[Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype 1b infection and compensated cirrhosis].

Objective: To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. Methods: An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. Results: A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. Conclusion: Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

Isolation and molecular analysis of genes Stpk-V2 and Stpk-V3 homologous to powdery mildew resistance gene Stpk-V in a Dasypyrum villosum accession and its derivatives.

Wheat-Dasypyrum villosum translocated chromosomes T6V#2S•6AL and T6V#4S•6DL are known to confer excellent resistance to wheat powdery mildew (PM). However, it is difficult to distinguish the two sources of PM resistance genes through multi-pathotype testing because to date no virulence for them has been found. To reveal the relationship between the PM resistance genes from the two translocations, the sequence of the Stpk-V gene, a key member of powdery mildew resistance locus Pm21, was used as a reference to isolate homologous genes from a D. villosum accession No.1026 and its derivatives 6V#4(6D) disomic substitution (DS) line RW15 and T6V#4S•6DL translocation line Pm97033. Two genes Stpk-V2 and Stpk-V3 were cloned from No.1026. Sequence alignment showed that Stpk-V2 and Stpk-V3 shared 98.2 % and 96.2 % of their DNA and 99.3 % and 100 % of their amino acids in identity with Stpk-V. Compared with Stpk-V, a 22-bp direct sequence repeat and a miniature inverted-repeat transposable element (MITE) were found in the intron 4 of Stpk-V2 and Stpk-V3, respectively. However, Stpk-V2 was not present in DS line RW15 and translocation line Pm97033 based on the PCR result, indicating that Stpk-V2 did not contribute to the PM resistance of RW15 and Pm97033. In the promoter region, a 78-bp insertion was found not only in Stpk-V2 and Stpk-V3, but also in its orthologous gene Stpk-A of wheat. In addition, there was a 17 bp/8 bp deletion/insertion in the putative promoter of Stpk-V3 in comparison with that of Stpk-V/Stpk-V2. Real-time quantitative RT-PCR analysis indicated that the expression levels of Stpk-V and Stpk-V3 genes in the translocation lines were induced by the pathogen, but Stpk-V had a higher expression level than Stpk-V3 at 12 h after inoculation with Bgt. The diversity of Stpk-V gene will help to explore new resistance genes to PM in D. villosum for wheat breeding.

Expressed sequence tag-PCR markers for identification of alien barley chromosome 2H in wheat.

We developed EST-PCR markers specific to barley chromosome 2H, for the purpose of effectively tracing alien chromosomes or chromosome parts in the wheat genetic background. The target alien chromosome 2H confers high resistance to pre-harvest sprouting, which is a worldwide natural disaster in wheat. A total of 120 primer pairs were selected by combining the wheat group 2 chromosomes of the EST database and the genome sequences of the new model plant Brachypodium distachyon. Seventy-seven of 120 primer pairs were polymorphic and 31 of 120 primer pairs were monomorphic between a set of wheat-barley chromosome 2H disomic addition/substitution lines and their parents by agarose gel electrophoresis and polyacrylamide gel electrophoresis. Thirty of 77 polymorphic primer pairs including primer pair P120 derived from the basi gene were chromosome 2H-specific. These markers are expected to be valuable in screening of wheat-barley chromosome 2H recombination lines and pre-harvest sprouting resistant varieties.

The electronic structure of RbTiOPO4 and the effects of the A-site cation substitution in KTiOPO4-family crystals.

The electronic structure of RbTiOPO(4) has been investigated with x-ray photoemission spectroscopy. Detailed photoemission spectra of the element core levels have been recorded under excitation by nonmonochromatic Al Kα radiation (1486.6 eV). The chemical bonding parameters are compared to those reported for complex titanates and phosphates. The band structures of KTiOPO(4), RbTiOPO(4), K(0.535)R(0.465)TiOPO(4) and TlTiOPO(4) have been calculated by ab initio methods and compared to available experimental results. It is found that the band structure of KTP-type phosphate crystals is weakly dependent on the nature of the A-site (A=K, Rb, Tl) element.

Ab initio studies on the optical effects in the deep ultraviolet nonlinear optical crystals of the KBe2BO3F2 family.

Electronic structures of the deep ultraviolet nonlinear optical crystals of the KBe(2)BO(3)F(2) (KBBF) family, including KBBF, RbBe(2)BO(3)F(2) and CsBe(2)BO(3)F(2), have been investigated based on a plane-wave pseudopotential method. Their linear and nonlinear optical coefficients are also calculated, and are in good agreement with the experimental results. A real-space atom-cutting method is adopted to analyze the respective contributions of the alkali metal cations and anionic groups to optical response. The results show that the contributions of anionic groups to the nonlinear optical anisotropic responses are dominant, but the influence of the A-site alkali metal cations becomes slightly more pronounced with the increase of their radius. Moreover, the birefringence difference among these crystals strongly depends on the volume effect, i.e., the spatial density of the (BO(3))(3-) anionic groups.

Energy band gap engineering in borate ultraviolet nonlinear optical crystals: ab initio studies.

The development of ultraviolet (UV) nonlinear optical (NLO) crystals demands optical materials with wide energy band gaps. Here we report first-principles studies on the electronic structures in several UV NLO borates with representative structures. Combined with model analysis, we find that the oxygen non-bonding 2p orbitals play an important role on the top of valence bands. The energy band gap can be adjusted by modifying the coordination environment around the oxygen atoms. Under ideal conditions the energy band gaps achieve 9 eV if the non-bonding orbitals are totally eliminated, despite the original values varying from 6.6 to 8.3 eV.

Development of EST-PCR markers for Thinopyrum intermedium chromosome 2Ai#2 and their application in characterization of novel wheat-grass recombinants.

A series of expressed sequence tags-derived polymerase chain reaction (EST-PCR) markers specific to chromosome 2Ai#2 from Thinopyrum intermedium were developed in this study using a new integrative approach. The target alien chromosome confers high resistance to barley yellow dwarf virus (BYDV), which is a severe virus disease in wheat. To generate markers evenly distributed on 2Ai#2, a total of 105 primer pairs were designed based on mapped ESTs from 8 bins of wheat chromosome 2B with intron-prediction by aligning ESTs with genomic sequences of the new model plant Brachypodium distachyon. Eight and seven polymorphic markers on the short arm and the long arm of chromosome 2Ai#2, respectively, were obtained with a polymorphism rate of 14.3%. These chromosome 2Ai#2-specific EST-PCR markers were then used in tracing and exploring the structural variation of the alien chromosome in the population derived from the immature embryo culture of the cross between N452, a 2Ai#2(2D) substitution line, and common wheat CB037. Two centric fusion of translocations involving 2Ai#2 short or long arm with wheat chromosome 2D and some new genetic stocks including telosomes with the alien chromosome short or long arm were identified in the SC(3) generations, which provided basic materials to further study the mechanism of the BYDV resistance. BYDV tests in two field seasons suggest that the BYDV resistance was mainly conferred by the short arm, gene interaction on both arms of the alien chromosome was discussed.

Habitat destruction and the extinction debt revisited: the Allee effect.

Habitat destruction, often caused by anthropogenic disturbance, can lead to the extinction of species at an unprecedented rate. It is important, therefore, to consider habitat destruction when assessing population viability. Another factor often ignored in population viability analysis, is the Allee effect that adds to the risk of populations already on the verge of extinction. Understanding the Allee effect on species dynamics and response to habitat destruction has intrinsic value in conservation prioritization. Here, the Allee effect was considered in a multi-species hierarchical competition model. Results showed that species persistence declines dramatically due to the Allee effect, and certain species become more susceptible to habitat destruction than others. Two extinction orders emerged under habitat destruction: either the best competitor becomes extinct first or the best colonizer first. The extinction debt and order, as well as the time lag between habitat destruction and species extinction, were found to be determined by species abundance and the intensity of the Allee effect.

Optical properties of LiGaS(2): an ab initio study and spectroscopic ellipsometry measurement.

Electronic and optical properties of lithium thiogallate crystal, LiGaS(2), have been investigated by both experimental and theoretical methods. The plane-wave pseudopotential method based on DFT theory has been used for band structure calculations. The electronic parameters of Ga 3d orbitals have been corrected by the DFT+U methods to be consistent with those measured with x-ray photoemission spectroscopy. Evolution of optical constants of LiGaS(2) over a wide spectral range was determined by developed first-principles theory and dispersion curves were compared with optical parameters defined by spectroscopic ellipsometry in the photon energy range 1.2-5.0 eV. Good agreement has been achieved between theoretical and experimental results.

Patchy environment as a factor of complex plankton dynamics.

We study the role of the diffusive interaction in plankton dynamics in a patchy environment. We use a minimal reaction-diffusion model of the nutrient-plankton-fish food chain to simulate the diffusive interaction between fish-populated and fish-free habitats. We show that such interaction can give rise to spatiotemporal plankton patterns. The plankton dynamics depend on the fish predation rate and can exhibit both regular and chaotic behavior. We show that limit cycle and chaotic attractor coexist in the system. The entire basin of attraction of the limit cycles is found to be riddled with "holes" leading to the competitive chaotic attractors. The chaotic dynamics is typical of a wide range of the fish predation rates.

[Molecular cytogenetic characterization of a new wheat line YW443 with resistance to barley yellow dwarf virus].

A new wheat line YW443 with BYDV resistance and good traits was developed from the combination of PP9-1/Shan7859¿Fengkang 8. The wheat line YW443 was identified by BYDV resistance analysis, genomic in situ hybridization (GISH), RFLP and RAPD analysis. The results indicated as follows: (1) YW443 was resistant to GPV and GAV strains of BYDV; (2) YW443 is a homozygous wheat-Thinopyrum intermedium translocation line with a pair of BYDV resistance genes; (3) The 7StL segment of Th. intermedium carring BYDV resistance gene was transferred onto the distal end of the wheat chromosome 7D long arm, the line YW443 was 7DS.7DL-7StL translocation; (4) A RAPD marker OPR19(-900) could detect the DNA of Th. intermedium 7StL in L1 and L1 derivatives including translocation lines YW443, YW642 etc. The markers may be used as a selecting marker for the BYDV resistance breeding program.

[Identification of the barley chromosome in wheat by GISH and RFLP].

The barley chromosome in wheat was identified by genomic in situ hybridization (GISH) in which biotin labelled total genomic DNA of barley Betzes was used as probe and the unlabelled total DNA of common wheat Chinese Spring (CS) as blocking DNA. A series of wheat materials were tested as follows: two disomic alien substitution and monosomic alien addition lines, 2n = 43; two monosomic alien substitution lines, 2n = 42; seven disomic alien substitution lines, 2n = 42. RFLP probe psr131 on the short arm of the homologous group 2 was used to analyze the barley chromosome in wheat. The result indicated that there was a same band in barley Betzes and substitution line A5. The chromosome 2A of A5 was substituted by the chromosome 2H of barley. These materials will be useful in transferring the valuable genes in the chromosome 2H to wheat.

[Surgical treatment for the recurrent patients after palatopharyngoplasty].

OBJECTIVE: To study the surgical treatment for the recurrent patients after palatopharyngoplasty (PPP). METHOD: Five patients which were confirmed recurrence by sleep survey and examinations were reported. RESULT: The pharyngeal cavity was narrower obviously ten months after ppp than before ppp. The anteroposterior and transverse distances were (4.06 +/- 2.94) mm and (11.40 +/- 4.16) mm respectively. After dilatation, the distances were (11.90 +/- 3.25) mm and (21.00 +/- 4.18) mm separately, and were increased significantly than before (P < 0.01). Two patients were cured and three cases marked, and all patients were not recurrent post-operation with no complications. CONCLUSION: The recurrence was mainly concerned with the unsuitable manipulation in PPP. Selecting the cooperation and proper surgical treatment, the better effect was also obtained for the recurrent patients.

A new fourier transform approach for protein coding measure based on the format of the Z curve.

MOTIVATION: At the core of most protein gene-finding algorithms are the coding measures used to make a decision on coding/non-coding. Of the protein coding measures, the Fourier measure is one of the most important. However, due to the limited length of the windows usually used, the accuracy of the measure is not satisfactory. This paper is devoted to improving the accuracy by lengthening the sequence to amplify the periodicity of 3 in the coding regions. RESULTS: A new algorithm is presented called the lengthen-shuffle Fourier transform algorithm. For the same window length, the percentage accuracy of the new algorithm is 6-7% higher than that of the ordinary Fourier transform algorithm. The resulting percentage accuracy (average of specificity and sensitivity) of the new measure is 84.9% for the window length 162 bp. AVAILABILITY: The program is available on request fromC.-T. Zhang. CONTACT: ctzhang@tju.edu.cn

A novel approach to distinguish between intron-containing and intronless genes based on the format of Z curves.

A novel method to distinguish between intron-containing and intronless DNA sequences has been proposed, based on different statistic behaviors between them. In this method, DNA sequences are first represented as Z curves. Three exponents alpha, beta and gamma for each given sequence are calculated based on the format of the Z curve for the DNA sequence. A three-dimensional space is spanned by the three exponents. Each DNA sequence may be represented by a point in this space. One hundred intronless and intron-containing genes, respectively, were selected randomly from the GenBank or EMBL database. It is shown that the 200 points are roughly distributed in different regions. The best separating plane to separate the two regions is obtained by using Fisher's discriminant algorithm. For any given sequence to be discriminated, calculate three exponents alpha, beta and gamma, corresponding to a point in the three-dimensional space. If the point is situated at the upper region of the separating plane, the sequence is discriminated as an intronless one; otherwise, the sequence is an intron-containing one. A test of the method for the sequences in an independent test set shows that the discriminant accuracy reaches as high as 89.0%.

Prediction of the helix/strand content of globular proteins based on their primary sequences.

An improved multiple linear regression method has been proposed to predict the content of alpha-helix and beta-strand of a globular protein based on its primary sequence. The amino acid composition and the auto-correlation functions based on the hydrophobicity profile of the primary sequence have been taken into account in the algorithm. The resubstitution test shows that the average absolute errors are 0.077 and 0.073 with the standard deviations 0.059 and 0.057 for the prediction of the content of alpha-helix and beta-strand, respectively. A stringent cross-validation test, i.e., the jackknife test, shows that the average absolute errors are 0.087 and 0.081 with the standard deviations 0.067 and 0.065 for the prediction of the content of alpha-helix and beta-strand, respectively. Both tests indicate the self-consistency and the extrapolating effectiveness of the new algorithm. This greatly improves on previous results (Eisenhaber,F., Imperiale,F., Argos,P. and Frommel,C., 1996, Proteins, 25, 157-168). Compared with other methods currently available, our method has the merits of simplicity and ease-of-use as well as a higher prediction accuracy. The only input of the method is the primary sequence of the query protein to be predicted. The program is available on request via e-mail: ctzhang@tju.edu.cn.

Dopaminergic control of light-adaptive synaptic plasticity and role in goldfish visual behavior.

Dopamine has been implicated in processes of retinal light and dark adaptation. In goldfish retina, horizontal cell dendrites elaborate neurite processes (spinules) into cone terminals, in a light- and dopamine-dependent manner. However, the functions of retinal dopamine and the horizontal cell spinules in visual behavior are unknown. These issues were addressed in behavioral, electroretinographic, and anatomical studies of normal fish and those with unilateral depletion of retinal dopamine induced by intraocular (i.o.) injections with 6-hydroxydopamine (6-OHDA). Dopamine interplexiform cells (DA-IPC) disappear within 2 weeks after 6-OHDA injection; cell bodies appear at the marginal zone within 6 weeks at which time neurites slowly reinnervate the retina with a sparse plexus over the next 12 months. We found that dopamine depletion increased light sensitivity at photopic but not scotopic backgrounds by 2.5 log units, an effect mimicked by i.o. injections of dopamine D1 and D2 antagonists. The ERG b-wave increment thresholds were the same for control and dopamine depleted eyes, indicating a normal transition from rod to cone systems in the ON pathway. Light-dependent spinule formation was reduced by about 60% in dopamine-depleted retinas, but returned to normal by 3 months and 9 months after injection in the entire retina, even areas not directly innervated with DA-IPC processes. Spinule formation in vivo was inhibited 50% with i.o. injection of SCH 23390 in control retinas as well as throughout 3 month 6-OHDA injected retinas, including DA-IPC free areas. This latter result indicates a volume effect of dopamine, diffusing laterally through the retina over several millimeters, in regulating spinules. We conclude that DA-IPCs regulate sensitivity to background at photopic levels not via the ON pathway, but perhaps the OFF pathway. Goldfish display both increased sensitivity to light and a normal Purkinje shift in the ERG b-wave whether or not horizontal cell spinules are present, indicating that dopamine control of photopic vision in fish is not mediated through light-induced spinule formation of horizontal cell dendrites.

Outcome of severe brain injury: a multimodality neurophysiologic study.

We screened all head-injured trauma patients admitted to Lehigh Valley Hospital during a 2-year period. From 725 screened patients, 69 patients in a coma on the second day after trauma were entered into this study. During the first week, these patients underwent electroencephalography (EEG), evoked potentials, ocular pneumoplethysmography, and transcranial Doppler (TCD) sonography. Clinical examinations were undertaken 2 and 7 days after trauma. Test results were correlated with functional clinical outcome at 6 months. In a multiple regression analysis, EEG was the major independent variable that significantly predicted 6-month outcome based on Glasgow Outcome Scale score. Transcranial Doppler sonography contributed a small additional component. Though EEG was the most significant predictive factor in this neurophysiological battery, it did not add significantly to the predictive power of Glasgow Coma Scale score determined at day 7. These findings suggest that in neurophysiologic testing in this type of patient is not useful in improving predictive outcome data.

Differential effects of dopamine depletion on the distribution of [3H]SCH 23390 and [3H]spiperone binding sites in the goldfish retina.

The distributions of dopamine D1 and D2 receptors were studied in intact goldfish retina with in vitro autoradiography. Specific [3H]SCH 23390 binding (D1 receptors) was greatest over the outer plexiform layer (OPL)/horizontal cell bodies and less so over the inner nuclear and inner plexiform layers (IPL). Specific [3H]spiperone binding (D2 receptors) appeared in two bands, over the OPL/horizontal cell bodies and the IPL. Depletion of retinal dopamine, by intraocular injections of 6-hydroxydopamine, had no effect on the pattern and density of [3H]SCH 23390 binding; however, specific [3H]spiperone binding over the OPL and IPL was virtually eliminated, suggestive of D2 autoreceptors on dopamine interplexiform cells. These data are consistent with electrophysiological studies indicating the presence of D1 and D2 receptors in both plexiform layers of the goldfish retina.