Star formation involves the flow of gas and dust within molecular clouds into protostars and young stellar objects (YSOs) due to gravity. Along the way, these flows are shaped significantly by many other mechanisms, including pressure, turbulent motions, magnetic fields, stellar feedback, jets, and angular momentum. How all these mechanisms interact nonlinearly with each other on various length scales leads to the formation and evolution of substructures within clouds, including filaments, clumps, cores, disks, outflows, the protostars/YSOs themselves, and planets. In this white paper, prepared for the 2020 Long Range Plan panel which will recommend Canada's future directions for astronomy, we describe the observational and theoretical leadership in the star formation field that Canada's vibrant community has demonstrated over the past decade. Drawing from this extensive background, we identify five key questions that must be addressed for further progress to be made in understanding star formation in the next decade. Addressing these questions will improve our understanding of the dynamics of the dense gas and the role of the magnetic field in star formation, the optical properties of the dust used to trace mass and magnetic fields, the sources of variability in star-forming objects on short timescales, and the physical processes that specifically promote the clustering of stars. We further highlight key facilities in which Canada should become involved to continue making progress in this field. Single-dish facilities we recommend include LSST, trans-atmospheric far-infrared telescopes like BLAST-TNG and SPICA, and ground-based telescopes like JCMT, GBT, and CCAT-p. Interferometric facilities we recommend include ALMA, ngVLA, and SKA1.


Primary ciliary dyskinesia (PCD) is a rare heterogenic genetic disorder associated with perturbed biogenesis or function of motile cilia. Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage. Current approaches to treat PCD are symptomatic, only, indicating an urgent need for curative therapeutic options. Here, we developed an in vitro model for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures. Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient specific hiPSC lines carrying mutations in DNAH5 and NME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level.


Abstract. A snowpack has a profound effect on the hydrology and surface energy
conditions of an area through its effects on surface albedo and roughness and
its insulating properties. The modeling of a snowpack, soil water dynamics,
and the coupling of the snowpack and underlying soil layer has been widely
reported. However, the coupled liquid–vapor–air flow mechanisms considering
the snowpack effect have not been investigated in detail. In this study, we
incorporated the snowpack effect (Utah energy balance snowpack model, UEB) into a
common modeling framework (Simultaneous Transfer of Energy, Mass, and
Momentum in Unsaturated Soils with Freeze-Thaw, STEMMUS-FT), i.e.,
STEMMUS-UEB. It considers soil water and energy transfer physics with three
complexity levels (basic coupled, advanced coupled water and
heat transfer, and finally explicit consideration of airflow, termed
BCD, ACD, and ACD-air, respectively). We then utilized in situ observations
and numerical experiments to investigate the effect of snowpack on soil
moisture and heat transfer with the abovementioned model complexities.
Results indicated that the proposed model with snowpack can reproduce the
abrupt increase of surface albedo after precipitation events while this was
not the case for the model without snowpack. The BCD model tended to
overestimate the land surface latent heat flux (LE). Such overestimations
were largely reduced by ACD and ACD-air models. Compared with the
simulations considering snowpack, there is less LE from no-snow simulations
due to the neglect of snow sublimation. The enhancement of LE was found
after winter precipitation events, which is sourced from the surface ice
sublimation, snow sublimation, and increased surface soil moisture. The
relative role of the mentioned three sources depends on the timing and
magnitude of precipitation and the pre-precipitation soil hydrothermal
regimes. The simple BCD model cannot provide a realistic partition of mass
transfer flux. The ACD model, with its physical consideration of vapor flow,
thermal effect on water flow, and snowpack, can identify the relative
contributions of different components (e.g., thermal or isothermal liquid
and vapor flow) to the total mass transfer fluxes. With the ACD-air model,
the relative contribution of each component (mainly the isothermal liquid
and vapor flows) to the mass transfer was significantly altered during the
soil thawing period. It was found that the snowpack affects not only the
soil surface moisture conditions (surface ice and soil water content in the
liquid phase) and energy-related states (albedo, LE) but also the transfer
patterns of subsurface soil liquid and vapor flow.


Drawing on the writings of Joseph Schumpeter, we develop a theory of international conflict that challenges proponents of the liberal peace research programs. We outline a simple mechanism whereby industrialization fosters peaces, suggesting that industrialized states are more peaceful because they can gain more by investing at home than by pursuing foreign military conquest. We borrow from Schumpeter to argue that our mechanism is distinct from traditional measures of liberalism. Empirically, we propose a measure of industrial development, based on the size of a state's industrial GDP. Using World Bank sector-specific economic data, our analysis shows that a large industrial GDP significantly reduces the likelihood that a state will be involved in a fatal military conflict. We show that this result is robust across a number of model specifications, holds at both the monadic and dyadic levels, and suggests a larger substantive effect than either democracy or capitalism.


In order to improve risk characterization and remediation measures for soil and groundwater contamination, there is a need to improve in situ vadose zone characterization. However, most available technologies have been developed in the context of agricultural soils. Such methodologies are not applicable at industrial sites, where soils and contamination differ in origin and composition. In addition, most technologies are applicable only in the first meters of soils, leaving deeper vadose zones with lack of information, in particular on field scale heterogeneity. In order to overcome such difficulties, a vadose zone experiment has been setup at a former industrial site in Belgium. Industrial activities carried out on site left a legacy of soil and groundwater contamination in BTEX, PAH, cyanide and heavy metals. The experiment comprises the combination of two techniques: the Vadose Zone Monitoring System (VMS) and cross-hole geophysics. The VMS allows continuous measurements of water content and temperature at different depths of the vadose zone. In addition, it provides the possibility of pore water sampling at different depths. The system is formed by a flexible sleeve containing monitoring units along its depth which is installed in a slanted borehole. The flexible sleeve contains three types of monitoring units in the vadose zone: Time Domain Transmissometry (TDT), which allows water content measurements; Vadose Sampling Ports (VSP), used for collecting water samples coming from the matrix; the Fracture Samplers (FS), which are used for retrieving water samples from the fractures. Cross-hole geophysics techniques consist in the injection of an electrical current using electrodes installed in vertical boreholes. From measured potential differences, detailed spatial patterns about electrical properties of the subsurface can be inferred. Such spatial patterns are related with subsurface heterogeneities, water content and solute concentrations. Two VMS were installed in two slanted boreholes on site, together with four vertical boreholes containing electrodes for geophysical measurements. Currently the site is being monitored under natural recharge conditions. Initial results show the reaction of the vadose zone to rainfall events, as well as chemical evolution of soil water with depth.


This Paper reports a new test of capital structure theories. It uses a filtering technique to identify large investment spikes. We find that the spikes are predominantly financed with debt by large firms and by new equity by small loss-making firms. In the process, firms move significantly away from their previous capital structures but then revert back to them by making frequent issues of small amounts of equity. Neither the pecking order nor the trade-off theories on their own provide satisfactory descriptions of these dynamic features of corporate financing.


Slow pasture growth rates during winter limit the potential gross margins from autumn and early winter lambing in southern New South Wales (NSW) by limiting stocking rates and/or increasing supplementary feed requirements. Dual-purpose crops can reduce the winter feed gap in mixed-farming systems by increasing the available feed in winter. The simulation software AusFarm was used to model a mixed-farming system at Wagga Wagga with Merino ewes joined to terminal sires and grazing lucerne-subterranean clover pasture over a 41-year period. A paddock of dual-purpose wheat was then added to the system, and ewes were allowed to graze the wheat crop when feed on offer reached 850 kg DM/ha and before GS31. Weaned lambs were sold after late August if lamb growth rates fell below 20 g/head.day, mean lamb weight reached 45 kg or production feeding of lambs was required. Lambing in June resulted in the highest median gross margin whether or not ewes were able to graze the wheat crop during winter. Grazing of a dual-purpose wheat crop resulted in greater proportional increases in gross margins as stocking rate was increased, increased lamb production and reduced supplementary feeding costs, and reduced interannual variability in gross margin returns.


Background. Measurement of treatment outcomes is critical for the spectrum of voice treatments (ie, surgical, behavioral, or pharmacological). Outcome measures typically include visual (eg, stroboscopic data), auditory (eg, Consensus Auditory-Perceptual Evaluation of Voice; Grade, Roughness, Breathiness, Asthenia, Strain), and objective correlates of vocal fold vibratory characteristics, such as acoustic signals (eg, harmonics-to-noise ratio, cepstral peak prominence) or patient self-reported questionnaires (eg, Voice Handicap Index, Voice-Related Quality of Life). Subjective measures often show high variability, whereas most acoustic measures of voice are only valid for signals where some degree of periodicity can be assumed. However, this assumption is often invalid for dysphonic voices where signal periodicity is suspect. Furthermore, many of these measures are not useful in isolation for diagnostic purposes. Objective. We evaluated a recently developed algorithm (Auditory Sawtooth Waveform Inspired Pitch Estimator— Prime [Auditory-SWIPE′]) for estimating pitch and pitch strength for dysphonic voices. Whereas fundamental frequency is a physical attribute of a signal, pitch is its psychophysical correlate. As such, the perception of pitch can extend to most signals irrespective of their periodicity. Methods. Post hoc analyses were conducted for three groups of patients evaluated and treated for voice problems at a major voice center: (1) muscle tension dysphonia/functional dysphonia, (2) vocal fold mass(es), and (3) presbyphonia. All patients were recorded before and after surgical/behavioral treatment for voice disorders. Pitch and pitch strength for each speaker were computed with the Auditory-SWIPE′ algorithm. Results. Comparison of preand posttreatment data provides support for pitch strength as a measure of treatment outcomes for dysphonic voices.


In modern obstetrics, the frequency of abdominal accouchement is constantly increasing. Therefore, the problem of restoring the state of health of women after surgical delivery requires the introduction of new medical knowledge and technologies into practical rehabilitation, in particular, methods of physical therapy. The purpose of the study was to determine the influence of the developed program of physical therapy on the dynamics of the parameters of the motor ability of women in the postpartum period after cesarean section. Materials and methods. 112 women were examined after childbirth. The comparison group consisted of 47 women who had a natural childbirth. The main group 1 consisted of 32 women who did not want to carry out the proposed program of physical therapy; they were provided with general recommendations for self-observation in the postpartum period after cesarean section. The main group 2 consisted of 33 women after cesarean section who underwent postpartum physical therapy for 12 months (kinesitherapy (therapeutic exercises, functional training to improve motor skills and abilities), abdominal wall bandage, kinesiotaping, abdominal and general massage, wellness nutrition, psychological relaxation, education of women). Determination of motor ability according to the Functional Movement Screen was performed in the late postpartum period (6-8 weeks), 6 and 12 months after childbirth. Results and discussion. In women in the late postpartum period, regardless of the type of delivery, signs of impaired motor ability are revealed, which was established by the results of the Functional Movement Screen test exercises. Within a year after childbirth, there is a gradual improvement in the motor ability of women, regardless of the type of delivery and their performance of active restorative interventions. The use of a physical therapy program starting from the early postpartum period in women after cesarean section revealed advantages regarding the state of their motor ability in relation to women who underwent natural delivery and those who recovered from cesarean section on their own, according to separate Functional Movement Screen tests already at the end of the late postpartum period. After 1 year after childbirth, women who underwent cesarean section and performed the developed physiotherapy intervention on all Functional Movement Screen tests demonstrated a statistically significantly better result compared to women who underwent natural delivery and those who recovered from cesarean section on their own. Women who underwent cesarean section, but recovered on their own with the help of general recommendations, according to the signs of impaired movement capacity 1 year after childbirth could not reach the levels of women who gave birth by vaginal delivery and women who underwent a physical therapy program. Conclusion. It is advisable to prescribe physical therapy means from the first day of postpartum rehabilitation in order to level the signs of impaired motor capacity for quick postpartum recovery of women and their return to full functioning


Prior work on continual learning often operate in a "task-aware" manner, by assuming that the task boundaries and identifies of the data instances are known at all times. While in practice, it is rarely the case that such information are exposed to the methods (i.e., thus called "task-free")--a setting that is relatively underexplored. Recent attempts on task-free continual learning build on previous memory replay methods and focus on developing memory management strategies such that model performance over priorly seen instances can be best retained. In this paper, looking from a complementary angle, we propose a principled approach to "edit" stored examples which aims to carry more updated information from the data stream in the memory. We use gradient updates to edit stored examples so that they are more likely to be forgotten in future updates. Experiments on five benchmark datasets show the proposed method can be seamlessly combined with baselines to significantly improve the performance. Code has been released at this https URL.


The Fourier series expansions are used to obtain the expressions for the components of the electromagnetic field at an arbitrary point of observation and for the total energy loss of a gyrating charged particle in a non-ionized medium having a uniform magnetic field. For a non-relativistic particle, it is shown that the total energy loss is split into the collision loss, whose formula is found to be the familiar one for linear motion, and the loss due to cyclotron radiations. The relative magnitude of the latter to the former is less than (wo/wp )2, where Wo is the cyclotron frequency and wT}=4rrnee~/me where ne and me are the density and mass of electrons in the medium. In the relativistic case, we get the explicit formula of the polarization loss, depending upon the external magnetic field, and of the losses due to the Cerenkov and synchrotron radiations. The spectral and angular distributions of these two radiations are discussed.


The New Brunswick illustration index is an index to the illustrations in the Legislative Library's New Brunswick Collection. The illustrations include photographs, engravings, woodcuts, etc. and each is described in a database entry comprised of ten distinct fields. The project, begun in 1989, is not yet complete. The Index is designed to make the unique New Brunswick Collection more accessible.


A single kenaf plant with smaller than normal, white colored flowers was observed and selected from PI 324922 (Iran) in 1990 at a winter seed increase nursery in Mexico. Subsequent plantings of the mutant plant resulted in a homogeneous population of white flowered plants, designated as PVWF90. To determine the mode of inheritance of the mutant white flower trait, crosses were made between PVWF-90 and two normal, yellow flowered kenaf cultjvars, Tainung 2 and 117. Segregation of flower cokx fit a 3: 1 normal-to-mutant ratio in F2 progeny and 1:1 normal-to-mutant ratio in progeny resulting from a single backcross to PVWF-90. The mutant white flower phenotype, which is described for the first time, was controlled by a single recessive allele, designated wf. Because the white flower character is qualitatively inherited by a single, recessive gene and is easy to identify visually, it should be valuable as a genetic marker for linkage studies and investigations of floral color in kenaf.


Hypergraphs have shown great power in representing high-order relations among entities, and lots of hypergraph-based deep learning methods have been proposed to learn informative data representations for the node classification problem. However, most of these deep learning approaches do not take full consideration of either the hyperedge information or the original relationships among nodes and hyperedges. In this article, we present a simple yet effective semi-supervised node classification method named Hypergraph Convolution on Nodes-Hyperedges network, which performs filtering on both nodes and hyperedges as well as recovers the original hypergraph with the least information loss. Instead of only reducing the cross-entropy loss over the labeled samples as most previous approaches do, we additionally consider the hypergraph reconstruction loss as prior information to improve prediction accuracy. As a result, by taking both the cross-entropy loss on the labeled samples and the hypergraph reconstruction loss into consideration, we are able to achieve discriminative latent data representations for training a classifier. We perform extensive experiments on the semi-supervised node classification problem and compare the proposed method with state-of-the-art algorithms. The promising results demonstrate the effectiveness of the proposed method.


Suppose we aim to use data obtained by studying a biomolecular interaction system with a surface plasmon resonance (SPR) biosensor in quantifying some system feature. We assume a parametric mathematical model for biosensor response due to sources of mass such as analyte-ligand complexes. Some parameters represent interaction features, such as rate constants. Whenever we attempt to estimate parameters from data, we may obtain multiple estimates, regardless of the amount and quality of data. Inconveniently, we may be unable to distinguish between alternatives. This is problematic when alternative parameter values lead to very different predictions of system behaviour for a situation where we lack data. Anticipating this issue prior to data collection allows us to redesign the combination of planned experiments and model, replacing a certain failure to achieve our study's aim with the possibility of success. The literature on SPR biosensors (and computational biology more generally) has paid little attention to this matter. In order to remedy this, it is appropriate to begin with a consideration of the assumed models. These are rarely specified completely, causing ambiguity that impedes scrutiny of their properties and comparison with other models. We demonstrate this by reviewing some model types seen in the Biacore™ biosensor literature. We propose to eliminate model ambiguity by providing a suitable framework for specifing models for biosensor data. This framework will aid future efforts to compose models for data arising from particular interaction mechanisms in a form that is amenable to scrutiny. We expect that the issues raised here will have relevance to the modelling of data obtained from other apparatus employed in quantifying binding behaviour.


Polyaniline/TiO2 nanocomposites have been prepared by sol-gel technique using citric acid and saturated solution of α-dextrose as a surfactant in presence of hydroxyl group at an anomeric position in sugar chain. The FTIR spectrum indicates the benzenoid, quinoid and MO peaks confirm the formation of PANI/TiO2 nanocomposites. The XRD studies show the monoclinic structure and the TEM study of nano TiO2 reveals that the average particles size is 9 ±2 nm whereas the composite size is 13 ± 2 nm and further it is observed that the TiO2 nanoparticles are intercalated to form a core shell of PANI. The formation of core shell is significant up to 30wt% observed from the SEM. The TGA-DSC curves show the thermal stability of polyaniline and its nanocomposites at 660 ° C of temperature. Copyright © 2013 VBRI press.


Abstract : A number of experiments have recently been conducted to compare aspects of depth judgment due to stereoscopic and monocular motion perception. In these experiments, it has been shown that from stereo vision humans over-estimate depth (relative to fronto-parallel size) at near fixations and under-estimate it at far fixations, whereas human depth estimates from visual motion are not affected by the fixation point. On the other hand, the orientation of an object in space does not affect depth judgment in stereo vision while it has a strong effect in motion vision, for the class of motions tested. This paper develops a computational geometric model that explains why such distortion might take place. The basic idea is that, both in stereo and motion, we perceive the world from multiple views. Given the rigid transformation between the views and the properties of the image correspondence, the depth of the scene can be obtained. Even a slight error in the rigid transformation parameters causes distortion of the computed depth of the scene. The unified framework introduced here describes this distortion in computational terms, in order to explain a number of recent psychophysical experiments on the perception of depth from motion or stereo.


Active aging is associated with well-being and quality of life. The aim of this cross-sectional study was to adapt and analyze the applicability of the Adelaide Activities Profile (AAP) in Brazil, and characterize the frequency and type of activities carried out by older adults who belong to the Japanese community. The questionnaire was translated and adapted to Brazilian Portuguese. The sample was composed by two groups: 30 mahjong players and 30 gateball players, men and women. Women were more active in domestic chores, service to others, and intellectual leisure; men were more active in social activities. The AAP may be useful to analyze the activity profile of older adults and guide the indication of gerontological interventions.


This study was conducted with the aim of isolating and identifying banana endophytic bacteria on the basis of their potential  as biological  fertilizer. Banana  materials were  collected from five different geographical regions to enhance diversity. Isolation of bacteria was done using five (5) different isolation media  and the isolates were characterized on the basis of their morphology, biochemical and molecular characteristics. A total of 214 bacterial isolates were obtained and characterized. Microorganism profiling was done using MALDI-TOF/MS and the isolates were clustered into 53 genotypes. Based on their functional characteristics, 43 isolates were selected for 16S rRNA gene sequencing. The 43 strains showed varied levels of positive nitrogenase activity as measured by the acetylene reduction assay and 37 strains were observed to solubilize phosphates by the formation of visible dissolution halos on agar plates (NBRIP medium). Siderophore  production of the isolates was determined using Chrome Azurol  S (CAS) agar plates and  all the isolates were observed to be positive for siderophore production with  3  strains showing distinctively high level of production. Using the 16S rRNA gene sequencing, the 43 strains were identified as Serratia spp. (17 strains), Pseudomonas spp. (12 strains), Enterobacter spp. (4 strains), Rahnella spp. (4 strains), Raoultella spp. (2  strains), Bacillus spp. (1 strain),  Klebsiella spp. (1 strain),  Yersinia spp. (1 strain) and Ewingella spp. (1 strain).  In  conclusion, banana endophytic bacteria were successfully isolated and identified, and  some of the isolates  showed  potential  of being  biological  fertilizers. However, greenhouse and field investigations are necessary to confirm this potentiality.


Purpose. Complexity of biochemical processes in marine environment entails the problem of parameterizing their interactions in constructing the marine ecosystem mathematical models. The aim of the investigation is to simplify solution of this problem by applying the concept of the ecosystem stationary state and the hypothesis on balance of the processes' mutual influence based on the matter balances of biochemical reactions in substance transformations. Methods and Results. To simplify the ecosystem model, applied is the method of the adaptive balance of causes which now is being developed by the authors. The method equations contain negative feedbacks between the ecosystem model variables and the velocities of their change. These feedbacks stabilize the equations' solutions and make the model adaptive to the external effects on the ecosystem. The concept of the solutions' convergence to the stationary state permitted to propose a simple methods (based on the normalized relationships between their average values) for estimating the coefficients of the processes' mutual influences. To test these methods, the adaptive model of the Sevastopol Bay ecosystem was constructed. The data of multi-year observations of the chemical processes in the bay were used for assimilating the observations of the nitrate and ammonia concentrations in the model. The data were assimilated both through their reducing to the dimension and scales of the variability corresponding to the model variable, and their including to the right parts of the model equations as the additional sources and sinks. The numerical experiments carried out using the integral model of the Sevastopol Bay ecosystem showed that application of the normalized relationships between their average values as the estimates of the processes' mutual influences permitted to reproduce the scenarios of all the processes in the ecosystem based on the limited observational data. The model response to the external effects at the constant and varying normalizing factors in the model coefficients is studied. It shows that the variable factors provide the model with higher sensitivity to the external effects. Conclusions. The adaptive models of marine ecosystems constructed by the method of the adaptive balance of causes provide fast solutions' convergence to the stationary state. According to the laws of the matter balances' conservation in the biochemical reactions in substance transformations, the adaptive model tends to establishing dynamical balances in the external and intra-system influences. Therefore the proposed methods of estimating the intra-system relationships' coefficients in the marine ecosystem adaptive model permit to reconstruct the scenarios of those processes in which only their average values are known.


Two crucial problems arise from a microarray experiment in which the primary objective is to locate differentially expressed genes for the diagnosis of diseases such as cancer and Alzheimer's. The first problem is the detection of a subset of genes which provides an optimum discriminatory power between diseased and normal subjects, and the second problem is the statistical estimation of discriminatory power from the optimum subset of genes between two groups of subjects. We develop a new method to select an optimum subset of discriminatory genes by searching over possible linear combinations of gene expression profiles and locating the one which provides the maximum discriminatory power between two sources of RNA as measured by the area under the receiver operating characteristic (ROC) curve. We further provide an estimate to the optimum discriminatory power between the diseased and the healthy subjects over the selected subsets of genes. The proposed stepwise approach takes in account of the gene-to-gene correlations in the estimation of discriminating power as well as the associated variability and allows the number of genes to be selected based on the increment of the discriminating power. Finally, the proposed methodology is applied to a benchmark microarray experiment and compared to the results obtained through existing approaches in the literature.


Arduino Uno microcontroller (ATmega328) is an automatic control device which function to control, capture and store data that can be used to design electronic circuits to control on/off irrigation. In order to determine its performance, application of on/off irrigation control circuit in agriculture field need to be conducted. Mustard plant were selected for this experiment due to its sensitivity on irrigation. Purpose of this study was to applied control system based drip irrigation using Arduino microcontroller on mustard plant cultivation to compare growth and productivity of mustard plant using automatic irrigation based microcontroller and using manual irrigation, which adjusted to plants water requirement. Method used in this research was experimental method by trial on the field. Observed parameter consist of changes in moisture content, performance of on/off irrigation control system, quantity of irrigation water, plant height, number of leaves, length and width of the leaves, plants weight and crop productivity. Setting point for lower limit soil moisture content was 25.47% and the upper limit was 28.73%. During the experiment, three times watering were conducted, i.e. at 11, 16 and 20 days after planting, with total quantity of water 5,200 ml. Height of mustard plants using automatic irrigation was 21.26 cm and using manual irrigation was 22.6 cm; number of mustard plant leaf using automatic irrigation was 13 leaves and using manual irrigation was 13.4 leaves; length and width of mustard plant leaf using automatic irrigation was 17.07 cm and 8.05 cm, while using manual irrigation was 20.75 cm and 9.73 cm; mustard plant productivity using automatic irrigation was 13.54 ton/ha and using manual irrigation was 17.41 ton/ ha.


Although fair use is an intentionally vague doctrine, its application to education has been described as only one of two categories where outcomes remain "quite difficult to predict." To combat this uncertainty, courts have looked to negotiated educational guidelines, which Congress included in its House of Representatives Report accompanying the Copyright Act of 1976. Courts' use of the guidelines has had two unintended and destructive consequences. First, it erroneously gave the guidelines the appearance of law under § 107's fair use analysis, sometimes inadvertently characterizing them as setting maximum limits on permissible copying. Second, it forced educational institutions to rely on the guidelines as the law, improperly crafting their own copyright policies to reflect the guidelines' contours. Educational institutions began using the guidelines as maximum limits on allowable copying under their policies, constraining their instructors' ability to teach effectively.To remedy these problems, this Article proposes a new model for evaluating educational fair use: the administrative agency. Although previous scholars have delineated new approaches to copyright infringement and fair use, few deal explicitly with fair use in education. That is exactly what this Article does. Building off of a previous scholar's suggestion that Congress create an agency to administer fair use, this Article takes an additional step by creating a model that develops and enforces regulations specific to educational fair use. This new agency is likely to reduce uncertainty for educators, slenderize educators' risk of litigation - thereby simultaneously decreasing educational expenses and increasing the amount of time and money spent on educational advancement - and substantially ameliorate, if not eliminate, the guidelines' negative effects on education.


Tertiary relicts often show evolutionary stasis in morphology and ecology and have been hypothesized to retain stable population sizes in refugia. However, recent studies have reported that some relicts evolutionarily shifted their physiology, ecology, and morphology and experienced various patterns of demography. To understand the historical survival of relict plants, a multidimensional study investigating the evolution of ecological and morphological traits as well as population demographic history is needed. The genus Tanakaea (Saxifragaceae) comprises two species in China and Japan. These species share most vegetative characteristics and are sometimes treated as a single species. The distribution pattern is relictual, as the populations are confined to small areas in mesic warm temperate forests less influenced by Quaternary glacial climates. Focusing on the relictual plant group, this study tested the hypotheses of evolutionary stasis and population stability in long‐term refugia. Genetic analyses using plastome sequences and genome‐wide single‐nucleotide polymorphisms revealed divergence of the two species approximately 6.8 million years ago and strong genetic differentiation of the regional populations. Demographic analysis revealed that almost all populations retained stable population sizes during glacial–interglacial climate changes, supporting the traditional view. However, morphological assessments revealed a simultaneous shift in breeding systems (from hermaphrodite to dioecy/non‐clonal to clonal reproduction) in Japanese species and intraspecific differentiation of leaf traits. Therefore, the relict species do not show evolutionary stasis in every aspect. Changes in reproductive characteristics may have contributed to their long‐term in situ survival.


Previous work has shown that sexual maturation of female mice is accelerated by the presence of a male. This report identifies male odor as a critical stimulatory masculine agent. Groups of females in contact with 1) an adult male, 2) with a male behind a wire mesh barrier, or 3) the odor of a male display vaginal opening and first estrus about 15 days earlier than females exposed to a castrate male, forced activity, or no male influences. The data alsosuggest that odors derived from males exposed to estrous females are more effective than odorsfrom solitary males in accelerating sexual maturation. (Endocrinology84: 658, 1969)


To reveal the characteristics of organic phosphorus release from lake sediments and its potential impact on water quality, six lake sediments from Yunnan Plateau and the middle and lower reaches of the Yangtze River in China were selected. We studied the differences in the kinetics of dissolved organic phosphorus (DOP) and dissolved inorganic phosphorus (SRP) release from sediments. The effects of organic phosphorus morphology and dissolved organic matter (DOM) characteristics on sediment phosphorus release were investigated, and the water quality risks of sediment DOP release were discussed. The results showed that:① the release kinetics of sediment DOP and SRP were similar; both followed the second-order kinetic model, starting with a rapid release phase, followed by a slow release, and the release curve gradually leveled off and reached the maximum release. ② The release of organic phosphorus was related to organophosphorus morphology and organic matter. Active organic phosphorus (LOP) and medium active organic phosphorus (MLOP) were the DOP forms mainly released into the overlying water during the rapid release phase. The proportion of LOP and MLOP to total organic phosphorus (DTP) decreased in the late release stage, whereas the proportion of non-active organic phosphorus (NLOP) increased; further, the degree of humification and aromaticity of organic matter gradually increased with phosphorus release, and its activity decreased, resulting in a slower release rate at the later stage. ③ Compared with that of SRP, the risk of DOP release was higher, accounting for 47%-77% of the total amount of DTP. It was also found that the higher the nutrient level of the lake, the greater the release of DOP and the higher the water quality risk. Therefore, not only the release of inorganic phosphorus but also that of organic phosphorus should be of concern in the process of phosphorus release from lake sediments to prevent the underestimation of phosphorus release and water quality risk.


Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL

Triple negative breast cancer (TNBC) is characterized by lack of estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. It is known to be particularly aggressive and refractory to current chemotherapies. Tumor-initiating cells (TICs) have been postulated as responsible for treatment failure for this type of cancer. Recent evidence suggests that Notch signaling may play a role in regulation of TIC self-renewal and differentiation hence present a promising target for development of novel therapies for TNBC. We previously discovered a mouse monoclonal Ab (mu-hN1) that produces robust efficacy in both T-cell acute lymphoblastic leukemia and TNBC by specifically blocking human Notch1 signaling in tumor cells. We subsequently produced a humanized Notch1 mAb (hu-hN1) that retained similar characteristics and activities compared to the mouse prototype mu-hN1. To gain insights into the mechanisms of Notch1 blockade on TNBC tumor grow inhibition (TGI), we evaluated the effect of hu-hN1 on apoptosis, proliferation and TIC self-renewal in Notch-driven Sum149 and a patient derived xenograft (PDX) TNBC models. We showed that hu-hN1 inhibited Notch signaling by reduction of NICD (Notch intracellular domain) and target genes Hes-1 and cMyc in Sum149 tumors. Inhibition of Notch signaling led to significant TGI either as a single agent or in combination with Docetaxel. TGI of hu-hN1 appeared to be in part due to induction of apoptosis in the tumor cells. More interestingly, treatment with this Ab caused reduction in mammosphere formation and CD44+/CD133+/ESA+ cell population. It also resulted in decrease in tumor incidence and delay in tumor recurrence, suggesting an anti-TIC activity of the agent. Further investigation in a PDX TNBC model confirmed the robust tumor efficacy and anti-TIC effect of hu-hN1. Taken together, our findings suggest that anti-Notch1 mAbs may provide novel therapies to improve the efficacy of conventional treatments by directly targeting the TIC niche. They may also delay tumor recurrence and hence have a major impact on cancer patient survival.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3485. doi:1538-7445.AM2012-3485


Recommender system is the most successful commercial technology in the past decade. Technical mammoth such as Temu, TikTok and Amazon utilize the technology to generate enormous revenues each year. Although there have been enough research literature on accuracy enhancement of the technology, explainable AI is still a new idea to the field. In 2022, the author of this paper provides a geometric interpretation of the matrix factorization-based methods and uses geometric approximation to solve the recommendation problem. We continue the research in this direction in this paper, and visualize the inner structure of the parameter space of matrix factorization technologies. We show that the parameters of matrix factorization methods are distributed within a hyper-ball. After further analysis, we prove that the distribution of the parameters is not multivariate normal.


abstract:The article focuses on The Wall: Growing Up Behind the Iron Curtain (Peter Sís, 2007) and Marzi (Sylvain Savoia and Marzena Sowa, 2004–2017), two widely translated autobiographical comics written in English and French, respectively, as an entry point into the afterlives of European state socialisms in global contexts. The author examines how Sís, a Czech-born illustrator and children book author, who defected to the United States, and Sowa, a Polish-born writer who left for France, remember their lives under state socialism, and how they make them legible to present-day transgenerational and transnational audiences. The author explores how comics, specifically the seriality, multimodality, and the meanings created at the intersection of texts and images, undermine the cultural scripts which inform the narratives of these two diasporic artists. By focusing on paratextual elements, the author also demonstrates that the transnational trajectories of the two works are path-dependent on mainstream tropes about state socialism. Lastly, given that the two comics feature internationally in school curricula and are adopted by teachers as important methodological tools, the author argues for the crucial importance of comics and life writing pedagogy when teaching graphic autobiographies about post/socialism.


3,9-Dihydroxy-5H-benzofuro[3,2-c]quinoline-6-one (KCA-012), the chemical structure of which is closely similar to that of the phytoestrogen coumestrol, inhibited parathyroid hormone-, 1 alpha,25-dihydroxyvitamin D3- and prostaglandin E2-induced bone resorption of cultured fetal rat bones. KCA-012 also increased the calcium content of 9-day chick embryonic femur cultured in vitro. KCA-012 did not show any estrogenic activity as determined by an increase in the uterine weight of ovariectomized rats, whereas coumestrol did. These results indicate that KCA-012 has no estrogenic activity and has unique effects of inhibiting bone resorption and stimulating bone mineralization.


[1] We present a technique to measure the magnetic field-aligned vorticity of mesoscale plasma flows in the F region ionosphere using line-of-sight velocity measurements made by the Super Dual Auroral Radar Network (SuperDARN). Vorticity is often used as a proxy for magnetic field-aligned current (FAC) intensity in the ionosphere but also provides information about turbulent processes in the ionosphere and magnetosphere. Using 6 years (2000–2005 inclusive) of vorticity measurements made by six SuperDARN radars in the Northern Hemisphere, we have compiled, for the first time, maps of average vorticity across the northern polar ionosphere. These maps have been subdivided according to different seasonal and interplanetary magnetic field (IMF) conditions. The variations in the morphology of the vorticity maps with IMF direction match very closely those seen in maps of average FAC intensity (determined using different methods and instrumentation), suggesting that vorticity is a good proxy for FAC in an averaged sense. The variations in the morphology of the vorticity maps with season show differences from those seen in the FAC maps, illustrating that ionospheric conductance plays a major role in determining the differences between measurements of vorticity and FAC.


The non-relativistic dynamics of an electric dipole in a uniform and stationary electromagnetic field is considered. The equations of motion are derived ab initio. It is shown that they are Hamiltonian with respect to a certain degenerated Poisson structure. The system has a 'hidden' symmetry which allows its dimension to be reduced. The reduced system is also Hamiltonian with respect to a degenerated Poisson structure. We show how to perform this reduction in the framework of the Lagrange formalism. Integrability of the reduced system is investigated. It was proved that the system is non-integrable except for two cases when, for specific values of parameters, the system admits an additional first integral.


The coordination chemistry of five N,N′-bidentate ligands that contain a 1-substituted benzotriazole subunit has been studied. Spectroscopic and electrochemical studies of their chelated ruthenium bis(2,2′-bipyridine) complexes have shown that the benzotriazole group is a relatively electron rich component. X-Ray crystal structures are reported for one-dimensional polymeric copper and silver complexes of di(benzotriazol-1-yl)methane, mononuclear and dinuclear copper and silver complexes of 1-(2-pyridyl)benzotriazole (in which the ligand displays chelating, monodentate and bridging modes of coordination, respectively), bridged binuclear palladium, copper and silver complexes of 1-(2-pyridylmethyl)benzotriazole and a tetranuclear copper complex of 1-(1-isoquinolyl)benzotriazole.


This study was conducted to compare the quality characteristics of Korean traditional wine fermented from different rice cultivars. Two kinds of rice cultivars, Seolgaengbyeo and Chucheongbyeo, were used. The hardness values of Seolgaengbyeo and Chucheongbyeo were 2126.6 g/sec and 4056.1 g/sec. The alkali digestion value (ADV) and amylose contents of Seolgaengbyeo and Chucheongbyeo were 6.6 and 6.4, 19.8 and 19.3%, respectively. Amylogram results were not significantly different between Seolgaengbyeo and Chucheongbyeo using a rapid visco analyzer (RVA). After fermentation for 7 days, the alcohol contents of the fermented wines ranged from 17.34 to 17.53%. The pH, total acidity, and glucose contents of the wines fermented with Seolgaengbyeo and Chucheongbyeo were 3.63 and 3.64, 0.17 and 0.17 mg/mL, 3.22 and 3.65 mg/mL, respectively. Finally, sensory evaluation of wine fermented with Seolgaengbyeo showed better taste than that of wine made with Chucheongbyeo.


This is a brief progress report, covering our research in general plasma theory and simulation, plasma-wall physics theory and simulation, and code development. Reports written in this period are included with this mailing. A publications list plus abstracts for two major meetings are included.


Purpose: The purpose of this study was to identify the influence of moral distress, empowerment, and nursing practice environment on nurses' person-centered care in long-term care hospitals.Methods: A cross-sectional descriptive study was conducted using self-report questionnaires. Participants included 128 nurses working in eight long-term care hospitals. Data were collected from July 24 to August 31, 2018 and analyzed using the independent t-test, one-way ANOVA, Pearson correlation, and multiple linear regression using the SPSS/WIN 26.0 program.Results: Person-centered care showed significantly negative correlations with moral distress (r=-.18, p=.048) and positive correlations with empowerment (r=.52, p<.001) and nursing practice environment (r=.46, p<.001). Person-centered care was significantly affected by empowerment (β=.42, p<.001) and nursing practice environment (β=.26, p=.002), and the explanatory power of these variables was 34% (F=22.29, p<.001).Conclusion: Research results suggest it is necessary to develop a program to improve the empowerment of nurses for person-centered care and nursing practice environment in long-term care hospitals.


Nowadays, the role of mass media shifted from informing citizen to influencing and shaping their opinion about the environment they live in. Communication channels have also diversified over time, people having the opportunity to choose to obtain information from the online environment: websites, social platforms, blog, as well as from offline: television, radio. In this regard, the influence of mass media can be discussed in the context of the opinions people hold about the quality and performance of public services. Given the way messages are sent and the professionalism of journalists, trust becomes a fundamental element that underlies the power of the media to influence people's perception. Taking into account the aspects previously mentioned, this paper aims to identify the way mass media influences people's perception about the quality of public services in Brasov County, so as to find methods to improve this services. In order to conduct the research, several methods will be used. Firstly, a content analysis will be carried out, to obtain information from online platforms. Further, people's perception, types of news they have seen about public services, and people's trust in media channels, will be measured through a questionnaire as well as through interviews applied to people living in several areas of Brasov County such as Rupea, Codlea, Fagaras, Brasov. Considering that generally, perception about public services is negative in Romania, as results we expect to find out that media has a significant contribution in negatively influencing citizens opinions about quality and performance of these services.


Recent studies have revealed a remarkable molecular diversity of Plasmodium parasites in great apes in Africa, as well as parasite exchange events between these primates and humans. We review the different points of view proposed on the origin of human malaria, and discuss ape Plasmodium parasites as a source of human outbreaks.


Information about muscle length is transmitted to the cerebellum from muscle spindle receptors through the dorsal spinocerebellar tract (DSCr). The "transinformation" about muscle length in single DSCT fibers was calculated from steady-state spike trains by two different methods, assuming that the decoding mechanisms use a frequency code. By the first method, the number of distinguishable muscle lengths (and thus the transinformation) was determined from the rate of convergence of the mean frequency of firing (with increasing number of intervals). The observation time necessary to estimate the mean frequency of the impulse train with a certain accuracy was independent of the stretch level, even though the number of intervals necessary to make this estimate was different at high and low levels of stretch. By the second method an input frequency-output frequency matrix was calculated. The transinformations and the rate of transinformation was thea calculated from this matrix. There was an acceptable agreement in the estimates of transinformation by the two methods. The rates of transinformation are significantly increased by the particular time structure of the discharge patterns of the nerve cells. Consequently, the loss of information due to the synaptic coupling is appreciably reduced.


The ants (Hymenoptera, Formicidae) associated with aphids (Hemiptera, Aphididae) in the province of Valencia Twenty-six species of ants associated with aphids, belonging to twelve genera, are collected. Three subfamilies are identified, being the Formicinae the more represented about number of samples, genera and species. On the other hand, Lasius niger has been the species that is found with a more number of aphids (fifty eight species), and it seems to be the ant with a more capacity to establish associations with the different species of aphids. 224 different associations between the ants and the aphids are established and 164 of them are not recorded in the bibliography consulted for Spain.


Background: Predicting cup size after reduction mammaplasty is a challenge well recognized by plastic surgeons. This study presents a method whereby the weight of tissue to be excised can be predicted on the basis of the initial and desired cup size. Methods: Breast density was calculated from resection specimens. Cup volumes of a specific range of bra style were then measured by filling the bra cups with modeling clay on a mannequin and the volume measured via water displacement. These data were then correlated to breast tissue volume and weight. Results: The average breast tissue density calculated was 0.98 g/ml (SD = 0.05). Bra cup volume measurements showed a steady progression according to both cup and band sizes. A table was constructed to predict the weight of tissue required for excision to achieve the desired change in cup size. Conclusion: These results can assist plastic surgeons in predicting the amount of breast tissue to excise to achieve a given cup size. A secondary use of these results is a breast volume guide for implant planning.


Anthracyclines are commonly used antineoplastic drugs. However, their clinical utility is tempered by a dose-dependent risk of cardiotoxicity and congestive heart failure. Current preventive measures focus on dose reduction, use of less cardiotoxic anthracycline analogues and prophylactic use of dexrazoxane. Recent research has focused on early monitoring and risk stratification to identify patients that are 'at risk' for cardiotoxicity, using biochemical markers and the prophylactic use of novel cardioprotectants. This article reviews the clinical course, pathogenesis, cardiac monitoring and new concepts in diagnosing and preventing anthracycline cardiotoxicity.


Peripheral somatic and autonomic nerve function have been studied in 79 teenage (16–19 yr) diabetics and 20 age- and sex-matched normal controls. Almost three-quarters of the diabetics (72%) had abnormal peripheral somatic nerve function tests, and one-third (31%) had abnormal cardiac parasympathetic tests. Both motor and sensory peripheral somatic nerve abnormalities were related to poor prevalling glycemic control (HbA1) and duration of diabetes. Thus, the 27 patients with three or more (maximum six) peripheral nerve abnormalities had significantly higher HbA1 levels (P < 0.001) and longer duration of diabetes (P < 0.01) than the 22 with no abnormalities. Individual peripheral somatic nerve tests almost invariably correlated only with HbA1 (median motor, P < 0.05; peroneal motor, P < 0.001; sural sensory, P < 0.001) or duration of diabetes (median sensory, P < 0.001). Sensory potential amplitude, as well as conduction velocity, was frequently reduced, implying axonal involvement. These findings suggest that abnormal peripheral and autonomic nerve function are common in young insulin-dependent diabetics and that poor metabolic control is a major determinant of the damage.


The silvopastures systems promote the production and environment protection, several benefits should to be reached. However, to that benefits result in the tree-grass association, it is necessary that the trees provide, mainly, increase production and quality grass grown below their tops. The objetive was, evaluate the influence of four leguminous arboreal species in seventeen variables of Brachiaria brizantha cv. Marandu growing at different distances (D) from the trunk of leguminous of these trees: D1= 50 cm from the trunk; D2= half of the radius of the projection of the top; D3= the radius of the projection of the top; D4= one and half the radius of the projection of the top ; and D5= twice the radius of the projection of the top. Distances (D4 e D5) corresponding to the areas out of the tops and considered as controls. The used species were Samanea guachapele (albizia), Acacia holosericea (olosericea), Mimosa tenuiflora (jurema preta) e Mimosa artemisiana (jurema branca). Were evaluates the variables in grass: tenor crude protein , digestibility in vitro of dry matter, neutral detergent fiber, acid detergent fiber, lignin in sulfuric acid, lignin in permanganate of potassium, cellulose, silica and dry matter production. To analyse the datas utilized a multivariate analysis method, the factor analysis. The rotative factor F1, wich explained the highest variance percentage of datas, associated to the results of the factorial scores, showed that the leguminous arboreal specie A. holosericea proporcioned the majors accumulation of dry matter, protein, digestibility in vitro of dry matter in aereal part of Marandu grass, growing in distances more next of the trunk. The rotative factor F1 also showed that the lowest values for these variables were found in grass growing out of the influence of cup is specie Mimosa tenuiflora in the area no tree. The partial results indicate that the arboreal leguminous Acacia holosericea (olosericea) proportioned the higher quality and quantity in Marandu grass, when it growed under influence of its top.


with the development of computer technology, especially the rapid development of the network, information security is becoming more and more important. In practical applications, access control is the system security technology implement of security policy. It manages all the access request of resource according to the security policy and determines the access request of resource authorities whether or not. And it can effectively prevent illegal users access system resources and legitimate users illegally use of resources. This paper combined the requirements of access control model in scientific data sharing platform. By comparing several major models currently, we summed up their advantages and disadvantages. Finally, according to the characteristics of scientific data sharing platform, we are combining MAC model with ERBAC model and expecting to apply to this platform.


Objective:To study the effect of celery seed extract on the leve of uric acid in rats with hyperuricemia and the control of joint inflammation in gouty arthritis. Methods:Uric acid nephropathy rats models were established by feeding yeast and adenine. Fifty male Wistar rats were divided into five groups including control group,model group and celery seed extrac treatment groups(high-,moderate-and low-doses). The serum uric acid(UA),urea nitrogen(BUN),creatinine(Cr) and activity of liver xanthine oxidase were measured and the pathological changes in renal were detected. The model of acute arthritis was induced by injecting monosodium urate(MSU) into unilateral ankle of rat. Results:The level of serum uric acid of the high-dose treatment group is significantly different from that of the model group(p0.05). In the high and moderate-dose groups,the activity of the liver xanthine oxidase reduces,but there are no obvious difference between the model group and the two groups(p0.05). The swelling rate of the high-dose group is obviously lower than that of the model group(p0.01). The pathological changes in renal of all the treat ment groups are lower than that of the model group. Conclusion:The celery seed extrac has some protective effects on the hyperuricemia and the damage of kidney'function.


Keynes's revolution in macroeconomic theory is based on his application in the General Theory of his Inexact measurement approach from the A Treatise on Probability. This involves the use of interval valued probability and interval valued outcomes. Keynes called this approach approximation. It entails nonadditive (sub and super) probabilities, imprecise probabilities, indefinite and indeterminate probabilities,to which Keynes added interval valued outcomes in the General Theory. Except in special cases, Keynes rejected both Exact measurement,which involved the use of precise, definite, determinate, additive, linear probabilities, which imply that the decision maker knows an exact probability distribution.

Keynes developed Boole's original logical theory of probability by developing an alternative method of solving Boole's problems. Like Boole, Keynes's approach involved solving systems of equations, the constraints, using linear and non linear, mathematical programming techniques. Keynes uses special aggregation assumptions in order to use and present an exact mathematical analysis in his D-Z model of chapter 20, which is the foundation for his IS-LM(LP) model of chapter 21. The D-Z model deals with expectations and uncertainty that results in a specific Y value. That Y value is an actual value that is certain, quantitative, and deterministic. Keynes then combines Y with r, the nominal, long run rate of interest, to derive the IS and LM(LP) curves on pp.298-299 of the General Theory.

The General Theory has, unfortunately, attracted two completely different types of interpreters, both of which conflict directly with Keynes's use of inexact measurement.

The first type of interpreter essentially follows the views of Hicks(1937), Tinbergen(1940), Modigliani(1944) and Klein(1947), for example, in asserting that Keynes's approach in the General Theory was, in fact, a purely verbal, literary, prose approach, with no mathematical or statistical foundation whatsoever, that needed to be reworked in order to present it in mathematical form.

The second approach follows the Joan Robinson and G LS Shackle nihilist approach in asserting that Keynes argued that no mathematical, technical, analytic or quantitative approaches involving mathematical modeling or equations could ever be possible in macroeconomics because of the existence of what they called unknowledge or fundamental uncertainty, which meant that no decision maker has any knowledge whatsoever of anything that can occur in the future, be it the near future or the distant future, be it one day in the future, one month in the future, one year in the future, five years in the future, ten years in the future, twenty years in the future, etc. The best that could be done was to assume that decision makers could sometimes make use of a weak, ordinal probability approach. Both approaches have no support whatsoever in anything actually written by Keynes in his lifetime. The nihilistic approach of the Keynesian Fundamentalists (Moggridge, Skidelsky, Meeks, O'Donnell, Carabelli, Fitzgibbons, Runde, Davis, Winslow, etc.) is based on a gross misinterpretation of the diagram on page 39 of the A Treatise on Probability.

Once this error is corrected, it is clear that Keynes used a mathematical approach involving non linear and non additive analysis in his approach to lower and upper probabilities that Tinbergen, Modigliani, and Klein simply overlooked because they were not familiar with the concept of interval valued probability. Keynes's Inexact approach was evolved and can be studies in the work of Hailperin (1986) and Walley (1991).There are no macroeconomists who are familiar with this work.

Keynes described his pp.298-299 model in a summary in the GT using the following words or phrases:
• One can calculate a quantitative answer
• The model is composed of three elements a), b),and c)
• It provides an analysis that is valuable in introducing order and method to the enquiry
• It is a set of simultaneous equations
• It provides a determinate answer or result.
• This result is an equilibrium

Keynes is describing his IS-LM(LP) model in the General Theory.


Objective: Retinal arteriolar imaging represents a promising method to assess microcirculation in humans. A recently developed non-invasive opto-electronic technology (Adaptive Optics Camera, AOC, RTX1® -ImagineEye,Orsay, France) provides a morphologic analysis of the retinal arteriolar tree, through the measurement of a novel remodeling index, the wall-to-lumen ratio (WLR). Our aim was to evaluate the effects of blood pressure (BP) drop on retinal arteriolar remodeling in newly diagnosed hypertensive patients in a short-term vs long-term follow-up. Design and Method: 57 hypertensive subjects without diabetes were consecutively enrolled and evaluated at baseline, 6 weeks (short-term) and 40 weeks (long-term). Among them, 28 had stable BP and 29 had BP drop after starting antihypertensive therapy after baseline visit. Wall Thickness (WT), Internal Diameter (ID), Wall Cross Sectional Area (WCSA) and WLR were measured with AOC. Results: In the "BP drop" group, mean SBP/DBP, WT, ID, WLR and WCSA at baseline were 157/86 mmHg, 24.7 ± 4.7 &mgr;m, 73.3 ± 8.8 &mgr;m, 0.342 ± 0.07 and 3352 ± 943 &mgr;m2, respectively. At short and long-term follow up SBP decrease was – 13% and −21% and DBP −7 % and −12%, respectively. While WCSA remained stable at 6 weeks, a statistically significant reduction in WLR (−6%) was observed due to lumen dilatation (+2.4%) and wall thinning (−4%). After 40 weeks, while WCSA still remained stable, a further WLR decrease was observed compared to baseline (−11%) due to both further lumen dilatation (+5.6%) and arterial wall thickness decrease (−6.5%). No changes in BP or in retinal arteriole anatomical indices were observed in the "stable BP" group throughout. Conclusions: After antihypertensive treatment induced BP drop, the observed WLR decrease is due to lumen dilatation and wall thinning without any significant WCSA change. This suggests that this retinal arteriole reverse eutrophic remodeling depends on changes in BP, myogenic tone and wall components rearrangements more than on wall mass changes.


A barrier to the wider adoption of neural networks is their lack of interpretability. While local explanation methods exist for one prediction, most global attributions still reduce neural network decisions to a single set of features. In response, we present an approach for generating global attributions called GAM, which explains the landscape of neural network predictions across subpopulations. GAM augments global explanations with the proportion of samples that each attribution best explains and specifies which samples are described by each attribution. Global explanations also have tunable granularity to detect more or fewer subpopulations. We demonstrate that GAM's global explanations 1) yield the known feature importances of simulated data, 2) match feature weights of interpretable statistical models on real data, and 3) are intuitive to practitioners through user studies. With more transparent predictions, GAM can help ensure neural network decisions are generated for the right reasons.


Introduction: Urethral stricture is a common cause of lower urinary tract symptoms in the middle aged and elderly men in our environment. Its diagnosis and management is hinged mainly on a retrograde urethrogram (RUG) that is associated with variable lengths and sites with that found intraoperatively due to difference in magnification (source patient as well as source image distance), penile stretch, and positioning during the procedure. We hereby sort to validate this tool in defining urethral strictures. Materials and Methods: Adult patients with lower urinary tract symptoms suspected to be due to urethral strictures who presented to the outpatient department and emergency departments of the hospital between January 2016 to December 2016 were recruited into the study. This was followed by obtaining an informed consent from the patient and ethical clearance from the institution. Patients who were not fit or not willing to have a urethroplasty were excluded from the study. The recruited patients had RUG to characterize the strictures. The intraoperative findings at urethroplasty were compared with that found on RUG. Data were collected and analyzed using SPSS version 23 to determine sensitivity specificity of the test. Results: A total of 84 patients were studied during the period. The mean age of the patients was 44.1 years. Bulbar strictures accounted for 65% of the strictures. Most of the strictures were single (72%) and long segment (52%). Sensitivity and specificity of RUG in determination of the length of stricture were 76.9% and 74.6%, respectively, whereas the sensitivity and specificity of RUG in determination of site of stricture were 92.9% and 96.4%, respectively. The determination of number of stricture on RUG has a sensitivity of 94.2% and specificity of 90.8%. Conclusion: RUG is a valuable tool in the management of urethral strictures with a higher sensitivity and specificity for the determination of site and number of strictures as compared to length of stricture that is more affected by magnification and techniques in contrast administration. This should be considered during procedure as well as during interpretation of images.


Colorectal cancer is among the three leading causes of cancer-related deaths worldwide. Nearly 50% of patients with colon cancer develop liver metastases. Mortality associated with the advanced stage of colon cancer has principally been attributed to the development of liver metastases. Therefore, clarifying the biological mechanisms underlying liver metastasis from colon cancer and accelerating the development of new treatment strategies are needed. We isolated Zinc finger protein 185 (ZNF185) as a metastasis-related protein by global quantitative proteome analysis of the in vivo liver metastasis model of super immunodeficient NOG mice with the highly liver-metastatic subline SW48-LM2 (Matsuo E, et al. AACR, #3947, 2008). LIM domain proteins have many fundamental biological processes including cell lineage specification, cytoskeleton organization, and organ development. ZNF185 is one of the LIM domain proteins and is considered to be involved in regulating cellular differentiation and/or proliferation. However, the functions and properties of ZNF185 in the multi-step process of cancer biology have not yet been elucidated in detail. In the present study, we analyzed the relationships between ZNF185 and the clinicopathological features of colon cancer (age, gender, histological type, lymphatic involvement, venous involvement, T and N statuses, liver metastasis, and stage). The expression of the ZNF185 protein was immunohistochemically analyzed. The expression of ZNF185 was detected in the cancer cells of 78 of 87 colon cancer patients. A correlation was observed between ZNF185 and the histological type (p=0.010, G-test). The expression of ZNF185 was also correlated with liver metastasis (p=0.030, G-test). Multivariate analysis using the Cox proportional hazards model was performed among the cause-specific survival rate, ZNF185 expression, and clinicopathological features. The histological type, liver metastasis, and ZNF185 expression were found to be independent prognostic indicators (p= 0.028, p Citation Format: Daisuke Furukawa, Tsuyoshi Chijiwa, Masahiro Matsuyama, Masaya Mukai, Ei-ichi Matsuo, Osamu Nishimura, Kenji Kawai, Hiroshi Suemizu, Nobuyoshi Hiraoka, Toshio Nakagohri, Seiei Yasuda, Masato Nakamura. Zinc finger protein 185 is a key molecule of liver metastasis in colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 49. doi:10.1158/1538-7445.AM2014-49


We develop and analyze stochastic approximation algorithms for solving nested compositional bi-level optimization problems. These problems involve a nested composition of $T$ potentially non-convex smooth functions in the upper-level, and a smooth and strongly convex function in the lower-level. Our proposed algorithm does not rely on matrix inversions or mini-batches and can achieve an $\epsilon$-stationary solution with an oracle complexity of approximately $\tilde{O}_T(1/\epsilon^{2})$, assuming the availability of stochastic first-order oracles for the individual functions in the composition and the lower-level, which are unbiased and have bounded moments. Here, $\tilde{O}_T$ hides polylog factors and constants that depend on $T$. The key challenge we address in establishing this result relates to handling three distinct sources of bias in the stochastic gradients. The first source arises from the compositional nature of the upper-level, the second stems from the bi-level structure, and the third emerges due to the utilization of Neumann series approximations to avoid matrix inversion. To demonstrate the effectiveness of our approach, we apply it to the problem of robust feature learning for deep neural networks under covariate shift, showcasing the benefits and advantages of our methodology in that context.


Abstract Original models of RPAS communication channels based on IEEE 802.11b Standard, including both Base Station transmission within the Radio Line of Sight, and through the satellite using Beyond Radio Line of Sight, were built. Dependencies of the Bit Error Rate on the Signal-Noise Ratio for different payload data rates were obtained. Transponder nonlinearity and Base Station antenna diameter impact were analysed.


DEAR SIR, Dr Mark's article (Journal, November 1978, 133, 46 1—5) on rehearsal relief of a nightmare concerns a rather involved case, but I would suggest the method should be more widely used. I am a trainee GP, and with the help ofmy trainer have been treating an 80year-old man with a recurrent nightmare. Treatment consisted of rehearsal relief which has been dramatic ally successful. The patient's dream was of his experience as a 17-year-old boy during the First World War. He remembered learning how to bayonet a dummy and how horrifying it was to perform this in real life on a man who shouted †̃¿ mother' as the bayonet plunged in and how it was necessary to stamp on his chest to extract the bayonet. He then had to continue running and passed a comrade who, mortally wounded, implored him to stop and help. The patient was unable to do so because of his infantry training and fear ofcourt-martial or being shot in the back for cowardice. The guilt involved in this sequence had not left him for 63 years and he had apparently relived the nightmare most nights. He had not talked out the nightmare with his wife and had only briefly mentioned it to one of his sons 5 years previously during a period of increased guilt and depression. Consultation was conducted in his bedroom since the original contact came following a heart attack. I feel this setting encouraged him to talk, but he is a religious man and, fearing death, may have wanted to make peace with God. He repeated the nightmare in detail on four separate occasions and was exhausted after each session. He also revealed that his father was an alcoholic who at times threatened his mother with a razor, and she had taught him to pray regularly and never to be a coward; also that one of his sons was killed in the Second World War and he felt this was God's punishment for the murder he had committed. Guilt was further increased since he could not tell his wife it was his fault. Following these sessions the patient was relieved of the nightmare, although he still had vivid dreams. I suggest that this technique, although time consuming, could be used successfully in general practice, especially in the patient's home.


We study the parameterized complexity of computing the tree-partition-width, a graph parameter equivalent to treewidth on graphs of bounded maximum degree. On one hand, we can obtain approximations of the tree-partition-width efficiently: we show that there is an algorithm that, given an $n$-vertex graph $G$ and an integer $k$, constructs a tree-partition of width $O(k^7)$ for $G$ or reports that $G$ has tree-partition width more than $k$, in time $k^{O(1)}n^2$. We can improve on the approximation factor or the dependence on $n$ by sacrificing the dependence on $k$. On the other hand, we show the problem of computing tree-partition-width exactly is XALP-complete, which implies that it is $W[t]$-hard for all $t$. We deduce XALP-completeness of the problem of computing the domino treewidth. Finally, we adapt some known results on the parameter tree-partition-width and the topological minor relation, and use them to compare tree-partition-width to tree-cut width.


Cyclins D1 and E play critical roles in the progression of cells through the G1 phase of the cell cycle. Amplification and/or overexpression of the cyclin D1 gene and aberrant expression of cyclin E have been described in several forms of human cancer. In the present study, we examined the expression of these two genes by Western, Northern and Southern blot analyses in a series of primary human colon carcinomas of various stages and degrees of differentiation and in paired adjacent normal mucosa samples, and also in a series of human colon carcinoma cell lines. About 50% of the colon carcinomas displayed a two to five fold increase in the expression of cyclin D1 mRNA and protein, when compared with the paired normal mucosa samples. Six out of eight carcinomas examined showed a four to nine fold increase in cyclin E mRNA and about 50% of the carcinomas displayed a two to three fold increase in cyclin E protein. Low molecular weight cyclin E-related proteins were observed in four out of ten carcinomas. These changes in cyclins D1 and E occurred in both early and late stage tumors. Three of the six cell lines examined displayed a high expression of cyclin D1 mRNA and protein. A very high level of cyclin E mRNA expression was seen in HCT116 cells and this was associated with the presence of low molecular weight cyclin E-related proteins. None of the primary colon carcinomas nor the six cell lines examined displayed amplification of either the cyclin D1 or cyclin E genes. Thus, an aberrant expression of both cyclins D1 and E occurs in a significant fraction of human colon carcinomas.


Research in the past four years under this omnibus title has covered a whole gamut of investigations from origin of rocks to crust-mantle evolutionary history to cosmological fractionation processes. Two new areas can be added to the list. An extensive amount of trace-element work has been done on the lunar samples. In addition, trace-element studies related to plate tectonics have come into vogue. This short report covering such wide fields can only be cursory at best. The coverage in the bibliography includes references on many trace-element studies in terrestrial materials and meteorites, as well as the trace-element studies on lunar samples, for completeness. However, since studies on lunar samples are covered in another report, no discussion in this area is presented here. The bibliography does not include references on rare gases, a serious omission on many counts, and one that ought to be remedied in the future. The bibliography is divided under the topical headings of (1) analytical techniques, (2) alkalis, alkaline earths, uranium, and thorium, (3) rare earth elements, (4) studies related to global tectonics, and (5) other trace-element studies.


Here we present the production of monodispersed carbonaceous microspheres directly from wood sawdust by a novel hydrothermal method, combining hydrothermal carbonization and hydrothermal extraction. This is the first time to obtain high-quality carbonaceous microspheres from crude biomass except carbohydrates, the morphology of which is quite different from the hydrochar obtained from woody biomass by traditional hydrothermal carbonization processes. Carbonaceous microspheres obtained from two wood sawdust samples have uniform spherical morphologies and yields as high as ≥16%, with sizes ranging from 0.1 to 6.9 μm. The analysis of yields and functional groups on the surface indicates that these carbonaceous microspheres were formed from the extraction of hydrochar, and it forecasts that this novel hydrothermal method will be effective with different wood feedstocks. Based on the evidence of morphology, yield, elemental composition, and functional groups, an initial mechanism was proposed to explain the production of carbonaceous microspheres from wood sawdust. During the hydrothermal treatment, a liquid-phase precursor formed first from the carbonization of wood sawdust and extraction of hydrochar, together with some decarboxylation reactions, and then carbonaceous microspheres appeared from this precursor and grew during the cooling process. This research opened a new door for the application of wood sawdust, and extended the sources of carbonaceous microspheres greatly.


"Human life" is a most key asset and Life insurance is the most significant type of insurance, which provides monetary fortification to an individual and his relatives at the time of undecided risks or break. 'Life insurance' provides both safeties, fortification to persons too motivates reserves with people. Life Insurance Corporation of India plays essential role in the comfort of human well-being by given that, insurance to more people alongside life risks, such as unsure loss or misfortune. Policyholders are not fully aware about the concept and details relating to e-Insurance services provided by insurance companies. The measurement of policyholder's awareness, technology and service attributes and indentifying the gap becomes more important for E-Insurance.  Policyholders of insurance companies still right of entry services through conformist channels, which provide face to face services.  They do not come forward to use the E-Services offered by insurance industries, because they do not trust the technology and services, at the same time they are afraid of adopting technology innovation given by insurance companies.  Technology services proffer increased elasticity and manage, and set aside time.  Policyholders only made use of the payment through Debit, credit card and net banking.


Aims To assess whether auscultation findings at presentation with bronchiolitis vary with age or viral aetiology. Methods We conducted an opportunistic prospective cohort study of infants who presented to the Emergency Department (ED) with bronchiolitis (diagnosed by ED doctors). Chest auscultation findings in all children were assessed and recorded prospectively at presentation. Viral PCR was carried out on nasopharyngeal aspirates when requested by clinician. Chest auscultation findings were correlated with age and viral aetiology. Our outcome measures were variation of auscultatory signs with age and viral aetiology Results 86 children were recruited to the study. The mean age (±SE) was 22±1.5 weeks and 40% were female. Infants who presented with wheeze were significantly older ((mean ±SE) 26.6±1.9 weeks) than babies who presented without wheeze (17.3±2.1 weeks) (ANOVA, p=0.002). Those who presented without normal auscultation findings were younger than those with wheeze or crackles or both (15.1±2.6 weeks vs 24.4±1.7 weeks) (ANOVA, p=0.006). There was no difference in auscultation findings depending on the virus responsible for bronchiolitis. In 68% of cases (n=34) bronchiolitis was caused by RSV, 32% (n=16) by rhinovirus, 10% (n=5) by adenovirus. Conclusion Chest auscultation findings associated with bronchiolitis vary according to age, with infants older than 24 weeks likely to present with wheeze and those younger than 16 weeks more likely to present without auscultatory chest signs. This is a crucial finding as it has been previously reported that crackles are a consistent feature of bronchiolitis1. Differences in chest signs may reflect differences in pathomechanisms of bronchiolitis and may explain why there are variations in response to medical treatment reported in the literature. Clinicians should be especially vigilant with young infants (<16 weeks) who are relatively more likely to present without any auscultatory chest signs.


Abstract Ingeo® PLA (polylactic acid) knitted fabric was scoured through an exhaust technique. The scouring was carried out with sodium carbonate in the presence of a detergent at various concentrations and temperatures. The scoured fabric was bleached with various oxidative bleaching agents. Bleaching was carried out with hydrogen peroxide, sodium chlorite and sodium hypochlorite. Hydrogen peroxide was applied by exhaust and cold pad batch (CPB) techniques. It was observed that during scouring PLA fabric was degraded at high alkali concentrations and processing temperatures. The scouring temperature above 60ºC proved to be deleterious due to the scouring solution penetrating into the polymer structure and damaged the fiber. Sodium chlorite and sodium hypochlorite caused little damage to the mechanical properties of PLA. Hydrogen peroxide when applied by the CPB technique did not reduce strength appreciably but when applied by the exhaust technique decreased the strength significantly. SEM analysis revealed that hydrogen peroxide caused holes and slit formation in the fiber structure.


: Biochemical and cytochemical latency of alkaline phosphatase activity was demonstrated in periotoneal guinea pig leucocytes. By incorporation of a cell homogenate containing intact granules or a cell sonicate into polyacrylamide films, cytochemical latency up to 75% could be demonstrated.


This paper utilises the occupational attainment approach to investigate immigrant labour market assimilation, complementing other assimilation approaches such as employability, earnings, skills-match and job satisfaction. While immigrants from English speaking backgrounds attain occupations similar to that of the native-born, this is not true for those from non-English speaking backgrounds. Worryingly for the latter, no 'catch-up' over time is evident even when disaggregated to reflect different cultures and backgrounds. Nor is there much evidence that younger arrivals can 'catch-up', despite being immersed in local mores and institutions while undertaking schooling in Australia. Newer cohorts of immigrants (those who arrived between 2000 and 2013) are also more prone to suffering an occupational penalty. We recommend policymakers subsidise bridging courses to aid recognition of overseas-obtained qualifications and encourage immigrants to obtain local qualifications that can complement their overseas-obtained work experience. This will increase their 'Australian-ready' skill-set and occupational attainment in their new host country.


Context. Kepler observations have revealed a class of short-period exoplanets, of which Kepler-1520 b is the prototype, which have comet-like dust tails thought to be the result of small, rocky planets losing mass. The shape and chromaticity of the transits constrain the properties of the dust particles originating from the planet's surface, offering a unique opportunity to probe the composition and geophysics of rocky exoplanets.
Aims. We aim to approximate the average Kepler long-cadence light curve of Kepler-1520 b and investigate how the optical thickness and transit cross section of a general dust tail can affect the observed wavelength dependence and depth of transit light curves.
Methods. We developed a new 3D model that ejects sublimating particles from the planet surface to build up a dust tail, assuming it to be optically thin, and used 3D radiative transfer computations that fully treat scattering using the distribution of hollow spheres (DHS) method, to generate transit light curves between 0.45 and 2.5 μm.
Results. We show that the transit depth is wavelength independent of optically thick tails, potentially explaining why only some observations indicate a wavelength dependence. From the 3D nature of our simulated tails, we show that their transit cross sections are related to the component of particle ejection velocity perpendicular to the planets orbital plane and use this to derive a minimum ejection velocity of 1.2 km s−1. To fit the average transit depth of Kepler-1520 b of 0.87%, we require a high dust mass-loss rate of 7−80 M⊕ Gyr−1 which implies planet lifetimes that may be inconsistent with the observed sample. Therefore, these mass loss rates should be considered to be upper limits.


'Governing: still the strong centre?' looks at the British reputation for strong government, and whether this is the same as effective government. Britain is a traditional example of a 'power-hoarding' polity, and the power of the British government was evident in the response to the financial crisis. However, there are tensions, not least between the priorities of ministers and civil servants. Historically, disagreements between prime ministers and their chancellors have led to breakdowns. Policy formulation is not the same as policy delivery, and governments have struggled to square their departmental structure and the need for collective strategy when actions are required outside the nation state.


The differential susceptibility hypothesis maintains that children have differential susceptibility to rearing environments' influence. Some children are not only more vulnerable than others to the negative effects of adversity, but also disproportionately susceptible to the beneficial effects of supportive and enriching rearing environment. Firstly, this article elaborated the basic theoretical perspectives of differential susceptibility theory and the statistical criteria for establishing differential susceptibility. Secondly, empirical research evidence consistent with differential susceptibility model in recent years was reviewed from behavioral, endophenotypic and genetic factors, namely, how these factors moderated the effects of rearing environments on the children's development as moderators. Finally, the limitations of previous studies and the directions of future researches were summarized.


We propose a new approach to Generative Adversarial Networks (GANs) to achieve an improved performance with additional robustness to its so-called and well-recognized mode collapse. We first proceed by mapping the desired data onto a frame-based space for a sparse representation to lift any limitation of small support features prior to learning the structure. To that end, we start by dividing an image into multiple patches and modifying the role of the generative network from producing an entire image, at once, to creating a sparse representation vector for each image patch. We synthesize an entire image by multiplying generated sparse representations to a pre-trained dictionary and assembling the resulting patches. This approach restricts the output of the generator to a particular structure, obtained by imposing a Union of Subspaces (UoS) model to the original training data, leading to more realistic images, while maintaining a desired diversity. To further regularize GANs in generating high-quality images and to avoid the notorious mode-collapse problem, we introduce a third player in GANs, called reconstructor. This player utilizes an auto-encoding scheme to ensure that first, the input-output relation in the generator is injective and second each real image corresponds to some input noise. We present a number of experiments, where the proposed algorithm shows a remarkably higher inception score compared to the equivalent conventional GANs.


Developed under the auspices of the Partnership for Market Readiness (PMR) and with advice and input from its Baselines Working Group, this document offers guidance and options for the development of emissions baselines, a key component for assessing the emission reductions in in both market and non-market based mechanisms. In the context of this document, a baseline refers to a scenario that describes expected or desired greenhouse gas emissions levels and that can be used as a basis for determining the amount of emissions reductions achieved as the result of a crediting, trading, or other mechanism. This document is divided into two parts. Part one (sections two and three) presents the context for emissions baselines, introduces key concepts and terms, and describes principles, considerations, and potential trade-offs that can inform decisions in the development of robust and transparent baselines. Part two provides a step-by-step description of how 'guidance users', a term we use here for those using this guidance, can develop baselines. Part two begins with a brief description of options for baseline development and approval, and proceeds in six further sections (5-10) to present options to define and update baselines. In the future, this document will be supplemented by additional documents illustrating how the guidance presented here can be applied to specific market or non-market mechanisms involving a variety of economic sectors and GHG emission sources. Finally, this document is intended to be dynamic. Over time, as experience is gained and consensus emerges on best practices, this document may evolve to provide more specific guidelines, where and as appropriate.


Changes in the demographic and socioeconomic structure of the population, such as the decreasing number of school students and the increasing elderly population influence the mobility needs of the society. These mobility needs have in turn, an effect on public transport: e.g. barrier-free access to public transport, simplifying ticketing and funding problems. At the same time, technology boosts all types of industries including services of general interest (SGI) like public transport. Internet, RFID (radio-frequency identification) and NFC (near field communication) are just a few examples which have made possible the introduction of mobile ticketing and electronic tickets in the transportation industry. Electronic ticketing in public transport can have, unlike electronic ticketing in air transport, a significant influence on the tariff system. This research focuses on the identification of weaknesses in current tariff systems and the identification of opportunities for improvement with the implementation of an electronic fare management system (EFM) using the example of the Rhein-Main Verkehrsverbund GmbH (RMV).


Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC

Abnormal PI3K pathway activation plays a major role in cancer, as a result of either RTK activation or somatic mutations of major components of the pathway, including activating point mutations and amplification of the PIK3CA gene as well as loss of negative regulatory proteins such as PTEN. Most of the ATP-competitive PI3K inhibitors currently in clinical development inhibit all class I PI3K isoforms: however, several recent reports support the development of isoform-specific inhibitors. In particular, while PI3Kα specific inhibitors are predicted to inhibit growth of tumors with PIK3CA mutations, PTEN-deficient tumors have been shown to depend on PI3Kβ. In addition, isoform specific PI3K inhibitors may exhibit better safety profiles compared to pan-selective PI3K inhibitors, and thus may be easier to combine with other targeted or cytotoxic therapies. Here we report the discovery of ATP-competitive inhibitors with selectivity for PI3Kα, PI3Kα/mTOR, or PI3Kβ, which were identified and optimized by means of high-throughput screening and medicinal chemistry. These inhibitors exhibit biochemical IC50 values below 100 nM and good selectivity over other PI3K isoforms and a diverse panel of protein kinases. Cellular assays demonstrate that PI3Kα or PI3Kα/mTOR compounds inhibit phosphorylation of targets downstream of PI3K (Akt) and mTOR (S6 and p70S6 kinase) in the PI3Kα-activated MCF7 cell line, and that effects on PI3K pathway readouts are less pronounced in PC3 cells lacking PTEN. In contrast, PI3Kβ compounds potently inhibit phosphorylation of AKT (cellular IC50s < 200 nM) in the PTEN-deficient PC3 tumor cell line, and the most PI3Kβ-selective inhibitors are inactive on AKT phosphorylation in PI3Kα-activated H460 cells. In vivo pharmacodynamic analyses following oral administration of these isoform-selective inhibitors to mice bearing xenografted tumors demonstrate dose-dependent inhibition of phosphorylation of PI3K and mTOR effectors at well-tolerated doses.

These results strongly argue for the development of isoform-selective PI3K inhibitors for the treatment of cancer patients harboring tumors with PTEN- deficient or PI3Kα-activated specific genotypes.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4475.


Developing an athlete's ability to generate power is a key goal of periodisation. This development can be enhanced through manipulation of the force-velocity curve, whereby athletes first increase force output (maximum strength), and then the ability to apply this force under progressively time constrained movement skills specific to their sport. The first part of this article looks at the physiological and biomechanical theories that govern the efficacy of power training, and reviews the effect of strength training and ballistic training on power development. The second part focuses on training prescription.


This paper reviews our first miniature nuclear magnetic resonance (NMR) system originally reported in [1], [2], which, weighing only 2 kg, is 60 times lighter, 40 times smaller, yet 60 times more spin mass sensitive than a 120-kg state-of-the-art commercial benchtop NMR system. The miniaturization was made possible by combining the physics of NMR with a high-performance CMOS radio-frequency integrated circuit. The system is aimed at sensing biomolecules such as cancer marker proteins, and represents a circuit designer's approach to pursue low-cost diagnostics in a portable platform. Our most recent development of even smaller NMR systems [3] will not be reviewed here, as it has yet to be exposed in full through a journal publication first.