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We present new zircon U-Pb ages and Hf isotope compositions as well as whole-rock major- and trace-element geochemical and Sr-Nd isotopic data for silicic plutonic and volcanic rocks from the Duolong area of central Tibet. Combined with existing data, our new data indicate that these plutonic and volcanic rocks were formed in two stages ca. 120 Ma and ca. 110 Ma, respectively, in a postcollisional extensional setting that was triggered by slab breakoff. The similar geochemical compositions of granitoids and rhyolites, combined with their close spatial and temporal relationships, suggest that they were both derived from juvenile crustal material within a single magmatic system. We propose that the two inferred crustal melting events in the Duolong area were caused by two episodes of deep mantle activity triggered by the transition of the plate subduction angle from steep to shallow in response to the ascent of buoyant continental lithosphere during slab breakoff. Furthermore, rapid surface uplift during the late Early Cretaceous caused by slab breakoff made an important contribution to the formation of the proto–Tibetan Plateau. This study provides new insights into postcollisional tectonomagmatism and plateau uplift in central Tibet triggered by slab breakoff. We propose more generally that tectonic uplift during postcollisional processes (i.e., slab breakoff and lithospheric delamination) is a major contributor to plateau uplift in collision zones.

Supplementary methods, tables, figures and legends to figures Supplementary Figure 1. The structure of AB loops for sIFN-I and IFNα-2b and comparison on the sequences for sIFN-I and IFNα-21. Supplementary Figure 2. Quantification of phosphorylaiton of STAT1/3 in Figure 3C Supplementary Figure 3. Analysis of the cell surface IFNAR1 levels in the A549-IFNAR1-KO cell clones by FACS. Supplementary Figure 4. sIFN-I shows potent anti-solid tumor effect in immunocompromised mice models. Supplementary Figure 5. sIFN-I treatment decreases cell proliferation and induces senescence in vivo. Supplementary Figure 6. The antitumor effect of sIFN-I in immunocompetent tumor models. Supplementary Figure 7. FACS analysis of splenocytes from tumor-bearing mice treated with sIFN-I. Supplementary Table 1. Primer sequences used in this study. Supplementary Table 2. Primary antibodies used in this study. Supplementary Table 3. The pharmacokinetic index of human IFNα-2b or sIFN-I administered as in Figure 4B was analyzed by WinNonlin version 6.2 software.

Purpose: Antiproliferative, antiviral, and immunomodulatory activities of endogenous type I IFNs (IFN1) prompt the design of recombinant IFN1 for therapeutic purposes. However, most of the designed IFNs exhibited suboptimal therapeutic efficacies against solid tumors. Here, we report evaluation of the in vitro and in vivo antitumorigenic activities of a novel recombinant IFN termed sIFN-I.Experimental Design: We compared primary and tertiary structures of sIFN-I with its parental human IFNα-2b, as well as affinities of these ligands for IFN1 receptor chains and pharmacokinetics. These IFN1 species were also compared for their ability to induce JAK–STAT signaling and expression of the IFN1-stimulated genes and to elicit antitumorigenic effects. Effects of sIFN-I on tumor angiogenesis and immune infiltration were also tested in transplanted and genetically engineered immunocompetent mouse models.Results: sIFN-I displayed greater affinity for IFNAR1 (over IFNAR2) chain of the IFN1 receptor and elicited a greater extent of IFN1 signaling and expression of IFN-inducible genes in human cells. Unlike IFNα-2b, sIFN-I induced JAK–STAT signaling in mouse cells and exhibited an extended half-life in mice. Treatment with sIFN-I inhibited intratumoral angiogenesis, increased CD8+ T-cell infiltration, and robustly suppressed growth of transplantable and genetically engineered tumors in immunodeficient and immunocompetent mice.Conclusions: These findings define sIFN-I as a novel recombinant IFN1 with potent preclinical antitumorigenic effects against solid tumor, thereby prompting the assessment of sIFN-I clinical efficacy in humans. Clin Cancer Res; 23(8); 2038–49. ©2016 AACR.

A number of sediment-hosted, Carlin-type/-like gold deposits are distributed in the Youjiang basin of SW China. The gold ores are characterized by high As, Hg, and Sb contents but with low base metal contents (Cu+Pb+Zn &lt, 500&ndash, 1000 ppm). The Nibao deposit is unique among these gold deposits by having tennantite&ndash, tetrahedrite-series minerals in its ores. The deposit is also unique in being primarily hosted in the relatively unreactive siliceous pyroclastic rocks, unlike classic Carlin-type gold deposits that are hosted in carbonates or calcareous clastic rocks. In this study, we have identified tennantite-(Zn), tennantite-(Hg), and tetrahedrite-(Zn) from the tennantite&ndash, tetrahedrite-series mineral assemblage. The tennantite-(Zn) can be further divided into two sub-types of Tn-(Zn)-I, and Tn-(Zn)-II, Tn-(Zn)-I, usually occurs in the core of a Tennantite&ndash, tetrahedrite composite and appears the darkest under the SEM image, whereas Tn-(Zn)-II overgrows on Tn-(Zn)-I and is overgrown by tetrahedrite-(Zn). Tennantite-(Hg) occasionally occurs as inclusions near the uneven boundary between Tn-(Zn)-I and Tn-(Zn)-II. An appreciable amount of Au (up to 3540 ppm) resides in the tennantite&ndash, tetrahedrite-series minerals, indicating that the latter is a major Au host at Nibao. The coexistence of tennantite&ndash, tetrahedrite-series minerals and Au-bearing pyrite indicates the Nibao ore fluids were more oxidized than the Carlin-type ore fluids. The tennantite&ndash, tetrahedrite series at Nibao evolved from Tn-(Zn)-I through Tn-(Zn)-II to tetrahedrite-(Zn), which is likely caused by Sb accumulation in the ore fluids. This indicates that the Nibao ore fluids may have become more reduced and less acidic during Au precipitation.

The continuous model is introduced, and the nonlinear partial differential equations of taut-slack mooring line system are transferred to nonlinear algebraic equations through tanh method, and four solitary solutions are obtained further. At the same time, to express the results clearly, the curve surfaces of strains, displacements, and tension are plotted. The results show that there are four different solutions in the system. With the pretension increasing, the tension changes from one solitary solution to snap tension, and when the pretension is increased further, the curve converts to continuous line, until straight line, which is corresponding to the taut mooring line. In the process of increasing of pretension, the mooring line transfers from slack to taut, accompanied with tension skipping, which is reduced by the system parameters, and different combination of parameters may introduce different tension in line, and the uncertainty may cause the breakage of mooring system. The results have an agreement with experiment, which shows that the calculating method in this paper may be believable and feasible. This work may provide reference for design of mooring system.

Nibao is a unique thrust fault-controlled and strata-bound disseminated gold deposit in southwestern Guizhou Province, China. In Nibao, pyrite is the major sulfide mineral and Au is structurally bound (Au+) within the pyrite lattice. In this study, we conducted detailed analyses of the pyrite chemistry and S isotope composition in Nibao using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS), respectively. Through petrographic and pyrite chemical studies, four pyrite generations (Py1–Py4) were distinguished: framboidal pyrite (Py1, pre-ore sedimentary stage), clean pyrite overgrowing framboidal pyrite (Py2, pre-ore diagenetic stage), “spongy” pyrite (Py3, early ore stage), and overgrowth of narrow pyrite rims surrounding Py2/Py3 and disseminated pyrite associated with arsenopyrite (Py4, main ore stage). Among these, Py2 and Py4 are the most abundant. The trace element content in Py2 is characterized by a wide range of As, Cu, Sb, and Pb concentrations (~2480–58100 ppm, ~55.4–1610 ppm, ~29.1–232 ppm, and ~24.1–376 ppm, respectively), while Py4 has the highest Au, As, Cu, and Se contents (~70 ppm, ~4200, ~1630 ppm, and ~38.3 ppm, respectively). The δ34S values of pre-ore pyrites measured by LA-MC-ICP-MS in this study and the available data in the literature range broadly from −53.3 to 114.8‰, indicating that they were most likely generated by bacterial reduction from marine sulfate during sedimentation/diagenesis. Meanwhile, the δ34S values of ore pyrites have relative narrow δ34S values, mostly varying from −5 to 5‰, and indicating that the S was derived either from the average of sedimentary rocks or from a magmatic source. Since igneous rocks are scarce in the region and the exposed (~77–99 Ma) are clearly younger than the mineralization age of the Nibao gold deposit (~141 Ma), a magmatic source is unlikely in Nibao. All pyrites in this study show a positive correlation (R2 = 0.71) between Co and Ni, and the Co/Ni and Zn/Ni ratios of main stage Py4 are close to or within the range defined for a sedimentary–diagenetic origin, suggesting a sedimentary source is more likely in Nibao.

Background To explore the differences and correlations between the target volumes defined using preoperative prone diagnostic magnetic resonance imaging (MRI) and postoperative prone computed tomography (CT) simulation imaging based on deformable image registration (DIR) for external-beam partial breast irradiation (EB-PBI) after breast-conserving surgery (BCS). Methods Eighteen breast cancer patients suitable for EB-PBI were enrolled. Preoperative prone diagnostic MRI and postoperative prone CT scan sets for all the patients were acquired during free breathing. Target volumes and ipsilateral breast were all contoured by the same radiation oncologist. The gross tumor volume (GTV) delineated on the preoperative MRI images was denoted as the GTVpreMR and the tumor bed (TB) delineated on the postoperative prone CT images was denoted as the GTVpostCT. The MIM software system was used to deformably register the MRI and CT images. Results When based on the coincidence of the compared target centers, there were statistically significant increases in the conformity index (CI) and degree of inclusion (DI) values for GTVpostCT-GTVpreMR, GTVpostCT-CTVpreMR + 10, CTVpostCT + 10-GTVpreMR, and CTVpostCT + 10-CTVpreMR + 10 when compared with those based on the DIR of the thorax (Z = − 3.724, − 3.724, − 2.591, − 3.593, all P

Detection of community structures in complex networks is a common challenge in the study of complex networks. Recently, various methods have been proposed to discover community structures at different scales. Here, the multiscale methods based on Potts spin model for community detection are described and compared in the analysis of community structures of several networks. We give a critical analysis of the multiscale methods, showing a kind of limitation that the methods may suffer from when the community size difference is very broad, the breakup of (large) communities will appear before the merger of (small) communities disappears. In particular, we give the explicit expressions for the critical points of the merger and breakup of communities and derive the sufficient conditions (in the form of upper limits) that indicate when the Potts model methods suffer from the limitation. We apply the theoretical results to model networks and show that the method using the configuration null model (i.e., a random graph model as comparison that has the same degree distribution as the network under study) may not recover the full structure of the model network, whereas the method using the Erdös-Rényi null model will do so.

Purpose: Antiproliferative, antiviral, and immunomodulatory activities of endogenous type I IFNs (IFN1) prompt the design of recombinant IFN1 for therapeutic purposes. However, most of the designed IFNs exhibited suboptimal therapeutic efficacies against solid tumors. Here, we report evaluation of the in vitro and in vivo antitumorigenic activities of a novel recombinant IFN termed sIFN-I. Experimental Design: We compared primary and tertiary structures of sIFN-I with its parental human IFNα-2b, as well as affinities of these ligands for IFN1 receptor chains and pharmacokinetics. These IFN1 species were also compared for their ability to induce JAK–STAT signaling and expression of the IFN1-stimulated genes and to elicit antitumorigenic effects. Effects of sIFN-I on tumor angiogenesis and immune infiltration were also tested in transplanted and genetically engineered immunocompetent mouse models. Results: sIFN-I displayed greater affinity for IFNAR1 (over IFNAR2) chain of the IFN1 receptor and elicited a greater extent of IFN1 signaling and expression of IFN-inducible genes in human cells. Unlike IFNα-2b, sIFN-I induced JAK–STAT signaling in mouse cells and exhibited an extended half-life in mice. Treatment with sIFN-I inhibited intratumoral angiogenesis, increased CD8+ T-cell infiltration, and robustly suppressed growth of transplantable and genetically engineered tumors in immunodeficient and immunocompetent mice. Conclusions: These findings define sIFN-I as a novel recombinant IFN1 with potent preclinical antitumorigenic effects against solid tumor, thereby prompting the assessment of sIFN-I clinical efficacy in humans. Clin Cancer Res; 23(8); 2038–49. ©2016 AACR.

The aim of this study was to determine a method of dose prescription that minimizes normal tissue irradiation outside the planning target volume (PTV) during stereotactic body radiotherapy (SBRT) for patients with non-small cell lung cancer.Previous research and patients with typical T1 lung tumors with peripheral lesions in the lung were selected for analysis. A PTV and several organs at risk (OARs) were constructed for the dose calculated; six treatment plans employing intensity modulated radiotherapy (IMRT) were produced, in which the dose was prescribed to encompass the PTV, with the prescription isodose level (PIL) set at 50, 60, 70, 80, 90 or 95% of the isocenter dose. Additionally, four OARs around the PTV were constructed to evaluate the dose received in adjacent tissues.The use of higher PILs for SBRT resulted in improved sparing of OARs, with the exception of the volume of lung treated with a lower dose.The use of lower PILs is likely to create significant inhomogeneity of the dose delivered to the target, which may be beneficial for the control of tumors with poor conformity indices.

Mixed adenoneuroendocrine carcinoma (MANEC) is exceedingly rare with a poor outcome. In this article, we reported a MANEC in a 68-year-old woman with a symptom of abdominal pain and distension. MANEC derived from the ascending colon with highly aggressive behavior. The diagnosis and distinguish of MANEC must base on histological findings and immunohistochemical findings. In this case, microscopic observation showed tumor cells were arranged in conglobate and nested by fibrous tissue with a visible cell atypia and mitotic. NEC-like and exocrine glandular cells were also been seen in a single neoplasm. MANEC tissues were immunopositive for CK, CK20, P53, CK7, CDX-2, Ki-67 (70%+), E-cad, CD56, CEA, Syn, villin and CgA, and immunonegative for CA125, NSE, ER and PR. Here, the patient was treated by surgical operation and was followed-up near 3 months, no local recurrence and distant metastasis.

AIM: To investigate the association between nuclear β-catenin overexpression in rectal adenocarcinoma and radioresistance. METHODS: A retrospective analysis was conducted. The analysis involved 136 patients with locally advanced rectal adenocarcinoma who underwent short-course preoperative radiotherapy and radical resection. The expression of β-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry. The correlation of β-catenin expression with radioresistance was evaluated using the tumor regression grading (TRG) system. The relationship between β-catenin expression and clinicopathological characteristics was also analyzed. Univariate and logistic multivariate regression analyses were adopted to determine the independent factors of radioresistance. RESULTS: Nuclear β-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma (57.6% vs 16.7%, P < 0.001). Nuclear β-catenin was overexpressed in favor of poor TRG (≤ 2), whereas membrane β-catenin was expressed in favor of good TRG (≥ 3). Nuclear β-catenin expression in tumor cell differentiation (P = 0.018), lymph node metastasis (P = 0.022), and TRG (P < 0.001) showed significant differences. Univariate analyses demonstrated that radioresistance is associated with nuclear β-catenin overexpression (P < 0.001). In addition, logistic multivariate regression analysis indicated that only three factors, namely, tumor size (P < 0.001), tumor cell differentiation (P < 0.001), and nuclear β-catenin overexpression (P < 0.001), are associated with radioresistance. By using radioresistance as a prediction target, nuclear β-catenin-based prediction alone achieved 83% accuracy, 65% sensitivity, and 88% specificity. CONCLUSION: Nuclear β-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.