Miracle-dz/UniFAR-FTUs huggingface dataset:
Transient Receptor Potential Melastatin-3 (TRPM3)–Induced Activation of AP-1 Requires Ca2+ Ions and the Transcription Factors c-Jun, ATF2, and Ternary Complex Factor

The steroid pregnenolone sulfate activates the transcription factor activator protein-1 (AP-1) via stimulation of transient receptor potential melastatin-3 (TRPM3) channels. Here, we show that the signaling pathway requires an influx of Ca2+ ions into the cells and a rise in the intracellular Ca2+ levels. The upregulation of AP-1 was attenuated in cells that overexpressed mitogen activated protein kinase phosphatase–1, indicating that Ca2+ ions prolong the signaling cascade via activation of mitogen activated protein kinases. On the transcriptional level, expression of a dominant-negative mutant of the basic region leucine zipper protein c-Jun, a major constituent of the AP-1 transcription factor complex, or expression of a c-Jun–specific short hairpin RNA attenuated pregnenolone sulfate–induced AP-1 activation. In addition, stimulation of TRPM3 channels increased the transcriptional activation potential of the basic region leucine zipper protein ATF2. Inhibition of ATF2 target gene expression via expression of a dominant-negative mutant of ATF2 or expression of an ATF2-specific short hairpin RNA interfered with TRPM3-mediated stimulation of AP-1. Moreover, we show that a dominant-negative mutant of the ternary complex factor (TCF) Elk-1 attenuated the upregulation of AP-1 following stimulation of TRPM3 channels. Thus, c-Jun, ATF2, and TCFs are required to connect the intracellular signaling cascade elicited by activation of TRPM3 channels with enhanced transcription of AP-1–regulated genes. We conclude that pregnenolone sulfate–induced TRPM3 channel activation changes the gene expression pattern of the cells by activating transcription of c-Jun-, ATF2-, and TCF-controlled genes.
A New Evolutionary Learning Model for Handwritten Character Prototyping

The work reported in this paper is aimed at exploiting evolutionary learning algorithms for producing the set of prototypes to be used by a handwriting recognition system. In this paper we propose a new evolutionary learning model that combines the power of search of a classical evolutionary algorithm, namely a breeder genetic algorithm, with a novel mechanism for implementing the interaction between the evolving population and the environment. The proposed model allows the system to search for the prototypes by means of a simple iterative strategy rather than through a parallel and adaptive search, as generally happens in evolutionary learning. Experimental results on handwritten digits have shown that the performance of the proposed algorithm is similar to that exhibited by more complex evolutionary learning algorithms, and better than that provided by a neural network.
Relationships between oleic acid uptake and lipid metabolism in Mycobacterium smegmatis.

Mycobacterium smegmatis rapidly incorporated tracer amounts of oleic acid into triglycerides. When cells were incubated with greater amounts of oleate, the fatty acid was incorporated into triglycerides with saturating kinetics, after which the fatty acid taken up remained free in the cytoplasm as globules. Most of the oleate incorporated into the triglycerides was added to the carbon 3 position of the molecule.
On the Fusion of Compton Scatter and Attenuation Data for Limited-view X-ray Tomographic Applications

In this paper we demonstrate the utility of fusing energy-resolved observations of Compton scattered photons with traditional attenuation data for the joint recovery of mass density and photoelectric absorption in the context of limited view tomographic imaging applications. We begin with the development of a physical and associated numerical model for the Compton scatter process. Using this model, we propose a variational approach recovering these two material properties. In addition to the typical data-fidelity terms, the optimization functional includes regularization for both the mass density and photoelectric coefficients. We consider a novel edge-preserving method in the case of mass density. To aid in the recovery of the photoelectric information, we draw on our recent method in \cite{r15} and employ a non-local regularization scheme that builds on the fact that mass density is more stably imaged. Simulation results demonstrate clear advantages associated with the use of both scattered photon data and energy resolved information in mapping the two material properties of interest. Specifically, comparing images obtained using only conventional attenuation data with those where we employ only Compton scatter photons and images formed from the combination of the two, shows that taking advantage of both types of data for reconstruction provides far more accurate results.
Fukutin-related Protein Associates with the Sarcolemmal Dystrophin-Glycoprotein Complex*

Mutations in fukutin-related protein (FKRP) give rise to mild and more severe forms of muscular dystrophy. FKRP patients have reduced glycosylation of the extracellular protein dystroglycan, and FKRP itself shows sequence similarity to glycosyltransferases, implicating FKRP in the processing of dystroglycan. However, FKRP localization is controversial, and no FKRP complexes are known, so any FKRP-dystroglycan link remains elusive. Here, we demonstrate a novel FKRP localization in vivo; in mouse, both endogenous and recombinant FKRP are present at the sarcolemma. Biochemical analyses revealed that mouse muscle FKRP and dystroglycan co-enrich and co-fractionate, indicating that FKRP coexists with dystroglycan in the native dystrophin-glycoprotein complex. Furthermore, FKRP sedimentation shifts with dystroglycan in disease models involving the dystrophin-glycoprotein complex, and sarcolemmal FKRP immunofluorescence mirrors that of dystroglycan in muscular dystrophy mice, suggesting that FKRP localization may be mediated by dystroglycan. These data offer the first evidence of an FKRP complex in muscle and suggest that FKRP may influence the glycosylation status of dystroglycan from within the sarcolemmal dystrophin-glycoprotein complex.
Does Current Oral Antiplatelet Agent or Subtherapeutic Anticoagulation Use Have an Effect on Tissue-Plasminogen-Activator-Mediated Recanalization Rate in Patients with Acute Ischemic Stroke?

Objective: Our goal is to assess if current antiplatelet (AP) use has an effect on recanalization rate and outcome in acute stroke patients. Methods: We conducted a retrospective analysis of acute stroke patients who received intravenous (IV) recombinant tissue plasminogen activator (rt-PA) and had transcranial Doppler examination within 3 h of symptom onset. The TCD findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion or complete recanalization. Complete recanalization was defined as established Thrombolysis in Brain Ischemia 4 or 5 within 2 h of IV rt-PA. The patients were divided based on their current use of AP agents. Comparisons were made between the different groups based on recanalziation rate, reocclusion and good long-term outcome (mRS ≤2) using χ2 test. Multiple regression analysis was used to identify AP use as a predictor for recanalization and outcome including symptomatic intracranial hemorrhage after controlling for age, baseline NIHSS score, time to treatment, previous vascular event, hypertension and diabetes mellitus. Results: Two hundred and eighty-four patients were included; 154 (54%) males, 130 (46%) females, with a mean age of 69.5 ± 13 years. The median baseline NIHSS score was 16 ± 5. The median time to TCD examination was 131 ± 38 min from symptom onset. The median time to IV rt-PA was 140 ± 34 min. One hundred eighty patients were not on AP prior to their stroke, 76 were on aspirin, 15 were on clopidogrel, 2 were on aspirin-dipyridamole combination, 2 were on both aspirin and clopidogrel, and 9 patients on subtherapeutic coumadin. In patients who were naïve to AP, 68/178 (38.2%) had complete recanalization, whereas in the AP group, 25/91 (28%) had complete recanalization. Patients on aspirin alone had a lower recanalization rate (16/72) as compared to those not on AP (22 vs. 39%) (p = 0.017), while those on clopidogrel had higher rates of complete recanalization (9/19, 60%). There was no difference in the rate of symptomatic intracranial hemorrhages in patients on AP agents as compared to those not on AP (9/180, 5% vs. 9/95, 9.5%) (p = 0.13). A good long-term outcome (mRS ≤2) was achieved in 85/160 (53%) of the patients naïve to AP and in 33/84 (39%) of the patients on AP (p = 0.035). In multiple regression, AP use was not a predictor of either recanalization rate (p = 0.057) or good outcome (p = 0.27). Conclusions: No correlation was found between AP use and recanalization rate and good outcome in patients with acute stroke who received IV rt-PA treatment. Prior AP use should not defer patients from receiving IV rt-PA treatment in an acute stroke setting.
Comprehensive Clinical Assessment in Community Setting: Applicability of the MDS‐HC

OBJECTIVE: To describe the results of an international trial of the home care version of the MDS assessment and problem identification system (the MDS‐HC), including reliability estimates, a comparison of MDS‐HC reliabilities with reliabilities of the same items in the MDS 2.0 nursing home assessment instrument, and an examination of the types of problems found in home care clients using the MDS‐HC.
Rapid colorimetric hybridization assay for detecting amplified Helicobacter pylori DNA in gastric biopsy specimens

A very simple, practical, sensitive, and specific colorimetric hybridization assay for detecting amplified Helicobacter pylori DNA is described. This assay, which combines a sensitive sandwich DNA hybridization reaction and a colorimetric protocol similar to those used in conventional enzyme immunoassays, was shown to be suitable for detecting H. pylori-infected gastric biopsy specimens and for monitoring the eradication of the pathogen after treatment. The specificity and sensitivity of the colorimetric hybridization assay were tested by assaying 27 H. pylori strains (4 reference and 23 clinical isolates), 9 strains of other Helicobacter spp. or Campylobacter spp. , and 11 clinical isolates of other urease-positive bacteria. The likelihood of H. pylori detection in gastric biopsy specimens by the colorimetric hybridization assay was evaluated with 23 H. pylori-positive and 41 H. pylori-negative biopsy specimens on the basis of positive and negative results, respectively, of culture, rapid urease test, histological examination, and PCR. Biopsy specimens from 33 treated patients, endoscopied 4 to 8 weeks after the end of treatment, were also tested. All H. pylori strains showed positive results in the colorimetric hybridization assay, presenting optical densities at 450 nm (OD450S) of > or = 3.0. None of the other Helicobacter spp. , Campylobacter spp. , or the clinical isolates of other urease-positive bacteria showed OD450S equal to or greater than the cutoff (mean OD450 cutoff, 0.208). The colorimetric hybridization assay detected all 23 H. pylori-positive biopsy specimens (mean OD450, 2.910 +/- 0.295), while none of the H. pylori-negative biopsy specimens was shown to be positive in the assay (mean OD450, 0.108 +/- 0.025). H. pylori was considered to be not eradicated from three of the posttreatment biopsy specimens by culture, rapid urease test, histological examination, and PCR. They were all positive by the colorimetric hybridization assay, and their OD450S were > or = 3.0. The colorimetric hybridization assay also detected two other H. pylori-positive patients. Specimens from these two patients had negative culture, rapid urease test, and histology results, and a specimen from one of them also tested negative by PCR. These results indicate that the colorimetric hybridization assay is a suitable method both for the diagnosis of H. pylori in biopsy specimens and for the follow-up of patients after the end of treatment.
5-Lipoxygenase Is a Direct Target of miR-19a-3p and miR-125b-5p

5-Lipoxygenase (5-LO) is the key enzyme in leukotriene biosynthesis. Leukotrienes are mediators of the innate immune system and inflammatory processes, and they might also be involved in cancer development. MicroRNAs (miRNAs) are important translational regulators and have been shown to be involved in development, differentiation, and cancer. Unraveling the miRNA network is important for understanding the cellular regulation processes. We identified two new miRNAs, miR-19a-3p and miR-125b-5p, regulating 5-LO and confirmed direct interaction by reporter gene assays. Furthermore, we investigated the regulation of 5-LO by these two miRNAs in several cell types. Inhibition of both miRNAs by antagomirs during differentiation of the myeloid cell line Mono Mac 6 led to a significant increase in 5-LO protein expression. Stimulation of human T lymphocytes with PHA resulted in a strong downregulation of 5-LO mRNA expression and in the induction of miR-19a-3p. The inhibition of miR-19a-3p with an antagomir led to a significant increase in 5-LO mRNA expression in T lymphocytes. Taken together, our data reveal that miR-19a-3p and miR-125b-5p target 5-LO in a cell type– and stimulus-specific manner.
High-Quality Exome Sequencing of Whole-Genome Amplified Neonatal Dried Blood Spot DNA

Stored neonatal dried blood spot (DBS) samples from neonatal screening programmes are a valuable diagnostic and research resource. Combined with information from national health registries they can be used in population-based studies of genetic diseases. DNA extracted from neonatal DBSs can be amplified to obtain micrograms of an otherwise limited resource, referred to as whole-genome amplified DNA (wgaDNA). Here we investigate the robustness of exome sequencing of wgaDNA of neonatal DBS samples. We conducted three pilot studies of seven, eight and seven subjects, respectively. For each subject we analysed a neonatal DBS sample and corresponding adult whole-blood (WB) reference sample. Different DNA sample types were prepared for each of the subjects. Pilot 1: wgaDNA of 2x3.2mm neonatal DBSs (DBS_2x3.2) and raw DNA extract of the WB reference sample (WB_ref). Pilot 2: DBS_2x3.2, WB_ref and a WB_ref replica sharing DNA extract with the WB_ref sample. Pilot 3: DBS_2x3.2, WB_ref, wgaDNA of 2x1.6 mm neonatal DBSs and wgaDNA of the WB reference sample. Following sequencing and data analysis, we compared pairwise variant calls to obtain a measure of similarity—the concordance rate. Concordance rates were slightly lower when comparing DBS vs WB sample types than for any two WB sample types of the same subject before filtering of the variant calls. The overall concordance rates were dependent on the variant type, with SNPs performing best. Post-filtering, the comparisons of DBS vs WB and WB vs WB sample types yielded similar concordance rates, with values close to 100%. WgaDNA of neonatal DBS samples performs with great accuracy and efficiency in exome sequencing. The wgaDNA performed similarly to matched high-quality reference—whole-blood DNA—based on concordance rates calculated from variant calls. No differences were observed substituting 2x3.2 with 2x1.6 mm discs, allowing for additional reduction of sample material in future projects.
a SU 2 , an Epithelial Integrin That Binds aminin in the Sea Urchin Embryo

At gastrulation in the sea urchin embryo dramatic cell adhesion changes contribute to primary mesenchyme cell ingression movements and to cell rearrangements during archenteron invagination. At ingression, quantitative adhesion assays demonstrated previously that primary mesenchyme cells (PMCs) change their affinity for neighboring cells, for a fibronectin-like substrate, and for the hyaline layer. To investigate the molecular basis for these and other differential cell affinities at gastrulation, we have identified an integrin that appears to be responsible for specific alterations in cell–substrate adhesion to laminin. During early cleavage stages blastomeres adhere poorly to laminin substrates. Around hatching there is a large increase in the ability of blastomeres to bind to laminin and this increase correlates temporally with the expression of an integrin on the basal surface all blastomeres. PMCs, after undergoing their epithelial–mesenchymal transition, have a strongly reduced affinity for laminin relative to ectoderm cells and, correspondingly, do not stain for the presence of the integrin. We identified the a integrin cDNA from Lytechinus variegatus by RT-PCR. Overlapping clones ere obtained from a midgastrula cDNA library to provide a complete sequence for the integrin. The composite cDNA ncoded a protein that was most similar to the a5 subgroup of vertebrate integrins, but there was not a definitive vertebrate ntegrin homolog. Northern blots and Western immunoblots showed that the sea urchin integrin, which we have named aSU2, is present in eggs and during all stages of development. Immunolocalization with specific polyclonal antibodies showed that aSU2 first appears on the basal cell surface of epithelia at the midblastula stage, at a time correlating with the increase in adhesive affinity for laminin. The protein remains at high levels on the basal surface of ectoderm cells but is temporarily reduced or eliminated from endoderm cells during their convergent–extension movements. To confirm integrin binding specificity, aSU2 was transfected into an a-integrin-deficient CHO cell line. aSU2-expressing CHO cells bound well to isolated sea urchin basal lamina and to purified laminin. The transfected cells bound weakly or not at all to fibronectin, type I collagen, and type IV collagen. This is consistent with the hypothesis that aSU2 integrin functions by binding epithelial cells to laminin in the basal lamina. In vivo, modulation of aSU2 integrin expression correlates with critical dhesive changes during cleavage and gastrulation. Thus, this protein appears to be an important contributor to the orphogenetic rearrangements that characterize gastrulation in the sea urchin embryo. © 1999 Academic Press
Understanding game design for affective learning

Affective learning is an important aspect of education that can be supported through games. This paper focuses on how games can and do address affective learning, especially in light of the growing trend of educational and serious games aiming at changing behavior and attitudes. To support affective learning though games, player emotions need to be recognized and interpreted, and an emotional experience needs to be created that motivates players and deepens learning. Moreover, there is also a need to understand affective representations and mechanisms that games support. The paper begins with a presentation of the different perspectives on affective learning, and then takes a focus on the socio-emotional component of the affective domain. An "affective walkthrough" technique is then introduced to understand and analyze affective strategies in games. This technique is then applied to the game Ico, showing its affective strategies and how these strategies can be leveraged for designing socio-emotional learning. The paper is concluded with an outline of an approach to designing games especially for affective learning, by identifying the key principles, creating a repertory of affective learning game patterns, and using methods to contextualize gameplay and facilitate learning.
OPTICAL CHARACTER RECOGNITION TECHNIQUE ALGORITHMS

In this paper, we present a new neural network (NN) based method for optical character recognition (OCR) as well as handwritten character recognition (HCR). Experimental results show that our proposed method achieves increased accuracy in optical character recognition as well as handwritten character recognition. We present through an overview of existing handwritten character recognition techniques. All the algorithms describes more or less on their own. Handwritten character recognition is a very popular and computationally expensive task; we describe advanced approaches for handwritten character recognition. In the present work, we would like to compare the most important once out of the variety of advanced existing techniques, and we will systematize the techniques by their characteristic considerations. It leads to the behaviour of the algorithms reaches to the expected similarities. KeywordsOCR, HCR, Neural Network. Recognition Technique
Age-Group and Gender Classification through Class-Dependent Phone Recognition

This study proposes a method to determine the gender and age group of a speaker by means of an automatic speech recognition system that is trained on six different sets of phones: one for each intersection of the two gender and three age-group classes. The study uses the Australian National Database of Spoken Language (ANDOSL) with 18 speakers in each class reading a set of 200 phonetically rich sentences. The system trains 44 context-independent phone models for each of the six classes and determines the gender and age group of an unknown utterance by finding the best matching phone sequence against the combined set of 264 phone models. Two methods of utilising the resulting phone sequences for gender and age-group recognition are evaluated: firstly, simple counting of the number of phones that belong to each class is used as the basis for the six-way class decision; secondly, the recognised phone sequence is converted to a 264-dimensional vector, whose components contain the phone counts in the phone sequence for each of the 6 x 44 phones in the combined set. An artificial neural network is trained to make the final gender and age-group decision using the count vectors as input. The artificial neural network outperforms the simple counting method with an average correct recall for gender of 97.7%, an average correct recall for age group of 60.5% and an average correct recall for combined gender and age group of 58.9%. Index Terms: Gender classification, age classification, speaker characterisation.
The dynamics of genetic control in the cell: the good and bad of being late

The expression of genes in the cell is controlled by a complex interaction network involving proteins, RNA and DNA. The molecular events associated with the nodes of such a network take place on a variety of time scales, and thus cannot be regarded as instantaneous. In many cases, the cell is robust with respect to the delay in gene expression control, behaving as if it were instantaneous. However, there are specific cases in which delay gives rise to temporal oscillations. This is the case, for example, of the expression of tumour-suppressor protein p53, of protein Hes1, involved in the differentiation of stem cells, of NFkB and Wnt, in which case delay arises implicitly from the structure of the associated network. By means of delay rate equations, we study the kinetics of small regulatory networks, emphasizing the role of delay in an evolutionary context. These models suggest that oscillations are a typical outcome of the dynamics of regulatory networks, and evolution has to work to avoid them when not required (and not vice versa).