Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of environmental damages from mining pollution : the Marinduque Island mining accident

Pollution, in general, can cause damages on natural resource systems which provide valuable though unpriced services to society. Oftentimes, the harmful effects of pollution are not considered by the polluter in decision-making, thus creating excessive environmental externalities. To estimate the externalities generated by pollution, it is necessary to develop economic measures of values of the environmental and resource services provided by the affected resource systems. The estimation process is undertaken primarily to provide inputs to the information base supporting public resource and environmental management decisions (Freeman 1993). One of these decisions that is of primary relevance to this study has to do with determining the natural resource damage liability of responsible parties in pollution cases, which can be used as basis for damage compensation to affected parties. Mining pollution has historically been a major source of degradation of natural resource systems such as river, coastal, and air (USEPA 1995). For this reason, mining, as an economic activity, is subject to major environmental regulations worldwide, including the Philippines.1 Unfortunately, the current information on mining externalities is insufficient to be useful for policy setting. This study was undertaken partly to partly fill this information gap, particularly in the development of policy instruments which require information on social costs of mining, and partly to assist in the formulation of guidelines on damage assessment and compensation for the mining sector. A case study of an accident-induced mining pollution was implemented.
Hyperinsulinemia promotes aberrant histone acetylation in triple negative breast cancer

Excess levels of insulin relative to glucose in the blood, or hyperinsulinemia, is considered to be a poor prognostic indicator for patients with triple negative breast cancer (TNBC). While this association has been recognized for some time, the mechanistic role of hyperinsulinemia in promoting TNBC remains unclear. We show that insulin treatment leads to genome-wide increase in histone acetylation, in particular at H3K9, through the PI3K/AKT/mTOR pathway in MDA-MB-231 cells. Genome-wide analysis showed that the increase in histone acetylation occurs primarily at gene promoters. In addition, insulin induces higher levels of reactive oxygen species and DNA damage foci in cells. In vivo, hyperinsulinemia also enhances growth of MDA-MB-231 derived tumors through increased histone acetylation. These results demonstrate the impact of hyperinsulinemia on altered gene regulation through chromatin and the importance of targeting hyperinsulinemia-induced processes that lead to chromatin dysfunction in TNBC.
Adipose-derived mesenchymal stem cells in wound healing: A clinical review

The aim of this article was to review clinical studies on the use of adipose derived mesenchymal stem cells in the treatment of chronic wounds. A search on PubMed was performed on April 30th, 2014 to identify the relevant clinical studies. We reviewed 13 articles that reported the use adipose-derived stem cells in the treatment of different types of wounds. Adipose-derived stem cells have the potential to be used in the treatment of chronic wounds. However, standard methods for isolation, storage and application of these cells are needed. New materials to transfer these stem cells to injured tissues should be investigated.
The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells.

BACKGROUND Decidualization, the differentiation of endometrial stromal cells is a crucial step for successful implantation of an embryo, development of the placenta and completion of pregnancy to term. Epigenetic mechanisms are thought to be strongly involved in the regulation of processes controlling implantation, placentation, organ formation and foetal growth. Recent studies suggest that decreased DNA methylation facilitates a receptive endometrium. Hence, the aim of this project was to compare the transcriptional profile changes induced by the inhibitor of DNA methylation, 5-Aza-2'-deoxycytidine (AZA) to the transcriptional changes that happen during decidualization. METHODS AND RESULTS When DNA methylation was inhibited in a human endometrial stromal cell (HESC) line with AZA, it resulted in the fibroblast-like stromal cells being transformed into decidual-like morphology after 9 days. Expression of both prolactin and insulin-like growth factor binding protein-1, the two established decidualization marker genes, were minimally up-regulated by AZA after 10 days of treatment. In a microarray of a three-way experiment between AZA-treated and oestradiol/progestin/cAMP-treated [medroxy-progesterone acetate (MPA)-mix] HESC and the untreated controls, we detected more than 1000 common genes that had a significant difference of expression compared with the controls. AZA-treated cells in the microarray significantly expressed 76 genes in common with the MPA-mix treated cells, and AZA treatment also differentially regulated 148 genes independently to that of MPA-mix treatment. The MPA-mix regulated at least 36 genes in the cell adhesion, extracellular matrix remodelling and RhoGTPase cytoskeletal reorganization pathway; AZA regulated 19 of these genes in common and 15 other RhoGTPase pathway genes. CONCLUSION AZA induced some decidualization-like responses of endometrial stromal cells independently of progestins or cAMP, possibly via the cytoskeletal reorganization pathway of the RhoGTPase family.
The role of direct oral anticoagulants in the treatment of cancer associated venous thromboembolism

Cancer disease is one of the most significant risk factors for venous thromboembolic complications. In this review features of treatment and unsolved questions of alternative anticoagulant therapy of can-cer-associated thromboembolism (CAT) are considered. The modern guidelines advocate the use of low-molecular-weight heparin (LMWH) over a vitamin K antagonist (VKA) for the first 3–6 months after diagnosis of VTE in cancer patients. Few years ago direct oral anticoagulants (DOACs) have been approved for the treatment of venous thromboembolism (VTE). DOACs have demonstrated comparable efficacy and safety with VKA in general population. But efficacy and safety of DOACs as compared with long-term LMWH for the treatment of CAT have not been definitely established. The review focuses on the results of the first two prospective randomized studies (HOKUSAI VTE Cancer and SELECT-D) in which the efficacy and safety of edoxaban and rivaroxaban was compared with low-molecular-weight heparin dalteparin for the treatment of VTE in cancer patients and the latest recommendations from SSC of the ISTH on the feasibility of using DOACs in the treatment of CAT.
Werner Syndrome

Werner syndrome is a premature aging disease caused by the mutation in the WRN gene. The cloning and characterization of the WRN gene and its product allows investigators to study the disease and the human aging process at molecular level. This review summarizes the recent progresses on various aspects of the WRN research including functional analysis of the protein, interactive cloning, complexes formation, mouse models, and SNPs (single nucleotide polymorphisms). These in depth investigations have greatly advanced our understanding of the disease and elucidated future research direction for Werner syndrome and the human aging process.
Treatment selection bias for chemotherapy persists in colorectal cancer patient cohort studies even in comprehensive propensity score analyses

and III CC patients, Charlson comorbidity scores 1, 2 and 3+ were associated with 57%, 66% and 70% lower odds of chemotherapy use, respectively. In combination with older age and poor FS, comorbidity was associated with 97% and 83% decreased odds of adjuvant chemotherapy use in CC and rectal cancer patients, respectively. In stage III CC patients, lower comorbidity and higher FS explained 38% and 24% of the overall and disease-speci ﬁ c survival bene ﬁ ts of chemotherapy, respectively. Selection bias was observed even in the comprehensive models, as chemotherapy was still associated with substantially higher non-disease-speci ﬁ c survival (hazard ratio (HR): 0.66; 95% con ﬁ dence interval (CI): 0.46 – 0.92), especially in patients <75 years (HR: 0.33; 95% CI: 0.17 – 0.63). Conclusion: Lower comorbidity and higher FS of recipients of chemotherapy explain approximately 40% of the bene ﬁ ts of chemotherapy in stage III CC patients. Regardless of how comprehensive propensity score analyses might be in observational studies, treatment selection bias might persist and affect estimates of treatment effects. Odds ratio; CI, Con ﬁ dence interval; PVD, Peripheral vascular disease; COPD, Chronic obstructive pulmonary disease.
Electroconvulsive therapy in medication-nonresponsive patients with mixed mania and bipolar depression.

BACKGROUND The aim of this study was to investigate the effectiveness of electroconvulsive therapy (ECT) in medication-nonresponsive patients with mixed mania and bipolar depression. METHOD Forty-one patients with mixed mania (DSM-IV diagnosis of bipolar I disorder, most recent episode mixed) and 23 patients with bipolar depression (DSM-IV diagnosis of bipolar I disorder, most recent episode depressed) consecutively assigned to ECT treatment were included in this study. Subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions-Severity of Illness scale (CGI-S). Assessments were carried out the day before starting ECT, 48 hours after completion of the third session (T1), and a week after the last session of ECT (T2). RESULTS Both groups received an equal number of ECT sessions (mean +/- SD = 7.2 +/- 1.7 vs. 7.3 +/- 1.6). In both groups, within-group comparisons showed that there was a significant reduction in CGI-S score (mixed mania, p <.0001 at T1 and T2; bipolar depression, p < .01 at T1, p < .0001 at T2), MADRS total score (both groups, p < .0001 at T1 and T2), BPRS total score (mixed mania, p < .0001 at T1 and T2; bipolar depression, p < .001 at T1, p < .0001 at T2), and BPRS activation factor score (mixed mania, p < .0001 at T1 and T2; bipolar depression, NS at T1, p < .01 at T2). Between-group comparisons revealed that patients with mixed mania showed significantly greater decrease in MADRS score (p < .001) and a greater proportion of responders (CGI-S) than patients with bipolar depression at endpoint (56% [N = 23] vs. 26% [N = 6], p = .02). Patients with mixed mania showed a greater reduction in suicidality, as measured by MADRS score, than patients with bipolar depression (p < .02). CONCLUSION In our study, ECT was associated with a substantial reduction in symptomatology, in both patients with mixed mania and those with bipolar depression. However, the mixed mania group exhibited a more rapid and marked response as well as a greater reduction in suicidal ideation. Response to ECT was not influenced by the presence of delusions.
Combining remote sensing and economic analysis to assess water productivity; A demonstration project in the Inkomati Basin

This study is divided into two parts: (1) a technical analysis of remote sensing images, including the actual evapotranspiration for a one year period, and the resulting hydrological implications of these measurements; and (2) a secondary analysis and interpretation of the technical data, including social and economic indicators. The objective is to illuminate the implications of water reallocation between sectors (for example between agriculture and environment) as well as intra-sectoral indicators of water use and productivity (e.g. between commercial and emerging farmers). The analysis focused on the Inkomati basin, using both MODIS (large resolution images for large areas) and Landsat images (high resolution images for detailed small area analysis).
COMMON FIXED POINTS OF TWO PAIRS OF SELFMAPS SATISFYING A GERAGHTY-BERINDE TYPE CONTRACTION CONDITION IN b-METRIC SPACES

In this paper, we introduce Geraghty-Berinde type contraction for two pairs of selfmaps in b -metric spaces and we prove the existence of common ﬁxed points under the assumptions that these two pairs of maps are weakly compatible and satisfying a Geraghty-Berinde type contraction condition in complete b -metric spaces. The same is extended to a sequence of selfmaps. Also, we prove the same with diﬀerent hypotheses on two pairs of selfmaps in which one pair is compatible, reciprocally continuous and the other one is weakly compatible. Further, we also prove the same with diﬀerent hypotheses on two pairs in which these selfmaps are satisfy b -(E.A)-property. We also discuss the importance of L in our contraction condition. Our theorems extend/generalize some of the results in literature to two pairs of self maps.
Learning image from projection: a full-automatic reconstruction (FAR) net for sparse-views computed tomography

The sparse-views x-ray computed tomography (CT) is essential for medical diagnosis and industrial nondestructive testing. However, in particular, the reconstructed image usually suffers from complex artifacts and noise, when the sampling is insufficient. In order to deal such issue, a full-automatic reconstruction (FAR) net is proposed for sparse-views CT reconstruction via deep learning technique. Different with the usual network in deep learning reconstruction, the proposed neural network is an End-to-End network by which the image is predicted directly from projection data. The main challenge for such a FAR net is the space complexity of the CT reconstruction in full-connected (FC) network. For a CT image with the size $N \times N$ , a typical requirement of memory space for the image reconstruction is $O(N^{4})$, for which is unacceptable by conventional calculation device, e.g. GPU workstation. In this paper, we utilize a series of smaller FC layers to replace the huge based on the sparse nonnegative matrix factorization (SNMF) theory. By applying such an approach, the FAR net is able to reconstruct sparse-views CT images with the size $512\times 512$ on only one workstation. Furthermore, a Res-Unet structure is composed in the FAR net for suppressing the artifacts and noise caused by under-sampling data. The results of numerical experiments show that the projection matrix and the FAR net is able to reconstruct the CT image from sparse-views projection data with a superior quality than conventional method such as FBP and optimization based approach. Meanwhile, the factorization for the inverse projection matrix is validated in numerical.
Symbiotic organs shaped by distinct modes of genome evolution in cephalopods

Significance Animal–microbe associations are critical drivers of evolutionary innovation, yet the origin of specialized symbiotic organs remains largely unexplored. We analyzed the genome of Euprymna scolopes, a model cephalopod, and observed large-scale genomic reorganizations compared with the ancestral bilaterian genome. We report distinct evolutionary signatures within the two symbiotic organs of E. scolopes, the light organ (LO) and the accessory nidamental gland (ANG). The LO evolved through subfunctionalization of genes expressed in the eye, indicating a deep evolutionary link between these organs. Alternatively, the ANG was enriched in novel, species-specific orphan genes suggesting these two tissues originated via different evolutionary strategies. These analyses represent the first genomic insights into the evolution of multiple symbiotic organs within a single animal host. Microbes have been critical drivers of evolutionary innovation in animals. To understand the processes that influence the origin of specialized symbiotic organs, we report the sequencing and analysis of the genome of Euprymna scolopes, a model cephalopod with richly characterized host–microbe interactions. We identified large-scale genomic reorganization shared between E. scolopes and Octopus bimaculoides and posit that this reorganization has contributed to the evolution of cephalopod complexity. To reveal genomic signatures of host–symbiont interactions, we focused on two specialized organs of E. scolopes: the light organ, which harbors a monoculture of Vibrio fischeri, and the accessory nidamental gland (ANG), a reproductive organ containing a bacterial consortium. Our findings suggest that the two symbiotic organs within E. scolopes originated by different evolutionary mechanisms. Transcripts expressed in these microbe-associated tissues displayed their own unique signatures in both coding sequences and the surrounding regulatory regions. Compared with other tissues, the light organ showed an abundance of genes associated with immunity and mediating light, whereas the ANG was enriched in orphan genes known only from E. scolopes. Together, these analyses provide evidence for different patterns of genomic evolution of symbiotic organs within a single host.
The GATA transcription factor Gaf1 represses tRNA genes, inhibits growth, and extends chronological lifespan downstream of fission yeast TORC1

Target of Rapamycin Complex 1 (TORC1) signaling promotes growth and ageing. Inhibition of TORC1 leads to a down-regulation of factors that stimulate protein translation, including RNA polymerase III, which in turn contributes to longevity. TORC1-mediated post-transcriptional regulation of protein translation has been well studied, while analogous transcriptional regulation is less well understood. Here we screened fission yeast deletion mutants for resistance to Torin1, which inhibits TORC1 and cell growth. Mutants lacking the GATA transcription factor Gaf1 (gaf1Δ) grew normally even in high doses of Torin1. The gaf1Δ mutants shortened the chronological lifespan of non-dividing cells and diminished the lifespan extension triggered by Torin1 treatment. Expression profiling and genome-wide binding experiments showed that, after TORC1 inhibition, Gaf1 directly up-regulated genes for small-molecule metabolic pathways and indirectly repressed genes for protein translation. Surprisingly, Gaf1 also bound to the tRNA genes and down-regulated them, so functions as a transcription factor for genes transcribed by RNA polymerase III. We conclude that Gaf1 controls the transcription of both coding and tRNA genes to inhibit translation and growth downstream of TORC1.
Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex

Cortical collapse factors affect microtubule (MT) dynamics at the plasma membrane. They play important roles in neurons, as suggested by inhibition of axon growth and regeneration through the ARF activator Efa6 in C. elegans, and by neurodevelopmental disorders linked to the mammalian kinesin Kif21A. How cortical collapse factors influence axon growth is little understood. Here we studied them, focussing on the function of Drosophila Efa6 in experimentally and genetically amenable fly neurons. First, we show that Drosophila Efa6 can inhibit MTs directly without interacting molecules via an N-terminal 18 amino acid motif (MT elimination domain/MTED) that binds tubulin and inhibits microtubule growth in vitro and cells. If N-terminal MTED-containing fragments are in the cytoplasm they abolish entire microtubule networks of mouse fibroblasts and whole axons of fly neurons. Full-length Efa6 is membrane-attached, hence primarily blocks MTs in the periphery of fibroblasts, and explorative MTs that have left axonal bundles in neurons. Accordingly, loss of Efa6 causes an increase of explorative MTs: in growth cones they enhance axon growth, in axon shafts they cause excessive branching, as well as atrophy through perturbations of MT bundles. Efa6 over-expression causes the opposite phenotypes. Taken together, our work conceptually links molecular and sub-cellular functions of cortical collapse factors to axon growth regulation and reveals new roles in axon branching and in the prevention of axonal atrophy. Furthermore, the MTED delivers a promising tool that can be used to inhibit MTs in a compartmentalised fashion when fusing it to specifically localising protein domains.
Discovery of small molecule inhibitors of protein-protein interactions

Protein-protein interactions (PPIs) constitute an emerging class of targets for the next generation of therapeutic intervention. Despite their fundamental role in many biological processes and diseases such as cancer, PPIs are still largely underrepresented in drug discovery. Although small molecule PPI inhibitors are highly valuable due to a number of advantages relative to biological agents in terms of production, delivery, titratability and cost, the robust discovery of lead compounds remains a great challenge. Two structure-based drug discovery strategies are described in this work to generate small molecules to target PPIs. A receptor-based drug discovery approach can be applied when an accurate three-dimensional (3D) structure of a specific PPI complex is available. A novel, complementary and transformative approach for the rational design of small molecule inhibitors based on the crystal structure of the p53-Mdm2 complex was developed. This method is based on a tight interplay of structural biology information, the “anchor” concept, efficient chemical synthesis via multicomponent reactions (MCRs), as well as virtual and real screening processes. Applying the method we efficiently discovered several new scaffolds of inhibitors of the p53/Mdm2 interaction with lower micromolar affinity binding to Mdm2, which can serve as starting point for medicinal chemistry optimization. Advantages of our approach include high hit rates and less attrition based on the parallel discovery of multiple scaffolds, built-in optimization pathways using efficient MCRs, and fast generation of potential lead compounds. Potential anticancer drug candidates were identified by biochemical assays, co-crystallization, cell based assays, as well as further preclinical evaluations (solubility, metabolism, pharmacokinetics, and xenograft studies). A ligand-based drug discovery approach was explored since PPIs are critically dependent on “anchor” residues, which can serve as the pharmacophore model for small molecules. Multicomponent reactions were employed for design of novel scaffolds and DOS of drug-like compounds, since hit identification of PPI inhibitors via traditional approaches such as high throughput screening (HTS) is fundamentally limited by chemotypes present in the library collections. Novel and diverse scaffolds based on the privileged structures (1,4-benzodiazepines, 1,4-thienodiazepines) and “anchor” residues, which can be accessible from multicomponent reactions, were designed and synthesized. Compared with conventional methods, these approaches are advantageous to generate small molecules targeting PPIs in terms of efficiency, diversity, and economy. In summary, the approaches described in this dissertation constitute important contributions to the fields of medicinal chemistry and structure-based drug discovery, which combine structural insights and ligand design to expedite the discovery of novel small molecule inhibitors of PPIs.