Alleile loss of tumor suppressor genes on chromosome 17p has been implicated in the progression of breast cancer. This is in principle detectable by fluorescence in situ hybridization if the loss occurs by deletion. In order to determine if detectable deletions occur in primary breast cancer, we used dual-color hybridization with chromosome 17 pericentromeric and region-specific DNA probes to study 19 primary breast cancers. The copy numbers of 17 centromere and 17pl3.1 se quences were compared with the loss of heterozygosity (LOH) for probe YNZ22 at 17p13.3 detected by restriction fragment length polymorphism. Nine of 11 cases showing LOH also showed the major population of nuclei with a deletion. The remaining two tumors with LOH were trisomie for both the centromere and 17pl3.1 cosmid. In contrast, seven of eight tumors without LOH had no deletions by fluorescence in situ hybridi zation. These data suggest that the dominant mechanism of allelic loss at 17p in breast cancer is a physical deletion and that analysis of deletions by fluorescence in situ hybridization is a rapid and sensitive approach to studying chromosomal aberrations.


We present a computational pipeline for the quantification of peptides and proteins in label-free LC-MS/MS data sets. The pipeline is composed of tools from the OpenMS software framework and is applicable to the processing of large experiments (50+ samples). We describe several enhancements that we have introduced to OpenMS to realize the implementation of this pipeline. They include new algorithms for centroiding of raw data, for feature detection, for the alignment of multiple related measurements, and a new tool for the calculation of peptide and protein abundances. Where possible, we compare the performance of the new algorithms to that of their established counterparts in OpenMS. We validate the pipeline on the basis of two small data sets that provide ground truths for the quantification. There, we also compare our results to those of MaxQuant and Progenesis LC-MS, two popular alternatives for the analysis of label-free data. We then show how our software can be applied to a large heterogeneous data set of 58 LC-MS/MS runs.


Input vector control (IVC) is a popular technique for leakage power reduction. It utilizes the transistor stack effect in CMOS gates by applying a minimum leakage vector (MLV) to the primary inputs of combinational circuits during the standby mode. However, the IVC technique becomes less effective for circuits of large logic depth because the input vector at primary inputs has little impact on leakage of internal gates at high logic levels. In this paper, we propose a technique to overcome this limitation by replacing those internal gates in their worst leakage states by other library gates while maintaining the circuit's correct functionality during the active mode. This modification of the circuit does not require changes of the design flow, but it opens the door for further leakage reduction when the MLV is not effective. We then present a divide-and-conquer approach that integrates gate replacement, an optimal MLV searching algorithm for tree circuits, and a genetic algorithm to connect the tree circuits. Our experimental results on all the MCNC91 benchmark circuits reveal that 1) the gate replacement technique alone can achieve 10% leakage current reduction over the best known IVC methods with no delay penalty and little area increase; 2) the divide-and-conquer approach outperforms the best pure IVC method by 24% and the existing control point insertion method by 12%; and 3) compared with the leakage achieved by optimal MLV in small circuits, the gate replacement heuristic and the divide-and-conquer approach can reduce on average 13% and 17% leakage, respectively.


We consider the construction of guaranteed estimates of linear continuous function als of the unknown solutions and right-hand sides of the Helmholtz equation; the boundary value problems under study are associated with the wave diffraction by a bounded body D situated in a domain Omega is an element of R-n, n = 2, 3, whose boundary partial derivative Omega stretches to infinity (e.g., a wedge or a layer) and Green's function Phi(k) (x, y), (x, y is an element of Omega, x not equal y) corresponding to wave number k with k > 0 and boundary condition (I)k (x, y)vertical bar y is an element of Omega = 0 is known [4]. Here, for a function u(y) defined in (Omega) over bar Bu(y)vertical bar(y is an element of partial derivative Omega) + beta partial derivative u(y)/partial derivative y vertical bar(y is an element of partial derivative Q), alpha, beta = 0, 1, alpha + beta = 1, v is outward normal to aft We assume that right-hand sides of the equations entering the problem statement are not known; the only available information is that they belong to a bounded set of the space of square-integrable functions. In order to solve these estimation problems we need additional data: observations in the form of certain linear transformations of the solution distorted by noise. The latter are realizations of the random fields with the unknown second moment functions belonging to a given bounded set in the appropriate functional space. The approach set forth in and developed in this study allows us to obtain optimal estimates of the unknown solution or righthand sides of the equations and linear functionals, i.e., estimates sought in the class of functionals linear with respect to observations for which the maximal mean-square estimation error taken over all elements belonging to the aforementioned sets takes minimal value. Such estimates are called minimax or guaranteed estimates. We obtain representations for these estimates and estimation errors in terms of solutions to certain integro-differential or integral equations in bounded subdomains of domain Omega \ D.


We developed p-DTS(FBTTh2)2:PC71BM-based small molecule bulk heterojunction solar cells using 1,8-diiodooctane (DIO) and small amounts of PCDTBT polymer. In the film, PCDTBT effectively suppresses the over aggregation of the p-DTS(FBTTh2)2 donor phase and promotes formation of percolating networks between the donor and acceptor phases. Moreover, the portion of p-DTS(FBTTh2)2 crystallites with the face-on orientation in the blend film is significantly increased and phase separation is decreased, which enables efficient charge generation and transport. Consequently, these solar cells consistently exhibit high fill factors and photocurrent densities and high efficiencies in the range 6.68–8.13% regardless of the DIO content (0.4–3 v/v%). In contrast, a large variation was found in the performance of the solar cells with blend films processed with DIO alone, with efficiencies of 2.75–6.68% depending on the DIO content. More importantly, the PCDTBT-processed solar cells exhibit remarkably improved stability under heating and 65 °C/85% RH. Thus, processing photoactive layers utilizing a combination of DIO and PCDTBT is an effective way of preparing promising small molecule solar cells: DIO promotes the crystallinity of the donor phase, and the intermolecular interactions between the polymer and the push–pull moiety in p-DTS(FBTTh2)2 induce distribution of donor crystallites to form percolating networks by suppressing donor over-segregation.


Producing realistic surface water flow patterns can be difficult for hydrologic models when there is insufficient grid resolution as a result of computational constraints or when available digital elevation model (DEM) data are relatively coarse. This technical note describes an algorithm that allows for more realistic overland flow by incorporating subgrid-scale stream location data without increasing grid resolution. The algorithm takes stream location data from the National Hydrography Dataset (NHD), maps it to the hydrologic model horizontal grid coordinates, and produces a list of ordered points along the stream. Because the algorithm uses indexes to efficiently order points along the stream, large-scale meanders require special treatment, whereas small (grid) scale meanders are explicitly included in the algorithm logic. Slopes are ensured to be continuous along the stream's path as defined on the model grid, distinguishing this approach from traditional "stream burning" algorithms. Stream coordinates on the model grid are calculated along with corresponding elevation and slope values so that the stream can then be integrated into the DEM if desired. The algorithm's flow routing capabilities are demonstrated by using an integrated surface water-groundwater model, ParFlow, under rain and recession conditions. This case study is performed by using the real topography of Owens Valley, California, and NHD flowline data for the Owens River. An approach using a DEM that has undergone standard processing to fill sinks and a typical "stream burning" approach [similar to those often used in geographic information system (GIS) applications] fail to route flow out of the flood plain in ParFlow's overland flow model that partitions and routes topography-driven flow along adjacent cells in one of four cardinal directions. In contrast, this approach, with the river elevations and continuous slopes integrated into the DEM, routes water to the river and out of the catchment, creating more realistic surface flow patterns in the region. Although the method is applied here to address problems associated with a flat flood plain, it may also be applied to any area in which stream flow is discontinuous because of insufficient resolution of topography on a model grid. DOI: 10.1061/(ASCE)HE.1943-5584.0000340. (C) 2011 American Society of Civil Engineers.


The typical full-time employee in Australia works 70 minutes of unpaid overtime a day. This equates to 33 eight-hour days per year, or six and a half standard working weeks. Something for nothing - unpaid overtime in Australia examines the nature, extent and consequences of Australia's heavy reliance on unpaid overtime. Across the workforce, the 2.14 billion hours of unpaid overtime worked per year is a $72 billion gift to employers, equivalent to 6 per cent of all economic activity in Australia.


Introduction: The use of antimicrobial properties of medicinal plants can solve common problems in the use of antibiotics. The aim of this study was to evaluate the antibacterial properties of the Mentha longifolia essence on bacteria isolated from hospital infections. Materials & methods: In this experimental study the Mentha longifolia essence was extracted using Clevenger device and its antimicrobial activity agar disk diffusion method for determination of bacterial sensitivity and dilution method for determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was used separately. Findings: The results of bacterial sensitivity test in the case of the standard antibiotics of tetracycline, amikacine, and also disks impregnated with Mentha longifolia essence showed that the diameter of the zone of inhibition caused by the compound being tested on four strains of isolates was far larger and this difference about Escherichia coli and Klebsiella isolates was significant (p less-than 0.05). Also the results of MIC and MBC tests indicated that the inhibition of bacterial growth by Mentha longifolia essence had a direct relationship with the amount of available Mentha longifolia essence in the dilution and increasing of Mentha longifolia essence in each dilution reduced the number of cultured bacterial colonies and no bacterial growth was observed in the dilution equivalent to MBC of Mentha longifolia essence. Discussion & conclusions: The results suggest that Mentha longifolia essence can be used as a source of cheap and accessible replacing chemical drugs to treat some bacterial infections.


Abstract. Nitrogen deposition in remote areas has increased, but the effect on ecosystems is still poorly understood. For aquatic systems, knowledge of the main processes driving the observed variation is limited, as is knowledge of how changes in nitrogen supply affect lake biogeochemical and food web processes. Differences in dissolved inorganic nitrogen (DIN) between lakes cannot be understood without considering catchment characteristics. In mountains, catchment features (e.g., thermal conditions, land cover) vary considerably with elevation. The isotopic composition of nitrogen (δ15N) is increasingly used to study aquatic ecosystem dynamics. Here we explore the variability of δ15N in DIN in high mountain lakes and show that environmental conditions that change with altitude can affect the isotopic ratio. We measured ammonium and nitrate δ15N values in atmospheric deposition, epilimnetic water, deep chlorophyll maximum water (DCMW) and sediment pore water (SPW) from eight mountain lakes in the Pyrenees, both above and below the treeline. Lakes showed relatively uniform δ15N-NH4+ values in SPW (2.2±1.6‰), with no variation corresponding to catchment or lake characteristics. We suggest that organic matter diagenesis under similar sediment conditions is responsible for the low variation between the lakes. In the water column, the range of δ15N values was larger for ammonium (−9.4‰ to 7.4‰) than for nitrate (−11.4‰ to −3.4‰), as a result of higher variation both between and within lakes (epilimnetic vs. DCM water). For both compounds part of the difference correlated with altitude or catchment features (e.g., scree proportion). Based on concentration, chemical and isotopic tendencies, we suggest that patterns arise from the distinct relative contributions of two types of water flow paths to the lakes: one from snowpack melting, with little soil interaction; and another highly influenced by soil conditions. The snow-type flow path contributes low DIN concentrations depleted in 15N, whereas the soil-type flow path contributes high nitrate concentrations with higher δ15N. The proportion of these two types of source correlates with average catchment features when there is extensive snow cover during spring and early summer and probably becomes more dependent on local characteristics around the lake as summer advances. Lake depth and pore water ammonium concentrations, among other features, introduce secondary variation. In the context of nitrogen deposition studies, lakes with higher snow-type influence will probably register changes in N deposition and pollution sources better, whereas lakes with higher soil-type influence may reflect long-term effects of vegetation and soil dynamics.


Updating production software is a process that may require dozens, if not hundreds, of steps. These include creating and testing new code, building new binaries and packages, associating the packages with a versioned release, updating the jobs in production datacenters, possibly modifying database schemata, and testing and verifying the results. There are boxes to check and approvals to seek, and the more automated the process, the easier it becomes. When releases can be made faster, it is possible to release more often, and, organizationally, one becomes less afraid to "release early, release often". And that's what we describe in this article—making rollouts as easy and as automated as possible. When a "green" condition is detected, we can more quickly perform a new rollout. Humans are still needed somewhere in the loop, but we strive to reduce the purely mechanical toil they need to perform.


Background: The management of children's anxiety in dental offices is still a challenge for the treatment team. The most important factors which affect children's dental anxiety are the clinician-related factors and the physical factors of the dental operatory. Color is an environmental factor whose relationship with the perceptive and emotional factors of children has been reported. On the other hand, distraction is essential factors in a treatment environment that can be used to manage children's anxiety. Materials and Methods: In this randomized clinical trial study, from 132 6 to 9 years of age children, 52.3% were male, and 47.7% were female, with a mean age of 7.45 ± 1.1 years. The children's anxiety levels were determined using the Venham Picture Test and pulse oximetry before and after the administration of local anesthesia. The children were randomly assigned to two groups (n = 66): Group 1, music, and Group 2, animated cartoons. The data were analyzed with SPSS 25, using descriptive statistics and the statistical tests consisting of one-way analysis of variance (ANOVA), t-test, and repeated-measures ANOVA, followed by Tukey honestly significant difference tests. Statistical significance was set at P < 0.05. Results: The anxiety levels were the lowest in the blue and pink environments and the highest in the black and red. Anxiety levels between different colors in terms of physiologic markers and the questionnaire in each distraction technique at different intervals was significantly different. Conclusion: The use of blue, pink, green, and yellow for dentists' attire, and the interior design of the dental operatory decreased the child patients' anxiety.


The wood-chipping process is affected by several factors, notably chipper settings and wood characteristics. It is often difficult to test all of these factors in a full factorial experimental plan, due to the large number of trials required. On the other hand, a screening design of the experiment makes it possible to manage a large number of variables in a small number of trials. Hence, this approach is used to test six factors, in order to optimize the productivity and chip quality of a drum wood-chipper. These factors are: feeding speed, screen size, PTO-speed, wood species, wood moisture content, and wood diameter. Productivity was significantly affected by screen size, while chip quality was related to feeding speed, screen size, PTO-speed, and wood species. The results suggest that the optimal configuration can be achieved by adjusting feeding speed, the PTO-speed, and the wood species, as these settings maximize chip quality. Screen size requires further analysis, as larger sizes increase productivity but reduce quality, while the opposite is true for smaller sizes. Thus, the optimal screen size requires a consideration of costs and benefits that may change according to the retail price of premium and regular wood chips, and production costs.


In this paper the results of investigations of double-base propellants covered by inhibitors are presented. The method of Real Time Roentgenoscopy (RTR) has been applied to the studies. This method enables the observation in the real time the burning process of the propellant grain being located in subscale rocket motor. Performed tests allowed to confirm the influence on the burning process of solid propellants are having defects of different kind of the inhibitors. Among the effects, the acceleration of the burning process of propellants was observed as a result of growing the burning surface. This effect resulted from improper adhering of the inhibitors to the surface of propellant or the discontinuity of the structure of the inhibitor. The results obtained in these experiments allow in the simple way to assess the practical suitability of the new kind of inhibitors. The applied testing method allows also to get information about effectiveness of inhibitor functioning of rocket propellants after the long term storage.


Breast angiosarcomas represent the main histologic subtype of all breast sarcomas and they account for < 1% of all soft tissue tumours. Angiosarcomas arise from vascular endothelium and can develop de novo (primary angiosarcoma) or as a consequence of radiotherapy or chronic lymphedema after axillary dissection – Stewart-Trevers syndrome. Estimated incidence of postradiation angiosarcoma is 0.05 – 0.5%. Postradiation angiosarcoma typically occurs in older women (60-70 years of age) and it is a rare, aggressive tumour with a poor prognosis characterized by a high rate of local recurrence. Herein, we present a case of recurrent postradiation breast angiosarcoma with metastasis in contralateral breast.


Health care delivery is no longer a simple process of examining the patient and giving him a prescription. Over the years there has been rapid expansion in the various branches of health care services. As part of this expansion process and explosion of scientific medical knowledge, laboratory diagnosis has gained tremendous importance in today's practice. Especially in our country since the beginning of 80's we have been witnessing significant growth in laboratory services. Through quality management process the laboratory can ensure that the result being issued by the laboratory is reliable to allow decisions to be taken with confidence. Quality control and quality assurance are parts of quality management. Quality control is focused on fulfilling quality requirements, whereas quality assurance is focused on providing confidence that quality requirements are fulfilled. By utilizing quality control practices, a laboratory is able to find and correct flaws in the analytical processes of a lab before potentially incorrect patient results are released. Pulse Vol.8 January-December 2015 p.62-65


Flexibility is one of today's key business requirements. Transferring flexibility to the enterprise means that the enterprise needs to be able to operate in different ways. Classically this should be realized by a high degree of adaptability. However, you could also foresee and forethink possible ways of doing business and build your company accordingly. We call this state, where an enterprise is constructed in a way that it is able to seamlessly enter collaborations, Enterprise Interoperability. In this paper, we conceive the concept of Enterprise Interoperability. Furthermore, we depict its characteristics and decompose it into partial areas of interoperability that affects enterprises. Finally, we conclude in a framework that comprises and captures Enterprise Interoperability.


China's economy has been growing rapidly since the late 1970s and is expected to maintain this momentum in the foreseeable future. Coupled with the biggest population in the world, there is tremendous growth potential for China's capital markets and financial services industry, both vital to the continued development of the economy. The contributors present research on all facets of China's markets including: stock and bond markets; futures and over-the-counter markets; regulatory issues; and the development and roles of financial institutions such as brokerage firms, banks and insurance companies. Also addressed are the recent performance of equity markets, the emergence of small and medium enterprises, and the state banks' bids to be listed in overseas stock exchanges. Taken together, the book sheds a welcome light on China's overall economic growth.


He journeyed into space to find a new world, only to find a mirror image of his own. He fell in love with a woman from that other world. His inner voice, his deepest impulse, told him to bring her back to Earth. When she came, she brought gifts. He thrilled with inner excitement. Her precious gifts could mean no-limit happiness for all.


The social amoeba, Dictyostelium discoideum, has been commonly used to investigate cell motility, signal transduction, cell type differentiation and development. With the recent completion of the genome and the increasing number of experimental tools available for the organism, it has now become an attractive model for examining some well-defined biomedical questions.

Keywords:

amoeba;
cancer;
medical research;
model systems;
neuroprotection;
pharmacogenetics


This paper analyses the EU's response to the Eurozone sovereign debt crisis. It examines the background to the crisis and how the threat to the single currency taxed the decision-making capacity of the EU, while also exposing long-standing fears about an absence of democratic legitimacy. In particular, the paper reflects on the democratic credentials of the EU response, examining the important role that continues to be played by democratic politics at the national level. This role will continue to be important since this is the level at which enforcement of debt brakes will occur. In addition, the analysis highlights the political fault lines that became apparent, notably the North/South split and the separation between countries inside and outside the Eurozone. Consequently, the paper concludes that these fault lines will characterize the future of integration, thereby complicating the search for a consensus on how to complete the banking union or pursue a free trade deal with the US.


Drug treatment and vaccination remain the main strategies to control tuberculosis (TB), which is the leading infectious cause of death globally. Lengthy treatment is often cited as a major obstacle towards improved control of TB. It has been proposed that a combination of TB vaccination with pharmacological treatment, termed therapeutic vaccination, may provide a greater therapeutic value. Several therapeutic TB vaccine candidates have been developed and are currently progressing in the pipeline. We hypothesise that an ex-vivo mycobacterial growth inhibition assay (MGIA) can be implemented to investigate and accelerate development of therapeutic vaccination strategies for TB, in the context of both human clinical and animal murine studies. This thesis describes for the first time, the combined effect of immunoprophylaxis by routine vaccination with Bacillus Calmette–Guerin (BCG) and chemotherapy using the ex vivo immune assay platform. The first research chapter of the thesis elaborates a proofof- principle study investigating the combined effect between historical BCG vaccination and two major first-line TB drugs (isoniazid and rifampicin), which is considered essential to further expedite the development of therapeutic vaccination strategies for TB. The second part of the thesis describes a study in which immunisation of mice with RUTI, a novel therapeutic TB vaccine candidate, was shown to enhance inhibition of mycobacterial growth ex vivo by inducing a shift of monocyte phenotype. We also investigated the effects of RUTI and BCG vaccination towards ex vivo drug-mediated killing in mice. The third research part of the thesis discusses the impact of individual-level factors on ex-vivo mycobacterial growth inhibition, specifically the influence of immune cell phenotype, cytomegalovirus-specific response and sex on immunity following BCG vaccination in humans. In the absence of an immune correlate of protection following TB vaccination, implementation of the ex vivo MGIA assay could be beneficial to screen TB vaccine candidates at early phases in order to prioritise which candidates should be tested with the available funding and field sites. Collectively, our findings support the implementation of MGIA as an effort to accelerate the development of therapeutic TB vaccines.


This paper considers the problem of spatiotemporal object-centric reasoning in videos. Central to our approach is the notion of object permanence, i.e., the ability to reason about the location of objects as they move through the video while being occluded, contained or carried by other objects. Existing deep learning based approaches often suffer from spatiotemporal biases when applied to video reasoning problems. We propose Hopper, which uses a Multi-hop Transformer for reasoning object permanence in videos. Given a video and a localization query, Hopper reasons over image and object tracks to automatically hop over critical frames in an iterative fashion to predict the final position of the object of interest. We demonstrate the effectiveness of using a contrastive loss to reduce spatiotemporal biases. We evaluate over CATER dataset and find that Hopper achieves 73.2% Top-1 accuracy using just 1 FPS by hopping through just a few critical frames. We also demonstrate Hopper can perform long-term reasoning by building a CATER-h dataset that requires multi-step reasoning to localize objects of interest correctly.


Several proteins of Clostridium thermocellum possess a C-terminal triplicated sequence related to bacterial cell surface proteins. This sequence was named the SLH domain (for S-layer homology), and it was proposed that it might serve to anchor proteins to the cell surface (A. Lupas, H. Engelhardt, J. Peters, U. Santarius, S. Volker, and W. Baumeister, J. Bacteriol. 176:1224-1233, 1994). This hypothesis was investigated by using the SLH-containing protein ORF1p from C. thermocellum as a model. Subcellular fractionation, immunoblotting, and electron microscopy of immunocytochemically labeled cells indicated that ORF1p was located on the surface of C. thermocellum. To detect C. thermocellum components interacting with the SLH domains of ORF1p, a probe was constructed by grafting these domains on the C terminus of the MalE protein of Escherichia coli. The SLH domains conferred on the chimeric protein (MalE-ORF1p-C) the ability to bind noncovalently to the peptidoglycan of C. thermocellum. In addition, 125I-labeled MalE-ORF1p-C was shown to bind to SLH-bearing proteins transferred onto nitrocellulose, and to a 26- to 28-kDa component of the cell envelope. These results agree with the hypothesis that SLH domains contribute to the binding of exocellular proteins to the cell surface of bacteria. The gene carrying ORF1 and its product, ORF1p, are renamed olpB and OlpB (for outer layer protein B), respectively.


Today, Unmanned Aerial Vehicles (UAVs) have gained considerable importance, especially in the defense industry. Thanks to the cameras placed on these vehicles, a certain area can be explored for safety reasons. Various image processing techniques are used for this. Image mosaicing is one of these techniques. In this study, the effects of SIFT(Scale-Invariant Feature Transform), SURF(Speeded Up Robust Features), FAST(Features from Accelerated Segment Test) and Harris corner detector methods used for image mosaicing on images taken from unmanned aerial vehicles are tested and compared.


In an endeavour to ascertain the interplay of factors involving chlorine dose, turbidity and flow capacity on microbial quality of drinking water in small water treatment plants (SWTPs), data from a previous study were analysed.
The findings showed that most of the SWTPs were not producing water of safe microbial quality. Fifty one percent (51%) and seventy three (73%) of the SWTPs were below the stipulated limits for residual chlorine in final water and water at the point of use respectively. Current flow capacity was a major determinant of the microbial water quality indicators but no association was found between the dose of chlorine used for water treatment and the microbial water quality indicators. However, a combination of the amount of chlorine dose used up during treatment, flow capacity and change in turbidity contributed to about 65% of the amount of heterotrophic plate counts removed from raw water. Current flow capacity contributed less than 14% of the variation in chlorine dose used in water treatment at the plants. Turbidity tended to correlate and contribute more to the prediction of total coliform counts while faecal coliform counts were determined by current flow capacity and conductivity. Treatment plants with current flow capacity of over 50 Ml / d tended to be more efficient in heterotrophic plate count removal.
In conclusion, this study noted that most of the SWTPs were using a chlorine dosage that was below the amount required by their respective current flow capacity; possible micro-organism resistance to chlorine and the significant effect of the level of turbidity on the microbial quality of treated water.


Animals play an important role in the seed dispersal of many plants. It is increasingly recognized, however, that the actions of a single disperser rarely determine a seed's fate and final location; rather, multiple abiotic or animal dispersal vectors are involved. Some carnivores act as secondary dispersers by preying on primary seed dispersers or seed predators, inadvertently consuming seeds contained in their prey's digestive tracts and later depositing viable seeds, a process known as diploendozoochory. Carnivores occupy an array of ecological niches and thus range broadly on the landscape. Consequently, secondary seed dispersal by carnivores could have important consequences for plant dispersal outcomes, with implications for ecosystem functioning under a changing climate and across disturbed landscapes where dispersal may be otherwise limited. For example, trophic downgrading through the loss of carnivores may reduce or eliminate diploendozoochory and thus compromise population connectivity for lower trophic levels. We review the literature on diploendozoochory and conclude that the ecological impact of a secondary vs. primary seed disperser depends on the relative dispersal distances, germination success, and the proportion of seeds exposed to secondary dispersal by carnivores. None of the studies up to present day have been able to rigorously assess the ecological significance of this process. We provide a framework of the components that determine the significance of diploendozoochory across systems and identify the components that must be addressed in future studies attempting to assess the ecological importance of diploendozoochory.


In models of stock returns where investors with extrapolative beliefs on future stocks (e.g., Barberis and Shleifer (2003)), price momentum and the value premium both arise naturally. The key insight from these models is that, the strength and timing of these cross- sectional return anomalies will be conditional on the degree of extrapolative bias. More specifically, higher (lower) degree of over-extrapolation leading to stronger value premium (momentum). Using the time-series variation in the degree of over-extrapolation documented in Cassella and Gulen (2018), I first directly test the hypothesis that both value and momentum stem from over-extrapolation in financial markets. I find that the average momentum return is 1.00% (0.10%) per month when the degree of over-extrapolation is low (high), whereas the average value premium is 0.51% (1.29%) per month following low (high) levels of over- extrapolation. Furthermore, I extend the model in Barberis and Shleifer (2003) by having both within- equity extrapolators and across asset-class extrapolator. The extension is based on the idea that when extrapolators move capital in and out of the equity market, they disproportionately buy growth stocks in good times and sell value stocks in bad times. The model predicts that the cross-sectional value premium should be stronger following states of large market- wide over- or undervaluation due to additional extrapolative demand to buy or sell. This prediction is tested empirically and I find strong support for it. The value premium is 3.42% per month following market-wide undervaluation and 1.70% per month following market overvaluation. In the remainder 60% to 80% of the sample, when the market is neither significantly over or under-valued, there is no significant value premium in a monthly horizon and the value premium is only 0.54% per month in an annual horizon. I provide some suggestive evidence regarding portfolio return dynamics, investor expectation errors and fund flows that supports the extrapolative demand channel. Overall, this work examines more closely at the effect of extrapolative beliefs on the cross-section of asset prices and offers some support for extrapolation-based asset-pricing theories.


Surgical treatment for intra-abdominal/retroperitoneal desmoid-type fibromatosis (IA/RPDF) is still controversial. Studies regarding en bloc resection in IA/RPDF with adjacent organ involvement are scanty. This study aims to evaluate the safety and effectiveness of en bloc resection in IA/RPDF with adjacent organ involvement. This retrospective clinical study included 21 patients who were diagnosed with IA/RPDF and underwent tumor resection at a single center between March 2013 and June 2018. All patients included in the study underwent surgery with curative intent, and IA/RPDF with adhesive organs was removed en bloc. The safety of surgical treatment was verified by the analysis of intraoperative bleeding, postoperative morbidity and perioperative mortality. The efficacy of surgical treatment was evaluated based on the status of tumor infiltration of adjacent organs and patient follow-up results. Complete macroscopic (R0 or R1) resection was achieved in all cases. A median of 2 (range, 1-7) organs were resected. The median operating time was 300 (90-650) minutes. The median intraoperative bleeding was 300 (20-4,500) milliliters. For postoperative pathological diagnosis at our center, tumor infiltrated at least one organ in each patient. Infiltration was noted in 45 resected organs (45/57, 78.9%). Grade III-V postoperative morbidity developed in one patient (4.8%). During the follow-up, one patient developed local recurrence. No DF-related death was noted during the follow-up. The 3-year disease-free survival rate was 94.1% (95% confidence interval: 83.6-100%). Therefore, en bloc resection of the tumor and involved adjacent organs is a safe and effective treatment modality for IA/RPDF.


Abstract:Where does Spain fit on the post-revolutionary map? Contemporary Spain remains marginalized at the periphery of European civilization, as if deemed not yet ready, like its colonies, to put Enlightenment ideals into practice. Chateaubriand perpetuates this remoteness of the Iberian Peninsula by setting an interracial, interfaith romance, Les Aventures du dernier Abencérage, in the distant past of Moorish Spain, when, in fact, interracial romances prompted much contemporary debate in the American colonies. This article analyzes the contrast between an idealized vision of aristocratic liberty and equality set in 1526 and the pragmatic politics of liberal imperialism when it came to Spain's future and the fate of its Spanish colonies. The first part interprets the story against the backdrop of its writing in 1810 shortly after Napoleon's invasion of Spain. The second part connects the novella's 1826 publication with Chateaubriand's political role when, named Minister of Foreign Affairs, he instigated a military intervention in Spain in 1823.


Legal rules do more than provide incentives; they change people. When preferences and norms are endogenously determined via a process of imitation and learning, legal rules, by affecting the market outcome, may affect the dynamics of preference formation. Analyzing the effect of different legal rules should, therefore, go beyond the analysis of the incentives they provide. It should also include an analysis of their effect on the distribution of preferences and norms of behavior. We illustrate this claim by considering a simple market game in which individuals may have preferences that include fairness concerns. We show that different legal rules change not only the pattern of trade in a market game, but also the individuals' fairness concern. That is, different rules may eventually make individuals care more (or less) about a fair outcome. Specifically, our model suggests that enhanced remedies for breach of contract may reduce equilibrium preferences for fairness.


Purpose - In recent years many organizations have implemented performance management because this technique leads to better organizational results as reported in many articles and case studies. However, often the reported improvement relates to qualitative performance and there is little solid empirical evidence of the actual effects performance management has on the quantitative results of organizations. This article aims to describe the results of a study that explored the quantitative impact of performance management on the results of a non-profit organization. Design/methodology/approach - Quantitative performance data of the organization, before and after the introduction of performance management, were collected and linked to key activities and events that occurred in the organization during and after the implementation. Findings - The research shows that several key activities related to the introduction of performance management have an impact on the results of an organization although not always in an expected positive way. Research limitations/implications - A research limitation is that it is always difficult to isolate the effects of a particular event on the overall results of an organization. Although the effects of other events have been taken into account, it cannot be ruled out that unlisted events and factors are in play. Practical implications - The results support managers who want to introduce performance management to improve the results of their non-profit organisation. At the same time, the research indicates that introducing and using performance management needs continuous attention of management in order to become and stay successful in the long run. Originality/value - This article contributes to the literature as it is one of the few longitudinal research studies into the effects of performance management, specifically in non-profit organizations.


For over the last two decades biotechnology and its techniques in various fields have attracted much media attention. All over the globe, syllabi have been directed to teach biotechnology and biotechnological techniques to undergraduate and post graduate students in almost all public funded and private universities. Biotechnology is beset with many ethical and social controversies. Earlier, there was much hue and cry at the introduction of 'Genetically Modified foods' and 'Bt Cotton' and even a muchhyped project like the 'Human Genome Project' did not achieve its pace because of ethical concerns. Social scientists started conducting opinion research on such 'modern technologies' before giving concrete shape to their adoption. In more recent years the issue of public perception, attitude and understanding towards science, in general, and towards specific technologies like genetic engineering, cloning, genetically modified foods, biotechnology and even nuclear technology, is increasing at a fast pace all over the world. One such study has been carried out registering the perceptions of undergraduate students who are studying biology subject in India and Tanzania, on biotechnology and cloning. The survey was conducted through a questionnaire (partially structured). This analysis revealed that students favoured production of genetically modified foods but they responded that 'biotechnological experiments' should be conducted on plants rather than animals. Furthermore, the students were strongly supportive of medical applications of biotechnology to avoid genetic diseases. Students from the two countries gave similar responses on some issues but differed on other issues. It is worth mentioning here that, though these perception survey studies are indicative yet these are quite important in framing policies related to the introduction of new technologies and framing strategies for communication/ popularisation of these issues among the general public.


This essay is written to present a prospective stance on how learning analytics, as a core evaluative approach, must help instructors uncover the important trends and evidence of quality learner data in the online course. A critique is presented of strategic and tactical issues of learning analytics. The approach to the critique is taken through the lens of questioning the current status of applying learning analytics to online courses. The goal of the discussion is twofold: (1) to inform online learning practitioners (e.g., instructors and administrators) of the potential of learning analytics in online courses and (2) to broaden discussion in the research community about the advancement of learning analytics in online learning. In recognizing the full potential of formalizing big data in online coures, the community must address this issue also in the context of the potentially "harmful" application of learning analytics.


This paper addresses the role of Artificial Intelligence (AI) in a variety of game genres. Every game aims to entertain (though educational games have secondary objectives). Each genre approaches entertainment in a unique way. We explore the methods used to draw the game player's attention. We then consider how the AI interacts with the player to promote both entertainment and an interactive environment. We also consider some of the techniques that will shape tomorrow's games. Included are opponent strategies, interactive environments, and multiagent systems (MAS). While different, each approach can aid in creating more immersive and challenging gaming experiences. Our goal is to create an AI opponent that is not only a capable opponent but also reacts to and improves with player. We consider what elements are necessary to create an opponent capable of creative use of its environment. The game environment, too, is extremely important in creating an immersive experience. Finally, we consider the possibility of creating games that include emergent behavior and multiagent systems.


A 64-year-old man was referred to our hospital for treatment of a cerebral aneurysm that was incidentally found. The aneurysm was 7 mm in size and located on the left anterior communicating artery. Using a balloon assisted technique, we performed coil embolization. During the second coil insertion, the first coil was dislodged into the anterior communicating artery. We attempted coil retrieval using a snare, which was unsuccessful. We applied a direct aspiration first pass technique (ADAPT) and advanced a Penumbra 4MAX immediately proximal to the dislodged coil; the dislodged coil was then successfully retrieved. ADAPT is a simple procedure for retrieval of a detached coil, and it can be used as an alternative to the snare technique.


The question of whether a plausible case for native title in radio spectrum exists in Australia is not yet fully understood. The relevant literature is lacking in both breadth and depth. To date, no case has been developed and tested in the courts. Subsequently this thesis examined whether a plausible case could be constructed that demonstrates native title in radio spectrum in Australia. This thesis proposed that native title exists in radio spectrum, but is yet to be proven in Australian law; particularly when considerations are given to impediments as represented by the current government and by the current structure of native title legislation and its processes. Since there was a scarcity of available literature on the concept of native title in radio spectrum, and the fact that there was no relevant precedent that existed in Australian law, a comparative study of Maori rights in radio spectrum in New Zealand was undertaken to a) provide both an initial reference point for Indigenous Australians to consider if they were to pursue native title in radio spectrum, and b) to gauge the applicability of the Maori experience to the legislative conditions currently facing Indigenous Australians who might wish to express native title rights in radio spectrum. Eventually, the findings of this thesis support the existence of native title in radio spectrum; however, this cannot be expressed at the present time. Consequently, Indigenous Australians are strongly encouraged to pursue this issue with an enduring view to achieve economic and wider parity enjoyed by other Australians.


Different approaches and tools are required in Cultural Heritage Documentation to deal with the complexity of monuments and sites. The documentation process has strongly changed in the last few years, always driven by technology. Accurate documentation is closely relied to advances of technology (imaging sensors, high speed scanning, automation in recording and processing data) for the purposes of conservation works, management, appraisal, assessment of the structural condition, archiving, publication and research (Patias et al., 2008). We want to focus in this paper on the recording aspects of cultural heritage documentation, especially the generation of geometric and photorealistic 3D models for accurate reconstruction and visualization purposes. The selected approaches are based on the combination of photogrammetric dense matching and Terrestrial Laser Scanning (TLS) techniques. Both techniques have pros and cons and recent advances have changed the way of the recording approach. The choice of the best workflow relies on the site configuration, the performances of the sensors, and criteria as geometry, accuracy, resolution, georeferencing, texture, and of course processing time. TLS techniques (time of flight or phase shift systems) are widely used for recording large and complex objects and sites. Point cloud generation from images by dense stereo or multi-view matching can be used as an alternative or as a complementary method to TLS. Compared to TLS, the photogrammetric solution is a low cost one, as the acquisition system is limited to a high-performance digital camera and a few accessories only. Indeed, the stereo or multi-view matching process offers a cheap, flexible and accurate solution to get 3D point clouds. Moreover, the captured images might also be used for models texturing. Several software packages are available, whether web-based, open source or commercial. The main advantage of this photogrammetric or computer vision based technology is to get at the same time a point cloud (the resolution depends on the size of the pixel on the object), and therefore an accurate meshed object with its texture. After matching and processing steps, we can use the resulting data in much the same way as a TLS point cloud, but in addition with radiometric information for textures. The discussion in this paper reviews recording and important processing steps as geo-referencing and data merging, the essential assessment of the results, and examples of deliverables from projects of the Photogrammetry and Geomatics Group (INSA Strasbourg, France).


Abstract Evidence of reflective awareness and metacognitive monitoring during REM sleep dreaming poses a significant challenge to the commonly held view of dream cognition as necessarily deficient relative to waking cognition. To date, dream metacognition has not received the theoretical or experimental attention it deserves. As a result, discussions of dream cognition have been underrepresented in theoretical accounts of consciousness. This paper argues for using a converging measures approach to investigate the range and limits of cognition and metacognition across the sleep–wakefulness cycle. The paradigm developed by LaBerge and his colleagues to study "lucid-control" dreaming offers one such framework for relating phenomenological, cognitive, and physiological measures. In a lucid-control dream, the dreamer is both aware that the experimental context is a dream (lucidity) and has the ability to intentionally regulate aspects of the dream (control). Subjects can make patterns of deliberate eye movements to signal from the dream and thus index significant events such as the time of lucidity onset and the completion of previously agreed-upon tasks in the dream. Lucid dreaming and other examples of reflective awareness during dreaming have important implications for models of human cognition. The existence of these phenomena raises fundamental questions about current assumptions regarding "state" constraints on consciousness and cognition (i.e., the notion that dreaming involves exclusively nonconscious processing while waking involves conscious processing).


A growing scientific literature supports the existence of placebo effects from a wide range of health interventions and for a range of medical conditions. This Article reviews this literature, examines the implications for law and policy, and suggests future areas for research on placebo effects. In particular, it makes the case for altering the drug approval process to account for, if not credit, placebo effects. It recommends that evidence of placebo effects be permitted as a defense in cases alleging violations of informed consent or false advertising. Finally, it finds that tort law already has doctrines such as joint and several liability to account for placebo effects. Future research on placebo effects should focus on whether awareness of placebo effects can disable these effects and whether subjects can control their own placebo effects.


Abstract We describe a method for rapidly creating language proficiency assessments, and provide experimental evidence that such tests can be valid, reliable, and secure. Our approach is the first to use machine learning and natural language processing to induce proficiency scales based on a given standard, and then use linguistic models to estimate item difficulty directly for computer-adaptive testing. This alleviates the need for expensive pilot testing with human subjects. We used these methods to develop an online proficiency exam called the Duolingo English Test, and demonstrate that its scores align significantly with other high-stakes English assessments. Furthermore, our approach produces test scores that are highly reliable, while generating item banks large enough to satisfy security requirements.


The Wnt/β-catenin signaling pathway plays pivotal roles in axis formation during embryogenesis and in adult tissue homeostasis. Glutathione peroxidase 4 (GPX4) is a selenoenzyme and participates in the reduction of peroxides. Its synthesis depends on the availability of the element selenium. However, the roles of GPX4 in vertebrate embryonic development and underlying mechanisms are largely unknown. Here, we show that maternal loss of zebrafish gpx4b promotes embryonic dorsal organizer formation, whereas overexpression of gpx4b inhibits the development of the dorsal organizer. Depletion of human GPX4 and zebrafish gpx4b (GPX4/gpx4b) increases, while GPX4/gpx4b overexpression decreases, Wnt/β-catenin signaling in vivo and in vitro. Functional and epistatic studies showed that GPX4 functions at the Tcf/Lef level, independently of selenocysteine activation. Mechanistically, GPX4 interacts with Tcf/Lefs and inhibits Wnt activity by preventing the binding of Tcf/Lefs to the promoters of Wnt target genes, resulting in inhibitory action in the presence of Wnt/β-catenin signaling. Our findings unravel GPX4 as a suppressor of Wnt/β-catenin signals, suggesting a possible relationship between the Wnt/β-catenin pathway and selenium via the association of Tcf/Lef family proteins with GPX4. Summary: The selenoenzyme Gpx4 regulates Wnt signaling and hence zebrafish axis formation by preventing the binding of Tcf/Lefs to the promoters of Wnt target genes, independently of selenocysteine activation.


The aim of this survey was to investigate the characteristics of the Hovawart breed in a sample of dogs bred in Italy. A questionnaire was developed and piloted on Hovawart owners. The questionnaire included general information about the owners and the dogs, with more detailed questions on the behaviours exhibited by the dogs. One hundred questionnaires were received and processed, including 59 female and 41 male dogs. The results revealed that the main activities for Hovawart dogs were shows (57%), followed by rescue, utility, and defence. No dogs showed aggressive behaviour towards their owners, however 50% and 48% showed aggressive behaviour towards other animals due to competition or hierarchical reasons and towards unfamiliar people in self-defence. Only 28% of the dogs ever showed wariness, however a large number of owners did not refer to any nuisance behaviour in relation to their dog.The majority of owners did not mention any health problems. Cancer and hip dysplasia were the problems most complained.


Abstract This paper evaluates both the ideas and empirical evidence pertaining to the control of species density in herbaceous plant communities. While most theoretical discussions of species density have emphasized the importance of habitat productivity and disturbance regimes, many other factors (e.g. species pools, plant litter accumulation, plant morphology) have been proposed to be important. A review of literature presenting observations on the density of species in small plots (in the vicinity of a few square meters or less), as well as experimental studies, suggests several generalizations: (1) Available data are consistent with an underlying unimodal relationship between species density and total community biomass. While variance in species density is often poorly explained by predictor variables, there is strong evidence that high levels of community biomass are antagonistic to high species density. (2) Community biomass is just one of several factors affecting variations in species density. Multivariate analyses typically explain more than twice as much variance in species density as can be explained by community biomass alone. (3) Disturbance has important and sometimes complex effects on species density. In general, the evidence is consistent with the intermediate disturbance hypothesis but exceptions exist and effects can be complex. (4) Gradients in the species pool can have important influences on patterns of species density. Evidence is mounting that a considerable amount of the observed variability in species density within a landscape or region may result from environmental effects on the species pool. (5) Several additional factors deserve greater consideration, including time lags, species composition, plant morphology, plant density and soil microbial effects. Based on the available evidence, a conceptual model of the primary factors controlling species density is presented here. This model suggests that species density is controlled by the effects of disturbance, total community biomass, colonization, the species pool and spatial heterogeneity. The structure of the model leads to two main expectations: (1) while community biomass is important, multivariate approaches will be required to understand patterns of variation in species density, and (2) species density will be more highly correlated with light penetration to the soil surface, than with above-ground biomass, and even less well correlated with plant growth rates (productivity) or habitat fertility. At present, data are insufficient to evaluate the relative importance of the processes controlling species density. Much more work is needed if we are to adequately predict the effects of environmental changes on plant communities and species diversity.


BACKGROUND & AIMS
The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure.

METHODS
We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12.

RESULTS
The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%-98%), 97% receiving the drugs for 12 weeks (95% CI, 96%-98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%-97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%-99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%-99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%-99% vs 98%; 95% CI, 95%-99%). Factors that predicted SVR12 were higher albumin (≥3.5 g/dL), lower total bilirubin (≤1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use.

CONCLUSIONS
Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.


This paper explores the links between international trade theory and the practice of trade and industrial policy in open economies, with special attention to three areas where theoretical lessons have been misunderstood in policy debates. I argue that the ''concertina rule'' for tariff reform justifies reductions in high tariffs, but not moves towards uniformity, and particularly not increases in low tariffs. I show that the basic principles of tariff reform are the same in unilateral, multilateral and customs union contexts. Finally, I show that the theory of strategic trade policy does not justify export subsidies to high-technology industries.


Motivated by the debate over how to deal with the huge backlog of untested sexual assault kits in the U.S.A., we construct and analyze a mathematical model that predicts the expected number of hits (i.e., a new DNA profile matches a DNA sample in the criminal database) as a function of both the proportion of the backlog that is tested and whether the victim–offender relationship is used to prioritize the kits that are tested. Refining the results in Ref. (Criminol Public Policy, 2016, 15, 555), we use data from Detroit, where government funding was used to process ≈15% of their backlog, to predict that prioritizing stranger kits over nonstranger kits leads to only a small improvement in performance (a 0.034 increase in the normalized area under the curve of the hits vs. proportion of backlog tested curve). Two rough but conservative cost‐benefit analyses—one for testing the entire backlog and a marginal one for testing kits from nonstranger assaults—suggest that testing all sexual assault kits in the backlog is quite cost‐effective: for example, spending ≈$1641 to test a kit averts sexual assaults costing ≈$133,484 on average.


Lorenz curves and second-order dominance criteria are known to be sensitive to data contamination in the right tail of the distribution. We propose two ways of dealing with the problem: (1) Estimate Lorenz curves using parametric models for income distributions, and (2) Combine empirical estimation with a parametric (robust) estimation of the upper tail of the distribution using the Pareto model. Approach (2) is preferred because of its flexibility. Using simulations we show the dramatic effect of a few contaminated data on the Lorenz ranking and the performance of the robust approach (2). Statistical inference tools are also provided.


Fictitious play is a popular game-theoretic model of learning in games. However, it has received little attention in practical applications to large problems. This paper introduces two variants of fictitious play that are implemented in behavioural strategies of an extensive-form game. The first variant is a full-width process that is realization equivalent to its normal-form counterpart and therefore inherits its convergence guarantees. However, its computational requirements are linear in time and space rather than exponential. The second variant, Fictitious Self-Play, is a machine learning framework that implements fictitious play in a sample-based fashion. Experiments in imperfect-information poker games compare our approaches and demonstrate their convergence to approximate Nash equilibria.


In many learning problems, the learning system is presented with values for features that are actually irrelevant to the concept it is trying to learn. The FOCUS algorithm, due to Almuallim and Dietterich, performs an explicit search for the smallest possible input feature set S that permits a consistent mapping from the features in S to the output feature. The FOCUS algorithm can also be seen as an algorithm for learning determinations or functional dependencies, as suggested in [6]. Another algorithm for learning determinations appears in [7]. The FOCUS algorithm has superpolynomial runtime, but Almuallim and Dietterich leave open the question of tractability of the underlying problem. In this paper, the problem is shown to be NP-complete. We also describe briefly some experiments that demonstrate the benefits of determination learning, and show that finding lowest-cardinality determinations is easier in practice than finding minimal determinations.


We study the role of firm heterogeneity in affecting business cycle dynamics and optimal stabilization policy. Firms differ in their degree of cyclicality, and hence, exposure to aggregate risk, leading to firm-specific risk premia that influence resource allocations. The heterogeneous firm economy can be recast in a representative firm formulation, but where total factor productivity (TFP) is endogenous and depends on the resource allocation. The model uncovers a novel tradeoff between the long-run level and volatility of TFP. Inefficiencies distort this tradeoff and result in either excessive volatility or depressed output, implying a role for corrective policy. Embedding this mechanism into a workhorse New Keynesian model, we show that allocational considerations can strengthen the incentives for leaning against the wind, i.e., optimal policy is more strongly countercyclical than in an observationally equivalent economy that abstracts from heterogeneity. A quantitative exercise suggests that the losses from ignoring heterogeneity can be substantial, which stem largely from a less productive allocation of resources and so depressed TFP and output.


There is a prevalent and growing trend of adults labeling themselves as non-singers. This crisis of singer identity becomes a factor as music education programs strive to promote singing, especially community singing. This qualitative research study addressed the self-perceptions of singing identity, ability, and attitudes in adolescents. The purpose of this study was to investigate how adolescent students view their own singing abilities in order to gain insight and understanding about what factors play an important role in the shaping of views about their own singing identity. Previous studies shaped the framework for this investigation. Studies reviewed included: (1) the prevalence of inaccurate self-labeling of non-singers in adults; (2) attribution theories; and (3) adolescent views. A 10-question survey was designed and given to students (N=98) from a suburban K-8 school in the Midwest to understand attitudes about singing, opinions of identity as a singer, whether it is a learned behavior or a natural talent, and how those ideas developed. The analysis of the initial survey responses provided information used to design the interview questions for the six case studies. These six participants provided perspectives on singer identity in adolescence. Five themes emerged from the study which include: (1) Reasons for singing; (2) Nature of singing ability; (3) Vocabulary/lack of vocabulary; (4) Confidence/lack of confidence; and (5) Formations of opinions. Findings aligned with past studies showing that adolescence is a notable time when people develop their singing identity, but new ideas were revealed. Adolescents have all levels of vocal ability and music educators have the opportunity to guide students through a continuum of singing development. Music teachers should be aware of the concept of singer identity and find ways to improve singer confidence. Fear and anxiety over singing ability should be addressed as normal rather than as an indicator of singing potential. Helping students to have vocabulary to describe their voice, their ability level, and ways to improve their voice will empower them to see themselves as singers.


We construct English audio-visual integration teaching mode by fuzzy mathematics method which is based on the references, and the practice of actual learning for the related English teaching. And optimize the module design based on the integration of multiple evaluation decision thorough investigation, so we can get the weight proportion of each module in the teaching of English. Through actual comparison and combining with the theoretical calculation domain, this paper established the Moodle platform English audiovisual teaching in each learning combination plan of module teaching, and finds the key direction of implementation, which provides the reference for teaching of English audiovisual integration based on the Moodle platform construction.


Abstract. Lumbini, in southern Nepal, is a UNESCO world heritage site of universal value as the birthplace of Buddha. Poor air quality in Lumbini and surrounding regions is a great concern for public health as well as for preservation, protection and promotion of Buddhist heritage and culture. We present here results from measurements of ambient concentrations of key air pollutants (PM, BC, CO, O3) in Lumbini, first of its kind for Lumbini, conducted during an intensive measurement period of 3 months (April–June 2013) in the pre-monsoon season. The measurements were carried out as a part of the international air pollution measurement campaign; SusKat-ABC (Sustainable Atmosphere for the Kathmandu Valley – Atmospheric Brown Clouds). The main objective of this work is to understand and document the level of air pollution, diurnal characteristics and influence of open burning on air quality in Lumbini. The hourly average concentrations during the entire measurement campaign ranged as follows: BC was 0.3–30.0 µg m−3, PM1 was 3.6–197.6 µg m−3, PM2. 5 was 6.1–272.2 µg m−3, PM10 was 10.5–604.0 µg m−3, O3 was 1.0–118.1 ppbv and CO was 125.0–1430.0 ppbv. These levels are comparable to other very heavily polluted sites in South Asia. Higher fraction of coarse-mode PM was found as compared to other nearby sites in the Indo-Gangetic Plain region. The ΔBC ∕ ΔCO ratio obtained in Lumbini indicated considerable contributions of emissions from both residential and transportation sectors. The 24 h average PM2. 5 and PM10 concentrations exceeded the WHO guideline very frequently (94 and 85 % of the sampled period, respectively), which implies significant health risks for the residents and visitors in the region. These air pollutants exhibited clear diurnal cycles with high values in the morning and evening. During the study period, the worst air pollution episodes were mainly due to agro-residue burning and regional forest fires combined with meteorological conditions conducive of pollution transport to Lumbini. Fossil fuel combustion also contributed significantly, accounting for more than half of the ambient BC concentration according to aerosol spectral light absorption coefficients obtained in Lumbini. WRF-STEM, a regional chemical transport model, was used to simulate the meteorology and the concentrations of pollutants to understand the pollutant transport pathways. The model estimated values were ∼ 1. 5 to 5 times lower than the observed concentrations for CO and PM10, respectively. Model-simulated regionally tagged CO tracers showed that the majority of CO came from the upwind region of Ganges Valley. Model performance needs significant improvement in simulating aerosols in the region. Given the high air pollution level, there is a clear and urgent need for setting up a network of long-term air quality monitoring stations in the greater Lumbini region.


Changes in US health care financing have prompted changes in technology assessment in US health care institutions. Emphasis is shifting from capital budgeting proposals in support of revenue enhancement to marginal cost analysis in support of cost-reducing measures. This requires skills related to marginal cost finding and analysis, detailed process and activity mapping, outcome mapping, and integrative modelling. The implementation of these skills also calls for structural adjustments related to top management involvement and governance processes, multidisciplinary analysis teams, financial management outside of capital budgeting, and institutional values with respect to resource allocation, skills which many institutions currently lack. If they are not to be at the mercy of vendors and payers who are trying to specify the technologies to be used, they must be equipped to make independent judgments about efficiency, effectiveness, quality and value.


This paper conducts a comparative analysis of academic research on location-allocation of electric vehicle fast chargers into the pattern of the actual fast-charger allocation in the United States. The work aims to highlight the gap between academic research and actual practice of charging-station placement and operation. It presents evidence that the node-serving approach is, in fact, applied in the actual location-allocation of fast charging stations. However, little evidence suggests that flow-capturing, which has been much more predominantly applied in research, is being applied in practice. The author argues that a large-scale location-allocation plan for public fast chargers should be formulated based on explicit consideration of stakeholders, the objective, practical constraints, and underlining assumptions.


Napoleon's invasion of Russia in 1812 remains one of the greatest military and humanitarian disasters of all time. Within six months a million lives were lost, the largest army ever assembled was destroyed, and the Emperor himself transformed from the master of a continent to a fugitive. General Count de Segur's first-hand account remains our chief source of information about this most dramatic of military debacles. From the Grand Army's first steps on Russian soil, to its miraculous escape at the River Berezina, this must rank as one of the greatest war stories ever written. First published in 1824, it caused a sensation. The author, who had served on the Emperor's staff, dared to present him as a flawed genius, resulting in a duel with Napoleon's former aide-de-camp, General Gourgaud. The public blood-letting (de Segur was wounded) only heightened demand and it was translated into every major European language.


Diabetic Mellitus is a reason for concern as it significantly increases one's risk of developing microvascular, and macrovascular complications and adversely affects the quality of life (QoL).QoL is a term used to appraise the patient's functional capacity, psychological, social health, and over all sense of well- being. For chronic illnesses like diabetes mellitus the therapeutic success is conventionally measured by disease-free and overall survival, and control of chief physical symptoms. Number of tools is available for assessing the quality of life in diabetes each with their advantage and disadvantages. The aim of this study was to design and test the reliability and validity of Modified Diabetes Quality of Life questionnaire (MDQoL-17) and to assess the quality of life of south Indian diabetic patients. The tool was developed and validated appropriately. The tool was translated into kannada for use in the local patients and appropriately validated for translation. The developed tool had appropriate reliability and internal consistency. Overall Quality of life of Diabetic patients was analyzed from the data collected of 100 patients and has shown moderate QoL by both the questionnaires. The QoL predicted by RAND-36, which consists of 36 questions, and MDQoL-17, which consists of 17 questions, was almost the same. This showed that MDQoL-17 was good enough to predict the Quality of life as RAND-36. The QoL score was correlated with demographic and other variables.This study showed that the developed MDQoL-17 questionnaire performed similar to the established RAND-36 and could be used as a tool to assess the quality of life in diabetic patients.


Background and Purpose: Identification of the effects of sleep disturbances on the quality of life could result in proper treatment of patients with heart failure. This study aimed to investigate the relationship between sleep disorders and erectile dysfunction, depression and quality of life in male patients with systolic heart failure. Methods: This correlational study was conducted on 100 male patients with systolic heart failure selected by convenience sampling. Data were collected using Epworth Sleepiness Scale (ESS), STOP-Bang questionnaire, Pittsburgh Sleep Quality Index (PSQI), Minnesota Living with Heart Failure questionnaire (MLHFQ), Center for Epidemiologic Studies Depression Scale (CES-D) and International Index of Erectile Function (IIEF-5). Data analysis was performed using descriptive statistics, Pearson's correlation-coefficient and linear regression model. Results: In this study, sleep quality (P<0.001) and possibility of obstructive sleep apnea (OSA) (P=0.001) were significantly associated with depression and could explain 32.6% of variance in depression. In addition, possibility of OSA (P=0.006) was associated with erectile dysfunction and could explain 12% of variance in erectile dysfunction. Also, possibility of OSA (P=0.001) and sleep quality (P<0.001) had a statistically significant correlation with quality of life and could explain 36% of variance in quality of life. Conclusion: According to the results of this study, poor sleep quality and sleep-disordered breathing were negatively correlated with mood, sexual function and overall quality of life in male patients with systolic heart failure. Therefore, proper screening and treatment of sleep disorders in patients with heart failure is of paramount importance.


Objective – This project sought to identify the five most used evidence based bedside information tools used in Canadian health libraries, to examine librarians' attitudes towards these tools, and to test the comprehensiveness of the tools.

Methods – The author developed a definition of evidence based bedside information tools and a list of resources that fit this definition. Participants were respondents to a survey distributed via the CANMEDLIB electronic mail list. The survey sought to identify information from library staff regarding the most frequently used evidence based bedside information tools. Clinical questions were used to measure the comprehensiveness of each resource and the levels of evidence they provided to each question.

Results – Survey respondents reported that the five most used evidence based bedside information tools in their libraries were UpToDate, BMJ Clinical Evidence, First Consult, Bandolier and ACP Pier. Librarians were generally satisfied with the ease of use, efficiency and informative nature of these resources. The resource assessment determined that not all of these tools are comprehensive in terms of their ability to answer clinical questions or with regard to the inclusion of levels of evidence. UpToDate was able to provide information for the greatest number of clinical questions, but it provided a level of evidence only seven percent of the time. ACP Pier was able to provide information on only 50% of the clinical questions, but it provided levels of evidence for all of these.

Conclusion – UpToDate and BMJ Clinical Evidence were both rated as easy to use and informative. However, neither product generally includes levels of evidence, so it would be prudent for the practitioner to critically appraise information from these sources before using it in a patient care setting. ACP Pier eliminates the critical appraisal stage, thus reducing the time it takes to go from forming a clinical question to implementing the answer, but survey respondents did not rate it as high in terms of usability. There remains a need for user-friendly, comprehensive resources that provide evidence summaries relying on levels of evidence to support their conclusions.


This study evaluated the differences in dietary adequacy between elderly (age 65 and older) who missed meals and those who did not. Data were obtained from the National Food Consumption Survey (1987-1988). Three-day food consumption records were used to collect the dietary data. Elderly persons who missed a meal during the 3-day period were classified as missing a meal (N=577), and those who did not miss a meal during the 3-day period were classified as not missing a meal (N=479). Nutrient adequacy ratios (NARs) for nutrients were computed and analyzed using analysis of covariance (ANCOVA). The results indicated that the elderly who missed a meal had significantly lower NARs for calcium, phosphorus, iron, magnesium. vitamin E, ascorbic acid, thiamin, riboflavin, folate, and vitamin B6 compared to elderly people who did not miss a meal. These findings may suggest. that elderly who miss meals may consume less than the recommended amounts of macronutrients and micronutrients. Nutritionists and other health practitioners should stress to the elderly the importance of proper nutrition and encourage them to avoid missing meals.


This paper responds directly to the call for strategy-as-practice research to more intently focus on 'the stuff of strategizing, the material artefacts, objects, tools and technologies which are part and parcel of the social practice of strategy' (Sub-theme call for papers). In taking the 'stuff of strategizing' seriously, and in deepening the accounts of 'practices' ( Jarzabkowski and Whittington 2008) offered by strategy-as-practice approaches, we argue that technology is especially important. In the process of considering how technology might best be understood in strategy-as-practice research we advocate a sociomaterial lens. We seek to demonstrate the potential utility of a sociomaterial approach to strategy-as-practice research through the analysis of an empirical case of strategic change at a manufacturing organisation in which strategizing activity was mediated by technological artefacts. We explore the implications of the analysis, and of sociomaterial approaches to technology implementations more generally, for strategy-as-practice research. Publication Details Hall, R., Dery, K., Wailes, N. & Wiblen, S. L. (2013). Sociomateriality and strategy-as-practice: taking technology seriously and applying actor-network theory. European Group for Organizational Studies (EGOS): Bridging Continents, Cultures and Worldviews (pp. 1-23). This conference paper is available at Research Online: http://ro.uow.edu.au/buspapers/950


The field of toxicology has traditionally assessed the risk of contaminants by using laboratory experiments and a range of pesticide concentrations that are held constant for short periods of time (1-4 days). From these experiments, one can estimate the concentration that causes no effect on survival. However, organisms in nature frequently experience multiple, applications of pesticides over time rather than a single constant concentration. In addition, organisms are embedded in ecological communities that can propagate indirect effects through a food web. Using outdoor mesocosms, we examined how low concentrations (10-250 microg/L) of a globally common insecticide (malathion) applied at various amounts, times, and frequencies affected aquatic communities containing zooplankton, phytoplankton, periphyton, and larval amphibians (reared at two densities) for 79 days. All application regimes caused a decline in zooplankton, which initiated a trophic cascade in which there was a bloom in phytoplankton and, in several treatments, a subsequent decline in the competing periphyton. The reduced periphyton had little effect on wood frogs (Rana sylvatica), which have a short time to metamorphosis. However, leopard frogs (Rana pipiens) have a longer time to metamorphosis, and they experienced large reductions in growth and development, which led to subsequent mortality as the environment dried. Hence, malathion (which rapidly breaks down) did not directly kill amphibians, but initiated a trophic cascade that indirectly resulted in substantial amphibian mortality. Importantly, repeated applications of the lowest concentration (a "press treatment" consisting of seven weekly applications of 10 microg/L) caused larger impacts on many of the response variables than single "pulse" applications that were 25 times as great in concentration. These results are not only important because malathion is the most commonly applied insecticide and is found in wetlands, but also because the mechanism underlying the trophic cascade is common to a wide range of insecticides, offering the possibility of general predictions for the way in which many insecticides impact aquatic communities and the populations of larval amphibians.


The caregivers of persons living with dementia (PLwD) have to provide full-time caregiving to the individual, in addition to other responsibilities in their own life.[1] Providing care to a PLwD affects their quality of life[2] and mental health. In such a context, clinicians have to guide caregivers in decreasing caregiver's burden through appropriate referrals. Day-care centers can be one such service, which is illustrated with the support of a case here.


MicroRNAs (miRNAs) represent a class of small noncoding RNAs that regulate gene expression. Recent studies have shown that miRNAs are mis-expressed in various human cancers and that some miRNAs have the potential to act as tumor suppressors or oncogenes. MiR-10b is one miRNA that has been shown to be deregulated in breast cancer. However, current findings regarding miR-10b's role in breast cancer are controversial. MiR-10b was originally reported to be downregulated in breast cancer compared to normal breast tissue. Subsequently, miR-10b was argued to be upregulated in metastatic breast cancer cell lines, acting as a potent pro-metastatic agent via regulation of HOXD10. This report was soon challenged by another group who reported that miR-10b expression in a large patient cohort correlated inversely and significantly with tumor size, grade, and vascular invasion, but did not correlate with development of distant metastases or survival. These latter data suggest that miR-10b may impede specific functions associated with breast cancer progression. In this thesis, I present my analysis of miR-10b function in breast carcinoma cells, which revealed that it suppresses their migration and invasion. To define a mechanism that accounts for this suppressive function, I identified T-lymphoma invasion and metastasis 1 (TIAM1), a guanine nucleotide exchange factor for Rac1, as a miR-10b target and demonstrated that miR-10b inhibits TIAM1-dependent Rac1 activation, migration, and invasion. In addition, I identified the VEGF receptor fms-related tyrosine kinase 1 (FLT-1) as a second target of miR-10b and discovered a novel function for FLT-1 in promoting breast carcinoma cell migration and invasion. My results show, for the first time, that Rac activation can be regulated by a specific miRNA and provide a novel mechanism for the regulation of TIAM1 and FLT-1 in breast cancer. These data support the conclusion from clinical data that miR-10b expression correlates inversely with breast cancer progression, and suggest that miR-10b functions to impede breast carcinoma progression by regulating key target genes involved in cell motility.


The marine areas of the polar regions represent some of the most pristine and environmentally sensitive habitats in the world, as well as hosting a variety of threatened species. Environ-mental assessment of human activities with the potential for significant impacts on the spe-cies, habitats and ecosystems of these remote marine areas is an essential component of any governance regime for the polar regions. The term "environmental assessment" as used in this chapter encompasses not only prior environmental impact assessment (EIA), but also ongoing monitoring of impacts on the marine environment, post EIA obligations, strategic envi-ronmental assessment (SEA) and transboundary implementation of these processes. The wellestablished process of EIA with its recognized stages of screening, scoping and public con-sultation is critical to minimizing adverse human impacts on these areas and developing suit-able mitigation measures for the duration of such activities and beyond. EIA can alert states to the potential for transboundary harm from certain activities in marine areas and in many cases requires states to notify and consult other states where risks to marine areas under their jurisdiction emerge. EIA is an integral component of a precautionary approach to human ac-tivities with the potential for adverse effects on the marine environment. Undertaking prior EIA and ongoing monitoring of activities with the potential for adverse effects on the marine environment is also vital in incorporating environmental concerns into the development process and facilitating sustainable development.


It is believed that the power sector, particularly hydroelectric power, contributes to a very high consumption of fresh water in terms of evaporation from storage reservoirs. Robust methods of water footprint (WFP) assessment will eventually help in the pricing of water and energy. Conventionally, WFP for hydropower plants is estimated by dividing the gross/net evaporation losses by power generation. This approach is highly biased when it comes to a small hydropower plant connected to a large reservoir. In this study, a two-pronged subjective–objective method is suggested for a reservoir with primary functions of power generation and downstream water release. The objective part is concerned with giving weight to the evaporation loss proportional to the water use while the subjective part is concerned with refining this by considering the real time reservoir operation conditions and taking into account the recommendations of the decision making authorities. The effect of time scale in WFP analysis is also studied and conclusions are drawn. Thumb rules for WFP estimation are evolved which will aid in such analysis. The implementation of the proposed methodology for any reservoir system is recommended using LabVIEW platform.


The understanding of the relationship between culture and nature as manifested in the UNESCO declarations and practices has changed over the last few years. The World Heritage Convention is continuing to evolve its definitions to reflect the increasing complexities of world cultures as they grapple with the heritage conservation policies that reflect their multiple stakeholders. They are also integrating a greater cultural perspective in their recent resolutions to the convention. Although the links between nature and culture have been clarified through this new attention to cultural landscapes, many countries and their bureaucracies have not yet adopted these new perspectives. The article suggests that to achieve an integrated approach to conservation, national, regional, and international bodies and their professionals must be involved. Two examples are discussed to address the shortcomings of the application of the convention and to illustrate the complexities of defining and conserving cultural landscapes.


We propose a new analytical edge spread function (ESF) fitting model to measure the modulation transfer function (MTF). The ESF data obtained from a slanted-edge image are fitted to our model through the non-linear least squares (NLLSQ) method. The differentiation of the ESF yields the line spread function (LSF), the Fourier transform of which gives the profile of two-dimensional MTF. Compared with the previous methods, the MTF estimate determined by our method conforms more closely to the reference. A practical application of our MTF measurement in degraded image restoration also validates the accuracy of our model.


Technetium is an artificial element and its isotope 99mTc is now used for several years as radio-imaging agent. Much research effort is directed towards enhanced targeting of the imaging agents in order to improve accuracy of the diagnosis and reduce the radiation doses delivered to the patient. Technetium(I) complexes are promising in this field and especially those with the fac-[(CO)3Tc]+ entity. Rhenium which is closely related to technetium, is used as model compound, but has also its own radiopharmaceutical potential with the isotopes 186Re and 188Re. The preparative chemistry of 99mTc has to be performed in water. Therefore, it is of importance to know its actual form in solution and understand its reactivity. Thus the goal of the present work was to investigate the reactivity of fac- [(CO)3Mn(H2O)3]+, fac-[(CO)3Tc(H2O)3]+, fac-[(CO)3Re(H2O)3]+ et fac- [(CO)2(NO)Re(H2O)3]2+ by multinuclear magnetic resonance. The water exchange rates on these complexes have been determined as a function of acidity and for tow of them (Mn and Tc) as a function of temperature. The water exchange rate decreases when going from manganese to technetium and then to rhenium. In the latter case it was found that the replacement of a CO ligand by an NO+ ligand decreases again the lability of the water molecules. For the two rhenium complexes an increase of the water exchange rate with decreasing acidity has been observed. Water molecules on fac-[(CO)3Mn(H2O)3]+, fac-[(CO)3Tc(H2O)3]+, fac- [(CO)3Re(H2O)3]+ complexes are easily substituted. This reaction has been investigated with selected ligands of various types. The complexes show a stronger affinity for soft ligands such as dimethylsulfide than for harder ligands like acetonitrile. Variable pressure experiments for the ligand substitution on fac- [(CO)3Re(H2O)3]+ provided activation volumes. The substitution by the soft ligand was found to be associatively activated whereas the substitution by hard ligands is dissociatively activated. Although activation volumes could not be determined for the substitution reaction on fac-[(CO)3Mn(H2O)3]+ and fac-[(CO)3Tc(H2O)3]+ their similar reactivity suggests that they exhibit the same mechanistic behaviour as fac- [(CO)3Re(H2O)3]+.


We present a framework of maturity indicators that can be used to assess the maturity of a company in terms of e-learning and to promote new approaches to corporate e-learning. This framework is the result of a study that included semi-structured interviews with prime companies of several sectors such as banking, insurance, retail, energy, telecommunications, pharmaceuticals, food and beverage, and transports. In common, all of these companies have annual training budgets about or higher than 6 million dollars and several years of experience using e-learning to promote corporate development and training. The result of this study is not a maturity path or a set of maturity levels but a list of maturity indicators, classified in seven dimensions: strategy, structure, experience, learning design, learning products, learning process, and people. Each dimension includes several indicators of maturity. Each company can be assessed for every indicator to determine its strength and maturity in each dimension. This framework helps companies assess their own maturity in several areas, self diagnose their e-learning practices, and design strategies to improve their practices.


In the article that we presented, we referred to the process
of producing information at a biological level describing the characteristics
of the brain, as we know about it's existence and can justify it's decisive
role in the production of information we described the four principal flows of
information, were it is demostrated stage by stage how the brain is shaped
trough expierence.
From this perspective we think that the function of intelligence is linked
to part of the quantity and quality of the stimuli processed by the individual
which he or she receives from the environment.
Taking into account then, that the objective of education is to build the
subject, refering naturally to the building of individual personality, and that
such construction is carried out by actions which imply the modification of
already existing structures and the appearance of new ones, at least in the
functional sense, and that this activity is realised by the subject him or herself
(levels of «ability» and formation); education acquires from this perspective
a preponderant role.
In the educational environment, one tries to achieve that the shaping of
the individual is brought about by «activity of the individual provoked by
educational action


Growing evidence is unveiling a role for poly(ADP-ribose) polymerase (PARP)-1 in the regulation of inflammatory/immune responses. In the current study, we investigated the effects of PARP-1 deficiency on regulatory T cell differentiation. Increased numbers of regulatory CD4+CD25+/Foxp3+ T cells were found in thymus, spleen, and lymph nodes of PARP-1 knockout (KO) mice compared with wild-type (WT) controls. The increased frequency of regulatory T cells in the periphery resulted in impaired CD4 cell proliferation and IL-2 production, which could be restored by CD25+ cell depletion. Phenotype and inhibitory functions of PARP-1 KO regulatory T cells were similar to WT cells, indicating that PARP-1 affects regulatory T cell differentiation rather than function. Purified naive CD4 cells from PARP-1 KO mice stimulated in vitro expressed forkhead box p3 mRNA at higher levels and generated a greater number of Foxp3+ cells (inducible regulatory T [iTreg] cells) than the WT counterpart. This finding was due to a higher rate of naive CD4 cell to Foxp3+ iTreg cell conversion rather than to higher resistance to apoptosis induction. Interestingly, PARP-1 deficiency did not affect retinoid-related orphan receptor-γt mRNA expression and differentiation of purified naive CD4 cells to Th17 cells. PARP-1 KO iTreg cells showed features similar to WT regulatory T cells, suggesting that modulation of PARP-1 during the immune response might be used to induce greater numbers of functional regulatory T cells. In conclusion, our findings represent the first evidence that PARP-1 can affect regulatory T cell differentiation and open new perspectives on potential targets for modulating immune responses.