gene, both in transfected cells and in HTLV-I-infected leukemic T-cell lines. Furthermore, the physical interaction of Tax with p100 leads to the inhibition of Tax-induced activation of the HTLV-I and human immunodeficiency virus type 1 long terminal repeats, reflecting p100-mediated cytoplasmic sequestration of the normally nuclearly expressed Tax protein. In contrast, a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100. Together, these results suggest that the cytoplasmic interplay of Tax and p100 may play an important role in the initiation and maintenance of HTLV-1 latency observed in adult T-cell leukemia.

The predominant inducible form of the NF-kappa B transcription factor is a heteromeric complex containing two Rel-related DNA-binding subunits, termed p65 and p50. Prior transfection studies have shown that when these p65 and p50 subunits are expressed independently as stable homodimers, p65 stimulates kappa B-directed transcription, whereas p50 functions as a kappa B-specific repressor. While authentic p50 homodimers (previously termed KBF1) have been detected in nuclear extracts from nontransfected cells, experimental evidence supporting the existence of p65 homodimers in vivo was lacking. We now provide direct biochemical evidence for the presence of an endogenous pool of inducible p65 homodimers in intact human T cells. As with the prototypical NF-kappa B p50-p65 heterodimer, this novel p65 homodimeric form of NF-kappa B is functionally sequestered in the cytoplasm but rapidly appears in the nuclear compartment following cellular stimulation. Site-directed mutagenesis studies indicate that the homodimerization function of p65 is dependent upon the presence of cysteine 216 and a conserved recognition motif for protein kinase A (RRPS; amino acids 273 to 276), both of which reside within a 91-amino-acid segment of the Rel homology domain that mediates self-association. In contrast, mutations at these two sites do not affect heterodimerization of p65 with p50 or its functional interaction with I kappa B alpha. These later findings indicate that neither homo- nor heterodimer formation is an absolute prerequisite for I kappa B alpha recognition of p65. Taken together with prior in vivo transcription studies, these results suggest that the biological activities of p65 and p50 homodimers are independently regulated, thereby providing an integrated and flexible control mechanism for the rapid activation and repression of NF-kappa B/Rel-directed gene expression.

The constitution of N 2 O oxide has been investigated by using Auger analyses, ellipsometry measurement, and Fourier transform infrared (FTIR) spectroscopy in this paper. We found a nitrogen-rich layer formed at the interface of SiO 2 /Si by Auger analyses. From the results of ellipsometry, we found the thinner the N 2 O oxide, the larger the refractive index. A two-layer model construction of N 2 O oxide was proposed for modeling the interfacial layer. We found that this layer thickness is 14 to 20 A when the refractive index was set to 1.77. FTIR analyses show that some of the Si-O bonds were replaced by Si-N bonds. This is the reason that N 2 O oxide has better electrical properties and a lower growth rate than those of the conventional dry O 2 oxide

The Mutatox® test (commercial name for the bioluminescent bacterial genotoxicity test) has been shown to be a good alternative to the Ames test. The test uses dark mutants of luminous bacteria (Vibrio fischeri) and determines the ability of various genotoxic agents to restore the luminescence by inducing mutation. It provides a rapid screening test which can be used to assay the genotoxicity of large numbers of pure and complex compounds. The test is completed in 1 day, and by serially diluting the compound, dose response data plus toxicity data can be generated for a number of samples simultaneously. For the direct assay (without exogenous metabolic activation), the positive controls selected were 3,6-diaminoacridine (proflavine) and N-methyl-N-nitro-nitrosoguanidine. For the S-9 assay, which incorporated the microsome fraction (S-9) from rat liver as an exogenous metabolic activation system, the positive controls selected were aflatoxin B1 and benzo(a)pyrene. This study also indicated that methyl-imidazo-quinoline and tryptophan pyrolysates were genotoxic in the presence of S-9 activation, aflatoxin B1 epoxide and fumonisin B1 showed direct genotoxic activity, and aflatoxin B2 and ochratoxin A were not genotoxic.

In this paper we first report an exothermic phenomenon of silicon oxidation by N 2 O. This phenomenon results from the decomposition of N 2 O at high temperature. The heat generated by introducing N 2 O increases the furnace temperature during the oxidation process and results in an increased oxide thickness. To control temperature well, we developed a two-table profiling technique to obtain a more stable processing temperature. We also found the growth kinetic of N 2 O decomposed into N 2 and O 2 is similar to dilute O 2 (10%)/Ar

This study proposed and tested a refined customer satisfaction index (CSI) for the mobile phone service industry in China. Data were collected from 1,440 randomly selected mobile phone subscribers through telephone interviewers using customer lists of the two primary mobile phone service companies. Results showed the validity of adding the perceived equity construct to the CSI model. Corporate image was found to have a direct positive impact on customer loyalty; and customer satisfaction was influenced by corporate image, perceived value, and perceived equity. This study contributed to the continued refinement of CSI and derived practical implications for mobile phone service providers.

The relationship of inhibitory quotient (IQ) with the virologic response to specific inhibitors of human hepatitis C virus (HCV) and the best method to correct for serum protein binding in calculating IQ have not been addressed. A common method is to determine a fold shift by comparing the EC(50) values determined in cell culture in the absence and presence of human serum (fold shift in EC(50) ), but this method has a number of disadvantages. In the present study, the fold shifts in drug concentrations between 100% human plasma (HP) and cell culture medium (CCM) were directly measured using a modified comparative equilibrium dialysis (CED) assay for three HCV protease inhibitors (PIs) and for a novel HCV inhibitor GS-9132. The fold shift values in drug concentration between the HP and CCM (CED ratio) were ∼1 for SCH-503034, VX-950 and GS-9132 and 13 for BILN-2061. These values were ∼3-10-fold lower than the fold shift values calculated from the EC(50) assay for all inhibitors except BILN-2061. Using the CED values, a consistent pharmacokinetic and pharmacodynamic relationship was observed for the four HCV inhibitors analysed. Specifically, an approximate 1 log(10) reduction in HCV RNA was achieved with an IQ close to 1, while 2-3 and greater log(10) reductions in HCV RNA were achieved with IQ values of 3-5 and greater, respectively. Thus, use of CED to define IQ provides a predictive and quantitative approach for the assessment of the in vivo potency of HCV PIs and GS-9132. This method provides a framework for the evaluation of other classes of drugs that are bound by serum proteins but require the presence of serum for in vitro evaluation.

Both the Ogden-Tschoegl nonlinear elastic constitutive law and a contact algorithm in the general-purpose finite-element program AFEM have been used to examine the use of IRHD values to relate the elastic properties of elastomers. We are aware that large deformations of rubber specimens and complicated interface conditions are involved in this so-called simple test. However, from the finite-element results, we find that the linearly elastic Hertz contact solution is a reasonably accurate model. This can be attributed to several points. First, the hardness test involves mainly compression and shear deformation and the linearly elastic behavior is more closely followed in rubbers for the above two types of deformation. Second, although nonlinear effects become significant in soft rubbers and higher indentation cases, the ASTM D 1415 standard defines larger indentation depth differences for smaller IRHD values. The definition itself compensates for the nonlinear effects. Third, although the interfacial stress field changed due to different frictional conditions, we calculated the IRHD values only from indentation depth difference and total load applied to the steel ball. Both the indentation depth difference and the total load are obtained from far-field conditions and do not change significantly. We should note that using linear elasticity to correlate the elastic moduli and IRHD values is simply a special case in rubber elasticity. We conveniently get rubber's elastic moduli from IRHD values based on linear elasticity, but the complete rubber-like material behavior has to be obtained from more general experiments and described by a nonlinear constitutive law such as the Ogden-Tschoegl model.

Racemic (R,S) AM1241 is a cannabinoid receptor 2 (CB(2))-selective aminoalkylindole with antinociceptive efficacy in animal pain models. The purpose of our studies was to provide a characterization of R,S-AM1241 and its resolved enantiomers in vitro and in vivo.Competition binding assays were performed using membranes from cell lines expressing recombinant human, rat, and mouse CB(2) receptors. Inhibition of cAMP was assayed using intact CB(2)-expressing cells. A mouse model of visceral pain (para-phenylquinone, PPQ) and a rat model of acute inflammatory pain (carrageenan) were employed to characterize the compounds in vivo.In cAMP inhibition assays, R,S-AM1241 was found to be an agonist at human CB(2), but an inverse agonist at rat and mouse CB(2) receptors. R-AM1241 bound with more than 40-fold higher affinity than S-AM1241, to all three CB(2) receptors and displayed a functional profile similar to that of the racemate. In contrast, S-AM1241 was an agonist at all three CB(2) receptors. In pain models, S-AM1241 was more efficacious than either R-AM1241 or the racemate. Antagonist blockade demonstrated that the in vivo effects of S-AM1241 were mediated by CB(2) receptors.These findings constitute the first in vitro functional assessment of R,S-AM1241 at rodent CB(2) receptors and the first characterization of the AM1241 enantiomers in recombinant cell systems and in vivo. The greater antinociceptive efficacy of S-AM1241, the functional CB(2) agonist enantiomer of AM1241, is consistent with previous observations that CB(2) agonists are effective in relief of pain.

In this study, the physical and electrical properties of tungsten nitride thin films deposited by thermal decomposition of bis(tertbutylimido)bis(tertbutylamido)tungsten have been investigated. The films have an excellent step coverage over high aspect‐ratio contact holes as well as a low carbon concentration. Strong W–N double bonds in the precursor preserved the nitrogen atoms during the pyrolysis process. This method subsequently yielded low‐resistivity films. A decrease in film resistivity from 4300 to 620 μΩ cm corresponded to an increase in the deposition temperature from 500 to 650 °C. X‐ray diffraction (XRD) and wavelength dispersive spectroscopy (WDS) results indicated that the as‐deposited films have face centered cubic (fcc) phase polycrystalline structures with excessive nitrogen atoms.

This work reports on the effect of postdeposition thermal treatment using rapid thermal annealing on the physical and electrical properties of metalorganic chemical‐vapor‐deposited (MOCVD) titanium nitride (TiN) thin films. When ammonia is used as the annealing ambient, the resistivity decreases with increasing annealing temperature. The resistivity of MOCVD TiN was reduced from 6000 to 320 μΩ cm after 800 °C rapid thermal annealing in ammonia (RTN). Annealing in nitrogen ambient was found to be not nearly as effective as that in ammonia. The decrease in resistivity may be attributed to a reduction in the carbon and oxygen content, growth in grain size through polycrystalline recrystallization, as well as to an increase in film density.

We deposited tantalum nitride (TaN) films by low‐pressure metalorganic chemical vapor deposition (LP‐MOCVD) using a new precursor tertbutylimidotris(diethylamido)tantalum (TBTDET). Strong Ta–N double bond in the precursor preserved the ‘‘TaN’’ portion during the pyrolysis process. This method has yielded low‐resistivity films. It changed from 10 mΩ cm (deposited at 500 °C) to 920 μΩ cm (obtained at 650 °C). The carbon and oxygen concentrations were low in the films deposited at 600 °C, as determined by x‐ray photoelectron spectroscopy. Transmission electron microscopy and x‐ray diffraction analysis indicated that the as‐deposited films exhibited polycrystalline structures with the lattice constants close to the bulk TaN value. The TaN barrier layer was successfully applied as a glue layer for CVD tungsten (W) metallization schemes.

This paper reports the investigation of a newly developed WNx film by metalorganic chemical vapor deposition (MOCVD). The WNx material provided an excellent diffusion barrier for Cu metallization.

In this paper, the barrier properties of metalorganic CVD TiN and CVD TaN between Cu and Si under similar process conditions are compared. Thermal stability was investigated by microstructural analysis and junction diode leakage current. Results indicate that CVD TiN and CVD TaN films have comparable thermal stability. A post-deposition treatment using rapid thermal annealing in ammonia at temperatures greater than 600/spl deg/C was found to improve the thermal stability and to lower the film resistivity.