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The development of mobile computing and the Internet of Things (IoT) has led to a surge in traffic volume, which creates a heavy burden for efficient network management. The network management requires high computational overheads to make traffic classification, which is even worse when in edge networks; existing approaches sacrifice the efficiency to obtain high-precision classification results, which are no longer suitable for limited resources edge network scenario. Given the problem, existing traffic classification generally has huge parameters and especially computational complexity. We propose a lightweight traffic classification model based on the Mobilenetv3 and improve it for an ingenious balance between performance and lightweight. Firstly, we adjust the model scale, width, and resolution to substantially reduce the number of model parameters and computations. Secondly, we embed precise spatial information on the attention mechanism to enhance the traffic flow-level feature extraction capability. Thirdly, we use the lightweight multiscale feature fusion to obtain the multiscale flow-level features of traffic. Experiments show that our model has excellent classification accuracy and operational efficiency. The accuracy of the traffic classification model designed in our work has reached more than 99.82%, and the parameter and computation amount are significantly reduced to 0.26 M and 5.26 M. In addition, the simulation experiments on Raspberry Pi prove the proposed model can realize real-time classification capability in the edge network.

Biogenic quartz in the Upper Ordovician Wufeng Formation to Lower Silurian Longmaxi Formation (Wufeng– Longmaxi) shale layers in the Sichuan Basin and its periphery is qualitatively analyzed and quantitatively characterized by organic petrologic, mineralogic, and geochemical methods to find out the coupling effect between organic matter and quartz. (1) There are two types of biogenic quartz in the shale layers: Type I quartz is submicron quartz appearing in clusters around the organic matter. Type II quartz is in nano-scale grain size and floats in spherical shape on organic matter, with grains in point-to-point or surface-to-surface contact; this type of quartz is mainly biologic origin and slightly affected by hydrothermal activity in local parts. (2) The reservoirs in the Wufeng–Longmaxi formations is consistent in distribution with biogenic silica content in them, and mainly concentrated at the bottom of the Wufeng–Longmaxi formations, and is thinner in the Changning and Weiyuan regions, while thicker in the Fuling region. (3) The biogenic quartz in the Wufeng–Longmaxi shale worked through the entire evolution process of hydrocarbon generation. The presence of biogenic quartz can enhance the development of organic matter pores and microcracks, and can effectively preserve the organic matter pores and residual intergranular pores, forming “biological silicon intergranular pores, organic pores and micro-fractures”. This would benefit later hydraulic fracturing and result in high production/stable production of well. The coupling effect between biogenic quartz development and organic matter evolution and hydrocarbon generation is a critical factor for high-quality shale reservoir development.

In order to provide technical support for the shale gas exploration and development in the Lower Silurian Longmaxi Formation of the Sichuan Basin, this paper takes the Longmaxi Formation in the Changning and Fuling Shale Gas Fields as the research object to quantitatively characterize the development characteristics of natural fractures in the Longmaxi Formation shale by means of helium pycnometry, X-ray diffraction (XRD), true density testing and other methods, with the aid of the modified petrophysical model. Then, the development types and genetic mechanisms of natural fractures and their influences on shale gas development are discussed. The following research results are obtained. First, the modified petrophysical model can accurately describe the pore system in the Changning shale with a fitting rate of 0.74. Second, the development of natural fractures in shale is different in various regions. The natural fractures in the Changning Shale Gas Field, controlled by basement thrust faults, decollement layers and internal folds, are locally developed and filled with calcareous, and the average fracture porosity is 0.15%. In the Fuling Shale Gas Field, however, natural fractures, mainly controlled by reverse faults and slippage effect, are commonly more developed and unfilled or semi-filled with siliceous, and the average fracture porosity is 1.30%. Third, under the formation conditions, the opening of natural fractures is different. The natural fractures in the Changning Shale Gas Field are basically closed with weaker flowing ability, while those in the Fuling Shale Gas Field are relatively open with stronger flowing ability. Fourth, the occurrence mode of shale gas is influenced by natural fractures, and it is internally dominated by free gas. The initial gas production of shale gas wells is higher. In conclusion, (1) the regression coefficient is introduced to calculate the actual total organic matter content, which promotes the modified petrophysical model to describe matrix pores and fracture pores more accurately; (2) the development of natural fractures in the shale producing pay of the Sichuan Basin is relatively beneficial to shale gas enrichment and exploitation, but the flowing ability of the natural fractures will be weakened under the original formation conditions.

We developed a method based on the mechanically controllable break junction technique to investigate the electron transport properties of single molecular junctions upon fiber waveguided light. In our strategy, a metal-coated tapered optical fiber is fixed on a flexible substrate, and this tapered fiber serves as both the optical waveguide and metal electrodes after it breaks. For an imidazole bridged single-molecule junction, two probable conductance values below 1G0 are observed. The higher value shows an approximately 40% enhancement under illumination, while the lower one does not show distinguishable difference under illumination. Theoretical calculations reveal these two conductance values resulting from the imidazole monomer junction and the imidazole dimer junction linked via a hydrogen bond, respectively. In imidazole monomer junctions, the absorption of a single photon strongly shifts the transmission function resulting in optical-induced conductance enhancement. In contrast, the transmission function of imidazole dimer junctions remains at the same level in the bias window despite the light illumination. This work provides a robust experimental framework for studying the underlying mechanisms of photoconductivity in single-molecule junctions and offers tools for tuning the optoelectronic performance of single-molecule devices in situ.

Lung cancer is a major health concern and is influenced by air pollution, which can be affected by the density of urban built environment. The spatiotemporal impact of urban density on lung cancer incidence remains unclear, especially at the sub-city level. We aimed to determine cumulative effect of community-level density attributes of the built environment on lung cancer incidence in high-density urban areas.We selected 78 communities in the central city of Shanghai, China as the study site; communities included in the analysis had an averaged population density of 313 residents per hectare. Using data from the city cancer surveillance system, an age-period-cohort analysis of lung cancer incidence was performed over a five-year period (2009-2013), with a total of 5495 non-smoking/non-secondhand smoking exposure lung cancer cases. Community-level density measures included the density of road network, facilities, buildings, green spaces, and land use mixture.In multivariate models, built environment density and the exposure time duration had an interactive effect on lung cancer incidence. Lung cancer incidence of birth cohorts was associated with road density and building coverage across communities, with a relative risk of 1·142 (95 % CI: 1·056-1·234, P = 0·001) and 1·090 (95 % CI: 1·053-1·128, P0·001) at the baseline year (2009), respectively. The relative risk increased exponentially with the exposure time duration. As for the change in lung cancer incidence over the five-year period, lung cancer incidence of birth cohorts tended to increase faster in communities with a higher road density and building coverage.Urban planning policies that improve road network design and building layout could be important strategies to reduce lung cancer incidence in high-density urban areas.

Recently, shale gas research and industrial production in China have been significantly developed, which has enriched the theory of natural gas geology in China and increased the supply of domestic natural gas production. In the future, shale gas will obtain great achievements among the developments of the natural gas industry in China. The following four geological and geochemical issues about the exploration and research of shale gas have great significance: (1) China has to break through the single economic shale gas formation. The United States found at least thirty sets of economic shale gas formations in 29 basins. To date, only one basin in China (Sichuan Basin) has found one set of economic shale gas formation (Wufeng-Longmaxi formations). (2) In regards to the interval RO value of the economic shale gas formations and segment RO value of the gas fields, the interval RO values are 3.31% for the economic shale gas formation in China. However, it is 4.1% for that in the USA. The segment RO values are 2.34% for the gas fields in China and 3.5% for that in the USA. So the values are small in China, but big in the USA. Several shale gas fields derived from sapropelic sources in the United States were found in the oil generation window with RO = 1.0%–1.3%. Therefore, shale gas exploration in China also needs to pay attention to this stage. At the same time, attention should be paid to the exploration of shale gas derived from humic sources. (3) When it comes to the continuous high-yield period of the gas field, the world's first commercially developed shale gas field (Barnett) shows a high-yield forecast of 10 × 109 m3 per year for about twenty years. The development of the shale gas field in China is still in the construction stage. (4) In terms of the role of fracture in shale gas preservation and development, the fault has a dual effect on the enrichment of shale gas. In the United States, tectonic in the shale gas basin is stable, and faults are few, while structures in China in the shale gas basin are active, and faults are developed. Therefore, faults have more harm than good to the shale gas in China, which caused the fragmentation of the continuously distributed Wufeng-Longmaxi formations, limiting the area of the gas field.

The shales in the 2nd Member of Shanxi Formation in the east margin of the Ordos Basin were deposited in a marine-nonmarine transitional environment during the Permian. Based on the recent breakthroughs in the shale gas exploration and theoretical understandings on the shale gas of the study area, with a comparison to marine shale gas in the Sichuan Basin and marine-nonmarine transitional shale gas in the U.S., this study presents the geological characteristics and development potential of marine-nonmarine transitional gas in the study area. Four geological features are identified in the 2nd Member of the Shanxi Formation in the study area has: (1) stable sedimentary environment is conductive to deposition of widely distributed organic shale; (2) well-developed micro- and nano- scale pore and fracture systems, providing good storage capacity; (3) high content of brittle minerals such as quartz, leading to effectively reservoir fracturing; and (4) moderate reservoir pressure and relatively high gas content, allowing efficient development of shale gas. The 2nd Member of Shanxi Formation in the east margin of Ordos Basin is rich in shale gas resource. Three favorable zones, Yulin-Linxian, Shiloubei-Daning-Jixian, and Hancheng-Huangling are developed, with a total area of 1.28×104 km2 and resources between 1.8×1012 and 2.9×1012 m3, indicating a huge exploration potential. Tests of the 2nd Member of Shanxi Formation in vertical wells show that the favorable intervals have stable gas production and high reserves controlled by single well, good recoverability and fracability. This shale interval has sufficient energy, stable production capacity, and good development prospects, as evidenced by systematic well testing. The east margin of the Ordos Basin has several shale intervals in the Shanxi and Taiyuan formations, and several coal seams interbedded, so collaborative production of different types of natural gas in different intervals can be considered. The study results can provide reference for shale gas exploration and development and promote the rapid exploitation of shale gas in China.

The mechanism of cancer occurrence and development could be understood with multi-omics data analysis. Discovering genetic markers is highly necessary for predicting clinical outcome of lung adenocarcinoma (LUAD).Clinical follow-up information, copy number variation (CNV) data, single nucleotide polymorphism (SNP), and RNA-Seq were acquired from The Cancer Genome Atlas (TCGA). To obtain robust biomarkers, prognostic-related genes, genes with SNP variation, and copy number differential genes in the training set were selected and further subjected to feature selection using random forests. Finally, a gene-based prediction model for LUAD was validated in validation datasets.The study filtered 2071 prognostic-related genes and 230 genomic variants, 1878 copy deletions, and 438 significant mutations. 218 candidate genes were screened through integrating genomic variation genes and prognosis-related genes. 7 characteristic genes (RHOV, CSMD3, FBN2, MAGEL2, SMIM4, BCKDHB, and GANC) were identified by random forest feature selection, and many genes were found to be tumor progression-related. A 7-gene signature constructed by Cox regression analysis was an independent prognostic factor for LUAD patients, and at the same time a risk factor in the test set, external validation set, and training set. Noticeably, the 5-year AUC of survival in the validation set and training set was all ˃ 0.67. Similar results were obtained from multi-omics validation datasets.The study builds a novel 7-gene signature as a prognostic marker for the survival prediction of patients with LUAD. The current findings provided a set of new prognostic and diagnostic biomarkers and therapeutic targets.

Early pro-inflammatory signaling in the endocrine pancreas involves activation of NF-κB, which is believed to be important for determining the ultimate fate of β−cells and hence progression of Type 1 diabetes (T1D). Thus, early non-invasive detection of NF-κB in pancreatic islets may serve as a potential strategy for monitoring early changes in pancreatic endocrine cells eventually leading to T1D. We investigated the feasibility of optical imaging of NF-κB transcription factor activation induced by low-dose streptozocin (LD-STZ) treatment in the immunocompetent SKH1 mouse model of early stage diabetes. In this model we showed that the levels of NF-κB may be visualized and measured by fluorescence intensity of specific near-infrared (NIR) fluorophore-labeled oligodeoxyribonucleotide duplex (ODND) probes. In addition, NF-κB activation following LD-STZ treatment was validated by using immunofluorescence and transgenic animals expressing NF-κB inducible imaging reporter. We showed that LD-STZ treated SKH1 mice had significantly higher (2–3 times, p

Through the logically centralized control plane, software-defined network (SDN) provides giant convenience for the design of the network strategies, like load balancing, fault recovery, etc. However, when deploying those strategies on the data plane, transient link congestions may occur since the updating process among the distributed switches is asynchronous. To address this issue, we propose a congestion-aware mechanism for multi-flow updating in SDN. We first obtain the real-time traffic size of each flow to be updated through the link monitoring model. Then we use the congestion-aware algorithm to find the potential congested link and construct the dynamic dependency graph of the updating process, to generate the final updating sequence. Finally, the meter table is configured to limit the flow of crucial predecessor nodes that may have congestion deadlocks to mitigate the transient congestion.

With the development of data encryption technology, encrypted traffic has shown an explosive growth trend. More and more malicious network services rely on encryption to evade detection, which brings huge challenges to traditional rule-based traffic classification methods. In recent years, artificial intelligence technology provides feasible ideas to solve this problem. However, conventional machine learning depends on expert experience for manual feature extraction, and the training of deep learning models requires large number of high-quality labeled data, which makes the research of encrypted traffic detection hard to conduct. To address these issues, we propose a transfer learning method based on Efficientnet to detect the encrypted malicious traffic. Efficientnet-B0, a pre-trained model based on the Imagenet dataset, is transferred to an encrypted traffic dataset, extracting features automatically from the original traffic data without expert experience. The experimental results show that our method can achieve 100% detection accuracy and recall rate. Furthermore, our method can also achieve high detection performance with a small amount of training samples.

Introduction High-speed rail (HSR), with its remarkable time-space shrinkage, has potentially enlarged labour market catchment areas and encouraged inter-city commuting; much literature, however, links long-distance commutes with health risks. Methods This study develops a conceptual framework in which a set of HSR-informed independent variables (shift in long-commute modes, transfer modes and travel time to and from HSR stations, job prospects and living conditions, and socio-economic attributes) are explored to discern physical and mental health variations. Ordinal logistic regression models are used to analyse 288 questionnaire samples from a cross-sectional study of HSR commuters travelling between Suzhou and Shanghai, China. Results Gaining insight into factors associated with HSR commuters’ physical and mental health, the findings from descriptive analyses reveal a slightly negative association. While travel-related instrumental factors (shift long commute from non-HSR to HSR, active transfer modes, shorter travel times to and from HSR stations) and noninstrumental factors (intimate family and social relationships) show significantly positive health benefits, commuters, such as technicians and professionals, with low rent/mortgage levels (implying lower quality of residence and relative inability to afford home ownership), report significantly negative associations with their health. Conclusion This paper concludes that HSR commuting requires personal commitment and a healthy work/life balance. Association with physical and mental health reflects a combination of structural inequality and personal travel experiences and living conditions. To promote the health of HSR commuters, a coordinated spatial-economic strategy at the mega-city regional level should be implemented to improve distribution of employment opportunities and consider users’ perspectives on long-distance commuting, taking a holistic approach to door-to-door travel, infrastructure provision, and services operation.

Effective control of the COVID-19 pandemic via appropriate management of the built environment is an urgent issue. This study develops a research framework to explore the relationship between COVID-19 incidence and influential factors related to protection of vulnerable populations, intervention in transmission pathways, and provision of healthcare resources. Relevant data for regression analysis and structural equation modeling is collected during the first wave of the pandemic in the United States, from counties with over 100 confirmed cases. In addition to confirming certain factors found in the existing literature, we uncover six new factors significantly associated with COVID-19 incidence. Furthermore, incidence during the lockdown is found to significantly affect incidence after the reopening, highlighting that timely quarantining and treating of patients is essential to avoid the snowballing transmission over time. These findings suggest ways to mitigate the negative effects of subsequent waves of the pandemic, such as special attention of infection prevention in neighborhoods with unsanitary and overcrowded housing, minimization of social activities organized by neighborhood associations, and contactless home delivery service of healthy food. Also worth noting is the need to provide support to people less capable of complying with the stay-at-home order because of their occupations or socio-economic disadvantage.

The dynamic factors affecting the carbon fiber industry are computed on the basis of the maximum entropy configuration model of objective index weight based on grey class sensitivity coefficient (G-MEC model for short), which determines the importance of each dynamic factor to the development of carbon fiber industry. Firstly, classes of evaluation objects are preset, based on which grey class sensitivity coefficient is defined to reveal various influences of evaluation index on the classification of the evaluation objects, which is used to characterize and measure the relative importance of evaluation index on evaluation objects and the whole system. In view of military strategic background, carbon fiber industry has the characteristic of poor data information. In this case, a G-MEC model is constructed and solved to give objective weight to the evaluation index influencing the classification results. Finally, this paper, taking the carbon fiber industry of Jiangsu province, China, as an example, ranks the driving factors of carbon fiber industry. Based on the results and analyses, a series of constructive suggestions are put forward to promote the sustainable development of carbon fiber industry.

Constitutively activated signal transducer and activator of transcription 3 (STAT3) factor is an important therapeutic target in head and neck cancer (HNC). Despite early promising results, a reliable systemic delivery system for STAT3- targeted oligonucleotide (ODN) drugs is still needed for future clinical translation of anti-STAT3 therapies. We engineered and tested a novel ODN duplex/gold nanoparticle (AuNP)-based system carrying a therapeutic STAT3 decoy (STAT3d) payload. This strategy is two-pronged because of the additive STAT3 antagonism and radiosensitizing properties of AuNP. The specificity to head and neck cancer cell surface was imparted by using a nucleolin aptamer (NUAP) that was linked to AuNP for taking the advantage of an aberrant presentation of a nuclear protein nucleolin on the cell surface. STAT3d and nucleolin aptamer constructs were independently linked to AuNPs via Au-S bonds. The synthesized AuNP constructs (AuNP-NUAP-STAT3d) exhibited internalization in cells that was quantified by using radiolabeled STAT3d. AuNP-NUAP-STAT3d showed radiosensitizing effect in human HNC FaDu cell culture experiments that resulted in an increase of cell DNA damage as determined by measuring γ-H2AX phosphorylation levels by flow cytometry. The radiosensitization study also demonstrated that AuNP-NUAP-STAT3d as well as STAT3d alone resulted in the efficient inhibition of A431 cell proliferation. While FaDu cells did not show instant proliferation inhibition after incubating with AuNP-NUAP-STAT3d, the cell DNA damage in these cells showed nearly a 50% increase in AuNP-NUAP-STAT3d group after treating with radiation. Compared with anti-EGFR humanized antibody (Cetuximab), AuNP-NUAP-STAT3d system had an overall stronger radiosensitization effect in both A431 and FaDu cells.

The ongoing coronavirus disease (COVID-19) pandemic has had a far-reaching impact on urban living, prompting emergency preparedness and response from public health governance at multiple levels. The Chinese government has adopted a series of policy measures to control infectious disease, for which cities are the key spatial units. This research traces and reports analyses of those policy measures and their evolution in four Chinese cities: Zhengzhou, Hangzhou, Shanghai and Chengdu. The theoretical framework stems from conceptualisations of urban governance and its role in public health emergencies, wherein crisis management and emergency response are highlighted. In all four cities, the trend curves of cumulative diagnosed cases, critical policies launched in key time nodes and local governance approaches in the first wave were identified and compared. The findings suggest that capable local leadership is indispensable for controlling the coronavirus epidemic, yet local governments’ approaches are varied, contributing to dissimilar local epidemic control policy pathways and positive outcomes in the fight against COVID-19. The effectiveness of disease control is determined by how local governments’ measures have adapted to geospatial and socioeconomic heterogeneity. The coordinated actions from central to local governments also reveal an efficient, top-down command transmission and execution system for coping with the pandemic. This article argues that effective control of pandemics requires both a holistic package of governance strategies and locally adaptive governance measures/processes, and concludes with proposals for both a more effective response at the local level and identification of barriers to achieving these responses within diverse subnational institutional contexts.

Pairs of electrodes with nanometer gap, termed as nano-gapped electrodes, are fundamental building blocks for the fabrication of nanometer-sized devices and are essential for the examination of molecular properties and extreme nano-optics. Although modern fabrication techniques make it feasible to fabricate nanometer gaps, it is still a formidable challenge to fabricate adjustable gaps arrays with angstrom precision. Here, we demonstrate that in-situ adjustable nanogaps (arrays) with sub-angstrom precision can be fabricated via laser irradiation on the substrate which supports the electrode pairs. We further demonstrate that atomic-level metal contacts can be switched and the direction of the switching can be selectively controlled by the laser irradiation position. By varying the laser power gradually, the nanogap’s size can be continuously changed, providing a reliable break junction technique to address the properties of single-molecule junctions. The small spatial focus size of the laser beam makes it feasible to realize addressable on-chip molecular junction arrays.

Urban green space (UGS) plays an important role in maintaining and promoting public health because it provides opportunities for outdoor physical activities (PA). Many studies have proved that different UGS characteristics, such as area, shape, distance, etc., have a certain impact on the intensity or frequency of PA. It is noteworthy that most studies are completed on a city scale, which explains how ensemble characteristics of a park affect PA. However, few researchers have explored the relations between UGS features and physical activities at the parcel level. To address this gap, this study has investigated the effect of multiple features of UGS on the diversity of PA, with downtown Shanghai as the study site. To identify types of PA and features of UGS based on on-site observation of a total of 101 sites in five urban parks located in a central district of Shanghai, China, we established an ordinal logistic regression with total types of PA (PA diversity hereafter) as the dependent variable and UGS characteristics as independent variables. The results show that green coverage ratio and diversity of shrubs are positively related to PA diversity, while diversity of trees has an inverse impact. Moreover, the paved area shape index and green view ratio are negatively correlated with PA diversity, which suggests that the irregular shape of paved areas with winding edges and excessive green view ratio are factors detrimental to PA diversity. These findings provide pertinent guidance in the design of UGS for the promotion of PA.

Pleiotropic and evolutionally conserved components of transcription nuclear factor - NF-B play key roles in progression of various diseases by regulating expression of antiapoptotic and cytokine responsive genes [1] [2]. We previously demonstrated that rapidly activating transcription factors (TF) can be detected by using sequence-specific self-quenched reporter probes (oligonucleotide-molecular sensors (ODN-MS), which ideally remain “silent” in the absence of activated TF but emit photons upon specific binding to them [3-5]. Recently we were investigating sensor-based optical imaging of early inflammation in the endocrine pancreas using type 1 diabetes (T1D) model because NF-κB activation is essential for determining the fate of pancreatic β-cells and hence the progression of T1D. Using an immunocompetent SKH1 mouse model of early stage T1D we showed that NF-κB activation was induced by low-dose streptozotocin (LD-STZ). ODNMS probes that carried near-infrared (NIR) fluorophores formed a complex with NF-κB subunits in in vitro assays and in situ after LD-STZ treatment. Imaging studies of pancreas (sections and isolated islets) were corroborated with electrophoresis mobility shift assays (EMSA). A higher specific NIR fluorescence intensity in nuclei and cytoplasm of islets from LD-STZ treated groups compared to non-treated control animals was observed. Our results demonstrate that: 1) the use of ODN-MS probes in non-fixed islets and tissue sections may be used for distinguishing differences in inflammatory pathway activation in animal models of early stage diabetes; 2) early, non-invasive detection of NF-κB in pancreatic islets may serve as a potential strategy for imaging of early T1D-mediated sustained pro-inflammatory changes in the endocrine pancreas.

The rapid development of the Internet has also brought opportunities for some illegal elements. Network attackers steal sensitive information from victims through phishing webpages to obtain economic benefits. Currently, the commonly used detection methods for phishing webpages, based on blacklist detection and webpage content feature detection, have the problems of being unable to detect newly emerging phishing webpages or requiring manual extraction of webpage features. Therefore, researchers have used Convolution Neural Network (CNN) to detect phishing webpages by automatically extracting URL features. However, its method has some limitations: (1) The memory is limited when the URL is transformed into the feature matrix, and the embedding vector of new words cannot be obtained or the effective information of sensitive words is lost; (2) the long-distance dependent feature of the URL cannot be obtained. In response to the above challenges, we proposes a phishing detection method based on CNN and Bi-directional Long Short-Term Memory (Bi-LSTM) based on existing work: based on sensitive word segmentation-- comprehensively using two existing URL segmentation methods before converting URL into eigenvector matrix; adding Bi-LSTM on the basis of convolutional neural network to obtain URL long-distance dependent features. Experimental results show that this method can achieve high accuracy, recall rate and F1 value.

China has become the second-largest producer of shale gas after the United States. This paper aims to explore other unique factors resulting in China's success by reviewing the history and experience of Chinese developers. The following findings were obtained. (1) The development of shale gas is less related to company size and is more related to a company's goals and motivations. (2) Construction of state-level demonstration zones is an efficient way to accelerate shale gas development. (3) Hopes for opening the shale gas market by auctions were dashed in China. (4) Technology localization is the key to shale gas development.

As the number of diagnostic and therapeutic applications utilizing gold nanoparticles (AuNPs) increases, so does the need for AuNPs that are stable in vivo, biocompatible, and suitable for bioconjugation. We investigated a strategy for AuNP stabilization that uses methoxypolyethylene glycol-graft-poly(l-lysine) copolymer (MPEG-gPLL) bearing free amino groups as a stabilizing molecule. MPEG-gPLL injected into water solutions of HAuCl4 with or without trisodium citrate resulted in spherical (Zav = 36 nm), monodisperse (PDI = 0.27), weakly positively charged nanoparticles (AuNP3) with electron-dense cores (diameter: 10.4 ± 2.5 nm) and surface amino groups that were amenable to covalent modification. The AuNP3 were stable against aggregation in the presence of phosphate and serum proteins and remained dispersed after their uptake into endosomes. MPEG-gPLL-stabilized AuNP3 exhibited high uptake and very low toxicity in human endothelial cells, but showed a high dose-dependent toxicity in epithelioid cancer cells. Highly stable radioactive labeling of AuNP3 with (99m)Tc allowed imaging of AuNP3 biodistribution and revealed dose-dependent long circulation in the blood. The minor fraction of AuGNP3 was found in major organs and at sites of experimentally induced inflammation. Gold analysis showed evidence of a partial degradation of the MPEG-gPLL layer in AuNP3 particles accumulated in major organs. Radiofrequency-mediated heating of AuNP3 solutions showed that AuNP3 exhibited heating behavior consistent with 10 nm core nanoparticles. We conclude that PEG-pPLL coating of AuNPs confers "stealth" properties that enable these particles to exist in vivo in a nonaggregating, biocompatible state making them suitable for potential use in biomedical applications such as noninvasive radiofrequency cancer therapy.

On the basis of the topographical and landscape features in Zimbabwe, an ultra-low density regional geochemical survey was conducted over all of Zimbabwe using stream sediment sampling of catchment basins. Sampling methods, elements to be determined and analytical methods for the ultra-low density survey of Zimbabwe are discussed. Regional geochemical maps were compiled based on the sample data and the features of the catchment basins, and the characteristic parameters of the geochemical background throughout Zimbabwe were calculated and are presented. The result of the nationwide geochemical mapping in Zimbabwe was evaluated. A summary of the features of the nationwide ultra-low density geochemical background in Zimbabwe is presented, a preliminary analysis was performed on the distribution of mineral resources and the geochemical provinces in Zimbabwe, and regional prospecting problems are discussed.

Three oligodeoxyribonucleotides (ODN) covalently labeled with near-infrared (NIR) fluorochromes were synthesized and characterized with a goal of comparing in vitro a hairpin-based and a duplex-based FRET probe designed for the detection of human recombinant NF-κB p50/p65 heterodimer binding to DNA. Using deoxyguanosine phosphoramidite with a phosphorus-linked aminoethylene (diethylene glycol) hydrophilic linker, we synthesized ODNs with internucleoside reactive sites. The hairpin loop amino linker was modified with IRDye 800CW (FRET acceptor), and the 3'-end was modified with Cy5.5 (FRET donor) using a dithio-linker. To obtain a duplex probe, we conjugated Cy5.5 and 800CW to complementary strands at the distance of ten base pairs in the resultant duplex. No quenching of dyes was observed in either probe. The FRET efficiency was higher in the duplex (71%) than in the hairpin (56%) due to a more favorable distance between the donor and the acceptor. However, the hairpin design allowed more precise ratiometric measurement of fluorescence intensity changes as a result of NF-κB p50/p65 binding to the probe. We determined that as a result of binding there was a statistically significant increase of fluorescence intensity of Cy5.5 (donor) due to a decrease of FRET if normalized by 800CW intensity measured independently of FRET. We conclude that the hairpin based probe design allows for the synthesis of a dual fluorescence imaging probe that renders signal changes that are simple to interpret and stoichiometrically correct for detecting transcription factor-DNA interactions.

Pretargeting with bivalent effectors capable of bridging antitumor antibodies (affinity enhancement pretargeting) has been reported to provide superior results by affinity enhancement. Phosphorodiamidate morpholinos (MORFs) and other DNA analogues used for pretargeting are ideally suited as bivalent effectors since they are easily synthesized and the distance between binding regions, a determinant of binding, may be adjusted simply by lengthening the chain. We have shown by surface plasmon resonance that bivalent MORFs will provide superior affinity enhancement provided that suitable spacing exists between the binding regions. The goals of this study were to synthesize a bivalent MORF with a MAG(3) group attached for technetium-99m ((99m)Tc) radiolabeling, investigate whether the bivalent MORF showed improved cell accumulation in culture compared to its corresponding monovalent MORF and compare biodistributions in normal mice and in pretargeted tumored mice. An excess of an amine derivatized 18 mer MORF with 6 nonbinding bases for spacing was reacted with Fmoc-l-beta-homoglutamic acid to form duplexes via their carboxylate groups and, after deprotection, conjugated with NHS-MAG(3) to attach the chelator. The anti-CEA antibody MN14 was conjugated with a 12 mer complementary MORF (i.e., cMORF). The binding behavior between radiolabeled monovalent and bivalent MORFs was compared in LS174T tumor cells at 4 degrees C pretargeted with MN14-cMORF. Biodistributions of radiolabeled monovalent and bivalent MORFs at 3 h postadministration were measured in normal mice and in tumor mice pretargeted with MN14-cMORF. In the pretargeted cells in culture, the accumulation of the bivalent MORF was significantly higher than the monovalent MORF (p = 0.002), thus providing strong evidence for affinity enhancement. In normal mice, whole body clearance of the bivalent and monovalent MORFs was equally rapid. In tumored mice, tumor accumulation of the radiolabeled bivalent MORF was significantly higher than that of the monovalent MORF. In conclusion, a bivalent MAG(3)-MORF was successfully synthesized and radiolabeled with (99m)Tc. While a pharmacokinetic effect for the higher tumor accumulations in pretargeted mice of the radiolabeled bivalent MORF cannot be excluded, the results may be best explained by affinity enhancement. Thus two monovalent MORFs were covalently conjugated into a bivalent MORF effector to improve tumor targeting by both pharmacokinetics and affinity enhancement influences.

We previously developed prototype oligodeoxyribonucleotide (ODN) duplex fluorescence energy transfer (FRET) reporters for optical sensing of NF-κB transcription factor. We report here a plate-binding assay designed for optimizing the above reporters. Nitrilotriacetate-bearing plates were prepared by using either sequential 1) aminosilylation; 2) carboxylation; 3) coupling of Nα,Nα-bis(carboxymethyl)-L-lysine or, alternatively, by replacing steps 1 and 2 by treating the glass with 3-(triethoxysilyl)propylsuccinic anhydride. FRET reporters were obtained by covalent linking of Cy5.5 (fluorescence donor) and IRdye800CW (fluorescence acceptor) to complementary ODN strands encoding a high affinity p50 binding site. Recombinant 6xHis tagged NF-κB p50 was used for immobilizing the protein on glass plates via linked NTA-Ni(II) groups. Imaging and quantification of the fluorescence intensity in the wells was performed in two channels (700 and 800 nm) using a near-infrared scanning device with microscopic resolution. The fluorescence intensity of the ODN duplex reporter was detectible in the plates at the concentration of 5 pM. NF-κB p50-ODN reporter interaction was studied by measuring the ratio of 700 nm (donor) to 800 nm (acceptor) fluorescence intensities. Using the plate assay we were able to measure p50-mediated interference with FRET at low density of plate binding.