Nanotechnology: fundamental research to product development

The concept of an integrated "lab on a chip" has long been a goal for the micro-electro-mechanical-systems(MEMS) community.This would entail the integration of not only the sampling and analysis of various functions,but also the ability to transmit this information off the chip to a central repository.This paper describes the initial steps in the fabrication of a "lab on a chip" which would continually analyze blood sampled via microneedles using techniques such as nano plasmonics,specifically,concentrations of glucose.The analysis could then be transmitted off the chip using digital signal processing.This paper describes the analysis and optimization of the microneedle shape and size and the fabrication of the resulting needles in silicon using deep reactive ion etching(DRIE).The paper also describes the opportunities for fabrication of such needles in alternative materials and describes the issues that still have to be overcome before such an integrated device is realized.     

Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy

In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.     

Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors

Mutationally activated kinases define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumours harbour such alleles is invariably limited by innate or acquired drug resistance. The identification of resistance mechanisms has revealed a recurrent theme—the engagement of survival signals redundant to those transduced by the targeted kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell-survival effectors—most notably, phosphatidylinositol-3-OH kinase (PI(3)K) and mitogen-activated protein kinase (MAPK). Consequently, an increase in RTK-ligand levels, through autocrine tumour-cell production, paracrine contribution from tumour stroma or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signalling output. Here, using a panel of kinase-'addicted' human cancer cell lines, we found that most cells can be rescued from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical implications was the observation that hepatocyte growth factor (HGF) confers resistance to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF-mutant melanoma cells. These observations highlight the extensive redundancy of RTK-transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.     

Coupled oscillators control morning and evening locomotor behaviour of Drosophila

Daily rhythms of physiology and behaviour are precisely timed by an endogenous circadian clock. These include separate bouts of morning and evening activity, characteristic of Drosophila melanogaster and many other taxa, including mammals. Whereas multiple oscillators have long been proposed to orchestrate such complex behavioural programmes, their nature and interplay have remained elusive. By using cell-specific ablation, we show that the timing of morning and evening activity in Drosophila derives from two distinct groups of circadian neurons: morning activity from the ventral lateral neurons that express the neuropeptide PDF, and evening activity from another group of cells, including the dorsal lateral neurons. Although the two oscillators can function autonomously, cell-specific rescue experiments with circadian clock mutants indicate that they are functionally coupled.     

DESIGN METHODOLOGY OF NETWORKED SOFTWARE EVOLUTION GROWTH BASED ON SOFTWARE PATTERNS

Recently,some new characteristics of complex networks attract the attentions of scientistsin different fields,and lead to many kinds of emerging research directions.So far,most of the researchwork has been limited in discovery of complex network characteristics by structure analysis in large-scalesoftware systems.This paper presents the theoretical basis,design method,algorithms and experiment results ofthe research.It firstly emphasizes the significance of design method of evolution growth for networktopology of Object Oriented(OO)software systems,and argues that.the selection and modulationof network models with various topology characteristics will bring un-ignorable effect on the processof design and implementation of OO software systems.Then we analyze the similar discipline of“negation of negation and compromise”between the evolution of network models with different topologycharacteristics and the development of software modelling methods.According to the analysis of thegrowth features of software patterns,we propose an object-oriented software network evolution growthmethod and its algorithms in succession.In addition,we also propose the parameter systems for OOsoftware system metrics based on complex network theory.Based on these parameter systems,it cananalyze the features of various nodes,links and local-world,modulate the network topology and guidethe software metrics.All these can be helpful to the detailed design,implementation and performanceanalysis.Finally.we focus on the application of the evolution algorithms and demonstrate it by a casestudy.Comparing the results from our early experiments with methodologies in empirical software engi-neering,we believe that the proposed software engineering design method is a computational softwareengineering approach based on complex network theory.We argue that this method should be greatlybeneficial for the design,implementation,modulation and metrics of functionality,structure and per-formance in large-scale OO software complex system.     

An Approach to Extracting Fractal in Remote Sensing Image

In order to apply the spatial structure information to remote sensing interpretation through fractal theory, an algorithm is introduced to compute the single pixd fraetal dimension in remote sensing images. After a computer program was written according to the algorithm, the ETM＋ images were calculated to obtain their fractal data through the program. The algorithm has following characteristics： The obtained fractal values indicate the complexity of image, and have positive correlation with the complexity of images and ground objects. Moreover, the algorithm is simple and reliable, and easy to be implemented.     

DESIGN SAMPLING AND REPLICATION ASSIGNMENT UNDER FIXED COMPUTING BUDGET

1. Introduction The essence of any decision problem is an optimization problem. Whether it is a decision on the production schedule of a manufacturing plant, a decision on the routing rules of networking, or a decision on the make-up of investment portfolios, the problem always revolves around making a choice from a population of alternatives (either finite or infinite) so as to optimize certain targeted objective. Without loss of generality, the objective can be represented by Mθ ∈iΘn J(…     

Identification and characterization of two novel box H/ACA snoRNAs from Schizosaccharomyces pombe

Ineukaryotes,alargenumberofsmallnucleolar RNAs(snoRNAs)accumulatedwithinthenucleolus playimportantrolesinprecursorribosomalRNA(pre RNA)processingandmaturation[1].AllsnoR NAs,withtheexceptionofRNaseMRP,canbe broadlydividedintotwoexpendinggroups,boxC/D andH/ACAsnoRNAs,basedonconservedsequence elements[2].BoxC/DsnoRNAscontaintwocon servedshortsequencemotifs,boxC(UGAUGA)and boxD(CUGA),locatedonlyafewnucleotidesaway fromthe5′and3′ends,respectively,generallyas partofatypical5′3…     

A resetting signal between Drosophila pacemakers synchronizes morning and evening activity

The biochemical machinery that underlies circadian rhythms is conserved among animal species and drives self-sustained molecular oscillations and functions, even within individual asynchronous tissue-culture cells. Yet the rhythm-generating neural centres of higher eukaryotes are usually composed of interconnected cellular networks, which contribute to robustness and synchrony as well as other complex features of rhythmic behaviour. In mammals, little is known about how individual brain oscillators are organized to orchestrate a complex behavioural pattern. Drosophila is arguably more advanced from this point of view: we and others have recently shown that a group of adult brain clock neurons expresses the neuropeptide PDF and controls morning activity (small LN(v) cells; M-cells), whereas another group of clock neurons controls evening activity (CRY+, PDF- cells; E-cells). We have generated transgenic mosaic animals with different circadian periods in morning and evening cells. Here we show, by behavioural and molecular assays, that the six canonical groups of clock neurons are organized into two separate neuronal circuits. One has no apparent effect on locomotor rhythmicity in darkness, but within the second circuit the molecular and behavioural timing of the evening cells is determined by morning-cell properties. This is due to a daily resetting signal from the morning to the evening cells, which run at their genetically programmed pace between consecutive signals. This neural circuit and oscillator-coupling mechanism ensures a proper relationship between the timing of morning and evening locomotor activity.     

Distribution Regularity of Debris Flow and Its Hazard in Upper Reaches of Yangtze River and Other Rivers of Southwestern China

In the upper reaches of Yangtze River and other rivers of southwestern China, the debris flows develop and lead to most serious disasters because of the various landforms, complex geological structures and abundant rainfall. The distribution of debris flows has regularity in the regions with different landform, geological structure, and precipitation. The regularities of distribution of debris flows are as following： （1） distributed in transition belts of different morphologic regions; （2） distributed in the area with strong stream trenching; （3） distributed along fracture zones and seismic belts： （4） distributed in the area with abundant precipitation; （5） distribution of debris flow is azonal. The activity of abundant debris flows not only brings harm to Towns, Villages and Farmlands, Main Lines of Communication, Water-Power Engineering, Stream Channels etc., but also induces strong water and soil loss. According to the present status of debris flow prevention, the problems in disasters mitigation and soil conservancy are found out, and the key works are brought up for the future disasters prevention and soil conservancy.