Miracle-dz/UniFAR-FTUs huggingface dataset:
Crohn's disease-associated adherent invasive Escherichia coli modulate levels of microRNAs in intestinal epithelial cells to reduce autophagy.

BACKGROUND & AIMS Levels of microRNAs are altered in intestinal tissues of patients with Crohn's disease (CD). The adherent-invasive Escherichia coli (AIEC), which colonize the ileal mucosa of patients with CD, adhere to and invade intestinal epithelial cells. We investigated the mechanism by which AIEC infection alters the expression of microRNAs and the host immune response. METHODS Levels of microRNAs in human intestinal epithelial T84 cells and in mouse enterocytes were measured using quantitative reverse-transcription polymerase chain reaction. Luciferase assays were used to measure binding of microRNAs to the 3'-untranslated region of messenger RNA targets. Binding of nuclear factor-κB to promoters of genes encoding microRNAs was assessed by chromatin immunoprecipitation assays. Autophagy was measured by immunoblot analyses and immunofluorescent labeling of LC3. Anti-microRNAs were transferred to mice using ileal loops. Biopsy specimens from the terminal ileum of patients with ulcerative colitis (n = 20), CD (n = 20), or individuals without inflammatory bowel disease undergoing surveillance colonoscopies (controls, n = 13) were collected during endoscopic examination. RESULTS AIEC infection up-regulated levels of microRNA (MIR) 30C and MIR130A in T84 cells and in mouse enterocytes by activating nuclear factor-κB. Up-regulation of these microRNAs reduced the levels of ATG5 and ATG16L1 and inhibited autophagy, leading to increased numbers of intracellular AIEC and an increased inflammatory response. In ileal biopsy samples of patients with CD, there was an inverse correlation between levels of MIR30C and MIR130A and those of ATG5 and ATG16L1, supporting in vitro findings. Inhibition of MIR30C and MIR130A in cultured intestinal epithelial cells and in mouse enterocytes blocked AIEC-induced inhibition of ATG5 and ATG16L1 expression and restored functional autophagy. This resulted in more effective clearance of intracellular AIEC and reduced AIEC-induced inflammation. CONCLUSIONS Infection with AIEC up-regulates microRNAs to reduce expression of proteins required for autophagy and autophagy response in intestinal epithelial cells. Ileal samples from patients with CD have increased levels of these same microRNAs and reduced levels of ATG5 and ATG16L1.
The relationship between the Early Childhood Environment Rating Scale and its revised form and child outcomes: A systematic review and meta-analysis

The Early Childhood Environment Rating Scale (ECERS) and its revised version (ECERS-R) were designed as global measures of quality that assess structural and process aspects of Early Childhood Education and Care (ECEC) programs. Despite frequent use of the ECERS/ECERS-R in research and applied settings, associations between it and child outcomes have not been systematically reviewed. The objective of this research was to evaluate the association between the ECERS/ECERS-R and children’s wellbeing. Searches of Medline, PsycINFO, ERIC, websites of large datasets and reference sections of all retrieved articles were completed up to July 3, 2015. Eligible studies provided a statistical link between the ECERS/ECERS-R and child outcomes for preschool-aged children in ECEC programs. Of the 823 studies selected for full review, 73 were included in the systematic review and 16 were meta-analyzed. The combined sample across all eligible studies consisted of 33, 318 preschool-aged children. Qualitative systematic review results revealed that ECERS/ECERS-R total scores were more generally associated with positive outcomes than subscales or factors. Seventeen separate meta-analyses were conducted to assess the strength of association between the ECERS/ECERS-R and measures that assessed children’s language, math and social-emotional outcomes. Meta-analyses revealed a small number of weak effects (in the expected direction) between the ECERS/ECERS-R total score and children’s language and positive behavior outcomes. The Language-Reasoning subscale was weakly related to a language outcome. The enormous heterogeneity in how studies operationalized the ECERS/ECERS-R, the outcomes measured and statistics reported limited our ability to meta-analyze many studies. Greater consistency in study methodology is needed in this area of research. Despite these methodological challenges, the ECERS/ECERS-R does appear to capture aspects of quality that are important for children’s wellbeing; however, the strength of association is weak.
Tectonic evolution of Syria Interpreted from Integrated Geophysical and Geological Analysis

Basement depth in the Arabian plate beneath eastern Syria is found to be much deeper than previously supposed. Deep-seated faulting in the Euphrates fault system is also documented. Data from a detailed, 300 km long, reversed refraction profile, with offsets up to 54 km, are analyzed and interpreted, yielding a velocity model for the upper ~ 9 km of continental crust. The interpretation integrates the refraction data with seismic reflection profiles, well logs and potential field data, such that the results are consistent with all available information. A model of sedimentary thicknesses and seismic velocities throughout the region is established. Basement depth on the north side of the Euphrates is interpreted to be around 6 km, whilst south of the Euphrates basement depth is at least 8.5 km. Consequently, the potentially hydrocarbon-rich pre-Mesozoic section is shown, in places, to be at least 7 km thick. The dramatic difference in basement depth on adjacent sides of the Euphrates graben system may suggest that the Euphrates system is a suture / shear zone, possibly inherited from Late Proterozoic accretion of the Arabian plate. Gravity modeling across the southeast Euphrates system tends to support this hypothesis. Incorporation of previous results allows us to establish the first-order trends in basement depth throughout Syria. * Originally published as “Basement depth and sedimentary velocity structure in the northern Arabian Platform, eastern Syria” by G. Brew, R. Litak, D. Seber, M. Barazangi, A. Al-Imam, and T. Sawaf, Geophysical Journal International, 128, 618-631, 1997.
Structural insights into NusG regulating transcription elongation

NusG is an essential transcription factor that plays multiple key regulatory roles in transcription elongation, termination and coupling translation and transcription. The core role of NusG is to enhance transcription elongation and RNA polymerase processivity. Here, we present the structure of Escherichia coli RNA polymerase complexed with NusG. The structure shows that the NusG N-terminal domain (NGN) binds at the central cleft of RNA polymerase surrounded by the β' clamp helices, the β protrusion, and the β lobe domains to close the promoter DNA binding channel and constrain the β' clamp domain, but with an orientation that is different from the one observed in the archaeal β' clamp–Spt4/5 complex. The structure also allows us to construct a reliable model of the complete NusG-associated transcription elongation complex, suggesting that the NGN domain binds at the upstream fork junction of the transcription elongation complex, similar to σ2 in the transcription initiation complex, to stabilize the junction, and therefore enhances transcription processivity.
Refection, a Transmissible Change in the Intestinal Content, enabling Rats to grow and thrive without Vitamin B in the Food

1. When refected rats are fed on adequate diet, containing vitamin B in the form of yeast, the defect in their starch-digestion disappears, and their faeces become normal. 2. Attempts to cause refection in rats receiving an adequate diet by feeding white faeces from refected rats do not influence the starch digestion of the former. 3. When refected rats, growing normally, are fed upon a diet devoid of starch (as well as of vitamin B) their body weight decreases rapidly, but in spite of this decrease they live for a considerable time. 4. Refection cannot be induced in young rats fed upon a diet devoid of starch and of vitamin B. 5. Rats may become or may remain refected when the starch of their 1. diet is replaced by dextrin containing a small amount of starch. The faeces of these rats do not seem able to refect other rats. 6. Rats may be refected without producing white faeces, but starch grains have always been present in the faeces of such rats. 7. The results of special experiments and the clinical observation of refected rats suggest an essential connection between the ability to grow and thrive without vitamin B and the defective digestion of starch. 8. Attempts at refection have no beneficial influence upon rats suffering from a deficiency of vitamin A. 9. Refection has been transmitted to albino mice receiving a diet devoid of vitamin B, but the refection lasted only for a short time. Attempts at refection of rice-fed pigeons have not succeeded. 10.The bearing of studies in refection upon several problems connected with vitamin B is discussed.
Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.
A Correlational Encoder Decoder Architecture for Pivot Based Sequence Generation

Interlingua based Machine Translation (MT) aims to encode multiple languages into a common linguistic representation and then decode sentences in multiple target languages from this representation. In this work we explore this idea in the context of neural encoder decoder architectures, albeit on a smaller scale and without MT as the end goal. Specifically, we consider the case of three languages or modalities X, Z and Y wherein we are interested in generating sequences in Y starting from information available in X. However, there is no parallel training data available between X and Y but, training data is available between X & Z and Z & Y (as is often the case in many real world applications). Z thus acts as a pivot/bridge. An obvious solution, which is perhaps less elegant but works very well in practice is to train a two stage model which first converts from X to Z and then from Z to Y. Instead we explore an interlingua inspired solution which jointly learns to do the following (i) encode X and Z to a common representation and (ii) decode Y from this common representation. We evaluate our model on two tasks: (i) bridge transliteration and (ii) bridge captioning. We report promising results in both these applications and believe that this is a right step towards truly interlingua inspired encoder decoder architectures.
Virtual Screening of Specific Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors from the National Cancer Institute (NCI) Molecular Database

Insulin-like growth factor 1 receptor (IGF1R) is an attractive drug target for cancer therapy and research on IGF1R inhibitors has had success in clinical trials. A particular challenge in the development of specific IGF1R inhibitors is interference from insulin receptor (IR), which has a nearly identical sequence. A few potent inhibitors that are selective for IGF1R have been discovered experimentally with the aid of computational methods. However, studies on the rapid identification of IGF1R-selective inhibitors using virtual screening and confidence-level inspections of ligands that show different interactions with IGF1R and IR in docking analysis are rare. In this study, we established virtual screening and binding-mode prediction workflows based on benchmark results of IGF1R and several kinase receptors with IGF1R-like structures. We used comprehensive analysis of the known complexes of IGF1R and IR with their binding ligands to screen specific IGF1R inhibitors. Using these workflows, 17 of 139,735 compounds in the NCI (National Cancer Institute) database were identified as potential specific inhibitors of IGF1R. Calculations of the potential of mean force (PMF) with GROMACS were further conducted for three of the identified compounds to assess their binding affinity differences towards IGF1R and IR.
Diagnostic Levels in Dental Public Health Planning

This concept paper discusses the rationale for using different diagnostic criteria for dental caries in public health programs. The author contends that epidemiological data or needs assessment surveys should collect data to provide information on the epidemiology of different stages of the caries process in order to enable planners to design tailored programs to prevent dental caries. In a rapidly progressing caries environment, conventional approaches to delivering preventive measures may not work. The author also contends that dental public health programs should expand their vision to influence how dentists are detecting, diagnosing and managing dental caries. Dentists’ restorative decisions have significant impact on the oral health status of a nation. Henceforth, detecting the early or noncavitated caries level and preventing these lesions from progressing to the cavitated stage (or being restored) could have a significant impact on the oral health status around the world. There is a need for more research on the best methods to detect, prevent and treat early carious lesions.
Phonological Development in a Child with Cri du Chat Syndrome (CDCS)

Cri du chat syndrome (CDCS) is a genetic disorder resulting from loss of genetic material from the short arm of chromosome 5. Symptoms include delayed linguistic development. In my paper I present results from a longitudinal study of a girl with CDCS, focussing on two areas of phonological development, firstly, the development of consonant inventories, and, secondly, the development of syllable structure. It is shown that although her consonant inventory hardly develops over a period of 2 1/2 years, the way she uses her consonants to build syllables and words develops considerably. At 4;6 her syllables are dominantly of the CV-type, and bisyllabic words are mostly reduplications. At 5;9 the picture is very different: She uses a variety of syllable shapes, and there are almost no reduplications left. This development continues from 5;9 to 7;0. On the basis of these results I conclude my paper with some remarks on possible causes of the articulatory problems seen in children with CDCS.
Central IT or Shadow IT? Factors Shaping Users' Decision to Go Rogue With IT

Shadow Information Technology (IT) occurs when users develop systems outside of the central information technology department. It provides both benefits and risks. Users procuring shadow IT often do not consider integration with existing enterprise architecture, privacy and security protection, maintenance cost, and legal ramifications. Problems with shadow IT must often be resolved by central IT. It is, thus, important for central IT to determine when users will consider shadow IT, and how shadow IT can be managed. This research analyzes paired interviews with CIOs and senior users to identify factors causing shadow IT. The paper finds that the form the shadow IT/central IT duality takes is based on: (a) perceptions of legitimacy of the Shadow IT by the organization and central IT; and (b) the ability of user departments to procure IT independently.
VARTRA: A Comparable Corpus for Analysis of Translation Variation

This paper presents a comparable translation corpus created to investigate translation variation phenomena in terms of contrasts between languages, text types and translation methods (machine vs. computer-aided vs. human). These phenomena are reflected in linguistic features of translated texts belonging to different registers and produced with different translation methods. For their analysis, we combine methods derived from translation studies, language variation and machine translation, concentrating especially on textual and lexico-grammatical variation. To our knowledge, none of the existing corpora can provide comparable resources for a comprehensive analysis of variation across text types and translation methods. Therefore, the corpus resources created, as well as our analysis results will find application in different research areas, such as translation studies, machine translation, and others.
Effects of curing on grassfires: I. Fuel dynamics in a senescing grassland

Grass senescence, or grassland curing, is a dynamic process in which grass fuels transition from a live to dead state and, in turn, influence fire dynamics. In the present study we examined the process of curing with specific consideration of changes in fuel structure that will affect potential fire behaviour. Our sampling protocol expanded the fuel component groups from two (live and dead) to four (green, senescing, new dead and old dead fuel). We found that all these components had significant fuel moisture content differences, thereby justifying our sampling protocol. Visual curing assessment predominantly resulted in an over-prediction bias of curing level and failed to capture the effect of the senescing process on fuel availability to combust due to misclassification of fuel components (e.g. senescing fuels with high fuel moisture content were classified as dead fuels because of their colouration). Models were developed to estimate the: (1) proportion of senescing and green fuels from knowledge of the current year’s dead fuel proportion; and (2) actual curing level from fuel moisture content and soil dryness level.
Hematopoietic cell transplantation for sickle cell disease: state of the art

Sickle cell disease is associated with considerable morbidity and premature mortality. Hematopoietic cell transplantation offers the possibility of cure and is associated with excellent results in pediatric patients receiving stem cell transplantation from a matched sibling donor. A reduced-intensity conditioning regimen has the potential to further reduce regimen-related morbidity and mortality. Improved understanding of the natural history of complications, such as stroke and pulmonary hypertension, effects of treatments such as hydroxyurea and blood transfusions, as well as the impact of transplantation on organ damage, are likely to influence the timing and indication of transplantation. Improvements in preparative regimens may enable the safe use of an alternative source of stem cells, such as unrelated matched donors, and further improve the applicability and acceptability of this treatment.
Dual-Task Interference Effects on Cross-Modal Numerical Order and Sound Intensity Judgments: The More the Louder?

In the current study, cross-task interactions between number order and sound intensity judgments were assessed using a dual-task paradigm. Participants first categorized numerical sequences composed of Arabic digits as either ordered (ascending, descending) or non-ordered. Following each number sequence, participants then had to judge the intensity level of a target sound. Experiment 1 emphasized processing the two tasks independently (serial processing), while Experiments 2 and 3 emphasized processing the two tasks simultaneously (parallel processing). Cross-task interference occurred only when the task required parallel processing and was specific to ascending numerical sequences, which led to a higher proportion of louder sound intensity judgments. In Experiment 4 we examined whether this unidirectional interaction was the result of participants misattributing enhanced processing fluency experienced on ascending sequences as indicating a louder target sound. The unidirectional finding could not be entirely attributed to misattributed processing fluency, and may also be connected to experientially derived conceptual associations between ascending number sequences and greater magnitude, consistent with conceptual mapping theory.
Functional Role of the C-Terminal Amphipathic Helix 8 of Olfactory Receptors and Other G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) transduce various extracellular signals, such as neurotransmitters, hormones, light, and odorous chemicals, into intracellular signals via G protein activation during neurological, cardiovascular, sensory and reproductive signaling. Common and unique features of interactions between GPCRs and specific G proteins are important for structure-based design of drugs in order to treat GPCR-related diseases. Atomic resolution structures of GPCR complexes with G proteins have revealed shared and extensive interactions between the conserved DRY motif and other residues in transmembrane domains 3 (TM3), 5 and 6, and the target G protein C-terminal region. However, the initial interactions formed between GPCRs and their specific G proteins remain unclear. Alanine scanning mutagenesis of the murine olfactory receptor S6 (mOR-S6) indicated that the N-terminal acidic residue of helix 8 of mOR-S6 is responsible for initial transient and specific interactions with chimeric Gα15_olf, resulting in a response that is 2.2-fold more rapid and 1.7-fold more robust than the interaction with Gα15. Our mutagenesis analysis indicates that the hydrophobic core buried between helix 8 and TM1–2 of mOR-S6 is important for the activation of both Gα15_olf and Gα15. This review focuses on the functional role of the C-terminal amphipathic helix 8 based on several recent GPCR studies.
Matter waves in a gravitational field: An index of refraction for massive particles in general relativity

We consider the propagation of massive-particle de Broglie waves in a static, isotropic metric in general relativity. We demonstrate the existence of an index of refraction that governs the waves and that has all the properties of a classical index of refraction. We confirm our interpretation with a Wentzel–Kramers–Brillouin solution of the general-relativistic Klein–Gordon equation. Finally, we make some observations on the significance of the optical action.
Using Agent-Based Technologies to Enhance Learning in Educational Games.

Recent research has shown that educational games positively motivate learning. However, there is a little evidence that they can trigger learning to a large extent if the game-play is supported by additional activities. We aim to support educational games development with an Agent-Based Technology (ABT) by using intelligent pedagogical agents that can intervene to offer hints, assistance and suggestions when the learner is lacking knowledge, but does not intervene otherwise, so as not to interrupt game flow. In this paper we describe the possibilities of using pedagogical agents to infer learner’s motivation and emotional state as they allow communication and interaction in a digital learning environment. Our approach emphasizes on improving pedagogical agent interactivity: from pedagogical agent techniques to Tutor and Tutee Agents’ techniques to create a high social and collaborative Digital Educational Game (DEG) environment.