地震波场模拟及叠前深度偏移的李群方法

The processes of seismic wave propagation in phase space and one way wave extrapolation in frequency-space domain, if without dissipation, are essentially transformation under the action of one parameter Lie groups. Consequently, the numerical calculation methods of the propagation ought to be Lie group transformation too, which is known as Lie group method. After a fruitful study on the fast methods in matrix inversion, some of the Lie group methods in seismic numerical modeling and depth migration are presented here. Firstly the Lie group description and method of seismic wave propagation in phase space is proposed, which is, in other words, symplectic group description and method for seismic wave propagation, since symplectic group is a Lie subgroup and symplectic method is a special Lie group method. Under the frame of Hamiltonian, the propagation of seismic wave is a symplectic group transformation with one parameter and consequently, the numerical calculation methods of the propagation ought to be symplectic method. After discrete the wave field in time and phase space, many explicit, implicit and leap-frog symplectic schemes are deduced for numerical modeling. Compared to symplectic schemes, Finite difference (FD) method is an approximate of symplectic method. Consequently, explicit, implicit and leap-frog symplectic schemes and FD method are applied in the same conditions to get a wave field in constant velocity model, a synthetic model and Marmousi model. The result illustrates the potential power of the symplectic methods. As an application, symplectic method is employed to give synthetic seismic record of Qinghai foothills model. Another application is the development of Ray+symplectic reverse-time migration method. To make a reasonable balance between the computational efficiency and accuracy, we combine the multi-valued wave field & Green function algorithm with symplectic reverse time migration and thus develop a new ray+wave equation prestack depth migration method. Marmousi model data and Qinghai foothills model data are processed here. The result shows that our method is a better alternative to ray migration for complex structure imaging. Similarly, the extrapolation of one way wave in frequency-space domain is a Lie group transformation with one parameter Z and consequently, the numerical calculation methods of the extrapolation ought to be Lie group methods. After discrete the wave field in depth and space, the Lie group transformation has the form of matrix exponential and each approximation of it gives a Lie group algorithm. Though Pade symmetrical series approximation of matrix exponential gives a extrapolation method which is traditionally regarded as implicit FD migration, it benefits the theoretic and applying study of seismic imaging for it represent the depth extrapolation and migration method in a entirely different way. While, the technique of coordinates of second kind for the approximation of the matrix exponential begins a new way to develop migration operator. The inversion of matrix plays a vital role in the numerical migration method given by Pade symmetrical series approximation. The matrix has a Toepelitz structure with a helical boundary condition and is easy to inverse with LU decomposition. A efficient LU decomposition method is spectral factorization. That is, after the minimum phase correlative function of each array of matrix had be given by a spectral factorization method, all of the functions are arranged in a position according to its former location to get a lower triangular matrix. The major merit of LU decomposition with spectral factorization (SF Decomposition) is its efficiency in dealing with a large number of matrixes. After the setup of a table of the spectral factorization results of each array of matrix, the SF decomposition can give the lower triangular matrix by reading the table. However, the relationship among arrays is ignored in this method, which brings errors in decomposition method. Especially for numerical calculation in complex model, the errors is fatal. Direct elimination method can give the exact LU decomposition But even it is simplified in our case, the large number of decomposition cost unendurable computer time. A hybrid method is proposed here, which combines spectral factorization with direct elimination. Its decomposition errors is 10 times little than that of spectral factorization, and its decomposition speed is quite faster than that of direct elimination, especially in dealing with a large number of matrix. With the hybrid method, the 3D implicit migration can be expected to apply on real seismic data. Finally, the impulse response of 3D implicit migration operator is presented.

准噶尔盆地中拐东北斜坡油气成藏条件研究——西部压性盆地含油气系统理论的研究与实践

This paper builds the model of oil accumulation and achieves the prediction of exploration goal. It uses multiple subject means, the ways of synthetic research and the viewpoint of analyzing genesis, with the academic guidance of sedimentology, structural geology, petroleum geology and geochemistry, the basis of strata sequence frame and structural frame, the frame of "four history" - the burying history, the structural history, the filling history and the evolving history of oil, the masterstroke of hydrocarbon's generation, migration and accumulation, the aim of revealing the genetic relation between mature source rock and oil reservoir in space and time. Some achievements and viewpoints in this study are following. 1. It is proposed that the structural evolution in this area had many periods, and the structural movement of the Xiazijie group telophase formed the structural pattern for the first time. 2. The character of strata sequence in this area is divided by the character of episodic cycle firstly. The study of dividing the facies of single well and the facies of well tie is based on the data of single well. The character of sedimentary facies is con-structed initially. 3. It is believed that Jiamuhe group is the main source rock, which can supply considerable oil and gas resources for the first time. Some criterions of source rock such as the type ,the abundance in Jiamuhe group are analysed. Using the thermal history of source rock, we drawn a conclusion that the original type of source rock in Jiamuhe group is II_1-III, and the abundance achived the level of good source rock, and this set of source rock had contributed to this area. 4. The reservoir strata in this area are assessed and analysed with the reservoir evaluation. There are multi-type reservoirs, such as volcanic lava facies, sedimentary clast facies, continental belch facies. The physical property in reservoir strata is characterized by low porosity and low permeability. The study of diagenetic stage show that the diageneses in Jiamuhe group is A-Bsubage, and the reservoir room is mainly secondary corroded hollow and cleft. 5. The synthetic research on oil system in Jiamuhe group is made for the first time. The type of petroleum system is divided , and we consider that the petroleum system of Jiamuhe group is at the reliable rank. There are two critical time in oil accumulation through studying the critical time of oil accumulation : the early generation of hydrocarbon is oil, and the later is gas. 6. The mechanism of accumulation is analysed. We consider that the accu-mulation of oil in this area has many periods, and the early generated hydrocarbon is expeled by the later , and formed the character of zonal distribution in planar. 7. A bran-new model of oil and gas is proposed. Beneficial enrichment area of oil and gas is analyzed, which can be divided into three sections: Section I can be divided into two sections: I_1 and I_2. The lower subgroup of Jiamuhe is covered by the triassic layer of I_1 section. Fault zone and near the foot wall of fault are charactered with thick phase belt. Then the cover capability in this area is relatively poor, oil can migrate into triassic layer by vertical or lateral migration , and forms I_1 Kelamayi triassic oil pool consequently. The lower subgroup of Jiamuhe is covered by the triassic layer of I_2 section ,which is charactered with thin phase belt. Then the cover capability in this area is relatively good, and forms I_1 Kelamayi triassic oil pool consequently. Section II can be divided into two sections: II_1-I_(I~2). The cover of Jiamuhe group in section II_1 is the low resistivity segment in Wuerhe group, which has thin lithology and poor porosity and permeability. Oil and gas in Jiamuhe group can be covered to form beneficial accumulation area. There are some wells in this area, such as Ke 007 well, 561 well. The thick phase belt layer of Wuerhe high resistivity segment in section II_2 has unconformable relation with Jiamuhe group. The cover ability of the high resistivity segment is poor, petroleum in Jiamuhe can migrate into Wuerhe layer vertically. This area is the beneficial area for accumulating petroleum in Wuerhe layer. there are some wells in this area, such as Ke 75 well, Ke 76 well, Ke 77 well, Ke 78 well, Ke 79 well. Section III can also be divided into two sections: III_1 and III_2. Wuerhe group in section III_1 has unconformable relation with Jiamuhe group. There is thick lithology and poor cover in Wuerhe group, but the strata sequence evolution character of upper subgroup in Jiamuhe group has determined that it has lateral and vertical cover ability. thus, this area is petroleum abundant belt of jiamuhe group, which has the trap. Section III_2 is an area controled by wedgeout of Fengcheng group, Fengcheng group in this area has quite thick lithology so that It has beneficial resevoir phase belt. It can accumulate oil in itself or accept some oil in Jiamuhe group. Jiamuhe group has some oil accumulation condition in this area. Thus, section III_2 is jiamuhe-Fengcheng multiple petroleum accumulation belt, such as Ke 80 well. 8. The goal of exploration is suggested: Depositional trap or combination trap is the important aspect in later exploration. Both types of traps are the goal of the next drilling: Fault block trap in the east of 576 well and the NO. 2 fault block trap in the north of Ke 102 well It is suggested that we should study the law of oil and gas in Jiamuhe group and enhance the study of combination in forming reservoir and trap scale. We do some lithology forecast and reservoir diatropic forecast in order to know the area of oil and gas.

职业倦怠与自我和谐、人际信任的关系研究：中学校长与一般教师的对比

Job Burnout has been a focus of the Occupational Stress Research. As a typical,helping occupation, teacher has attracted widely attention and researches in the areas of pedagogy and psychology. The special subgroup of teacher, headmasters who are the elites of the Basic Education, is ignored. The research about principals’ Job Burnout is nearly blank after analyzing related documents and information. With the development of the society, people pay more and more attention to the education and put more demands on the headmasters, especially middle-school principals. They are required not only to be good educators, who are equipped with all the inner qualities as a teacher, but also good managers. So the main purpose of this research was to compare the principal group with ordinary teacher group, and reveal underling factors, such as background variables and psychological protection variables. A representative sample of Wenzhou middle school principals sized 192 and a sample of middle school teacher sized 302 were sampled from various schools. The educational version of burnout inventory, self consistency scale, and interpersonal trust scale were administrated to the two samples, together with some demographic variables of interest. The applicability and equivalence of the three instruments used in this study were checked. Based on well-established reliability and cross-sample congruence of measures, the difference between principals and teachers was test. Then the contributing factors were analysis gradually. The five background variables were examined one by one in the two samples separately. A multiple covariance analysis was conducted to test whether there remained any difference between these two samples on the variables of interest. Regression analysis was used to further control the effect of self harmony and interpersonal trust to test the difference between two samples. Mediating analysis was conducted to build the relationship among the three constructs. The main results of the research were stated as following: 1. The internal consistency coefficients of all the scales were good, and no difference exited between the two groups. The measurement equivalence of three instruments was established well. The measures could be applied to and comparing the two samples. 2. The self-harmony, and interpersonal trust of principals were better than the ordinary middle-school teachers. Job Burnout of principals was significant lower than teachers. 3. Demographic variables like the gender, age groups, income levels, disricts, and the type of school, were important influencing factors. The difference patterns of the variables on these five variables in two samples had similarity and distinction. 4. After controlling the background variables, there remained significant difference between principals and teachers on the variables of interest. 5. Job Burnout negatively correlated with self-harmony and interpersonal trust. That is to say，the lower the degree of self-harmony and interpersonal are, the serious of the Job Burnout is, The correlation between the self-harmony and the interpersonal trust was positive. 6. After statistically controlling the background variables and psychological variables, there still exited significant difference between two groups of this study. Also, self harmony and interpersonal trust were significant protection predictors to different aspect of job burnout. 7. Mediating analysis was conducted to the residual score of the three constructs after controlling the five variables and group membership. Self harmony partially mediated the relationship between interpersonal trust and job burnout. That is, interpersonal trust had indirect effect to burnout mediated by self harmony, also had direct effect to burnout.

社会困境中的行为决策――社会身份与地位的影响

Social dilemmas are defined as such situations in which short-term individual and long-term collective interests are at odds (Hardin, 1968; Messick & Brewer, 1983). Severe social problems lead more and more researchers to pay attention to the issue of social dilemmas. Until now, research has widely examined the factors influencing cooperation in social dilemmas, and provided solutions to social dilemmas. In the need of theory development, previous research generally simplified the situation of realistic social dilemmas. Therefore, few studies have explored the issue of cooperation in social dilemmas in an intergroup situation. On the other hand, there has been little empirical attention for such issues in countries outside of United States and Western Europe. To meet this gap, the present study grounded itself in social identity theories and examined the effect of unequal group status on behavioral decision making in social dilemmas. To this end, the study designed three experiments to examine how individuals with different group status response psychologically and behaviorally to cooperation in intragroup and intergroup social dilemmas. In experiment 1, the study examined how independent and interdependent self- construals affect cooperative behavior in an intragroup social dilemma. The results showed that when individuals were primed with interdependent (as opposed to independent) self-construal, they consistently contributed highly, regardless of context manipulation. In contrast, those primed with independent self-construal contributed less in the investment game but only when placed in a context where group members were encouraged to think about their individual (versus shared) fate. Results supported the idea that independent self-construal in a low interdependent context produces the most competitive behavior and that this effect was partially mediated by the feeling of interaction within a group. In experiment 2, the study examined how the effect of group status on different level of cooperation in a nested social dilemma was moderated by individual status, and what roles ingroup and superordinate identifications played in the above effect. Results found that individuals in higher status groups tended to allocate more to private account and less to subgroup account compared to those in lower status group; individuals in higher status groups allocated more to higher level accounts than to private account, whereas those in lower status acted in a reverse way. The results indicated that group status (compared to individual status) exerted a positive influence on behavioral decision making in social dilemmas, with higher group status contributing more to subgroup as well as collective interests. Results also found that the effect of group status and/or individual status on cooperation in social dilemmas was moderated by sex. As for individual status, results showed that the effect of individual status on subgroup interest was significantly moderated only by the combination of higher ingroup identification and lower superordinate identification. In experiment 3, the study explored how group stability and cognitive categorization interactively influenced the relationship between group status and behavioral decision making in a social dilemma. Results did not support the prediction that group status and stability interactively affected behavioral decision-making in social dilemmas. However, it was found that this relationship was moderated by which level individuals categorized themselves at. When categorization at the individual level was salient, individuals in high status group contributed more to subgroup account than those in low status group if they perceived a stable status hierarchy; whereas they contributed more to private account and less to collective account if they perceived that the status was instable. On the other hand, when categorization at the subgroup level was salient, individuals in high status group contributed less to collective account than those in low status group if they perceived that the status was stable; whereas they contributed less to private account and more to subgroup account if they perceived an instable status relation. In summary, the present study suggests that cooperation with ingroup forms the basis of social harmony, and higher status for everyone in any given group is a necessary for social development. On the other hand, individuals in higher status group tend to be more selfish once they realize that their current status hierarchy is unstable. However, activating their collective identity will to some degree increase the level of their cooperation with the collective. The study thus provides psychological explanations on how to construct group harmony and management suggestions on how to solve social conflicts.

X-ray and optical studies of soft x-ray transients in M31

Soft X-ray transients (SXTs) are a subgroup of low-mass X-ray binaries consisting of a neutron star or a black hole and a companion low-mass star. SXTs exhibit a sudden outburst by increasing the luminosity from ∼ 1033 to ∼ 1036−38ergs1. After spending a few months in outburst, SXTs switch back to quiescence. Optical study of the binary system during the quiescence state of SXTs provides an opportunity to discriminate between BH binaries and neutron star binaries. The first part ot this research is composed of result of 10 years joint project between Hubble space telescope and Chandra, to study SXTs in M31. The other part of this thesis focused on the light curve of bright SXTs in M31. Disc irradiation is thought to be capable of explaining the global behaviour of the light curves of SXTs. Depending on the strength of the central X-ray emission in irradiating the disc, the light curve may exhibit an exponential or a linear decay. The model predicts that in brighter transients a transition from exponential decline to a linear one may be detectable. In this study, having excluded super-soft sources and hard X-ray transients, a sample of bright SXTs in M31 (Lpeak > 1038ergs1) has been studied. The expected change in the shape of the decay function is only observed in two of the light curves from the six light curves in the sample. Also, a systematic correlation between the shape of the light curve and the X-ray luminosity has not been seen.

Investigation of lantibiotic regulation, immunity and synergy

Due to the increasing incidence of antibiotic resistant strains, the use of novel antimicrobials, such as bacteriocins, has become an ever more likely prospect. Lacticin 3147 (of which there are two components, Ltnα and Ltnβ) and nisin belong to the subgroup of bacteriocins called the lantibiotics, which has attracted much attention in recent years. The lantibiotics are antimicrobial peptides that contain unusual amino acids resulting from a series of enzyme-mediated post translational modifications. Given that there have been relatively few examples of lantibiotic-specific resistance; these antimicrobials appear to represent valid alternatives to classical antibiotics. However, the fact that lantibiotics are naturally only produced in small amounts often hinders their commercialisation. In order to overcome this bottleneck, several approaches can be employed. For example, we can create a situation that reduces the quantity of a lantibiotic required to inhibit a target by combining it with other antimicrobials. Here, following an initial screen involving lacticin 3147 and several classical antibiotics, it was observed between lacticin 3147 and the commercial antibiotics polymyxin B/E function synergistically. This reduced the amounts of the individual antimicrobials required for kill and broadened the spectrum of inhibition of both agents. Upon combination with polymyxins, lacticin 3147, which has been associated with Gram positive targets only, actively targeted Gram negative species such as Escherichia coli and Cronobacter sp. An alternative means of addressing problems associated with lantibiotic yield is to better understand how production is regulated, and ultimately use this information to enhance peptide levels. With this in mind the regulation of lacticin 3147 production from the promoter Pbac was investigated using a green fluorescent protein (GFP) expression reporter system. This revealed that elements within both of the divergent operons of the lacticin 3147 gene cluster are involved in Pbac regulation. That is, LtnR, already established as a negative regulator of itself and the lacticin 3147 associated immunity genes, also acts as an activator of Pbac transcription. In contrast, an enhanced level of expression is observed in the absence of the lacticin 3147 structural genes, ltnA1 and ltnA2, indicating that these genes/gene products are involved in Pbac repression. In fact, through complementation of the ltnA2 gene, it was revealed that this regulation is more likely to be dependent on the presence of the gene transcript rather that the corresponding prepropeptide or modified Ltnβ. It may be that if lacticin 3147 production is successfully enhanced, the ability of the producing cell to protect itself may become an issue. To prepare for such a possibility a bioengineered derivative of the lacticin 3147 immunity protein LtnI (LtnI I81V) which provides enhanced protection was discovered through an in depth investigation involving the site and saturation mutagenesis of this protein. In addition, the creation of truncated forms of LtnI allowed the identification of important and essential regions of this immunity protein. Finally, as mentioned, self-immunity is essential to prevent self-killing. However the discovery of nisin U immunity and regulatory gene homologues (spiFEGRR’K) within the pathogenic strain S. infantarius subsp. infantarius is a cause for concern as it represents an example of immune mimicry, a form of lantibiotic-specific resistance. The ability of spiFEG to confer protection was apparent when they successfully provided protection to nisin A, F, Z, Q and U when expressed heterologously in the nisin sensitive L. lactis HP host. As a consequence of the studies presented in this thesis, it is likely that strategies will emerge that will facilitate the production of greater levels of lacticin 3147 production and lead to enhanced immunity in lactococcal backgrounds. Alternatively the need for enhanced production could be avoided through the use of antimicrobial combinations. In addition, providing awareness of the threats of the emergence of resistance through immune mimicry can allow researchers to develop strategies to prevent this phenomenon from leading to the dissemination of lantibiotic resistance.

Optical micro- and nanofibres: Higher mode generation and particle manipulation studies

This thesis is centred on two experimental fields of optical micro- and nanofibre research; higher mode generation/excitation and evanescent field optical manipulation. Standard, commercial, single-mode silica fibre is used throughout most of the experiments; this generally produces high-quality, single-mode, micro- or nanofibres when tapered in a flame-heated, pulling rig in the laboratory. Single mode fibre can also support higher transverse modes, when transmitting wavelengths below that of their defined single-mode regime cut-off. To investigate this, a first-order Laguerre-Gaussian beam, LG01 of 1064 nm wavelength and doughnut-shaped intensity profile is generated free space via spatial light modulation. This technique facilitates coupling to the LP11 fibre mode in two-mode fibre, and convenient, fast switching to the fundamental mode via computer-generated hologram modulation. Following LP11 mode loss when exponentially tapering 125μm diameter fibre, two mode fibre with a cladding diameter of 80μm is selected fir testing since it is more suitable for satisfying the adiabatic criteria for fibre tapering. Proving a fruitful endeavour, experiments show a transmission of 55% of the original LP11 mode set (comprising TE01, TM01, HE21e,o true modes) in submicron fibres. Furthermore, by observing pulling dynamics and progressive mode-lass behaviour, it is possible to produce a nanofibre which supports only the TE01 and TM01 modes, while suppressing the HE21e,o elements of the LP11 group. This result provides a basis for experimental studies of atom trapping via mode-interference, and offers a new set of evanescent field geometries for sensing and particle manipulation applications. The thesis highlights the experimental results of the research unit’s Cold Atom subgroup, who successfully integrated one such higher-mode nanofibre into a cloud of cold Rubidium atoms. This led to the detection of stronger signals of resonance fluorescence coupling into the nanofibre and for light absorption by the atoms due to the presence of higher guided modes within the fibre. Theoretical work on the impact of the curved nanofibre surface on the atomic-surface van der Waals interaction is also presented, showing a clear deviation of the potential from the commonly-used flat-surface approximation. Optical micro- and nanofibres are also useful tools for evanescent-field mediated optical manipulation – this includes propulsion, defect-induced trapping, mass migration and size-sorting of micron-scale particles in dispersion. Similar early trapping experiments are described in this thesis, and resulting motivations for developing a targeted, site-specific particle induction method are given. The integration of optical nanofibres into an optical tweezers is presented, facilitating individual and group isolation of selected particles, and their controlled positioning and conveyance in the evanescent field. The effects of particle size and nanofibre diameter on pronounced scattering is experimentally investigated in this systems, as are optical binding effects between adjacent particles in the evanescent field. Such inter-particle interactions lead to regulated self-positioning and particle-chain speed enhancements.

Career choice in medicine

Background: Career Choice in Medicine is an important and problematic topic. Medical education has been framed as professional identity development, yet career choice has not been viewed as a matter of identity. My primary aim was to offer new insights by exploring career choice using Figured Worlds theory, a socio-cultural theory of identity. Graduate retention is a challenge for many countries, including Ireland. My secondary aim was to address a gap in the data on postgraduate trainees in Ireland and to use the Irish case to illustrate points transferable to other contexts. Methodology & Methods: This was a predominantly qualitative Mixed Methods programme of research. My qualitative studies were oriented towards social constructionism. I collated existing data from the Royal College of Physicians of Ireland (RCPI) and HSE-MET to describe trainees and their career paths. I surveyed Basic Specialist Training trainees (n=333) about their career plans. I surveyed new trainees (n=527) about their expectations of training and all RCPI trainees about their experiences of training (n=1246). I conducted semi-structured interviews with 18 medical students and doctors. A subgroup (n=6) provided longitudinal data. Figured Worlds theory and Gee’s discourse tools were used for analysis. Results: I have used the case of medical training and career choice in Ireland to explain how social, political and cultural context, and day to day experiences in the cultural world of medicine, shaped doctors’ career choices. My qualitative findings described a unifying model of career choice, consisting of priming, exposure, positioning and open-endedness, which can guide the design of interventions to shape and support career choice. Conclusion: My original contribution has been to demonstrate the fruitfulness of framing career choice in terms of identity development. This represents a turn in the conversation about career choice, which brings new starting points and moves the dialogue forward.

Evaluation of HER2, p53, bcl-2, topoisomerase II-alpha, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes.

BACKGROUND: Breast cancer is a heterogeneous disease. Predictive biological markers (BM) of responsiveness to therapy need to be identified. Evaluation of BM is mainly done at the primary site. However, in the adjuvant therapy of breast cancer, the main goal is control of micrometastases. It is still unknown whether heterogeneity in the expression of BM between the primary site and its micrometastases exists. OBJECTIVE: To evaluate the expression of some BM with potential predictive value from the primary breast cancer site and metastatic ipsilateral axillary lymph nodes. PATIENTS AND METHODS: Focality (percentage of positive cells) and intensity staining scores were evaluated for each marker. Freshly cut sections (4 microm) from embedded blocks of breast cancer fixed in formalin or bouin were put onto superfrost slides (Menzel-Gläser). Protein expression was evaluated immunohistochemically (IHC) using monoclonal antibodies against: topo II-alpha (clone KiS1, 1 microg/ml, Roche) with a trypsine pre-treatment (P); HSP27 (clone G3.1, 1/60, Biogenex), HSP70 (clone BRM.22, 1/80, Biogenex) and HER2 (clone CB11, 1/40, Novocastra; without P); p53 (clone D07, 1/750, Dako) and bcl-2 (clone 124, 1/60, Dako) with citrate buffer as P. RESULTS: Overall, the percentage of discordant marker status in the primary tumour and its metastatic lymph nodes was 2% for HER2, 6% for p53, 15% for bcl-2, 19% for topoisomerase II-alpha, 24% for HSP27 and 30% for HSP70. For the subgroup of patients with positive BM in the primary tumour, the percentage of discordance was 6% for HER2, 7% for p53, 14% for bcl-2, 19% for HSP70, 21% for topoisomerase II-alpha and 36% for HSP27. For the subgroup of patients with positive BM in the lymph nodes, the percentage of discordance was 9% for bcl-2, 15% for HER2 and p53, 21% for topoisomerase II-alpha, 22% for HSP27 and 25% for HSP70. CONCLUSIONS: 1) No biological marker had 100% concordant results. 2) Although some discordant cases might be explained by the limitations of the IHC technique, future studies aiming to evaluate the predictive value of BM in the adjuvant therapy of breast cancer should take into account a possible difference in BM expression between the primary and the metastatic sites.

An entirely cell-based system to generate single-chain antibodies against cell surface receptors.

The generation of recombinant antibodies (Abs) using phage display is a proven method to obtain a large variety of Abs that bind with high affinity to a given antigen. Traditionally, the generation of single-chain Abs depends on the use of recombinant proteins in several stages of the procedure. This can be a problem, especially in the case of cell-surface receptors, because Abs generated and selected against recombinant proteins may not bind the same protein expressed on a cell surface in its native form and because the expression of some receptors as recombinant proteins is problematic. To overcome these difficulties, we developed a strategy to generate single-chain Abs that does not require the use of recombinant protein at any stage of the procedure. In this strategy, stably transfected cells are used for the immunization of mice, measuring Ab responses to immunization, panning the phage library, high-throughput screening of arrayed phage clones, and characterization of recombinant single-chain variable regions. This strategy was used to generate a panel of single-chain Abs specific for the innate immunity receptor Toll-like receptor 2. Once generated, individual single-chain variable regions were subcloned into an expression vector allowing the production of recombinant Abs in insect cells, thus avoiding the contamination of recombinant Abs with microbial products. This cell-based system efficiently generates Abs that bind to native molecules on the cell surface, bypasses the requirement of recombinant protein production, and avoids risks of microbial component contamination.

Cytokinesis proteins Tum and Pav have a nuclear role in Wnt regulation.

Wg/Wnt signals specify cell fates in both invertebrate and vertebrate embryos and maintain stem-cell populations in many adult tissues. Deregulation of the Wnt pathway can transform cells to a proliferative fate, leading to cancer. We have discovered that two Drosophila proteins that are crucial for cytokinesis have a second, largely independent, role in restricting activity of the Wnt pathway. The fly homolog of RacGAP1, Tumbleweed (Tum)/RacGAP50C, and its binding partner, the kinesin-like protein Pavarotti (Pav), negatively regulate Wnt activity in fly embryos and in cultured mammalian cells. Unlike many known regulators of the Wnt pathway, these molecules do not affect stabilization of Arm/beta-catenin (betacat), the principal effector molecule in Wnt signal transduction. Rather, they appear to act downstream of betacat stabilization to control target-gene transcription. Both Tum and Pav accumulate in the nuclei of interphase cells, a location that is spatially distinct from their cleavage-furrow localization during cytokinesis. We show that this nuclear localization is essential for their role in Wnt regulation. Thus, we have identified two modulators of the Wnt pathway that have shared functions in cell division, which hints at a possible link between cytokinesis and Wnt activity during tumorigenesis.

Identification of microRNAs expressed in two mosquito vectors, Aedes albopictus and Culex quinquefasciatus.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression in a variety of organisms, including insects, vertebrates, and plants. miRNAs play important roles in cell development and differentiation as well as in the cellular response to stress and infection. To date, there are limited reports of miRNA identification in mosquitoes, insects that act as essential vectors for the transmission of many human pathogens, including flaviviruses. West Nile virus (WNV) and dengue virus, members of the Flaviviridae family, are primarily transmitted by Aedes and Culex mosquitoes. Using high-throughput deep sequencing, we examined the miRNA repertoire in Ae. albopictus cells and Cx. quinquefasciatus mosquitoes. RESULTS: We identified a total of 65 miRNAs in the Ae. albopictus C7/10 cell line and 77 miRNAs in Cx. quinquefasciatus mosquitoes, the majority of which are conserved in other insects such as Drosophila melanogaster and Anopheles gambiae. The most highly expressed miRNA in both mosquito species was miR-184, a miRNA conserved from insects to vertebrates. Several previously reported Anopheles miRNAs, including miR-1890 and miR-1891, were also found in Culex and Aedes, and appear to be restricted to mosquitoes. We identified seven novel miRNAs, arising from nine different precursors, in C7/10 cells and Cx. quinquefasciatus mosquitoes, two of which have predicted orthologs in An. gambiae. Several of these novel miRNAs reside within a ~350 nt long cluster present in both Aedes and Culex. miRNA expression was confirmed by primer extension analysis. To determine whether flavivirus infection affects miRNA expression, we infected female Culex mosquitoes with WNV. Two miRNAs, miR-92 and miR-989, showed significant changes in expression levels following WNV infection. CONCLUSIONS: Aedes and Culex mosquitoes are important flavivirus vectors. Recent advances in both mosquito genomics and high-throughput sequencing technologies enabled us to interrogate the miRNA profile in these two species. Here, we provide evidence for over 60 conserved and seven novel mosquito miRNAs, expanding upon our current understanding of insect miRNAs. Undoubtedly, some of the miRNAs identified will have roles not only in mosquito development, but also in mediating viral infection in the mosquito host.

A kinesin motor in a force-producing conformation.

BACKGROUND: Kinesin motors hydrolyze ATP to produce force and move along microtubules, converting chemical energy into work by a mechanism that is only poorly understood. Key transitions and intermediate states in the process are still structurally uncharacterized, and remain outstanding questions in the field. Perturbing the motor by introducing point mutations could stabilize transitional or unstable states, providing critical information about these rarer states. RESULTS: Here we show that mutation of a single residue in the kinesin-14 Ncd causes the motor to release ADP and hydrolyze ATP faster than wild type, but move more slowly along microtubules in gliding assays, uncoupling nucleotide hydrolysis from force generation. A crystal structure of the motor shows a large rotation of the stalk, a conformation representing a force-producing stroke of Ncd. Three C-terminal residues of Ncd, visible for the first time, interact with the central beta-sheet and dock onto the motor core, forming a structure resembling the kinesin-1 neck linker, which has been proposed to be the primary force-generating mechanical element of kinesin-1. CONCLUSIONS: Force generation by minus-end Ncd involves docking of the C-terminus, which forms a structure resembling the kinesin-1 neck linker. The mechanism by which the plus- and minus-end motors produce force to move to opposite ends of the microtubule appears to involve the same conformational changes, but distinct structural linkers. Unstable ADP binding may destabilize the motor-ADP state, triggering Ncd stalk rotation and C-terminus docking, producing a working stroke of the motor.

Scientific writing: a randomized controlled trial comparing standard and on-line instruction.

BACKGROUND: Writing plays a central role in the communication of scientific ideas and is therefore a key aspect in researcher education, ultimately determining the success and long-term sustainability of their careers. Despite the growing popularity of e-learning, we are not aware of any existing study comparing on-line vs. traditional classroom-based methods for teaching scientific writing. METHODS: Forty eight participants from a medical, nursing and physiotherapy background from US and Brazil were randomly assigned to two groups (n = 24 per group): An on-line writing workshop group (on-line group), in which participants used virtual communication, google docs and standard writing templates, and a standard writing guidance training (standard group) where participants received standard instruction without the aid of virtual communication and writing templates. Two outcomes, manuscript quality was assessed using the scores obtained in Six subgroup analysis scale as the primary outcome measure, and satisfaction scores with Likert scale were evaluated. To control for observer variability, inter-observer reliability was assessed using Fleiss's kappa. A post-hoc analysis comparing rates of communication between mentors and participants was performed. Nonparametric tests were used to assess intervention efficacy. RESULTS: Excellent inter-observer reliability among three reviewers was found, with an Intraclass Correlation Coefficient (ICC) agreement = 0.931882 and ICC consistency = 0.932485. On-line group had better overall manuscript quality (p = 0.0017, SSQSavg score 75.3 +/- 14.21, ranging from 37 to 94) compared to the standard group (47.27 +/- 14.64, ranging from 20 to 72). Participant satisfaction was higher in the on-line group (4.3 +/- 0.73) compared to the standard group (3.09 +/- 1.11) (p = 0.001). The standard group also had fewer communication events compared to the on-line group (0.91 +/- 0.81 vs. 2.05 +/- 1.23; p = 0.0219). CONCLUSION: Our protocol for on-line scientific writing instruction is better than standard face-to-face instruction in terms of writing quality and student satisfaction. Future studies should evaluate the protocol efficacy in larger longitudinal cohorts involving participants from different languages.

Does improved access to diagnostic imaging results reduce hospital length of stay? A retrospective study.

BACKGROUND: One year after the introduction of Information and Communication Technology (ICT) to support diagnostic imaging at our hospital, clinicians had faster and better access to radiology reports and images; direct access to Computed Tomography (CT) reports in the Electronic Medical Record (EMR) was particularly popular. The objective of this study was to determine whether improvements in radiology reporting and clinical access to diagnostic imaging information one year after the ICT introduction were associated with a reduction in the length of patients' hospital stays (LOS). METHODS: Data describing hospital stays and diagnostic imaging were collected retrospectively from the EMR during periods of equal duration before and one year after the introduction of ICT. The post-ICT period was chosen because of the documented improvement in clinical access to radiology results during that period. The data set was randomly split into an exploratory part used to establish the hypotheses, and a confirmatory part. The data was used to compare the pre-ICT and post-ICT status, but also to compare differences between groups. RESULTS: There was no general reduction in LOS one year after ICT introduction. However, there was a 25% reduction for one group - patients with CT scans. This group was heterogeneous, covering 445 different primary discharge diagnoses. Analyses of subgroups were performed to reduce the impact of this divergence. CONCLUSION: Our results did not indicate that improved access to radiology results reduced the patients' LOS. There was, however, a significant reduction in LOS for patients undergoing CT scans. Given the clinicians' interest in CT reports and the results of the subgroup analyses, it is likely that improved access to CT reports contributed to this reduction.