bluuebunny/crossref_metadata_2025 huggingface dataset:
Elsinochrome A photosensitizers: Alternative drugs for photodynamic therapy
Authors: Li Tinghui , Deng Hong , Zhao Jingquan , Gu Ying
Published: January 2014

Photodynamic therapy (PDT) has already been a multifunctional modality for various tumors and nontumorous diseases. However, the development of photosensitizers is relatively delayed, compared with the tremendous progress in laser technology. Elsinochrome A (EA), a perylenequinonoid pigment from China, has all the typical advantages of perylenequinones. Moreover, singlet oxygen quantum yield of EA is superior to other kinds of photosensitizers and EA could be artificially biosynthesized at present, which make it an alternative candidate for PDT. In this review, the photophysics, photochemistry, photobiology and chemical or biological syntheses of EA photosensitizers are briefly presented. Besides, the future prospects of EA photosensitizers are also proposed.
Studies on photodynamic mechanism of a novel chlorine derivative (TDPC) and its antitumor effect for photodynamic therapy in vitro and in vivo
Authors: Ye Ying , Wang Lai-Xing , Zhang Dan-Ping , Yan Yi-Jia , Chen Zhi-Long
Published: January 2014

Photodynamic therapy (PDT) represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer (PS) play key roles in the treatment efficacy. In this study, a novel PS, 5,10,15,20-tetrakis((5-dipropylamino)pentyl)-chlorin (TDPC) which displayed a characteristic long wavelength absorption peak at 650 nm were synthesized. It also shows a singlet oxygen generation rate of 4.257 min-1. Generally, TDPC is localized in mitochondria and nucleus of cell. After light irradiation with 650 nm laser, it can kill many types of cell, in addition, TDPC–PDT can destroy ECA-109 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following TDPC–PDT. The results showed that it either increased or decreased, among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. In general, TDPC is an effective antitumor PS in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new PSs.
Indium-substituted ZnO/reduced graphene oxide nanocomposites: Solvothermal synthesis and enhanced visible-light-driven photocatalytic activity
Authors: Zhu Jie , He Wanhong , Zhang Lu , Xiang Xu , Li Zhiwei
Published: January 2014

A new protocol was developed to obtain a composite photocatalyst by incorporating indium to ZnO and subsequently assembling it with reduced graphene oxide (RGO) sheets. The incorporation of indium led to lattice distortion of ZnO and introduction of defect levels. The hybridization with RGO could improve the electron transport and extend the lifetime of photo-generated carriers, leading to enhanced activity for dye degradation driven by visible light. The photocatalytic activity appeared to be dependent on the relative quantity of RGO. The optimized quantity resulted in the highest activity due to the dual role of electron shuttle and "shielding effect" of RGO. In addition, the composite photocatalyst exhibited excellent repeatable use performance, suggestive of its high stability. This study proposed a promising strategy to construct photocatalysts by rational bandgap engineering and tunable composite technology.
Modification of Intestinal Microbiota and Its Consequences for Innate Immune Response in the Pathogenesis of Campylobacteriosis
Authors: Masanta Wycliffe Omurwa , Heimesaat Markus M. , Bereswill Stefan , Tareen Abdul Malik , Lugert Raimond , Groß Uwe , Zautner Andreas E.
Published: January 2014

Campylobacter jejuniis the leading cause of bacterial food-borne gastroenteritis in the world, and thus one of the most important public health concerns. The initial stage in its pathogenesis after ingestion is to overcome colonization resistance that is maintained by the human intestinal microbiota. But how it overcomes colonization resistance is unknown. Recently developed humanized gnotobiotic mouse models have provided deeper insights into this initial stage and host’s immune response. These studies have found that a fat-rich diet modifies the composition of the conventional intestinal microbiota by increasing the Firmicutes and Proteobacteria loads while reducing the Actinobacteria and Bacteroidetes loads creating an imbalance that exposes the intestinal epithelial cells to adherence. Upon adherence, deoxycholic acid stimulatesC. jejunito synthesize Campylobacter invasion antigens, which invade the epithelial cells. In response, NF-κB triggers the maturation of dendritic cells. Chemokines produced by the activated dendritic cells initiate the clearance ofC. jejunicells by inducing the actions of neutrophils, B-lymphocytes, and various subsets of T-cells. This immune response causes inflammation. This review focuses on the progress that has been made on understanding the relationship between intestinal microbiota shift, establishment ofC. jejuniinfection, and consequent immune response.
The New Mathematical Model of Motion Compensation for Stepped‐Frequency Radar Signal
Authors: Lin Yun , Xu Xiaochun , Pang Jinfeng , Li Bin , Zhou Ruolin
Published: January 2014

When a stepped‐frequency radar is used to obtain the high‐resolution range profile (HRRP) of high‐speed target, accurate speed estimation and motion compensation must be considered. Therefore, in this paper, a novel mathematical method is presented for estimating the target speed. Firstly, the pulse Doppler method is used to calculate the initial estimation value. Secondly, based on the initial estimation value, the minimum entropy method is used to calculate the coarse estimation value. Finally, based on the coarse estimation value, the minimum l1‐Norms method is used to calculate the accurate estimation value. The numeric simulation results confirm that this new method is effective and predominant, which has a much higher estimation accuracy in a low SNR and a much larger estimation range of target speed. The final estimation value can be used to well compensate for the influence of target speed on HRRP.
γ-H2AX: A Novel Prognostic Marker in a Prognosis Prediction Model of Patients with Early Operable Non-Small Cell Lung Cancer
Authors: Chatzimichail E. , Matthaios D. , Bouros D. , Karakitsos P. , Romanidis K. , Kakolyris S. , Papashinopoulos G. , Rigas A.
Published: January 2014

Cancer is a leading cause of death worldwide and the prognostic evaluation of cancer patients is of great importance in medical care. The use of artificial neural networks in prediction problems is well established in human medical literature. The aim of the current study was to assess the prognostic value of a series of clinical and molecular variables with the addition ofγ-H2AX—a new DNA damage response marker—for the prediction of prognosis in patients with early operable non-small cell lung cancer by comparing theγ-H2AX-based artificial network prediction model with the corresponding LR one. Two prognostic models of 96 patients with 27 input variables were constructed by using the parameter-increasing method in order to compare the predictive accuracy of neural network and logistic regression models. The quality of the models was evaluated by an independent validation data set of 11 patients. Neural networks outperformed logistic regression in predicting the patient’s outcome according to the experimental results. To assess the importance of the two factors p53 andγ-H2AX, models without these two variables were also constructed. JR and accuracy of these models were lower than those of the models using all input variables, suggesting that these biological markers are very important for optimal performance of the models. This study indicates that neural networks may represent a potentially more useful decision support tool than conventional statistical methods for predicting the outcome of patients with non-small cell lung cancer and that some molecular markers, such asγ-H2AX, enhance their predictive ability.
Intermuscular Fat: A Review of the Consequences and Causes
Authors: Addison Odessa , Marcus Robin L. , LaStayo Paul C. , Ryan Alice S.
Published: January 2014

Muscle’s structural composition is an important factor underlying muscle strength and physical function in older adults. There is an increasing amount of research to support the clear disassociation between the loss of muscle lean tissue mass and strength with aging. This disassociation implies that factors in addition to lean muscle mass are responsible for the decreases in strength and function seen with aging. Intermuscular adipose tissue (IMAT) is a significant predictor of both muscle function and mobility function in older adults and across a wide variety of comorbid conditions such as stroke, spinal cord injury, diabetes, and COPD. IMAT is also implicated in metabolic dysfunction such as insulin resistance. The purpose of this narrative review is to provide a review of the implications of increased IMAT levels in metabolic, muscle, and mobility function. Potential treatment options to mitigate increasing levels of IMAT will also be discussed.
A Batch Arrival Single Server Queue with Server Providing General Service in Two Fluctuating Modes and Reneging during Vacation and Breakdowns
Authors: Baruah Monita , Madan Kailash C. , Eldabi Tillal
Published: January 2014

We study the behavior of a batch arrival queuing system equipped with a single server providing general arbitrary service to customers with different service rates in two fluctuating modes of service. In addition, the server is subject to random breakdown. As soon as the server faces breakdown, the customer whose service is interrupted comes back to the head of the queue. As soon as repair process of the server is complete, the server immediately starts providing service in mode 1. Also customers waiting for service may renege (leave the queue) when there is breakdown or when server takes vacation. The system provides service with complete or reduced efficiency due to the fluctuating rates of service. We derive the steady state queue size distribution. Some special cases are discussed and numerical illustration is provided to see the effect and validity of the results.
Synthesis of Thermally Spherical CuO Nanoparticles
Authors: Tamaekong Nittaya , Liewhiran Chaikarn , Phanichphant Sukon
Published: January 2014

Copper oxide (CuO) nanoparticles were successfully synthesized by a thermal method. The CuO nanoparticles were further characterized by thermogravimetric analysis (TGA), differential thermal analysis (DTA), X‐ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X‐ray spectrometry (EDS), and high resolution transmission electron microscopy (HRTEM), respectively. The specific surface area (SSABET) of CuO nanoparticles was determined by nitrogen adsorption. The SSABET was found to be 99.67 m2/g (dBET of 9.5 nm). The average diameter of the spherical CuO nanoparticles was approximately 6–9 nm.
Experimental Investigations of Cochannel Interference Reduction Effect at High Elevation Base Station Using Beam Tilt and Orthogonal Polarization
Authors: Uwano Shuta , Ando Atsuya , Seki Tomohiro , Takatori Yasushi , Hiraguri Takefumi
Published: January 2014

This paper addresses the problem of cochannel interference (CCI) generated in a mixed cell architecture in microcellular systems. In this type of microcellular systems in which both microcells and macrocells coexist in the same geographical urban area, the base station antennas mounted on the rooftops of buildings to cover wide circular radio zones suffer severe CCI from the surrounding low base stations. A dielectric-loaded slotted-cylinder antenna (DSCA) is applied to horizontally polarized omnidirectional array antennas in a height-diversity configuration with the high gain of 8 dBi, which is comparable to that of a collinear antenna, to reduce the CCI. The measurements conducted in a suburban area clarify the reduction in the CCI for three techniques. The beam-tilt technique reduces the CCI level by approximately 10 dB for both collinear antennas and the DSCA array antennas. The use of horizontal polarization reduces the CCI level by approximately 13 dB for the DSCA array antennas with and without beam tilt. The combination of the beam tilt and horizontal polarization or the DSCA array antennas with beam tilt significantly reduces the CCI level by approximately 23 dB.
Magnetohydrodynamic Boundary Layer Flow of Nanofluid over an Exponentially Stretching Permeable Sheet
Authors: Bhattacharyya Krishnendu , Layek G. C.
Published: January 2014

A mathematical model of the steady boundary layer flow of nanofluid due to an exponentially permeable stretching sheet with external magnetic field is presented. In the model, the effects of Brownian motion and thermophoresis on heat transfer and nanoparticle volume friction are considered. Using shooting technique with fourth-order Runge-Kutta method the transformed equations are solved. The study reveals that the governing parameters, namely, the magnetic parameter, the wall mass transfer parameter, the Prandtl number, the Lewis number, Brownian motion parameter, and thermophoresis parameter, have major effects on the flow field, the heat transfer, and the nanoparticle volume fraction. The magnetic field makes enhancement in temperature and nanoparticle volume fraction, whereas the wall mass transfer through the porous sheet causes reduction of both. For the Brownian motion, the temperature increases and the nanoparticle volume fraction decreases. Heat transfer rate becomes low with increase of Lewis number. For thermophoresis effect, the thermal boundary layer thickness becomes larger.
Modeling of Car‐Following Required Safe Distance Based on Molecular Dynamics
Authors: Qu Dayi , Chen Xiufeng , Yang Wansan , Bian Xiaohua
Published: January 2014

In car‐following procedure, some distances are reserved between the vehicles, through which drivers can avoid collisions with vehicles before and after them in the same lane and keep a reasonable clearance with lateral vehicles. This paper investigates characters of vehicle operating safety in car following state based on required safe distance. To tackle this problem, we probe into required safe distance and car‐following model using molecular dynamics, covering longitudinal and lateral safe distance. The model was developed and implemented to describe the relationship between longitudinal safe distance and lateral safe distance under the condition where the leader keeps uniform deceleration. The results obtained herein are deemed valuable for car‐following theory and microscopic traffic simulation.
A Model for Recognizing Key Factors and Applications Thereof to Engineering
Authors: Shi Baofeng , Chi Guotai
Published: January 2014

This paper presents an approach to recognize key factors in data classification. Using collinearity diagnostics to delete the factors of repeated information and Logistic regression significant discriminant to select the factors which can effectively distinguish the two kinds of samples, this paper creates a model for recognizing key factors. The proposed model is demonstrated by using the 2044 observations in finical engineering. The experimental results demonstrate that the 13 indicators such as “marital status,” “net income of borrower,” and “Engel′s coefficient” are the key factors to distinguish the good customers from the bad customers. By analyzing the experimental results, the performance of the proposed model is verified. Moreover, the proposed method is simple and easy to be implemented.
Photochemical Behaviour of Carbamates Structurally Related to Herbicides in Aqueous Media: Nucleophilic Solvent Trapping versus Radical Reactions
Authors: Passananti Monica , Cermola Flavio , DellaGreca Marina , Iesce Maria Rosaria , Previtera Lucio , Sferruzza Rosalia , Temussi Fabio
Published: January 2014

Irradiation ofN-arylO-aryl carbamates has been carried out in H2O/CH3CN (1 : 1 v/v) solutions atλ>290 nm. When chlorine is on theN-aryl ring, halogen-substituted products are found. These photoproducts derive from the trapping of the intermediate radical cation by water and, even, by acetonitrile leading to phenols andN-arylacetamides (photo-Ritter products), respectively. UnsubstitutedN-aryl carbamates slowly undergo photo-Fries reaction.
IMM Filter Based Human Tracking Using a Distributed Wireless Sensor Network
Authors: Zhang Sen , Xiao Wendong , Gong Jun
Published: January 2014

This paper proposes a human tracking approach in a distributed wireless sensor network. Most of the efforts on human tracking focus on vision techniques. However, most vision‐based approaches to moving object detection involve intensive real‐time computations. In this paper, we present an algorithm for human tracking using low‐cost range wireless sensor nodes which can contribute lower computational burden based on a distributed computing system, while the centralized computing system often makes some information from sensors delay. Because the human target often moves with high maneuvering, the proposed algorithm applies the interacting multiple model (IMM) filter techniques and a novel sensor node selection scheme developed considering both the tracking accuracy and the energy cost which is based on the tacking results of IMM filter at each time step. This paper also proposed a novel sensor management scheme which can manage the sensor node effectively during the sensor node selection and the tracking process. Simulations results show that the proposed approach can achieve superior tracking accuracy compared to the most recent human motion tracking scheme.
A New Model for Predicting Dynamic Surge Pressure in Gas and Drilling Mud Two‐Phase Flow during Tripping Operations
Authors: Kong Xiangwei , Lin Yuanhua , Qiu Yijie , Zhu Hongjun , Dong Long , Chen Yanchao
Published: January 2014

Investigation of surge pressure is of great significance to the circulation loss problem caused by unsteady operations in management pressure drilling (MPD) operations. With full consideration of the important factors such as wave velocity, gas influx rate, pressure, temperature, and well depth, a new surge pressure model has been proposed based on the mass conservation equations and the momentum conservation equations during MPD operations. The finite‐difference method, the Newton‐Raphson iterative method, and the fourth‐order explicit Runge‐Kutta method (R‐K4) are adopted to solve the model. Calculation results indicate that the surge pressure has different values with respect to different drill pipe tripping speeds and well parameters. In general, the surge pressure tends to increase with the increases of drill pipe operating speed and with the decrease of gas influx rate and wellbore diameter. When the gas influx occurs, the surge pressure is weakened obviously. The surge pressure can cause a significant lag time if the gas influx occurs at bottomhole, and it is mainly affected by pressure wave velocity. The maximum surge pressure may occur before drill pipe reaches bottomhole, and the surge pressure is mainly affected by drill pipe operating speed and gas influx rate.
miR-30c-2-3p and miR-30a-3p: New Pieces of the Jigsaw Puzzle in HIF2α Regulation
Authors: Moch Holger , Lukamowicz-Rajska Magdalena
Published: January 2014

Summary: Clear cell renal cell carcinoma (ccRCC), the most frequent subtype of renal cell cancer, is characterized by mutation of the von Hippel–Lindau (VHL) tumor suppressor gene, which results in stabilization of hypoxia-inducible factor (HIF) α proteins. In this issue of Cancer Discovery, Mathew and colleagues report that miR-30c-2-3p and miR-30a-3p downregulation in ccRCC promotes increased expression of HIF2α.Cancer Discov; 4(1); 22–4. ©2014 AACR.

See related article by Mathew et al., p. 53
Faulty ECM Signaling Facilitates Autoimmune Lymphomagenesis
Authors: Brekken Rolf A.
Published: January 2014

Summary: The contribution of the extracellular matrix (ECM) to the microenvironment of solid tumors is appreciated although not completely understood; however, the contribution of the ECM to the development of hematopoietic tumors has not been investigated in depth. A new study by Sangaletti and colleagues demonstrates that faulty ECM signaling can facilitate malignant lymphoproliferation in mice predisposed to autoimmunity. Similar changes in ECM construction, consistent with a loss of inhibitory ECM signaling, were identified in the transition from reactive lymphoid hyperplasia to malignant chronic lymphocytic leukemia in patients. These results reveal a critical contribution of reduced collagen signaling in lymphoma and highlight the importance of appropriate ECM construction for maintenance of tissue homeostasis. Cancer Discov; 4(1); 25–6. ©2014 AACR.

See related article by Sangaletti et al., p. 110
Towards a Unified Model of RAF Inhibitor Resistance
Authors: Solit David B. , Rosen Neal
Published: January 2014

ATP-competitive RAF inhibitors elicit profound but often temporary antitumor responses in patients with BRAF-mutant melanoma. Analysis of tumor samples collected at the time of disease progression indicates that alterations within the extracellular signal-regulated kinase (ERK) pathway that result in reactivation of ERK signaling are present in most patients. Mutations in the phosphoinositide 3-kinase/AKT pathway that enhance the adaptive response to RAF inhibitors also contribute to RAF inhibitor resistance in a subset of patients. Cancer Discov; 4(1); 27–30. ©2014 AACR.

See related articles by Wagle et al., p. 61 Shi et al., p. 69 Shi et al., p. 80 and Van Allen et al., p. 94
Thermodilution-Derived Coronary Microvascular Resistance and Flow Reserve in Patients With Cardiac Syndrome X
Authors: Luo Chufan , Long Ming , Hu Xun , Huang Zhibin , Hu Chengheng , Gao Xiuren , Du Zhimin
Published: January 2014

Background—

Although increased coronary microvascular resistance (CMR), resulting in coronary microvascular dysfunction, is speculated to be responsible for myocardial ischemia in patients with cardiac syndrome X (CSX), it has never been directly demonstrated, and the correlation between CMR and severity of myocardial ischemia has not been elucidated in this setting. This study aimed to ascertain the increased CMR directly and to explore the relationship between CMR and severity of ischemia in patients with CSX.

Methods and Results—

We studied 18 patients with CSX and 18 age- and sex-matched control subjects. Thermodilution-derived coronary flow reserve and index of microvascular resistance were measured using a pressure–temperature sensor-tipped coronary wire. Exercise treadmill test was performed by the Bruce protocol for calculating Duke treadmill score. Coronary flow reserve was significantly lower (2.37±0.81 versus 3.68±0.72;
P
<0.001) and index of microvascular resistance was higher (33.1±7.9 versus 18.8±5.6 U;
P
<0.001) in patients with CSX compared with those in control subjects. The Duke treadmill score was correlated positively to coronary flow reserve (
r
=0.539;
P
=0.021) and negatively to index of microvascular resistance (
r
=−0.742;
P
<0.001) in patients with CSX.

Conclusions—

Using an intracoronary thermodilution method, we for the first time directly demonstrated an increased microvascular resistance in patients with CSX. Furthermore, severity of ischemia was found to be intimately associated with CMR in this setting.
Bone Mineral Density and Incidence of Stroke
Authors: Myint Phyo Kyaw , Clark Allan B. , Kwok Chun Shing , Loke Yoon Kong , Yeong Jessica Ka-Yan , Luben Robert N. , Wareham Nicholas J. , Khaw Kay-Tee
Published: January 2014

Background and Purpose—

The prospective link between osteoporosis and future risk of stroke requires evidence from large-scale population-based long-term studies.

Methods—

Calcaneum broadband ultrasound attenuation was measured in the Norfolk cohort of the European Prospective Investigation into Cancer-Norfolk between 1997 and 2000. Incident strokes were ascertained by hospital record linkage and death certificates in March 2009 and December 2011, respectively. A search of MEDLINE and EMBASE was performed to evaluate the relationship between bone mineral density and incident stroke. After data extraction of relevant studies, pooled risk of stroke was estimated using meta-analysis.

Results—

In 14 290 participants (mean follow-up of 9.3 years; total person-years 132 574), there were 599 incident strokes. Participants in the lowest 10% of the calcaneum broadband ultrasound attenuation distribution had an increased stroke risk (hazard ratio 1.41; 95% confidence intervals, 1.02–1.94) compared with those in the top 30% of the distribution after adjustments. A decrease of ~1 standard deviation in broadband ultrasound attenuation (20 db/MHz) was associated with a 17% increase in relative risk of stroke (95% confidence intervals, 5%–30%).

Meta-analysis of 4 studies (25 760 participants, 1237 cases of stroke) found that for every decrease in 1 standard deviation in bone mineral density, there was an increased risk of incident stroke among women (pooled relative risk 1.22; 95% confidence intervals, 1.09–1.37; I
2
=0%, 3 studies) but not in men (pooled relative risk 1.05; 95% confidence intervals, 0.94–1.17; I
2
=0%, 2 studies).

Conclusions—

Bone mineral density predicts total stroke risk. The evidence is stronger in women with regard to the continuous relationship.
Tuning Extreme NEXRAD and CMORPH Precipitation Estimates
Authors: Woody Jonathan , Lund Robert , Gebremichael Mekonnen
Published: January 2014

High-resolution satellite precipitation estimates, such as the Climate Prediction Center morphing technique (CMORPH), provide alternative sources of precipitation data for hydrological applications, especially in regions where adequate ground-based instruments are unavailable. These estimates are, however, subject to large errors, especially at times of heavy precipitation. This paper presents a method to distributionally convert a set of CMORPH estimates into ground-based Next Generation Weather Radar (NEXRAD) estimates. As our concern lies with floods and extreme precipitation events, a peaks-over-threshold extreme value approach is adopted that fits a generalized Pareto distribution to the large precipitation estimates. A quantile matching transformation is then used to convert CMORPH values into NEXRAD values. The methods are applied in the analysis of 6 yr of precipitation observations from 625 pixels centered around eastern Oklahoma.
Salt Feedback in the Adiabatic Overturning Circulation
Authors: Wolfe Christopher L. , Cessi Paola
Published: January 2014

The adiabatic overturning circulation is the part of the meridional overturning circulation that persists in the limit of vanishing diffusivity. Two conditions are required for the existence of the adiabatic overturning circulation: a high-latitude zonally reentrant channel subject to surface westerlies and a set of outcropping isopycnals shared between the channel and the opposite hemisphere. This paper examines how different buoyancy forcing regimes, particularly freshwater flux, affect the surface buoyancy distribution and the strength of the adiabatic overturning circulation. Without freshwater forcing, salinity is uniform and buoyancy is determined by temperature only. In this case, the size of the shared isopycnal window is effectively fixed by the coupling between atmospheric and sea surface temperatures. With freshwater forcing (applied as a surface flux), the salinity, and thus the sea surface buoyancy and the size of the shared isopycnal window, is not specified by the atmospheric state alone. It is found that a salt–advection feedback leads to surface buoyancy distributions that increase the size of the isopycnal window and strengthen the adiabatic overturning circulation. The strength of the feedback is controlled by processes in high latitudes—the southern channel, where the surface salinity is determined by a balance between freshwater input from the atmosphere, salt input from upwelling deep water, and freshwater export by Ekman transport; and the Northern Hemisphere, where the overturning and wind-driven transport in the thermocline advect salty water from the subtropics, mitigating the freshening effect of the surface freshwater flux. The freshwater budget in the channel region provides an estimate of the size of the isopycnal window.
Spatio-temporal analysis on enterovirus cases through integrated surveillance in Taiwan
Authors: Chan Ta-Chien , Hwang Jing-Shiang , Chen Rung-Hung , King Chwan-Chuen , Chiang Po-Huang
Published: January 2014

Background

Severe epidemics of enterovirus have occurred frequently in Malaysia, Singapore, Taiwan, Cambodia, and China, involving cases of pulmonary edema, hemorrhage and encephalitis, and an effective vaccine has not been available. The specific aim of this study was to understand the epidemiological characteristics of mild and severe enterovirus cases through integrated surveillance data.

Methods

All enterovirus cases in Taiwan over almost ten years from three main databases, including national notifiable diseases surveillance, sentinel physician surveillance and laboratory surveillance programs from July 1, 1999 to December 31, 2008 were analyzed. The Pearson’s correlation coefficient was applied for measuring the consistency of the trends in the cases between different surveillance systems. Cross correlation analysis in a time series model was applied for examining the capability to predict severe enterovirus infections. Poisson temporal, spatial and space-time scan statistics were used for identifying the most likely clusters of severe enterovirus outbreaks. The directional distribution method with two standard deviations of ellipse was applied to measure the size and the movement of the epidemic.

Results

The secular trend showed that the number of severe EV cases peaked in 2008, and the number of mild EV cases was significantly correlated with that of severe ones occurring in the same week [r = 0.553, p < 0.01]. These severe EV cases showed significantly higher association with the weekly positive isolation rates of EV-71 than the mild cases [severe: 0.498, p < 0.01 vs. mild: 0.278, p < 0.01]. In a time series model, the increase of mild EV cases was the significant predictor for the occurrence of severe EV cases. The directional distribution showed that both the mild and severe EV cases spread extensively during the peak. Before the detected spatio-temporal clusters in June 2008, the mild cases had begun to rise since May 2008, and the outbreak spread from south to north.

Conclusions

Local public health professionals can monitor the temporal and spatial trends plus spatio-temporal clusters and isolation rate of EV-71 in mild and severe EV cases in a community when virus transmission is high, to provide early warning signals and to prevent subsequent severe epidemics.
Nanoscale observation of surface potential and carrier transport in Cu2ZnSn(S,Se)4 thin films grown by sputtering-based two-step process
Authors: Kim Gee Yeong , Kim Ju Ri , Jo William , Son Dae-Ho , Kim Dae-Hwan , Kang Jin-Kyu
Published: January 2014

Stacked precursors of Cu-Zn-Sn-S were grown by radio frequency sputtering and annealed in a furnace with Se metals to form thin-film solar cell materials of Cu2ZnSn(S,Se)4 (CZTSSe). The samples have different absorber layer thickness of 1 to 2 μm and show conversion efficiencies up to 8.06%. Conductive atomic force microscopy and Kelvin probe force microscopy were used to explore the local electrical properties of the surface of CZTSSe thin films. The high-efficiency CZTSSe thin film exhibits significantly positive bending of surface potential around the grain boundaries. Dominant current paths along the grain boundaries are also observed. The surface electrical parameters of potential and current lead to potential solar cell applications using CZTSSe thin films, which may be an alternative choice of Cu(In,Ga)Se2.

PACS number: 08.37.-d; 61.72.Mm; 71.35.-y
Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis: -KOGC04-
Authors: Matsuda Satoru , Takahashi Tsunehiro , Fukada Junichi , Fukuda Kazumasa , Kawakubo Hirofumi , Saikawa Yoshiro , Kawaguchi Osamu , Takeuchi Hiroya , Shigematsu Naoyuki , Kitagawa Yuko
Published: January 2014

Background

In patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression was frequently observed, leading to treatment delay in several cases. To decrease toxicity and improve efficacy, we planned a phase I study with a modified chemotherapy regimen with biweekly cisplatin.

Methods

Patients with advanced gastric cancer and lymph node metastasis who were treated by our institution between 2011 and 2012 were eligible for inclusion. The initial chemoradiotherapy schedule consisted of 6 weeks of S-1 orally administered on days 1–15 with an escalating dose of cisplatin administered on days 1 and 15. The starting dose (level 1) of cisplatin was 15 mg/m2, the second dose (level 2) was 20 mg/m2, and the third dose (level 3) was 25 mg/m2. Radiation of 40 Gy was administered in 20 fractions. After initial chemoradiotherapy, one cycle of combination chemotherapy with S-1 plus cisplatin was delivered. The second cycle was 42 days in duration and included S-1 administered on days 1–29 plus biweekly cisplatin administered on days 1, 15, and 29. After neoadjuvant treatment, a curative gastrectomy with extended (D2) lymph node dissection was planned.

Results

Nine patients were enrolled. At level 3, one patient had dose-limiting grade 3 diarrhea. Another patient experienced grade 3 nausea and intended to discontinue the treatment. Overall, because 2 of 3 patients experienced dose-limiting toxicity at level 3, we confirmed level 3 (Cisplatin 25 mg/m2) as the maximum tolerated dose and level 2 (Cisplatin 20 mg/m2) as the recommended dose (RD). The response rate was 78%, and 8 patients underwent curative gastrectomy. Resected specimens showed a histological response in 6 patients (75%), including one with a pathological complete response.

Conclusions

In this phase I trial, RD of cisplatin was identified as 20 mg/m2. Generally, S-1 plus biweekly cisplatin can be given safely with concurrent radiation. We have initiated a multicenter phase II trial to further confirm the efficacy and safety of this approach.

Trial registration

UMIN000008941
Recombinant human mannose-binding lectin dampens human alveolar macrophage inflammatory responses to influenza A virus in vitro
Authors: Nelson Benjamin , Zhou Xiuqin , White Mitchell , Hartshorn Kevan , Takahashi Kazue , Kinane T Bernard , Anandaiah Asha , Koziel Henry
Published: January 2014

IAV pneumonia remains a serious global health problem, and preventative and therapeutic strategies remain limited. AM are critical effector cells in the control of influenza, impairing IAV replication, promoting IAV clearance, and promoting efferocytosis and resolution of lung inflammation. MBL, an innate immune pattern recognition molecule, present in the lungs, binds IAV, and plasma MBL deficiency is associated with increased susceptibility to IAV, although the mechanism remains incompletely understood, and the influence of MBL on the IAV-AM interaction has not been established. In the current study, focusing on human macrophages (U937 cell line and clinically relevant human AM), data demonstrated that unopsonized IAV is readily internalized, induced release of TNF and ROS, and promoted macrophage apoptosis. In contrast, IAV, opsonized with rhMBL, reduced IAV uptake and macrophage apoptosis and dramatically reduced TNF release and ROS. Macrophage host-defense responses were reduced further in the presence of MASPs. Taken together, these data support the concept that rhMBL may serve a protective innate host response and a critical biological response modifier function by limiting AM inflammation, oxidative injury, and AM apoptosis, which may allow effective IAV clearance while limiting collateral damage to vital organs, such as the lungs.
Rac1 and Rac2 control distinct events during antigen-stimulated mast cell exocytosis
Authors: Baier Alicia , Ndoh Vivian N E , Lacy Paige , Eitzen Gary
Published: January 2014

The release of preformed mediators from immune cells is through a process described as exocytosis. In mast cells, exocytosis is regulated by several coordinated intracellular signaling pathways. Here, we investigated the role of the hematopoietic-specific Rho GTPase, Rac2, and the ubiquitously expressed Rac1, in controlling mast cell exocytosis. These two isoforms showed equivalent levels of expression in mouse BMMCs. Although Rac1 and Rac2 share 92% sequence identity, they were not functionally redundant, as Rac2−/− BMMCs were defective in exocytosis, even though Rac1 levels were unaffected. Antigen-stimulated WT mast cells underwent a series of morphological transitions: initial flattening, followed by actin-mediated peripheral membrane ruffling and calcium influx, which preceded exocytosis. Whereas membrane ruffling was unaffected in Rac2−/− BMMCs, calcium influx was decreased significantly. Calcium influx was studied further by examining SOCE. In Rac2−/− BMMCs, the activation of PLCγ1 and calcium release from intracellular stores occurred normally; however, activation of plasma membrane calcium channels was defective, shown by the lack of extracellular calcium influx and a reduction of YFP-STIM1 puncta at the plasma membrane. Additionally, we used the small molecule Rac inhibitor, EHT 1864, to target Rac signaling acutely in WT BMMCs. EHT 1864 blocked exocytosis and membrane ruffling completely in conjunction with exocytosis. Our findings suggest that antigen-stimulated membrane ruffling in mast cells is a Rac1-mediated process, as this persisted in the absence of Rac2. Therefore, we define distinct modes of Rac-regulated mast cell exocytosis: Rac2-mediated calcium influx and Rac1-mediated membrane ruffling.
Macrophage uptake and accumulation of folates are polarization-dependent in vitro and in vivo and are regulated by activin A
Authors: Samaniego Rafael , Palacios Blanca Soler , Domiguez-Soto Ángeles , Vidal Carlos , Salas Azucena , Matsuyama Takami , Sánchez-Torres Carmen , de la Torre Inmaculada , Miranda-Carús Maria Eugenia , Sánchez-Mateos Paloma , Puig-Kröger Amaya
Published: January 2014

Vitamin B9, commonly known as folate, is an essential cofactor for one-carbon metabolism that enters cells through three major specialized transporter molecules (RFC, FR, and PCFT), which differ in expression pattern, affinity for substrate, and ligand-binding pH dependency. We now report that the expression of the folate transporters differs between macrophage subtypes and explains the higher accumulation of 5-MTHF—the major folate form found in serum—in M2 macrophages in vitro and in vivo. M1 macrophages display a higher expression of RFC, whereas FRβ and PCFT are preferentially expressed by anti-inflammatory and homeostatic M2 macrophages. These differences are also seen in macrophages from normal tissues involved in folate transit (placenta, liver, colon) and inflamed tissues (ulcerative colitis, RA), as M2-like macrophages from normal tissues express FRβ and PCFT, whereas TNF-α-expressing M1 macrophages from inflamed tissues are RFC+. Besides, we provide evidences that activin A is a critical factor controlling the set of folate transporters in macrophages, as it down-regulates FRβ, up-regulates RFC expression, and modulates 5-MTHF uptake. All of these experiments support the notion that folate handling is dependent on the stage of macrophage polarization.
Regulation of Osteoblast Differentiation Mediated by Bone Morphogenetic Proteins, Hedgehogs, and Cbfa1
Authors: Yamaguchi Akira , Komori Toshihisa , Suda Tatsuo
Published: January 2014

Osteoblasts arise from common progenitors with chondrocytes, muscle and adipocytes, and various hormones and local factors regulate their differentiation. We review here regulation of osteoblast differentiation mediated by the local factors such as bone morphogenetic proteins (BMPs) and hedgehogs and the transcription factor, core-binding factor α-1 (Cbfa1). BMPs are the most potent regulators of osteoblast differentiation among the local factors. Sonic and Indian hedgehogs are involved in osteoblast differentiation by interacting with BMPs. Cbfa1, a member of the runt domain gene family, plays a major role in the processes of a determination of osteoblast cell lineage and maturation of osteoblasts. Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation, because Cbfa1-deficient mice completely lacked bone formation due to maturation arrest of osteoblasts. Although the regulatory mechanism of Cbfa1 expression has not been fully clarified, BMPs are an important local factor that up-regulates Cbfa1 expression. Thus, the intimate interaction between local factors such as BMPs and hedgehogs and the transcription factor, Cbfa1, is important to osteoblast differentiation and bone formation.
Premature Adrenarche—Normal Variant or Forerunner of Adult Disease?*
Authors: Ibáñez Lourdes , DiMartino-Nardi Joan , Potau Neus , Saenger Paul
Published: January 2014

Adrenarche is the puberty of the adrenal gland. The descriptive term pubarche indicates the appearance of pubic hair, which may be accompanied by axillary hair. This process is considered premature if it occurs before age 8 yr in girls and 9 yr in boys.

The chief hormonal product of adrenarche is dehydroepiandrosterone (DHEA) and its sulfated product DHEA-S. The well documented evolution of adrenarche in primates and man is incompatible with either a neutral or harmful role for DHEA and implies most likely a positive role for some aspect of young adult pubertal maturation and developmental maturation. Premature adrenarche has no adverse effects on the onset and progression of gonadarche in final height.

Both extra- and intraadrenal factors regulate adrenal androgen secretion. Recent studies have shown that premature adrenarche in childhood may have consequences such as functional ovarian hyperandrogenism, polycystic ovarian syndrome, and insulin resistance in later life, sometimes already recognizable in childhood or adolescence. Premature adrenarche may thus be a forerunner of syndrome X in some children. The association of these endocrine-metabolic abnormalities with reduced fetal growth and their genetic basis remain to be elucidated.
The Somatomedin Hypothesis: 2001
Authors: Le Roith Derek , Bondy Carolyn , Yakar Shoshana , Liu Jun-Li , Butler Andrew
Published: January 2014

Since the original somatomedin hypothesis was conceived, a number of important discoveries have allowed investigators to modify the concept. Originally somatic growth was thought to be controlled by pituitary GH and mediated by circulating insulin-like growth factor-I (IGF-I, somatomedin C) expressed exclusively by the liver. With the discovery that IGF-I is produced by most, if not all, tissues, the role of autocrine/paracrine IGF-I vs. the circulating form has been hotly debated. Recent experiments using transgenic and gene-deletion technologies have attempted to answer these questions. In the liver-specific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF-I levels are normal. Thus, the normal postnatal growth and development in these animals may be due to normal free IGF-I levels (from as yet unidentified sources), although the role of autocrine/paracrine IGF-I has yet to be determined.
Signal Transducer and Activator of Transcription (STAT)-A and STAT5B Differentially Regulate Human Mammary Carcinoma Cell Behavior
Authors: Tang Jian-Zhong , Zuo Ze-Hua , Kong Xiang-Jun , Steiner Michael , Yin Zhinan , Perry Jo K. , Zhu Tao , Liu Dong-Xu , Lobie Peter E.
Published: January 2014

Increased signal transducer and activator of transcription (STAT)-5 activation has been reported in various malignancies including mammary carcinoma. However, it is only recently that potentially distinct roles of STAT5A and STAT5B in neoplasia have begun to emerge. Herein we systematically delineate the functions of STAT5A and STAT5B in human mammary carcinoma cells. Forced expression of constitutively active (CA) STAT5A enhanced both survival and anchorage-independent growth of human mammary carcinoma cells but concordantly suppressed cell motility as revealed in colony scattering, cell migration, and invasion assays. In contrast, forced expression of CA STAT5B exhibited lower potency than CA STAT5A in enhancing survival and anchorage-independent growth of mammary carcinoma cells and exerted no effects on cell motility. Differential expression of genes that regulate cellular survival and motility was concomitantly observed on forced expression of CA STAT5A or CA STAT5B. We also observed that functions of STAT5A and STAT5B were similarly differential in T47D cells. Small interfering RNA-mediated depletion of STAT5A significantly impaired anchorage-independent growth of MCF-7 cells, whereas a smaller reduction was observed upon small interfering RNA-mediated depletion of STAT5B. Depletion of endogenous STAT5A also significantly enhanced cell motility, whereas depletion of endogenous STAT5B exhibited no effect. Xenograft studies provided data concordant with the in vitro effects of the two STAT5 isoforms. We therefore demonstrate that STAT5A and STAT5B differentially regulate behavior of human mammary carcinoma cells.
The Central Regulation of Bone Mass, the First Link between Bone Remodeling and Energy Metabolism
Authors: Karsenty Gerard , Oury Franck
Published: January 2014

Evolutionary consideration and clinical observations led us to hypothesize 10 yr ago that there may be a coordinated regulation, endocrine in nature, of bone remodeling and energy metabolism. The existence of this coordinated regulation is motivated by the energetic needs of the skeleton; therefore, this regulation relies on hormones that appear during evolution with the skeleton, not with energy metabolism. Leptin is such a hormone, and it is a critical regulator of bone mass as well as of appetite and energy expenditure. This review goes over the anatomical route and molecular pathways used by leptin to inhibit both bone mass accrual and appetite through its signaling in the brain.
Does a Short Loop Feedback Mechanism for the Control of Luteinizing Hormone Secretion Exist in the Ewe?*
Authors: Skinner Donal C. , Evans Neil P. , Malpaux BenoÎt
Published: January 2014

It is not known whether a short loop feedback mechanism for the regulation of LH exists in sheep. This study on ovariectomized ewes investigated whether a bolus injection (10, 1, and 0.1 μg LH or 1μ g BSA; n = 4) or a 3-h continuous infusion of exogenous LH (100 or 1 ng/min; n = 7) into the third ventricle through a permanent indwelling cannula could influence the activity of the GnRH pulse generator, as determined by measurement of endogenous LH secretion. To assess the potential for involvement in a LH short loop feedback system and to estimate the level of LH in the hypothalamic milieu, the concentrations of LH in the peripheral circulation, portal circulation, and third ventricle were measured during an estradiol-induced preovulatory LH surge (n = 4).

Neither the bolus nor continuous administration of LH into the third ventricle had any effect on the mean interpulse interval, nadir, pulse amplitude, or circulating level of systemic LH. Furthermore, despite portal LH concentrations being more than 20-fold higher than jugular LH concentrations, LH levels in third ventricular cerebrospinal fluid remained barely detectable and did not reflect dynamic secretory events in the peripheral or hypothalamo-hypophyseal portal blood. These data demonstrate that in ewes, little pituitary LH reaches the third ventricle, and the small amount that does is unable to affect peripheral gonadotropin release. Our study suggests, therefore, that a short loop feedback system for LH does not exist in the ewe.