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Internet of Things (IoT) techniques have been employed in many areas, e.g., vehicles, smart home, and medicine. Among the applications of IoTs, the Internet of Vehicles (IoV) is one of the most popular techniques. IoVs are protected by public key cryptographic systems, such as RSA and ECC. However, such systems are vulnerable to quantum computer attacks. Thus, we improve the security of IoV-based post-quantum signatures, which can resist quantum computer attacks. The key operations are divisions in a finite field. Hence, we improve the security of IoV-based post-quantum signatures with division by employing systolic architectures. We propose a systolic architecture for computing division in composite fields. After that, we improve the IoT security-based post-quantum signatures with systolic divisions. We test and verify our design on a Field-Programmable Gate Array (FPGA); the experimental results confirm our estimates. Furthermore, the optimized method proposed can be further applied to various applications like solving system of linear equations and cryptographic applications for IoT security.

PDF file - 85K, Relationship between TP53 (A) or KRAS (B) gene status and TAK 960 concentration producing EC50 values. Each data point represents a mean concentration producing 50% efficacy (EC50) value for TAK 960 in an individual cell line.

PDF file - 144K, Comparison of dosing regimens.

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Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase involved in key processes during mitosis. Human PLK1 has been shown to be overexpressed in various human cancers, and elevated levels of PLK1 have been associated with poor prognosis, making it an attractive target for anticancer therapy. TAK-960 [4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl) benzamide] is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1). Consistent with PLK1 inhibition, TAK-960 treatment caused accumulation of G2–M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3) in vitro and in vivo. TAK-960 inhibited proliferation of multiple cancer cell lines, with mean EC50 values ranging from 8.4 to 46.9 nmol/L, but not in nondividing normal cells (EC50 >1,000 nmol/L). The mutation status of TP53 or KRAS and MDR1 expression did not correlate with the potency of TAK-960 in the cell lines tested. In animal models, oral administration of TAK-960 increased pHH3 in a dose-dependent manner and significantly inhibited the growth of HT-29 colorectal cancer xenografts. Treatment with once daily TAK-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model. TAK-960 has entered clinical evaluation in patients with advanced cancers. Mol Cancer Ther; 11(3); 700–9. ©2011 AACR.

PDF file - 130K, Anti-tumor activity of TAK-960 in MV4-11luc disseminated leukemia model.

The blood-brain barrier (BBB) plays a critical role in preventing harmful endogenous and exogenous substances from penetrating the brain. Optimal brain penetration of small molecule CNS drugs is characterized by a high unbound brain/plasma ratio (Kp,uu). While various medicinal chemistry strategies and in silico models have been reported to improve BBB penetration, none were developed to predict Kp,uu directly. We describe a physics-based computational approach, solvation free energy calculations (energy of solvation or E-sol), to predict Kp,uu. Prospective application of this method to internal CNS drug discovery programs highlighted the utility and accuracy of this new method, which showed a categorical accuracy of 79% and a R2 of 0.61 from a linear regression model.

The generation frequency of grid-connected units determines the power supply reliability of the grid and primary frequency regulation, as the first guarantee to stabilize the grid frequency is affected by the category of generating units and operation mode and lacks systematic real-time optimization and monitoring means. This paper takes a 300MW sub-critical heating unit as the research object, and researches, and analyzes three aspects of signal homologation, multi-dimensional optimization, and intelligent decision-making to establish the evaluation model of the primary frequency regulation capability of the unit. The evaluation accuracy of the assessment model reaches 83%, develops the control platform based on autonomous controllable PLC, realizes intelligent dynamic control and the replacement of traditional optimization technology means, also improves the qualification rate of primary frequency regulation by about 23.2%.

This paper is concerned with the outer exponential synchronization of the drive-response complex dynamical networks subject to time-varying delays. The dynamics of nodes is complex valued, the interactions among of the nodes are directed, and the two coupling matrices in the drive system and the response system are also different. The intermittent pinning control is proposed to achieve outer exponential synchronization in the aperiodical way. Some novel sufficient conditions are derived to guarantee outer exponential synchronization of the considered complex-valued complex networks by using the Lyapunov functional method. Finally, two numerical examples are presented to illustrate the effectiveness of the proposed control protocols.

Histone demethylase LSDl (KDMlA) belongs to the flavin adenine dinucleotide (FAD) dependent family of monoamine oxidases and is vital in regulation of mammalian biology. Dysregulation and overexpression of LSD1 are hallmarks of a number of human diseases, particularly cancers that are characterized as morphologically poorly differentiated. As such, inhibitors of LSD1 have potential to be beneficial as a cancer therapy. The most clinically advanced inhibitors of LSDl are covalent inhibitors derived from tranylcypromine (TCP). Herein, we report the discovery of a novel series of reversible and selective LSDl inhibitors. Exploration of structure-activity relationships (SARs) and optimization of ADME properties resulted in the identification of clinical candidate CC-90011. CC-90011 exhibits potent on-target induction of cellular differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cell lines, and antitumor efficacy in patient-derived xenograft (PDX) SCLC models. CC-90011 is currently in phase 2 trials in patients with first line, extensive stage SCLC (ClinicalTrials.gov identifier: NCT03850067).

Human islet amyloid polypeptide (hIAPP, also known as amylin) is a co-secreting protein of insulin in human pancreatic β-cells. It is encapsulated in vesicles and secreted out of the cells with insulin. hIAPP can promote insulin secretion and regulate blood glucose homeostasis in the body under the normal physiological conditions. However, hIAPP misfolding or excessive accumulation can cause toxic effects on the β cells, which in turn affect cell function, resulting in type 2 diabetes mellitus (T2DM) for the affected individuals. In order to eliminate the excessive accumulation of hIAPP in the cell and to maintain its normal synthetic function, we have adopted a new protein degradation technology called Trim-Away, which can degrade the target protein in a short time without affecting the mRNA transcription and translation synthesis function of the target protein. First, we overexpressed hIAPP in the rat insulinoma cells (INS1) to simulate its excessive accumulation and analyzed its effect in INS1 cells by measuring the release of LDH (lactate dehydrogenase), CCK8 activity and PI-Annexin V positive ratio. Results showed that excessive accumulation of hIAPP caused β cell apoptosis. Second, real-time quantitative PCR analysis and ELISA detection showed that the synthesis and secretion of insulin were hindered. We used Trim-Way technology to specifically eliminate the excessive accumulation of hIAPP protein in hIAPP overexpressing INS1 cells. Cell activity experiments confirmed that clearance of hIAPP reduced the cell death phenotype. Further ELISA experiments confirmed that INS1 cells restored insulin secretion ability. This study examined the toxic effect of hIAPP excessive accumulation in INS1 cells and demonstrated the cytotoxicity clearance effect of Trim-Way technology in pancreatic β-cells. Our research has provided a new strategy for using Trim-Away technology for treatment of diabetes.人胰岛淀粉样多肽(human islet amyloid polypeptide, hIAPP)又称胰淀素(Amylin),是胰岛β细胞中胰岛素的共分泌蛋白,与胰岛素共同包裹在囊泡中被分泌出细胞。正常生理条件下,hIAPP有助于胰岛素分泌并调节机体血糖平衡;但其蛋白错误折叠或过量积累则会对细胞造成毒性,进而影响β细胞功能,导致机体罹患2型糖尿病(type 2 diabetes mellitus, T2DM)。为了清除细胞内过度积累的hIAPP,且不影响其正常的合成功能,本研究选用一种新的蛋白质降解技术——Trim-Away,该技术可以在短时间内降解目标蛋白质,且不会对靶蛋白的mRNA转录、翻译等功能产生影响。首先在大鼠(

Among Internet of Things (IoTs), cloud-based IoTs help retain the confidentiality of both device-to-cloud and cloud-to-device messages by setting up individual identities and credentials for each IoT devices. As recently been emphasized by two American institutes, National Institute of Standards and Technology (NIST) and National Security Agency (NSA), cloud-based IoTs that use RSA and ECC signatures are insecure under quantum computer attacks. To ensure the security in the cloud-based IoTs under quantum computer attacks, there is a critical need for implementations of new quantum-resistance signature systems, such as Unbalanced Oil and Vinegar (UOV), for making the cloud-based IoTs more secure and reliable. In order to analyze the security of UOV for cloud-based IoTs, we present an efficient algorithm based on side channel analysis of UOV, which combines inducing faults and Hamming distance power analysis. We implement UOV signature schemes on Sakura-G FPGA board via using Verilog-HDL code and Xilinx ISE software, where the power collection uses a 350 MHz Keysights oscilloscope. Based on the experimental results, we successfully recover all the secret keys of UOV signature, which shows that we should protect UOV and related signatures against side channel attacks when they are adopted in cloud-based IoTs.

This paper presents the exponential synchronization of complex dynamical networks, in which the dynamics of nodes is complex-valued, the interactions among of the nodes are directed, and subject to time-varying delays. The aperiodically intermittent pinning control is proposed to achieve synchronization. Based on the Lyapunov functional method, complex-valued differential equations, stability theory, matrix theory and modern control technique, some novel sufficient conditions are derived to guarantee exponential synchronization of the proposed complex-valued dynamical directed networks. To illustrate the effectiveness of the theoretical results, some numerical examples are finally given.

The Internet of Medical Things (IoMTs) are the group of medical devices connected to Internet, to perform the processes and services that support healthcare. The amount of data handled by medical devices grows exponentially, which means higher exposure of personal sensitive data. RSA, ECC and, other related public key cryptographic systems with countermeasures of power analysis and fault analysis, e.g., random masking, are often adapted by medical devices for guaranteing security and privacy. However, Shor algorithm has proven that they are not secure to quantum computer attacks. Fortunately, there exists a few quantum-resistant public key cryptographic schemes, e.g., Rainbow. To ensure end-to-end service delivery in the IoMTs under quantum attacks, there is a critical need for research into new designs and evaluation for the hardware security of new quantum-resistance cryptographic systems, e.g., rainbow, to make the medical devices more secure and reliable. Therefore, we present a physical analysis model of Rainbow by combining fault analysis and differential power analysis. The proposed model is implemented on cloud computing platform. Based on the experimental results, we successfully recover all the secret keys of Rainbow signature, which shows the importance of protecting multivariate signature with countermeasures on medical devices.

In order to improve MQ cryptographic systems on Internet of Things (IoTs) devices, we propose an efficient hardware architecture of Gaussian Elimination in finite fields where area usage is more of a priority. In order to validate our design and verify its effectiveness, an experiment is carried out by using TSMC-0.18 µ m standard cell CMOS Application Specific Integrated Circuit (ASIC), which shows that our design is well suit for MQ cryptographic systems.

Secure storage devices are a good example of the Internet of Things (IoTs), which require secure access control mechanisms via using the prominent pubic key cryptographic systems, e.g. RSA, ECC and related systems. However, quantum computer is in a position to attack RSA, ECC and other signature algorithms adopted by many storage devices. Therefore, storage security is facing severe threats. In this paper, an efficient hardware architecture based on multivariate scheme for storage devices is proposed. Multivariate scheme belongs to multivariate public key cryptography (MPKC), which uses affine transformations and central map transformations during cryptographic operations. The advantage of adopting multivariate scheme is that multivariate scheme is immune to quantum computer attack. The efficient hardware architecture is composed of processor module, cryptographic module, storage module, display module, power module, keyboard module, export module and terminal module (off-chip). We implement the hardware architecture on the methodology of TSMC-0.18 μm standard cell CMOS Application Specific Integrated Circuit. The implementation results show that the architecture based on multivariate scheme is very efficient and well suit for storage devices.

Here, the exponential synchronization about mean square problem of two complex dynamical networks with stochastic perturbations is investigated. A novel drive-response complex network model is formulated which is linear coupling with both time-varying delay and non-delay, meanwhile, this model also includes stochastic perturbations of vector-form. Based on the Lyapunov steady theory, stochastic differential equations, and matrix theory, several effective synchronous conditions are obtained to ensure exponential synchronization in mean square of the proposed complex dynamical networks by periodically intermittent pinning. Finally, several numerical simulations are performed to verify the theoretical results and the control methodology.

Introduction: MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a key mediator of the NF-κB signaling pathway, the main driver of a subset of B-cell lymphomas and functions by forming a complex with CARMA1 and BCL10 to mediate antigen receptor-induced lymphocyte activation. MALT1 is considered a potential therapeutic target for several subtypes of non-Hodgkin B-cell lymphomas and chronic lymphocytic leukemia (CLL). Previously, we described the discovery of novel and potent MALT1 inhibitors with anti-proliferative effects in non-Hodgkin B-cell lymphoma cells. Here, we highlight the strong anti-tumor activity of our MALT1 inhibitors across multiple tumor models and the combination potential with agents including standard-of-care. Results: Novel small molecule MALT1 inhibitors were identified using Schrodinger's proprietary physics-based free energy perturbation (FEP+) modeling technology. These molecules demonstrate strong MALT1 protein binding affinity, potent inhibition of MALT1 enzymatic activity and anti-proliferative activity in the activated B-cell (ABC) subtype of diffuse large B cell lymphoma (DLBCL) cell lines such as OCI-LY3 and OCI-LY10. In combination with approved agents, these inhibitors demonstrate strong combination potential with Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib in ABC-DLBCL cell lines. In ABC-DLBCL CDX models, our representative MALT1 inhibitor induces tumor regression as a single agent and complete tumor regression in combination with ibrutinib. Our representative MALT1 inhibitor, when tested in LY2298 PDX models, demonstrates similar results. In addition, our representative MALT1 inhibitor was explored in a CDX model derived from a Mantle cell lymphoma REC-1 cell line, and demonstrates strong anti-tumor activity of ~78% tumor growth inhibition (TGI) as a single agent. Conclusions: Schrodinger's novel, potent MALT1 protease small molecule inhibitors are efficacious in in vitro B-cell lymphoma cell proliferation assays and in in vivo B-cell lymphoma xenograft models. These data suggest that targeting MALT1 may expand therapeutic options for patients with selected B-cell lymphomas, such as ABC-DLBCL, with the possibility of expanding into other B-cell lymphomas such as MCL. Furthermore, these small molecule MALT1 inhibitors demonstrate potential in combination with BTKi to overcome drug-induced resistance in patients with relapsed/refractory B-cell lymphomas. Taken together, the data presented here strongly underscore the therapeutic potential of our MALT1 inhibitor and support further evaluation in clinical trials. Disclosures Weiss: Schrodinger: Current Employment; ARTham Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Blockchain is a distributed and append-only data management system maintained by many nodes from Peer-to-Peer (P2P) networks, where one of the most important and successful applications is Bitcoin. In blockchain P 2 P networks, consensus algorithms are playing a key role and take a lot of time. For example, Bitcoin uses Proof-of-Work (PoW) consensus algorithm, which takes 60 minutes to acknowledge a new transaction. Compared with the traditional data management technology, blockchain systems are very inefficient. Thus, it is very crucial to improve the blockchain consensus. We present threshold digital signature techniques to exploit the blockchain consensus mechanism. First, we propose a threshold signature scheme based on NP-hard problem, i.e., solving quadratic equations in a finite field, which is considered to be secure against quantum computer attacks and traditional attacks. Second, we further propose an efficient blockchain consensus algorithm based on the new threshold signature scheme. Third, we build a new blockchain system based on the consensus algorithm. The analysis of the blockchain system shows that the efficiency and security is must better than current blockchain systems.

The diffusion of selenite (labeled with 75Se) in compacted Beishan granite (BsG) was investigated using the in-diffusion capillary method at pH values from ∼2.0 to ∼11.0 under oxic and anoxic conditions. The results indicate that the apparent diffusion coefficient (Da) values of selenite in BsG always reached the minimum at approximately pH 5. Unexpectedly, the Da values under oxic conditions are nearly one order of magnitude lower than those under the anoxic conditions. Further characterization reveals the existence of redox-sensitive Fe(II)-containing components, which can be responsible for the great difference in Da values. Fe(2p) X-ray photoelectron spectroscopy (XPS) results show that more Fe(III)-oxyhydroxide coating is formed on the granite’s surface under aerobic conditions than is formed under anaerobic conditions. Correspondingly, Se(3d) spectra indicate that more selenium is sorbed under oxic conditions, and the sorbed amount always reached the maximum at pH values from ∼4 to ∼5. A linear combination fit of X-ray absorption near edge structure (XANES) spectroscopy data revealed that Se(0) was formed under anoxic condition and that selenite preferred to form inner-sphere complexes with Fe(III)-oxyhydroxide. Overall, this study indicates that natural Fe-bearing minerals can greatly attenuate selenite diffusion and the retardation would be enhanced under aerobic conditions.

Smart Connected Health Systems (SCHSs) belong to health systems that provide services of health care remotely. They provide the doctors with access to electronic medical records with the aid of medical sensors, smart wearable devices and smart medical instruments. Although SCHSs have many applications in the area of health care, securing massive amount of valuable and sensitive data of the patients and preserving the privacy are challenging. User authentication based on public key cryptographic techniques is playing a crucial role in SCHSs for protecting the privacy of patients. However, quantum computers will break such techniques. Rainbow signature is one of the candidates of the next generation of cryptographic algorithms which can resist attacks on quantum computers. However, it is vulnerable to Differential Power Analysis (DPA) attacks, which is based on information gained from the cryptographic implementations. We present techniques to exploit the countermeasures to protect Rainbow against DPA attacks. We propose a variant of Rainbow with resistance to DPA attacks. First, we take a random vector to randomize the power consumption of private keys during computing the first affine transformation; Second, random variables are adopted during computing central map transformation; Third, we take two random vectors during computing the second affine transformation to randomize the power consumption of private keys. We analyze the efficiency and implement the scheme on hardware. Compared with the related implementations, our scheme is efficient and suitable for signature generations on hardware. Besides, we propose a secure authentical scheme based on the implementation for protecting record of patients in SCHSs.

Environmental scientists and geoscientists working in different fields regard the reactivity of calcite and corresponding changes in its trace elemental- or isotopic composition from diametrically opposed points of view. As one extreme, calcite based environmental remediation strategies rely on the fast recrystallization of calcite and the concurrent uptake and immobilization of pollutants. Paleo-ecological investigations denote the other extreme, and rely on the invariability of calcite composition over geological periods of time. We use long-term radiotracer experiments to quantify recrystallization rates of seven types of calcite powder with diverse morphology and particle size distribution. On the one hand our results demonstrate the long-term metastability of calcite with equilibrated crystal surfaces even at isotopic dis-equilibrium. On the other hand, we document the extremely high reactivity and interfacial free energy of freshly ground, rough calcite. Our results indicate that bulk calcite recrystallization is an interfacial free energy driven Ostwald-ripening process, in which particle roughness effects dominate over the effect of crystal habitus and particle size. We confirm that the dynamic equilibrium exchange of crystal constituents between kink sites involves an activation barrier of about 25 kJ/mol. At room temperature the equilibrium exchange is limited to a near surface region and proceeds at a rate of (3.6 ± 1.4)·10

This present work aims to functionalize poly(amidoamine) (PAMAM) dendrimers with various reported adhesive peptides, including Arg-Gly-Asp (RGD), Tyr-Ile-Gly-Ser-Arg (YIGSR), and Ile-Lys-Val-Ala-Val (IKVAV) for enhancing cell responses. The RGD, YIGSR, or IKVAV functionalized PAMAM coated substrate could promote cell adhesion of bone marrow mesenchymal stem cells (BMSCs) within 1 h after incubation. The neurite differentiation and proliferation of pheochromocytoma (PC12) cells were also significantly enhanced after culturing on the peptide functionalized PAMAM dendrimers for two and four days. This peptide functionalized PAMAM dendrimers are considered as the potential candidates for various tissue engineering applications.

The histone demethylase LSD1 is a key enzyme in the epigenetic regulation of gene transcription. Here we present our efforts to discover small molecule reversible inhibitors of LSD1 as an attractive approach to treat hematologic malignancies and certain solid tumors. Using structure-based drug design, we designed and synthesized a novel series of heteroaromatic imidazole inhibitors that demonstrate potent inhibition of the demethylase activity and low nanomolar cell-based activity. This novel LSD1 inhibitor series was further optimized by attenuating the hERG inhibition and improving oral bioavailability.

As the use of Internet, computers and mobile devices expands, a learning management system for college students has become necessary. Therefore, we design an efficient learning management system based on cloud computing for programming learning, which can advance student learning and interacting. We divide the learning management system into three platforms, i.e. SaaS learning platform, PaaS learning platform and IaaS learning platform. SaaS learning platform provides lesson system, learning system, examining system, document system, forum system and programming system for programming learning. PaaS learning platform provides VS 2015 Community, C-free, Eclipse, SQL Server, Oracle, IIS, Apache for programming learning. IaaS learning platform provides network infrastructure, computing infrastructure, storage infrastructure for programming learning. By integrating the designs of three learning platforms, we implement our designs on OpenStack cloud computing system, by using Microsoft ASP. Net (version 4.0) and SQL Server (version 2008). The experimental results show that the learning management system based on cloud computing for programming learning is very efficient and provides learning services on SaaS, PaaS, IaaS platforms for computer major students.

Some nodes may perform in selfish way in opportunistic networking activities to save their own resources. Once selfish nodes become more, how they will affect the whole networking system is an interesting research question. In this paper, we analyze the selfish behaviors for several popular routing protocols in opportunistic network. Also we made some simulations to check the influence of varying the degree of cooperation. Besides, we also study some strategies in MobiCent in preventing selfish behavior. The experiment result shows encouraging signal that MobiCent and other strategies are useful to prevent selfish behaviors.

Many Chinese cities have been experiencing severe pollution. To reduce the environmental impacts of transport pollution and purse sustainable developments of society, many cites in China have adopted transport policies that primarily aim to reduction in ownership and usage of motor vehicles and promote use of public transport. The primary solution should be the development of mass public transit systems, e.g. public bike rental systems. Public bike rental systems have received increasing attention in recent years with initiatives to increase public transport usage and lessen the environmental impacts. However, most of the universities in China are located in the suburbs. The limited coverage of public bike rental systems and transportation network offers college students limited access to public transit systems. We design an efficient mobile system for bike sharing on campus, with the aim of improving travel conditions for students at institutions of higher education. The bike sharing system includes two parts, i.e. client and server. Client is designed based on Android system and server is designed based on Openstack cloud computing system. The bike sharing system can bring information of bike sharing and entertainment together from diverse sources on campus in a uniform way. The bike sharing system provides a consistent look and feel with access control and procedures for multiple applications and databases of bike sharing and entertainment. We divide the bike sharing system into five functional modules, i.e. login module, lessor module, lessee module and administrator module. By integrating the designs of four modules, we use Eclipse and MySQL to implement the bike sharing system based on Android.

Knowledge of the geochemical behavior of selenium and strontium is critical for the safe disposal of radioactive wastes. Goethite, as one of the most thermodynamically stable and commonly occurring natural iron oxy-hydroxides, promisingly retains these elements. This work comprehensively studies the adsorption of Se(IV) and Sr(II) on goethite. Starting from electrokinetic measurements, the binary and ternary adsorption systems are investigated and systematically compared via batch experiments, EXAFS analysis, and CD-MUSIC modeling. Se(IV) forms bidentate inner-sphere surface complexes, while Sr(II) is assumed to form outer-sphere complexes at low and intermediate pH and inner-sphere complexes at high pH. Instead of a direct interaction between Se(IV) and Sr(II), our results indicate an electrostatically driven mutual enhancement of adsorption. Adsorption of Sr(II) is promoted by an average factor of 5 within the typical groundwater pH range from 6 to 8 for the concentration range studied here. However, the interaction between Se(IV) and Sr(II) at the surface is two-sided, Se(IV) promotes Sr(II) outer-sphere adsorption, but competes for inner-sphere adsorption sites at high pH. The complexity of surfaces is highlighted by the inability of adsorption models to predict isoelectric points without additional constraints.

In this paper we propose a new routing protocol-MDPRP for mobile wireless sensor networks, which adopts Markov Decision Process to make the decision of best next hop to forward the messages. In this scheme, we mainly integrate trust, congestion and distance as the main judgment criterion of the next hop decision. We evaluate the protocol by simulations and the performance results are encouraging.

The mobility and bioavailability of selenium is a major health and environmental issue and a main concern for geological disposal of high-level radioactive waste. Chemically and/or microbially mediated oxidation of insoluble Se-bearing particulate, such as iron selenides, to dissolved and mobile phases controls the transport and distribution of Se in the environment. The oxidation of ferroselite (FeSe2) by ferric iron was investigated in anoxic conditions. The redox reaction can be represented by: FeSe2 + 2Fe3+ = 2Se0 + 3Fe2+. Kinetic studies indicated that the reaction can be described by second-order rate law, with rate constants of 0.49±0.01, 0.85±0.02, 1.84±0.04, and 3.29±0.13 L mol−1 s−1 at pH 1.62, 1.87, 2.23, and 2.49, respectively. The positive correlation between reaction rate and pH implies that diffusion of Fe3+ oxidant to the mineral surface is the rate-determining step. The strong reactivity of FeSe2 towards Fe3+ suggests that ferric iron may play a significant role in FeSe2 oxidation process (e.g., by Se4+, O2, etc.) and Se0 should be the first reaction product. Also, it was shown that the reduction rate of Fe3+ or Se4+ by pyrite (FeS2) can be significantly increased in the presence of FeSe2, suggesting a stronger reactivity of FeSe2 compared with pyrite. The results obtained extend our knowledge about the subtle interaction between Se, pyrite and iron selenides in the environment, and give insight into the transfer of selenium from iron selenides to bio-available selenium (i.e., selenite and selenate) in the Se-rich environment.

This work presents the first report of a method for simultaneous speciation of inorganic selenium and iodine using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Baseline separation of selenite, selenate, iodide and iodate within a single chromatographic run of 10 min was achieved with the optimized mobile phase of 3 mM ammonium citrate, 25 mM ammonium perchlorate and 2% (v/v) methanol at pH 8.5. The mass spectrometric operating conditions were optimized to detect selenium and iodine simultaneously. Potential matrix effects were addressed and corrected using the standard addition method, and the recoveries (95.7–103%) were satisfactory. The repeatability and intermediate precision were satisfactory (the coefficients of variation were all less than 5% and 8%, respectively). The obtained detection limits were 22 ng L−1 and 23 ng L−1 for selenite and selenate, respectively, and 4.3 ng L−1 and 5.4 ng L−1 for iodide and iodate, respectively, which allows for the speciation of selenium and iodine in groundwater at the ultra-trace level. Groundwater samples collected from a candidate site for the Chinese high-level radioactive waste repository were analyzed. Within the three different groundwater samples, selenate was observed to be the dominant Se species; in addition, the iodide concentration increased and the iodate concentration decreased with increasing sampling depth. With its satisfactory sensitivity and accuracy, this method provides a promising tool for studying the environmental behaviors of selenium and iodine, thereby supporting safety assessments of high-level radioactive waste repositories.

Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.

Spleen Tyrosine Kinase (SYK) is a non-receptor cytoplasmic tyrosine kinase that is primarily expressed in hematopoietic cells. SYK is a key mediator for a variety of inflammatory cells, including B cells, mast cells, macrophages and neutrophils and therefore, an attractive approach for treatment of both inflammatory diseases and oncology indications. Using in house co-crystal structure information, and structure-based drug design, we designed and optimized a novel series of heteroaromatic pyrrolidinone SYK inhibitors resulting in the selection of the development candidate TAK-659. TAK-659 is currently undergoing Phase I clinical trials for advanced solid tumor and lymphoma malignancies, a Phase Ib study in advanced solid tumors in combination with nivolumab, and PhIb/II trials for relapsed/refractory AML.

Multiplications in finite fields are crucial due to the fact that they are widely used in areas of cryptography. We propose bit-parallel multipliers in finite fields for trinomials, Equally-Spaced-Polynomials (ESPs), pentanomials, All-One-Polynomials (AOPs), and Successive-One-Polynomials (SOPs). Main improvements of this paper with known results are as follows. First, SOP is first studied for finite field multiplication, which represents a polynomial with successive one. Second, we firstly propose multiplications for different pentanomials. We analyze our design theoretically and its executing time and area usage are given. Our design is well suited for Field Programmable Logic Arrays (FPGAs). We back up the claims with implementations of our design on Altera FPGAs.

The diffusion of selenite (labeled with

Inversions in finite field have been playing a key role in areas of cryptography and engineering. The main algorithms for finite field inversions are based on Fermat's little theorem, extended Euclidean algorithm and other methods. We present techniques to exploit special irreducible polynomials for fast inversions in finite fields (2 ) n GF , where n is a positive integer. We propose fast inversions based on Fermat's theorem for two special irreducible polynomials, i.e. trinomials and All-One-Polynomials (AOPs). Trinomials can be represented by polynomials 1 n m x x   and AOPs can be represented by polynomials 1 ... 1 n n x x     , where m is a positive integer and 0

Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase involved in key processes during mitosis. Human PLK1 has been shown to be overexpressed in various human cancers, and elevated levels of PLK1 have been associated with poor prognosis, making it an attractive target for anticancer therapy. TAK-960 [4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl) benzamide] is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1). Consistent with PLK1 inhibition, TAK-960 treatment caused accumulation of G2–M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3) in vitro and in vivo. TAK-960 inhibited proliferation of multiple cancer cell lines, with mean EC50 values ranging from 8.4 to 46.9 nmol/L, but not in nondividing normal cells (EC50 >1,000 nmol/L). The mutation status of TP53 or KRAS and MDR1 expression did not correlate with the potency of TAK-960 in the cell lines tested. In animal models, oral administration of TAK-960 increased pHH3 in a dose-dependent manner and significantly inhibited the growth of HT-29 colorectal cancer xenografts. Treatment with once daily TAK-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model. TAK-960 has entered clinical evaluation in patients with advanced cancers. Mol Cancer Ther; 11(3); 700–9. ©2011 AACR.

The network curriculum is an important component of the omni-directional course resource construction. The key of the omni-directional course resource construction is how to combining the network curriculum and the traditional classroom teaching together efficiently. This paper puts forward the corresponding design principles of building a collaborative network curriculum based on the blended learning technology. The corresponding design principles includes emphasizing the teaching design strategy based on task-driven of the network curriculum tent presentation and emphasizing the learning situation strategy base on project- driven of the curriculum implementation strategies. With a series of security strategy, it realizes the powerful and practical cooperative network curriculum..

A series of cyclo-3beta-(4-aminophenyl)-2beta-tropanemethanol analogues (5a-m) possessing varying linker groups between the 2- and 3-position on the tropane ring were synthesized and evaluated for their monoamine transporter binding properties. The results show that binding to the dopamine and serotonin transporters (DAT and 5-HTT) is highly dependent on the specific linker used. Cyclo-3beta-(4-aminophenyl)-2beta-tropanemethanol pimelic acid ester/amide (5b) had an IC50 of 3.8 nM at the DAT. Cyclo-3beta-(4-aminophenyl)-2beta-tropanemethanol sebacic acid ester/amide (5e) had a Ki of 1.9 nM at the 5-HTT and was 68- and 737-fold selective for the 5-HTT relative to the DAT and NET. Small changes to the size as well as the electrostatic and hydrophobic properties of the 2,3-linker in 5b or 5e led to much less potent analogues at all three transporters. These results suggest that the high affinity for 5b and 5e at the DAT and 5-HTT may be due to their specific conformational properties.

The structure-based design, synthesis, and biological activity of a novel indazole-containing inhibitor series for S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Use of 5-aminoindazole as the core scaffold provided a structure-guided series of low nanomolar inhibitors with broad-spectrum antimicrobial activity. The implementation of structure-based methodologies provided a 6000-fold increase in potency over a short timeline (several months) and an economy of synthesized compounds.

Evidence is presented that 5-imidazolylpropynyl-2'-deoxyuridine 5'-monophosphate (IP-dUMP) is a mechanism-based, irreversible inactivator of Escherichia coli thymidylate synthase (TS), which covalently modifies Tyr94 at the active site of the enzyme. The inactivation of TS was time and concentration dependent and did not require the folate cofactor. Due to the rapidity of the inactivation process, accurate kinetic parameters could be determined only in the presence of saturating concentrations (1000K(M)) of the competing substrate, dUMP. Under these conditions, a K(I) of 0.36 +/- 0.09 microM and an inactivation rate constant (k(inact)) of 0.53 +/- 0.15 min(-1) were obtained from Kitz-Wilson plots. Electrospray ionization-mass spectrometry (ESI-MS) determined a 412 amu mass increase of TS after inhibition by IP-dUMP with no mass difference being detected for the TS mutants Tyr94Phe or Cys146Ala, thus indicating the importance of these residues for complex formation. The change in WT-TS mass was consistent with covalent modification by IP-dUMP, which was confirmed by proteolytic digestion of the modified protein followed by ESI-MS. By these means, a 43-residue trypsin peptide (residues 54-96), a 16-residue endoAspN peptide (residues 89-104), and an 8-residue endoAspN/endoLysC peptide (residues 89-96), each containing the IP-dUMP adduct, were observed. MS/MS analysis of the IP-dUMP-endoAspN peptide identified a modified 3-residue daughter ion, YGK (residues 94-96). A mechanistic scheme requiring the participation of Cys146 is proposed for the covalent modification of IP-dUMP by Tyr94, which, unlike an earlier proposal [Kalman, T. I., Nie, Z., and Kamat, A. (2001) Nucleosides Nucleotides Nucleic Acids 20, 869-871], does not require the release of imidazole for the activation of the inhibitor.

A novel series of 5-propynylpyrimidine nucleosides are proposed as potential antimetabolites of DNA-thymine biosynthesis. This proposal is based on the results of detailed mechanistic analyses of the molecular interactions between dTMP synthase and its inhibitors. It is proposed that a propynyl side-chain at the 5-position of dUMP, bearing an appropriate leaving group, would cause irreversible inactivation of dTMP synthase, which would not require the presence of the cofactor, CH2H4folate.

To prepare the monoclonal antibodies (mAbs) against human Apo B₁₀₀ and establish a double-antibody sandwich ELISA system for human Apo B₁₀₀ detection.The BALB/c mice were immunized with human Apo B₁₀₀ antigen. After cell fusion and screening, the hybridoma cells were cultured in serum-free medium and the supernatant was purified to obtain mAbs using protein A. The affinity, subtype, specificity and epitope of the mAbs were characterized and the sandwich ELISA system was established.Four hybridoma cell lines 4-1-2, 4-2-2, 4-3-2 and 4-6-3 were obtained. The affinity of the anti-Apo B₁₀₀ mAbs was up to 1×10⁹ L/mol and nearly had no cross reaction with other relevant proteins. Linear detection of the sandwich ELISA system using 4-3-2 and 4-6-3 covered a range from (1.3-80) ng/mL, and its sensitivity was 1.24 ng/mL. The intra-assay coefficient of variation (CV) and inter-assay CV were less than 10% and 15%, respectively, and the recovery rate was above 90%.The mAbs against human Apo B₁₀₀ have been prepared and a sandwich ELISA system for human Apo B₁₀₀ detection has been established successfully, which provide a basis for human Apo B₁₀₀ detection and disease diagnosis.

Through analyzing and studying the BBS topic model, topic similarity, topic inspection, topic evaluation standards and topic developing trends, This paper designs and implements the Chinese BBS topic detection algorithm based on the content analysis, which includes obtaining BBS information by web crawler, processing BBS information based on the URL and Xpath page templates, realizing BBS information participle by ICTLAS, clustering BBS topic by Carrot2, analyzing hot topic based on the power spectrum and predicting of BBS topic based on time series. Finally, this paper developed the Chinese BBS Topic detection system used J2EE development kit, based on the eclipse integrated development environment, combined with Hibernate and GWT technology, and getting good results by tested in various BBS forums.