Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinase Drug Discovery by Affinity Selection/Mass Spectrometry (ASMS): Application to DNA Damage Checkpoint Kinase Chk1

Kinase enzymes are involved in a vast array of biological processes associated with human disease; therefore, selective kinase inhibition by small molecules and therapeutic antibodies is an area of intense study. The authors show that drug candidates with immediate value for biological preclinical evaluation can be identified directly through ultra-efficient affinity screening of kinase enzymes and random compound mixtures. The screening process comprises sampling and trapping equilibrium binding between candidate ligands and protein in solution, followed by removal of unbound ligands via 3 rounds of ultrafiltration and direct identification of bound ligands by mass spectrometry. Evaluation of significant peaks is facilitated by automated integration and collation of the mass spectral data and import into custom software for analysis. One Chk1-selective ligand found by using this process is presented in detail. The compound is potent in both enzymatic and Chk1-dependent cellular assays, and specific contacts in the Chk1 active site are shown by X-ray crystallography.
The Neuristor

The NEURlSTOR, derived from neuron, is a term assigned to a class of structures that exhibits attenuationless signal propagation, as in the attenuationless propagation of the chemical burning zone along a simple fuse, or the attenuationless propagation of the ionic discharge along the axon of a nerve fiber. Totally distributed, one-dimensional electronic lines, exhibiting such a propagation mode, can also be realized. Attenuationless propagation represents no violation of energy conservation since, as the signal propagates, energy flows transversely into the line. A line consists essentially of a distributed, triggerable active element arranged so that when any portion of line is triggered, some or all of the locally available energy is converted into a form suitable for triggering the neighboring section of line. Thus, in a chemical fuse, if the temperature at any point passes threshold the resulting combustion generates a local temperature rise sufficient to activate the adjacent section of line. Although a fuse is a one-time device, the axon heals after each discharge and can be used an indefinite number of times. In conformity with the terminology of neurophysiologists, the period of healing, or recovery, is referred to as the refractory period.
The Effects of Initial Cell Density on the Growth and Proliferation of the Potentially Toxic Cyanobacterium Microcystis aeruginosa

Increasing input of nutrients is leading to significant eutrophication in aquatic systems across the globe. Toxin production in those blooms is correlated with high cell density. A study was done to investigate the effects of initial cell density on the growth rate of the potentially toxic cyanobacterium Microcystis aeruginosa, in unfiltered lake water as well a common algal growth medium under laboratory conditions. Five treatments were established in the laboratory varying the initial cell density of M. aeruginosa and the growth medium. Unfiltered lake water was inoculated with a low, medium, and high initial cell density and Bold’s medium was inoculated with low and high initial cell densities. There was a significant difference in final cell density between the lake water treatments with the high inoculum of cell treatment reaching the highest final cell density. There was also a significant difference in final cell density between the Bold’s medium treatments. These results indicate there is a relationship between initial cell density of M. aeruginosa and final cell density, however, the results are similar when nutrients are available. Diverse algal communities can keep toxin producing algae in low density therefore precluding the need of toxin production.
Anti-hemostatic Effects of a Serpin from the Saliva of the Tick Ixodes ricinus*

Serpins (serine protease inhibitors) are a large family of structurally related proteins found in a wide variety of organisms, including hematophagous arthropods. Protein analyses revealed that Iris, previously described as an immunomodulator secreted in the tick saliva, is related to the leukocyte elastase inhibitor and possesses serpin motifs, including the reactive center loop (RCL), which is involved in the interaction between serpins and serine proteases. Only serine proteases were inhibited by purified recombinant Iris (rIris), whereas mutants L339A and A332P were found devoid of any protease inhibitory activity. The highest Ka was observed with human leukocyte-elastase, suggesting that elastase-like proteases are the natural targets of Iris. In addition, mutation M340R completely changed both Iris substrate specificity and affinity. This likely identified Met-340 as amino acid P1 in the RCL. The effects of rIris and its mutants were also tested on primary hemostasis, blood clotting, and fibrinolysis. rIris increased platelet adhesion, the contact phase-activated pathway of coagulation, and fibrinolysis times in a dose-dependent manner, whereas rIris mutant L339A affected only platelet adhesion. Taken together, these results indicate that Iris disrupts coagulation and fibrinolysis via the anti-proteolytic RCL domain. One or more other domains could be responsible for primary hemostasis inhibition. To our knowledge, this is the first ectoparasite serpin that interferes with both hemostasis and the immune response.
Overexpression of Nerve Growth Factor in Skin Increases Sensory Neuron Size and Modulates Trk Receptor Expression

Sensory neuron development and differentiation is dependent on a family of growth factors known as neurotrophins. Neurotrophins modulate neuron development via trk tyrosine kinase receptor proteins trkA, trkB and trkC. To determine how elevated levels of a target‐derived neurotrophin might affect neuronal differentiation, we analysed trk expression in the trigeminal ganglion of transgenic mice that overexpressed nerve growth factor (NGF) in the skin. increased levels of NGF caused a five‐fold increase in neurons expressing trkA mRNA and a two‐fold increase in neurons expressing trkC. In control mice, cell size distributions of neuronal subpopulations expressing each trk mRNA showed the three subpopulations distributed over a narrow, overlapping range. In contrast, cell size distribution in NGF‐transgenic mice was significantly divergent due in large part to hypertrophy of trkA neurons and, to a lesser extent, trkC neurons. In addition, we examined neurons that bound the isolectin B4 from Bandeiraea simplicifolia (BS‐IB4) because most of these neurons do not express any trk receptor in the adult. There was a significant increase in the size of BS‐IB4–positive neurons in transgenic mice; however, there was no increase in their number. These studies indicate that an increased level of target‐derived NGF affects the development of sensory neurons that in the adult express trkA or trkC, as well as neurons that do not express trk receptors.
Aeromonas hydrophila AH-3 Type III Secretion System Expression and Regulatory Network

ABSTRACT The Aeromonas hydrophila type III secretion system (T3SS) has been shown to play a crucial role in this pathogen's interactions with its host. We previously described the genetic organization of the T3SS cluster and the existence of at least one effector, called AexT, in A. hydrophila strain AH-3. In this study, we analyzed the expression of the T3SS regulon by analyzing the activity of the aopN-aopD and aexT promoters (T3SS machinery components and effector, respectively) by means of two different techniques: promoterless gfp fusions and real-time PCR. The expression of the A. hydrophila AH-3 T3SS regulon was induced in response to several environmental factors, of which calcium depletion, a high magnesium concentration, and a high growth temperature were shown to be the major ones. Once the optimal conditions were established, we tested the expression of the T3SS regulon in the background of several virulence determinant knockouts of strain AH-3. The analysis of the data obtained from axsA and aopN mutants, both of which have been described to be T3SS regulators in other species, allowed us to corroborate their function as the major transcription regulator and valve of the T3SS, respectively, in Aeromonas hydrophila. We also demonstrated the existence of a complicated interconnection between the expression of the T3SS and several other different virulence factors, such as the lipopolysaccharide, the PhoPQ two-component system, the ahyIR quorum sensing system, and the enzymatic complex pyruvate deshydrogenase. To our knowledge, this is the first study of the A. hydrophila T3SS regulatory network.
Using Psychodynamic, Cognitive Behavioral, and Control Mastery Prototypes to Predict Change: A New Look at an Old Paradigm for Long-Term Single-Case Research.

This article illustrates a method of testing models of change in individual long-term psychotherapy cases. A depressed client was treated with 208 sessions of control mastery therapy (CMT), an unmanualized approach that integrates elements of psychodynamic therapy (PDT) and cognitive behavioral therapy (CBT). Panels of experts developed prototypes of ideal PDT, CBT, and CMT process using the Psychotherapy Process Q-set (PQS; J. S. Ablon & E. E. Jones, 1999; E. E. Jones, L. A. Parke, & S. Pulos, 1992; E. E. Jones & S. M. Pulos, 1993). Independent observers rated every 4th session (N 53) with the PQS. Using correlations between ideal and actual PQS ratings followed by paired t tests, the authors compared adherence to the CMT prototype with adherence to plausible alternative models advocated by the PDT and CBT experts. Bivariate time series analyses determined whether prototype adherence predicted an estimated index of symptom change. Results showed that the therapist’s behavior was most consistent with the CMT prototype and that this aspect of the CMT prototype along with particular aspects of the other prototypes influenced estimated symptom change. The results, which replicate and extend earlier findings, support the validity of this approach to studying long-term therapies but also highlight its limitations.
Sexual selection and temporal phenotypic variation in a damselfly population

Temporal variation in selection can be generated by temporal variation in either the fitness surface or phenotypic distributions around a static fitness surface, or both concurrently. Here, we use within‐ and between‐generation sampling of fitness surfaces and phenotypic distributions over 2 years to investigate the causes of temporal variation in the form of sexual selection on body size in the damselfly Enallagma aspersum. Within a year, when the average female body size differed substantially from the average male body size, male body size experienced directional selection. In contrast, when male and female size distributions overlapped, male body size experienced stabilizing selection when variances in body size were large, but no appreciable selection when the variances in body size were small. The causes of temporal variation in the form of selection can only be inferred by accounting for changes in both the fitness surface and changes in the distribution of phenotypes.
The Effect of Investment Tax Credit: Evidence from an Atypical Programme in Italy

This paper examines how business investment responds to investment tax credit, as enacted by Italyi? ½s Law 388/2000. To assess whether the programme made investments possible that otherwise would not have been made, it exploits some features of the tax credit scheme, such as the fact that some Italian regions are not deemed eligible or that the amount of the bonus differs across eligible regions. Although the programme was fiscally unsustainable, and was therefore downsized well ahead of the expiry date, our findings suggest that it has been effective in stimulating investment.
Keypoint density-based region proposal for fine-grained object detection using regions with convolutional neural network features

Recent changes to the topology of regional convolutional neural networks (rCNN) have allowed them to obtain near real-time speeds in image detection. We propose a method for region proposal alternate to selective search which is used in the current state of the art object detection [3] and introduce the fine grained image datasets. In a maritime surveillance setting, it may be important to not only identify an object approaching your position but also know the type of vessel (e.g., a civilian fishing vessel or an enemy destroyer). Our region proposal technique Keypoint Density Region Proposal (KDRP) is able to achieve levels of performance that are not no worse than selective search at a very high level of significance, while only taking 49% of the time of selective search in the rCNN pipeline.
Variation in cell content of milk associated with time of sample collection. I. Diurnal variation.

Abstract Data were analyzed to delineate the diurnal variation in body cell content of quarter-milk samples. Frequent foremilk samplings indicate that cell counts are lowest just prior to milking, rise sharply in the strippings, remain high during the next 4 hr, then decrease progressively to a minimum value near the end of the intermilking period. The body cell level and the magnitude of cyclic change varied widely between groups of cows, cows within group, and to a lesser degree between quarters of a cow. These results emphasize the necessity for care in selecting the optimum time of sampling according to the type of information desired in research or routine health surveys. Variation in time of sampling can introduce real uncertainty in the interpretation of cell count data.
The Value of Patents as Indicators of Inventive Activity

This paper summarizes a number of studies which use patent data to examine different aspects of technological change. It describes our firm level data set construction effort; reports on the relationship between RLD expenditures and the level of patenting; analyzes the relationship between patents, RD reports on the estimation of the value of patent rights based on European patent renewal data; and describes the use of patent data to estimate the importance of R&D spillovers. It concludes that patent data represent a valuable resource for the analysis of technological change. They can be used to study longer-run interfirm differences in inventive activity and as a substitute for R&D data where they are not available in the desired detail. It is possible also to use a firm's distribution of patenting by field to infer its position in "technological space" and use it in turn to study how R&D spills over from one firm to another. Moreover, patent renewal data, which are also becoming available in the U.S., allow one to construct more relevant "quality weighted" inventive "output" measures .
Linking Psychological Empowerment to Innovation Capability: Investigating the Moderating Effect of Supervisory Trust

The purpose of this study is to explore the effects of psychological empowerment and trust in supervisor on employees’ innovation capability. Blue collar employees from various manufacturing organizations performing in Turkey are selected as the main target of this study. Data was collected via a structured questionnaire. A total of 518 questionnaires were analyzed. The results indicate that all three of the four dimensions of psychological empowerment, namely meaning, competence and impact, and trust in supervisor are strongly and positively related to innovation capability. Furthermore, analysis has also revealed that trust in supervisor moderates the relationships between two psychological empowerment dimensions, which are meaning and impact, and innovation capability. Some practical implications are also discussed.
Employing Technologies to Engage Students with Diverse Needs in Rural School Communities

This paper considers the use of information and communication technologies (ICT) to enable students to access the curriculum in inclusive classrooms. The research considers the latest trends regarding promotion of the use of ICT in education in Australia and then considers the outcome from the perspective of one state, that of Western Australia. In particular, the focus is on the use of ICT in remote and rural school communities for supporting inclusive practices. While it seems clear that considerable financial support has been allocated to the enhancement of access to ICT across Australia by various education departments, there are several issues that are impacting on the implementation for more isolated schools. Concerns regarding staffing, cultural sensitivity, software selection and hardware maintenance are all discussed from the perspective of increasing the engagement of students with diverse needs in regular classes in remote and rural schools in Australia.
Financing of women-owned ventures: The impact of gender and other owner -and firm-related variables

Abstract While women-owned ventures represent an increasing proportion of new businesses in most western countries, most of them have particular financing patterns and encounter barriers in their access to financing. Recent research on the question argues that barriers to financing are mainly dependent on factors other than gender, such as owner- and firm-related characteristics. This quantitative and qualitative study, through descriptive statistics and interview analysis, examines the relationship between financing patterns and barriers and gender from the woman entrepreneur's viewpoint. It explores the behaviours and representations of women entrepreneurs towards financing, and considers to what extent the women see their own approaches as being different from those of men. Our study suggests that a gender effect still exists, and tries to identify its location and the corresponding implications for further research and action.
Characteristics and management of rash following lenalidomide and rituximab in patients with untreated indolent non-Hodgkin lymphoma

Low-grade rash may occur with lenalidomide, rituximab, or their combination (R2) in non-Hodgkin lymphoma (NHL). From our phase II study of R2 in previously untreated indolent lymphoma (n=110), 52 (47%) patients had rash, which was associated with pruritus in 22 (42%). Worst grade 1, 2, and 3 rash
SoK: Uncentralisable Ledgers and their Impact on Voting Systems

As we observe a trend towards the recentralisation of the Internet, this paper raises the question of guaranteeing an everlasting decentralisation. We introduce the properties of strong and soft uncentralisability in order to describe systems in which all authorities can be untrusted at any time without affecting the system. We link the soft uncentralisability to another property called perfect forkability. Using that knowledge, we introduce a new cryptographic primitive called uncentralisable ledger and study its properties. We use those properties to analyse what an uncentralisable ledger may offer to classic electronic voting systems and how it opens up the realm of possibilities for completely new voting mechanisms. We review a list of selected projects that implement voting systems using blockchain technol- ogy. We then conclude that the true revolutionary feature enabled by uncentralisable ledgers is a self-sovereign and distributed identity provider.
Multi-interval mapping of correlated trait complexes

Employing Monte Carlo simulations, we demonstrate the advantages of multitrait analysis in detection of linked QTL effects within the framework of mixture models. In spite of an increased number of parameters to be estimated, compared to the single-trait formulation, the proposed method allows for an improvement of detection power and estimation precision of linked QTLs in both adjacent or nonadjacent intervals, with coupling and repulsion effects. The results obtained are illustrated by examples based on data of the North American Barley Genome Mapping Project.
An evaluation method of web energy based on content tendency and users' focus

Different web contents have an immediate influence on users' intuitions after they browse the web page. The term “web energy” in this paper is defined as the user's overall sense of the web page. The evaluation of the web energy is not only related to the contents on the web pages, but also more concerned with the contents' positions. In addition, the level of users' attention for the positions is the most important factor in the evaluation process. In this paper, we put forward an algorithm to evaluate the web energy based on those three factors: content, position, and user's attention to the position. The tendency of the content is obtained by the user ratings in virtue of subjective experiments. The location information of the content is acquired by analyzing the web source code to obtain its corresponding location parameters. The user's attention to different locations of the web page is gained with the help of an Eye Tracker, which can be used to obtain and analyze the visual information of the user. Combined with the user's tendency of contents and the level of attention for different locations, we can assess the user's overall feeling of the web page as the web energy. Taking the Phoenix (http://news.ifeng.com/) as an example in the experiment, the paper carries on the test for several days in a row to assess its web energy. Experimental results verify the effectiveness of the proposed algorithm. Moreover, the importance of location information proposed in this paper is also analyzed in detail in this section.
Context-sensitive Sentiment Propagation in WordNet

In this paper we present a comprehensive overview of recent methods of the sentiment propagation in a wordnet. Next, we propose a fully automated method called Classifier-based Polarity Propagation, which utilises a very rich set of features, where most of them are based on wordnet relation types, multi-level bag-of-synsets and bag-of-polarities. We have evaluated our solution using manually annotated part of plWordNet 3.1 emo, which contains more than 83k manual sentiment annotations, covering more than 41k synsets. We have demonstrated that in comparison to existing rule-based methods using a specific narrow set of semantic relations our method has achieved statistically significant and better results starting with the same seed synsets.
The NoXi database: multimodal recordings of mediated novice-expert interactions

We present a novel multi-lingual database of natural dyadic novice-expert interactions, named NoXi, featuring screen-mediated dyadic human interactions in the context of information exchange and retrieval. NoXi is designed to provide spontaneous interactions with emphasis on adaptive behaviors and unexpected situations (e.g. conversational interruptions). A rich set of audio-visual data, as well as continuous and discrete annotations are publicly available through a web interface. Descriptors include low level social signals (e.g. gestures, smiles), functional descriptors (e.g. turn-taking, dialogue acts) and interaction descriptors (e.g. engagement, interest, and fluidity).