Miracle-dz/UniFAR-FTUs huggingface dataset:
Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase

DNA methyltransferase 1 (Dnmt1) has a central role in copying the pattern of DNA methylation after replication which is one manifestation of epigenetic inheritance. With oligonculeotide substrates we show that mouse Dnmt1 has a 30- to 40-fold preference for hemimethylated DNA that is almost lost after addition of fully methylated oligonucleotides. Using long hemimethylated DNA substrates that carry defined methylation patterns and bisulfite analysis of the methylation reaction products, we show a 15-fold preference for hemimethylated CG sites. Dnmt1 moves along the DNA in a random walk methylating hemimethylated substrates with high processivity (>50 sites are visited on average which corresponds to linear diffusion over 6000 bp). The frequency of skipping sites is very low (<0.3%) and there is no detectable flanking sequence preference. CGCTC sites tend to terminate the processive methylation of DNA by Dnmt1. Unmethylated DNA is modified non-processively with a preference for methylation at CCGG sites. We simulate the propagation of methylation patterns using a stochastic model with the specificity of Dnmt1 observed here and conclude that either methylation of several sites is required to propagate the methylation information over several cellular generations or additional epigenetic information must be used.
THE USE OF SONGS AS A PROMPT IN GENRE-BASED APPROACH IN TEACHING NARRATIVE TEXT : A Case Study in a Senior High School in Bandung

The research paper entitled, “The use of Songs as a Prompt in Genre-based Approach in Teaching Narrative Text: a Case Study in a Senior High School in Bandung”, aimed to examine in what stages of the genre-based approach (GBA) that songs as a prompt can be incorporated in teaching narrative text. Moreover, the study investigated to what extent songs as a prompt can help the students in writing narrative text. This study was conducted in one senior high school in Bandung using a case study research design. The data were collected from the observations, document analysis, and interview. The findings of this study show that, songs can be incorporated in every stage in GBA including Building Knowledge of Field, Modeling of Text, Joint Construction, and Independent Construction. Furthermore, the analysis reveals that songs as a prompt can help the students to write narrative text in several aspects, as in helping the students to understand context and social purpose of narrative text, generating ideas to write narrative texts, enhancing students’ vocabularies and the use of expressions in writing narrative text, and promoting students’ motivation. Regarding this, it is recommended to use songs a as a prompt incorporated in GBA to teach writing in any text types, such as descriptive, recount, etc.
Exposure to parental psychopathology and offspring's risk of suicide-related thoughts and behaviours: a systematic review

Aims. The primary objective of this systematic review was to identify and synthesise analytic studies examining the association between exposure to parental psychopathology in childhood and the nature of subsequent suicide-related thoughts (SRT) and suicide-related behaviour (SRB) (severity of ideation, planned/unplanned attempts/lethality) and to describe the direction, and magnitude of associations. The secondary objective was to determine if the associations from the primary objective differ by the type(s) and timing of parental psychopathology, sex/gender of the parent and child and is mediated by child psychiatric symptoms and family functioning. Methods. A systematic review was conducted using guidelines from the PRISMA statement. MEDLINE, CINAHL, EMBASE, psycINFO, Web of Science and grey literature sources were searched by two reviewers to March, 2017. Studies were included if they examined any parental psychopathology (Diagnostic and Statistical Manual of Mental Disorders criteria or equivalent) or SRT or SRB and offspring SRT or SRB occurring from birth <25 years of age. Results. Out of 10 231 studies identified, 54 were included for review. Studies were clinically and methodologically heterogeneous with none at low risk of bias (ROB). Nine studies with moderate ROB indicated a significantly increased risk of offspring SRT, suicide attempts (SA) and suicide among those exposed to maternal SA and suicide in childhood or adolescence. In the remaining 45 studies with higher ROB this association persisted. Several studies (67%) did not confirm that the exposure occurred in the offspring's childhood or adolescence. Findings were suggestive of a mediating effect of offspring psychiatric symptoms, however, few studies examined mediation and effect modification of contextual variables. Conclusions. Offspring exposed to maternal SA are at an increased risk of these same behaviours early in life. Prospective attention to the types and timing of maternal and paternal psychopathology and the intermediate pathways to offspring SRT and SRB onset is needed and could have implications for informing modifiable targets for early intervention and prevention.
High mobility group box chromosomal protein 1, a DNA binding cytokine, induces arthritis.

OBJECTIVE To examine the potential role of high mobility group box chromosomal protein 1 (HMGB-1) in the pathogenesis of arthritis. METHODS Mice were injected intraarticularly with 1 microg or 5 microg of HMGB-1. Joints were dissected on days 4, 7, and 28 after injection and were evaluated histopathologically and immunohistochemically. To investigate the importance of different white blood cell populations for the development of arthritis, in vivo cell depletion procedures were performed. In addition, spleen cells were cultured in the presence of HMGB-1, and nuclear factor kappaB (NF-kappaB) activation was detected by electrophoretic mobility shift assay. RESULTS Injection of recombinant HMGB-1 (rHMGB-1) into different mouse strains resulted in an overall frequency of arthritis in 80% of the animals. The inflammation was characterized by mild to moderate synovitis and lasted for at least 28 days. The majority of cells found in the inflamed synovium were Mac-1+ macrophages, whereas only a few CD4+ lymphocytes were detected. Pannus formation was observed in some cases 7 and 28 days after HMGB-1 injection. No significant differences were found with respect to incidence and severity of arthritis between mice depleted of monocytes, granulocytes, or lacking T/B lymphocytes. However, combined removal of monocytes and neutrophils resulted in a 43% lower incidence of arthritis. Mice rendered deficient in the interleukin-1 (IL-1) receptor did not develop inflammation upon challenge with HMGB-1. In vitro data corroborate this finding, showing that rHMGB-1 activated NF-kappaB, a major pathway leading to IL-1 production. CONCLUSION Our results indicate that HMGB-1 is not a mere expression of inflammatory responses, but on its own, it triggers joint inflammation by activating macrophages and inducing production of IL-1 via NF-kappaB activation.
Characteristics and Clinical Outcomes in Overhead Sports Athletes after Rotator Cuff Repair

Rotator cuff tears in young overhead sports athletes are rare. The pathomechanism causing rotator cuff tears in young overhead athletes is different from that in aged patients. The purpose of this study was to investigate rotator cuff tear characteristics in young overhead sports athletes to reveal the pathomechanism causing these injuries. This study included 25 overhead sports athletes less than 30 years old with atraumatic rotator cuff tears necessitating repair. Rotator cuff tear characteristics were evaluated intraoperatively, including rotator cuff tear shape and injured rotator cuff tendon. Clinical outcome measures were assessed before surgery and at the final follow-up. In this study, 22 patients reported minimal to no shoulder pain and returned to sports without significant complaints at last follow-up. The isolated infraspinatus tendon was most often injured; the incidence rate of the tear at this site was 32% (8 cases). In the deceleration phase of overhead motion, the eccentric contraction force of the ISP (infraspinatus) tendon peaks and the increased load leads to injury at the ISP tendon. The pathomechanism of rotator cuff injuries in young overhead athletes might be not only internal or subacromial impingement, but also these mechanisms.
Sparse Auto-Calibration for Radar Coincidence Imaging with Gain-Phase Errors

Radar coincidence imaging (RCI) is a high-resolution staring imaging technique without the limitation of relative motion between target and radar. The sparsity-driven approaches are commonly used in RCI, while the prior knowledge of imaging models needs to be known accurately. However, as one of the major model errors, the gain-phase error exists generally, and may cause inaccuracies of the model and defocus the image. In the present report, the sparse auto-calibration method is proposed to compensate the gain-phase error in RCI. The method can determine the gain-phase error as part of the imaging process. It uses an iterative algorithm, which cycles through steps of target reconstruction and gain-phase error estimation, where orthogonal matching pursuit (OMP) and Newton’s method are used, respectively. Simulation results show that the proposed method can improve the imaging quality significantly and estimate the gain-phase error accurately.
SAAMBE: Webserver to Predict the Charge of Binding Free Energy Caused by Amino Acids Mutations

Predicting the effect of amino acid substitutions on protein–protein affinity (typically evaluated via the change of protein binding free energy) is important for both understanding the disease-causing mechanism of missense mutations and guiding protein engineering. In addition, researchers are also interested in understanding which energy components are mostly affected by the mutation and how the mutation affects the overall structure of the corresponding protein. Here we report a webserver, the Single Amino Acid Mutation based change in Binding free Energy (SAAMBE) webserver, which addresses the demand for tools for predicting the change of protein binding free energy. SAAMBE is an easy to use webserver, which only requires that a coordinate file be inputted and the user is provided with various, but easy to navigate, options. The user specifies the mutation position, wild type residue and type of mutation to be made. The server predicts the binding free energy change, the changes of the corresponding energy components and provides the energy minimized 3D structure of the wild type and mutant proteins for download. The SAAMBE protocol performance was tested by benchmarking the predictions against over 1300 experimentally determined changes of binding free energy and a Pearson correlation coefficient of 0.62 was obtained. How the predictions can be used for discriminating disease-causing from harmless mutations is discussed. The webserver can be accessed via http://compbio.clemson. edu/saambe_webserver/.
Krüppel is a gap gene in the intermediate germband insect Oncopeltus fasciatus and is required for development of both blastoderm and germband-derived segments

Segmentation in long germband insects such as Drosophila occurs essentially simultaneously across the entire body. A cascade of segmentation genes patterns the embryo along its anterior-posterior axis via subdivision of the blastoderm. This is in contrast to short and intermediate germband modes of segmentation where the anterior segments are formed during the blastoderm stage and the remaining posterior segments arise at later stages from a posterior growth zone. The biphasic character of segment generation in short and intermediate germ insects implies that different formative mechanisms may be operating in blastoderm-derived and germband-derived segments. In Drosophila, the gap gene Krüppel is required for proper formation of the central portion of the embryo. This domain of Krüppel activity in Drosophila corresponds to a region that in short and intermediate germband insects spans both blastoderm and germband-derived segments. We have cloned the Krüppel homolog from the milkweed bug, Oncopeltus fasciatus (Hemiptera, Lygaeidae), an intermediate germband insect. We find that Oncopeltus Krüppel is expressed in a gap-like domain in the thorax during the blastoderm and germband stages of embryogenesis. In order to investigate the function of Krüppel in Oncopeltus segmentation, we generated knockdown phenotypes using RNAi. Loss of Krüppel activity in Oncopeltus results in a large gap phenotype, with loss of the mesothoracic through fourth abdominal segments. Additionally, we find that Krüppel is required to suppress both anterior and posterior Hox gene expression in the central portion of the germband. Our results show that Krüppel is required for both blastoderm-derived and germband-derived segments and indicate that Krüppel function is largely conserved in Oncopeltus and Drosophila despite their divergent embryogenesis.
An Alternative Form of IL-18 in Human Blood Plasma: Complex Formation with IgM Defined by Monoclonal Antibodies1

Monoclonal Abs 21 and 132 were raised against human functionally inactive rIL-18, and plasma IL-18 levels were determined by the sandwich ELISA established with these mAbs. Plasma IL-18, designated type 2, was detected by this ELISA, and the levels found were not consistent with those obtained with the commercially available kit for determination of functionally active IL-18 (type 1). Type 1 was detected in all volunteers, whereas type 2 was detected in ∼30% of healthy subjects, and the levels of type 2 in their blood plasma were high (25–100 ng/ml) compared with those of type 1 (0.05–0.3 ng/ml). We purified IL-18 type 2 from blood plasma of volunteers with high IL-18 type 2 concentrations, and its Mr was determined to be 800 kDa by SDS-PAGE and molecular sieve HPLC. The purified 800-kDa protein, either caspase-1-treated or untreated, expressed no or marginal IL-18 function in terms of potentiation of NK-mediated cytolysis and IFN-γ induction, and it barely bound IL-18R-positive cells. N-terminal amino acid analysis indicated that the purified protein was IgM containing a minimal amount of IL-18 proform and its fragment. Again, the purified IgM from IL-18 type2-positive volunteers exhibited cross-reaction with mAb 21 against IL-18. This band was not detected with 125-2H, an mAb against functionally active IL-18. Hence, human IgM carries functionally inactive IL-18 forming a disulfide-bridged complex, and this IL-18 moiety is from 10- to 100-fold higher than the conventional type 1 IL-18 in blood circulation in ∼30% normal subjects.
CFT/AdS correspondence, massive gravitons, and a connectivity index conjecture

We discuss the general question of which conformal field theories have dual descriptions in terms of quantum gravity theories on anti-de Sitter space. We analyze in detail the case of a deformed product of $n$ conformal field theories (each of which has a gravity dual), and we claim that the dual description of this is by a quantum gravity theory on a union of $n$ anti-de Sitter spaces, connected at their boundary (by correlations between their boundary conditions). On this union of spaces, ($n\ensuremath{-}1$) linear combinations of gravitons obtain a mass, and we compute this mass both from the field theory and from the gravity sides of the correspondence, finding the same result in both computations. This is the first example in which a graviton mass in the bulk of anti-de Sitter space arises continuously by varying parameters. The analysis of these deformed product theories leads us to suggest that field theories may be generally classified by a ``connectivity index,'' corresponding to the number of components (connected at the boundary) in the space-time of the dual gravitational background. In the field theory this index roughly counts the number of independent gauge groups, but we do not have a precise general formula for the index.
Long-term treatment of systemic lupus erythematosus with cyclosporin A.

OBJECTIVE To evaluate the efficacy of long-term treatment with cyclosporin A (CSA) in systemic lupus erythematosus (SLE). METHODS Thirty patients with SLE whose condition was either poorly responsive or unresponsive to treatment with steroids and/or cytotoxic drugs were enrolled in a prospective, nonrandomized study of CSA. Patients with hypertension or hypercreatinemia were excluded. Disease activity was evaluated according to the systemic lupus activity measure. Assessments were made prior to study entry and after 6, 12, 18, and 24 months. RESULTS Twenty-seven patients completed at least 24 months of treatment with CSA. The mean disease activity score significantly decreased after 6 months of therapy (P < 0.01); this result was maintained throughout the study. A conspicuous steroid-sparing effect was observed following administration of CSA (P < 0.01). Side effects included hypertrichosis (63% of patients), paresthesias (23%), gastrointestinal symptoms (20%), gingival hyperplasia (17%), hypertension (10%), tremors (7%), and nephrotoxicity (13%). No significant changes in serum creatinine levels were observed. CONCLUSION CSA represents a helpful second-choice treatment for patients with active SLE. Administration of CSA necessitates expert and careful followup of patients.
A Sparsity Promoting Adaptive Algorithm for Distributed Learning

In this paper, a sparsity promoting adaptive algorithm for distributed learning in diffusion networks is developed. The algorithm follows the set-theoretic estimation rationale. At each time instance and at each node of the network, a closed convex set, known as property set, is constructed based on the received measurements; this defines the region in which the solution is searched for. In this paper, the property sets take the form of hyperslabs. The goal is to find a point that belongs to the intersection of these hyperslabs. To this end, sparsity encouraging variable metric projections onto the hyperslabs have been adopted. In addition, sparsity is also imposed by employing variable metric projections onto weighted l1 balls. A combine adapt cooperation strategy is adopted. Under some mild assumptions, the scheme enjoys monotonicity, asymptotic optimality and strong convergence to a point that lies in the consensus subspace. Finally, numerical examples verify the validity of the proposed scheme compared to other algorithms, which have been developed in the context of sparse adaptive learning.
COX-2 Inhibitors as Radiosensitizing Agents for Cancer Therapy

Prostaglandins have long been known to impact the radiosensitivity of cells and tissues, and many studies have centered on exploiting nonspecific prostaglandin inhibitors such as NSAIDs for therapeutic gain. These studies have ultimately been unsuccessful due to the lack of targeted specificity against the tumor. The discovery of the inducible cyclooxygenase enzyme (COX-2) and development of some highly selective inhibitors (which spare the constitutive COX-1 activity) has renewed excitement for modulating tumor prostaglandins as a method of specific radiosensitization of tumors, while sparing normal tissues. This review discusses these new data and generates a rationale for use of COX-2 inhibitors as radiosensitizing agents in cancer therapy.
Radio Sources in Low-Luminosity Active Galactic Nuclei. III

This paper presents the results of a high resolution radio imaging survey of all known (96) low-luminosity active galactic nuclei (LLAGNs) at $D \leq 19$ Mpc. We first report new 2 cm (150 mas resolution using the VLA) and 6 cm (2 mas resolution using the VLBA) radio observations of the previously unobserved nuclei in our samples and then present results on the complete survey. We find that almost half of all LINERs and low-luminosity Seyferts have flat-spectrum radio cores when observed at 150 mas resolution. Higher (2 mas) resolution observations of a flux-limited subsample have provided a 100% (16 of 16) detection rate of pc-scale radio cores, with implied brightness temperatures $\ga$ $10^8\,$K. The five LLAGNs with the highest core radio fluxes also have pc-scale “jets”. Compact radio cores are almost exclusively found in massive ellipticals and in type 1 nuclei (i.e. nuclei with broad H α emission). Only a few “transition” nuclei have compact radio cores; those detected in the radio have optical emission-line diagnostic ratios close to those of LINERs/Seyferts. This indicates that some transition nuclei are truly composite Seyfert/LINER+$\ion{H}{II}$ region nuclei, with the radio core power depending on the strength of the former component. The core radio power is correlated with the nuclear optical “broad” H α luminosity, the nuclear optical “narrow” emission-line luminosity and width, and with the galaxy luminosity. In these correlations LLAGNs fall close to the low-luminosity extrapolations of more powerful AGNs. The scalings suggest that many of the radio-non-detected LLAGNs are simply lower power versions of the radio-detected LLAGNs. The ratio of core radio power to nuclear optical emission-line luminosity increases with increasing bulge luminosity for all LLAGNs. Also, there is evidence that the luminosity of the disk component of the galaxy is correlated with the nuclear emission-line luminosity (but not the core radio power). About half of all LLAGNs with multiple epoch data show significant inter-year radio variability. Investigation of a sample of ~150 nearby bright galaxies, most of them LLAGNs, shows that the nuclear ( ≤ 150 mas size) radio power is strongly correlated with both the black hole mass and the galaxy bulge luminosity; linear regression fits to all ~150 galaxies give: $\log P_{\rm 2~cm} = 1.31$( ± 0.16) log M MDO + 8.77 and $\log P_{\rm 2~cm} = 1.89$( ± 0.21$)\,\log\, L_{B}$(bulge$) -0.17$. Low accretion rates ( ≤ $10^{-2}{-}10^{-3}$ of the Eddington rate) are implied in both advection- and jet-type models. In brief, all evidence points towards the presence of accreting massive black holes in a large fraction, perhaps all, of LLAGNs, with the nuclear radio emission originating in either the accretion inflow onto the massive black hole or from jets launched by this black hole–accretion disk system.
Hymenolepis diminuta: changes in intestinal morphology and the enterochromaffin cell population associated with infection in male C57 mice

SUMMARY Mean villus height, crypt depth and the number of 5-HT-positive enterochromaffin (EC) cells have been examined in two regions of the small intestine (20–30° and 60–70° distance from the pylorus) of male, 6 to 8-week-old, C57 mice following a 5-cysticercoid infection of the rat tapeworm, Hymenolepis diminuta. Test mice and sham-infected controls were autopsied 0, 4, 8, 10, 14 and 28 days post-primary infection (p-1°-i) and 2, 4, 5, 7 and 14 days post-secondary infection (p-2°-i), administered 28 days p-1°-i. Morphometric analysis revealed a statistically significant increase in crypt depth in the 60–70°o intestine region in infected mice during both primary and secondary infections; no significant deviation from the control was observed for villus height in infected mice. Statistical analysis showed a significant increase in the number of 5-HT-positive EC cells in infected mice. This response occurred in the lower portion of the intestine on days 10-p-1°-i and 5-p-2°-i, and was not due to increased mucosal surface area in this region. Results are discussed with reference to murine cestode rejection and the possible involvement therein of the neuroendocrine system.