Abstracts: AACR Special Conference on Tumor Metastasis; November 30-December 3, 2015; Austin, TX

Neogenin-1, a transmembrane receptor involved in axonal guidance, angiogenesis, neuronal cell migration, and cell death, is activated when bound to the Netrin and RGM ligand families during development and adult homeostasis. While Neogenin-1 and its ligands have been shown to be involved in tumoral progression, little is known about the specific function of the proteins and the cell signaling events that occur in cancer cells. Here, we demonstrate the exclusive presence of Neogenin-1 and Netrin-4 in SK-N-SH and SH-SY5Y neuroblastoma cells. Our research elucidates the function of Neogenin-1 and its autocrine ligand Netrin-4 in cell migration, proliferation, survival, and metastasis, the cellular aspects of cancer.

To evaluate the contribution of Neogenin-1, the protein was knocked down using shRNAs (shNeo1) and overexpressed. We also knocked down Netrin-4 with shRNA (shNTN4) and performed gain of function studies using a human recombinant of this protein. Cell migration was analyzed via wound healing and transwell assays using increasing concentrations of Netrin-4. In addition, we evaluated cell proliferation and cell apoptosis after treatments. We also assessed metastasis and tumoral progression via chick chorioallantoic membrane (CAM) assay and quantitative-PCR to evaluate presence of human Alu sequences in genomic DNA extracted from chick embryonic lungs.

We observed that shNeo1 and shNTN4 cells migrate less in transwell assays, possibly due to their insensibility to the chemotactic stimuli of Netrin-4. shNeo1 cells migrated less in wound healing assays as well. We detected increased cell migration when overexpressing Neogenin-1, but observed that cells were insensible to the Netrin-4 stimulus when overexpressing only the intracellular domain of Neogenin-1. We found less proliferation of shNTN4 cells in comparison to control cells, indicating that endogenous expression of Netrin-4 is required. This may be the case if Netrin-4 acts as a survival factor via its receptor Neogenin-1. Additionally, we observed increased cell death when knocking down Netrin-4 and that exogenous Netrin-4 was able to reduce this effect. Also, when Neogenin-1 is overexpressed, cell death increases and Netrin-4 is able to rescue cells from apoptosis. Finally, in vivo analysis showed that the weight of primary tumors in shSCR (control), shNeo1, and shNetrin-4 cells are similar. However, shNeo1 and shNTN4 did not produce secondary tumors. Metastasis analysis indicated that shNeo1 and shNTN4 metastasize less than control cells.

Overall these results demonstrate that Neogenin-1 is involved in cell migration via Netrin-4 in neuroblastoma cells, and that endogenous Netrin-4 is important for cell survival, as it reduces apoptosis induced by Neogenin-1. We demonstrate that the Neogenin-1/Netrin-4 signaling complex modulates metastasis of neuroblastoma cells: Netrin-4 induces cell migration when bound to Neogenin-1, and conversely mediates apoptosis when not bound to Neogenin-1. Thus, endogenous Netrin-4 maintains the cells in a pro-survival and pro-migratory state. Our results shed light on the cellular mechanics of Netrin-4 and its receptor, Neogenin-1, which provides further information on their potential use as therapeutic targets to reduce metastasis in neuroblastoma.

Citation Format: Andrea Villanueva, Natalie Andrea Espinoza, Luis Solano, Luis Milla, Veronica Palma. Neogenin-1 promotes cell migration, survival, and metastasis through Netrin-4 in neuroblastoma cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B50.


Background: Functional communication requires proficiency in the adaptation of language to varied contexts. Recent research has demonstrated that individuals with traumatic brain injury (TBI) experience difficulty with communicative effectiveness across a variety of discourse genres. Analysis of conversation following TBI is of particular interest because of its importance in the process of socialisation. The development and maintenance of social relationships has been noted to be difficult for individuals with TBI. It has been suggested that these interactional difficulties are the result of social skills deficits which may be a reflection of impaired language use. A variety of analyses have been applied to samples of conversation from individuals with TBI. These analyses have included pragmatic rating scales, exchange structure analysis, Conversation Analysis, as well as measures of topic initiation, topic maintenance, and response appropriateness. Overall, individuals with TBI have been noted to have difficulties with topic management and expressing information in a logical fashion. Further, their conversations have been rated as less interesting, less appropriate, and more effortful. Aims: The present study sought to validate the clinical utility of Blank and Franklin's (1980) procedure for analysis of conversation with larger groups of TBI and non-brain-injured individuals. Methods & Procedures: The examiner engaged 32 closed-head-injured (CHI) and 43 nonbrain-injured adults in individual conversations. The conversational performance of each participant, as well as the examiner, were analysed for various dimensions of response appropriateness and topic initiation. Outcomes & Results: Results indicated that the individuals with CHI were dependent on the examiner to maintain the flow of the conversation and that they often contributed information that did not facilitate the social interaction. It was also noted that the examiner compensated by asking more questions and introducing more topics in conversations with the individuals with CHI. In contrast, the conversations with the non-brain-injured controls were characterised by a shared responsibility for sustaining the interactional flow. Conclusions: In general these findings are consistent with previous investigations of conversational skills of individuals with TBI. Blank and Franklin's analysis procedure for conversation did delineate differences between the participant groups and in the examiner's performance when interacting with these individuals. However, it is important to note that the tenor of the conversational interactions (i.e., the status and roles of the participants) may have constrained the individuals with CHI and therefore their apparent dependence on the examiner may not have been solely the result of their brain injuries.


Background: For vertebroplasty, newly synthesized bone cements are proposed to replace traditional polymethylmethacrylate (PMMA). Most inventors initially evaluated these newly developed cements in animal spine models. However, even these time- and work-consuming histological inspections performed meticulously by experienced hands, there are still lots of specimen lost during the processing procedures. Although the histological sections can reveal new bone formations and surrounding tissue reactions to implanted materials, it is difficult to identify the degradation processes of the injected cement. In fact, there is no standard method to quantify the volume changes of injected substitutes postoperation. Methods: Previously, we developed two new biodegradable cements and evaluated performances in fixed-volume and fixed-shaped holes in vertebral bodies of porcine lumbar spine. The animals were sacrificed and the retrieved spines were analyzed after 3 and 6 months. Herein, we further used computed tomography (CT) and three-dimensional CT (3D-CT) to quantitate volumes and biodegradation of cements inside vertebral bodies after previous attestation of CT findings. Exteriors of controls and injected materials were reconstructed with different Hounsfield units (HU); changes of HU as well as cement volumes were later calculated. Results: The results revealed that the volumes and shapes of these biodegradable cements can be determined by 3D-CT. After meticulous comparisons among gross specimens, histologies, and CT images, the different patterns observed in CT implied consistency among all three observations. Gradual reductions of HU and volumes of newly synthesized cements showed the degradability. Meanwhile, consistent HU and volumes of PMMA meant its inertness. Conclusion: CT imaging may be a preliminary, quantitative, and liable way for evaluating injectable bone cements in the vertebral bodies.


Salmonellosis is an infection caused by specific or non specific serotypes of theSalmonella genus, responsible for losses in the poultry industry. Fowl typhoid, caused by S. Gallinarum (SG) is important because it causes elevated mortality in adult birds, leading to economic losses in the poultry industry. This study aimed at quantifying the number of viable SG cells in the liver, spleen, lung, cecum, and reproductive tract (ovary and testicles) of experimentally inoculated Japanese quails (Coturnix coturnix), as well as SG shedding in their feces. One hundred and two Japanese quails, with four months of age at the beginning of the experiment, were used. The birds were inoculated with three bacterial cultures containing different concentrations (6x104CFU/0.1mL, 2x105 CFU/0.4mL, or 5x106CFU/0.2mL) of SG resistant to nalidixic acid. On days 1, 4, 7, and 14 after the inoculation (dpi) individual cloacal swabs were collected from six birds per group, which were subsequently sacrificed for organ sampling. The swab samples were streaked directly on plates containing brilliant green agar and nalidixic acid (VBNal). Samples that were negative after 24h, were streaked again. The collected organs were individually macerated and transferred to buffered peptone water at 0.1%. The solutions were immediately diluted serially for CFU counting in VBNal. SG was successfully recovered from one quail, which was inoculated with 2x105 CFU/0.4mL, and from five quails of the group inoculated with 5x106CFU/0.2mL inoculum. All of the analyzed cloacal swab samples were negative. Therefore, this study demonstrated it was difficult to isolate SG from the analyzed organs and that it was not possible to recover thepathogen in the cloacal swabs collected from inoculated quails. These results may be explained by the absence of flagella in SG, inducing weak intestinal immune response in the beginning of the infection and preventing its isolation in cloacal swab samples. The low positivity rate of the analyzed organs may be due to the immune status of the euthanized birds, since the SG dissemination in the animal organism occurs mostly close to death, which was observed in the birds found dead during the experiment.


Sodium Excretion, Cardiovascular Disease, and Chronic Kidney Disease To the Editor In the study by Mills and colleagues,1 high urinary sodium excretion was associated with increased cardiovascular disease (CVD) risk in patients with chronic kidney disease (CKD). Patients were divided into 4 groups based on quartiles of calibrated urinary sodium excretion (<2894 mg/24 hours; 2894-3649 mg/24 hours; 3650-4547 mg/24 hours; and ≥4548 mg/24 hours) and were followed up for a median of 6.8 years. The cumulative incidence of CVD for each group from lowest to highest urinary sodium excretion was 18.4%, 16.5%, 20.6%, and 29.8%, respectively. After multivariable adjustment, no significant association was found between urinary potassium excretion and CVD events. The authors did not mention whether there was an interaction between sodium and potassium excretion for the composite outcome measure.2 A urinary sodium to potassium excretion ratio might yield a different association with CVD risk.3 Also, they did not evaluate CVD mortality risk in their study. In a study of patients with established CVD or diabetes mellitus, O'Donnell and colleagues2 found an increased risk of CVD with urinary sodium excretion of more than 7000 mg/24 hours and, surprisingly, an increased risk of cardiovascular mortality at urinary sodium excretion of less than 3000 mg/24 hours. Additionally, higher urinary potassium excretion rates were associated with a decreased risk of stroke. Although Mills and colleagues did not evaluate cardiovascular mortality and their study population was different from the patients in the study by O'Donnell and colleagues, the results of increasing CVD risk with higher sodium excretion are similar. Further studies are needed before using these findings in the management of such patients.


This paper evaluates how economic theory deals with analyses of current real estate dynamics and urban residential structure. It shows the fundamental axioms of neoclassical spatial synthesis and their explanations in terms of equilibrium, and highlights ambiguous and unsatisfactory, but elegant, solutions to urban spatial economic structure and dynamics. It presents the critical heterodox approach to the fundamental axioms and the hypothesis of spatial equilibrium, and shows the main aspects of the central heterodox contribution to residential real estate dynamics.


This thesis provides an analysis of profit efficiency of Australian banks in the period from 2000 to 2008. The directional (technology) distance function, data envelopment analysis (DEA) and the norm-based profit index approach are utilised to compute profit efficiency scores. Technicaland allocative efficiency scores are provided by the decomposition of profit efficiency, and price efficiency scores are also provided by a separate calculation. The profit efficiency of Australian banks is found to have not been improved in the period of study. In contrast to the previous Australian studies, allocative inefficiency is found to be the main source of the overall profit inefficiency of the banks, rather than technical inefficiency. This study also found strong implications for the negative impacts of highly concentrated market structure of the Australian banking sector on Australian banks' efficiency, which are observed from the results of allocativeand price efficiencies. Spearman Rank Correlation (SRC) analysis is conducted to examine correlation between profit efficiency and the conventional accounting measures of profitability of Australian banks. The correlation is found between the profit efficiency and return on equity (ROE). However, return on assets (ROA) is found to be negatively correlated to the profit efficiency. The size factors, such as bank's total assets and total equity, are observed to be positively correlated to the profit efficiency.


This research project has investigated the mechanical behaviour of artificial turf surface systems used for sports under a range of real player movements, and the contribution of component layers to the overall system response by developing advanced measurement systems and methods.
Artificial turf surface systems are comprised of a number of different materials and commonly with several layers, all of which contribute to their composite behaviour. During sports movements a player loads the surface, resulting in deformation that can change the surface behaviour, which in turn modifies the player biomechanical response. Improving the understanding of surface response to actual player loading is important for developing enhanced products for improving play performance. Likewise, by improving knowledge of surface effects on players, the understanding of injury risk can be improved. However, there is currently no published research to measure and analyse the behaviour of artificial turf system during real player locomotion. This research was undertaken to address this current lack of knowledge within the interaction between player and sports surface regarding the effects of player loading on the mechanical behaviour of artificial turf systems.
In addition to support player loading regime, mechanical behaviour of hockey and third generation artificial turf surface systems and their component shockpad layers (a rubber shreds bonded shockpad and a polyurethane foam shockpad) was examined through dynamic cyclic compressive loading using an advanced material testing machine in laboratory environment. Each layer and carpet-shockpad system was subjected to controlled loading designed with previous biomechanical data at various loading frequencies (0.9 Hz, 3.3 Hz and 10 Hz) and under two different contact areas (50 mm and 125 mm diameter) to simulate aspects of player walking, running and sprinting. All layers and surface systems tested showed nonlinear stress-strain behaviour with hysteresis. Increasing the contact area resulted in reduced surface vertical deflection and more linear response. Increasing the loading frequency led to stiffer response in the lower stress range ( 600 kPa) and a decrease in maximum strain as the loading frequency increased. Hysteresis loops obtained at different loading frequencies indicated that the amount of energy lost at the same peak load of 1900 N in each surface system decreased with an increase in loading rate.
Player loading regime was performed to quantify the load/stress and the resulting surface deformation/strain under subject loading. Measurement systems including motion capture system, force plate and high speed were developed to characterise the response behaviour in a novel way. The mechanical behaviour of artificial turf surface systems under three player movement patterns (heel-toe walking, forefoot running and forefoot single leg landing) was measured. Boot-surface contact area of each movement varied during the stance. The heel-toe walking results indicated that the maximum applied stress and surface strain occurred in very early stance (first 10%) when the boot-surface contact area was small. For forefoot running and landing, the peak surface strain occurred around mid-stance concurrent with the time of peak applied stress. The maximum strain measured under running was smaller than under landing.
A thin-film pressure sensing mat was used in both mechanical and player loading regimes and proved to be a useful tool for evaluating the pressure distributions and contact areas at different interfaces of the surface system. The applied stress on surface was observed to greatly reduce with depth over increasing contact area through the surface systems. Although the average pressure was reduced, pressure distribution contour showed directly under the surface load area the pressure at depth was still relatively large and that outside of this area the pressure was much lower.
A comparison of the mechanical behaviour of artificial turf systems in terms of compressive strain, modulus of elasticity, stress distribution and energy loss under mechanical and player loading was evaluated. Key loading parameters in different loading regimes and their influence on surface system response were determined. The structure and material intrinsic properties of shockpad were considered to further explain the observed surface system behaviour. Two mathematical models were used to fit through the experimental data and found to be able to describe the loading behaviour.
A breakthrough in understanding of the effects of real player loading on the mechanical behaviour response of artificial turf systems, and the contribution of the components to the whole system response has been achieved through the development of advanced measurement techniques.


Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and administered worldwide. There have been reports of neurological adverse events following immunization (AEFIs). We herein report a case of refractory longitudinally extensive transverse myelitis in a 75-year-old Japanese man following the first dose of the BNT162b2 vaccine. The patient developed total sensory loss below the umbilicus and complete paralysis in both legs. Although he was treated with steroid therapy and plasma exchange, his recovery was limited, and severe sequelae remained. Further studies, including large epidemiological studies, are required to understand the association between SARS-CoV-2 vaccines and neurological AEFI.


Prostanoids, consisting of prostaglandins (PGs) and thromboxanes (TXs), are oxygenated products of C20 unsaturated fatty acids. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. Given that aspirin-like nonsteroidal anti-inflammatory drugs exert their actions by suppressing prostanoid production, prostanoids have been implicated in processes inhibited by these drugs, including inflammation, fever, and pain. Prostanoids also contribute to vascular homeostasis, reproduction, and regulation of kidney and gastrointestinal functions. How prostanoids exert such a variety of actions had remained unclear, however. Prostanoids are released outside of cells immediately after their synthesis and exert their actions by binding to receptors on target cells. We have identified a family of eight types or subtypes of G protein–coupled receptors that mediate prostanoid actions. Another G protein–coupled receptor was also identified as an additional receptor for PGD2. Genes for these receptors have been individually disrupted in mice, and analyses of these knockout mice have not only elucidated the molecular and cellular mechanisms of known prostanoid actions but also revealed previously unknown actions. In this article, I review the physiological and pathophysiological roles of prostanoids and their receptors revealed by these studies.


The BIRD mission was designed by the German Aerospace Center for hot spot detection and the measurement of vegetation conditions. To keep the instruments in accurate calibration, high demands were required to the structure. For this reason, a structure development was needed for the BIRD qualification. The test requirements for the qualification were adapted from KOSMOS specifications first, than from PSLV specifications. For more flight like tests, a dynamic analysis of the flight configuration for BIRD was performed; in consequence, the qualification levels could be reduced. BIRD passed all mechanical qualification tests successful.


The Ordovician Trenton Group (Sherman Fall and Cobourg formations) and the Lindsay (Collingwood Member) and Blue Mountain formations of southwestern Ontario were examined using Rock-Eval pyrolysis, gas chromatography, gas chromatography-mass spectrometry, and incident-light microscopy to evaluate their paleodepositional environments, thermal maturities, and source rock potential. All units contain sufficient amount of oil-prone (type II), predominantly marine organic matter to be considered as petroleum source rocks. Unstructured bituminite with varying proportions of unicellular alginite are the dominant dispersed organic matter macerals. The bituminite typically occurs in massive to laminated, granular or patchy populations that commonly show microtextural relationships. Persistent inclusions of Leiosphaeridia telalganite demonstrate that planktonic algal debris was a primary organic substrate for blooming microbes. Disseminated coccoidal Gloeocapsomorpha prisca is found in minor amounts, usually in association with common to abundant acritarchs. Zooclasts (chitinozoa, graptolites, scolecodonts) and solid bitumen also are present as maceral inclusions within the bituminite network. The biomarker distributions for all of the studied units are those expected for marine organic matter deposited in a clastic-dominated environment. The extracts are characterized by a smooth n-alkane profile, with low abundance of C20+ members, typical for marine derived organic matter. Pristane/phytane ratios range from 0.97 to 1.72, indicating dysoxic conditions during deposition. Smooth C31-C35 homohopane profiles, Ts/Tm ratios (typically above 1.0), and a higher concentration of diasteranes relative to regular steranes all appear to indicate the clay-bearing character of these rocks. The predominance of C30 hopane over C29 regular sterane is interpreted to reflect a primary microbial input and extensive reworking of the organic matter. Optical (reflectance, fluorescence) and geochemical (Tmax, biomarker data) thermal maturity parameters indicate that the Trenton and Blue Mountain strata are within the zone of prolific oil generation throughout the whole area of study. The Collingwood shales are mature with respect to petroleum generation in the eastern part (Toronto area) and only marginally mature in the northern part (Georgian Bay area) of the study area. In general, the biomarker composition of the extracts from all examined units is compatible with that of the oils found in the Trenton reservoirs of southwestern Ontario; however, geochemical and geological evidence suggests that the organic-rich shaly laminae within the Trenton Group are the principal source of these oils. Accumulation of organic carbon in the Ordovician sediments of southern Ontario is suggested to derive from low-energy, normal-marine environments grading from shallow-shelf into deep-shelf and open-basinal settings. The nutrient availability and, consequently, higher bioproductivity, more intense consumption of oxygen, and progressing anoxia, controlled by a low-latitude location, diminished water circulation, stratification of the water column, and a depressed pycnocline resulted in high preservation rates. The amorphous nature of kerogen reflects significant microbial interaction at the water/ sediment interface and within the sediments where reducing conditions must have periodically predominated.


Since the passage of the Court Interpreters Act in 1978, defendants have had a statutory right to a language interpreter when the district court determines that the defendant's language barrier inhibits his comprehension. When defendants have appealed their convictions, claiming that the court erroneously denied them an interpreter, courts of appeals review the lower court determinations for clear error or abuse of discretion. This Article argues that this deferential standard is not proper for reviewing interpreter determinations under the Act, which are mixed questions of law and fact. Instead, appellate courts should review findings of fact for clear error and legal conclusions de novo.


We present kinematics, design, control, characterization and user evaluation of AssistOn-Arm, a novel, powered, self-aligning exoskeleton for robot-assisted upper extremity rehabilitation that allows for movements of the shoulder girdle as well as shoulder rotations. AssistOn-Arm can both actively and passively enable translational movements of the center of glenohumeral joint, while also passively compensating for the translational movements at elbow and wrist. Automatically aligning all its joint axes, AssistOn-Arm provides an ideal match between human joint axes and the exoskeleton axes, guaranteeing ergonomy and comfort throughout the therapy, and extending the usable range of motion for upper extremity movement therapies. Furthermore, self-aligning feature of AssistOn-Arm significantly shortens the setup time required to attach the patient to the exoskeleton. In addition to the typical shoulder rotation exercises, AssistOn-Arm can deliver glenohumeral mobilization (scapular elevation/depression and protraction/retraction) and scapular stabilization exercises, extending the type of therapies that can be administered using the upper-arm exoskeletons. To ensure safety and gentle interactions with the patient, AssistOn-Arm is designed to be passively backdriveable, thanks to its capstan-based multi-level transmission and spring-based passive gravity compensation mechanism. Open and closed-loop impedance controllers have been implemented to safely regulate interactions of AssistOn-Arm with patients and performance of the device has been experimentally characterized. Ergonomy and useability of the device has also been demonstrated through human subject experiments.


The surface of six different archaeological obsidian tools are analyzed systematically with Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) and Quad-SIMS for both the evaluation of the surface topography, as well as, the detection of remaining organic compounds via various amino acids, that may have been trapped in the surfaces. This initiates a new way to wear analysis and dating of prehistoric glass tools. The three basic criteria in surface topography and diffusion dating that has been investigated here for first time is the detection of organics, the elemental concentration mapping and 3D versus depth, and the simul-taneous recording of several cations (C, F, Al, Mg). In any H + depth profile in obsidian hydration rim, C and Mg must also be included in measurement. A non-conformity of cation profiles between H + and these cations point an area with inclusions and the measurement has to be repeated in different spot.


The following analysis is based on a case study of three years
duration (1983-1986), and focuses on a physical education department
at a large English comprehensive school which became involved in a
teacher initiated curriculum innovation when a new Head of
Department was appointed in September 1983. The research process
was guided by the grounded theory approach, and the use of
prolonged observation coupled with reflexive interviews allowed the
emergent concerns of the teachers in relation to the innovation to
be made evident, as competing definitions of both subject paradigm
and pedagogy clashed. Within the department, several micropolitical
strategies were constructed to cope with the pressures of change,
which legitimised a dislocation between the 'classroom' and
'educational' contexts of the school, allowing some of the teachers
to deflect the implications of the innovation for their own practice.
It is suggested that the strategies employed by teachers arise
within the social context of the school as a work place that
provides, dilemmas, opportunities and possibilities within which the
teacher constructs, modifies and abandons coping strategies to
enhance both long and short term self interests.


In reference to professional training for trainee teachers, the tutor or cooperative teacher (CT) is considered as an alternation between two environments, academia and training, contributing to the training by the advice and support. Our research provides "support for physical education student teachers (PE-STs)" as determinants of teaching advice of CT. This study includes a qualitative analysis which aims to identify the advice of CTs to the student teachers for whom they are responsible for training. It's a descriptive/exploratory methodology based on observation and video recorded six (6) physical education (PE) sessions lasting one hour each and six semi structured interviews (30 minutes each) and gave CTs the opportunity to share their perspectives on broad topics such as professional training, teaching, and characteristics of the training environment and succinct topics such as training program and their preoccupation. Data were collected during 2 months of observations and interviews with six CTs during professional training of 12 PE-STs in Level 3 (third year, BAC+3). CTs justify their teaching by six categories in which we have grouped the different types of advice. The CTs are more interested by problems of organization and control students. They believe that educational content is worthless without a good control of the class.


This work presents the current oscillation phenomena observed in an electrochemical Cu/0.5 M CF3COOH system. The dynamical response of this new oscillator was followed by both current density-potential (j-E) and current density-time (j-t) curves. The current oscillation phenomena of the investigated system were monitored over various potential scan rates and constant applied potentials as control parameters. The increase of potential scan rate significantly decreases both the potential range of current oscillations and the frequency of oscillations. At the j-t curves both the simple and the complex (period adding) oscillations were found. Moreover, with the increase of applied potential, the increase of period of oscillations and current oscillation amplitudes were observed. It appears that the period of current oscillations exponentially grows with applied potential.


Purpose:Femtosecond lasers are nowadays routinely used in corneal surgery, mainly in the context of refractive surgery. Some of the clinical systems also have options for corneal grafting. However, interventions in the depth of the tissue are difficult in the case of oedematous or otherwise pathological corneas. This difficulty principally arises from the fact in those corneas, the propagation of the laser beam is perturbed by optical scattering. This phenomenon can be greatly reduced by using a better suited laser wavelength. Methods:The laser is a femtosecond Ti:sapphire laboratory laser followed by an Optical Parametric Amplifier. The wavelength can be parameters from 1200 nm to 2400 nm. Incisions are performed on human eyes obtained under permission from the French Eye Bank, Paris. These corneas are positioned on an anterior chamber which may be moved in three dimensions by a step motor system. Penetrating and lamellar incisions have been performed using different pulse energies and varying wavelengths. Results:Several experiments of incisions have been done at wavelengths around 1600 nm and have been compared to those already performed at 800 nm and 1000 nm. We have compared penetration depth and incision quality as a function of wavelength and energy. We could demonstrate a significant improvement when performing penetrating and depth lamellar keratoplasty pathological corneas using the modified wavelength. Conclusion: The use of longer infrared wavelengths for femtosecond laser keratoplasty significantly improves the quality and reproducibility of the incisions. Future systems may be further optimised by the use of deformable mirrors.


Interfaces are inherent in and essential to organic electronic devices. At every interface, both organic/organic and organic/inorganic, the potential to utilize nanostructuring to control device performance is very high. In this paper, we focus on one example of nanostructuring at the donor/acceptor heterojunction in organic photovoltaics, with the purpose of modifing efficiency by four orders of magnitude. We show that the length of the exciton dissociating interface can be tuned by changing the substrate temperature for small molecule heterojunction photodiodes based on crystalline DIP/C60 mixtures. Due to the tuneable interface morphology, the performance of such devices can be changed from poor performing planar heterojunctions to higher efficiency ordered nanoscale bulk heterojunction structures. In this way, highly crystalline DIP can be thought of as a natural "bulk" heterojunction.


Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China Abstract: In recent years, a growing consensus is emerging that the mechanical microenvironment of tumors is far more critical in the onset of tumor, tumor progression, invasion, and metastasis. Matrix stiffness, one of the sources of mechanical stimulation, affects tumor cells as well as non-tumor cells in multiple different molecular signaling pathways in solid tumors such as colorectal tumors, which lead to tumor invasion and metastasis, immune evasion and drug resistance. This review will illustrate the relationship between matrix stiffness and colorectal cancer from the following aspects. First, briefly introduce the mechanical microenvironment and colorectal cancer, then explain the origin of colorectal cancer extracellular matrix stiffness, and then synthesize the study of matrix stiffness of colorectal cancer in recent years to elaborate the effects of extracellular matrix stiffness in colorectal cancer's biological behavior and signaling pathways, and finally we will discuss the transformation treatment for the matrix stiffness of colorectal cancer. An in-depth understanding of matrix stiffness and colorectal cancer can help researchers conduct further experiments to find new targets for the treatment of colorectal cancer.


This paper describes the solution of Laplace's equation for an asymmetrically excited electrostatic quadrupole comprising four spherical electrodes. The introduction explains the advantages of such a lens and the failure of numerical relaxation techniques to solve its potential distribution. The mathematical techniques employed to arrive at an analytic solution are then developed. A description of the various coordinate systems employed, and the connexions between them, is presented first. This is followed by the solution of Laplace's equation in the various systems by the method of separation of variables. At this stage the geometry of the chosen system is described and a comparison is made with the usual cylindrical polar form near the axis. The process of obtaining the full solution by superposing two bispherical systems is then developed, with details of the method employed to fit the boundary conditions; and finally the transformation of this solution into the standard form is described.


The electrical detection of DNA hybridization still faces the challenge of detecting very low concentrations. In this work we present the possibility of detecting DNA probes by measuring a capacitance change between interdigitated aluminum micro-fingers coated with a thin alumina layer and constructed over an oxidized silicon wafer. DNA Labeling was performed by biotinylated nucleotides and reaction with anti-biotin/gold nanoparticles, increased in size by silver crystal precipitation. The capacitance change ratio observed was at least of two, using 0.2 nM DNA solutions. This detection method appears compatible with microarray technology and paves the way for further use in biological applications.


Many companies rely on the promised benefits of product lines, targeting systems between fully custom made software and mass products. Such customized mass products
account for a large number of applications automatically derived from a product line. This results in the special importance of product lines for companies with a large part of their product portfolio based on their product line. The success of product line development efforts is highly dependent on tailoring the development process. This paper presents an integrative model of influence factors to tailor product line development processes according to different project needs, organizational goals, individual
goals of the developers or constraints of the environment. This model integrates goal models, SPEM models and requirements to tailor development processes.


Abstract There is limited research on second language (L2) vocabulary teaching and learning which provides fine-grained descriptions of how vocabulary explanations (VE) are interactionally managed in beginning-level L2 classrooms where learners have a limited L2 repertoire, and how the VEs could contribute to the learners' conceptual understanding of the meaning(s) of the target vocabulary items (VIs). To address these research gaps, we used a corpus of classroom video data from a beginning-level adult ESOL classroom in the United States and applied Conversation Analysis to examine how the class teacher employs various gestural and linguistic resources to construct L2 VEs. We also conducted a 4-month microgenetic analysis to document qualitative changes in learners' understanding of the meaning of specific L2 VIs which were previously explained by the teacher. Findings revealed that the learners' use of gestures allows for an externalisation of thinking processes providing visible output for inspection by the teacher and peers. These findings can inform educators' understanding about L2 vocabulary development as a gradual process of controlling the right gestural and linguistic resources for appropriate communicative purposes.


Porous graphitised carbon (PGC) based chromatographic separation of glycans achieves high-resolution separation of glycan mixtures released from glycoproteins, including structurally similar isomers. While there is some understanding of glycan separation on PGC, system-independent retention values have not been established. Using hydrolysed dextran as an internal standard, and Skyline software for post-acquisition normalisation, retention time and glycan peak area variation of replicate injections of glycan mixtures was significantly reduced. Normalisation of retention time to the dextran ladder allowed assignment of system-independent retention values, values that are applicable to all PGC-based separations regardless of chromatographic system. We have built a library of over 300 PGC-separated glycan structures with assigned normalised glucose unit (GU) PGC retention values. To further define the mechanism of glycan separation with PGC, we identified predictive models for the chromatographic effects resulting from addition and/or removal of core-fucosylation and bisecting GlcNAc based on the PGC normalised retention time library. A dextran ladder spectral library was also built to ensure correct retention time assignment of the internal standard added to glycan mixtures. Using the spectral matching feature in Skyline, isomeric discrimination between O-mannosylated glycans and the glucose-based dextran ladder was achieved. As a result, system-independent automated assignment of glycan structure based on precursor mass and glucose unit value, using a glycan structure reference library, can be achieved using PGC-LC-MS.


A new method based on multi-objective particle swarm optimization is proposed to deal with the flexible job shop scheduling problems with multiple objectives, minimizing completion time, total machine workload and the biggest machine workload. This algorithm adopts linear weighting method to change multi-objective optimization problem into the single objective optimization problem, and introduces random and uniform design method to produce weight coefficient, which ensures the diversity and uniform distribution of pare to set. Besides, elite reserved strategy and dynamic neighborhood operator are designed to maintain the diversity of population and improve search capabilities of particles. Particle is presented in the form of binary group. In order to solve process scheduling priority issues and machinery distribution, encoding process, consisting of extended operation and priority rule, is designed. Finally, the corresponding computational experiments are reported. The results indicate that the proposed algorithm is an efficient approach for the flexible job shop scheduling problems.


The elongator complex consists of 6 highly conserved subunit proteins and is indispensable for various cellular functions, such as transcription elongation, histone acetylation, and tRNA modification. The elongator complex contains 2 subunits, each of which consists of 3 different proteins (encoded by the ELP1–3 and ELP4–6 genes). According to the OMIM database, ELP2 gene variations have been reported to be associated with autosomal recessive mental retardation type 58. Here, we report a male patient with severe intellectual disability, spastic diplegia, and stereotypic behavior; in addition, we also provide a review of the current literature. Using whole-exome sequencing analysis, we detected a novel compound heterozygous variation in the ELP2 gene. We present this case report to clarify the clinical findings of a very rare neurodevelopmental phenotype and to contribute new information to the current literature on genotype-phenotype correlations.


The finite temperature Casimir free energy is calculated for a dielec-tric ball of radius a embedded in an infinite medium. The condition ǫµ = 1 is assumed for the inside/outside regions. Both the Green function method and the mode summation method are considered, and found to be equivalent. For a dilute medium we find, assuming a simple " square " dispersion relation with an abrupt cutoff at imaginary frequencyˆω = ω0, the high temperature Casimir free energy to be negative and proportional to x0 ≡ ω0a. Also, a physically more realistic dispersion relation involving spatial dispersion is considered, and is shown to lead to comparable results.


The present work deals with the synthesis of Na-A zeolite using 10 Å halloysite (collected near Grosseto, Italy) as the starting material, instead of the more expensive chemicals currently used in industry (Na aluminates and Na silicates). The process of synthesizing Na-A zeolite from 10 Å halloysite is rather simple as the reaction of halloysite with alkali occurs very readily and is achieved without prior thermal activation at high temperature. The optimal conditions of crystallization of Na-A zeolite from 10 Å halloysite are reached at 80°C. At lower temperatures, transformation of halloysite into an amorphous material requires more time, and the field within which Na-A zeolite exists overlaps that of 7 Å halloysite, G and HS zeolites. The products of synthesis at 80°C were characterized by X-ray diffraction, scanning electron microscopy, inductively coupled plasma optical emission spectrometry and infrared spectroscopy. We also propose a model to study the reaction kinetics of zeolite (Na-A and HS) nucleation and growth by real-time X-ray powder diffraction data.


This paper explores the theoretical debates on extraction and development in Amazonia, and the emergence of extractive reserves (ERs) as a tropical development alternative. It reviews the role of women in Amazonian rural economies and then analyzes the (often invisible) tasks of women within the reserves through an analysis of the gender division of labour in the collecting and processing of non-timber forest products and agriculture. It then considers how lack of attention to rural women's labour obligations played out in a development project, Projeto Castanha, that began as an urban factory, but was later recast as a neoliberal decentralized processing and outsourcing programme. The project failed to appreciate the demands on, and the opportunity costs, of women's time and thus had very limited success as women withdrew their labour. The paper argues that there may be many more options for supporting extractive economies (and the women who work in them) in more peri-urban and village projects even though extractive reserves are valuable ecologically and socially in the regional economy.


Similarity search is a fundamental operation for applications that deal with multimedia data. For a query in a multimedia database it is meaningless to look for elements exactly equal to a given one as query. Instead, we need to measure the similarity (or dissimilarity) between the query object and each object of the database. The similarity search problem can be formally defined through the concept of metric space, which provides a formal framework that is independent of the application domain. In a metric database, the objects from a metric space can be stored and similarity queries about them can be efficiently answered. In general, the search efficiency is understood as minimizing the number of distance calculations required to answer them. Therefore, the goal is to preprocess the dataset by building an index, such that queries can be answered with as few distance computations as possible. However, with very large metric databases is not enough to preprocess the dataset by building an index, it is also necessary to speed up the queries by using high performance computing, as GPU. In this work we show an implementation of a pure GPU architecture to build the Pemutation Index, used for approximate similarity search on databases of different data nature. Our proposal is able to solve many queries at the same time.


Contests have a long history of driving innovation, and web-based information technology has opened up new possibilities for managing tournaments. One such possibility is the visibility of entries – some web-based platforms now allow participants to observe others' submissions while the contest is live. Seeing other entries could broaden or limit idea exploration, redirect or anchor searches, or inspire or stifle creativity. Using a unique data set from a series of field experiments, we examine whether entry visibility helps or hurts innovation contest outcomes and (in the process) also address the common problem of how to deal with opt-in participation. Our eight contests resulted in 665 contest entries for which we have 11,380 quality ratings. Based on analysis of this data set and additional observational data, we provide evidence that entry visibility influences the outcome of tournaments via two pathways: (1) changing the likelihood of entry from an agent and (2) shifting the quality characteristics of entries. For the first, we show that entry visibility generates more entries by increasing the number of participants. For the second, we find the effect of entry visibility depends on the setting. Seeing other entries results in more similar submissions early in a contest. For single-entry participants, entry quality "ratchets up" with the best entry previously submitted by other contestants if that entry is visible, while moving in the opposite direction if it's not. However, for participants who submit more than once, those with better prior submissions improve more when they cannot see the work of others. The variance in quality of entries also increases when entries are not visible, usually a desirable property of tournament submissions.


Contact metamorphic marbles, affected by metasomatic fluids at the contact to the Bergell and Adamello Intrusives, contain various accessory minerals (zirconolite, allanite, titanite, rutile, geikielite, hoegbomite), which provide new evidence for the hydrothermal mobility of Ti and Zr. In both examples, Ti and Zr migrated along with U, Th, Y and REE in a metasomatic fluid rich in potassium. The composition of the main minerals (fluorine-rich phlogopite, pargasite and titanian clinohumite) and the abundance of fluor-apatite demonstrate that fluorine and phosphorus were important components of the fluid. The textural relationships indicate that the formation of the accessory phases is linked to the crystallization of the hydrous minerals.


The specification of patterned R8 photoreceptors at the onset of eye development depends on timely inhibition of Atonal (Ato) by the Enhancer of split (E(spl) repressors. Repression of Ato by E(spl)-M8 requires the kinase CK2 and is inhibited by the phosphatase PP2A. The region targeted by CK2 harbors additional conserved Ser residues, raising the prospect of regulation via multi-site phosphorylation. Here we investigate one such motif that meets the consensus for modification by MAPK, a well-known effector of Epidermal Growth Factor Receptor (EGFR) signaling. Our studies reveal an important role for the predicted MAPK site of M8 during R8 birth. Ala/Asp mutations reveal that the CK2 and MAPK sites ensure that M8 repression of Ato and the R8 fate occurs in a timely manner and at a specific stage (stage-2/3) of the morphogenetic furrow (MF). M8 repression of Ato is mitigated by halved EGFR dosage, and this effect requires an intact MAPK site. Accordingly, variants with a phosphomimetic Asp at the MAPK site exhibit earlier (inappropriate) activity against Ato even at stage-1 of the MF, where a positive feedback-loop is necessary to raise Ato levels to a threshold sufficient for the R8 fate. Analysis of deletion variants reveals that both kinase sites (CK2 and MAPK) contribute to 'cis'-inhibition of M8. This key regulation by CK2 and MAPK is bypassed by the E(spl)D mutation encoding the truncated protein M8*, which potently inhibits Ato at stage-1 of R8 birth. We also provide evidence that PP2A likely targets the MAPK site. Thus multi-site phosphorylation controls timely onset of M8 repressor activity in the eye, a regulation that appears to be dispensable in the bristle. The high conservation of the CK2 and MAPK sites in the insect E(spl) proteins M7, M5 and Mγ, and their mammalian homologue HES6, suggest that this mode of regulation may enable E(spl)/HES proteins to orchestrate repression by distinct tissue-specific mechanisms, and is likely to have broader applicability than has been previously recognized.


The purpose of the study is to establish the factors influencing demand of consumer products among supermarket shoppers in Kimilili Municipal Council Bungoma County in Kenya. The study used descriptive survey to collect data. The objective of the study was to assess the influence of product certification on demand of consumer products. To establish the influence of consumer preference on demand of consumer products. To assess the influence of product price on demand of consumer products. The study had the following conclusions; demand of consumer products is greatly influenced by four variables, product certification, brand equity, consumer preference and product price. The target population consisted of 2,733 consumers (supermarket shoppers) in the leading supermarkets of Kimilili Municipal Council which included both males and females. The sample size was 118 respondents'. A questionnaire was constructed and used to collect the data. The received data was arranged, coded and analyzed descriptively. It was facilitated by the use of SPSS (statistical package for social sciences). The sample was described using frequencies, cross tabulation, tables, percentages, correlation and phrases and sentences were used to explain the meaning of the data and to make conclusions. The major findings of the study was that consumers are greatly influenced by four variables in their purchases. That is product certification, brand equity, consumer preference and product price. The study revealed that 57.14% of supermarket shoppers in Kimilili Municipality were females while 42.86% were males. From the findings the following recommendations were suggested:The manufacturers of products such as alcohol drinks, foodstuffs and cosmetics should give attractive names to their goods since names of these goods carry the value of their products. The government should open a department within the Ministry of Trade and Industry to handle consumer complains. Further research on factors influencing consumer preference for certain foods should be done.


Introduction Tobacco use remains a global public health challenge. While studies report that smoking cessation reduces the risk of cancer and other NCDs, evidence is scarce in African region on socio-economic determinants of smoking cessation behavior. This study examined the socio-economic differentials of smoking cessation behavior among smokers in four African countries. Methods The study was conducted through secondary analysis of Global Adult Tobacco Survey (GATS) data from four African countries (Ethiopia, Kenya, Senegal and Tanzania). Smoking cessation behavior was assessed using two variables i) intention to quit smoking in next 12 months and ii) previous quit attempts made within 12 months preceding the survey. The weighted percentages for intention to quit smoking and previous quit attempts were computed. The adjusted odds ratios were computed using multinomial logistic regression to identify the association between socio-economic factors and smoking cessation behavior. Results Across the four countries studied, the previous quit attempts among smokers were in the range of 39.6% to 53.7%. Around 7.6% to 15.8% of the smokers tried to quit with an assistance. In Ethiopia over 76.5% of current smokers reported no intention to quit in next 12 months after survey, whereas the same was 50.4% in Senegal. While country specific differences were observed, females, those belonging to the poorest wealth index, unemployed and those without any formal education reported significantly lower odds of previous quit attempts or having an intention to quit smoking. Conclusion The socio-economic vulnerabilities were found to compromise smoking cessation behavior among the smokers in countries studied. Targeted interventions, adherence to smokefree laws, and provision of cessation support are essential to improve quit rates and mitigate tobacco risks among socio-economically vulnerable population.


Guinea pigs are a commonly used model for tuberculosis vaccine research. Loss of body weight is the most frequently described humane endpoint for animals used in these studies. During a chronic study, we noted labored breathing in some tuberculosis-infected guinea pigs. To develop consistent humane endpoints for these guinea pigs, we performed an observational study using multiple clinical signs. A combination of body weight loss, labored breathing, and activity level during handling estimated the time to euthanasia within approximately 7 d. Histologic severity scores of lesions in the cranial or caudal lung lobe (or both) supported clinical endpoints. This study presents humane endpoints for the refinement of studies using guinea pigs in tuberculosis research.


Shock wave speeds are often measured by comparing arrival times at the tips of electrical shorting pins in a hexagonal array over two elevations (called up and down). In the conventional arrangement, the center pin is solely responsible for measuring the curvature of the wave front. Without this datum the shock speed cannot be precisely determined. In some experiments this pin fails frequently enough to be a problem. We report a simple rearrangement between up and down designated pins which eliminates the critical reliance on a single pin.


After a brief account of an old study on sociopolitical vs formalist styles of literary criticism and the lessons it taught about relating cultural objects to context, I turn to more recent work on talk-in-interaction and engage three themes: (1) That the events of conversation have a sense and import to participants which are at least partially displayed in each successive contribution, and which are thereby put to some degree under interactional control. Accordingly, academic accounts of the import of conversational `texts' can be endogenously grounded, and this is a worthy analytic aspiration; (2) The pursuit of this goal mandates relevant senses of context to be consulted for analysis, and these are senses and aspects of context which are demonstrably relevant to the participants in the event being examined, not necessarily ones relevant to the inquirer doing the analysis; and (3) Its technical grounds and mandate aside, this is a useful contraint on analysis in disciplining work to the indigenous preoccupations of the everyday world being grasped, and serving as a buffer against the potential for academic and theoretical imperialism which imposes intellectuals' preoccupations on a world without respect to their indigenous resonance.


Urbanisation and economic growth leading to life style changes are major factors responsible for food and nutrition transitions, a shift from indigenous traditional food to diversified global foods. The present study was undertaken to explore food transitions across rural-urban gradients of the South Indian mega city of Bengaluru covering a northern and a southern transect. From the geocoded localities 300 middle income households comprising of rural (n=100), transition (n=100) and urban area (n=100) were selected by purposive random sampling technique. Information pertaining to food habits, dietary diversity and food intake was elucidated through standardised questionnaire. The findings revealed, that quite all of urban respondents (99.0 %) had three meals per day, but in rural environment it was only 67%. Interestingly, majority of rural families were non-vegetarians (94.0 %) against transition (82.0%) and urban (85.0 %). Statistically meal pattern and food habits were significant across the rural-urban gradient. Differences in inclusion of high value foods such as fruits, vegetables, processed foods, meat and eggs contributed to slight changes in household dietary diversity score from rural to urban. It was observed that consumption of cereals, oils and fats, and sugars, which are predominant sources of energy, was more than the recommended dietary allowances in all three study areas in both the transects. However, highest intake of cereals was observed in the most rural parts of both transects. Intake of oils, fats and sugars was comparatively higher in urban families. Interestingly, an increasing trend in consumption of milk and milk products was observed from rural to urban gradient, Its adequacy ranged from 57.57% (rural) to 77.92% (urban) in the north transect. However, in the southern transect it ranged from 53.90% to 70.07% among rural and urban, respectively. Consumption of vegetables was higher among all the study areas compared to roots, tubers and green leafy vegetables. Fruit consumption was comparatively higher among females in south transect compared to the north. These transitional changes in food consumption in the rural-urban food system were attributed to availability, accessibility and diversity in food across the rural-urban gradient which may impact on nutritional and health status of families.


We here report a 34-years old male who had nattou-(fermented-soybean) induced late-onset anaphylaxis following SCUBA diving to about 20 m in the ocean off a small remote Japanese island (Kuroshima, Okinawa). He had eaten nattou for breakfast at 7:30 am. He traveled by boat to the dive site, dove twice and then ate lunch at 12:30 on the diving boat (no nattou at lunch). After lunch at 14:30 he dove again (third dive of the day) during which time itchiness started. Back on the diving boat, urticarial was noticed. At 15:30, while washing his diving gear at the diving shop near the harbor, he fainted. A physician arrived on the scene at 15:45. Chest sound was clear and SpO2 was 98%, and blood pressure was 60/- mmHg. Intra-venous hydrocortisone was given, however, his recovery was not satisfactory. Then he was transferred to the Yaeyama Hospital by helicopter at 17:45. The examination of diving computer analysis reveals no sign of increased residual nitrogen, denying the possibility of decompression syndrome. Prick to prick test shows a strongly positive response to nattou. Nattou-induced late-onset anaphylaxis following SCUBA diving was suspected.


Copper is a cofactor in the mitochondrial enzymes cytochrome c oxidase (CcO) and superoxide dismutase. Delivery and insertion of copper to CcO is mediated by a series of metallochaperones localized in the intermembrane space and inner membrane of mitochondria. The soluble protein Cox17 transiently binds copper in the intermembrane space and delivers it to inner membrane-tethered Sco1 and Cox11, which then deliver copper to the appropriate CcO subunits. CcO has two distinct catalytic copper sites, CuA and CuB, assembled by Sco1 and Cox11, respectively. Metallation of mitochondrial superoxide dismutase 1 is dependent on the copper chaperone for Sod1 in the intermembrane space. CcO and Sod1 account for between 10 and 40% of the total copper present in mitochondria depending on the conditions and organism. The remainder of the copper is found in a labile pool within the matrix. Matrix copper is relocalized to the intermembrane space as a source of copper for the aforementioned copper chaperones. Herein, we discuss the current understanding of storage, binding and utilization of copper in mitochondria and address the major unresolved questions concerning the nature of mitochondrial copper.


N-phosphonooxymethyl derivatives of tertiary amine containing drugs have been identified as a novel prodrug approach for improving aqueous solubility. The in vivo reversion of two prodrugs to the corresponding parent compounds following iv and im administration to rats and dogs was investigated. Equimolar doses of parent drugs (loxapine or cinnarizine) and the corresponding prodrugs were each administered via a rapid iv infusion to rats and dogs. Equimolar doses of loxapine and its prodrug were each administered im to rats only. Blood samples were collected over 12 h, and plasma was assayed for both parent drug and intact prodrug by HPLC. Comparison of the plasma AUC for the parent drugs following administration of the parent drugs and prodrugs allowed estimation of the apparent bioavailability of parent drug from prodrug dosing. Plasma levels of the prodrugs fell below the limit of detection 5 min after iv infusion with an approximate half-life of 1 min. The mean AUCs following iv and im dosing of parent drugs were not statistically different from the parent drug AUCs obtained after prodrug dosing. The results are consistent with rapid and quantitative prodrug to parent drug reversion following administration of the phosphonooxymethyl prodrugs to the rats and dogs. This information, together with previous studies on the synthesis and physicochemical evaluation of the prodrugs, suggests that this novel prodrug strategy is a very promising approach for overcoming solubility limitations seen with many tertiary amine containing drugs at physiological pH values.


A kind of self-shielded carbonitride alloying flux-cored wire was developed. Wear resistant coatings was prepared on the surface of the Q235 low-carbon steel by HAVS using the wire. Detection and analysis on the microstructure and properties of the coatings were done by the equipments such as scanning electron microscope, microhardness tester and wear tester. The forming, the wear resistance and its mechanism of the coating were studied. The results show that the coating has good forming property, uniformity of microstructure and compact structure, but the coating also has large oxidate and porosity, this may due to gasforming and slagforming constituents in the wire; the coatings has high hardness, the average microhardness value reachs 510 HV0.1, and the highest value up to about 560 HV0.1; the coatings has good abrasive wear performance and bonding strength.


Abstract We study private shareholder engagements with 2,465 listed firms about environmental, social, and governance (ESG) issues from 2007 to 2020. We examine the extent to which private engagements address financially material ESG issues and contribute to firm performance. We find that material engagements succeed more often than immaterial engagements and that the targets of successful material engagements significantly outperform their peers by 2.5% over the next 14 months. Further, we find that material engagements are more often associated with improvements in profitability and cost ratios than immaterial engagements. Finally, our evidence indicates that a decrease in CO2e emission intensity accompanies environmental engagements.


Following the Warsaw Pact invasion of Czechoslovakia on 21 August 1968, the Soviet bloc entered into a period of strictly limited tolerance to deviations from the Soviet model of socialism. The theory of "socialist international relations" became the theoretical rationalization of the new drive for bloc unity. Since the late 1970s, howeveer, the collapse of economic and political stability in Eastern Europe and the Soviet Union itself undermined the whole consept of chesion in the bloc.

This study examines the evolution of Soviet thinking on Soviet East European relations from 1968 to late 1989, and discusses the role of the "theory" for relations between socialist states. From the early 1980s, the Soviets were forced to adjust their thinking to keep pace with developments in Eastern Europe. DUring 1989 the "theory" finally disappeared as a Soviet foreign policy instrument.


As evinced by the dumping phenomenon caused by the rapid economic growth of developing countries, many markets in advanced economies have rapidly declined. In such declining markets, however, the price of domestic products has been increasing instead of decreasing. To understand price increases in a declining market due to the rush in imports of new products, this paper empirically investigates changes in product quality using POS data on PC monitors sold at major mass retailers in Japan (January 2009--December 2011). The paper utilizes the hedonic approach to estimate the impact of product features on price. As a result of calculating the Quality Index developed by Feenstra (1988) with the estimates, this paper demonstrates that the quality of Japanese PC monitors increased by 6.6% in 2010 (compared to the previous year) and 8.5% in 2011. The result shows that the price increase in a declining market can be explained by increasing product quality.


In this paper, we consider the link and network layer performance aspects of a WCDMA/UTRA system with high speed downlink packet access. The study considers packet scheduling and the tradeoff among user fairness and cell throughput. We show performance numbers for different network setups and study the applicability of proportional scheduling methods. Even with conservative system and traffic settings, the best effort methods produce high user data rates and cell throughput.


An experiment was carried out which enabled a separate assessment to be made of the influence of, firstly, pre-emergence growth rate, and secondly, the competitive environment at emergence on the subsequent growth of individual plants of subterranean clover. Swards of the Bacchus Marsh variety were grown in large seed boxes at the Waite Agricultural Research Institute, Adelaide. Four different sowing treatments were applied whereby the sowing of alternate plants in a checkerboard grid was delayed by 0, 2, 4, and 8 days. Emergence date and final dry weight were recorded individually for each plant in the experimental swards. There was considerable overlap in emergence times between the earlier and the later-sown plants. Consequently by a comparison of the separate regressions for earlier and later-sown plants of yield per plant on day of emergence for each treatment, it could be demonstrated that plants with very different pre-emergence growth rates but emerging on the same day in the same sward, and hence into the same competitive environment, gave essentially the same subsequent growth. In other words, in the absence of differential competitive effects, there was no detectable influence of pre-emergence growth rate on subsequent growth. On the other hand, the final dry weights of individual plants were very strongly related to day of emergence. A delay in emergence of 5 days brought about a reduction in final yield of about 50%, and a delay of 8 or 9 days of at least 75%. In view of the negligible influence of pre-emergence growth rate, per se, this reduction is attributable solely to the increased severity of competition from plants already emerged. In spite of the wide variation in emergence patterns, the total yields of all swards were very similar, indicating an almost complete compensation between plants in the utilization of available growth factors.


This paper combines matching frictions with e¢ ciency wages to deter shirking in a model that is estimated for the USA and the UK to derive the underlying structural parameters. Methods robust to weak instruments are used to show that, for both countries, both matching frictions and e¢ ciency wages play a signi…cant role in enabling the model to …t the data even with non-prescriptive formulations for wage determination. The results indicate that adding an e¢ ciency wage element to matching frictions may be a better way to …t the data than simply searching for an alternative wage formulation. Keywords: Matching frictions, e¢ ciency wages, unemployment, shirking, robust inference JEL classi…cation: E2, J3, J6


Managing God's Higher Learning: U.S.-China Cultural Encounter and Canton Christian College (Lingnan University), 1888-1952, by Dong Wang. Lanham: Lexington Books, 2007. xiv + 210 pp. US$85.00 (hardcover), US$34.95 (paperback). Before 1952 there were eighteen Christian colleges and universities in China, only three of which were run by the Catholic Church. These then ceased to exist as separate institutions and were forced to amalgamate with other universities and colleges, or simply had their names and their administrative structures changed. In the case of Lingnan University, over sixty years of educational endeavor was brought to a close when it merged with Sun Yat-sen (Zhongshan) University in Guangzhou. In December 1987, however, the Chinese Ministry of Education approved the establishment of Lingnan College as an identifiably separate part of Zhongshan University, thereby revivifying the dreams of the Chinese and Western educators who had established Lingnan a century earlier. The earliest historical studies about these types of institutions were marked by two different types of tone, that of hagiography or of hostility. The educators, be they Christian missionaries, priests, sisters or their lay colleagues (Chinese and otherwise), were either enlightened heroes or imperialist villains. Wang Dong cites the forthcoming work of Daniel H. Bays and Ellen Widmer (China's Christian Colleges: Transpacific Connections, 1900-1950) which argues that historical studies on Christian educational institutions in China can be divided into three different kinds. The first two kinds of works, from the earliest publications in the years after the closure of these institutions to the end of the 1970s, were either celebratory valedictions or testaments to confrontation and failure (especially as regards the conversion of China to Christianity). A new type of scholarship about these universities and colleges has only come into being in recent times, according to Bays and Widmer. More often than not, these newer works have been produced by scholars affiliated with the Center for Historical Research on the History of the China Christian Colleges (Zhongguo jiaohuishi daxue yanjiu zhongxin) at the Central China Normal University (Huazhong shifan daxue) in Wuhan and the Centre for the Study of Religion and Chinese Society of Chung Chi College at the Chinese University of Hong Kong. Wang Dong's volume about Lingnan is a welcome and worthy addition to this more recent and less partisan body of scholarship. Her work is based on extensive research in libraries and archives on both sides of the Pacific Ocean, utilizing Chinese and English language sources, and includes interviews with graduates from the original Lingnan. The monograph is organized thematically. First, Wang Dong examines Lingnan's geographical setting and the influence that its south China location had on its development. Next, she examines the "cultural migration" that took place at Lingnan; that is, the way in which this college functioned as both a foreign and a local institution. The financial management and governance of the university, an often understudied area, is discussed in Chapter 3. …


Classic Big Push industrialization envisions state planners coordinating economic activity to internalize a range of externalities that otherwise lock in a low-income equilibrium, but runs afoul of well-known government failure problems. Successful Big Push coordination may occur instead when a large business group, acting in its controlling shareholder's self-interest, coordinates the establishment and expansion of businesses in diverse sectors. Where business groups play this role, many basic axioms of Anglo-American corporate governance, including the advocacy of shareholder value maximization and contestable corporate control, must be qualified.


ABSTRACT Background The onset of menopause increases the risk of metabolic syndrome (MetS). Adiponectin is an adipokine associated with insulin sensitivity that is lower in people with MetS. Supplementing diets with linoleic acid (LA)-rich oil increased adiponectin concentrations and improved glucose control in women with type 2 diabetes. The effect of LA on adipokines, especially total and the bioactive form of adiponectin, high-molecular-weight (HMW) adiponectin, in women with MetS is unknown. Objectives The aim of this study was to explore the effect of supplementation of the diet with an oil rich in LA on adipokines in women with MetS. The effect of the LA-rich oil (LA-oil) on oxylipins, key metabolites that may influence inflammation and metabolism, was also explored. Methods In this open-label single-arm pilot study, 18 postmenopausal nondiabetic women with MetS enrolled in a 2-phase study were instructed to consume LA-rich vegetable oil (10 mL/d) as part of their habitual diets. Women consumed an oleic acid–rich oil (OA-oil) for 4 wk followed by an LA-oil for 16 wk. Fasting concentrations of adipokines, fatty acids, oxylipins, and markers of glycemia and inflammation were measured. Results After 4 wk of OA-oil consumption, fasting glucose and total adiponectin concentrations decreased whereas fasting C-reactive protein increased. After 16 wk of LA-oil supplementation total and HMW adiponectin and plasma oxylipins increased. Markers of inflammation and glycemia were unchanged after LA-oil consumption. Conclusions Supplementation with LA-oil increased total and HMW adiponectin concentrations and altered plasma oxylipin profiles. Larger studies are needed to elucidate the links between these changes and MetS. This trial was registered at clinicaltrials.gov as NCT02063165.


Because Irish myth and folklore had been suppressed by church doctrine and British control of school system, W.B.Yeats used his poetry as a tool for re-educating the Irish population about their heritage and as a strategy for developing Irish nationalism. Thus the participation of Yeats in the Irish political system had its origins in his interest in Irish myth and folklore. Yeats retold entire folktales in epic poems and plays and used fragments of stories in shorter poems. Moreover, he presented poems which deal with subjects, images, and themes called from folklore. Most important, Yeats infused his poetry with a rich sense of Irish culture. Even poems that do not deal explicitly with subjects from myth retain powerful tinges of indigenous Irish culture. Yeats often borrowed word selection, verse form, and patterns of imagery directly from traditional Irish myth and folklore.


In this work, we report molecular layer deposition (MLD) of ultrathin poly(ethylene terephthalate) (PET) films on gram-scale batches of ultrafine particles for the first time. TiO2 P25 nanoparticles (NPs) are coated up to 50 cycles in an atmospheric-pressure fluidized bed reactor at 150 °C using terephthaloyl chloride and ethylene glycol as precursors. Ex-situ diffuse reflectance infrared Fourier transform spectroscopy, thermogravimetric analysis and transmission electron microscopy show the linear growth at 0.05 nm/cycle of uniform and conformal PET films, which are unattainable with conventional wet-phase approaches. The subnano and nano PET films not only suppress the photocatalytic activity of TiO2 NPs by reducing the generation of hydroxyl radicals, but also improve the dispersibility of TiO2 NPs in both organic and aqueous media. Still, the bulk optical properties, electronic structure and surface area of TiO2 are essentially unaffected by the MLD process. This study demonstrates the industrial relevance of MLD to simultaneously tune the photoactivity and dispersibility of the commercial photocatalyst TiO2 P25. Moreover, by rapidly modifying the surface properties of particles in a controlled manner at the subnanometer scale, particle MLD can serve many applications ranging from nanofluids to emulsions to polymer nanocomposites.


The objective was to evaluate whether norepinephrine (NE) and other hormonal factors have direct effects on protein degradation in brown fat cells. NE inhibited proteolysis by 35-45% in mouse brown adipocytes differentiated in culture. Insulin also inhibited protein degradation but significantly less than NE, whereas glucagon and leptin had no effect. The inhibitory effect of NE was partially antagonized by propranolol but not by prazosin, and dose-response curves with BRL-37344 (a beta(3)-agonist), isoproterenol (a beta(1)/beta(2)-agonist) and dobutamide (a beta(1)-agonist) were consistent with the involvement of a beta(3)-adrenergic receptor. Furthermore, forskolin mimicked the effects of NE, whereas additions of A-23187 or phorbol esters had no effect, alone or in combination with NE or forskolin. Thus inhibition of proteolysis by NE likely involves a beta(3)-adrenergic receptor-mediated increase in cAMP. In contrast, NE, BRL-37344, and dobutamide had no effect on proteolysis in preadipocytes. Inhibition of proteolysis by NE was due at least in part to inhibition of autophagy. Thus inhibition of proteolysis by NE and insulin in mature brown adipocytes is likely an important process contributing to brown fat growth and atrophy under many physiological or pathological conditions.


Erwinia chrysanthemi mutants, containing transcriptional fusions of one of the minor pectate lyase genes (pelI, pelL, pelZ) with the reporter gene encoding β-glucuronidase activity, were studied for their ability to cause disease symptoms and to synthesize pectinases after inoculation of potato tubers. The strains affected in pelI and pelL genes displayed reduced virulence on potato tubers, demonstrating the important role of these isoenzymes in soft rot disease. Inactivation of the pelZ gene slightly influences the ability to macerate. Analysis of the bacterial population showed rapid multiplication of bacteria during infection. Similar kinetics of growth were observed for all mutants and for the wild-type strain. Comparison of the mutants and the wild-type strain showed that the pelI, pelL, and pelZ mutants synthesized reduced levels of Pels. The expression of pelZ is fivefold higher in planta than in bacterial cultures. In contrast, both pelI and pelL are highly (10-fold factor) induced in planta, whic...


When Professor Joe Lee wrote his magisterial history of twentieth century Ireland in the late 1980s one of the most important issues he addressed was the apparent economic failure of the Republic of Ireland. The main reasons advanced for this failure included slow and erratic patterns of economic growth, low productivity in key economic sectors, high and persistent levels of unemployment, exceptionally high emigration rates and a preponderance of enduring social problems. That this remained the case after more than a decade of EU membership seemed to call into question the wisdom of the Irish decision in 1973 to join the then European Community (EEC). Two decades later Ireland's membership of the EU was thrown into serious question by the Irish electorate's rejection in June 2008 of the Lisbon Treaty. This was the third such referendum on Europe held in Ireland since the millennium and the second referendum in three to result in a rejection of an EU Treaty following the failed Nice poll in 2001 (O'Brennan, 2003, 2004). The debate on the Lisbon Treaty offers the opportunity to look back at and reflect on Ireland's membership of the EU, to examine whether and to what extent membership has been good for Ireland, and the fundamental changes which European integration has wrought. And although the No to Lisbon was reversed in a second referendum held in October 2009, it remains the case that European integration is now seriously questioned in Ireland. This chapter examines the Irish experience of European integration. It assesses the impact of the EU on key aspects of Irish economic and political life and the different modes of adaptation and contestation which have characterised the Irish experience of membership.


Abstract Forested depressional wetlands are an important seasonal wetland type across eastern and central North America. Macroinvertebrates are crucial ecosystem components of most forested depressional wetlands, but community compositions can vary widely across the region. We evaluated variation in macroinvertebrate faunas across eastern and central North America using 5 published taxa lists from forested depressional wetlands in Michigan, Ontario, Wisconsin, Florida, and Georgia. We supplemented those data with quantitative community descriptions generated from 17 forested depressional wetlands in South Carolina and 74 of these wetlands in Minnesota. Cluster analysis of presence/absence data from these 7 locations indicated that distinct macroinvertebrate communities existed in northern and southern areas. Taxa characteristic of northern forested depressional wetlands included Sphaeriidae, Lumbriculidae, Lymnaeidae, Physidae, Limnephilidae, Chirocephalidae, and Hirudinea (Glossophoniidae and/or Erpodbellidae) and taxa characteristic of southern sites included Asellidae, Crangonyctidae, Noteridae, and Cambaridae. Quantitative sampling in South Carolina and Minnesota indicated that regionally characteristic taxa included some of the most abundant organisms, with Sphaeriidae being the 2nd most abundant macroinvertebrate in Minnesota wetlands and Asellidae being the 2nd most abundant macroinvertebrate in South Carolina wetlands. Mollusks, in general, were restricted to forested depressional wetlands of northern latitudes, a pattern that may reflect a lack of Ca needed for shell formation in acidic southern sites. Differences in community composition probably translate into region-specific differences in the ecological functions performed by macroinvertebrates in forested depressional wetlands.


A Publication of the Association for Iron & Steel Technology Ironand steelmaking processes present a largely untapped opportunity to transform some of the world's most problematic waste streams into raw materials for production. This opportunity lies in their high-temperature environments, which offer sustainable pathways for utilizing chemical reactions to repurpose waste materials as resources, such as reducing iron oxide to iron and dissolving the carbon in waste materials into metal. Hightemperature environments can be leveraged to revolutionize the role steelmakers play in globally significant, large-scale recycling, without making fundamental changes to manufacturing processes. This presentation describes the broad opportunities available to ironand steelmakers to utilize waste streams — ranging from polymeric materials to agricultural wastes — as raw materials. The potential to implement such novel recycling solutions are not generally available to many other materials industries because they operate at relatively lower temperatures, which may not be suitable for triggering useful chemical transformations. Recycling waste polymeric materials in steelmaking is one solution for end-of-life products, which currently impose a serious burden on overstretched landfills, as is the case with some plastics. Specifically, this lecture presents fundamental understanding of different plastic wastes — melamine, high-density polyethylene, polycarbonate and Bakelite, as well as agricultural waste and tires — and their transformations and chemical reactions at high temperatures. Plant results from EAF steelmaking in Sydney, Australia, where recycling waste is now standard practice, will also be included.


Systems which combine fast and slow motions lead to complicated two scale equations and the averaging principle suggests to approximate the slow motion by averaging in fast variables. When the fast motion does not depend on the slow one this approximation usually works for all or almost all initial conditions but when the slow and fast motions depend on each other (fully coupled), as is usually the case, the averaging prescription cannot always be applied, and when it is valid then only in the sense of convergence in measure (or in average) with respect to initial conditions. A nonconvergence example for fixed initial conditions constructed for small perturbations of integrable Hamiltonian fast motions is due to Neishtadt and it is based on the well known phenomenon of resonances there. We construct nonconvergence examples in the discrete time averaging setup in a completely different situation where fast motions are expanding maps and Markov chains. In this case large deviations results provide an exponentially fast convergence in measure on initial conditions while for almost all fixed initial conditions there is no convergence at all. The proof for Neishtad's example requires only elementary ordinary differential equations tools but even for simplest expanding maps of the circle the proof of non convergence is not trivial and it relies on thermodynamic formalism and large deviations results. It seems that this situation is typical for chaotic fast motions but how to extend the proof to even a bit more general situation is not clear yet. The work is joint with Victor Bakhtin.


BACKGROUND The review of outside biopsy slides before performing surgery is the standard of care in many surgical specialties. Previous studies have shown high discrepancy rates between the original and second‐opinion diagnoses. The frequency with which this practice changes the diagnosis and management of patients undergoing Mohs surgery is undocumented in the literature. It is standard practice at our institution to review all outside biopsy slides before Mohs surgery. OBJECTIVE To investigate how often review of outside biopsies by an internal dermatopathologist changes patients' initial referral diagnosis and subsequent management. METHODS & MATERIALS This is a retrospective review of all patients referred to Mohs surgery from January 2003 through March 2007. The number of cases in which the diagnosis changed and how this change affected management were recorded. RESULTS Seventy‐four of 3,345 (2.2%) cases were identified in which the diagnosis changed after review of the biopsy slides. Management was affected in the majority (61%) of cases. Board‐certified dermatopathologists originally read nearly half of the biopsies. CONCLUSION Review of outside biopsy slides before surgery can change the diagnosis in a large proportion of patients, with a resulting change in management. This quality‐assurance practice may improve patient care. The authors have indicated no significant interest with commercial supporters.


Celiac Disease (CD) is an immune-mediated systemic disease, caused by gluten and related prolamins, in genetically susceptible individuals. It is characterized by gluten-dependent clinical manifestations, CD-specific antibodies, HLA DQ2 or DQ8 haplotypes, and enteropathy. Most patients are asymptomatic or with mild manifestations. It mainly affects the gastrointestinal system causing symptoms and signs such as diarrhea, recurrent abdominal pain and abdominal distension; also extradigestive manifestations. Patients with CD may have oral manifestations that include recurrent aphthous stomatitis (RAS), enamel hypoplasia, atrophic glossitis, among others. The diagnosis of CD is based on clinical history, serology, endoscopy and histology. There are other entities that should be differentiated from CD, such as non-celiac gluten sensitivity and wheat allergy. The aim of this study is to present three patients with a history of RAS and other clinical manifestations associated with the early diagnosis of CD and food allergy.


Context: Engineering education historically has been shaped by professional accreditation and internal university imperatives. The recent strengthening of the Australian Qualifications Framework (AQF) adds a new layer of thinking and has required many universities to re-examine how embedded honours degrees are awarded and the degree to which undergraduate programs reflect the level 8 requirements. The AQF is necessarily broad as it applies to all disciplines and fields of education. What is needed is a way of contextualising AQF requirements for engineering education and a means for understanding how these are similar to, or differ from, Engineers Australia's Stage One Competencies. This paper represents a work in progress that is designed to ignite thinking about AQF8 implications - particularly those around research in the final year engineering project. Purpose: An Office for Learning and Teaching (OLT) project set out to map practices in relation to final year engineering projects and to consider the implications for compliance with AQF8 outcomes. One aspect of the study looked specifically at how AQF8 outcomes are understood by coordinators and the team came to examine the nature and role of research in final year projects. From here, the team sought to generate a contextualised definition for AQF8 outcomes as they might apply to engineering education. Although there are other points of differentiation between AQF7 and AQF8, the team sought, in particular, to develop a broadly accepted definition for research. Approach: This paper reports on one part of the larger project. The wider project methodology was largely qualitative, adopting a case study approach. Data was gathered from 16 universities across Australia (from all states and territories) and included university documentation such as subject outlines, rubrics and student guidelines. Additionally, interviews were conducted with coordinators of final year project courses. It was within these interviews that participants were asked specifically about AQF8 outcomes. Additional data was gathered from participants during a conference workshop designed to explore understanding of AQF8 outcomes. The notion of a contextualised definition of research is derived from this data together in collaboration with Engineers Australia. Results: The data revealed that universities are at different stages of AQF compliance. Further, there is mixed understanding in relation to AQF8 with degrees of uncertainty about some terms used in the document, particularly around what comprises research. There is some sense that some engineering programs are already meeting the higher order requirements of AQF8 outcomes and that compliance is merely procedural. Beyond this, however, is the revelation that there is a great deal of contention around research and autonomy as defined by AQF. It was in this context that the OLT team sought to develop a definition of research as applied to the final year or capstone project. The definition delineates specific engineering knowledge, skills and application as would be seen in the final year project. Conclusions: This paper proposes a nationally supported definition of what research means within the undergraduate engineering education context and in doing so assists linking AQF8 directly to final year projects specifically, but to embedded honours programs more generally.


Entrepreneurs and their upstart companies are challenging the health care industry's high costs, frequent lack of transparency, and outdated processes. These innovators are responding to opportunities created by artificial intelligence, internet-based technologies, and regulatory pressure to provide value-based, outcome-driven care on an individual level. But entrepreneurs must find incumbent partners to navigate the risks and uncertainties inherent in health care and to understand its complex processes, regulatory approvals, and patient sensitivities.
For their part, many payers and commercial vendors recognize that the status quo is unsustainable. The United States is experiencing stagnating patient outcomes despite oversize increases in costs. In response, the Center for Medicaid and Medicare Services (CMS) and Congress have championed new reimbursement plans that increase efficiencies and outcomes.
Tackling health care's recurring problems and scaling these new models require entrepreneurship and fresh thinking, but many incumbents will attempt to control the transition to health care's future. They will fail in this misguided effort. Those that adapt to a changing environment - by listening to entrepreneurs, responding to the demands of consumers, and urgently scaling new experiments - will thrive.


Plate cylinder is the core component of the offset printing unit to complete the image transfer. The plate cylinder's deformation will occur under pressure, resulting in the image's deformation on the plate and the low printing quality. In this article, the three-dimensional digital model of plate, packing and cylinder are established by using solidworks software, they are assembled as a whole, the whole is imported into ANSYS finite element analysis software. The shaft of both sides of the cylinder are fixed, and the contact relations between plate, packing and cylinder body are defined, the pressure are load on the area with 5mm width on the surface of the plate cylinder. After solving, the flexural deformation of plate, packing and cylinder are obtained, through analyzing the axial and radial deformation of the plate, the graphic's elongation which transferred from plate to blanket are received, consequently, an important basis of researching the image expansion will be provided.


For various research questions in metabolism, it is highly desirable to have means available, with which the flux through specific pathways can be perturbed dynamically, in a reversible manner, and at a timescale that is consistent with the fast turnover rates of metabolism. Optogenetics, in principle, offers such possibility. Here, we developed an initial version of a photo-switchable isocitrate dehydrogenase (IDH) aimed at controlling the metabolic flux through the citric acid cycle in budding yeast. By inserting a protein-based light switch (LOV2) into computationally identified active/regulatory-coupled sites of IDH and by using in vivo screening in Saccharomyces cerevisiae, we obtained a number of IDH enzymes whose activity can be switched by light. Subsequent in-vivo characterization and optimization resulted in an initial version of photo-switchable (PS) IDH. While further improvements of the enzyme are necessary, our study demonstrates the efficacy of the overall approach from computational design, via in vivo screening and characterization. It also represents one of the first few examples, where optogenetics were used to control the activity of a metabolic enzyme.


Since 1998, large investment banks have become active as issuers of options, generally referred to as call warrants or bank-issued options. This has led to an interesting situation in the Netherlands, where simultaneously call warrants are traded on the stock exchange, and long-term call options are traded on the options exchange. Both entitle their holders to buy shares of common stock. We start with a direct comparison between call warrants and call options, written on the same stock and with the same exercise price, but where the call option has a longer time to maturity. In 13 out of 16 cases we find that the call warrants are priced higher, which is a clear violation of basic option pricing rules. In the second part of the analysis we use option pricing models to compare the pricing of call warrants and call options. If implied standard deviations from options are used to price the call warrants, we find that the call warrants are strongly overpriced during the first five trading days. The average overpricing is between 25 and 30%. Only a small part of the overpricing can be explained by rational arguments such as transaction costs. We suggest that the overvaluation can be explained by a combination of an active financial marketing by the banks and the framing effect.