jimnoneill/paper-to-field-training huggingface dataset:
Acceptance of stakeholder comments during EMA scientific guidelines public consultations: legitimacy of the quadruple helix model of innovation

Aim: Guidelines establish a framework for how therapeutics and vaccines are developed, assessed and approved. They influence which innovations are likely to be approved in the EU, and by that, they have an impact on the pipeline decisions taken by the research-based industry. This study analyses the level of acceptance for changes suggested by stakeholders within the authoring groups at the EMA. Methods: We looked at 87 guidelines from EMA Working Parties (WPs) launched for consultation between 2013-2017. Acceptance of stakeholder proposals and the time between the end of consultation and guideline adoption were studied as well as the openness of different Working Parties to accept changes. Results: Adoption of a guideline after the close of public consultation took at least 4 months, with average 12-16 months. The number of accepted and rejected comments were nearly equal across the stakeholders, with government having slightly higher chance for acceptance. Academia and NGOs had generally higher chances to have their comments accepted for general and indication-level guidelines. Government and individual companies had highest acceptance for molecule-level guidelines and trade associations for indication-level guidelines. The EMA WPs working with emerging technologies were more open to accept proposed changes. Conclusion: This pattern of progress in regulatory science at EMA demonstrates the essential and interrelated role of academia, industry, government and civil society – described as the quadruple helix model - to promote establishment of a strong innovation ecosystem in Europe. Further integration and utilisation of competences of each stakeholder is necessary for guideline development.

Topic: Chemistry and Chemical Engineering
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Role of Terms of Trade in Indian Agricultural Growth: A National and State Level Analysis

Using time series data, this paper analyses the relative contributions of terms of trade and non-price variables in explaining agricultural growth in recent decades in India. Agricultural growth is largely explained by expansion of irrigation, (which in the model is also a proxy for HYVs and other capital investments), and, until the 1970s, by increases in the net cultivated area. Agricultural output is inelastic, and is becoming increasingly more so over time. The terms of trade was not an important factor in explaining past growth. Even during the late 1960s and early 1970s when the terms of trade improved by 18 percent for agriculture, they only accounted for 15 percent of the growth in output. Increases in agricultural output are also found to worsen the terms of trade for agriculture, despite government attempts to control prices. The results highlight the importance of further investments in agricultural research, extension, irrigation and other supply-enhancing inputs if the ongoing policy reforms in India are to translate into more rapid and sustained agricultural growth.

Topic: Agricultural Economics and Practices
Subfield: General Agricultural and Biological Sciences
Field: Agricultural and Biological Sciences
Domain: Life Sciences
A Kinetic Assay for Drug Discovery: Part 2, Sodium Sulfate

Clumped cells are generally more dangerous than single cells in cancer spread, thrombocytosis and biofilm infectivity. Here a simple direct kinetic assay is used to examine a specific reagent for anti-clumping activity using a Prefer fixed yeast (Saccharomyces cerevisiae) model that has been recently described by us in detail using other reagents. In 1212 trials by 17 investigators sodium sulfate (1-3 mg per ml deionized water) was examined by measuring percentage single cells, number of clumps and number of cells per clump over a 60 min time course, with standard deviations and t-tests to determine any significant differences between controls and experimentals. Sodium sulfate showed sometimes inconsistent unclumping activity especially in magnitude of effects. When percentage of single cells increased, clump number and/or number of cells per clump generally decreased, helping to validate the assay. An example of these findings in 60 trials at 60 min with 1-3 mg sodium sulfate per ml deionized water: 1 mg 15% increased singles (p<0.01), 29% decreased clumps (p<0.01), 11% decreased cells per clump (p>0.05); 2 mg 12% increased singles (p<0.01), 20% decreased clumps (p<0.01), 30% decreased cells per clump (p<0.01); 3 mg 27% increased singles (p<0.01), 36% decreased clumps (p<0.01), 28% decreased cells per clump (p<0.02). Here sodium sulfate showed promise as an anti-cell-clumping reagent together with sodium citrate reported previously in part 1 of this study. Sodium citrate is a known human anticoagulant independently identified with this assay, helping to validate the assay for drug discovery applications.

Topic: Biosimilars and Bioanalytical Methods
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
[Evaluation of the toxic action of prophylactic and therapeutic preparations on cell cultures of different types and origin. II. The cytotoxic action of adsorbed DPT vaccine and its components on cells of the continuous L132 line].

Different batches of the same preparation manufactured at the same enterprise, or at different enterprises, in accordance with the same manufacturing regulations have been found to be capable of producing a damaging effect of different intensity on the continuous cell culture L132. The titers vary, according to their cytotoxic effect, from 1 : 32 to 1 :2048. The components of B. pertussis antigens and thimerosal solutions have been found to produce the most pronounced cytotoxic effect on the cells. The comparison of the results of the titration of adsorbed DPT vaccine in cell cultures with clinical manifestations has shown correlation between a greater degree of cell damage in vitro and severe local reaction. Therefore, in the process of the quality control of preparations cell cultures provide more sensitive tests than laboratory animals, which is confirmed by our data obtained in revealing the toxic properties of adsorbed DPT vaccine and its components.

Topic: Chemical Reactions and Isotopes
Subfield: Pharmaceutical Science
Field: Pharmacology, Toxicology and Pharmaceutics
Domain: Life Sciences
Beyond budgeting: review and research agenda

Purpose Beyond budgeting has received an increased amount of scholarly attention in recent years. However, because most of the published research is discrete and unconnected, an overall picture of what is known about beyond budgeting has not evolved. Therefore, the purpose of this paper is to provide an overview of the available research on beyond budgeting. In particular, the authors compare conceptual papers that mostly stress the benefits of beyond budgeting with empirical evidence on beyond budgeting implementation and offer ideas for future research on beyond budgeting. Design/methodology/approach This paper uses systematic literature review methods. After an extensive database search and examination of references/citations, 32 papers were analysed with regard to bibliographical information, research design and findings. Findings Although proponents of beyond budgeting have put substantial effort into developing and promoting this concept, numerous empirical studies demonstrate that many organizations being investigated would still rather improve traditional budgeting than abandon it completely. This review also highlights the main criticisms of traditional budgeting, development of management control systems under beyond budgeting and factors hindering the implementation of beyond budgeting. Research limitations/implication This paper suggests that further research is needed on the scaling of beyond budgeting, organizational changes under beyond budgeting and challenges resulting from the implementation of beyond budgeting. Originality/value The paper is the first comprehensive literature review on beyond budgeting.

Topic: Accounting and Organizational Management
Subfield: Management Information Systems
Field: Business, Management and Accounting
Domain: Social Sciences
GBDT_KgluSite: An improved computational prediction model for lysine glutarylation sites based on Feature Fusion and GBDT classifier

Abstract Background Lysine glutarylation(Kglu) is one of the most important Post-translational modifications(PTMs), which plays significant roles in various cellular functions, including metabolism, mitochondrial processes, and translation. Therefore, accurate identification of Kglu site is important for elucidating protein molecular function. Due to the time-consuming and expensive limitations of traditional biological experiment, computational-based Kglu site prediction research are gaining more and more attention. Results In this study, we proposed a new model named GBDT_KgluSite to identify Kglu and non-Kglu sequences based on the gradient-boosting decision tree (GBDT). Here, sequence-based features, physicochemical property-based features, structural-based features, and evolutionary-derived features were used to characterize proteins. The imbalance between positive and negative samples was addressed using the NearMiss-3 approach, and extraneous data was eliminated using the Elastic Net. The experimental results show that GBDT_KgluSite has good robustness and generalization ability, with accuracy and AUC values of 93.73%, and 98.14% on five-fold cross-validation as well as 90.11%, and 96.75% on the independent test dataset, respectively. Conclusion GBDT_KgluSite is an effectively computational method for identifying Kglu sites in protein sequences. It has good stability and generalization ability and could be useful for the identification of new Kglu sites in Mus musculus protein. The code and dataset of GBDT_KgluSite is available at https://github.com/flyinsky6/GBDT_KgluSite.

Topic: Machine Learning in Bioinformatics
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Influence of the Linking Bridge on the Photoreactivity of Benzophenone–Thymine Conjugates

Benzophenone (BP) is present in a variety of bioactive molecules. This chromophore is able to photosensitize DNA damage, where one of the most relevant BP/DNA interactions occurs with thymine (Thy). In view of the complex photoreactivity previously observed for dyads containing BP covalently linked to thymidine, the aim of this work is to investigate whether appropriate changes in the nature of the spacer could modulate the intramolecular BP/Thy photoreactivity, resulting in an enhanced selectivity. Accordingly, the photobehavior of a series of dyads derived from BP and Thy, separated by linear linkers of different length, has been investigated by steady-state photolysis, as well as femtosecond and nanosecond transient absorption spectroscopy. Irradiation of the dyads led to photoproducts arising from formal hydrogen abstraction or Paterno-Büchi (PB) photoreaction, with a chemoselectivity that was clearly dependent on the nature of the linking bridge; moreover, the PB process occurred with complete regio- and stereoselectivity. The overall photoreactivity increased with the length of the spacer and correlated well with the rate constants estimated from the BP triplet lifetimes. A reaction mechanism explaining these results is proposed, where the key features are the strain associated with the reactive conformations and the participation of triplet exciplexes.

Topic: Photochromic and Fluorescence Chemistry
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Server based DoS vulnerabilities in SSL/TLS Protocols Master Thesis

When availability is an important security requirement for the organizations then (D)DOS ((Distributed) Denial of Service) attack is one of the important attacks that needs to be addressed. The SSL protocols are widely used to secure e-commerce and other sensitive online transactions. The SSL protocol imposes a significant overhead on the web server. However, it does not create a significant overhead on the client-side. This creates an opportunity for an attacker to execute the computational DoS attacks on the SSL servers. In addition, the SSL protocols are complex in nature. In this thesis, we perform a number of experiments to analyse the DoS attack possibilities on the SSL protocol. To do so, we study the SSL protocols to come up with a number of SSL functionalities those are likely to be the weak-link and can be exploited to execute the DoS attacks. We also review the Openssl implementation to investigate the presence of DoS attack vulnerabilities in the implementation. Our experimental results show that the client authentication can create a significant computational overhead on the server side. The compression utility does not introduce any buffer overflow condition. The cryptographic operations involved in the SSL protocols are expensive and these operations are unbalanced. The server has to perform more expensive operations than the client especially when RSA key exchange method is used. We also perform the comparative experiments in which, we measure the impact of the three different DoS attack strategies on the SSL server performance. We found that the SSL renegotiation based DoS attack outperforms the other two DoS attack strategies. We describe the SSL renegotiation feature and working of the thc-ssl-dos tool [1] which is based on the SSL renegotiation feature. The results of these tests also indicate that the SSL protocol is processor intensive. Therefore, adding more CPUs can help in alleviating the impact of the DoS attack. Since, SSL renegotiation based DoS attack only works when the renegotiation is supported, it is easy to mitigate such attack just by disabling the renegotiation. Our results suggest that there is no simple fix to completely mitigate the DoS attacks. However, the likelihood of the DoS attacks can be reduced by employing enough CPU power, hardware accelerators, memory and network bandwidth. The SSL server needs be configured carefully according to the business requirements.

Topic: Network Security and Intrusion Detection
Subfield: Computer Networks and Communications
Field: Computer Science
Domain: Physical Sciences
Perceived Threat of COVID-19 and Future Travel Avoidance: Results froman Early Convenient Sample in Slovenia

The present study provides a snapshot of Slovenian tourists' perceptions in a historically unique point of time -the early days of the covid-19-related lockdown.Based on an online survey performed in March and April 2020 the study provides first insights into Slovenian tourists' perceived threats of covid-19 on two dimensions: severity and susceptibility; how this depends on their demography and past travel experience and what, in this specific point in time, they think about future travel avoidance.The results have shown that age affects the two measured dimensions of perceived threat and future travel avoidance, but only with women.Furthermore, people who have travelled the most in the past express the least likelihood of avoidance to travel due to the covid-19 pandemic.Those who are more educated, on the other hand, perceive higher risk, yet education has no role in their expressed future travel avoidance.The results, moreover, show that the moral obligation towards taking care of others might be a highly important element in the success factor of covid-19 measures and thus future appeals by the tourism industry.Finally, the results show that we cannot easily predict how the general population will behave regarding their future travel avoidance since the opinions are not polarised in the extremes.This does indicate, however, that tourists will be susceptible to the context-specific factors of future travel decisions, such as assurances of health safety provided by the tourism industry.

Topic: Halal products and consumer behavior
Subfield: Sociology and Political Science
Field: Social Sciences
Domain: Social Sciences
Towards a common European approach for energy labelling and assessment of existing dwellings

Energy performance assessment and energy labelling of existing buildings is being introduced in most of the EU Member States. The new European Directive on Energy Performance of Buildings will probably support this trend in the future. Furthermore the Directive also prescribes common rules and contents for the future energy assessment procedures. Will this lead to a more common approach of energy assessment in existing buildings and what country or region specific elements are necessary to implement successful local programmes? Starting from a comparison of energy labelling and assessment schemes in different EU Member States (recent SAVE project), it is demonstrated how common elements (e.g. parts in calculation procedures, training of energy experts,…) and country specific items (types of dwellings, financial support schemes,…) should be linked to achieve an effective local approach. In Belgium, a research group has been working with support of the Belgian government for the last 5 years towards an effective Belgian programme for the introduction of energy assessment. This programme, including the technical approach, financial support, training schemes, etc., is explained as an example how to integrate common and country specific elements.

Topic: Sustainable Building Design and Assessment
Subfield: Building and Construction
Field: Engineering
Domain: Physical Sciences
A Comprehensive Review on Varti Kalpana

Ayurveda holds a prominent and exceptional place in Indian scientific heritage. Ayurveda places a strong emphasis on prevention and aids in promoting and extending a happy, healthy life. Chikitsa in Ayurveda is the result of diligent effort and judicious use of Chatushpada (Four pillars of treatment). Bhaishajya kalpana is an important branch of Ayurveda which mainly deals with the development of diverse Ayurvedic formulations. Panchavidha Kashaya Kalpana is the basic five therapeutic preparations. Varti Kalpana is a unique Ayurvedic dosage form and it is an Upakalpana of Kalka Kalpana mentioned in Panchavidha kashaya kalpana. Its mode of action and administration is different from Vati Kalpana even though it has similar physical structure and method of preparation. Bruhatrayees were extensively explains about different types of Varti like Netra Varti, Guda Varti, Yoni Varti etc. Siras, Basthi and Hrudayam are collectively called as Trimarma and Guda is one among the Maha marma. Diseases of these vital parts can be safely managed with Varti prayoga without causing any complications. Varti prayoga is included in Stanika chikitsa (local treatment) but it can impart local as well as systemic effect. Manasiladi Dhumavarti indicated in Kasa, Kayastyadi Varti and Yashtyadi Varti in Apasmara, Sallakadi dhumavarti in Unmada are the examples of Varti prayoga which exert systemic effect. The convenience of Varti is enhanced by its simple administration, quick response, and user-friendliness.

Topic: Phytochemicals and Medicinal Plants
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Attention and Cognitive Bias Modification Apps: Review of the Literature and of Commercially Available Apps (Preprint)

<sec> <title>BACKGROUND</title> Automatic processes, such as attentional biases or interpretative biases, have been purported to be responsible for several psychiatric disorders. Recent reviews have highlighted that cognitive biases may be modifiable. Advances in eHealth and mHealth have been harnessed for the delivery of cognitive bias modification. While several studies have evaluated mHealth-based bias modification intervention, no review, to our knowledge, has synthesized the evidence for it. In addition, no review has looked at commercial apps and their functionalities and methods of bias modification. A review is essential in determining whether scientifically validated apps are available commercially and the proportion of commercial apps that have been evaluated scientifically. </sec> <sec> <title>OBJECTIVE</title> The objective of this review was primarily to determine the proportion of attention or cognitive bias modification apps that have been evaluated scientifically and secondarily to determine whether the scientifically evaluated apps were commercially available. We also sought to identify commercially available bias modification apps and determine the functionalities of these apps, the methods used for attention or cognitive bias modification, and whether these apps had been evaluated scientifically. </sec> <sec> <title>METHODS</title> To identify apps in the published literature, we searched PubMed, MEDLINE, PsycINFO, and Scopus for studies published from 2000 to April 17, 2018. The search terms used were “attention bias” OR “cognitive bias” AND “smartphone” OR “smartphone application” OR “smartphone app” OR “mobile phones” OR “mobile application” OR mobile app” OR “personal digital assistant.” To identify commercial apps, we conducted a manual cross-sectional search between September 15 and 25, 2017 in the Apple iTunes and Google Play app stores. The search terms used to identify the apps were “attention bias” and “cognitive bias.” We also conducted a manual search on the apps with published evaluations. </sec> <sec> <title>RESULTS</title> The effectiveness of bias modification was reported in 7 of 8 trials that we identified in the published literature. Only 1 of the 8 previously evaluated apps was commercially available. The 17 commercial apps we identified tended to use either an attention visual search or gamified task. Only 1 commercial app had been evaluated in the published literature. </sec> <sec> <title>CONCLUSIONS</title> This is perhaps the first review to synthesize the evidence for published mHealth attention bias apps. Our review demonstrated that evidence for mHealth attention bias apps is inconclusive, and quite a few commercial apps have not been validated scientifically. </sec>

Topic: Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
CHONDROITIN SULFATE AND GLUCOSAMINE SULFATE AS PROTECTIVE AND ANTI-INFLAMMATORY AGENTS IN THE ULCERATIVE COLITIS DSS MODEL IN RATS.

Chondroitin sulfate (CS) and glucosamine (GlcN) are indicated for the treatment of some inflammatory diseases, such as osteoarthritis, mainly because of the anti-inflammatory effects in reducing metalloproteinases activities (MMP), and other inflammatory mediators. Herein, we reported the structure of the CS, the anti-inflammatory and protective effects of the CS, and GlcN administration in ulcerative colitis model induced by dextran sulfate sodium (DSS) in rats. Experimental data indicated that CS disaccharide composition is very similar to the C4S standard, with modal molecular weight at 30.4 kDa. Orally administration of the CS/GlcN improved the severity of acute colitis with reduction the histological score and goblet cells destruction. We also observed a decreasing in NO production, myeloperoxidase and MMP, especially MMP-9, activities. Moreover, CS/GlcN not cytotoxic in the intestinal epithelial cells. These results indicate that combination CS/GlcN showed improvements in intestinal inflammation and protection intestinal barrier, suggesting CS/GlcN might have beneficial effects in treatment of IBD.

Topic: Liver Disease Diagnosis and Treatment
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences