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The Ordovician rocks on the Qinghai-Tibetan Plateau represent the oldest non-metamorphic strata, and are critical to understanding the history of regional geology and biotic evolution of the entire plateau. Strata of Floian, Darriwilian, Sandbian, Katian and Hirnantian are represented in the plateau with a hiatus of variable duration occurring underneath the basal Ordovician across the area. Five stratigraphical regions, including the Himalaya, Gangdise-Zayu, Qiangtang-Qamdo, Songpan-Garze, and Karakoram-Kunlun-Altun, are differentiated for the Ordovician strata, which are correlated with their equivalents in the Sibumasu, Indochina, Qaidam-Qilian, Tarim-Tianshan, and the Yangtze (western margin) stratigraphical regions. On the Qinghai-Tibetan Plateau, graptolites, conodonts, and cephalopods are the most common and useful fossils for the Ordovician biostratigraphy. The Ordovician biotas of the Qinghai-Tibetan Plateau bear some distinguishable palaeobiogeographical signatures, among which the cephalopods are characterized by the flourishing actinocerids of North China affinity in the Early-Middle Ordovician, and by the thriving lituitids and orthocerids of South China affinity in the Middle-Late Ordovician. Fossil occurrences and their palaeobiogeographical evolution provide critical evidence bearing on the reconstruction of the geological history of the Qinghai-Tibetan Plateau and surrounding terranes in northeastern peri-Gondwana. The stratigraphical successions of the Cambrian-Ordovician transition in the Himalaya and Lhasa and nearby Sibumasu terranes were significantly affected by the Kurgiakh Orogeny, which resulted in the extensive unconformity between the Ordovician and the underlying rocks in most areas of the Qinghai-Tibetan Plateau. In southern Xizang, a warm-water biota of Middle Ordovician age was recovered from oolitic limestones, suggesting a likely palaeogeographical location in low-latitudes near the equator. In the Himalaya and Sibumasu regions, the Upper Ordovician was typified by the occurrence of red carbonates with distinctive reticulate structures, which are correlative to their equivalents in the Yangtze region of South China, and might be deposited under similar geological conditions. The global end-Ordovician glaciation and sea-level drop likely caused the wide absence of late Katian strata in western Yunnan of China and the Shan State of Myanma, and may have also affected deposition in the Xainza and Nyalam areas of the Qinghai-Tibetan Plateau during this time interval. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical value of the expression levels of tumor protein D52 (TPD52) and miR-133a on the prognosis assessment of pancreatic cancer surgery. Methods: This was a retrospective study. Ninety-seven patients who underwent radical surgery for pancreatic cancer in Cangzhou Central Hospital from January 2018 to January 2022 were selected and divided into four groups: TPD52 high expression group, TPD52 low expression group, miR-133a high expression group and miR-133a low expression group. The relationship between the expression levels of TPD52 and miR-133a and the clinicopathological features of patients with pancreatic cancer was analyzed. The COX regression model was used to analyze the risk factors affecting the prognosis of patients with pancreatic cancer. Results: The high expression rate of TPD52 and the low expression rate of miR-133a in pancreatic cancer tissues were higher than those in normal paracancerous tissues(P<0.05). Based on the comparison of prognosis and survival, the median survival time of patients with high expression of TPD52 and low expression of miR-133a was lower than that of patients with low expression of TPD52 and high expression of miR-133a, with a statistically significant difference(P<0.05). Moreover, multivariate Cox regression analysis showed that low differentiation of pancreatic cancer, III-IV stage of TNM, high expression of TPD52, as well as low expression of miR-133a were independent risk factors for postoperative survival of patients with pancreatic cancer(P<0.05). Conclusion: TPD52 is expressed at a high level whereas miR-133a at a low level in pancreatic cancer tissues, both of which together with low differentiation of pancreatic cancer and III-IV stage of TNM constitute independent risk factors affecting the surgical prognosis of patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the efficacy and safety of the full-endoscopic lumbar discectomy (FELD) via lateral superior articular process (LSAP) approach and full-endoscopic transforaminal discectomy (FETD) for treating far lateral lumbar disk herniation (FFLDH). Methods: From January 2020 to June 2022, patients who were diagnosed as FLLDH underwent the FELD via LSAP approach or FETD. The operation time, estimated blood loss, length of hospital stays, and complications were recorded. The visual analog scale (VAS) for back pain, VAS for leg pain, and the Oswestry Disability Index (ODI) scores was measured during preoperative and postoperative follow-up. Results: Thirty-two patients were enrolled in this study, of which 12 patients were treated with the FELD via LSAP approach (LSAP-FELD group) and 20 patients underwent FETD (FETD group). The LSAP-FELD group exhibited significantly shorter operation times and hospital stays compared to the FETD group, while no statistically significant differences were observed in intraoperative blood loss and complication rates. There were no significant differences in the VAS for back pain, the VAS for leg pain, and the ODI score between the two groups preoperatively and three days, three months, and the last follow-up postoperatively. Conclusions: Both the FELD via LSAP approach and FETD have demonstrated favourable clinical efficacy in the treatment of FLLDH. Notably, the FELD via LSAP approach shows the advantages of shorter operation time and hospital stays. [ABSTRACT FROM AUTHOR]

Recovering germanium from zinc oxide dust (ZOD) produced from Pb–Zn smelter is an important pathway to extract germanium. However, the leaching efficiency of industrial germanium production is not satisfactory (usually less than 75 %). Therefore, the leaching behavior of Ge in different phases was discovered in this work. Ge in the ZOD mainly occurs in oxide, sulfide, silicate, and solid insoluble. The potential decides the oxidative dissolution of sulfide. The leaching recovery of zinc and germanium were 90 % and 80 % with oxidant, and 78 % and 80 % without oxidant, respectively. The effect sequence of oxidant type on the Zn leaching efficiency was MnO2 > H2O2 ≈ oxygen > air, but the type and addition of oxidant had no obvious effect on the leaching recovery of germanium. The final pH of leaching slurry limits the dissolution of oxide and hydrolysis-polymerization of impurity ions (such as Fe(III) and Si). Decreasing the final pH is beneficial to the leaching reaction of Zn and Ge. The germanium presented in oxide and sulfide is easy to leach, while the leaching of germanium existed in silicate and solid insoluble is relatively difficult. The structure of aluminate can be destroyed effectively using a 40 g/L HF solution. When the leaching percent of SiO2 is 86.82 %, the leaching recovery of Ge is 96.57 %. For the ZOD with higher content of Fe and Si, germanium leaching is negatively correlated with the content of Fe and Si in the ZOD. The results provide a scientific basis for improving the leaching recovery of germanium. [ABSTRACT FROM AUTHOR]

Using pre-synthesized high-entropy (Ta 0.2 W 0.2 Nb 0.2 Mo 0.2 V 0.2)C carbide as the reinforcing phase, Ti(C 0.7 N 0.3)-based cermets were prepared by pressureless sintering at 1600 °C. The results revealed that due to the solid solution reaction between the mono-carbide and (Ta 0.2 W 0.2 Nb 0.2 Mo 0.2 V 0.2)C, only one set of face-centered-cubic diffraction peaks in XRD was detected in the as-sintered cermets, alongside the typical core-rim structure. Compared to the Ti(C 0.7 N 0.3)-based cermets without high-entropy reinforcing phase, the Vickers hardness was increased from 17.06 ± 0.09 GPa to 18.42 ± 0.33 GPa and the fracture toughness was increased from 9.21 ± 0.31 MPa m1/2 to 12.56 ± 0.23 MPa m1/2 by adding 10 wt% (Ta 0.2 W 0.2 Nb 0.2 Mo 0.2 V 0.2)C. The wear resistance of the cermet was enhanced significantly with increasing (Ta 0.2 W 0.2 Nb 0.2 Mo 0.2 V 0.2)C content. This work provided a potential that the high-entropy carbide can be applied as an effective reinforcing phase in the preparation of high-performance Ti(C 0.7 N 0.3)-based cermets. [ABSTRACT FROM AUTHOR]

Purpose : Current findings suggest that minimally percutaneous endoscopic lumbar discectomy (PELD) is a practical therapeutic approach for lumbar disc herniation (LDH). However, some patients still end up with residual low back pain, even after surgery. Our study aims to construct and validate a nomogram to predict residual low back pain after PELD. Methods: The medical records of 355 LDH patients admitted to the author's hospital were retrospectively analyzed between January 2019 and December 2021. The patients were randomly divided into two groups with a ratio of 7:3, namely a modelling group and a validation group. The univariable logistics and multivariable regression methods were used to screen the independent risk factors. A nomogram was then drawn using independent risk factors selected from the univariable and multivariable regression analyses. The concordance index (C-index), the receiver operating characteristic (ROC) curve, the calibration curve, and the decision curve analysis were used to evaluate the nomogram's performance. Finally, the accuracy of the nomogram was verified by a validation cohort. Results: 36.6% (130/355) of patients showed low back pain after percutaneous endoscopic lumbar discectomy, while 63.4% (225/355) showed no symptoms. Multivariable logistical regression analysis showed that Modic change (p < 0.05, OR = 1.813), fatty infiltration of the paravertebral muscle (p < 0.05, OR = 2.935), and edema of lumbodorsal fascia (p = 0.049, OR = 1.611) were significant risk factors for post-operative residual back pain. Moreover, the C-index of the predictive nomogram was 0.743 (0.681–0.805), the area under the receiver operating characteristic curve (AUC) value was 0.739, and the DCA results exhibit a net benefit between 0.16 and 0.66. The above internal validation methods demonstrate the nomogram's good predictive capability. Conclusion: Each variable in the model had a quantitatively corresponding risk score, which can be used in predicting residual low back pain after PELD. [ABSTRACT FROM AUTHOR]

Based on abundant topotype specimens from the Oil Creek Formation at the type locality in southern Oklahoma, Histiodella labiosa is described and revised. The morphological variation of the Pa, Pb, and M elements of this previously little-known species is also systematically documented and illustrated. The revised species definition, with formal designation of a lectotype and a new diagnosis supported by morphological comparison with its ancestral and descendent species, has enhanced its value for correlation of the lower Darriwilian. The inferred phylogeny of Histiodella that resulted from this study is based on both cladistic and morphological analyses. It supports the monophyletic grouping of Histiodella species and their evolutionary relationships. This has wide biostratigraphic implications because many Histiodella species are valuable for detailed global correlation of upper Dapingian to middle Darriwilian strata. [ABSTRACT FROM AUTHOR]

With d-dimensional single photons, two semi-quantum private comparison protocols are presented to compare the size relation between two classical parties’ private secrets. The first protocol transmits particles with the distribution model, whereas the second one transmits particles with the circle model. In the two designed protocols, it is not necessary for the classical participants to possess the abilities to measure quantum states, which greatly reduces the consumption of quantum resources. It is demonstrated that the output results of the two presented semi-quantum private comparison protocols are correct, and the private secrets of participants will not be leaked out to others. Security analyses indicate that the two proposed semi-quantum private comparison protocols could counteract some common attacks, including external attacks and participant attacks. [ABSTRACT FROM AUTHOR]

Background. Accumulating evidence has implicated long noncoding RNAs (lncRNAs) in glioma progression. Here, we aimed to explore the potential roles of a novel lncRNA, LINC00355, in glioma and to clarify the underlying mechanisms. Methods. RT-PCR was used to examine the relative expressions of LINC00355 in glioma cell lines and specimen samples. The clinicopathological and prognostic significances of LINC00355 in glioma patients were statistically analyzed. To determine cell activities, CCK-8, clonogenic assays, flow cytometry, migration, and invasion assays were performed. Moreover, the potential mechanisms of LINC00355 were investigated by bioinformatics assays and luciferase reporter assays. Results. LINC00355 expression was increased in glioma cell lines and specimens, and higher LINC00355 expression predicted advanced clinical progress and reduced overall survival and disease-free survival in glioma patients. Functionally, LINC00355 depletion promoted cell proliferation, invasion, and migration in glioma cells and induced apoptosis of glioma cells, whereas LINC00355 upregulation resulted in the opposite effects in vitro. Mechanistic assays revealed that LINC00355 as a sponge for miR-1225 repressed fibronectin type III domain-containing 3B (FNDC3B) expressions. Conclusion. Our findings revealed the tumor-promotive roles of LINC00355 in the progression of glioma, indicating that LINC00355 exhibited ceRNA functions via modulating miR-1225/FNDC3B axis. [ABSTRACT FROM AUTHOR]

Ordovician conodonts representing 28 genera and 28 named and three unnamed species were identified from 740 chert and siliceous siltstone spot samples (>3 000 thin sections) from deep-water turbiditic sequences of the Lachlan Orogen in central and southern New South Wales, Australia. Based on these faunas, a new conodont biozonal scheme has been established to divide the Ordovician turbiditic successions of the Lachlan Orogen into 12 superbiozones and biozones. They are (in ascending order) the Paracordylodus gracilis Superbiozone (including the Prioniodus oepiki Biozone), Periodon flabellum Superbiozone (including the Oepikodus evae Biozone in the lower part), Periodon hankensis Biozone, Periodon aculeatus Superbiozone (including the Histiodella labiosa, Histiodella holodentata, Histiodella kristinae, Pygodus serra and Pygodus anserinus biozones) and the Periodon grandis Biozone. The Pygodus anserinus Biozone is divided further into the lower and upper subbiozones. This new conodont biozonation scheme spanning the upper Tremadocian to middle Katian interval permits precise age-dating and correlation of deep-water siliciclastic rocks that characterize the Ordovician Deep-Sea Realm regionally and internationally. [ABSTRACT FROM AUTHOR]

Seven conodont biozones are recognized in the carbonate-dominated shelf-marine Middle Ordovician developed in the intracratonic sedimentary basins (Canning, Amadeus and Georgina) of central and north-western Australia, in the Lachlan and New England orogens of New South Wales, and in the Takaka Terrane of New Zealand. A separate scheme identifying seven conodont biozones spanning the Middle Ordovician has also been developed for siliciclastic sequences deposited in slope-basinal environments in the Lachlan Orogen in New South Wales and Victoria. This biozonal classification consisting of two parallel biostratigraphic schemes for the shelf-marine and deep-marine successions respectively has significantly increased precision in regional and global biostratigraphic correlation and laid a solid foundation for the Middle Ordovician chronostratigraphy of Australia and New Zealand. Recognition of short-ranging pandemic species as the eponymous species of the biozones also supports direct correlation with the classical conodont successions established in Baltoscandia and the North American Midcontinent, and with those of the major Chinese terranes (South and North China and Tarim). The Lachlan Orogen appears to be globally unique in enabling correlation of contemporaneous conodont faunas over a considerable spectrum of water depths and biofacies ranging from carbonate shelves, slopes to deep-water basins. [ABSTRACT FROM AUTHOR]

B4C‐TiB2 ceramics (TiB2 ranging 5~70 vol%) with Mo‐Co‐WC as the sintering additive were prepared by spark plasma sintering. In comparison with B4C‐TiB2 without additive, the enhanced densification was evident in the sintered specimen with Mo‐Co‐WC additive. Core‐rim structured grain was observed around TiB2 grains. The interface of the rim between TiB2 and B4C phases demonstrated different feature: the inner borderline of the rim exhibited a smooth feature, whereas a sharp curved grain boundary was observed between the rim and the B4C grain. The formation mechanism is discussed: the epitaxial growth of (Ti,Mo,W)B2 rim around the TiB2 core may occur as a result of the solid solution and dissolution‐precipitation between TiB2 phase and the sintering additive. It was revealed that the fracture toughness increased as the content of TiB2 content increased, alongside the decreased hardness. B4C‐30 vol% TiB2 specimen demonstrated the optimal combination of mechanical properties, reaching Vickers hardness of 24.3 GPa and fracture toughness of 3.33 MPa·m1/2. [ABSTRACT FROM AUTHOR]

RecD family helicases play an important role in prokaryotic genome stability and serve as the structural models for studying superfamily 1B (SF1B) helicases. However, RecD-catalyzed duplex DNA unwinding behavior and the underlying mechanism are still elusive. RecD family helicases share a common proto-helicase with eukaryotic Pif1 family helicases, which are well known for their outstanding G-quadruplex (G4) unwinding ability. However, there are still controversial points as to whether and how RecD helicases unfold G4 structures. Here, single-molecule fluorescence resonance energy transfer (smFRET) and magnetic tweezers (MT) were used to study Deinococcus radiodurans RecD2 (DrRecD2)-mediated duplex DNA unwinding and resolution of G4 structures. A symmetric, repetitive unwinding phenomenon was observed on duplex DNA, revealed from the strand switch and translocation of one monomer. Furthermore, we found that DrRecD2 was able to unwind both parallel and antiparallel G4 structures without obvious topological preferences. Surprisingly, the unwinding properties of RecD on duplex and G4 DNA are different from those of Pif1. The findings provide an example, in which the patterns of two molecules derived from a common ancestor deviate during evolution, and they are of significance for understanding the unwinding mechanism and function of SF1B helicases. • RecD2-catalyzed duplex and G4 DNA unwinding was investigated; • Single-molecule fluorescence resonance energy transfer (smFRET) and magnetic tweezers (MT) were used; • DrRecD2 was shown to differ from its structural/functional analog, Pif1, in terms of unwinding mechanism and specificity. [ABSTRACT FROM AUTHOR]

An effective vaccine for hepatitis C virus (HCV) is a major unmet need, and it requires an antigen that elicits immune responses to key conserved epitopes. Based on structures of antibodies targeting HCV envelope glycoprotein E2, we designed immunogens to modulate the structure and dynamics of E2 and favor induction of broadly neutralizing antibodies (bNAbs) in the context of a vaccine. These designs include a point mutation in a key conserved antigenic site to stabilize its conformation, as well as redesigns of an immunogenic region to add a new N-glycosylation site and mask it from antibody binding. Designs were experimentally characterized for binding to a panel of human monoclonal antibodies (HMAbs) and the coreceptor CD81 to confirm preservation of epitope structure and preferred antigenicity profile. Selected E2 designs were tested for immunogenicity in mice, with and without hypervariable region 1, which is an immunogenic region associated with viral escape. One of these designs showed improvement in polyclonal immune serum binding to HCV pseudoparticles and neutralization of isolates associated with antibody resistance. These results indicate that antigen optimization through structure-based design of the envelope glycoproteins is a promising route to an effective vaccine for HCV. [ABSTRACT FROM AUTHOR]

Purpose: This study aims at evaluating the effects of RTS (rotation softened trauma fixation system) compared with PCPSF (percutaneous conventional pedicle screw fixation) on type A thoracolumbar fractures. Methods: In this retrospective cohort study, 116 patients with type A thoracolumbar fractures from March 2014 to June 2018 were enrolled. PCPSF was performed in 60 patients, meanwhile the other 56 patients accepted RTS. VAS scores, Cobb angle, anterior vertebral height (AVH) and perioperative data were compared between the two groups. Results: Both groups were consistent with baseline on demographic and clinical characteristics. No significant difference was observed in VAS score between-group before and after operation. One year after surgery, the VAS score of RTS group was lower than that of PCPSF group (0.7 ± 0.3 vs. 1.5 ± 0.4). The postoperative AVH (%) in PCPSF was 82.3% (95%CI, 81.7–84.6), and 91.78% (95% CI, 91.1–92.4) in RTS. The postoperative improvement rate of AVH (%) in RTS was higher than that in PCPSF (30.6 ± 5.0 [95% CI, 29.2–32.0] vs. 22.0 ± 7.3 [95% CI, 20.2–24.2]). The postoperative Cobb angle (°) in PCPSF was 2.6 ± 3.4 (95%CI,11.7–13.5), and 7.5 ± 2.0 (95%CI,7.0–8.0) in RTS. The postoperative correction of Cobb angle (°) in RTS was higher than that in PCPSF (16.1 ± 3.8 95%CI,15.1–17.1] vs. 11.6 ± 5.2 95%CI,10.3–13.1]). Conclusions: Compared with PCPSF, RTS has advantages in restoring the anterior vertebral height and reducing local kyphosis. [ABSTRACT FROM AUTHOR]

High quality crystalline nanostructured CeO2 thin films were fabricated by pulsed laser deposition on R-cut sapphire substrates. As-grown and postannealed (in oxygen) films were investigated by atomic force microscopy, x-ray diffraction, and optical transmission and reflectance spectroscopy. The optical spectra changed as the microstructure varied from small grains to large quasi-two-dimensional islands. Hence, the band gap energy (Eg) was found to increase systematically with the decrease in the grain size and ranged from 3.58 to 3.71 eV for the direct and from 3.01 to 3.26 eV for the indirect transitions. This is consistent with the quantum confinement model and, up to now, not observed in a convincing manner in the CeO2 thin films. Results indicate that Eg can be controlled in nanostructured thin films through thickness control and postannealing. [ABSTRACT FROM AUTHOR]

• Germanium was extracted with a new orgnic phase YW100 + D2EHPA + N235. • Compared to the "YW100 + D2EHPA" traditional extraction system, 80% of the water solubility loss of YW100 was reduced and improved the phase separation performance. • The phase separation performance was improved. • The mechanism of germanium extraction and phase separation has been studied. In this study, germanium was selectively extracted using an organic phase containing 3% C7-9 hydroxamic acid (YW100), 15% Di(2-ethylhexyl)phosphoric acid (D2EHPA), 35% Tri(octyl-decyl) amine (N235), and 47% kerosene from the Ge-slag sulfuric acid leaching solution. Then, the solution was stripped by the 1 mol/L NH4F solution to obtain a germanium extraction ratio of 99.4% and a stripping ratio of 96.2% after three extraction and stripping stages. The total organic carbon (TOC) was used to characterize the total organic matter amount in the raffinate. Compared to the "YW100 + D2EHPA" extraction system, the "YW100 + D2EHPA + N235" extraction system reduced 80% of the water solubility loss of YW100 and improved the phase separation performance. In addition, the mechanisms of germanium extraction and phase separation improvement were studied. The coordination number of YW100 and germanium is 3, while the coordination number of D2EHPA is 1. [ABSTRACT FROM AUTHOR]

Background: The outbreak of the 2009 H1N1 influenza pandemic (H1N1pdm) affected thousands of people in Mexico and the United States, and spread rapidly throughout the world from April 2009 to July 2010. To explore the age-specific prevalence of seroprotection against H1N1pdm infection, we estimated pre-existing humoral and cellular immunities of residents in Northern China against H1N1pdm and seasonal H1N1 virus in an age-dependent manner.Methods: Anonymous serum samples were collected from 1425 to 1434 adult healthy individuals before and after the pandemic outbreak, and then grouped by birth year 1913-1990. The antibody titers of H1N1pdm and seasonal H1N1 were determined using microneutralization (MN) assays, and the proportion of seropositive was estimated based on the year of birth. Separately, another 63 blood samples were collected in 2006 and prepared for analysis of virus specific memory B and IFN-γ+ T cells using the ELISpot assays.Results: The prevalence of pre-existing H1N1pdm-specific sero-antibodies in the elderly population (>60 years old) was 7.8%. The younger group, aged 19 to 60 years, exhibited a significant increase in seropositivity for H1N1pdm after the pandemic (4.9% before pandemic and 18.9% after pandemic, p < 0.05). The prevalence of H1N1pdm specific MBCs before the pandemic in the elderly (>60 years) and younger populations (<60 years) was 38% (8/21) and 48% (20/42), respectively (p = 0.6). The IFN-γ+ T cell responses to the pandemic and seasonal viruses were significantly lower in the elder group than those in the younger group (<60 years) (p < 0.05).Conclusions: Pre-existing serum antibodies and memory B cells against H1N1pdm were low in all age group, whereas diminished memory T cell responses to this virus were observed in the elderly population both before and after the pandemic. [ABSTRACT FROM AUTHOR]

Summary: Robots often need to accomplish some complex tasks such as surveillance, response and obstacle avoidance. In this paper, a dynamic search method is proposed to generate optimal robot trajectories satisfying complex task requirement in uncertain environment. The LTL-A* algorithm is presented to generate a global optimal path and the A* algorithm is provided to modify the global optimal path. The task is specified by a linear temporal logic (LTL) formula, and a weighted transition system according to the known information in uncertain environment is modeled to describe the robot motion. Subsequently, a product automaton is constructed by combining the transition system with the task requirement. Based on the product automaton, the LTL-A* algorithm is proposed to generate a global optimal path. The local path planning based on the A* algorithm is employed to deal with the environment change during the process of tracking the global optimal path for the robot. The results of the simulation and experiments show that the proposed method can not only meet the complex task requirement in uncertain environment but also improve the search efficiency. [ABSTRACT FROM AUTHOR]

Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity of the B cell response associated with clearance is crucial to inform vaccine design. From an individual who cleared three sequential HCV infections with genotypes 1b, 1a and 3a strains, respectively, we employed peripheral B cells to isolate and characterize neutralizing human monoclonal antibodies (HMAbs) to HCV after the genotype 1 infections. The majority of isolated antibodies, designated as HMAbs 212, target conformational epitopes on the envelope glycoprotein E2 and bound broadly to genotype 1–6 E1E2 proteins. Further, some of these antibodies showed neutralization potential against cultured genotype 1–6 viruses. Competition studies with defined broadly neutralizing HCV HMAbs to epitopes in distinct clusters, designated antigenic domains B, C, D and E, revealed that the selected HMAbs compete with B, C and D HMAbs, previously isolated from subjects with chronic HCV infections. Epitope mapping studies revealed domain B and C specificity of these HMAbs 212. Sequential serum samples from the studied subject inhibited the binding of HMAbs 212 to autologous E2 and blocked a representative domain D HMAb. The specificity of this antibody response appears similar to that observed during chronic infection, suggesting that the timing and affinity maturation of the antibody response are the critical determinants in successful and repeated viral clearance. While additional studies should be performed for individuals with clearance or persistence of HCV, our results define epitope determinants for antibody E2 targeting with important implications for the development of a B cell vaccine. [ABSTRACT FROM AUTHOR]

A conodont fauna of late Tremadocian to early Floian age (Early Ordovician) is documented from the Yinchufu Formation of Zhejiang Province, South China. It is characterized by the occurrence of two species of Prioniodontidae, a new species of Prioniodus and Acodus triangularis. Prioniodus antiquus sp. nov. may represent the most primitive species of Prioniodus , which is one of the earliest conodont genera with a ramiform—pectiniform apparatus. Based on the review of nearly 200 species originally assigned to Prioniodus , six multielement species are confirmed to belong to this genus. Morphological changes of these six species shows that they form an evolutionary lineage directly evolved from an adentate species, likely Acodus triangularis which has been reported from South China, Australia and from the Precordillera of western Argentina. Origination of the ramiform—pectiniform apparatuses as represented by the appearances of Prioniodus through late Tremadocian to Floian of the Early Ordovician might be a major response of the 'conodont animals' to occupy and adapt to the increasingly diversified environments in the shelf and slope settings. The biofacies distribution of the six Prioniodus species indicates that Prioniodus might have originated in deep-water slope settings and progressively spread into distal and then interior shelves in the late Tremadocian and diversified in the Floian, with Prioniodus amadeus possibly representing a relict species that survived into the Middle Ordovician and was restricted to shallow water environments. • A case study investigates the origination of the ramiform—pectiniform apparatus. • The grouping of the six Prioniodus species and their evolutionary relationships are discussed. • Prioniodus probably originated in deep-water environments and progressively spread into distal and then interior shelves. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to explore refractive regression and central corneal thickness (CCT) following laser-assisted subepithelial keratectomy (LASEK) performed for the correction of high myopia in eyes with thin corneas. Forty patients (19 male, 21 female; mean age, 28.5 years) representing 76 treated eyes were included. The mean optical zone was 6.10 ± 0.32 mm, and the mean ablation depth was 121.53 ± 15.48 µm. CCT was significantly greater three years after surgery than at three months after surgery (425.66 ± 15.44 vs. 385.20 ± 12.81, respectively; p<0.001). The mean change in CCT from three months to three years was 40.46 ± 14.02 µm. The SE at three years was greater than that at three months (p<0.001). Although there was refractive regression, these data suggest that LASEK may have utility in the correction of high myopia in eyes with thin corneas. [ABSTRACT FROM AUTHOR]

The binding sites of transcription factors (TFs) in upstream DNA regions are called transcription factor binding sites (TFBSs). TFBSs are important elements for regulating gene expression. To date, there have been few studies on the profiles of TFBSs in plants. In total, 4,873 sequences with 5ʹ upstream regions from 8530 wheat fl-cDNA sequences were used to predict TFBSs. We found 4572 TFBSs for the MADS TF family, which was twice as many as for bHLH (1951), B3 (1951), HB superfamily (1914), ERF (1820), and AP2/ERF (1725) TFs, and was approximately four times higher than the remaining TFBS types. The percentage of TFBSs and TF members showed a distinct distribution in different tissues. Overall, the distribution of TFBSs in the upstream regions of wheat fl-cDNA sequences had significant difference. Meanwhile, high frequencies of some types of TFBSs were found in specific regions in the upstream sequences. Both TFs and fl-cDNA with TFBSs predicted in the same tissues exhibited specific distribution preferences for regulating gene expression. The tissue-specific analysis of TFs and fl-cDNA with TFBSs provides useful information for functional research, and can be used to identify relationships between tissue-specific TFs and fl-cDNA with TFBSs. Moreover, the positional distribution of TFBSs indicates that some types of wheat TFBS have different positional distribution preferences in the upstream regions of genes. Identification and positional distribution analysis of transcription factor binding sites for genes from the wheat fl-cDNA sequences [ABSTRACT FROM PUBLISHER]

The article offers information on the people suffer from chronic hepatitis C virus (HCV) infection and mentions the treatment for chronic HCV infection. Topics discussed the HCV infection is one of the most important risk factors for liver disease, including liver fibrosis, cirrhosis and hepatocellular carcinoma; and mentions the patient derived neutralizing monoclonal antibodies to protect against or control an infection in liver.

In this study, we investigated the cutting performance and wear mechanisms of Ti(C,N)‐based cutting tools containing varying weight percentages (0%, 5%, 10%, and 15%) of high‐entropy carbide (HEC) (V0.2Nb0.2 Mo0.2Ta0.2W0.2)C phase, when used for turning nodular cast iron. According to the turning test results, the cermet cutting tools containing 0 wt%, 5 wt%, 10 wt%, and 15 wt% HEC phases demonstrated effective cutting lives of 402, 720, 632, and 465 s, respectively. The tool with 5 wt% HEC phase showed the best cutting performance. When cutting nodular cast iron with cermet cutting tools, the main wear mechanisms observed were diffusion, oxidation, adhesion, and abrasion on the flank surface, along with diffusion, oxidation, and abrasion on the rake surface. The results of this study indicated that (V0.2Nb0.2Mo0.2Ta0.2W0.2)C could be adopted as an effective reinforced phase in the cermet cutting tools. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to explore refractive regression and central corneal thickness (CCT) following laser-assisted subepithelial keratectomy (LASEK) performed for the correction of high myopia in eyes with thin corneas. Forty patients (19 male, 21 female; mean age, 28.5 years) representing 76 treated eyes were included. The mean optical zone was 6.10 ± 0.32 mm, and the mean ablation depth was 121.53 ± 15.48 µm. CCT was significantly greater three years after surgery than at three months after surgery (425.66 ± 15.44 vs. 385.20 ± 12.81, respectively; p<0.001). The mean change in CCT from three months to three years was 40.46 ± 14.02 µm. The SE at three years was greater than that at three months (p<0.001). Although there was refractive regression, these data suggest that LASEK may have utility in the correction of high myopia in eyes with thin corneas. [ABSTRACT FROM AUTHOR]

Ordovician conodont studies have revealed a depositional hiatus extending from the late Floian to early Darriwilian on the North China Platform. Recognition of this widespread gap entails revision of the original concept of the Huaiyuan Epeirogeny, with definition of two distinct regional tectonic events: Event 1, which initiated this hiatus, and a subsequent Event 2 that was responsible for terminating Early Palaeozoic sedimentation in the region from the late Katian. The timing of these two events partly coincides with widely recognized eustatic sea-level falls, and separates Ordovician sedimentation into two episodes that can be broadly correlated with eustatic sea-level rises. In combination with these sea-level changes, the Huaiyuan Epeirogeny played a decisive role in shaping and controlling Ordovician sedimentation and sequence stratigraphic architecture on the North China Platform. Lower Ordovician carbonates were deposited during an apparent regression (decreasing accommodation space), resulting from rapid sediment accumulation exceeding the overall rate of basement subsidence and eustatic sea-level rise. Sedimentation ceased in the middle to late Floian when basement uplift commenced in the south and extended northward to affect the entire platform. The diachronous top surface of the Lower Ordovician succession reflects extensive erosion that is most pronounced in the south and southwest parts of the platform where the disconformity surface cut down into Tremadocian (or even upper Cambrian) strata. Deposition of the younger sequence (Darriwilian to Katian) was the result of the interplay between rejuvenated basement subsidence and the late Middle Ordovician eustatic sea-level rise. Event 2, which was initially coupled with eustatic sea-level fall induced by the end-Ordovician glaciations, terminated Ordovician deposition in the region with the top of the Ordovician marked by an unconformity, representing a hiatus of some 122 Ma extending from latest Ordovician to latest Mississippian. [ABSTRACT FROM AUTHOR]

Clinical studies have demonstrated that a single dose of ketamine produces complete remission within 24 h in some depression patients. The ability of ketamine to produce fast-acting antidepressant-like effects in animal models depends on rapid synthesis of brain-derived neurotrophic factor (BDNF). Here we examined effects of a single dose dizocilpine, a non-competitive NMDA receptor antagonist, on the behavioral and neurobiological changes in rats treated with a single high dose reserpine, which is a monoamine re-uptake blocker and depletes monoamines in the brain with the outcome of depression-like symptoms in animals. A single high dose reserpine (4.0 mg/kg) was given to rats intraperitoneally. Forty-eight hours later, the rats showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swim test. Meanwhile, the treatment decreased BDNF levels and neurogenesis in the hippocampus. Pretreatment of a single dose dizocilpine (0.30 mg/kg), however, prevented all the reserpine-induced changes, except for GluN1 subunit. These results are suggestive of the involvement of neurogenesis and BDNF in the rapid-acting antidepressant-like behavioral effects of the NMDA receptor antagonists in the reserpinized rats. [ABSTRACT FROM AUTHOR]

Filoviruses cause highly lethal viral hemorrhagic fever in humans and nonhuman primates. Current immunotherapeutic options for filoviruses are mostly specific to Ebola virus (EBOV), although other members of Filoviridae such as Sudan virus (SUDV), Bundibugyo virus (BDBV), and Marburg virus (MARV) have also caused sizeable human outbreaks. Here we report a set of pan-ebolavirus and pan-filovirus monoclonal antibodies (MAbs) derived from cynomolgus macaques immunized repeatedly with a mixture of engineered glycoproteins (GPs) and virus-like particles (VLPs) for three different filovirus species. The antibodies recognize novel neutralizing and nonneutralizing epitopes on the filovirus glycoprotein, including conserved conformational epitopes within the core regions of the GP1 subunit and a novel linear epitope within the glycan cap. We further report the first filovirus antibody binding to a highly conserved epitope within the fusion loop of ebolavirus and marburgvirus species. One of the antibodies binding to the core GP1 region of all ebolavirus species and with lower affinity to MARV GP cross neutralized both SUDV and EBOV, the most divergent ebolavirus species. In a mouse model of EBOV infection, this antibody provided 100% protection when administered in two doses and partial, but significant, protection when given once at the peak of viremia 3 days postinfection. Furthermore, we describe novel cocktails of antibodies with enhanced protective efficacy compared to individual MAbs. In summary, the present work describes multiple novel, cross-reactive filovirus epitopes and innovative combination concepts that challenge the current therapeutic models. [ABSTRACT FROM AUTHOR]

ZrB 2 (ZB) and ZrB 2 –5 vol.% WC (ZW) were prepared by hot-pressing at 2100 °C. Combining experimental and theoretical methods, the tungsten (W) element in solid solution with ZrB 2 and ZrC was investigated. Experimentally, solid solution formation in ZW samples was supported by XRD and EDS. Theoretically; atomic scale computer simulations based on density functional calculations were used to interpret the different amount of solid solution and the changes in lattice parameters. The flexural strength of the samples was measured from room temperature to 1600 °C. The flexural strength of ZB and ZW changed differently as testing temperature increased. Then, the strength of ZB increased from 344 ± 12 MPa to 1281 ± 39 MPa, which is about 3.7 times of room temperature strength. Further temperature increasing led to strength decreasing. While for ZW, the strength increased continuously from room temperature to 1600 °C. SEM and TEM techniques were employed to clarify the different mechanism of fracture surfaces and grain boundaries of ZB and ZW. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to investigate the effect of posterior scleral reinforcement (PSR) combined with patching therapy for pre-school children with unilateral high myopia. Methods: A total of 32 pre-school children with unilateral high myopia were recruited. They were randomly divided into the PSR and control group, each of which had 16 patients. The patients in the PSR group underwent the simplified PSR surgery followed by rigid gas permeable contact lens wear and traditional patching therapy, while the patients in the control group were only prescribed contact lens wear and patching. Patients were reviewed and the axial length, refraction, best-corrected visual acuity, and stereoscopic vision were respectively examined postoperatively at yearly intervals for three years. Results: The best-corrected visual acuity was significantly higher in the PSR group than that in the control group at any study visit. A statistically significant difference in axial length was found between the PSR group (27.38 ± 1.30 mm) and the control group (28.29 ± 0.74 mm) at the postoperative three-year ( p = 0.03) time point. There was a statistical difference in refractive error between the PSR group (-13.13 ± 2.55 D) and the control group (-15.42 ± 1.83 D) at 3-year follow-up. No significant difference was found between the two groups with respect to the stereoscopic vision by the end of follow-up at 3 years ( p =0.103). Conclusions: PSR combined with the patching therapy has the potential to arrest the progression of high myopia and to help the treatment for amblyopia. [ABSTRACT FROM AUTHOR]

Gambogic acid (GA) inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of GA is limited. Objectives. To investigate the antitumor activity of gambogic acid lysinate (GAL) and its mechanism. Methods. Inhibition of cell proliferation was determined by MTT assay; intracellular ROS level was detected by staining cells with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism of GAL was investigated by Western blot. Results. GAL inhibited the proliferation of MCF-7 cells with IC50 values 1.46 μmol/L comparable with GA (IC50, 1.16 μmol/L). GAL promoted the production of ROS; however NAC could remove ROS and block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a, cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced the cleavage of caspase-3. Conclusions. GAL inhibited MCF-7 cell proliferation and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These results suggested that GAL might be useful as a modulation agent in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Wheat (Triticum aestivum) is one of the most important cereal crops, providing food for humans and feed for other animals. However, its productivity is challenged by various biotic and abiotic stresses such as fungal diseases, insects, drought, salinity, and cold. Transcription factors (TFs) regulate gene expression in different tissues and at various developmental stages in plants and animals, and they can be identified and classified into families according to their structural and specialized DNA-binding domains (DBDs). Transcription factors are important regulatory components of the genome, and are the main targets for engineering stress tolerance. Results: In total, 2407 putative TFs were identified from wheat expressed sequence tags, and then classified into 63 families by using Hmm searches against hidden Markov model (HMM) profiles. In this study, 2407 TFs represented approximately 2.22% of all genes in the wheat genome, a smaller proportion than those reported for other cereals in PlantTFDB V3.0 (3.33%-5.86%) and PlnTFDB (4.30%-6.46%). We assembled information from the various databases for individual TFs, including annotations and details of their developmental stage- and tissue-specific expression patterns. Based on this information, we identified 1257 developmental stage-specific TFs and 1104 tissue-specific TFs, accounting for 52.22% and 45.87% of the 2407 wheat TFs, respectively. We identified 338, 269, 262, 175, 49, and 18 tissue-specific TFs in the flower, seed, root, leaf, stem, and crown, respectively. There were 100, 6, 342, 141, 390, and 278 TFs specifically expressed at the dormant seed, germinating seed, reproductive, ripening, seedling, and vegetative stages, respectively. We constructed a comprehensive database of wheat TFs, designated as WheatTFDB (http://xms.sicau.edu.cn/wheatTFDB/). Conclusions: Approximately 2.22% (2407 genes) of all genes in the wheat genome were identified as TFs, and were clustered into 63 TF families. We identified 1257 developmental stage-specific TFs and 1104 tissue-specific TFs, based on information about their developmental- and tissue-specific expression patterns obtained from publicly available gene expression databases. The 2407 wheat TFs and their annotations are summarized in our database, WheatTFDB. These data will be useful identifying target TFs involved in the stress response at a particular stage of development. [ABSTRACT FROM AUTHOR]

A challenge for hepatitis C virus (HCV) vaccine development is to define epitopes that are able to elicit protective antibodies against this highly diverse virus. The E2 glycoprotein region located at residues 412–423 is conserved and antibodies to 412–423 have broadly neutralizing activities. However, an adaptive mutation, N417S, is associated with a glycan shift in a variant that cannot be neutralized by a murine but by human monoclonal antibodies (HMAbs) against 412–423. To determine whether HCV escapes from these antibodies, we analyzed variants that emerged when cell culture infectious HCV virions (HCVcc) were passaged under increasing concentrations of a specific HMAb, HC33.1. Multiple nonrandom escape pathways were identified. Two pathways occurred in the context of an N-glycan shift mutation at N417T. At low antibody concentrations, substitutions of two residues outside of the epitope, N434D and K610R, led to variants having improved in vitro viral fitness and reduced sensitivity to HC33.1 binding and neutralization. At moderate concentrations, a S419N mutation occurred within 412–423 in escape variants that have greatly reduced sensitivity to HC33.1 but compromised viral fitness. Importantly, the variants generated from these pathways differed in their stability. N434D and K610R-associated variants were stable and became dominant as the virions were passaged. The S419N mutation reverted back to N419S when immune pressure was reduced by removing HC33.1. At high antibody concentrations, a mutation at L413I was observed in variants that were resistant to HC33.1 neutralization. Collectively, the combination of multiple escape pathways enabled the virus to persist under a wide range of antibody concentrations. Moreover, these findings pose a different challenge to vaccine development beyond the identification of highly conserved epitopes. It will be necessary for a vaccine to induce high potency antibodies that prevent the formation of escape variants, which can co-exist with lower potency or levels of neutralizing activities. [ABSTRACT FROM AUTHOR]

Background: It is well recognized that intraoperative aneurysm rupture (IAR) is a serious event that is difficult to manage and has a relatively serious influence on a patient's prognosis. The aim of this study was to evaluate the prognostic value of different bleeding positions of IAR in patients, and to describe the technique that the authors have used to clip the ruptured aneurysms. Methods: From May 2009 to March 2012, a total of 148 aneurysms in 135 consecutive patients in our institution underwent clipping surgeries, and 31 IARs occurred in 30 patients. The clinical data of all patients were retrospectively analyzed. Statistics analysis was performed to analyze possible factors of different bleeding positions of IARs, to assist observation. Results: Outcome was estimated by Glasgow outcome scale via following up or calling back within 1, 3, and 6 months after surgery: 94 patients were 5', 23 patients were 4', nine patients were 3', two patients were 2' and eight patients were 1'. There was no significant difference between the outcome of IAR and that of no intraoperative aneurysm rupture (NIAR) in Hunt-Hess groups 0-III ( P = 0.802) and Hunt-Hess groups IV-V ( P = 0.229), and the different bleeding positions were shown to be an important factor that significantly influences the patients' prognosis ( P = 0.001). Conclusions: Different bleeding positions of IAR have a significant impact on surgical outcome; IAR of the neck is the most devastating complication. If surgeons take appropriate measures according to different bleeding positions, the efficiency, accuracy and security of the operation will be improved. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of age and conjunctivochalasis (CCh) on conjunctival thickness. Methods: One hundred and nineteen normal subjects aged 60-79 years and 83 subjects with CCh graded I-II (39 males and 44 females) aged 60-79 years were recruited. Cirrus HD-optical coherence tomography 4000 was used to measure the thickness of the lower temporal conjunctiva 3-5 mm from the corneal limbus. Results: The conjunctiva was significantly thicker in normal subjects compared to CCh patients ( p < 0.0001), and in normal subjects aged 60-69 years compared to normal subjects aged 70-79 years ( p = 0.0466). There was no significant difference between age groups for patients with CCh ( p = 0.1001). After subdividing groups by age, normal subjects had a thicker conjunctiva compared to CCh patients for those aged 60-69 years ( p = 0.0152) as well as those aged 70-79 years ( p = 0.0120). Conclusions: The conjunctiva is thinner in older subjects and subjects with CCh. [ABSTRACT FROM AUTHOR]

Ionotropic glutamate receptors ( iGluRs) are expressed in islets and insulinoma cells and involved in insulin secretion. However, the exact roles that iGluRs play in β cells remain unclear. Here, we demonstrated that GluR2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors ( AMPARs) were expressed in mouse β cells. Glutamate application increased both cytosolic calcium and the number of docked insulin-containing granules, which resulted in augmentation of depolarization-induced exocytosis and high-glucose-stimulated insulin release. While glutamate application directly depolarized β cells, it also induced an enormous depolarization when KATP channels were available. Glutamate application reduced the conductance of KATP channels and increased voltage oscillations. Moreover, actions of AMPARs were absent in Kir6.2 knock-out mice. The effects of AMPARs on KATP channels were mediated by cytosolic cGMP. Taken together, our experiments uncovered a novel mechanism by which AMPARs participate in insulin release. [ABSTRACT FROM AUTHOR]

The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1-6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1-6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418-446 and aa611-616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434-446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410-425. The isolation of four HC-84 HMAbs binding to the peptide, aa434-446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus. [ABSTRACT FROM AUTHOR]

A potent neutralizing antibody to a conserved hepatitis C virus (HCV) epitope might overcome its extreme variability, allowing immunotherapy. The human monoclonal antibody HC-1 recognizes a conformational epitope on the HCV E2 glycoprotein. Previous studies showed that HC-1 neutralizes most HCV genotypes but has modest potency. To improve neutralization, we affinity-matured HC-1 by constructing a library of yeast-displayed HC-1 single chain Fv (scFv) mutants, using for selection an E2 antigen from one of the poorly neutralized HCVpp. We developed an approach by parallel mutagenesis of the heavy chain variable (VH) and k-chain variable (Vk) genes separately, then combining the optimized VH and Vk mutants. This resulted in the generation of HC-i-related scFv variants exhibiting improved affinities. The best scFv variant had a 92-fold improved affinity. After conversion to IgG1, some of the antibodies exhibited a 30-fold improvement in neutralization activity. Both surface plasmon resonance and solution kinetic exclusion analysis showed that the increase in affinity was largely due to a lowering of the dissociation rate constant, Koff. Neutralization against a panel of HCV pseudoparticles and infectious 2a HCV virus improved with the affinity-matured IgG1 antibodies. Interestingly, some of these antibodies neutralized a viral isolate that was not neutralized by wild-type HC-1. Moreover, propagating 2a HCVcc under the selective pressure of WT HC-1 or affinity-matured HC-1 antibodies yielded no viral escape mutants and, with the affinity-matured IgG1, needed 100-fold less antibody to achieve complete virus elimination. Taken together, these findings suggest that affinity-matured HC-1 antibodies are excellent candidates for therapeutic development. [ABSTRACT FROM AUTHOR]

A critical first step in a "rational vaccine design" approach for hepatitis C virus (HCV) is to identify the most relevant mechanisms of immune protection. Emerging evidence provides support for a protective role of virus neutralizing antibodies, and the ability of the B cell response to modify the course of acute HCV infection. This has been made possible by the development of in vitro cell culture models, based on HCV retroviral pseudotype particles expressing E1E2 and infectious cell culture-derived HCV virions, and small animal models that are robust tools in studies of antibody-mediated virus neutralization. This review is focused on the immunogenic determinants on the E2 glycoprotein mediating virus neutralization and the pathways in which the virus is able to escape from immune containment. Encouraging findings from recent studies provide support for the existence of broadly neutralization antibodies that are not associated with virus escape. The identification of conserved epitopes mediating virus neutralization that are not associated with virus escape will facilitate the design of a vaccine immunogen capable of eliciting broadly neutralizing antibodies against this highly diverse virus. [ABSTRACT FROM AUTHOR]

An efficient route to construct a three-dimensional crystal structure is stacking of two-dimensional building blocks (2D-BBs). The crystal structures of potential thermoelectric compounds REOZnSb (RE= La, Ce, Pr, Nd) were virtually constructed from insulating [REO] and conducting [ZnSb] layers. Further optimizations performed by means of first-principles calculations show that REOZnSb should exhibit semimetal or narrow band-gap semiconductor behaviors, which is a prerequisite for high thermoelectric efficiency. The analysis of the electron localizability indicator for LaOZnSb reveals mostly covalent polar interactions between all four kinds of atoms. The electron density yields completely balanced ionic-like electronic formula La1.7+O1.2−Zn0.4+Sb0.9−. Furthermore, the samples of REOZnSb have been synthesized viasolid-state reaction, and their crystal structures were confirmed by powder X-ray diffraction. The differences in cell parameters between the theoretically optimized and the experimental values are smaller than 2%. The temperature dependence of the magnetic susceptibility shows that LaOZnSb is diamagnetic above 40 K, whereas CeOZnSb, PrOZnSb and NdOZnSb are Curie–Weiss-type paramagnets. Electrical conductivity and Seebeck effect measurements indicate that REOZnSb are p-type semiconductors. A considerably high Seebeck coefficient and low thermal conductivity were obtained for pure LaOZnSb, but its low electrical conductivity leads to a small ZT. The high adjustability of the crystal structure as well as properties by optimization of the chemical composition in the compounds REOZnSb provide good prospects for achieving high thermoelectric efficiency. [ABSTRACT FROM AUTHOR]

Rhein lysinate (RHL), easily dissolved in water, is one of the anthraquinones, and has been shown to have anti-tumor activity in different human cancer cell lines. In the present study, we observed that RHL could cause vacuolar degeneration in HeLa cells, which was not observed in human umbilical vein endothelial cells (HUVECs) and other cell lines (SKOV-3 and SK-BR-3). Therefore, the purpose of this study was to investigate the anti-tumor effect of rhein lysinate on human cervix cancer HeLa cells. The results indicated that RHL could induce HeLa cell S-phase arrest and RHL (higher than 80 μM) also induced HeLa cell G2/M-phase arrest in a dose-dependent manner. Compared to the HeLa cells, RHL induced HUVECs G1-phase arrest at all dose levels tested in a dose-dependent manner. Treatment with RHL led to a significant S or G2/M-phase arrest through promoting the expression of p53 and p21 and the phosphorylation of p53. Moreover, 80 μM RHL could increase 5-FU anti-tumor activity. In conclusion, RHL could be a novel chemotherapeutic drug candidate for the treatment of human cervix cancer in the future. [ABSTRACT FROM AUTHOR]

Rhein lysinate (RHL), easily dissolved in water, is one of the anthraquinones, and has been shown to have anti-tumor activity in different human cancer cell lines. In the present study, we observed that RHL could cause vacuolar degeneration in HeLa cells, which was not observed in human umbilical vein endothelial cells (HUVECs) and other cell lines (SKOV-3 and SK-BR-3). Therefore, the purpose of this study was to investigate the anti-tumor effect of rhein lysinate on human cervix cancer HeLa cells. The results indicated that RHL could induce HeLa cell S-phase arrest and RHL (higher than 80 μM) also induced HeLa cell G2/M-phase arrest in a dose-dependent manner. Compared to the HeLa cells, RHL induced HUVECs G1-phase arrest at all dose levels tested in a dose-dependent manner. Treatment with RHL led to a significant S or G2/M-phase arrest through promoting the expression of p53 and p21 and the phosphorylation of p53. Moreover, 80 μM RHL could increase 5-FU anti-tumor activity. In conclusion, RHL could be a novel chemotherapeutic drug candidate for the treatment of human cervix cancer in the future. [ABSTRACT FROM AUTHOR]

Abstract: The structural stability, chemical bonding, Mulliken populations, and charge-density distribution of REZnOSb (RE =La–Nd, Sm–Gd) were investigated by first-principles calculations. Unit cell parameters calculated by the generalized gradient approximation (GGA) are in better agreement with experimental results than those derived from the local density approximation (LDA). Binding energy comparisons indicate that the structural stability of REZnOSb decreases with the increment of the atomic number of the RE, as confirmed by X-ray diffraction (XRD) results. Semimetal or narrow band-gap semiconductor behaviors are found for selected REZnOSb. Moreover, chemical bonding analysis shows that there exist considerable polar covalent interactions between the participating atoms. It also reveals that the [ZnSb] layers receive some electrons from the [LaO] layers (donor) as an electrons acceptor and holes transport tunnel. The covalent interactions between the [ZnSb] and [LaO] layers, which are enhanced by 4f-electrons of the RE, are supposed to improve the electrical transport properties. [Copyright &y& Elsevier]

We describe the femtosecond laser–assisted midperipheral multilayer intrastromal ablation technique, which combines the benefit of radial keratotomy, ie, not disturbing the optical zone, with currently available technology to correct myopia. The technique was performed in 2 patients, both of whom experienced a decrease in mean corneal power. In 1 patient, the manifest refraction improved, with a 1-line increase in uncorrected visual acuity 1 day postoperatively. The multilayer intrastromal ablation technique, which flattens the cornea and decreases corneal power, can be used to correct moderate myopia without injuring the corneal epithelium. Financial Disclosure: Drs. Xing-Ru Zhang, Matthew R. Hoffman, and Xing-Tao Zhou have no financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes. [ABSTRACT FROM AUTHOR]

Broadly neutralizing antibodies are commonly present in the sera of patients with chronic hepatitis C virus (HCV) infection. To elucidate possible mechanisms of virus escape from these antibodies, retrovirus particles pseudotyped with HCV glycoproteins (HCVpp) isolated from sequential samples collected over a 26-year period from a chronically infected patient, H, were used to characterize the neutralization potential and binding affinity of a panel of anti-HCV E2 human monoclonal antibodies (HMAbs). Moreover, AP33, a neutralizing murine monoclonal antibody (MAb) to a linear epitope in E2, was also tested against selected variants. The HMAbs used were previously shown to broadly neutralize HCV and to recognize a cluster of highly immunogenic overlapping epitopes, designated domain B, containing residues that are also critical for binding of viral E2 glycoprotein to CD81, a receptor essential for virus entry. Escape variants were observed at different time points with some of the HMAbs. Other HMAbs neutralized all variants except for the isolate 02.E10, obtained in 2002, which was also resistant to MAb AP33. The 02.E10 HCVpp that have reduced binding affinities for all antibodies and for CD81 also showed reduced infectivity. Comparison of the 02.E10 nucleotide sequence with that of the strain H-derived consensus variant, H77c, revealed the former to have two mutations in E2, S501N and V506A, located outside the known CD81 binding sites. Substitution A506V in 02.E10 HCVpp restored binding to CD81, but its antibody neutralization sensitivity was only partially restored. Double substitutions comprising N501S and A506V synergistically restored 02.E10 HCVpp infectivity. Other mutations that are not part of the antibody binding epitope in the context of N501S and A506V were able to completely restore neutralization sensitivity. These findings showed that some nonlinear overlapping epitopes are more essential than others for viral fitness and consequently are more invariant during earlier years of chronic infection. Further, the ability of the 02.E10 consensus variant to escape neutralization by the tested antibodies could be a new mechanism of virus escape from immune containment. Mutations that are outside receptor binding sites resulted in structural changes leading to complete escape from domain B neutralizing antibodies, while simultaneously compromising viral fitness by reducing binding to CD81. [ABSTRACT FROM AUTHOR]

Discovery of Serratognathus bilobatus in the Early Ordovician Emanuel Formation of the Canning Basin. Western Australia, has regional biogeographic and biostratigraphic implications. Distribution of Serratognathus indicates a close biogeographic link between Australia and adjacent eastern Gondwanan plates and terranes during the latest Tremadocian to early Floian (Early Ordovician), and the formation of the so-called "Australasian Province", a distinctive biogeographic entity that existed throughout most of the Ordovician. The S. bilobatus fauna from the Canning Basin is much more diverse in comparison with those assemblages bearing Serratognathus from coeval Chinese Lower Ordovician successions and probably represents an assemblage inhabiting relatively deeper water (mid-outer shelf) environments. The Canning Basin fauna contains many pandemic forms, and bridges the gap in the regional correlation of this widely distributed fauna across eastern Gondwana. This well-preserved, diverse fauna includes Serratognathus bilobatus and 23 associated species: Acodus deltatus?, Acodus? transitans. Bergstroemognathus extensus, Cornuodus sp., Drepanodus arcuatus, Drepanoistodus sp. cf. D. nowlani, Fahraeusodus adentatus, Lissoepikodus nudus, Nasusgnathus dolonus, Paltodus sp., Paracordylodus gracilis, Paroistodus parallelus, Paroistodus proteus, Prioniodus adami, Protopanderodus gradatus, Protoprioniodus simplicissimus, Scolopodus houlianzhaiensis, Semiacontiodus sp. cf. S. cornuformis, Stiptognathus borealis, Triangulodus bifidus. Tropodus australis, gen. et sp. indet. A and gen. et sp. B. A P. adami-S, bilobatus Biozone is defined within the middle and upper Emanuel Formation. Correlation of this biozone suggests an early Floian (late P. proteus Biozone to possibly earliest P. elegans Biozone) age for the middle and upper members of the Emanuel Formation. [ABSTRACT FROM AUTHOR]

Effective immunization against hepatitis C virus (HCV) infections is likely to require the induction of both robust land B cell immunity. Although neutralizing antibodies may play an important role in control of infection, there is little understanding of the structure of the HCV envelope glycoproteins and how they interact with such antibodies. An additional challenge for vaccine design is the genetic diversity of HCV and the rapid evolution of viral quasispedes that escape antibody-mediated neutralization. We used a cell culture-infectious, chimeric HCV with the structural proteins of genotype la virus to identify envelope residues contributing to the epitope recognized by a broadly neutralizing, murine monoclonal antibody, AP33. By repetitive rounds of neutralization followed by amplification, we selected a population of viral escape mutants that resist stringent neutralization with AP33 and no longer bind the antibody. Two amino acid substitutions, widely separated in the linear sequence of the E2 envelope protein (N41 5Y and E655G), were identified by sequencing of cloned cDNA and shown by reverse genetics analysis to contribute jointly to the AP33 resistance phenotype. The N415Y mutation substantially lowered virus fitness, most likely because of a defect in viral entry, but did not reduce binding of soluble CD81 to immobilized HCV-pseudotyped retrovirus particles. The in vitro selection of an HCV escape mutant recapitulates the ongoing evolution of antigenic variants that contributes to viral persistence in humans and reveals information concerning the conformational structure of the AP33 epitope, its role in viral replication, and constraints on its molecular evolution. [ABSTRACT FROM AUTHOR]

An abstract of the article "A Point Mutation Leading to Hepatitis C Virus Escape from Neutralization by a Monoclonal Antibody to a Conserved Conformational Epitope," by Zhen-Yong Keck, Oakley Olson, Meital Gal-Tanamy, Jinming Xia, Arvind H. Patel, Marlène Dreux, and colleagues is presented.

An abstract of the article "Definition of a Conserved Immunodominant Domain on Hepatitis C Virus E2 Glycoprotein by Neutralizing Human Monoclonal Antibodies," by Zhen-Yong Keck, Ta-Kai Li, Jinming Xia, Meital Gal-Tanamy, Oakley Olson, Sophia H. Li, Arvind H. Patel, and colleagues is presented.