Miracle-dz/UniFAR-FTUs huggingface dataset:
Running title: A role for ASPP2 in human congenital disorder

Jaroslav Zak1, Virginie Vives1,24, Dorota Szumska2, Aude Vernet2, Jurgen E. 3 Schneider2, Paul Miller1, Elizabeth A. Slee1, Shelagh Joss3, Yves Lacassie4,5, 4 Emily Chen6, Luis F. Escobar7, Megan Tucker7, Arthur S. Aylsworth8, Holly A. 5 Dubbs9, A. Thomas Collins10, Joris Andrieux11, Anne Dieux-Coeslier12, Edda 6 Haberlandt13, Dieter Kotzot13, Daryl A. Scott14, Michael J. Parker15, Zubaidah 7 Zakaria16, Yew Sing Choy17, Dagmar Wieczorek18,19, A. Micheil Innes20, Kyung 8 Ran Jun21, Samuel Zinner10, Fabrice Prin22, Craig A. Lygate2, Pieter Pretorius23, 9 Jill A. Rosenfeld14, Timothy J. Mohun22, and Xin Lu1, * 10
DMD053595 1888..1895

Olmesartan medoxomil (OM) is a prodrug-type angiotensin II type 1 receptor blocker (ARB). We recently identified carboxymethylenebutenolidase homolog (CMBL) as the responsible enzyme for OM bioactivation in humans. In the present study, we compared the bioactivating properties of OM with those of other prodrug-type ARBs, candesartan cilexetil (CC) and azilsartan medoxomil (AM), by focusing on interspecies differences and tissue specificity. In invitro experiments with pooled tissue subcellular fractions of mice, rats, monkeys, dogs, and humans, substantial OM-hydrolase activities were observed in cytosols of the liver, intestine, and kidney in all the species tested except for dog intestine, which showed negligible activity, whereas lung cytosols showed relatively low activities compared with the other tissues. AM-hydrolase activities were well correlated with the OM-hydrolase activities. In contrast, liver microsomes exhibited the highest CC-hydrolase activity among various tissue subcellular fractions in all the species tested. As a result of Western blot analysis with the tissue subcellular fractions, the band intensities stained with anti-human CMBL and carboxylesterase 1 (CES1) antibodies well reflected OMand AM-hydrolase activities and CC-hydrolase activity, respectively, in animals and humans. Recombinant human CMBL and CES1 showed significant AMand CC-hydrolase activities, respectively, whereas CC hydrolysis was hardly catalyzed with recombinant carboxylesterase 2 (CES2). In conclusion, OM is bioactivated mainly via intestinal and additionally hepatic CMBL not only in humans but also in mice, rats, and monkeys, while CC is bioactivated via hepatic CES1 rather than intestinal enzymes, including CES2. AM is a substrate for CMBL.
Does it matter to have an ethical brand?

Background: Brand loyalty has been studied by a large number of scholars over the past few decades, including its impact on consumer purchase behavior and as a core concept when creating brand value. Having ethical business practice helps retain customers trust and enforce their loyalty to the brand. However, brand’s unethical behavior has always been a topic discussed by society, especially for the soft drinks industry. Problem: Previous research has shown that there is a link between brand loyalty, brand trust and brand attachment. It has also been implied that consumers with high commitment to a brand might justify a brands unethical behavior. However, there is a lack of research within the field of brand loyalty and ethical business practices within the beverage industry. Purpose: The purpose of this study is to understand how millennials with different levels of brand loyalty respond to unethical marketing activities to soft drink brands within the beverage industry. Furthermore, this research would like to give an insight to whether consumers care about ethical brands within this industry or not. Additionally, this study can help brands in the beverage industry to build their marketing strategies and maintain their consumer relationship. Method: This study used a qualitative research method, where 15 semi-structured interviews were conducted with a purposive sampling method, with millennials as research objects. Additionally, the brand Pepsi has been used as a case to measure the participants brand loyalty in order to classify them to one of the three levels of loyalty in the conceptual framework.
Operational Evaluation of Responsiveness Properties Operational Evaluation of Responsiveness Properties

In this paper, a new technique for ensuring run-time satisfaction of properties-specifically responsiveness property, a subset of liveness property, in responsive systems, is presented. Since whether the run-time behavior of a system is satisfied depends on the execution (operational) environment, we develop a translation which takes into account the constraints in the operational environment, and generates histories for each process in the system. Thus, every process can uti­ lize its history to operationally evaluate the system behavior and signal errors if its history is vio­ lated. Therefore, this technique provides software safety, handles error-detection, and ensures run-time satisfaction of responsiveness property in the operational environment. To illustrate this approach a train set example is presented.
Multimodality Imaging of Left Ventricular NonCompaction Cardiomyopathy Associated with Situs Inversus

Left Ventricular Non-Compaction Cardiomyopathy (LVNC) is characterized by hypertrabeculation and intratrabecular recesses. It has been mostly reported as an isolated entity, however, 1 in 8 cases of LVNC has been associated with various congenital heart defects. Whether such an association is genetically based or triggered by altered hemodynamic factors remains unsettled. We report a unique case of LVNC associated with situs inversus (dextrocardia with mirror image major visceral organs) in an adult. The patient’s clinical presentation (heart failure, left ventricular apical thrombus, atrial fibrillation and thromboembolic stroke) mandated a multimodality imaging approach to diagnosis and management. The role of cardiovascular imaging in evaluation of this complex heart disease is discussed.
Parak nanoparticles bioconjugation of colloidal inorganic Surface modification , functionalization and

References l.html#ref-list-1 http://rsta.royalsocietypublishing. org/content/368/1915/1333.ful This article cites 385 articles, 15 of which can be accessed free Subject collections (67 articles) nanotechnology  (19 articles) hydrology  collections Articles on similar topics can be found in the following Email alerting service here in the box at the top right-hand corner of the article or click Receive free email alerts when new articles cite this article sign up
II. Genetic approaches to pain therapy

Wood, John N. Pathobiology of Visceral Pain: Molecular Mechanisms and Therapeutic Implications. II. Genetic approaches to pain therapy. Am J Physiol Gastrointest Liver Physiol 278: G507–G512, 2000. —New analgesic drugs are necessary because a number of pain states are untreatable. Genetic approaches to the identification of analgesic drug targets include mapping genes involved in human pain perception (e.g., trkA involved in hereditary neuropathies), identifying regulators of sensory neuron function in simple multicellular organisms and then investigating the activity of their mammalian homologs (e.g., POU domain transcription factors that specify sensory cell fate), as well as difference, expression, and homology cloning of receptors, ion channels, and transcription factors present in sensory neurons. After target validation through the construction of null mutant mice, high-throughput cell-based screens can be used to identify potential drug candidates. As a result of these approaches, a number of receptors and ion channels present in sensory neurons such as voltage-gated sodium channels [sensory neuron specific (SNS) and Na channel novel] and ATP-gated (P2X3), capsaicin-gated [vanilloid receptor 1(VR1)], and proton-gated [acid-sensing ion channel (ASIC)] channels are now under investigation as potential new analgesic drug targets.
-Reactive Ligand k in Mice Expressing a Low Level of Ig Split Tolerance in Peripheral B Cell Subsets

Peripheral B cell tolerance differs from central tolerance in anatomic location, in the stage of B cell development, and in the diversity of Ag-responsive cells. B cells in secondary lymphoid organs are heterogeneous, including numerous subtypes such as B-1, marginal zone, transitional, and follicular B cells, which likely respond differently from one another to ligand encounter. We showed recently that central B cell tolerance mediated by receptor editing was induced in mice carrying high levels of a ubiquitously expressed (cid:1) -macroself Ag, a synthetic superantigen reactive to Ig (cid:1) . In this study, we characterize a new transgenic line that has a distinctly lower expression pattern from those described previously; the B cell tolerance phenotype of these mice is characterized by the presence of signiﬁcant numbers of immature (cid:1) (cid:2) B cells in the spleen, the loss of mature follicular and marginal zone B cells, the persistence of (cid:1) (cid:2) B-1 cells in the peritoneal cavity, and signiﬁcant levels of serum IgM, (cid:1) . These ﬁndings suggest distinct signaling thresholds for tolerance among peripheral B cell subsets reactive with an identical ligand. The Journal of Immunology, 2006, 176: 939–948.
VITAMIN D AND OXIDATIVE STRESS IN OBESE IRAQI SAMPLE WITH FIBROMYALGIA SYNDROME

Fibromyalgia syndrome(FMS) is chronic state characterized by generalized pain associated with fatigue, stiffness, altered s leep, depression, anxiety and cognitive dysfunction. It is the most common condition in women worldwide and causes pain all over the body . The exact cause of FMS is still unknown but several theories thought to be linked to abnormal levels of certain chemicals in brain ,vitamin D deficiency and oxidative stress . Obesity has been consistently associated with increased risk of FMS. Eighty nine subjects between (20-55)years ; (59) patients with FMS were divided in to : (39) obese women with FMS and (20) non obese women with FMS . In addition to two controls group ;(20) obese control and (10) apparently healthy control, age and sex matched subjects as controls. Five millilitres of venous blood sample were drawn from each women ,centrifuged to obtain serum to be used for measuring the following variables :25(OH)vitamin D, total calcium and myeloperoxidase. 25(OH)vitamin D and total calcium were significantly lower, while myeloperoxidase was significantly higher in FMS with obesity and non-obesity . Body mass index (BMI) is significantly higher in FMS with obesity and non-significant in FMS with non-obesity. A low 25(OH) vitamin D level was positively associated with low total calcium level in FMS with obesity and non-obesity . A high myeloperoxidase was associated with low levels of 25(OH) vitamin D and total calcium in FMS with obesity . The Lower serum levels of 25(OH)vitamin D , serum total calcium and higher serum myeloperoxidase and higher BMI are associated with FMS with obesity.
DOES THE IMPLEMENTATION OF MALAYSIAN PRIVATE ENTITY REPORTING STANDARD (MPERS) FOR SMEs AN ADDED VALUE FOR FINANCIAL REPORTING IN MALAYSIA?

The objective of the research is to analyze does the implementation of the MPERS for SMEs bring in value added to the financial reporting in Malaysia. The research used the descriptive analytical method to answer the questions and test the research hypotheses. By testing the hypothesis using the SPSS, the study used the theoretical aspect of the previous studies as the basis and analyzed the results of the applied study. A set of questionnaires using a sample of 118 respondents was distributed consists of accounting practitioners working in the financial departments of the SMEs in Malaysia. They are comprising of accountants, auditors, tax managers and financial controller. The results of the study designated that the implementation of the MPERS has many benefits in which directly improving the financial reporting quality, provide sufficiency information to the users and in the financial reports the level of disclosure and transparency will be increase. Thus, the study shows that all the SMEs shall adhere with the MPERS to enhance the financial reporting quality to gain investor confidence.
ROLE OF TET2 IN LUMINAL DIFFERENTIATION AND HORMONE THERAPY RESPONSE IN BREAST CANCER

Epigenetic mechanisms, including DNA methylation, play an important role in regulation of stem cell fate and tumorigenesis. The Ten-Eleven-Translocation 2 (TET2) is a core enzyme for DNA demethylation by catalyzing the conversion of 5-methylcytosine (5mC) to 5-hydromethylcytosine (5hmC). It has been shown that TET2 is the main regulator of hematopoietic stem cell homeostasis and loss of TET2 is highly associated with hematopoietic malignancies. Our previous work has also shown that loss of TET2 expression is linked to promotion of an epithelial-mesenchymaltransition phenotype and expansion of a breast cancer stem cell-like population with skewed asymmetric cell division in vitro (1); however, the in vivo role that TET2 plays in regulation of mammary stem cell (MaSC) fate and development of mammary pathology has yet to be determined. Here, using our newly established mammary-specific Tet2-knockout mouse model, the data reveals for the first time that TET2 plays a pivotal role in mammary gland development via directing MaSC to luminal lineage commitment in vivo. Furthermore, we find that TET2 coordinates with FOXP1 to target and demethylate FOXA1, GATA3, and ESR1, key transcription factors that orchestrate mammary luminal lineage specification and endocrine response and are often silenced by DNA methylation in aggressive human breast cancers. Finally, loss of TET2 expression leads to promotion of mammary tumor development with defective luminal cell differentiation and tamoxifen resistance in a PyMT;Tet2 deletion breast cancer mouse model. As a result, this study provides a previously unidentified role for TET2 in governing luminal lineage specification and endocrine response that underlies resistance to anti-estrogen treatments.
Circumvented in Combination with HDAC Inhibition

BIM (BCL2L11) is a BH3-only proapoptotic member of the Bcl-2 protein family. BIM upregulation is required for apoptosis induction by EGF receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in EGFRmutant forms of non–small cell lung cancer (NSCLC). Notably, a BIM deletion polymorphism occurs naturally in 12.9% of East Asian individuals, impairing the generation of the proapoptotic isoform required for the EGFR-TKIs gefitinib and erlotinib and therefore conferring an inherent drug-resistant phenotype. Indeed, patients with NSCLC, who harbored this host BIM polymorphism, exhibited significantly inferior responses to EGFR-TKI treatment than individuals lacking this polymorphism. In an attempt to correct this response defect in the resistant group, we investigated whether the histone deacetylase (HDAC) inhibitor vorinostat could circumvent EGFR-TKI resistance in EGFR-mutant NSCLC cell lines that also harbored the BIM polymorphism. Consistent with our clinical observations, we found that such cells were much less sensitive to gefitinib-induced apoptosis than EGFR-mutant cells, which did not harbor the polymorphism. Notably, vorinostat increased expression in a dose-dependent manner of the proapoptotic BH3 domain-containing isoform of BIM, which was sufficient to restore gefitinib death sensitivity in the EGFR mutant, EGFR-TKI– resistant cells. In xenograft models, while gefitinib induced marked regression via apoptosis of tumors without the BIM polymorphism, its combination with vorinostat was needed to induce marked regression of tumors with the BIM polymorphism in the same manner. Together, our results show how HDAC inhibition can epigenetically restore BIM function and death sensitivity of EGFR-TKI in cases of EGFR-mutant NSCLC where resistance to EGFR-TKI is associated with a common BIM polymorphism. Cancer Res; 73(8); 2428–34.
A hybrid simulation model for moving objects

: Following a discussion of the strengths and weaknesses of the current modeling paradigms used for movement simulation in movement ecology, a hybrid simulation model is proposed that jointly exploits the benefits offered by agent-based models (ABM), discrete event simulation (DES), and system dynamics (SD), respectively, while attempting to limit their drawbacks. We describe the transition from a conceptual model of movement to the logical structure that is able to support the hybrid simulation model. We use examples from ornithology to instantiate the components of the logical model. Compared to traditional movement simulation methods such as correlated random walk, the proposed model can provide a more holistic representation of the movement of objects within their environment, while also maintaining the perspective of the individual object. We argue that this multi-level approach and flexibility is possible through the combination of the capabilities of ABM to model interactions among individuals, with the strengths of DES to model discrete events and global rules, and finally with the capacity of SD to model causality and feedback loops. Additionally, the motivation of an individual, being a core driver of movement, has been embedded into the logical simulation model.
T-cell apoptosis in HIV-1–infected individuals receiving highly active antiretroviral therapy

1. Nussbaum RH. The linear no-threshold dose-effect relation: is it relevant to radiation protection regulation. Med Phys. 1998;25:291-299. 2. Nakanishi M, Tanaka K, Shintanti T, Takahashi T, Kamada N. Chromosomal instability in acute myelocytic leukemia and myelodysplastic syndrome patients among atomic bomb survivors. J Radiat Res (Tokyo). 1999;40:159-167. 3. Matsuo T, Tomonaga M, Bennett JM, et al. Reclassification of leukemia among A-bomb survivors in using the French-American-British (FAB) classification for acute leukemia. Jpn J Clin Oncol. 1988;18:91-96. 4. Deininger MW, Bose S, Gora-Tybor J, Yan XH, Goldman JM, Melo JV. Selective induction of leukemia associated fusion genes by high dose ionizing radiation. Cancer Res. 1998;58:421-425.
Provisioning Using Opendaylight OVSDB Into Openstack: Experiments

– Network function virtualization (NFV) and Software Defined Networking (SDN) are complementary technologies that support flexible development or virtual machines in various environments, e.g., multi-tenant / multi-domain. While SDN separates the architectural control plane, versus data plane, NFV implements a lot of functions (that traditionally have been performed by dedicated boxes), by software – using virtualized network functions (VNF). There are still open research issues in both SDN and NFV, especially related to their cooperation and integration. This paper presents an experiment of deploying networks and virtual machines (VMs) using Openstack and Open vSwitch Database Management Protocol (OVSDB) from Opendaylight project. The study is oriented towards implementation aspects. Its main objective is to deploy an Openstack controller, an Opendaylight controller and two compute nodes and to create on top of existing infrastructure several networks and illustrate how this is automatically achieved and how overlay networks can coexist. The paper describes step by step how to configure controllers, how connectivity is achieved and how OpenFlow is used to forward packets.
Identi¢cationof bacterial plasmidsbased onmobilityand plasmid population biology

Plasmids contain a backbone of core genes that remains relatively stable for long evolutionary periods, making sense to speak about plasmid species. The identification and characterization of the core genes of a plasmid species has a special relevance in the study of its epidemiology and modes of transmission. Besides, this knowledge will help to unveil the main routes that genes, for example antibiotic resistance (AbR) genes, use to travel from environmental reservoirs to human pathogens. Global dissemination of multiple antibiotic resistances and virulence traits by plasmids is an increasing threat for the treatment of many bacterial infectious diseases. To follow the dissemination of virulence and AbR genes, we need to identify the causative plasmids and follow their path from reservoirs to pathogens. In this review, we discuss how the existing diversity in plasmid genetic structures gives rise to a large diversity in propagation strategies. We would like to propose that, using an identification methodology based on plasmid mobility types, we can follow the propagation routes of most plasmids in Gammaproteobacteria, as well as their cargo genes, in complex ecosystems. Once the dissemination routes are known, designing antidissemination drugs and testing their efficacy will become feasible.
Involvement of the glycine-rich RNA-binding proteins (GRP) in osmotic stress response during seed germination: a comparison between GRP 2 and GRP 7

The plant glycine-rich RNA-binding proteins (GRP) are a major class of proteins known to be implicated in plant response to abiotic and biotic stress. Recent studies regarding this type of proteins focused mostly on two of them, namely GRP2 and GRP7, which are mainly involved in osmotic and oxidative plant adaptation mechanisms. The main purpose of this research was to assess the involvement of these two glycine-rich RNA-binding proteins (GRP2 and GRP7) in seed germination capacity under drought stress conditions using the model plant Arabidopsis thaliana. The plant material was composed out of seed batches obtained from the T-DNA insertion Arabidopsis thaliana mutant lines labelled grp2 (knock-out mutant for the glycine-rich RNA-binding protein 2), grp7-1 (knockout mutant for the glycine-rich RNA-binding protein 7), and the ecotype Columbia 0 (Col0), which was used as control. For the germination assay, the control medium 1⁄2 MS (Murashige&Skoog) was supplemented with three different concentrations (100mM, 200mM and 300mM) of mannitol. The germination was assessed each day during one week. After this period, the germination rate was estimated. Three independent replicates were used and the statistical analysis, namely the ANOVA test, was made using the Graph Pad Prism software (trial version). We observed a difference between the two mutants: grp2 seeds germinated similarly on the control medium as well as on the medium supplemented with various mannitol concentrations, while grp7-1 seeds showed a poor germination rate on all three mannitol culture mediums. The germination rate of the grp2 seeds was also increased, on all the culture mediums used, in comparison to the control Col0 seeds. In the present research work, we demonstrated that even though the two proteins GRP2 and GRP7 belong to the same family, their implication in the seed germination capacity under drought stress is opposite, one enhancing the germination, while the other is reducing it.
University of Birmingham PRMT5 is a critical regulator of breast cancer stem cell function via histone methylationand FOXP1 expression

Citation for published version (Harvard): Chiang, K, Zielinska, A, Shaaban, A, Sanchez-Bailon, M, Jarrold, J, Clarke, T, Zhang, J, Francis, A, Jones, LJ, Smith, S, Barbash, O, Guccione, E, Farnie, G, Smalley, MJ & Davies, C 2017, 'PRMT5 is a critical regulator of breast cancer stem cell function via histone methylationand FOXP1 expression. ', Cell Reports, vol. 21, no. 12, pp. 3498-3513. https://doi.org/10.1016/j.celrep. 2017.11. 096