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The article proposes a delivery strategy to enhance tumor-selective immune checkpoint inhibitors (ICI) accumulation, which leverages the responsiveness of platelets and platelet-derivatives to coagulation cascade signals. Topics include synthesis and characterization of fusion protein tissue factor-Arg-Gly-Asp (tTF-RGD), recruitment of plate membrane nanoparticles (PM-NP) to the tumor site by tTF-RGD in a patient-derived xenograft (PDX) model, and characterization of tTF and tTF-RGD.

Subgridding unconditionally-stable finiteelement time-domain method based on spatial modes filtering (SSMF-FETD) is combined with the Floquet theorem and used to analyze the transmission characteristics of 2-D dielectric pillar-array electromagnetic bandgap (EBG) structures with cross-section shapes of square and H. The computational stress is effectively reduced by exploiting the periodicity of the EBG structure and subgridding technique. Through the spatial modes filtering (SMF) method, the subgridding FETD (S-FETD) method is developed into the SSMF-FETD with larger time steps and higher computational efficiency. The effect of geometric and electromagnetic parameters on transmission characteristics of EBG structures are analyzed and compared in detail, the conclusions are as follows: the optimal filling ratio of the dielectric squarepillar EBG structure is 0.5, the composite H-pillar EBG structure has multiple bandgaps and can effectively save metal materials while satisfying the design requirements. The effect of electromagnetic parameters can be uniformly analyzed from the perspective of the average relative permittivity; with its increase, the central frequency of the bandgap becomes lower. It should be noted that the bandgap distribution and variation of composite H-pillar EBG structure are related to how its dielectric parameters change and combine. The results can serve as a reference for similar structures design. [ABSTRACT FROM AUTHOR]

Subgridding unconditionally-stable finiteelement time-domain method based on spatial modes filtering (SSMF-FETD) is combined with the Floquet theorem and used to analyze the transmission characteristics of 2-D dielectric pillar-array electromagnetic bandgap (EBG) structures with cross-section shapes of square and H. The computational stress is effectively reduced by exploiting the periodicity of the EBG structure and subgridding technique. Through the spatial modes filtering (SMF) method, the subgridding FETD (S-FETD) method is developed into the SSMF-FETD with larger time steps and higher computational efficiency. The effect of geometric and electromagnetic parameters on transmission characteristics of EBG structures are analyzed and compared in detail, the conclusions are as follows: the optimal filling ratio of the dielectric squarepillar EBG structure is 0.5, the composite H-pillar EBG structure has multiple bandgaps and can effectively save metal materials while satisfying the design requirements. The effect of electromagnetic parameters can be uniformly analyzed from the perspective of the average relative permittivity; with its increase, the central frequency of the bandgap becomes lower. It should be noted that the bandgap distribution and variation of composite H-pillar EBG structure are related to how its dielectric parameters change and combine. The results can serve as a reference for similar structures design. [ABSTRACT FROM AUTHOR]

The article offers information on the role of the anti–programmed cell death 1 ligand 1 (PD-L1) therapy in the treatment of the Cancer. It report development of the nanocomplex composed of fluorinated polymerized chemokine receptor type 4 antagonism and paclitaxel-loaded human serum albumin for pulmonary delivery of anti–PD-L1 small interfering RNA to treat orthotopic lung tumors.

Proliferative diabetic retinopathy (PDR) is the leading cause of blindness and accounts for approximately 12 % of all new cases of blindness. Prostaglandin E2 (PGE2) and nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes have been long considered to be associated with PDR. Levels of pro-inflammatory mediators were examined by Enzyme-linked immunosorbent assay (ELISA) measurements. PGE2 levels were analyzed by using the Prostaglandin E2 Monoclonal EIA Kit. Human retinal microvascular endothelial cells (HRMECs) were stained with Annexin V/ propidium iodide and analyzed by flow cytometry for testing the apoptosis. Expression levels of NLRP3 inflammasome components under various conditions were detected by Western blot and real-time PCR. Inflammasome markers and PGE2 were highly expressed in the vitreous of PDR patients. PGE2 and NLRP3 induced apoptosis of HRMECs. PGE2 upregulated the expression of NLRP3 inflammasome components and inflammatory chemokines. Knockdown of NLRP3 attenuated the expression of NLRP3 inflammasome components and inhibited the effect of PGE2. Our results suggest that PGE2 levels and NLRP3 inflammasome activation are closely related to the pathogenesis of PDR and nonsteroidal anti-inflammatory drugs may have a potential therapeutic effect on PDR. [ABSTRACT FROM AUTHOR]

Objective: Hemicastration is a unilateral orchiectomy to remove an injured testis, which can induce hormonal changes and compensatory hypertrophy of the remaining testis, and may influence spermatogenesis. However, the underlying molecular mechanisms are poorly understood. Here, we investigated the impact of hemicastration on remaining testicular function. Methods: Prepubertal mice (age 24 days) were hemicastrated, and their growth was monitored until they reached physical maturity (age 72 days). Subsequently, we determined testis DNA methylation patterns using reduced representation bisulfite sequencing of normal and hemicastrated mice. Moreover, we profiled the testicular gene expression patterns by RNA sequencing (RNA-seq) to examine whether methylation changes affected gene expression in hemicastrated mice. Results: Hemicastration did not significantly affect growth or testosterone (p>0.05) compared with control. The genome-wide DNA methylation pattern of remaining testis suggested that substantial genes harbored differentially methylated regions (1,139) in gene bodies, which were enriched in process of protein binding and cell adhesion. Moreover, RNA-seq results indicated that 46 differentially expressed genes (DEGs) involved in meiotic cell cycle, synaptonemal complex assembly and spermatogenesis were upregulated in the hemicastration group, while 197 DEGs were downregulated, which were related to arachidonic acid metabolism. Integrative analysis revealed that proteasome 26S subunit ATPase 3 interacting protein gene, which encodes a protein crucial for homologous recombination in spermatocytes, exhibited promoter hypomethylation and higher expression level in hemicastrated mice. Conclusion: Global profiling of DNA methylation and gene expression demonstrated that hemicastration-induced compensatory response maintained normal growth and testicular morphological structure in mice. [ABSTRACT FROM AUTHOR]

Based on the published Avian reticuloendotheliosis virus (REV) whole genome sequence, primers and TaqMan probes were designed and synthesized, and the TaqMan probe fluorescence real-time quantitative RT-PCR (qRT-PCR) method for detecting the REV pol gene was established by optimizing the reaction conditions. Sensitivity analysis showed that the qRT-PCR method had a sensitivity that was 1,000-fold higher than conventional PCR. Additionally, no amplification signals were obtained when we attempted to detect DNA or cDNA of ALV-A/B/J, MDV, CIAV, IBDV, ARV, NDV, AIV, or other viruses, suggesting a high specificity for our method. Various titers of REV were artificially "spiked" into the FPV and MDV vaccines to simulate REV contamination in attenuated vaccines to validate this qRT-PCR method. Our findings indicated that this qRT-PCR method could detect REV contamination at a dose of 1 TCID50/1,000 feathers, which was 10,000-fold more sensitive than the regular RT-PCR detection (104 TCID50/1000 feathers). [ABSTRACT FROM AUTHOR]

One-and-a-half syndrome with facial diplegia, also referred to as the fifteen-and-a-half syndrome, is an extremely rare clinical entity caused by involvement of bilateral tegmentum of pons. Herein, we report a 52-year-old male who presented with one-and-a-half syndrome with left facial paralysis, which was consistent with the so-called eight-and-a-half syndrome. Brain magnetic resonance imaging showed pontine infarction. Five days after initiation of antiplatelet therapy, the patient developed right facial paralysis, a diagnosis of fifteen-and-a-half syndrome was made, repeat MR imaging revealed bilateral pontine tegmentum infarction. Fifteen-and-a-half syndrome is a newly proposed concept associated with pontine infarction. The clinicoradiological features of this specific disease are as yet unclear due to its extreme rarity. The current case would help advance the current understanding of the disease spectrum of pontine infarction. [ABSTRACT FROM AUTHOR]

A large amount of studies show that real-world study has strong external validity than the traditional randomized controlled trials and can evaluate the effect of interventions in a real clinical setting, which open up a new path for researches of integrative medicine in coronary heart disease. However, clinical data of integrative medicine in coronary heart disease are large in amount and complex in data types, making exploring the appropriate methodology a hot topic. Data mining techniques are to analyze and dig out useful information and knowledge from the mass data to guide people's practices. The present review provides insights for the main features of data mining and their applications of integrative medical studies in coronary heart disease, aiming to analyze the progress and prospect in this field. [ABSTRACT FROM AUTHOR]

We have presented an innovative laser-assisted reduction surgery (LARS) based on plasma-induced ablation and photodisruption effects. In addition, we developed a laser operation system. Fetuses of mice from the Institute for Cancer Research that were immersed in physiological saline were irradiated by convergent-pulsed laser with a wavelength of 1064 nm, pulse width of 6 ns, and pulse energy of 50 mJ. The hearts of the postirradiated fetuses were significantly damaged, which resulted in rapid fetal death.We also substantiated the safety of LARS by analyzing the heat distribution of the induced laser pulse with thermal distribution equations. The results demonstrate that this innovative method for pregnancy reduction is feasible. [ABSTRACT FROM AUTHOR]

Single-cell technologies are revolutionizing the entire field of biology. The large volumes of data generated by single-cell technologies are high dimensional, sparse, and heterogeneous and have complicated dependency structures, making analyses using conventional machine learning approaches challenging and impractical. In tackling these challenges, deep learning often demonstrates superior performance compared to traditional machine learning methods. In this work, we give a comprehensive survey on deep learning in single-cell analysis. We first introduce background on single-cell technologies and their development, as well as fundamental concepts of deep learning including the most popular deep architectures. We present an overview of the single-cell analytic pipeline pursued in research applications while noting divergences due to data sources or specific applications. We then review seven popular tasks spanning different stages of the single-cell analysis pipeline, including multimodal integration, imputation, clustering, spatial domain identification, cell-type deconvolution, cell segmentation, and cell-type annotation. Under each task, we describe the most recent developments in classical and deep learning methods and discuss their advantages and disadvantages. Deep learning tools and benchmark datasets are also summarized for each task. Finally, we discuss the future directions and the most recent challenges. This survey will serve as a reference for biologists and computer scientists, encouraging collaborations. [ABSTRACT FROM AUTHOR]

Koi herpesvirus (KHV) is highly contagious and lethal to cyprinid fish, causing significant economic losses to the carp aquaculture industry, particularly to koi carp breeders. Vaccines delivered through intramuscular needle injection or gene gun are not suitable for mass vaccination of carp. So, the development of cost-effective oral vaccines that are easily applicable at a farm level is highly desirable. In this study, we utilized chitosan-alginate capsules as an oral delivery system for a live probiotic (Lactobacillus rhamnosus) vaccine, pYG-KHV-ORF81/LR CIQ249, expressing KHV ORF81 protein. The tolerance of the encapsulated recombinant Lactobacillus to various digestive environments and the ability of the probiotic strain to colonize the intestine of carp was tested. The immunogenicity and the protective efficacy of the encapsulated probiotic vaccine was evaluated by determining IgM levels, lymphocyte proliferation, expression of immune-related genes, and viral challenge to vaccinated fish. It was clear that the chitosan-alginate capsules protected the probiotic vaccine effectively against extreme digestive environments, and a significant level (P < 0.01) of antigen-specific IgM with KHV-neutralizing activity was detected, which provided a protection rate of ca. 85% for koi carp against KHV challenge. The strategy of using chitosan-alginate capsules to deliver probiotic vaccines is easily applicable for mass oral vaccination of fish. [ABSTRACT FROM AUTHOR]

Interference alignment (IA) is a promising technique to effectively manage the interference. The realization of IA requires a proliferation of feedback bits. In a general centralized feedback model, the feedback rate of the precoder and the decoder affects the performance of the IA directly. In this paper, to improve the feedback efficiency of the precoder and the decoder, a strategy that can adaptively allocate the feedback bits of the precoder and the decoder is proposed. We consider the effect of link loss on the throughput loss caused by the quantization error of the precoder and decoder. An upper bound of leaked interference as a function of the link loss and the feedback bits of the precoders and the decoders is derived. The feasibility conditions for dynamically allocating the feedback bits of the precoder and the decoder are analyzed. It is proven that the properties of general asymmetric interference network can satisfy the feasibility conditions for dynamic feedback scheme. According to the simulation results, our proposed scheme achieves higher throughput compared with the conventional schemes in the asymmetric interference network. [ABSTRACT FROM AUTHOR]

A highly site-selective acyloxylation of stable enamines with PhI(OAc)2 under metal-free conditions to afford (E)-vinyl acetate derivatives in good to excellent yields is described. Depending on the judicious choice of the solvent system, either the α- or β-site-selective product could be obtained with high selectivity. For the α-site-selective product, the rearranged amide compound is obtained as the major product. This reaction proceeds under mild reaction conditions (room temperature, metal-free, and open-flask) and features a broad substrate scope. [ABSTRACT FROM AUTHOR]

• Farmland shelterbelt systems (FSSs) can improve ecosystem functions over controls. • Environmental factors exhibit spatiotemporal heterogeneities in different FSSs. • Different patterns of FSSs had beneficial water retention and nutrient supply functions. • There were close relationships between environmental factors and ecosystem functions in FSSs. • Results provide a theoretical basis for ecological restoration in ecofragile regions. The farmland shelterbelt system is considered an effective form of land management to improve the eco-environment and soil quality in fragile agricultural areas. Clarifying the effects of farmland shelterbelt patterns on ecosystem functions can guide ecological restoration in fragile ecosystems. Four typical farmland shelterbelt patterns (i.e., two-line pattern, four-line pattern, five-line pattern, and eight-line pattern) in desert oasis ecotones of Hetao irrigated area, northern China, were selected in this study. In these treatments, measurements of soil properties at a depth of 0–100 cm; vegetation attributes; microclimate; and soil water, carbon, nitrogen, and phosphorus storage were performed during three growing seasons in 2019–2021. The results demonstrated that the four-line pattern had higher soil organic content (0.339 g·kg−1), total nitrogen content (0.517 g·kg−1), and total phosphorus content (0.577 g·kg−1) than the other treatments, as well as the highest soil water (237.44 mm), carbon (544.93 g·m−2), nitrogen (953.72 g·m−2), and phosphorus storage (859.04 g·m−2) at the 0–100-cm soil layer. Moreover, dynamic variations in soil water and salt contents showed opposite trends during the growing season, i.e., they showed a gradual decrease and increase, respectively. Furthermore, principal component analysis, correlation matrix analyses, and network association analyses indicated close relationships among environmental factors, nutrient storage, and related ecosystem functions under different farmland shelterbelt patterns. The results of this investigation provide a useful theoretical basis for agricultural management and ecological restoration in ecofragile regions. [ABSTRACT FROM AUTHOR]

It is necessary to improve the energy efficiency of batteries in wireless sensor networks (WSNs). The multiple-input multiple-output (MIMO) technique has become an important means to ameliorate WSNs, and interference management is the core of improving energy efficiency. A promising approach is interference alignment (IA), which effectively reduces the interference and improves the throughput of a system in the MIMO interference channels. However, the IA scheme requires perfect channel state information (CSI) at all transceivers in practice, which results in considerable feedback overhead. Thus, limited IA feedback has attracted much attention. In this paper, we analyze the throughput loss of the K-user MIMO interference channels when each transmitter delivers multiple streams in one slot, and derives the upper-bound of the system interference leakage and throughput loss. Then, to reduce the interference leakage and throughput loss for the MIMO interference alignment with limited feedback, a joint power and feedback bit allocation optimization scheme is proposed. The simulation results show that, compared with the conventional schemes, the presented optimal scheme achieves less residual interference and better performance in the system throughput. [ABSTRACT FROM AUTHOR]

The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERSCoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface. [ABSTRACT FROM AUTHOR]

A method to detect delamination in a composite material, using a surface mounted fiber Bragg grating (FBG) sensor, is proposed in this paper. In this method, the static strain is measured to accurately detect the delamination area. Experiments are carried out and results show the relation between the wavelength shift and the distance between the FBG center and the delaminated area. The sensitivity of this method is also discussed. Results show the feasibility of this technique for structural health monitoring applications. [ABSTRACT FROM AUTHOR]

We propose in this letter a simple and cost-effective method for a bandwidth enhancement of multimode fiber (MMF) using periodic mode scrambling. Simulations and experiments were carried out to verify the feasibility of this method, and results show that the bandwidth of multimode fiber is increased by about two times. This scheme can be used to support future large-bandwidth applications by upgrading existing MMF links. [ABSTRACT FROM AUTHOR]

Bovine viral diarrhea virus (BVDV) is the causative agent of the bovine viral diarrhea-mucosal disease, which is a leading cause of economic losses in the cattle industry worldwide. To date, many underlying mechanisms involved in BVDV-host interactions remain unclear, especially the functions of long noncoding RNAs (lncRNAs). In our previous study, the lncRNA expression profiles of BVDVinfected Madin-Darby bovine kidney (MDBK) cells were obtained by RNA-seq, and a significantly downregulated lncRNA IALNCR targeting MAPK8/JNK1 (a key regulatory factor of apoptosis) was identified through the lncRNA-mRNA coexpression network analysis. In this study, the function of IALNCR in regulating apoptosis to affect BVDV replication was further explored. Our results showed that BVDV infection-induced downregulation of the lncRNA IALNCR in the host cells could suppress the expression of MAPK8/JNK1 at both the mRNA and protein levels, thereby indirectly promoting the activation of caspase-3, leading to cell-autonomous apoptosis to antagonize BVDV replication. This was further confirmed by the small interfering RNA (siRNA)-mediated knockdown of the lncRNA IALNCR. However, the overexpression of the lncRNA IALNCR inhibited apoptosis and promoted BVDV replication. In conclusion, our findings demonstrated that the lncRNA IALNCR plays an important role in regulating host antiviral innate immunity against BVDV infection. [ABSTRACT FROM AUTHOR]

Proteolysis Targeting Chimeras (PROTACs), an emerging therapeutic entity designed to degrade target proteins by hijacking the ubiquitin–proteasome system, have the potential to revolutionize the healthcare industry. The broad applicability of this protein degradation strategy has been verified with a few E3 ligases and a variety of distinct targets through the construction of modular chimeric structures. Despite recent efforts to promote the use of PROTACs for clinical applications, most PROTACs do not make it beyond the preclinical stage of drug development. There are several reasons that prevent PROTACs from reaching the market, and the inadequate delivery to the target site is one of the most challenging hurdles. With the increasing need for accelerating the translational process, combining the concepts of PROTACs and delivery systems has been explored to enhance the in vivo performance of PROTACs. These improved delivery strategies can eliminate unfavorable physicochemical properties of PROTACs, improve their targetability, and decrease their off-target side effects. The integration of powerful PROTACs and versatile delivery systems will inaugurate a burgeoning orientation for the field of targeted protein degradation. In this review, we will survey the latest progress in improving the in vivo degradation efficacy of PROTACs through delivery strategies, outline design principles for PROTACbased delivery systems, discuss the current challenges with PROTACs, and outlook future opportunities in this field. [ABSTRACT FROM AUTHOR]

This article discusses the various schemes for generating typical advanced modulation formats in terms of configuration and cost, and particularly presents some recently proposed configurations for optical data generation with better performance or reduced components, including pulsed multichannel source generation for return-to-zero (RZ)-based WDM application, multichannel dual-mode pulse source for carrier-suppressed RZ (CSRZ)-based WDM application, CSRZ and CSRZ differential phase shift keyed (DPSK) signal generation using a single Mach-Zehnder modulator (MZM) together with an electrical mixer, chirped RZ generation with reduced modulator number, and RZ/CSRZ-DPSK generation using a single dual-drive MZM and optical minimum shift keying (MSK). [ABSTRACT FROM AUTHOR]

In this paper we propose a new method for the measurement of the relative group delay of WDM components, based on photonic microwave technique using a low frequency (below 1.3 GHz) scalar network analyzer. Experimental results demonstrate that this technique has the advantages of low cost, simplicity, and high accuracy (less than ±1 ps). © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 346–348, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10602 [ABSTRACT FROM AUTHOR]

Background: Trials reported there are beneficial effects of the addition of bevacizumab to chemotherapy in advanced cervical cancer but might have adverse effects. The purposes of the study were to evaluate the treatment response and safety of the addition of bevacizumab to paclitaxel plus carboplatin in advanced cervical cancer women. Methods: Data on treatment response, adverse effects, and overall survival of women who received paclitaxel plus carboplatin every 3 weeks (ACT cohort, n = 161) or paclitaxel, carboplatin, and bevacizumab every 3 weeks (PCB cohort, n = 127) until disease progression or severe adverse events were collected and analyzed. Results: The treatment response of paclitaxel plus carboplatin increased on addition of bevacizumab (P = .037). Neutropenia (grade ≥3, P = .001), leukopenia (grade 4, P = .041), anemia (grade ≥3, P = .031), hypertension (grade ≥2, P = .002), and gastrointestinal fistula (grade ≥2, P = 0.006) are reported in the PCB cohort. Women of ACT and PCB cohorts reported an overall survival of 20.11 ± 3.15 months and 24.52 ± 4.05 months, respectively. Conclusions: Addition of bevacizumab increases the treatment response of paclitaxel and carboplatin chemotherapy and overall survival of women with advanced cervical cancers, but it is not well tolerated. [ABSTRACT FROM AUTHOR]

Background: Pigeon crop has the unique ability to produce a nutrient rich substance termed pigeon ‘milk’ (PM), which has functional resemblance with the mammalian milk. Previous researches have demonstrated that a large number of exosomes and exosomal miRNAs exist in mammalian milk, and many of them are associated with immunity, growth and development. However, to date, little is known about the exosomes and exosomal miRNAs in PM. Results: In this study, we isolated the exosomes from PM and used small RNA sequencing to investigate the distribution and expression profiles of exosomal miRNAs. A total of 301 mature miRNAs including 248 conserved and 53 novel miRNAs were identified in five lactation stages i.e. 1d, 5d, 10d, 15d, and 20d. From these, four top 10 conserved miRNAs (cli-miR-21-5p, cli-miR-148a-3p, cli-miR-10a-5p and cli-miR-26a-5p) were co-expressed in all five stages. We speculate that these miRNAs may have important role in the biosynthesis and metabolism of PM. Moreover, similar to the mammalian milk, a significant proportion of immune and growth-related miRNAs were also present and enriched in PM exosomes. Furthermore, we also identified 41 orthologous miRNAs group (giving rise to 81 mature miRNA) commonly shared with PM, human, bovine and porcine breast milk. Additionally, functional enrichment analysis revealed the role of exosomal miRNAs in organ development and in growth-related pathways including the MAPK, Wnt and insulin pathways. Conclusions: To sum-up, this comprehensive analysis will contribute to a better understanding of the underlying functions and regulatory mechanisms of PM in squabs. [ABSTRACT FROM AUTHOR]

Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses, the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations. [ABSTRACT FROM AUTHOR]

Background: Avian leukosis virus (ALV) is one of the main causes of tumour development within the poultry industry in China. The subgroup J avian leukosis viruses (ALV-J), which induce erythroblastosis and myelocytomatosis, have the greatest pathogenicity and transmission ability within this class of viruses. ALV can be transmitted both horizontally and vertically; however, the effects of ALV infection in chickens-especially roosters-during the propagation, on future generations is not clear. Knowing the role of the cock in the transmission of ALV from generation to generation might contribute to the eradication programs for ALV. Results: The results showed that two hens inseminated with ALV-J-positive semen developed temporary antibody responses to ALV-J at 4-5 weeks post insemination. The p27 antigen was detected in cloacal swabs of six hens, and in 3 of 26 egg albumens at 1-6 weeks after insemination. Moreover, no viremia was detected at 6 weeks after insemination even when virus isolation had been conducted six times at weekly intervals for each of the 12 females. However, ALV-J was isolated from 1 of their 34 progeny chicks at 1 week of age, and its gp85 had 98.4%- 99.2% sequence identity with the gp85 of ALV-J isolated from semen samples of the six cocks. Conclusions: Our findings indicated that females that were late horizontally infected with ALV-J by artificial insemination might transmit the virus to progeny through eggs, which amounts to vertical transmission. [ABSTRACT FROM AUTHOR]

To investigate the possible causes of the massive spread of fowl adenovirus (FAdV) infection among chickens in recent years in China, 32 batches of live-virus vaccines were tested for contamination with FAdV by PCR. Among these, 1 live Newcastle disease virus (NDV) vaccine of the LaSota strain was demonstrated to be positive for contamination. The amplified hexon gene exhibited 99.8% identity with a recent Chinese field isolate (JSJ13) of FAdV-4. The positive LaSota vaccine was first neutralized with anti-NDV serum and then inoculated into specific pathogen-free embryos at embryonic day 5 through the yolk sac for isolation of the contaminated FAdV. The same hexon gene bands were amplified from extracted DNA of the liver tissues and chicken embryo allantoic fluid of the inoculated embryos, indicating the replication and isolation of the FAdV-4 virus strain that had contaminated the vaccine. This represents the first report of FAdV-4 contamination in a live vaccine for poultry in China. These findings suggest that contamination of live vaccine might represent one of the most important causes of massive outbreaks of FAdV infection among chickens and indicate that FAdV should therefore be included in the regular monitoring list for the detection of exogenous viral contamination of attenuated vaccines for poultry. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate possible causes of the pervasiveness of chicken infectious anemia virus (CIAV) infection in chickens in recent years in China. A total of 14 batches of live-virus vaccines were examined using PCR to detect CIAV contamination, of which only 2 samples (a Newcastle disease vaccine and a fowl pox vaccine) tested positive for CIAV. These Newcastle and fowl pox vaccines were then inoculated into 1-day-old specificpathogen- free chickens. Serum samples were collected from chickens infected with the PCR-positive vaccines, and these tested positive for CIAV-specific antibodies as tested using ELISA. In addition, DNA samples isolated from the serum samples also tested positive by PCR. The results indicated that the samples were contaminated with CIAV and identified 2 exogenous CIAV strains, designated CIAV-N22 and CIAV-F10, in the respective samples. The full genome sequences of these novel CIAV strains were sequenced and analyzed. Phylogenetic tree analysis indicated that the CIAV-F10 strain might represent a recombinant viral strain arising from the parental CIAV strains JQ690762 and KJ728816. Overall, the results suggested that vaccination with CIAV-contaminated vaccines contributed to the prevalence and spread of CIAV infection in chickens. Furthermore, the CIAV contaminant was likely subsequently transmitted to commercial chickens through congenital transmission. Our findings therefore highlight the need for more extensive screening of live-virus vaccines for poultry in China to reduce the threat of contamination with exogenous viruses. [ABSTRACT FROM AUTHOR]

Insulin resistance and diabetes can develop spontaneously with obesity and aging in rhesus monkeys, highly similar to the natural history of obesity, insulin resistance, and progression to type 2 diabetes in humans. The current studies in obese rhesus were undertaken to assess hepatic and adipose contributions to systemic insulin resistance--currently, a gap in our knowledge--and to benchmark the responses to pioglitazone (PIO). A two-step hyperinsulinemic-euglycemic clamp, with tracer-based glucose flux estimates, was used to measure insulin resistance, and in an intervention study was repeated following 6 wk of PIO treatment (3 mg/kg). Compared with lean healthy rhesus, obese rhesus has a 60% reduction of glucose utilization during a high insulin infusion and markedly impaired suppression of lipolysis, which was evident at both low and high insulin infusion. However, obese dysmetabolic rhesus manifests only mild hepatic insulin resistance. Six-week PIO treatment significantly improved skeletal muscle and adipose insulin resistance (by ~50%). These studies strengthen the concept that insulin resistance in obese rhesus closely resembles human insulin resistance and indicate the value of obese rhesus for appraising new insulin-sensitizing therapeutics. [ABSTRACT FROM AUTHOR]

Farmland shelterbelt system (FSS) in oasis desert ecotones can effectively improve ecosystem services, especially in fragile agricultural areas. However, the spatial-temporal heterogeneity of its ecological effects still needs further clarity, because the interactions are complex and multiple. Understanding this allows us to know the key practical significance of ecological construction and agricultural management. In this study, four typical patterns of FSS (i.e. two lines pattern, TWLP; four lines pattern, FOLP; five lines pattern, FILP; eight lines pattern, EILP) were selected in a desert oasis ecotone in northern China to assess the distributions at vertical (0–100 cm), horizontal (0–3 H) and temporal (May- October) scales of soil properties, vegetation attributes, microclimates and variations of soil moisture storage (SMS) and soil salt contents (C) during the three growing seasons. The results showed that the major difference in soil properties and vegetation attributes of FSSs are the soil particle composition and canopy size, respectively. In FOLP and EILP, the silt contents were 51.6% and 41.5% respectively. The canopy size ranked from the highest to lowest values as follows: FOLP (8.70 m2) > EILP (6.91 m2) > TWLP (4.64 m2) > FILP (4.47 m2). Compared to the control, all patterns of FSSs registered significant effects on microclimate improvement. The FOLP and FILP achieved the same effects as well as EILP, with less spatial costs. Moreover, the variations of SMS and C were mainly different at the vertical scale. As indicated by the Redundancy (RDA) and variation partitioning (VP) analyses, soil properties played a more important role in reserving soil water and controlling soil salinity than vegetation attributes and microclimates, which the independent influence can explain 48.5% of total influence among all factors. Our results provide an efficient theoretical basis for FSS construction and agricultural water management practices. • Farmland shelterbelt system (FSS) can improve ecosystem services. • A spatio-temporal heterogeneity of ecosystem functions in FSSs is observed. • Soil properties play a more important role in controlling soil water content and salinity. • Results provide an efficient theoretical basis for agricultural water management in deserts. [ABSTRACT FROM AUTHOR]

We present and demonstrate experimentally a new method for measuring the polarization mode dispersion (PMD) of chirped fiber Bragg gratings. The technique can also be used to measure chromatic dispersion (CD) more accurately by eliminating the influence of PMD. [ABSTRACT FROM AUTHOR]

With the open-loop fiber optic gyro (OFOG) model, output voltage and angular velocity can effectively compensate OFOG errors. However, the model cannot reflect the characteristics of OFOG errors well when it comes to pretty large dynamic angular velocities. This paper puts forward a modeling scheme with OFOG output voltage u and temperature T as the input variables and angular velocity error Δω as the output variable. Firstly, the angular velocity error Δω is extracted from OFOG output signals, and then the output voltage u, temperature T and angular velocity error Δω are used as the learning samples to train a Radial-Basis-Function (RBF) neural network model. Then the nonlinear mapping model over T, u and Δω is established and thus Δω can be calculated automatically to compensate OFOG errors according to T and u . The results of the experiments show that the established model can be used to compensate the nonlinear OFOG errors. The maximum, the minimum and the mean square error of OFOG angular velocity are decreased by 97.0%, 97.1% and 96.5% relative to their initial values, respectively. Compared with the direct modeling of gyro angular velocity, which we researched before, the experimental results of the compensating method proposed in this paper are further reduced by 1.6%, 1.4% and 1.2%, respectively, so the performance of this method is better than that of the direct modeling for gyro angular velocity. [ABSTRACT FROM AUTHOR]

Little is known about the molecular mechanisms underlying age-dependent deterioration in β-cell function. We now demonstrate that age-dependent impairment in insulin release, and thereby glucose homeostasis, is associated with subtle changes in Ca2+ dynamics in mouse β-cells. We show that these changes are likely to be accounted for by impaired mitochondrial function and to involve phospholipase C/inositol 1,4,5-trisphosphate-mediated Ca2+ mobilization from intracellular stores as well as decreased β-cell Ca2+ influx over the plasma membrane. We use three mouse models, namely, a premature aging phenotype, a mature aging phenotype, and an aging-resistant phenotype. Premature aging is studied in a genetically modified mouse model with an age-dependent accumulation of mitochondrial DNA mutations. Mature aging is studied in the C57BL/6 mouse, whereas the 129 mouse represents a model that is more resistant to age-induced deterioration. Our data suggest that aging is associated with a progressive decline in β-cell mitochondrial function that negatively impacts on the fine tuning of Ca2+ dynamics. This is conceptually important since it emphasizes that even relatively modest changes in β-cell signal transduction over time lead to compromised insulin release and a diabetic phenotype. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and response to treatment. [ABSTRACT FROM AUTHOR]

Objective. Initial optimized prescription of Chinese herb medicine for unstable angina (UA). Methods. Based on partially observable Markov decision process model (POMDP), we choose hospitalized patients of 3 syndrome elements, such as qi deficiency, blood stasis, and turbid phlegm for the data mining, analysis, and objective evaluation of the diagnosis and treatment of UA at a deep level in order to optimize the prescription of Chinese herb medicine for UA. Results. The recommended treatment options of UA for qi deficiency, blood stasis, and phlegm syndrome patients were as follows: Milkvetch Root + Tangshen + Indian Bread + Largehead Atractylodes Rhizome (ADR = 0.96630); Danshen Root + Chinese Angelica + Safflower + Red Peony Root + Szechwan Lovage Rhizome Orange Fruit (ADR = 0.76); Snakegourd Fruit + Longstamen Onion Bulb + Pinellia Tuber + Dried Tangerine peel + Largehead Atractylodes Rhizome + Platycodon Root (ADR = 0.658568). Conclusion. This study initially optimized prescriptions for UA based on POMDP, which can be used as a reference for further development of UA prescription in Chinese herb medicine. [ABSTRACT FROM AUTHOR]

Tipifarnib (T) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia (AML). Based on preclinical synergy, a phase 1 trial of T plus etoposide (E) yielded 25% complete remission (CR). We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults (age range, 70-90 years; median, 76 years) who were not candidates for conventional chemotherapy. Arm A (T 600 mg twice a day × 14 days, E 100 mg days 1-3 and 8-10) and arm B (T 400 mg twice a day × 14 days, E 200 mg days 1-3 and 8-10) yielded similar CR, but arm B had greater toxicity. Total CR was 25%, day 30 death rate 7%. A 2-gene signature of high RASGRP1 and low aprataxin (APTX) expression previously predicted for T response. Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78% CR rate and negative predictive value 87%. This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies. The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771. [ABSTRACT FROM AUTHOR]

We evaluate the performance of the externally modulated optical minimum shift keying (MSK) signal. The tolerance against fiber dispersion, linear crosstalk, self phase modulation (SPM), and stimulated Brillouin scattering (SBS) threshold for MSK is studied and compared with that of 50% duty cycle return-to-zero differential phase shift keying (RZ-DPSK) and 50% duty cycle RZ on-off-keying (RZ-OOK), via both experiment and simulation. Simulation results show that the MSK signal has the widest tolerance against SPM and the smallest linear crosstalk among these formats. Experimental results agree with the simulation on negative penalty against SPM tolerance and show widest tolerance against dispersion tolerance for MSK. The measured SBS threshold of both MSK and RZ-DPSK is more than 10 dB higher than that of an RZ-OOK system. [ABSTRACT FROM AUTHOR]

Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://www.nature.com/group/journalclub [ABSTRACT FROM AUTHOR]

A total of 45 moderately halophilic bacteria was isolated from sediment and saline water collected from the Weihai Solar Saltern (China). The phylogenetic position of all the isolated strains was determined by 16S rRNA sequencing. The halophilic strains were tested for their antimicrobial activity. Cytotoxicity assay was performed to determine which of the halophilic strains could inhibit proliferation of human hepatocellular carcinoma Bel 7402 cells. Our results showed that all of the isolated 45 strains displayed moderately halophilic characteristics. Phylogenetic analysis indicated that 17 of the isolated strains were related to the phylum Firmicutes and belonged to four genera, Bacillus, Halobacillus, Planococcus and Salinicoccus. The other strains identified as genus of Halomonas belonged to phylum γ-Proteobacteria. Most of the halophilic bacterial strains showed potent activities against Gram-positive bacteria, human pathogenic fungi and plant pathogenic fungi. In addition, the crude extracts from 14 halophilic bacterial strains showed cytotoxic activity against tumor cells Bel 7402, and five of them showed remarkable activities with IC50 less than 40 μg ml−1. Our results suggest that the moderately halophilic bacteria may be developed as promising sources for the discovery of novel bioactive substances. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis is the most important prognostic factor in gastric cancer. However, diagnosis by hematoxylin and eosin staining or immunohistochemistry is not always sufficient for the detection of cancer cells because only representative number of slices are examined. Cancer cells may, therefore, be missed by traditional histological methods. Recently, reverse transcription polymerase chain reaction (RT-PCR) methods have been introduced for improved detection of cancer cells. The purpose of this study was to evaluate the utility of a prototype RT-PCR assay run on the Cepheid SmartCycler® system compared to conventional RT-PCR using the LightCycler® system. Patients and Methods: Forty-seven overt metastatic lymph nodes from 8 patients with advanced gastric cancer and 22 benign lymph nodes from patients without malignant tumor who received surgery were obtained with informed consent. We examined the lymph nodes by RT-PCR, using markers for CEA and CK19 and the LightCycler and SmartCycler systems. Results: In the singlex assay, the sensitivity of CEA and CK19 was 91.5 and 70.2% in the LightCycler system, and 97.9 and 95.7% in the SmartCycler system, respectively. In the multiplex assay, the sensitivity was 91.5% in the LightCycler system and 100% in the SmartCycler system, respectively. Conclusion: In this study, rapid diagnosis using RT-PCR by the SmartCycler system had higher accuracy for detecting lymph node metastasis than the conventional LightCycler system. The SmartCycler system is more effective for the diagnosis of lymph node metastasis in gastric cancer when run with the prototype assay. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Breast cancers lacking the estrogen receptor (ER) can be distinguished from other breast cancers on the basis of poor prognosis, high grade, distinctive histopathology and unique molecular signatures. These features further distinguish estrogen receptor negative (ER2) tumor subtypes, but targeted therapy is currently limited to tumors overexpressing the ErbB2 receptor. Methodology/Principal Findings: To uncover the pathways against which future therapies could be developed we undertook a meta-analysis of gene expression from five large microarray datasets relative to ER status. A measure of association with ER status was calculated for every Affymetrix HG-U133A probe set and the pathways that distinguished ER2 tumors were defined by testing for enrichment of biologically defined gene sets using Gene Set Enrichment Analysis (GSEA). As expected, the expression of the direct transcriptional targets of the ER was muted in ER2 tumors, but the expression of genes indirectly regulated by estrogen was enhanced. We also observed enrichment of independent MYCand E2F-driven transcriptional programs. We used a cell model of estrogen and MYC action to define the interaction between estrogen and MYC transcriptional activity in breast cancer. We found that the basal subgroup of ER2 breast cancer showed a strong MYC transcriptional response that reproduced the indirect estrogen response seen in estrogen receptor positive (ER+) breast cancer cells. Conclusions/Significance: Increased transcriptional activity of MYC is a characteristic of basal breast cancers where it mimics a large part of an estrogen response in the absence of the ER, suggesting a mechanism by which these cancers achieve estrogen-independence and providing a potential therapeutic target for this poor prognosis sub group of breast cancer. [ABSTRACT FROM AUTHOR]

Purpose. To define the biology driving the aggressive nature of breast cancer arising in young women. Experimental Design. Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young ≤45 years; older ≥65 years), 411 eligible patients (n = 200≤45 years; n = 211≥65 years) with clinically-annotated Affymetrix microarray data were identified. GSEA, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts. Results. In comparing deregulation of oncogenic pathways between age groups, a higher probability of PI3K (p = 0.006) and Myc (p = 0.03) pathway deregulation was observed in breast tumors arising in younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with a higher probability of PI3K, Myc, and β-catenin, conferred a worse prognosis (HR = 4.15). In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, with concurrent low probability of PI3K, Myc and β-catenin deregulation, was associated with poorer outcome (HR = 2.7). In multivariate analyses, genomic clusters of pathway deregulation illustrate prognostic value. Conclusion. Results demonstrate that breast cancer arising in young women represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that are prognostic, independent of currently available clinico-pathologic variables. These results should enable refinement of targeted treatment strategies in this clinically challenging situation. [ABSTRACT FROM AUTHOR]

The association between large tumor size and metastatic risk in a majority of clinical cancers has led to questions as to whether these observations are causally related or whether one is simply a marker for the other. This is partly due to an uncertainty about how metastasis-promoting gene expression changes can arise in primary tumors. We investigated this question through the analysis of a previously defined ‘lung metastasis gene-expression signature’ (LMS) that mediates experimental breast cancer metastasis selectively to the lung and is expressed by primary human breast cancer with a high risk for developing lung metastasis. Experimentally, we demonstrate that the LMS promotes primary tumor growth that enriches for LMS+ cells, and it allows for intravasation after reaching a critical tumor size. Clinically, this corresponds to LMS+ tumors being larger at diagnosis compared with LMS- tumors and to a marked rise in the incidence of metastasis after LMS+ tumors reach 2 cm. Patients with LMS-expressing primary tumors selectively fail in the lung compared with the bone or other visceral sites and have a worse overall survival. The mechanistic linkage between metastasis gene expression, accelerated tumor growth, and likelihood of metastatic recurrence provided by the LMS may help to explain observations of prognostic gene signatures in primary cancer and how tumor growth can both lead to metastasis and be a marker for cells destined to metastasize. [ABSTRACT FROM AUTHOR]

Background: Published prognostic gene signatures in breast cancer have few genes in common. Here we provide a rationale for this observation by studying the prognostic power and the underlying biological pathways of different gene signatures. Methods: Gene signatures to predict the development of metastases in estrogen receptor-positive and estrogen receptor-negative tumors were identified using 500 re-sampled training sets and mapping to Gene Ontology Biological Process to identify over-represented pathways. The Global Test program confirmed that gene expression profilings in the common pathways were associated with the metastasis of the patients. Results: The apoptotic pathway and cell division, or cell growth regulation and G-protein coupled receptor signal transduction, were most significantly associated with the metastatic capability of estrogen receptor-positive or estrogen-negative tumors, respectively. A gene signature derived of the common pathways predicted metastasis in an independent cohort. Mapping of the pathways represented by different published prognostic signatures showed that they share 53% of the identified pathways. Conclusion: We show that divergent gene sets classifying patients for the same clinical endpoint represent similar biological processes and that pathway-derived signatures can be used to predict prognosis. Furthermore, our study reveals that the underlying biology related to aggressiveness of estrogen receptor subgroups of breast cancer is quite different. [ABSTRACT FROM AUTHOR]

In this article we present the details of a generalized multi-protocol label switching controlled wavelength-division multiplexing (WDM) optical network developed under the Optical Network Focused Interest Group (ONFIG) program in Singapore. The WDM network is controlled through a GMPLS control plane that consists of CR-LDP, LMP, and OSPF-TE. We conducted various field trials on the GMPLS-capable WDM optical network testbed with the main focus on distributed storage service application. We developed and evaluated a distributed storage services application on the WDM optical network testbed and demonstrated that incorporating a lightweight data transport protocol with optical network control could be an efficient approach for data-intensive storage applications by exploiting the dynamic connection establishment and backup protection features. [ABSTRACT FROM AUTHOR]

Background: Farnesyl protein transferase inhibitors (FTIs) were originally developed to inhibit oncogenic ras, however it is now clear that there are several other potential targets for this drug class. The FTI tipifarnib (ZARNESTRA™, R115777) has recently demonstrated clinical responses in adults with refractory and relapsed acute leukemias. This study was conducted to identify genetic markers and pathways that are regulated by tipifarnib in acute myeloid leukemia (AML). Methods: Tipifarnib-mediated gene expression changes in 3 AML cell lines and bone marrow samples from two patients with AML were analyzed on a cDNA microarray containing approximately 7000 human genes. Pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis tool. Results: The expression analysis identified a common set of genes that were regulated by tipifarnib in three leukemic cell lines and in leukemic blast cells isolated from two patients who had been treated with tipifarnib. Association of modulated genes with biological functional groups identified several pathways affected by tipifarnib including cell signaling, cytoskeletal organization, immunity, and apoptosis. Gene expression changes were verified in a subset of genes using real time RT-PCR. Additionally, regulation of apoptotic genes was found to correlate with increased Annexin V staining in the THP-1 cell line but not in the HL-60 cell line. Conclusions: The genetic networks derived from these studies illuminate some of the biological pathways affected by FTI treatment while providing a proof of principle for identifying candidate genes that might be used as surrogate biomarkers of drug activity. [ABSTRACT FROM AUTHOR]