Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma.
CLIL’s Role in Facilitating Intercultural Learning

Alongside the globalisation phenomenon, many European countries have already situated their educational practice in existing multilingual contexts. The multilingualism policies of the European Union provided an ideal backdrop to the development of integrative approaches such as Content and Language Integrated Learning (CLIL) and, as a result, the term CLIL was coined in 1996 through sustained interest and pedagogical activity in the field of bilingual education across Europe. CLIL environments can also facilitate the promotion of intercultural communicative competence as described in the Common European Framework of Reference for Languages. In addition, as culture seems to be one of the five dimensions of CLIL provision, it is essential to discuss and consider the incorporation of an intercultural perspective in CLIL. The integrative nature of CLIL gives an opportunity for a simultaneous combination of foreign language learning, content subject learning and intercultural learning.
On the Variability in Goblet Cell Density in Human Bulbar Conjunctival Samples Collected by Impression Cytology with Millicell-CM Biopore Membrane Units

ABSTRACT Purpose: To assess whether or not the numbers of goblet cells were different across regions of a conjunctival impression cytology (CIC) specimen. Methods: CIC specimens were obtained from the exposed nasal bulbar conjunctiva from 22 healthy young Caucasian adults, stained with Giemsa and evaluated at a final magnification of 200× (medium power fields). Up to 14 different non-overlapping microscope fields, depending on whether or not a field was without goblet cells, were randomly selected. Results: A microscope field could contain between 0 and 145 goblet cells. If only fields that included goblet cells were analyzed, the mean goblet cell counts (22 specimens, 10 fields/specimen) ranged from 37.8 to 44.8/field (equivalent to 259–313 goblet cells/mm2). When 3, 5 or 10 fields were used to calculate average goblet cell counts for each specimen, the standard deviation values were between 15.8/field and 21.7/field, with the lower values obtained if 10 fields were used. The resultant averaged inter-sample variability, as the coefficient of variation (COV), ranged from 40.0% to 57.5%, while the averaged intra-sample variability in counts ranged from 52.1% to 73.9%. If fields without goblet cells were also used, the resultant mean goblet cell count (from 10 fields/specimen) was statistically lower at 33.1/field (232 goblet cells/mm2). Conclusions: These analyses confirm various subjective comments made by early CIC investigators; the distribution of goblet cells across a CIC filter may be highly variable.
Modulation of extracellular signal‐regulated kinase (ERK) activity by acute and chronic opioid treatment in neuronal and glial cell lines

Acute mu opioid application has been shown to activate extracellular signal‐related kinases (ERKs) in various non‐neural cell lines. However, ERK activation in neuronal cells following acute morphine treatment is more questionable. Moreover, the ERK activation phenomenon observed in vivo after withdrawal of chronic opioids has never been demonstrated in vitro. The goal of this study was to determine if mu agonist treatment induced ERK activation acutely or after withdrawal of chronic opioids in one glial and three neuronal cell lines. We found that acute application of opioids was not able to activate ERK in neuronal cell lines but was able to activate ERK in a glial cell line. In another set of experiments, cells were chronically treated with escalating doses of a mu opioid agonist. After 8 days, the agonist was removed from the media and naloxone applied. Acute ERK activation was not seen in any tested cell line after agonist removal. These findings suggest that opioids may acutely activate ERK in non‐neuronal cells, and that the acute ERK activation observed in some brain regions during opioid withdrawal in vivo might be mediated by indirect effects on neuronal cells.
An evaluation of statistical procedures for comparing an individual's performance with that of a group of controls

The single case methodology that is widely used in cognitive neuropsychology often requires a comparison of data from a single individual (the patient) with that from a group of controls, in order to ascertain whether the patient's mean score can be viewed as significantly different from that of controls. This article reviews methods that have been used to deal with such data. Although Analysis of Variance (ANOVA) provides one possible solution of comparing group means, unequal group sizes and differences in variability between patient and controls can violate the assumptions of the test. Using Monte Carlo simulations, it was found that differences in group size and a group of N = 1 did not significantly affect the reliability of the analysis. In contrast, unacceptably high Type I errors were obtained when, in addition to unequal group sizes, there were relatively modest differences between the variance of the patient and that of the controls. We suggest that ANOVA can be used for the comparison of the mean score of an individual with that of a group of controls, but that when there is a difference in variability between the two groups, revised F criteria should be used in order to make the analysis reliable. A table of modified F values is given, which can be used for various departures from homogeneity of variance.
Designing subtilisin BPN' to cleave substrates containing dibasic residues.

The bacterial serine protease, subtilisin BPN', has been mutated so that it will efficiently and selectively cleave substrates containing two consecutive basic (dibasic) residues. Mutants were designed on the basis of both the structure of subtilisin BPN' and considerations of sequence differences between it and eukaryotic homologs, Kex2, PC2, and furin, which are known to cleave dibasic substrates. These eukaryotic proteases have high sequence homology to one another but differ substantially from subtilisin BPN' in loops that interact with the substrate. When these loops were grafted into subtilisin BPN', the mutated enzyme could not be expressed, presumably due to destabilization of the folded enzyme. We noted that several neutral residues in subtilisin BPN' (Gly 166, Ser 33, and Asn 62) that are positioned to interact with a dibasic substrate are acidic residues at analogous positions in Kex2. Mutating these residues individually to either Glu or Asp in subtilisin BPN' resulted in systematic shifts in substrate specificity (kcat/Km) toward basic residues and away from the natural preference for hydrophobic substrates. A combination mutant, where Asn 62 was changed to Asp and Gly 166 was changed to Asp (N62D/G166D), had a larger than additive shift in specificity toward dibasic substrates. This unexpectedly large change was confirmed by detailed analysis with a variety of synthetic substrates. Additional substrate determinants were revealed by sorting a library of phage particles (substrate phage) containing five contiguous randomized residues. This method identified a particularly good substrate (Asn-Leu-Met-Arg-Lys) that was selectively cleaved in the context of a fusion protein by the N62D/G166D subtilisin. (ABSTRACT TRUNCATED AT 250 WORDS)
The Mood‐Stabilizing Agent Valproate Inhibits the Activity of Glycogen Synthase Kinase‐3

Abstract : Valproic acid (VPA) is a potent broad‐spectrum anti‐epileptic with demonstrated efficacy in the treatment of bipolar affective disorder. It has previously been demonstrated that both VPA and lithium increase activator protein‐1 (AP‐1) DNA binding activity, but the mechanisms underlying these effects have not been elucidated. However, it is known that phosphorylation of c‐jun by glycogen synthase kinase (GSK)‐3β inhibits AP‐1 DNA binding activity, and lithium has recently been demonstrated to inhibit GSK‐3β. These results suggest that lithium may increase AP‐1 DNA binding activity by inhibiting GSK‐3β. In the present study, we sought to determine if VPA, like lithium, regulates GSK‐3. We have found that VPA concentration‐dependently inhibits both GSK‐3α and ‐3β, with significant effects observed at concentrations of VPA similar to those attained clinically. Incubation of intact human neuroblastoma SH‐SY5Y cells with VPA results in an increase in the subsequent in vitro recombinant GSK‐3β‐mediated 32P incorporation into two putative GSK‐3 substrates (~85 and 200 kDa), compatible with inhibition of endogenous GSK‐3β by VPA. Consistent with GSK‐3β inhibition, incubation of SH‐SY5Y cells with VPA results in a significant time‐dependent increase in both cytosolic and nuclear β‐catenin levels. GSK‐3β plays a critical role in the CNS by regulating various cytoskeletal processes as well as long‐term nuclear events and is a common target for both lithium and VPA ; inhibition of GSK‐3β in the CNS may thus underlie some of the long‐term therapeutic effects of mood‐stabilizing agents.
Organizational learning: cognitive and behavioural changes and implications in higher education institutions

Many facets of the concept of “organizational learning” and many ideas about it have been debated in the literature. One of the issues raised is whether organizational learning necessarily needs to encompass changes at both cognitive and behavioural levels in an organization or if one of these two types of changes is enough. The issue is even more complicated because changes in behaviour could be also related to adaptation and not learning. There is also the question if learning has really occurred if there is no change in behaviour, but only in cognition. Also, are organizational learning and changes in cognition or behaviour always beneficial for an organization? Therefore, the paper explores and expresses our position in the matter of the cognitive and behavioural dilemma regarding organizational learning. We are approaching these issues, as well as presenting some implications in the case of higher education institutions.
Primary “Cutaneous” T-Cell Anaplastic Large Cell Lymphoma, CD30+, Neutrophil-Rich Variant with Subcutaneous Panniculitic Lesions, in a Post-Renal Transplant Patient: Report of Unusual Case and Literature Review

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of “cutaneous” presentation by CD30+ (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30+ with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare “cutaneous” lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.
Extracting Requirements Patterns from Software Repositories

Open Source Software (OSS) hosted in Repositories such as GitHub can be valuable as a source of information for requirements engineers, especially in the apprentice phase of a new application. In this context, we propose a strategy to speed up the discovery of valuable information, since manual search may be time consuming in the vast dataset of GitHub projects. Our strategy is based on the identification of requirements patterns as a way to summarize requirements-related information. Initial work has been performed using Music Application as a domain exemplar, and focusing on the Read-me perspective of GitHub projects. We explore some of our earlier findings, as well as present an overall architecture where patterns will be central in organizing information.
Analysis of the effects of HIV‐1 Tat on the survival and differentiation of vessel wall‐derived mesenchymal stem cells

HIV infection is an independent risk factor for atherosclerosis development and cardiovascular damage. As vessel wall mesenchymal stem cells (MSCs) are involved in the regulation of vessel structure homeostasis, we investigated the role of Tat, a key factor in HIV replication and pathogenesis, in MSC survival and differentiation. The survival of subconfluent MSCs was impaired when Tat was added at high concentrations (200–1,000 ng/ml), whereas lower Tat concentrations (1–100 ng/ml) did not promote apoptosis. Tat enhanced the differentiation of MSC toward adipogenesis by the transcription and activity upregulation of PPARγ. This Tat‐related modulation of adipogenesis was tackled by treatment with antagonists of Tat‐specific receptors such as SU5416 and RGD Fc. In contrast, Tat inhibited the differentiation of MSCs to endothelial cells by downregulating the expression of VEGF‐induced endothelial markers such as Flt‐1, KDR, and vWF. The treatment of MSCs with Tat‐derived peptides corresponding to the cysteine‐rich, basic, and RGD domains indicated that these Tat regions are involved in the inhibition of endothelial marker expression. The Tat‐related impairment of MSC survival and differentiation might play an important role in vessel damage and formation of the atherosclerotic lesions observed in HIV‐infected patients. J. Cell. Biochem. 113: 1132–1141, 2012. © 2011 Wiley Periodicals, Inc.
Topic discovery of clusters from documents with geographical location

As smart phones with GPS become popular, more and more textual documents with geographical locations are published on the Web. Keyword‐based location services like vehicle navigation, tour planning, nearby object querying, and location pattern discovering of spatial objects are becoming popular and important. However, processing both text and geographical locations brings more challenges to information‐retrieval techniques. In this paper, we focus on the problem of finding textual topics of clusters containing spatial objects with text descriptions. The key is how to combine clustering techniques with topic‐retrieval models to integrate both geo‐location information and text information. We investigated methods that combine clustering methods with the Latent Dirichlet Allocation model to discover topics of clusters of documents with geo‐locations. Six different methods of combination are investigated, each having outputs with different meanings, which can be further leveraged to answer different types of queries over spatial documents. Experiments are conducted on both synthetic and real data. The results show that the combination of the probabilistic topic model with clustering algorithms is an efficient and effective way to discover meaningful clusters in different facets and levels of documents with textual and geographical information. Copyright © 2015 John Wiley & Sons, Ltd.
Health costs and benefits from a pilot rural sanitation intervention in India

India hosts two-thirds of the global population defecating in the open and faces a worrying trend of districts declared ‘water scarce’. This paper aims to assess the costs and health benefits of sanitation interventions undertaken by the National Rural Drinking Water Security Pilot Project in India between 2012 and 2015. To achieve this goal, a pretest–posttest control group study was undertaken in two study areas located in Karnataka and Uttar Pradesh states. Full software and infrastructure costs were included as well as health endpoints, sourced from primary health centers. In Karnataka, latrine coverage of households increased from 16% to 59% in villages with high level of interventions, and from 7% to 18% in villages with lower levels of intervention. In Uttar Pradesh, coverage increased from 33% to 70% in high intervention villages and from 27% to 39% in the low intervention villages. We found health-related net benefits of USD 13 and USD 10 per person per year and benefit/cost ratios of 2.5 and 5.0 in Karnataka Uttar Pradesh, respectively. Given the positive economic returns on the intervention in culturally heterogeneous sites of southern and northern India, this intervention has potential for bringing significant benefits to the Indian population.
Pain processing within the primary somatosensory cortex in humans

To investigate the processing of noxious stimuli within the primary somatosensory cortex (SI), we recorded magnetoencephalography following noxious epidermal electrical stimulation (ES) and innocuous transcutaneous electrical stimulation (TS) applied to the dorsum of the left hand. TS activated two sources sequentially within SI: one in the posterior bank of the central sulcus and another in the crown of the postcentral gyrus, corresponding to Brodmann's areas 3b and 1, respectively. Activities from area 3b consisted of 20‐ and 30‐ms responses. Activities from area 1 consisted of three components peaking at 26, 36 and 49 ms. ES activated one source within SI whose location and orientation were similar to those of the TS‐activated area 1 source. Activities from this source consisted of three components peaking at 88, 98 and 109 ms, later by 60 ms than the corresponding TS responses. ES and TS subsequently activated a similar region in the upper bank of the sylvian fissure, corresponding to the secondary somatosensory cortex (SII). The onset latency of the SII activity following ES (109 ms) was later by 29 ms than that of the first SI response (80 ms). Likewise, the onset latency of SII activity following TS (52 ms) was later by 35 ms than that of area 1 of SI (17 ms). Therefore, our results showed that the processing of noxious and innocuous stimuli is similar with respect to the source locations and activation timings within SI and SII except that there were no detectable activations within area 3b following noxious stimulation.
Unique Features of Plant Cleavage and Polyadenylation Specificity Factor Revealed by Proteomic Studies1[C][W][OA]

Cleavage and polyadenylation of precursor mRNA is an essential process for mRNA maturation. Among the 15 to 20 protein factors required for this process, a subgroup of proteins is needed for both cleavage and polyadenylation in plants and animals. This subgroup of proteins is known as the cleavage and polyadenylation specificity factor (CPSF). To explore the in vivo structural features of plant CPSF, we used tandem affinity purification methods to isolate the interacting protein complexes for each component of the CPSF subunits using Arabidopsis (Arabidopsis thaliana ecotype Landsberg erecta) suspension culture cells. The proteins in these complexes were identified by mass spectrometry and western immunoblots. By compiling the in vivo interaction data from tandem affinity purification tagging as well as other available yeast two-hybrid data, we propose an in vivo plant CPSF model in which the Arabidopsis CPSF possesses AtCPSF30, AtCPSF73-I, AtCPSF73-II, AtCPSF100, AtCPSF160, AtFY, and AtFIPS5. Among them, AtCPSF100 serves as a core with which all other factors, except AtFIPS5, are associated. These results show that plant CPSF possesses distinct features, such as AtCPSF73-II and AtFY, while sharing other ortholog components with its yeast and mammalian counterparts. Interestingly, these two unique plant CPSF components have been associated with embryo development and flowering time controls, both of which involve plant-specific biological processes.
Region‐specific plasticity in the epileptic rat brain: A hippocampal and extrahippocampal analysis

Purpose: Recent evidence suggests that aberrant neuro/gliogenesis and/or inflammation play critical roles in epileptogenesis. Although the plastic and inflammatory changes have been described in the postseizure hippocampus, little data is available concerning extrahippocampal regions, notably in the piriform and entorhinal cortices, amygdala, and parts of the thalamus. In this study, we examined histological changes in whole epileptic rat brain, with respect to cell death, cell genesis, and inflammation.
Brachybacterium ginsengisoli sp. nov., isolated from soil of a ginseng field.

A novel Gram-staining-positive, aerobic bacterium, designed DCY80(T), was isolated from soil of a ginseng field in the Republic of Korea. 16S rRNA gene sequence analysis revealed that strain DCY80(T) belonged to the genus Brachybacterium (95.8-98.2 % similarity) and was most closely related to Brachybacterium faecium DSM 4810(T) (98.2 %). Colonies were circular, entire, low-convex, opaque and 0.5-1.0 mm in diameter after growth for 2 days on TSA at 30 °C. Growth occurred at 4-34 °C (optimum, 25 °C), at pH 5.0-10.0 (optimum, pH 6.5-7.0) and in the presence of 0-7.0 % NaCl. Strain DCY80(T) produced siderophores and was sensitive to penicillin G, erythromycin, cefazolin, oleandomycin, ceftazidime, vancomycin, tetracycline, novobiocin, carbamicillin, rifampicin and neomycin. The DNA G+C content was 71.0 mol%. Levels of DNA-DNA relatedness between strain DCY80(T) and B. faecium DSM 4810(T), B. paraconglomeratum KCTC 9916(T), B. saurashtrense DSM 23186(T) and B. conglomeratum KCTC 9915(T) were 46.9±0.5, 28.9±0.6, 20.4±0.9 and 17.3±0.4 %, respectively. The cell-wall peptidoglycan of strain DCY80(T) contained meso-diaminopimelic acid as the diagnostic diamino acid. The menaquinones were MK-7 (85.8 %) and MK-8 (14.2 %). The major cellular fatty acids were anteiso-C15 : 0 (69.1 %) and anteiso-C17 : 0 (12.2 %). Phosphatidylglycerol, diphosphatidylglycerol, an unidentified glycolipid, two unidentified phospholipids and five unidentified polar lipids were found. On the basis of our phenotypic and genotypic analyses, strain DCY80(T) represents a novel species of the genus Brachybacterium, for which the name Brachybacterium ginsengisoli sp. nov. is proposed (type strain DCY80(T) = KCTC 29226(T) = JCM 19356(T)).