bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural evaluations of tau protein conformation: methodologies and approaches
Authors: Zabik Nicole L. , Imhof Matthew M. , Martic-Milne Sanela
Published: March 2017

Protein-misfolding diseases are based on a common principle of aggregation initiated by intra- and inter-molecular contacts. The structural and conformational changes induced by biochemical transformations such as post-translational modifications (PTMs), often lead to protein unfolding and misfolding. Thus, these order-to-disorder or disorder-to-order transitions may regulate cellular function. Tau, a neuronal protein, regulates microtubule (MT) structure and overall cellular integrity. However, misfolded tau modified by PTMs results in MT destabilization, toxic tau aggregate formation, and ultimately cell death, leading to neurodegeneration. Currently, the lack of structural information surrounding tau severely limits understanding of neurodegeneration. This minireview focuses on the current methodologies and approaches aimed at probing tau conformation and the role of conformation in various aspects of tau biochemistry. The recent applications of nuclear magnetic resonance, mass spectrometry, Förster resonance electron transfer, and molecular dynamics simulations toward structural analysis of conformational landscapes of tau will be described. The strategies developed for structural evaluation of tau may significantly improve our understanding of misfolding diseases.
Insight into hydraulic conductivity testing of geosynthetic clay liners (GCLs) exhumed after 5 and 7 years in a cover
Authors: Rowe R.K. , Brachman R.W.I. , Hosney M.S. , Take W.A. , Arnepalli D.N.
Published: March 2017

Four geosynthetic clay liners (GCLs) serving as single liners were exhumed from below 0.7 m of silty sand on a 3:1 (horizontal:vertical) north-facing slope at the QUELTS site in Godfrey, Ontario, after 5 and 7 years. The 300 mm GCL overlaps with 0.4 kg/m supplemental bentonite were all physically intact. The exchangeable bound sodium was completely replaced with divalent cations. The GCL with the smallest needle-punched bundle size (average of 0.7 mm) and percentage area covered by bundles (4%) maintained low hydraulic conductivity (k) when tested under 0.07–1.2 m head with 10 mmol/L CaCl2solution as the permeant. For GCLs with larger bundles (1.1–1.6 mm) and higher percentage area covered by bundles (9%–14%), k was low when the head was low (0.07 m). Once the applied head increased, k increased by 1–4 orders of magnitude depending on the (i) hydraulic gradient, (ii) size and number of the needle-punched bundles, and (iii) structure and mass of the bentonite per unit area. The results suggest that the GCLs can perform effectively as a single hydraulic barrier in covers providing that the head above the GCL is kept low (e.g., by a suitable drainage layer above the GCL).
Secondary migration of petroleum along syncline axes: a case study of the southern Kuqa Foreland Basin
Authors: Cai Jun , Lü Xiuxiang , Wang Ping
Published: March 2017

Tracing petroleum migration pathways for petroleum exploration in a sedimentary basin is challenging. Paleo-uplifts are generally considered to represent the primary migration directions of petroleum. Here we propose a model for the Kuqa Foreland Basin, in which petroleum migrates along the axes of synclines between paleo-uplifts, based on an integrated analysis of seismic, geochemical, and production data. Interpretation of detailed seismic data indicates that petroleum is unlikely to migrate to the paleo-uplifts because of their relatively low positions, fault disruptions, or a lack of Mesozoic reservoirs. Geochemical parameters, including the ratios of alkyl dibenzothiophenes and the gas wetness parameter, show that petroleum maturity gradually decreases along the axes of synclines between paleo-uplifts from northeast to southwest. Petroleum production data and gas/oil ratios also show decreasing trends from northeast to southwest. This evidence suggests that petroleum is likely to migrate along the axes of the synclines between the paleo-uplifts from northeast to southwest. This study not only enhances the scientific understanding of secondary migration, but also may be useful to guide petroleum exploration in the southern Kuqa Foreland Basin.
Structural phase transition, electronic, elastic, and vibrational properties of LiAl intermetallic compound: insights from first-principles calculations
Authors: Mogulkoc Y. , Ciftci Y.O. , Surucu G.
Published: March 2017

Using the first-principles calculations based on density functional theory (DFT), the structural, elastic, electronic, and vibrational properties of LiAl have been explored within the generalized gradient approximation (GGA) using the Vienna ab initio simulation package (VASP). The results demonstrate that LiAl compound is stable in the NaTl-type structure (B32) at ambient pressure, which is in good agreement with the experimental results and there is a structural phase transition from NaTl-type structure (B32) to CsCl-type structure (B2) at around 22.2 GPa pressure value. The pressure effects on the elastic properties have been discussed and the elastic property calculation indicates that the elastic instability could provide a phase transition driving force according to the variations relation of the elastic constant versus pressure. To gain further information about this, we also have investigated the other elastic parameters (i.e., Zener anisotropy factor, Poisson’s ratio, Young’s modulus, and isotropic shear modulus). The electronic band structure, total and partial density of states, phonon dispersion curves, and one-phonon density of states of B2 and B32 phases are also presented with results.
Changing nitrogen deposition with low δ15N−NH4 + and δ15N−NO3 − values at the Experimental Lakes Area, northwestern Ontario, Canada
Authors: Venkiteswaran J.J. , Schiff S.L. , Paterson M.J. , Flinn N.A.P. , Shao H. , Elgood R.J.
Published: March 2017

Ammonium deposition at the International Institute for Sustainable Development Experimental Lakes Area (IISD–ELA), in northwestern Ontario, Canada, has doubled in the last 45 years and thus is no longer among the low nitrogen (N) deposition sites in North America. This may be related to the concurrent intensification of Manitoba agriculture to the west and upwind of the ELA. Large increases in ammonium deposition at the ELA were important in driving the observed trend and increased the NH4 + to NO3 − ratio of input to aquatic and terrestrial systems. Stable isotope analyses of two years of bulk (wet and dry) atmospheric deposition revealed very large ranges in δ15N−NH4 + (22‰ range), δ15N−NO3 − (18‰), and δ18O–NO3 − (19‰). Few other δ15N−NH4 +, δ15N−NO3 −, and δ18O–NO3 − values have been published for Canadian precipitation. Increases in δ15N of NH4 + and NO3 − in July occurred with increases in total N deposition. The wide range and seasonal trends of δ15N and δ18O values in ELA precipitation mean that studies characterizing N inputs to watersheds and lakes require an ongoing and comprehensive annual sampling regime. Global trends of declining δ15N of N deposition evident in lake sediment records may be a result of increases in NH4 + deposition with lower δ15N−NH4 + values. Similarly, the relationship in Lake Superior between increasing NO3 − and lower δ15N−NO3 − values may be explained by increased atmospheric deposition of N with low δ15N values.
Mock BSPlib for Testing and Debugging Bulk Synchronous Parallel Software
Authors: Suijlen Wijnand
Published: March 2017

Testing parallel applications on a large number of processors is often impractical. Not only does it require access to scarce compute resources, but tracking down defects with the available debugging tools can often be very time consuming. Highly parallel codes should be testable on one processor at a time, so that a developer’s workstation is sufficient for executing and debugging test cases on millions of processes. Thanks to its supersteps, Bulk Synchronous Parallel programs are well suited for this kind of testing. This paper presents a mocking library for BSPlib which enables testing of fast and complex parallel algorithms at scale.
SPar: A DSL for High-Level and Productive Stream Parallelism
Authors: Griebler Dalvan , Danelutto Marco , Torquati Massimo , Fernandes Luiz Gustavo
Published: March 2017

This paper introduces SPar, an internal C++ Domain-Specific Language (DSL) that supports the development of classic stream parallel applications. The DSL uses standard C++ attributes to introduce annotations tagging the notable components of stream parallel applications: stream sources and stream processing stages. A set of tools process SPar code (C++ annotated code using the SPar attributes) to generate FastFlow C++ code that exploits the stream parallelism denoted by SPar annotations while targeting shared memory multi-core architectures. We outline the main SPar features along with the main implementation techniques and tools. Also, we show the results of experiments assessing the feasibility of the entire approach as well as SPar’s performance and expressiveness.
An Explicit Fourth-Order Runge–Kutta Method for Dynamic Force Identification
Authors: Lai Tao , Yi Ting-Hua , Li Hong-Nan , Fu Xing
Published: March 2017

This paper presents a new technique for input reconstruction based on the explicit fourth-order Runge–Kutta (RK4) method. First, the state-space representation of the dynamic system is discretized by the explicit RK4 method under the assumption of linear interpolation for the dynamic load, leading to a recurrence equation between the current state and the previous state. Then, the mapping from the sequences of input to output is established through the recursive operation of the system equation and observation equation. Finally, the stabilized force information is recovered using the Tikhonov regularization method. This approach makes use of the good stability and high precision of the RK4 method; in addition, the computational efficiency is enhanced by avoiding the computation of the inverse stiffness matrix. The proposed method is numerically illustrated and validated with various excitations on a simple four-story shear building and a more complicated 2D truss structure, along with a detailed parametric study. The simulation studies show that the external loads can be reconstructed with high efficiency and accuracy under a low noise environment.
THE ECONOMY-WIDE IMPACTS OF CLIMATE CHANGE AND IRRIGATION DEVELOPMENT IN THE NILE BASIN: A COMPUTABLE GENERAL EQUILIBRIUM APPROACH
Authors: KAHSAY TEWODROS NEGASH , KUIK ONNO , BROUWER ROY , VAN DER ZAAG PIETER
Published: March 2017

A multi-country, multi-sector computable general equilibrium (CGE) model is employed to evaluate the economy-wide impacts of climate change under the IPCC’s A2 and B1 scenarios and existing irrigation development plans in the Nile basin. The study reveals that climate change adversely affects mainly downstream Egypt and to a lesser extent Sudan, while it results in a limited impact in the upstream countries Ethiopia and the Equatorial Lakes region, where irrigated agriculture is still limited. The economic consequences for Egypt are especially substantial if the river basin countries pursue a unilateral irrigation development strategy. In order to prevent water use conflicts and ease water scarcity conditions, a cooperative water development strategy is needed as well as economic diversification in favor of less water-intensive sectors, combined with investments in water-saving infrastructure and improved irrigation efficiency.
A weak approximation with Malliavin weights for local stochastic volatility model
Authors: Yamada Toshihiro
Published: March 2017

This paper introduces a new efficient and practical weak approximation for option price under local stochastic volatility model as marginal expectation of stochastic differential equation, using iterative asymptotic expansion with Malliavin weights. The explicit Malliavin weights for SABR model are shown. Numerical experiments confirm the validity of our discretization with a few time steps.
Two Components of the Macroscopic General Field
Authors: Fedosin Sergey G.
Published: March 2017

The general field, containing all the macroscopic fields in it, is divided into the mass component, the source of which is the mass four-current, and the charge component, the source of which is the charge four-current. The mass component includes the gravitational field, acceleration field, pressure field, dissipation field, strong interaction and weak interaction fields, other vector fields. The charge component of the general field represents the electromagnetic field. With the help of the principle of least action we derived the field equations, the equation of the matter’s motion in the general field, the equation for the metric, the energy and momentum of the system of matter and its fields, and calibrated the cosmological constant. The general field components are related to the corresponding vacuum field components so that the vacuum field generates the general field at the macroscopic level.
Conglomerate categories in coarse-grained deltas and their controls on hydrocarbon reservoir distribution: a case study of the Triassic Baikouquan Formation, Mahu Depression, NW China
Authors: Tan Chengpeng , Yu Xinghe , Liu Beibei , Qu Jianhua , Zhang Lei , Huang Dingjie
Published: March 2017

There is great potential for hydrocarbon exploration in the Triassic Baikouquan Formation, in the Mahu Depression of the Junggar Basin, NW China. Controversy remains around the conglomerate categories in coarse-grained deltas, which has inhibited further exploration in this area. Based on a dataset of cores, test data, well logs and seismic, this study attempts to recognize different genetic types of conglomerates formed within coarse-grained deltas. The Baikouquan Formation conglomerate has been divided into nine facies on the basis of textures, grain size and sedimentary structures. From the associations of these nine facies, three conglomerate categories have been recognized: debris-flow conglomerate (DFC); hyperconcentrated-flow conglomerate (HCFC); and traction-flow conglomerate (TFC). These have diagnostic characteristics that are expressed in core, well logs, seismic character, grain-size distribution curves and maximum particle size/bed thickness analysis (MPS/BTh). A depositional model has been built after analysis of the sediment transport mechanisms to facilitate exploration of the Baikouquan Formation, in the Mahu Depression. The evaluation of reservoir characteristics, physical properties and pore-throat structures of these conglomerate categories has identified the HCFC reservoirs as the primary potential targets for exploration in the study area.
Risk and Uncertainty Communication
Authors: Spiegelhalter David
Published: March 2017

This review briefly examines the vast range of techniques used to communicate risk assessments arising from statistical analysis. After discussing essential psychological and sociological issues, I focus on individual health risks and relevant research on communicating numbers, verbal expressions, graphics, and conveying deeper uncertainty. I then consider practice in a selection of diverse case studies, including gambling, the benefits and risks of pharmaceuticals, weather forecasting, natural hazards, climate change, environmental exposures, security and intelligence, industrial reliability, and catastrophic national and global risks. There are some tentative final conclusions, but the primary message is to acknowledge expert guidance, be clear about objectives, and work closely with intended audiences.
Effect of diuretics on renal tubular transport of calcium and magnesium
Authors: Alexander R. Todd , Dimke Henrik
Published: March 2017

Calcium (Ca2+) and Magnesium (Mg2+) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca2+and Mg2+reclamation in kidney is dependent on a diverse array of proteins, which are important for both forming divalent cation-permeable pores and channels, but also for generating the necessary driving forces for Ca2+and Mg2+transport. Alterations in these molecular constituents can have profound effects on tubular Ca2+and Mg2+handling. Diuretics are used to treat a large range of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na+) transport, but also indirectly affect renal Ca2+and Mg2+handling, i.e., by establishing a prerequisite electrochemical gradient. It is therefore not surprising that substantial alterations in divalent cation handling can be observed following diuretic treatment. The effects of diuretics on renal Ca2+and Mg2+handling are reviewed in the context of the present understanding of basal molecular mechanisms of Ca2+and Mg2+transport. Acetazolamide, osmotic diuretics, Na+/H+exchanger (NHE3) inhibitors, and antidiabetic Na+/glucose cotransporter type 2 (SGLT) blocking compounds, target the proximal tubule, where paracellular Ca2+transport predominates. Loop diuretics and renal outer medullary K+(ROMK) inhibitors block thick ascending limb transport, a segment with significant paracellular Ca2+and Mg2+transport. Thiazides target the distal convoluted tubule; however, their effect on divalent cation transport is not limited to that segment. Finally, potassium-sparing diuretics, which inhibit electrogenic Na+transport at distal sites, can also affect divalent cation transport.
Effects of childbirth on podocyturia in women with normotensive, uncomplicated pregnancies
Authors: Furuta Itsuko , Zhai Tianyue , Umazume Takeshi , Ishikawa Satoshi , Nakagawa Kinuko , Kojima Takashi , Yamada Takahiro , Morikawa Mamoru , Minakami Hisanori
Published: March 2017

Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression were corrected by urine Cr concentration. Podocyturia increased significantly, concomitant with a significantly decreased Nep:Pod-mRNA ratio (NPR) in the urine, collected immediately before or after childbirth regardless of the delivery mode compared with urine collected before commencement of labor or on postpartum day 3 or later. Podocyturia was significantly negatively correlated with NPR [correlation coefficient ( r) = −0.614/−0.750 for VD/ECS women, respectively], as well as the Syn:Pod-mRNA ratio. Systolic blood pressure exceeded 140 mmHg during labor in 50% of VD women, and mean arterial pressure was significantly positively correlated with podocyturia during labor in VD women ( r = 0.733). Thus parturition induces a transient increase in urine podocytes with reduced Nep- and Syn-mRNA expressions. Glomerular podocytes with reduced Nep- and Syn-mRNA levels were suggested to be likely to detach from the glomerular basement membrane around childbirth.
CYP1B1 G199T Polymorphism Affects Prognosis of NSCLC Patients with the Potential to Be an Indicator and Target for Precise Drug Intervention
Authors: Li Fengzhou , Zhang Shaofeng , Zhang Qi , Li Jinxiu , Zhao Shilei , Gu Chundong
Published: March 2017

CYP1B1 gene single nucleotide polymorphisms G119T, C432G, and A453G were tested among 164 NSCLC patients treated by Video-Assisted Thoracoscopic Surgery. After a follow-up period of 5 years, it was found that CYP1B1 G119T mutant genotypes were related to a higher risk of tumor recurrence and death after surgical resection. However, C432G and A453G genotypes had no influence on long-term prognosis of the study cohort. Thus, G199T alleles are supposed to be an auxiliary predictor for prognosis of NSCLC patients and a potential target for precise drug intervention, as well as a candidate for further anticancer drug research.
Supervised and Unsupervised Subband Adaptive Denoising Frameworks with Polynomial Threshold Function
Authors: Gong Tierui , Yang Zhijia , Wang Gengshan , Jiao Ping
Published: March 2017

Unlike inflexible structure of soft and hard threshold function, a unified linear matrix form with flexible structure for threshold function is proposed. Based on the unified linear flexible structure threshold function, both supervised and unsupervised subband adaptive denoising frameworks are established. To determine flexible coefficients, a direct mean‐square error (MSE) minimization is conducted in supervised denoising while Stein’s unbiased risk estimate as a MSE estimate is minimized in unsupervised denoising. The SURE rule requires no hypotheses or a priori knowledge about clean signals. Furthermore, we discuss conditions to obtain optimal coefficients for both supervised and unsupervised subband adaptive denoising frameworks. Applying an Odd‐Term Reserving Polynomial (OTRP) function as concrete threshold function, simulations for polynomial order, denoising performance, and noise effect are conducted. Proper polynomial order and noise effect are analyzed. Both proposed methods are compared with soft and hard based denoising technologies—VisuShrink, SureShrink, MiniMaxShrink, and BayesShrink—in denoising performance simulation. Results show that the proposed approaches perform better in both MSE and signal‐to‐noise ratio (SNR) sense.
Visual Vehicle Tracking Based on Deep Representation and Semisupervised Learning
Authors: Cai Yingfeng , Wang Hai , Sun Xiao-qiang , Chen Long
Published: March 2017

Discriminative tracking methods use binary classification to discriminate between the foreground and background and have achieved some useful results. However, the use of labeled training samples is insufficient for them to achieve accurate tracking. Hence, discriminative classifiers must use their own classification results to update themselves, which may lead to feedback-induced tracking drift. To overcome these problems, we propose a semisupervised tracking algorithm that uses deep representation and transfer learning. Firstly, a 2D multilayer deep belief network is trained with a large amount of unlabeled samples. The nonlinear mapping point at the top of this network is subtracted as the feature dictionary. Then, this feature dictionary is utilized to transfer train and update a deep tracker. The positive samples for training are the tracked vehicles, and the negative samples are the background images. Finally, a particle filter is used to estimate vehicle position. We demonstrate experimentally that our proposed vehicle tracking algorithm can effectively restrain drift while also maintaining the adaption of vehicle appearance. Compared with similar algorithms, our method achieves a better tracking success rate and fewer average central-pixel errors.
Numerical Analysis on Flow Behavior of Molten Iron and Slag in Main Trough of Blast Furnace during Tapping Process
Authors: Wang Li , Pan Chien-Nan , Cheng Wen-Tung
Published: March 2017

The three-dimensional model was developed according to number 4 of the main trough of blast furnace at China Steel Co. (CSC BF4). The k-ε equations and volume of fluid (VOF) were used for describing the turbulent flow at the impinging zone of trough, indicating fluids of liquid iron, molten slag, and air in the governing equation, respectively, in this paper. The pressure field and velocity profile were then obtained by the finite volume method (FVM) and the pressure implicit with splitting of operators (PISO), respectively, followed by calculating the wall shear stress through Newton’s law of viscosity for validation. Then, the operation conditions and the main trough geometry were numerically examined for the separation efficiency of iron from slag stream. As shown in the results, the molten iron losses associated with the slag can be reduced by increasing the height difference between the slag and iron ports, reducing the tapping rate, and increasing the height of the opening under the skimmer.
Land Use Land Cover Changes in Detection of Water Quality: A Study Based on Remote Sensing and Multivariate Statistics
Authors: Hua Ang Kean
Published: March 2017

Malacca River water quality is affected due to rapid urbanization development. The present study applied LULC changes towards water quality detection in Malacca River. The method uses LULC, PCA, CCA, HCA, NHCA, and ANOVA. PCA confirmed DS, EC, salinity, turbidity, TSS, DO, BOD, COD, As, Hg, Zn, Fe,E. coli, and total coliform. CCA confirmed 14 variables into two variates; first variate involves residential and industrial activities; and second variate involves agriculture, sewage treatment plant, and animal husbandry. HCA and NHCA emphasize that cluster 1 occurs in urban area with Hg, Fe, total coliform, and DO pollution; cluster 3 occurs in suburban area with salinity, EC, and DS; and cluster 2 occurs in rural area with salinity and EC. ANOVA between LULC and water quality data indicates that built-up area significantly polluted the water quality throughE. coli, total coliform, EC, BOD, COD, TSS, Hg, Zn, and Fe, while agriculture activities cause EC, TSS, salinity,E. coli, total coliform, arsenic, and iron pollution; and open space causes contamination of turbidity, salinity, EC, and TSS. Research finding provided useful information in identifying pollution sources and understanding LULC with river water quality as references to policy maker for proper management of Land Use area.
Quantitative PCR and Digital PCR for Detection ofAscaris lumbricoidesEggs in Reclaimed Water
Authors: Acosta Soto Lucrecia , Santísima-Trinidad Ana Belén , Bornay-Llinares Fernando Jorge , Martín González Marcos , Pascual Valero José Antonio , Ros Muñoz Margarita
Published: March 2017

The reuse of reclaimed water from wastewater depuration is a widespread and necessary practice in many areas around the world and must be accompanied by adequate and continuous quality control.Ascaris lumbricoidesis one of the soil-transmitted helminths (STH) with risk for humans due to its high infectivity and an important determinant of transmission is the inadequacy of water supplies and sanitation. The World Health Organization (WHO) recommends a limit equal to or lower than one parasitic helminth egg per liter, to reuse reclaimed water for unrestricted irrigation. We present two new protocols of DNA extraction from large volumes of reclaimed water. Quantitative PCR (qPCR) and digital PCR (dPCR) were able to detect low amounts ofA. lumbricoideseggs. By using the first extraction protocol, which processes 500 mL of reclaimed water, qPCR can detect DNA concentrations as low as oneA. lumbricoidesegg equivalent, while dPCR can detect DNA concentrations as low as fiveA. lumbricoidesegg equivalents. By using the second protocol, which processes 10 L of reclaimed water, qPCR was able to detect DNA concentrations equivalent to 20A. lumbricoideseggs. This fact indicated the importance of developing new methodologies to detect helminth eggs with higher sensitivity and precision avoiding possible human infection risks.
Fault-Tolerant Control of a Nonlinear System Actuator Fault Based on Sliding Mode Control
Authors: He Jing , Mi Lin , Mao Songan , Zhang Changfan , Chu Houguang
Published: March 2017

This paper presents a fault-tolerant control scheme for a class of nonlinear systems with actuator faults and unknown input disturbances. First, the sliding mode control law is designed based on the reaching law method. Then, in view of unpredictable state variables and unknown information in the control law, the original system is transformed into two subsystems through a coordinate transformation. One subsystem only has actuator faults, and the other subsystem has both actuator faults and disturbances. A sliding mode observer is designed for the two subsystems, respectively, and the equivalence principle of the sliding mode variable structure is used to realize the accurate reconstruction of the actuator faults and disturbances. Finally, the observation value and the reconstruction value are used to carry out an online adjustment to the designed sliding mode control law, and fault-tolerant control of the system is realized. The simulation results are presented to demonstrate the approach.
Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity
Authors: Patnaik Akash , Swanson Kenneth D. , Csizmadia Eva , Solanki Aniruddh , Landon-Brace Natalie , Gehring Marina P. , Helenius Katja , Olson Brian M. , Pyzer Athalia R. , Wang Lily C. , Elemento Olivier , Novak Jesse , Thornley Thomas B. , Asara John M. , Montaser Laleh , Timmons Joshua J. , Morgan Todd M. , Wang Yugang , Levantini Elena , Clohessy John G. , Kelly Kathleen , Pandolfi Pier Paolo , Rosenblatt Jacalyn M. , Avigan David E. , Ye Huihui , Karp Jeffrey M. , Signoretti Sabina , Balk Steven P. , Cantley Lewis C.
Published: March 2017

Several kinase inhibitors that target aberrant signaling pathways in tumor cells have been deployed in cancer therapy. However, their impact on the tumor immune microenvironment remains poorly understood. The tyrosine kinase inhibitor cabozantinib showed striking responses in cancer clinical trial patients across several malignancies. Here, we show that cabozantinib rapidly eradicates invasive, poorly differentiated PTEN/p53-deficient murine prostate cancer. This was associated with enhanced release of neutrophil chemotactic factors from tumor cells, including CXCL12 and HMGB1, resulting in robust infiltration of neutrophils into the tumor. Critically, cabozantinib-induced tumor clearance in mice was abolished by antibody-mediated granulocyte depletion or HMGB1 neutralization or blockade of neutrophil chemotaxis with the CXCR4 inhibitor plerixafor. Collectively, these data demonstrate that cabozantinib triggers a neutrophil-mediated anticancer innate immune response, resulting in tumor clearance.

Significance: This study is the first to demonstrate that a tyrosine kinase inhibitor can activate neutrophil-mediated antitumor innate immunity, resulting in invasive cancer clearance. Cancer Discov; 7(7); 750–65. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 653
The Interaction of Childhood Maltreatment, Sex, and Borderline Personality Features in the Prediction of the Cortisol Awakening Response in Adolescents
Authors: Kaess Michael , Whittle Sarah , Simmons Julian G. , Jovev Martina , Allen Nicholas B. , Chanen Andrew M.
Published: March 2017

Aims: The study aimed to investigate childhood maltreatment, sex, and borderline personality disorder (BPD) symptoms as prospective predictors of adolescent hypothalamic-pituitary-adrenal (HPA) axis reactivity. Method: A sample of 69 adolescents (30 female and 39 male) were selected from a larger longitudinal study of adolescent development and assessed at 3 time points. BPD symptoms were assessed at T1 (approx. 12.5 years), childhood maltreatment was assessed at T2 (approx. 14.9 years), and multiple assessments of salivary cortisol (cortisol awakening response; CAR) were undertaken at T3 (approx. 15.5 years). Results: Multivariate linear regression analysis revealed a significant main effect for childhood maltreatment but not for early BPD symptoms as a predictor of lower CAR in adolescence (p = 0.047). The association between childhood maltreatment and attenuated CAR was moderated by both early BPD symptoms (p = 0.024; no childhood maltreatment-dependent attenuation of CAR in the presence of BPD symptoms) and sex (p = 0.012; childhood maltreatment-dependent attenuation of CAR in females only). Furthermore, a 3-way BPD × childhood maltreatment × sex interaction (p = 0.041) indicated that the moderating effect of BPD symptoms was present in females only. Conclusion: These findings indicate that attenuation of the HPA axis occurs as a response to early maltreatment rather than being related to the early occurrence of BPD pathology. Traumatized female individuals with BPD symptoms might bypass adaptive HPA axis attenuation.
Improved Visual Outcome and Low Recurrence with Early Treatment with Intravitreal Anti-Vascular Endothelial Growth Factor in Myopic Choroidal Neovascularization
Authors: Moon Byung Gil , Cho Ah Ran , Lee Junyeop , Kim Yoon Jeon , Lee Joo Yong , Kim June-Gone , Yoon Young Hee
Published: March 2017

Purpose: The aim of this study was to determine the correlation between the duration of myopic choroidal neovascularization (CNV) and treatment outcome after anti-vascular endothelial growth factor (VEGF) injections. Methods: We performed a retrospective review of treatment-naïve myopic CNV patients who were treated with anti-VEGF and followed for at least 24 months to identify factors predicting final outcome and recurrence. Results: Among 106 eyes, a shorter duration of CNV was a significant predictor of a better final best-corrected visual acuity, even after controlling for other factors (p = 0.042). When divided into 3 groups according to CNV duration before treatment (<2, 2-8, and 8-24 weeks), the recurrence rate (19, 25, and 52%, respectively; p = 0.006) and number of injections (3.5, 4.0, and 5.5, respectively; p = 0.021) were significantly lower in eyes with a shorter duration of CNV. Conclusions: Early anti-VEGF treatment of myopic CNV decreased the recurrence rate and number of injections and improved visual outcome.
Targeted Segment Transfer from Rye Chromosome 2R to Wheat Chromosomes 2A, 2B, and 7B
Authors: Ren Tianheng , Li Zhi , Yan Benju , Tan Feiquan , Tang Zongxiang , Fu Shulan , Yang Manyu , Ren Zhenglong
Published: March 2017

Increased chromosome instability was induced by a rye (Secale cereale L.) monosomic 2R chromosome into wheat (Triticum aestivum L.). Centromere breakage and telomere dysfunction result in high rates of chromosome aberrations, including breakages, fissions, fusions, deletions, and translocations. Plants with target traits were sequentially selected to produce a breeding population, from which 3 translocation lines with target traits have been selected. In these lines, wheat chromosomes 2A, 2B, and 7B recombined with segments of the rye chromosome arm 2RL. This was detected by FISH analysis using repeat sequences pSc119.2, pAs1 and genomic DNA of rye together as probes. The translocation chromosomes in these lines were named as 2ASMR, 2BSMR, and 7BSMR. The small segments that were transferred into wheat consisted of pSc119.2 repeats and other chromatin regions that conferred resistance to stripe rust and expressed target traits. These translocation lines were highly resistant to stripe rust, and expressed several typical traits that were associated with chromosome arm 2RL, which are better than those of its wheat parent, disomic addition, and substitution lines that show agronomic characteristics. The integration of molecular methods and conventional techniques to improve wheat breeding schemes are discussed.
Emphysematous Pyelonephritis and Cystitis: Unusual Adverse Events during Concurrent Chemoradiotherapy for Lung Cancer
Authors: Yokoyama Tetsuya , Shinozaki Seiji , Arimura Hidenobu , Nakatomi Keita , Wataya Hiroshi
Published: March 2017

Various adverse events can occur during antineoplastic therapy. A 67-year-old diabetic woman developed an emphysematous urinary tract infection (UTI) associated with chemoradiotherapy for lung cancer. She had received weekly carboplatin plus paclitaxel with thoracic radiotherapy and developed a fever on day 19. Computed tomography showed a large quantity of gas within the urinary tract. She was therefore diagnosed with emphysematous UTI. Poor diabetes control due to the weekly administration of dexamethasone, an existing urinary tract obstruction, and bone marrow suppression were involved in her serious infection. The potential development of emphysematous UTI during chemoradiotherapy should be considered in at-risk patients.
A Novel ABCA4 Mutation Associated with a Late-Onset Stargardt Disease Phenotype: A Hypomorphic Allele
Authors: Kaway Cindy S. , Adams Madeleine K.M. , Jenkins Kevin Sean , Layton Christopher J.
Published: March 2017

Background: Stargardt disease (STGD) is the most common juvenile hereditary macular dystrophy. In the majority of cases, the diagnosis is made prior to 20 years of age and usually leads to loss of central vision. Late-onset STGD affects a smaller number of patients. Identifying genetic changes which could be associated with clinically important differences in severity or presentation of the disease is important for understanding the mechanisms of visual loss and for planning future therapeutic approaches. Methods: We report a patient with the classic phenotype of STGD with late-onset mild disease exhibiting a slow clinical progression over 14 months of follow-up. Results: A 37-year-old man presented with STGD and good vision of 6/24 in the right eye and of 6/6 in the left eye as well as typical electrophysiology findings. Objective and subjective visual deterioration was not noted over a period of 14 months. Macular genetic testing revealed a novel missense mutation in ABCA4 (Thr829Met) combined with Gly1961Glu, a classic STGD mutation usually associated with a moderately severe phenotype. Conclusions: It is suggested that the Thr829Met mutation could give rise to a hypomorphic allele of the ABC transporter with a resultant phenotype of comparatively mild STGD.
IL-6 Enhances Osteocyte-Mediated Osteoclastogenesis by Promoting JAK2 and RANKL Activity In Vitro
Authors: Wu Qing , Zhou Xiaokang , Huang Danqing , JI Yingchen , Kang Feiwu
Published: March 2017

Background/Aims: Evidence suggests that IL-6 affects bone mass by modulating osteocyte communication towards osteoclasts. However, the mechanism by which IL-6 enhances osteocyte-mediated osteoclastogenesis is unclear. We aimed to investigate the inflammatory factors in serum after orthodontic surgery and their relationship between osteocytes and osteoclasts. Methods: Serum was obtained from 10 orthognathic surgery patients, and inflammatory factors were detected by ELISA. We treated the osteocyte-like cell line MLO-Y4 with recombinant mouse IL-6 and IL-6 receptor (IL-6R), and used quantitative RT-PCR and Western blotting to explore Receptor activator of nuclear factor-κB ligand (RANKL) expression at both the mRNA and protein level. MLO-Y4 cells were co-cultured with osteoclast precursor cells, and the formation of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. To explore the role of JAK2 in the osteocyte-mediated osteoclastogenesis, AG490, a JAK2 inhibitor, was used to inhibit the JAK2-STAT3 pathway in osteocytes. Results: In our study, we found that IL-6 and RANKL were stimulated in serum 3-7 days after orthognathic surgery. Therefore, IL-6 and IL-6 receptor enhanced the expression of RANKL at both the mRNA and protein level in MLO-Y4. Furthermore, when MLO-Y4 cells were co-cultured with osteoclast precursor cells, it significantly stimulated osteoclastogenesis. Our study indicated that osteocytes could promote osteoclastic differentiation and the formation of TRAP-positive multinucleated cells after stimulation with IL-6 and IL-6R. Our results also indicated that treatment with IL-6 and IL-6R increased RANKL mRNA expression and the RANKL/OPG expression ratio. Meanwhile, the phosphorylation of Janus kinase 2 (JAK2) and Signal transducer and activator of transcription (STAT3) also correlated with RANKL levels. Furthermore, we investigated the effects of a specific JAK2 inhibitor, AG490, on the expression of RANKL in osteocyte-like MLO-Y4 cells and osteocyte-mediated osteoclastogenesis. The results showed that AG490 inhibited (p)-JAK2 and RANKL expression. Osteoclastic differentiation was decreased after pretreatment in MLO-Y4 with mouse IL-6/IL-6R and AG490; therefore, we concluded that IL-6 increased osteocyte-mediated osteoclastic differentiation by activating JAK2 and RANKL. Conclusion: The effects of IL-6/il-6R and AG490 on osteocyte-mediated osteoclastogenesis contribute to our understanding of the role of inflammatory factors in the interaction between osteocytes and osteoclast precursors. IL-6 and RANKL are key factors for bone remodelling after the orthodontic surgery, and their roles in bone remodelling may be fundamental mechanisms accelerating tooth movement by orthodontic surgery.
Sipunculus marcusi spec. nov. (Sipuncula) from southern Brazil
Authors: Ditadi A. S. F.
Published: March 2017

Descreve-se Sipunculus marcusi spec. nov. da costa do Estado de São Paulo. A espécie em questão difere das outras do gênero Sipunculus principalmente pelas imensas bases dos músculos retrato res da probóscide; estas bases estão unidas umas às outras abrangendo cerca de 18 faixas musculares longitudinais em cada lado do cordão nervoso ventral.
The distribution of some Copepods (Crustacea) in the Southern Ocean and adjacent regions from 40º to 81º W long
Authors: Yamanaka Naoyo
Published: March 2017

A distribuição zoogeográfica das espécies de copépodos Rhincalanus gigas,R. nasutus, R. cornutus, Pseudeuchirella hirsuta, Valdiviella insigáis, V. brevicornis, Pseudeuchaeta brevicauda, Undeuchaeta major, U. intermedia, Euchaeta longicornis, E. marina, E. tenuis, Paraeuchaeta antárctica, P. aequatorialis, P. barbata, P biloba, P. birostrata, P. bisinuata, P californica, P. confusa, P dubia, P farrani, P. grandiremis, P hanseni, P. malayensis, P. pseudotonsa, P polita, P. rasa, P. sarsi, P. scotti, P- similis, P. tonsa, P weberi foi estudada de 129 amostras coletadas do U.S.N.S. “Eltanin” em águas entre as latitudes 2°34’ N e 67°28’S e longitudes 42°44’ e 81°61’W. Onde possível a distribuição das espécies foi correlacionada com a profundidade, os meses do ano e as massas dágua ocorrentes na região.Um ciclo migratório foi proposto, e as espécies mais freqüentes, assim como asnovas ocorrências, foram registradas.
The functional morphology of Anodontites trapezeus (Spix) and Anodontites trapesialis (Lamarck). (Bivalvia: Mycetopodidae)
Authors: Hebling Nilton José
Published: March 2017

A anatomia funcional comparada de duas espécies de bivalves límnicos, é analisada. Anodontites trapezeus e Anodontites trapesialis, pertencem à família Mycetopodidae e são comuns no interior do Estado de São Paulo. Vivem no mesmo local e são adaptadas ao ambiente de águas calmas. Foram, pela primeira vez, estudadas sob o ponto de vista da anatomia funcional e, o estudo do estômago contribuiu com valiosas informações, mostrando que, de maneira geral, a estrutura interna é de grande uniformidade nesses animais, tal como ocorre entre os Unionacea, estudados por outros autores.
The reproduction of some Phyllostomidae (Chiroptera) from the Northwestern region of the state of São Paulo
Authors: Taddei Valdir Antonio
Published: March 2017

A reprodução dos Phyllostomidae foi estudada examinando-se 1558 exemplares,obtidos no período de 1967 a 1972. Não existe uma estação sexual bem definidapara 9 das 16 espécies registradas. Os dados disponíveis para 7 espécies nãopermitiram conclusões a este respeito, porém, uma delas, Chiroderma v. villosum, aparentemente acompanha o padrão das espécies com atividade sexual não limitada a um período curto.Os períodos de aumento ou diminuição da incidência de gestações, sugerema existência de dois ciclos, um principal com gravidez incipiente, em junho-julho e recém-nascidos em outubro-novembro e outro secundário, em continuidade, com nascimentos em fevereiro-março. O maior número de recém-nascidos do ciclo principal ocorre no início da estação chuvosa e quente, de outubro a março, e os nascidos provenientes do ciclo secundário, no final dessa estação.Nos meses mais secos e mais frios, de junho e julho, observou-se ausênciaou uma porcentagem mínima de fêmeas lactantes.Para as espécies estudadas, o tempo de gestação estimado foi superior a trêsmeses e meio. Observou-se sempre um embrião por gestação, apesar de teremsido encontradas condições que poderiam sugerir a existência de mais do que um embrião.
Ciclo anual da gametogênese de Anomalocardia brasiliana (Gmelin, 1791) (Mollusca Bivalvia)
Authors: Narchi Walter
Published: March 2017

Este artigo não contém resumo.
Comparative morphology of the endocrine brain and retrocerebral complex of the honeybee worlker and queens (Hymenoptera-apinae)
Authors: Hofling Maria Alice da Cruz , Landim Carminda Da Cruz
Published: March 2017

Foi estudado o aspecto das células neurosecretoras da pars intercerebralis e dos corpora cardiaca e allata, em material obtido de rainhas e operárias de Apis mellifera em diferentes idades. O material foi corado com hematoxilina crômicafloxina, verificando-se urna degranulação das células neurosecretoras das operárias após os 15 dias de ida de com correspondente aumento da atividade dos corpora cardiaca e dos corpora allata.Nas rainhas, com exceção da rainha virgem e da rainha fecundada, com 3 anos de idade, a atividade desse sistema endocrino manteve-se constante, fato que parece indicar a atuação dos hormônios produzidos na vitelogênese.
Studies on Paratrigona subnuda (Moure) Hymenoptera, Apidae, Meliponinae - II. Behaviour of the virgin queen
Authors: Imperatriz Fonseca Vera Lúcia
Published: March 2017

O comportamento das rainhas virgens de Paratrigona subnuda (Moure) foi observado em cerca de 20 colônias. Verificou-se que elas possuem u m ciclo de atividades definido, constando de: a) eclosão, b) atividade na região dos potes, c) reclusão esporádica em potes e procura de contacto com as operárias, d) estabelecimento na colônia, e) tentativa de substituição da rainha fecundada da colônia, f) saída para u m novo ninho. O comportamento após a substituição da rainha foi relatado. Como acontece em outras espécies de Trigonini, as rainhas virgens de Paratrigona subnuda (Moure) também passam por u m a fase de reclusão, utilizando potes de alimentos vazios. Essa reclusão, porém, é considerada "voluntária”, pois as rainhas virgens saem dos potes e circulam livremente pela colmeia, mantendo contacto com operárias. A rainha virgem tem u m papel decisivo na substituição natural da rainha fecundada da colônia, visto que o processo de substituição é iniciado com a deposição de uma gota de substância mandibular, pela rainha virgem, sobre o corpo da rainha fisogástrica da colônia. Foram discutidas tanto a possibilidade de u m controle feromonal para a manutençâo da rainha poedeira na colonia como a importáncia dos prováveis feromónios nas diversas etapas do ciclo biológico da rainha virgem na colmeia.
Hydra intermedia sp. nov. and notes on Chlorohydra viridissima (Pallas) (Cnidaria)
Authors: Wolle Luzia De Carvalho
Published: March 2017

Hydra intermedia sp. nov. é descrita e comparada com as espécies descritas até agora. Exemplares da nova espécie foram coletados em alguns corpos de água do Estado de São Paulo entre 1972 e 1974. As hidras verdes coletadas em alguns pontos da Cidade Universitária foram identificadas com Chlo- rohydra viridissima (Palias) 1766.
Some Enchytraeidae (Oligochaeta) from Serra do Mar, São Paulo
Authors: Christoffersen Martin Lindsey
Published: March 2017

Os animais foram coletados num pequeno trecho da nossa floresta tropical latifoliada úmida de encosta. Hemienchytraeus (H.) stephensoni (Cognetti, 1927) foi encontrado pela primeira vez no Brasil, sendo redescrito. Discutem-se ainda pequenas diferenças morfológicas de Fridericia bulbosa (Rosa, 1887), F. agricola Moore, 1895 e F bollonsi Benham, 1914, com relação a descrições anterioresdo Estado de São Paulo.
Valor nutritivo de algumas dietas artificiais para Anastrepha obliqua (Diptera, Tephritidae)
Authors: Zucoloto Fernando Sergio , Puschel Suzana , Message Creusa M.
Published: March 2017

Valor nutritivo de algumas dietas artificias para Anastrepha obliqua (Diptera, Tephritidae). Algumas dietas artificias, em diferentes concentrações, foram testadas e sua eficiência foi calculada a partir do peso das pupas, do tempo para apupar e da porcentagem de empupação. Os melhores resultados foram obtidos com fermento 4,5 g/ 150 ml de dieta; os outros produtos testados foram: germe de trigo, feijão soja, leite em pó e aveia.