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Background Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. Aim This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. Methods The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC-MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. Results High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. Conclusion This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS. Keywords: Peutz-Jeghers syndrome, Metabolomics, LC-MS, Mucosa-associated microbiota, Bacteria, Author(s): Sui Wang[sup.2], Guan-Jun Kou[sup.1], Xiao-Han Zhao[sup.1], Gang Huang[sup.1], Jue-Xin Wang[sup.1], Lin Tian[sup.1], Xiu-Li Zuo[sup.1], Yan-Qing Li[sup.1], Jia-Yong Wang[sup.3] and Yan-Bo Yu[sup.1] Introduction Peutz-Jeghers syndrome (PJS) is a rare genetic [...]

Mycobacterium gordonae was first described 50 years ago as a slow-growing scotochromogenic nontuberculous mycobacterium. Previous research revealed vague molecular typing results for M. gordonae-like strains. For example, the RNA polymerase-[beta] [...]

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia- expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest that microglial TRPV4 channels reside at the center of the neuroimmune axis in the spinal cord, which transforms peripheral nerve injury into central sensitization and neuropathic pain, thereby identifying TRPV4 as a potential new target for the treatment of chronic pain., Introduction Whereas acute pain is a protective mechanism to avoid further damage, chronic pain is a maladaptive, debilitating condition affecting hundreds of millions of people worldwide (1, 2). About a [...]

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC. RSK4 was highly expressed in ESCC CSCs and associated with radioresistance and poor survival in patients with ESCC. RSK4 was found to be a direct downstream transcriptional target of [DELTA]Np63[alpha], the main p63 isoform, which is frequently amplified in ESCC. RSK4 activated the [beta]-catenin signaling pathway through direct phosphorylation of GSK-3[beta] at Ser9. Pharmacologic inhibition of RSK4 effectively reduced CSC properties and improved radiosensitivity in both nude mouse and patient-derived xenograft models. Collectively, our results strongly suggest that the [DELTA]Np63[alpha]/RSK4/GSK-3[beta] axis plays a key role in driving CSC properties and radioresistance in ESCC, indicating that RSK4 is a promising therapeutic target for ESCC treatment., Introduction Esophageal cancer is one of the most frequently occurring cancers and ranks as the seventh leading cause of cancer-related mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most [...]

Background Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma. Objectives To compare the diagnostic value of RDR and PD, by conducting leukotriene D.sub.4 (LTD.sub.4-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels. Methods Healthy subjects and asthmatic patients underwent LTD.sub.4-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20 % fall in forced expiratory volume in one second (PD.sub.20FEV.sub.1) and the RDR, defined as FEV.sub.1 fall (%) at the final step divided by the corresponding provocative dosage. Results Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. Log.sub.10RDR was positively correlated with log.sub.10PD.sub.20FEV.sub.1 in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PD.sub.20FEV.sub.1 and higher RDR (both P < 0.05). The differences in PD.sub.20FEV.sub.1 and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with log.sub.10PD.sub.20FEV.sub.1, the log.sub.10RDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤25th percentile) was associated with higher baseline FEV.sub.1 (P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PD.sub.20FEV.sub.1 led to an increased diagnostic value compared with either parameter alone. Conclusions RDR is a surrogate of PD.sub.20FEV.sub.1 for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants., Author(s): Wei-jie Guan[sup.1] , Jin-ping Zheng[sup.1] , Xu Shi[sup.1] , Yan-qing Xie[sup.1] , Cai-yu Jiang[sup.1] [sup.2] , Yi Gao[sup.1] , Zheng Zhu[sup.1] , Jia-ying An[sup.1] , Xin-xin Yu[sup.1] , Wen-ting [...]

Author(s): Ren-jie Han [sup.1] , Zhuo-ran Zeng [sup.2] , Qian Li [sup.2] , Qing Yan [sup.3] Author Affiliations: (1) grid.411578.e, 0000 0000 9802 6540, School of Economics, Chongqing Technology and [...]

Background Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma. Objectives To compare the diagnostic value of RDR and PD, by conducting leukotriene [D.sub.4] ([LTD.sub.4]-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels. Methods Healthy subjects and asthmatic patients underwent [LTD.sub.4]-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20 % fall in forced expiratory volume in one second ([PD.sub.20][FEV.sub.1]) and the RDR, defined as [FEV.sub.1] fall (%) at the final step divided by the corresponding provocative dosage. Results Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. [Log.sub.10]RDR was positively correlated with [log.sub.10] [PD.sub.20][FEV.sub.1] in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower [PD.sub.20][FEV.sub.1] and higher RDR (both P < 0.05). The differences in [PD.sub.20][FEV.sub.1] and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with [log.sub.10][PD.sub.20][FEV.sub.1], the [log.sub.10]RDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR ([less than or equal to]25th percentile) was associated with higher baseline [FEV.sub.1] (P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and [PD.sub.20][FEV.sub.1] led to an increased diagnostic value compared with either parameter alone. Conclusions RDR is a surrogate of [PD.sub.20][FEV.sub.1] for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants. Keywords Response-dose ratio * Cumulative provocative dosage * Asthma * Leukotriene [D.sub.4] * Methacholine, Abbreviations RDR Response-dose ratio FVC Forced vital capacity [FEV.sub.1] Forced expiratory volume in one second PEF Peak expiratory flow LT Leukotriene [LTD.sub.4]-BPT Leukotriene [D.sub.4] bronchial provocation test MCh-BPT Methacholine bronchial [...]

It is widely believed that the Sahara desert is no more than ~2-3 million years (Myr) old (1), with geological evidence showing a remarkable aridification of north Africa at the onset of the Quaternary ice ages (2-4). Before that time, north African aridity was mainly controlled by the African summer monsoon (ASM) (5-8), which oscillated with Earth's orbital precession cycles. Afterwards, the Northern Hemisphere glaciation added an ice volume forcing on the ASM, which additionally oscillated with glacial-interglacial cycles (2). These findings led to the idea that the Sahara desert came into existence when the Northern Hemisphere glaciated ~2-3 Myr ago. The later discovery, however, of aeolian dune deposits ~7 Myr old (9) suggested a much older age, although this interpretation is hotly challenged (1) and there is no clear mechanism for aridification around this time. Here we use climate model simulations to identify the Tortonian stage (~7-11 Myr ago) of the Late Miocene epoch as the pivotal period for triggering north African aridity and creating the Sahara desert. Through a set of experiments with the Norwegian Earth System Model (10) and the Community Atmosphere Model (11), we demonstrate that the African summer monsoon was drastically weakened by the Tethys Sea shrinkage during the Tortonian, allowing arid, desert conditions to expand across north Africa. Not only did the Tethys shrinkage alter the mean climate of the region, it also enhanced the sensitivity of the African monsoon to orbital forcing, which subsequently became the major driver of Sahara extent fluctuations. These important climatic changes probably caused the shifts in Asian and African flora and fauna observed during the same period (4,12-14), with possible links to the emergence of early hominins in north Africa (15,16)., The Sahara desert, the largest non-polar desert in the world today (~9,400,000 [km.sup.2]), is widely believed to have appeared during the past 2 or 3 Myr (ref. 1). A wealth [...]

Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous [...]

Lipid droplets (LDs) are intracellular organelles that store neutral lipids within cells. Over the last two decades there has been a dramatic growth in our understanding of LD biology and, [...]

Melamine-modified montmorillonite (MA-MMT) was prepared via cation exchange. The intercalation behavior was investigated by Fourier transform infrared spectrometer (FT-IR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The results showed that the d-spacing value increased from 1.25 nm for Na-montmorillonite ([Na.sup.+]MMT) to 1.53 nm for MA-MMT. Different kinds of montmorillonite combined with melamine pyrophosphate (MPP) were used to prepare flame-retardant polyamide 6 (FR-PA6). Flame retardance of FR-PA6 samples was investigated by limiting oxygen index (LOI), UL-94 vertical burning method, and cone calorimeter test. Morphology and component of char residues for FR-PA6 were investigated by scanning electron microscope (SEM) and XPS. It was found that MA-MMT/MPP system contributed both excellent flame retardance and anti-dripping ability for PA6. MA-MMT particles can fill flaws of char residues and strengthen the char layer, leading to form more intumescent char layer. POLYM. ENG. SCI., 51:377-385, 2011. [C]2010 Society of Plastics Engineers, INTRODUCTION Polyamide 6 (PA6) is one of the most important engineering plastics. It meets great demand in advanced technologies, and has been widely used in electronic industries and automotive production. [...]

The cone valve plays an important role in high-pressure sealing applications. In this paper, a new high-pressure cone valve, based on the titanium alloy poppet-to-polyetheretherketone seat sealing structure, is proposed for deep-sea gas-tight water samplers. In order to study the sealing performance of the new valve, both the conforming poppet-seat contact model and the nonconforming poppet-seat contact model were evaluated. Finite element analysis based on the two models was performed and validated by experiments. The results indicate that the nonconforming poppet-seat contact model has a better sealing performance than the conforming poppet-seat contact model. The new cone valve also was applied in a gas-tight hydrothermal fluid sampler and successfully tested in a sea trial during the KNOX18RR cruise from 9 July to 12 August 2008. [DOI: 10.1115/1.4001204] Keywords: high pressure, cone valve, finite element analysis, deep sea

Adenosine can exhibit cytotoxic activity in vivo and in vitro, though its mechanisms are still uncertain. In this study, we investigated the adenosine-mediated apoptotic signaling pathway and the role of NF-κB in human hepatocellular carcinoma HepG2 cells. HepG2 cells were treated with different concentrations of adenosine for 12-48 h, and the effect of adenosine on cell proliferation was evaluated by MTT assay. The cytotoxicity of adenosine alone or in combination with an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), was also evaluated by MTT assay and the mode of cell death was detected by Hoechst 33342 staining. Cell cycle progress was performed by flow cytometry with PI staining. The protein expressions of Bcl-2, p53, NF-κB subunit p65, and caspase-3 were assayed by Western blot. Caspase-3 activity was measured by spectrophotomteric assay. The results showed that adenosine significantly reduced the viability of HepG2 cells in a dose- and time-dependent manner, with [IC.sub.50] (24 and 48 h) of 2.52 and 1.89 mmol x [L.sup.-1], respectively. The apoptotic index (percentage of sub-[G.sub.1] phase) of HepG2 cells in adenosine treatment alone for 12 and 24 h or in combination with PDTC were 8.30%, 22.32% and 20.18%, 30.89%, respectively. All of them were higher than that in the control group (0.81%, p < 0.01). The characteristic changes of cell apoptosis (chromatin condensation and sub-G1 peak) were observed under fluorescent microscopy and flow cytometry. We also found that the apoptotic process triggered by adenosine was involved in [G.sub.0]-[G.sub.1] cell-cycle arrest, enhanced the activity of caspase-3, upregulated p53 and NF-κB p65 expression, and downregulated Bcl-2 expression. Inhibition of NF-κB by PDTC decreased NF-κB p65 expression, enhanced cell apoptosis ratio, and increased caspase-3 activity. NF-κB may play an anti-apoptosis role in adenosine-induced HepG2 cytotoxicity. Key words: adenosine, apoptosis, HepG2 cells, NF-κB. L'adenosine peut exercer une activite cytotoxique in vivo et in vitro mais son mecanisme d'action demeure incertain. Dans cette etude, nous avons examine la voie de signalisation de l'apoptose causee par l'adenosine ainsi que le role du facteur NF-κB dans les cellules de carcinome hepatocellulaire HepG2. Les cellules HepG2 ont ete traitees avec differentes concentrations d'adenosine pendant 12-18 h, et l'effet de l'adenosine sur la proliferation cellulaire a ete; evalue par un dosage au MTT. La cytotoxicite de l'adenosine seule ou combinee a un inhibiteur du NF-κB, le pyrrolidine dithiocarbamate (PDTC) a aussi ete evaluee par un dosage MTT, et le mode de mort cellulaire a ete detecte par coloration au Hoechst 33342. La progression du cycle cellulaire a etee suivie par cytometrie de flux apres coloration a l'iodure de propidium. L'expression de Bcl-2, p53, de la sous-unite p65 du NF-κB et de la caspase-3 a ete detectee par buvardage Western. L'activite de la caspase-3 a ete mesuree a l'aide d'une mesure spectrophotometrique. Les resultats ont montre que l'adenosine reduisait de facjon significative la viabilite des cellules HepG2 de maniere dependante de la concentration et du temps, avec des [CI.sub.50] (24 et 48 h) de 2.52 et 1.89 mmol x [L.sup.-1], respectivement. Les indices d'apoptose (pourcentage de cellules en phase sub-G1) des cellules HepG2 traitees a l'adenosine seule pendant 12 ou 24 h, ou combinee au PDTC etaient de 8.30% et 22.32%, et 20.18% et 30.89%, respectivement. Ils etaient tous superieurs a l'indice du groupe controle (0.81%, p < 0.01). Les changements caracteristiques de l'apoptose (condensation de la chromatine et pic en sub- [G.sub.1]) ont ete observees par microscopie en fluorescence et par cytometrie de flux. Nous avons aussi trouve que le processus d'apoptose enclenche par l'adenosine etait implique; dans l'arret du cycle cellulaire en [G.sub.0]-[G.sub.1], augmentait l'activite; de la caspase-3, augmentait l'expression de p53 et de la sous-unite p65 du NF-κB, et diminuait l'expression de Bcl-2. L'inhibition du NF-κB par le PDTC augmentait la cytotoxicite;, l'indice d'apoptose et l'activite; de la caspase-3, et diminuait l'expression de p65. L'inhibition du NF-κB pourrait augmenter l'apoptose a travers la voie de la caspase-3 et de Bcl-2. NF-κB peut jouer un role anti-apoptose dans la cytotoxicite; induite par l'adenosine dans les cellules HepG2. Mots-cles: adenosine, apoptose, HepG2, NF-κB. [Traduit par la Redaction], Introduction Apoptosis (programmed cell death), which plays a critical role during normal development, homeostasis, and pathology of a wide variety of diseases including cancer, occurs in response to various intracellular [...]

Morphine-induced analgesia and antinociceptive tolerance are known to be modulated by interaction between [delta]-opioid receptors (DORs) and [mu]-opioid receptors (MORs) in the pain pathway. However, evidence for expression of DORs in nociceptive small-diameter neurons in dorsal root ganglia (DRG) and for coexistence of DORs with MORs and neuropeptides has recently been challenged. We now report, using in situ hybridization, single-cell PCR, and immunostaining, that DORs are widely expressed not only in large DRG neurons but in small ones and coexist with MORs in peptidergic small DRG neurons, with protachykinin-dependent localization in large dense-core vesicles. Importantly, both DOR and MOR agonists reduce depolarization-induced [Ca.sup.2+] currents in single small DRG neurons and inhibit afferent C-fiber synaptic transmission in the dorsal spinal cord. Thus, coexistence of DORs and MORs in small DRG neurons is a basis for direct interaction of opioid receptors in modulation of nociceptive afferent transmission and opioid analgesia. dorsal root ganglion | spinal cord | peptides | pain | tolerance doi/ 10.1073/pnas.1008382107

Heterodimeric integrin adhesion receptors regulate diverse biological processes including angiogenesis, thrombosis and wound healing. The transmembrane-cytoplasmic domains (TMCDs) of integrins play a critical role in controlling activation of these receptors via an inside-out signaling mechanism, but the precise structural basis remains elusive. Here, we present the solution structure of integrin [alpha]IIb[beta]3 TMCD heterodimer, which reveals a right-handed coiled-coil conformation with 2 helices intertwined throughout the transmembrane region. The helices extend into the cytoplasm and form a clasp that differs significantly from a recently published [alpha]IIb[beta]3 TMCD structure. We show that while a point mutation in the clasp interface modestly activates [alpha]IIb[beta]3, additional mutations in the transmembrane interface have a synergistic effect, leading to extensive integrin activation. Detailed analyses and structural comparison with previous studies suggest that extensive integrin activation is a highly concerted conformational transition process, which involves transmembrane coiled-coil unwinding that is triggered by the membrane-mediated alteration and disengagement of the membrane-proximal clasp. Our results provide atomic insight into a type I transmembrane receptor heterocomplex and the mechanism of integrin inside-out transmembrane signaling. NMR | protein structure | transmembrane domain doi/ 10.1073/pnas.0909589106

Traditional classification algorithms can be limited in their performance on highly unbalanced data sets. A popular stream of work for countering the problem of class imbalance has been the application of a sundry of sampling strategies. In this correspondence, we focus on designing modifications to support vector machines (SVMs) to appropriately tackle the problem of class imbalance. We incorporate different "rebalance" heuristics in SVM modeling, including cost-sensitive learning, and over- and undersampling. These SVM-based strategies are compared with various state-of-the-art approaches on a variety of data sets by using various metrics, including G-mean, area under the receiver operating characteristic curve, F-measure, and area under the precision/recall curve. We show that we are able to surpass or match the previously known best algorithms on each data set. In particular, of the four SVM variations considered in this correspondence, the novel granular SVMs--repetitive undersampling algorithm (GSVM-RU) is the best in terms of both effectiveness and efficiency. GSVM-RU is effective, as it can minimize the negative effect of information loss while maximizing the positive effect of data cleaning in the undersampling process. GSVM-RU is efficient by extracting much less support vectors and, hence, greatly speeding up SVM prediction. Index Terms--Computational intelligence, cost-sensitive learning, granular computing, highly imbalanced classification, oversampling, support vector machines (SVMs), undersampling.

A quorum-sensing locus, pcoI/pcoR, which is involved in the regulation of root colonization and plant disease-suppressive ability, was previously identified in Pseudomonas fluorescens 2P24. In this study, we performed random mutagenesis using mini-Tn5 in order to screen the upstream transcriptional regulators of pcoI, a biosynthase gene responsible for the synthesis of N-acylhomoserine lactone signal molecules. Two mutants, PM400 and PM410, with elevated pcoI gene promoter activity, were identified from ~10 000 insertion clones. The amino acid sequences of the interrupted genes in these two mutants were highly similar to PhoQ, a sensor protein of the two-component regulatory system PhoP/PhoQ, which responds to environmental [Mg.sup.2+] starvation and regulates virulence in Salmonella typhimurium and antimicrobial peptide resistance in Pseudomonas aeruginosa. The promoter activity of pcoI was also induced under low-[Mg.sup.2+] conditions in the 2P24 strain of P. fluorescens. Deletion mutagenesis and complementation experiments demonstrated that the transcription of pcoI was negatively regulated by the sensor PhoQ but positively regulated by the response regulator PhoP. Genetic evidence also indicated that transcription of the outer-membrane protein gene oprH was induced by [Mg.sup.2+] starvation through regulation of the wild-type PhoP/PhoQ system. Additionally, PhoQ was involved in biofilm formation by 2P24 under low-[Mg.sup.2+] conditions through a PhoP-independent pathway.

The Energy Transfer Mode (ETM) in a Boost dc-dc converter is classified into two types, i.e., the Complete Inductor Supply Mode (CISM) and the Incomplete Inductor Supply Mode (IISM). The critical inductance and boundary condition of CISM and IISM are derived in the paper. Based on the classification, three operating modes are defined, and they are CISM, IISM in Continuous Conduction Mode (IISM-CCM) and IISM in Discontinuous Conduction Mode (IISM-DCM). Output voltage ripple (OVR) in three modes is analyzed, respectively. As for a Boost converter with certain load, output capacitance and switching frequency, the OVR in CISM is the lowest and independent of the inductance and OVR in IISM is higher and increases with the decrease of the inductance. It is concluded that the minimal inductance to guarantee the Maximum OVR (MOVR) to be the lowest is actually the critical inductance of CISM and IISM under the condition of the lowest input voltage and minimum load resistance. In addition, the lowest MOVR is independent of the inductance. The design method to find the minimal inductance is proposed in the paper. Experiment results are in positive to the analysis showing the feasibility of the proposed methods. Index Terms--Boost converter, critical inductance, dc-dc converter, energy transfer mode, minimum inductance, output voltage ripple.

Integrin activation is essential for dynamically linking the extracellular environment and cytoskeletal/signaling networks. Activation is controlled by integrins' short cytoplasmic tails (CTs). It is widely accepted that the head domain of talin (talin-H) can mediate integrin activation by binding to two sites in integrin [beta]'s CT; in integrin [[beta].sub.3] this is an NPL[Y.sup.747] motif and the membrane-proximal region. Here, we show that the C-terminal region of integrin [[beta].sub.3] CT, composed of a conserved T[S.sup.752]T region and NIT[Y.sup.759] motif, supports integrin activation by binding to a cytosolic binding partner, kindlin-2, a widely distributed PTB domain protein. Co-transfection of kindlin-2 with talin-H results in a synergistic enhancement of integrin [[alpha].sub.IIb][[beta].sub.3] activation. Furthermore, siRNA knockdown of endogenous kindlin-2 impairs talin-induced [[alpha].sub.IIb][[beta].sub.3] activation in transfected CHO cells and blunts [[alpha].sub.v][[beta].sub.3]-mediated adhesion and migration of endothelial cells. Our results thus identify kindlin-2 as a novel regulator of integrin activation; it functions as a coactivator.

A transmission-type variable optical attenuator (VOA) based on a polymer-stabilized dual-frequency liquid crystal (PSDFLC) is demonstrated at [lambda] = 1.55 [micro]m. The VOA is highly transparent in the voltage-off state but scatters light in the voltage-on state. By using a birefringent beam displacer incorporated with half-wave plates, we can obtain a VOA that is polarization independent and that exhibits a 31 dB dynamic range. The polymer networks and dual-frequency effect together reduce the response time (rise + decay) of a 16 [micro]m PSDFLC cell to 30 ms at room temperature and at a voltage of 24 [V.sub.rms]. OCIS codes: 230.3720, 160.5470.

Many problems in ion-enhanced etching are caused by the charge-up effect as the aspect ratio increases with the decrease of a semiconductor device size. The energy and angle distribution of particles are important factors in the etching process which can be controlled by the pressure of a plasma chamber. In the present paper, we varied the pressure of plasma and studied the charge-up phenomenon for the aspect ratios 5 and 10. In the low pressure RF-capacitively coupled plasma (CCP) chamber, ions with higher energy and small angle distribution have been detected. On the other hand, in the high-pressure RF-CCP chamber, ions with low-energy and high-angle distribution are observed. At a high-aspect ratio, the charge-up potential is reduced when the pressure of a plasma chamber is high. At a high pressure, more vertical etching feature is expected. Index Terms--Capacitively coupled plasma, charge-up simulation, plasma process induced damage.

Movement through the endocytic pathway occurs principally via a series of membrane fusion and fission reactions that allow sorting of molecules to be recycled from those to be degraded. Endosome fusion is dependent on SNARE proteins, although the nature of the proteins involved and their regulation has not been fully elucidated. We found that the endosome-associated hepatocyte responsive serum phosphoprotein (Hfs) inhibited the homotypic fusion of early endosomes. A region of Hrs predicted to form a coiled coil required for binding the Q-SNARE, SNAP-25, mimicked the inhibition of endosome fusion produced by full-length Hrs, and was sufficient for endosome binding. SNAP-25, syntaxin 13, and VAMP2 were bound from rat brain membranes to the Hrs coiled-coil domain. Syntaxin 13 inhibited early endosomal fusion and botulinum toxin/E inhibition of early endosomal fusion was reversed by addition of SNAP-[25.sub.(150-206)], confirming a role for syntaxin 13, and establishing a role for SNAP-25 in endosomal fusion. Hrs inhibited formation of the syntaxin 13-SNAP-25-VAMP2 complex by displacing VAMP2 from the complex. These data suggest that SNAP-25 is a receptor for Hrs on early endosomal membranes and that the binding of Hfs to SNAP-25 on endosomal membranes inhibits formation of a SNARE complex required for homotypic endosome fusion.

Phenotypic modification of dorsal root ganglion (DRG) neurons represents an important mechanism underlying neuropathic pain. However, the nerve injury-induced molecular changes are not fully identified. To determine the molecular alterations in a broader way, we have carried out cDNA array on the genes mainly made from the cDNA libraries of lumbar DRGs of normal rats and of rats 14 days after peripheral axotomy. Of the 7,523 examined genes and expressed sequence tags (ESTs), the expression of 122 genes and 51 expressed sequence tags is strongly changed. These genes encompass a large number of members of distinct families, including neuropeptides, receptors, ion channels, signal transduction molecules, synaptic vesicle proteins, and others. Of particular interest is the up-regulation of [gamma]-aminobutyric [acid.sub.A] receptor [alpha]5 subunit, peripheral benzodiazepine receptor, nicotinic acetylcholine receptor [alpha]7 subunit, P2Y1 purinoceptor, [Na.sup.+] channel [beta]2 subunit, and L-type [Ca.sup.2+] channel [alpha]2[??]-1 subunit. Our findings therefore reveal dynamic and complex changes in molecular diversity among DRG neurons after axotomy.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-[beta]-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Improved space-time coding for multiple-input and multiple-output orthogonal frequency division multiplexing is studied for wireless systems using QPSK modulation for four transmit and four receive antennas. A 256-state code is shown to perform within 3 dB of outage capacity (and within 2 dB with perfect channel estimation), which is better than any other published result without using iterative decoding. Index Terms--Antenna diversity, MIMO, OFDM, space-time codes.

Optimum distributed detection schemes base don the Neyman-Pearson criterion is examined.

In this paper, a new adaptive fuzzy reasoning method using compensatory fuzzy operators is proposed to make a fuzzy logic system more adaptive and more effective. Such a compensatory fuzzy logic system is proved to be a universal approximator. The compensatory neural fuzzy networks built by both control-oriented fuzzy neurons and decision-oriented fuzzy neurons cannot only adaptively adjust fuzzy membership functions but also dynamically optimize the adaptive fuzzy reasoning by using a compensatory learning algorithm. The simulation results of a cart-pole balancing system and nonlinear system modeling have shown that 1) the compensatory neurofuzzy system can effectively learn commonly used fuzzy IF-THEN rules from either well-defined initial data or ill-defined data; 2) the convergence speed of the compensatory learning algorithm is faster than that of the conventional backpropagation algorithm; and 3) the efficiency of the compensatory learning algorithm can be improved by choosing an appropriate compensatory degree. Index Terms - Fuzzy logic, machine learning, neural networks, neurofuzzy systems.

A series of dinuclear divanadium(III) complexes are prepared and structurally characterized using X-ray crystallography and UV-visible, paramagnetic, NMR, and resonance Raman spectroscopic methods. Protonation of the oxo-bridged species with HClO4 causes a rapid color change leading to crystallization of the hydroxo-bridged species. The study discusses the dependence of the V-O-V angle on the electronic and magnetostructural correlations and their use in assigning structures to complex biosystems.

X-ray crystallographic studies of the (mu-oxo)divanadium(III) complex reveal the presence of two intramolecular hydrogen bonds, which are responsible for the significantly small V-O-V angle in the unsupported (mu-oxo)divanadium complex. Resonance Raman spectroscopy supports the existence of V-O-V acute angle and intramolecular hydrogen bonds. The intramolecular hydrogen bonds break in the solution to form a linear V-O-V bridge.

Electron spectroscopy (ESCA) and reflectance infrared spectroscopy (ATR) were used to measure surface oxidation of photocrosslinked polyethylene. The deterioration of bulk properties during an artificial weathering test was also measured. It was found that the UV-irradiation during crosslinking process decreases the stability of the material considerably. Three kinds of antioxidants and photostabilizers (hindered phenols, hindered amines, and organic sulfides) which have no absorption in the UV region of 300 to 400 nm were added before crosslinking to improve the stability of the crosslinked material. Neither the rate nor the degree of photocrosslinking at different depths of the sample were affected significantly by these additives. It was found possible to prevent the decrease in stability due to the photocrosslinking by using small amounts of a stabilizer, e.g. 0.05% Tinuvin 770 (hindered amine).

Low density polyethylene (LDPE) is extruded, stretched, and photocrosslinked at different temperatures with different stretch ratios in a continuous production line. Three different sequences are adopted: crosslinking before drawing, crosslinking after drawing, and crosslinking during drawing. The effect of drawing is studied by measuring the tensile properties. The increase of tensile strength and the decrease of elongation at break after stretching are related to chain orientation in crystalline morphology measured by X-ray diffraction. Thermal analysis by differential scanning calorimetry (DSC) supports these results. Owing to chain relaxation, the effects of orientation by stretching are significant only when the samples are drawn at a temperature not much higher than the melting point. Annealing of the drawn samples at a temperature above the melting point shows that the orientation in a crosslinked sample is retained for a much longer time than in an uncrosslinked sample. For the crosslinked samples, it is found that crosslinking after or during drawing gives a material with lower shrinkage upon heating; however, crosslinking before drawing gives a heat-shrinkable material.

A new method is described for generating coherent microwaves in a nonlinear photonic crystal. The method relies on optical rectification.

Several studies are conducted to explain the properties of the photonic crystal fiber modal interferometer, which is used for the sensing applications. The significance of the sensing range in the inferometer is also analyzed.

Several studies are conducted to explain the various acousto-optic (AO) effects in the photonic crystals (PCs) containing defects. The different acoustic wavelengths are shown to lead to different synchronized and desynchronized modulations in a dual-defect situation in these crystals.

An intelligent machine-based automated calligraphy process is described. This process involves the digitization of original tablets and documents and it can preserve ancient examples of calligraphy while inspiring the creation of new calligraphic styles.

Systematic syntheses, structures, visible luminescence and magnetic properties of a series of new lanthanide hybrids are described. The structures contain trigonal dodecahedral chains and clustered lanthanide oxide ring tunnels and 3D Ln-O-Ln connectivity.

Integrin [alpha.sub.IIb][beta.sub.3] is used as a model to show that a previously reported activating mutation [alpha.sub.IIb]{[R.sup.995]D} that perturbs the electrostatic interface in the clasp only partially activates [alpha.sub.IIb][beta.sub.3] and that extensive activation of the receptor is achieved by complete deletion of [alpha.sub.IIb] cytoplasmic tail (CT). The results have provided the molecular insights into how distinct regions of the cytoplasmic tails differentially and cooperatively regulate integrin activation.

An examination is done of the optical diffraction properties of holographic polymer-dispersed liquid crystal (HPDLC)-based thick volume grating. In conclusion, when an electric field is applied, the s- and p-polarized lights exhibit different diffraction behaviors and the tunable dual-state or three-state polarization switching can be realized.

Acoustic waves can be a viable tool for the detection and identification of land mines, unexplored ordnance (UXO), and other buried objects. Design of acoustic instruments and interpretation and processing of acoustic measurements call for accurate numerical models to simulate acoustic wave propagation in a heterogeneous soil with buried objects. Compared with the traditional seismic exploration, high attenuation is unfortunately ubiquitous for shallow surface acoustic measurements because of the loose soil and the fluid in its pore space. To adequately model such acoustic attenuation, we propose a comprehensive multidimensional finite-difference time-domain (FDTD) model to simulate the acoustic wave interactions with land mines and soils based on the Biot theory for poroelastic media. For the truncation of the computational domain, we use the perfectly matched layer (PML). The method is validated by comparison with analytical solutions. Unlike the pure elastic wave model, this efficient PML-FDTD model for poroelastic media incorporates the interactions of waves and the fluid-saturated pore space. Several typical land mine detection measurements are simulated to illustrate the application. Index Terms--Acoustic waves, finite-difference time-domain (FDTD), landmine detection, perfectly matched layer, poroelasticity.