Miracle-dz/UniFAR-FTUs huggingface dataset:
The Cyclin-Dependent Kinase Inhibitor p21 Is a Crucial Target for Histone Deacetylase 1 as a Regulator of Cellular Proliferation

ABSTRACT Histone deacetylases (HDACs) are chromatin-modifying enzymes that are involved in the regulation of proliferation, differentiation and development. HDAC inhibitors induce cell cycle arrest, differentiation, or apoptosis in tumor cells and are therefore promising antitumor agents. Numerous genes were found to be deregulated upon HDAC inhibitor treatment; however, the relevant target enzymes are still unidentified. HDAC1 is required for mouse development and unrestricted proliferation of embryonic stem cells. We show here that HDAC1 reversibly regulates cellular proliferation and represses the cyclin-dependent kinase inhibitor p21 in embryonic stem cells. Disruption of the p21 gene rescues the proliferation phenotype of HDAC1−/− embryonic stem cells but not the embryonic lethality of HDAC1−/− mice. In the absence of HDAC1, mouse embryonic fibroblasts scarcely undergo spontaneous immortalization and display increased p21 expression. Chromatin immunoprecipitation assays demonstrate a direct regulation of the p21 gene by HDAC1 in mouse embryonic fibroblasts. Transformation with simian virus 40 large T antigen or ablation of p21 restores normal immortalization of primary HDAC1−/− fibroblasts. Our data demonstrate that repression of the p21 gene is crucial for HDAC1-mediated control of proliferation and immortalization. HDAC1 might therefore be one of the relevant targets for HDAC inhibitors as anticancer drugs.
Feasibility of Biventricular Repair in Right Dominant Unbalanced Atrioventricular Septal Defect: A New Echocardiographic Metric to Refine Surgical Decision-Making

Background: Unbalanced forms of atrioventricular septal defect continue to be challenging and present poor surgical outcomes. Echocardiographic indicators such as atrioventricular valve index, right ventricle/left ventricle inflow angle, and size of the ventricular septal defect have been identified as relevant discriminators that may guide surgical strategy. Our purpose is to describe another metric to refine surgical decision-making. Methods: We outline a geometrical description of the anatomic features of atrioventricular septal defect and describe equations that help explain the interplay between the main echocardiographic variables. Results: A new metric called “indexed ventricular septal defect” is defined as the size of the defect in relation to the valve diameter. We derive a final equation relating this index with the atrioventricular valve index and the right ventricle/left ventricle inflow angle. In the light of that equation, we discuss the interdependence of variables and employ data from a Congenital Heart Surgeons’ Society study to set the limits of the new index. Conclusion: Combined use of indexed ventricular septal defect and atrioventricular valve index might help clarify surgical decision-making in patients with mild and moderate unbalance (modified atrioventricular valve index between 0.2 and 0.39). For indexed ventricular septal defect smaller than 0.2, biventricular repair may be recommended. Between 0.2 and 0.35, this strategy could probably be achieved depending on other factors. However, other strategies should be considered for those patients showing an indexed ventricular septal defect between 0.35 and 0.5. For values above 0.5 to 0.55, univentricular palliation might be a reasonable strategy.
Recent progress in the treatment of Crimean–Congo hemorrhagic fever and future perspectives

Crimean–Congo hemorrhagic fever (CCHF) caused by the CCHF virus, a member of the family Bunyaviridae, genus Nairovirus, is a tick-borne acute viral hemorrhagic fever with a high case–fatality rate. Ribavirin has been used as a treatment for patients with CCHF. Although the efficacy of ribavirin in the treatment of CCHF has not yet been proven conclusively, its use in the early stage of the disease is recommended. A number of clinical and virological insights into CCHF have been revealed. Virus-associated hemophagocytic syndrome has been found to contribute to the exacerbation of CCHF in some patients, and the administration of methylprednisolone at high doses was observationally undertaken in patients with CCHF and virus-associated hemophagocytic syndrome, with promising results. It is expected that effective therapeutics and preventive measures will be developed in the future.
AGOCS — Accurate Google Cloud Simulator Framework

This paper presents the Accurate Google Cloud Simulator (AGOCS) – a novel high-fidelity Cloud workload simulator based on parsing real workload traces, which can be conveniently used on a desktop machine for day-to-day research. Our simulation is based on real-world workload traces from a Google Cluster with 12.5K nodes, over a period of a calendar month. The framework is able to reveal very precise, detailed parameters of the executed jobs, tasks, nodes as well as to provide actual resource usage statistics. The system has been implemented in Scala language with focus on parallel execution, an easy-to-extend design concept. The paper presents the detailed structural framework for AGOCS, discusses our main design decisions, whilst also suggesting alternative, possibly performance enhancing future approaches. The framework is available via the Open Source GitHub repository.
Serum carotenoids, α-tocopherol, and lung function among Dutch elderly

Antioxidant vitamins (provitamins) may protect against loss of lung function over time. We studied the association between serum carotenoids ( α -carotene, β -carotene, lycopene, β -cryptoxanthin, zeaxanthin, and lutein), α -tocopherol, and lung function among noninstitutionalized Dutch elderly age 65 to 85 yr (n = 528). Multiple linear regression analysis was performed with FEV1 or FVC as dependent variables and serum levels of antioxidants in quintiles as independent variables. We adjusted for age, gender, height, and pack-years of smoking. Subjects in the fifth quintile of serum β -carotene had a 195 ml (95% confidence interval [95% CI]: 40 to 351 ml) higher and those in the fifth quintile of α -carotene had a 257 ml (95% CI: 99 to 414 ml) higher FEV1 compared with subjects in the first quintile of these carotenoids. Significant (p < 0.05) positive trends were observed between α -carotene, β -carotene, lycopene, and FEV1 and between α -carotene, β -carotene, and FVC. Subjects in the highest quintile of.
Fiery spirits and supporting programs of action: keys to exploration and exploitation of open technologies

If telemedicine is to impact on and shape the hospital of the future, the challenge for strategic management will be to create and support a process where the technology's fields of application can be developed and diffused. Due to the technology's openness, this is required to occur in use of the technology, during a process of exploration and exploitation of its applications. The role of fiery spirits and supporting programmes of action are emphasised, by using Actor Network Theory as an analytical perspective on a longitudinal study of two Swedish telemedicine projects. It is concluded that fiery spirits are playing a significant role in the phase of exploring fields of application, but if applications are to be successfully exploited, the dependency of the fiery spirits has to be gradually decoupled. In this process, supporting programmes of action will facilitate the further exploitation and stabilisation of technology usage.
Disruption of the Hbs1l-Myb Locus Causes Hereditary Persistence of Fetal Hemoglobin in a Mouse Model

ABSTRACT The human β-globin locus is comprised of embryonic, fetal, and adult globin genes, each of which is expressed at distinct stages of pre- and postnatal development. Functional defects in globin proteins or expression results in mild to severe anemia, such as in sickle-cell disease or β-thalassemia, but the clinical symptoms of both disorders are ameliorated by persistent expression of the fetal globin genes. Recent genome-wide association studies (GWAS) identified the intergenic region between the HBS1L and MYB loci as a candidate modifier of fetal hemoglobin expression in adults. However, it remains to be clarified whether the enhancer activity within the HBS1L-MYB regulatory domain contributes to the production of fetal hemoglobin in adults. Here we report a new mouse model of hereditary persistence of fetal hemoglobin (HPFH) in which a transgene was randomly inserted into the orthologous murine Hbs1l-Myb locus. This mutant mouse exhibited typically elevated expression of embryonic globins and hematopoietic parameters similar to those observed in human HPFH. These results support the contention that mutation of the HBS1L-MYB genomic domain is responsible for elevated expression of the fetal globin genes, and this model serves as an important means for the analysis of networks that regulate fetal globin gene expression.
Semaphorin 3E Initiates Antiangiogenic Signaling through Plexin D1 by Regulating Arf6 and R-Ras

ABSTRACT Recent studies revealed that a class III semaphorin, semaphorin 3E (Sema3E), acts through a single-pass transmembrane receptor, plexin D1, to provide a repulsive cue for plexin D1-expressing endothelial cells, thus providing a highly conserved and developmentally regulated signaling system guiding the growth of blood vessels. We show here that Sema3E acts as a potent inhibitor of adult and tumor-induced angiogenesis. Activation of plexin D1 by Sema3E causes the rapid disassembly of integrin-mediated adhesive structures, thereby inhibiting endothelial cell adhesion to the extracellular matrix (ECM) and causing the retraction of filopodia in endothelial tip cells. Sema3E acts on plexin D1 to initiate a two-pronged mechanism involving R-Ras inactivation and Arf6 stimulation, which affect the status of activation of integrins and their intracellular trafficking, respectively. Ultimately, our present study provides a molecular framework for antiangiogenesis signaling, thus impinging on a myriad of pathological conditions that are characterized by aberrant increase in neovessel formation, including cancer.
Local navigation techniques by means of ICPF

The problem of mobile robot navigation is a broad topic and it covers a large spectrum of different methods and technologies. In this paper we will present the new concept for local navigation. The concept is based on object identification technique by means of origin fragment identification algorithm (ICPF). The main idea, theory and practical examples of object identification using ICPF are presented as main goal of the paper. One can use it for robot location and as support information in case of following local path planning. We also sketch in two different possibilities for image data measuring. The post-process of the antecedent steps can be local path planning of course.
Numerical simulation of spectrum wave propagating in pseudo three dimensional wave basin

The convention method of berthing stability study by physical scaled model was replaced by purely numerical model based on modified Boussinesq type wave equations in the paper. Directional spectrum wind wave was generated in pseudo three dimensional numerical wave basin. In front of vertical walls, typical reflection coefficient of 0.80 was introduced, and around the sloped breakwaters the reflection coefficients of 0.50∼0.60 were applied. The calculation domain was a real fishing port with directional wind wave incoming from Southeast, and South, Southwest. By purely numerical method, the berthing stability was studied in accordance with the Code of Hydrology for Sea Harbor, China (“the Code”). It is concluded the numerical model is of satisfactory accuracy and can be of engineering reference value in the design and planning of coastal structures and harbors.
Cooperative-Binding and Splicing-Repressive Properties of hnRNP A1

ABSTRACT hnRNP A1 binds to RNA in a cooperative manner. Initial hnRNP A1 binding to an exonic splicing silencer at the 3′ end of human immunodeficiency virus type 1 (HIV-1) tat exon 3, which is a high-affinity site, is followed by cooperative spreading in a 3′-to-5′ direction. As hnRNP A1 propagates toward the 5′ end of the exon, it antagonizes binding of a serine/arginine-rich (SR) protein to an exonic splicing enhancer, thereby inhibiting splicing at that exon's alternative 3′ splice site. tat exon 3 and the preceding intron of HIV-1 pre-mRNA can fold into an elaborate RNA secondary structure in solution, which could potentially influence hnRNP A1 binding. We report here that hnRNP A1 binding and splicing repression can occur on an unstructured RNA. Moreover, hnRNP A1 can effectively unwind an RNA hairpin upon binding, displacing a bound protein. We further show that hnRNP A1 can also spread in a 5′-to-3′ direction, although when initial binding takes place in the middle of an RNA, spreading preferentially proceeds in a 3′-to-5′ direction. Finally, when two distant high-affinity sites are present on the same RNA, they facilitate cooperative spreading of hnRNP A1 between the two sites.
Chromatinized Protein Kinase C-θ Directly Regulates Inducible Genes in Epithelial to Mesenchymal Transition and Breast Cancer Stem Cells

ABSTRACT Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. Signal transduction kinases play a pivotal role as chromatin-anchored proteins in eukaryotes. Here we report for the first time that protein kinase C-theta (PKC-θ) promotes EMT by acting as a critical chromatin-anchored switch for inducible genes via transforming growth factor β (TGF-β) and the key inflammatory regulatory protein NF-κB. Chromatinized PKC-θ exists as an active transcription complex and is required to establish a permissive chromatin state at signature EMT genes. Genome-wide analysis identifies a unique cohort of inducible PKC-θ-sensitive genes that are directly tethered to PKC-θ in the mesenchymal state. Collectively, we show that cross talk between signaling kinases and chromatin is critical for eliciting inducible transcriptional programs that drive mesenchymal differentiation and CSC formation, providing novel mechanisms to target using epigenetic therapy in breast cancer.
A Review Study on Punica granatum L

Punica granatum L (pomegranate) is a deciduous shrub, native to Iran. Nowadays, besides its use as a fruit, its medicinal properties have attracted the interest of researchers of many countries. Pomegranate fruit has medicinal properties such as anti-inflammatory and antibacterial activities. The pomegranate seed oil has inhibitory effect on skin and breast cancers. The pomegranate seed oil has phytoestrogenic compounds and the fruit is rich in phenolic compounds with strong antioxidant activity. Ellagic acid is one of the main components of pomegranate with phenolic structure and antioxidant activity. This review article presents the recently published findings on different aspects of this plant focusing on its medicinal properties
Activator-to-Repressor Conversion of T-Box Transcription Factors by the Ripply Family of Groucho/TLE-Associated Mediators

ABSTRACT The T-box family of transcription factors, defined by a conserved DNA binding domain called the T-box, regulate various aspects of embryogenesis by activating and/or repressing downstream genes. In spite of the biological significance of the T-box proteins, how they regulate transcription remains to be elucidated. Here we show that the Groucho/TLE-associated protein Ripply converts T-box proteins from activators to repressors. In cultured cells, zebrafish Ripply1, an essential component in somite segmentation, and its structural relatives, Ripply2 and -3, suppress the transcriptional activation mediated by the T-box protein Tbx24, which is coexpressed with ripply1 during segmentation. Ripply1 associates with Tbx24 and converts it to a repressor. Ripply1 also antagonizes the transcriptional activation of another T-box protein, No tail (Ntl), the zebrafish ortholog of Brachyury. Furthermore, injection of a high dosage of ripply1 mRNA into zebrafish eggs causes defective development of the posterior trunk, similar to the phenotype observed in homozygous mutants of ntl. A mutant form of Ripply1 defective in association with Tbx24 also lacks activity in zebrafish embryos. These results indicate that the intrinsic transcriptional property of T-box proteins is controlled by Ripply family proteins, which act as specific adaptors that recruit the global corepressor Groucho/TLE to T-box proteins.
PLRG1 Is an Essential Regulator of Cell Proliferation and Apoptosis during Vertebrate Development and Tissue Homeostasis

ABSTRACT PLRG1, an evolutionarily conserved component of the spliceosome, forms a complex with Pso4/SNEV/Prp19 and the cell division and cycle 5 homolog (CDC5L) that is involved in both pre-mRNA splicing and DNA repair. Here, we show that the inactivation of PLRG1 in mice results in embryonic lethality at 1.5 days postfertilization. Studies of heart- and neuron-specific PLRG1 knockout mice further reveal an essential role of PLRG1 in adult tissue homeostasis and the suppression of apoptosis. PLRG1-deficient mouse embryonic fibroblasts (MEFs) fail to progress through S phase upon serum stimulation and exhibit increased rates of apoptosis. PLRG1 deficiency causes enhanced p53 phosphorylation and stabilization in the presence of increased γ-H2AX immunoreactivity as an indicator of an activated DNA damage response. p53 downregulation rescues lethality in both PLRG1-deficient MEFs and zebrafish in vivo, showing that apoptosis resulting from PLRG1 deficiency is p53 dependent. Moreover, the deletion of PLRG1 results in the relocation of its interaction partner CDC5L from the nucleus to the cytoplasm without general alterations in pre-mRNA splicing. Taken together, the results of this study identify PLRG1 as a critical nuclear regulator of p53-dependent cell cycle progression and apoptosis during both embryonic development and adult tissue homeostasis.
VIScover: Visualizing, exploring, and analysing structured data

Today's challenging task in intelligent data processing is not to store large volumes of interlinked data but to visualize, explore, and understand its explicit or implicit relationships. Our solution to this is the VIScover system. VIScover combines semantic technologies with interactive exploration and visualization techniques able to analyze large volumes of structured data. We briefly describe our VIScover system and show its potential using the example of the VAST 2009 social network and geospatial data set.
Zero spectrum removal using joint bilateral filter for Fourier transform profilometry

Traditional Fourier transform profilometry (FTP) removes the zero spectrum of the acquired fringe image using the linear filtering approach. Such approach assumes there is no aliasing between the zero spectrum and the higher harmonics of the image, which however is not true in general. Thus it cannot adapt to sharp illuminant changes in the fringe image. One practical solution is to exploit one more fringe pattern with π phase shift to eliminate the zero spectrum. This however complicates the system in that the projection of the fringe patterns should be synchronized with the capturing device. Motion or imperfect synchronization makes the subsequent 3D reconstruction erroneous. In this paper, we introduce a 2D joint bilateral filter to help in removing the zero spectrum. Since the bilateral filter is sensitive to abrupt changes in the fringe image, we can accurately extract the zero spectrum even if there are sharp spatial variations in the pixel magnitude. Experimental results show that the proposed algorithm is superior to the traditional methods and facilitate accurate reconstruction of objects' 3D model.
The Assembly Pathway of the Mitochondrial Carrier Translocase Involves Four Preprotein Translocases

ABSTRACT The mitochondrial inner membrane contains preprotein translocases that mediate insertion of hydrophobic proteins. Little is known about how the individual components of these inner membrane preprotein translocases combine to form multisubunit complexes. We have analyzed the assembly pathway of the three membrane-integral subunits Tim18, Tim22, and Tim54 of the twin-pore carrier translocase. Tim54 displayed the most complex pathway involving four preprotein translocases. The precursor is translocated across the intermembrane space in a supercomplex of outer and inner membrane translocases. The TIM10 complex, which translocates the precursor of Tim22 through the intermembrane space, functions in a new posttranslocational manner: in case of Tim54, it is required for the integration of Tim54 into the carrier translocase. Tim18, the function of which has been unknown so far, stimulates integration of Tim54 into the carrier translocase. We show that the carrier translocase is built via a modular process and that each subunit follows a different assembly route. Membrane insertion and assembly into the oligomeric complex are uncoupled for each precursor protein. We propose that the mitochondrial assembly machinery has adapted to the needs of each membrane-integral subunit and that the uncoupling of translocation and oligomerization is an important principle to ensure continuous import and assembly of protein complexes in a highly active membrane.
Histone H3 Lysine 4 Hypermethylation Prevents Aberrant Nucleosome Remodeling at the PHO5 Promoter

ABSTRACT Recent studies have highlighted the histone H3K4 methylation (H3K4me)-dependent transcriptional repression in Saccharomyces cerevisiae; however, the underlying mechanism remains inexplicit. Here, we report that H3K4me inhibits the basal PHO5 transcription under high-phosphate conditions by suppressing nucleosome disassembly at the promoter. We found that derepression of the PHO5 promoter by SET1 deletion resulted in a labile chromatin structure, allowing more binding of RNA polymerase II (Pol II) but not the transactivators Pho2 and Pho4. We further showed that Pho23 and Cti6, two plant homeodomain (PHD)-containing proteins, cooperatively anchored the large Rpd3 (Rpd3L) complex to the H3K4-methylated PHO5 promoter. The deacetylation activity of Rpd3 on histone H3 was required for the function of Set1 at the PHO5 promoter. Taken together, our data suggest that Set1-mediated H3K4me suppresses nucleosome remodeling at the PHO5 promoter so as to reduce basal transcription of PHO5 under repressive conditions. We propose that the restriction of aberrant nucleosome remodeling contributes to strict control of gene transcription by the transactivators.
The USP1/UAF1 Complex Promotes Double-Strand Break Repair through Homologous Recombination

ABSTRACT Protein ubiquitination plays a key role in the regulation of a variety of DNA repair mechanisms. Protein ubiquitination is controlled by the coordinate activity of ubiquitin ligases and deubiquitinating enzymes (DUBs). The deubiquitinating enzyme USP1 regulates DNA repair and the Fanconi anemia pathway through its association with its WD40 binding partner, UAF1, and through its deubiquitination of two critical DNA repair proteins, FANCD2-Ub and PCNA-Ub. To investigate the function of USP1 and UAF1, we generated USP1−/−, UAF1−/−/−, and USP1−/− UAF1−/−/− chicken DT40 cell clones. These three clones showed similar sensitivities to chemical cross-linking agents, to a topoisomerase poison, camptothecin, and to an inhibitor of poly(ADP-ribose) polymerase (PARP), indicating that the USP1/UAF1 complex is a regulator of the cellular response to DNA damage. The hypersensitivity to both camptothecin and a PARP inhibitor suggests that the USP1/UAF1 complex promotes homologous recombination (HR)-mediated double-strand break (DSB) repair. To gain insight into the mechanism of the USP1/UAF1 complex in HR, we inactivated the nonhomologous end-joining (NHEJ) pathway in UAF1-deficient cells. Disruption of NHEJ in UAF1-deficient cells restored cellular resistance to camptothecin and the PARP inhibitor. Our results indicate that the USP1/UAF1 complex promotes HR, at least in part by suppressing NHEJ.