Everywhere surjections and related topics. Examples and counterexamples

This paper deals with everywhere surjections, i.e. functions defined on a topological space whose restrictions to any non-empty open subset are surjective. We introduce and discuss several constructions in different contexts; some constructions are easy, while others are more involved. Among other things, we prove that there is a vector space of uncountable dimension whose non-zero elements are everywhere surjections from Q to Q; we give an example of an everywhere surjection whose domain is the set of countably infinite real sequences; we construct an everywhere surjective linear map from the Cantor set into itself. Finally, we prove the existence of functions from R to R which are everywhere surjections in stronger senses

MicroRNAs mediate metabolic stresses and angiogenesis

MicroRNAs are short endogenous RNA molecules that are able to regulate (mainly inhibiting) gene expression at the post-transcriptional level. The MicroRNA expression profile is cell-specific, but it is sensitive to perturbations produced by stresses and diseases. Endothelial cells subjected to metabolic stresses, such as calorie restriction, nutrients excess (glucose, cholesterol, lipids) and hypoxia may alter their functionality. This is predictive for the development of pathologies like atherosclerosis, diabetes, and hypertension. Moreover, cancer cells can activate a resting endothelium by secreting pro-angiogenic factors, in order to promote neoangiogenesis, which is essential for tumor growth. Endothelial altered phenotype is mirrored by altered mRNA, microRNA, and protein expression, with a microRNA being able to control pathways by regulating the expression of multiple mRNAs. In this review we will consider the involvement of microRNAs in modulating the response of endothelial cells to metabolic stresses and their role in promoting or halting angiogenesis

CRISPR-Cas9 Gene Editing of Hematopoietic Stem Cells from Patients with Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by expansion of GAA repeats in intron 1 of the frataxin (FXN) gene, leading to significant decreased expression of frataxin, a mitochondrial iron-binding protein. We previously reported that syngeneic hematopoietic stem and progenitor cell (HSPC) transplantation prevented neurodegeneration in the FRDA mouse model YG8R. We showed that the mechanism of rescue was mediated by the transfer of the functional frataxin from HSPC-derived microglia/macrophage cells to neurons/myocytes. In this study, we report the first step toward an autologous HSPC transplantation using the CRISPR-Cas9 system for FRDA. We first identified a pair of CRISPR RNAs (crRNAs) that efficiently removes the GAA expansions in human FRDA lymphoblasts, restoring the non-pathologic level of frataxin expression and normalizing mitochondrial activity. We also optimized the gene-editing approach in HSPCs isolated from healthy and FRDA patients' peripheral blood and demonstrated normal hematopoiesis of gene-edited cells in vitro and in vivo. The procedure did not induce cellular toxic effect or major off-target events, but a p53-mediated cell proliferation delay was observed in the gene-edited cells. This study provides the foundation for the clinical translation of autologous transplantation of gene-corrected HSPCs for FRDA

alat pengendali hama padi berbasis internet of things (iot)

Dalam bercocok tanam padi salah satu proses yang dilakukan yaitu pemberantasan hama padi. Upaya pemberantasan hama padi sudah dilakukan oleh petani, bahkan perlakuan untuk setiap hama sudah dibedakan sesuai dengan jenis hama. Misalnya, mengeringkan air sawah dalam waktu beberapa hari untuk memberantas tikus, kemudian menggunakan orang-orangan sawah yang menimbulkan bunyian dengan harapan dapat mengusir burung. Namun langkah tersebut tetap saja menyulitkan petani, karena petani harus selalu mengontrol keadaan sawah setiap saat. Sehingga masih kurang efektif dalam mengontrol/ mengatasi hama padi. Dalam penilitian ini sebagai lanjutan dari sistem terdahulu dengan judul “Sistem Pendeteksi Hama Padi Berbasis Internet of Things (IOT)”. Sistem ini akan melakukan koneksi internet melalui jaringan wifi untuk pengambilan data masukan berupa status dan jenis hama ke file penyimpanan pada server, selanjutnya akan dilakukan pembangkitan frekuensi dan pemancaran frekuensi untuk pengendalian hama tikus dan burung pipit. Pengendalian hama tikus akan dilakukan melalui pemancaran frekuensi sebesar 40000 Hz yang menyebabkan hama tikus merasa terganggu dan berlarian di dalam prototype, sedangkan untuk hama burung pipit akan menggunakan pemancaran frekuensi sebesar 29000 Hz yang menyebabkan hama burung mencoba terbang di dalam prototype. Hasil pengujian nilai frekuensi ketika tidak ada hama terdeteksi dan ketika hama terdeteksi dengan percobaan sebanyak 23 kali berhasil di tampilkan melalui smartphone petani dengan persentase keberhasilan 100%

Resolution to the Problem of Consistent Large Transverse Momentum in TMDS

Parametrizing TMD parton densities and fragmentation functions in ways that consistently match their large transverse-momentum behavior in standard collinear factorization has remained notoriously difficult. We show how the problem is solved in a recently introduced set of steps for combining perturbative and nonperturbative transverse momentum in TMD factorization. Called a “bottom-up” approach in a previous article, here we call it a “hadron structure oriented” (HSO) approach to emphasize its focus on preserving a connection to the TMD parton model interpretation. We show that the associated consistency constraints improve considerably the agreement between parametrizations of TMD functions and their large-kT behavior, as calculated in collinear factorization. The procedure discussed herein will be important for guiding future extractions of TMD parton densities and fragmentation functions and for testing TMD factorization and universality. We illustrate the procedure with an application to semi-inclusive deep inelastic scattering (SIDIS) structure functions at an input scale Q0, and we show that there is improved consistency between different methods of calculating at moderate transverse momentum. We end with a discussion of plans for future phenomenological applications

The RNA Activator ds-p21 Potentiates the Cytotoxicity Induced by Fludarabine in Dohh2 Cells

Recently, it has been reported that, in several tumor cell lines, short double-stranded RNAs tailored for promoter regions of specific genes are able to activate their transcription. Such molecules (named RNA activators) act opposite to other double-stranded RNA molecules (named RNA inhibitors) in that the overexpression instead of underexpression of a given gene is triggered. In Dohh2 non-Hodgkin lymphoma cells, the transcriptional repressor BCL6, which negatively controls both p53 and p21, is overexpressed, so that the cells can escape the check point governed by p53 and proliferate. The aim of this work was to investigate whether the RNA activator p21 can represent a tool to circumvent the transcriptional control of BCL6 and induce the blockage of cell proliferation in Dohh2 non-Hodgkin lymphoma cells. For that, Dohh2 cells were transfected with either a control RNA activator (ds-NC) or an RNA activator specific for human p21 promoter (ds-p21). At various time points after transfection, the cells were collected and p21 was measured. Dohh2 cells transfected with ds-p21 showed a slight but significant overexpression of p21 at both mRNA and protein levels. Nonetheless, cell proliferation, cell cycle, and apoptosis were not significantly modified. In contrast, the exposure of Dohh2 cells transfected with ds-p21 to fludarabine potentiates the cytotoxicity of the drug, suggesting the RNA activator p21 complements the fludarabine-dependent cell death pathways

The analysis of the expression pattern of the intracellular and extracellular miRNAs in prostate tumor cell lines exposed to cytotoxic drugs.

It has been recently discovered that microRNAs are stably expressed in body fluids of several organisms and that the expression patterns in the plasma/serum of cancer patients could represent a diagnostic/predictive tool of the disease. Extracellular miRNAs have been also found in the growth medium of cells in culture and this prompted us to verify whether prostate tumor cell lines release miRNAs specific of prostate tumor patients and whether anticancer drugs affect the expression patterns of the extracellular miRNAs. First of all we determined the expression of either prostate specific (PS-miRNA) or non prostate specific (NPS-miRNA) miRNAs in the growth medium of PC3 and DU-145 cells (prostate metastatic tumor cell lines) in comparison to PNT1A (immortalized prostate cell line). We found that the levels of both the intracellular and extracellular PS-miRNAs were higher in PC3 and DU-145 tumor cell lines in comparison to the immortalized cell line PNT1A and that a positive correlation exists between the intracellular and the extracellular levels suggesting that the release of miRNA in the growth medium may be a manner to maintain the intracellular miRNAs at physiological level. Thereafter, we investigated whether the release of miRNAs is affected in cells upon their exposure to a cytotoxic drug. To address the point, PC-3 and DU-145 cells were exposed to a cytotoxic concentration of either fludarabine (10 μg/mL) or taxotere (30 nM) for 48 hours. At the end of the treatment both the intracellular and extracellular PS-miRNAs and NPS-miRNAs were quantified. Data showed that i) those miRNAs that were up regulated in cells surviving to either fludarabine or taxotere were not released and that ii) the up regulated miRNAs found in fludarabine-or in taxotere-surviving cells were not the same. Overall data indicate for the first time a possible involvement of miRNAs in the survival/resistance of tumor cells to cytotoxic drugs and suggest that the expression pattern of the intracellular and extracellular miRNAs could be an useful tool to identify in tumor cell lines miRNAs responsible of survival/resistance to cytotoxic drugs and in plasma/serum of cancer patients the efficacy of an anticancer treatment

Pengaruh intensitas penggunaan media sosial Tiktok terhadap prokrastinasi salat fardu pada siswa : Penelitian terhadap siswa kelas VII MTs Miftahul Falah Kota Bandung

Penggunaan media sosial Tiktok yang berlebihan dan tidak terkontrol akan memberikan dampak negatif bagi para siswa, misalnya sikap prokrastinasi atau menunda-nunda pada suatu pekerjaan. Berdasarkan informasi yang didapatkan, pokok permasalahan pada penelitian ini yakni bagaimana Intensitas penggunaan media sosial Tiktok dapat menjadi penyebab timbulnya sikap prokrastinasi atau menunda-nunda dalam melaksanakan salat fardu pada siswa. Tujuan dari penelitian ini yaitu untuk mengetahui: 1) Mengetahui realitas intensitas penggunaan media sosial Tiktok pada siswa kelas VII MTs Miftahul Falah Kota Bandung. 2) Mengetahui realitas prokrastinasi salat fardu pada siswa kelas VII MTs Miftahul Falah Kota Bandung. 3) Mengetahui realitas pengaruh intensitas penggunaan media sosial Tiktok terhadap Prokrastinasi salat fardu pada siswa kelas VII MTs Miftahul Falah Kota Bandung. Intensitas penggunaan media sosial Tiktok yang tinggi akan menyebabkan kelelahan bagi individu, kelelahan menjadi salah satu faktor terjadinya perilaku prokrastinasi, dengan demikian besar kemungkinan mereka yang memiliki Intensitas penggunaan media sosial yang tinggi akan melakukan sikap prokrastinasi atau menunda-nunda dalam melakukan suatu pekerjaan misalnya dalam melaksanakan salat fardu. Berdasarkan hal tersebut, maka hipotesis yang diajukan yaitu terdapat pengaruh antara intensitas penggunaan media sosial Tiktok terhadap sikap prokrastinasi salat fardu pada siswa. Penelitian ini menggunakan pendekatan kuantitatif dengan metode korelasional. Respondennya yaitu siswa kelas VII MTs Miftahul Falah Kota Bandung yang berjumlah 35 siswa. Teknik pengumpulan data yang digunakan adalah angket, observasi, dan dokumentasi. Teknik analisis datanya adalah analisis statistik deskriptif, uji normalitas, uji, linearitas, analisis regresi linear, uji hipotesis dan uji koefisien determinasi. Berdasarkan hasil penelitian, maka didapatkan kesimpulan: 1) Realitas intensitas penggunaan media sosial Tiktok dalam kategori sedang atau cukup hal ini berdasarkan dengan rata-rata skor yaitu sebesar 3,29 yang berada pada interval 2,51-3,50 2) Realitas prokrastinasi salat fardu pada siswa, dengan nilai rata-rata sebesar 2,74 berada pada interval 2,51-3,50 memiliki kategori sedang atau cukup 3) Realitas pengaruh intensitas penggunaan media sosial Tiktok berpengaruh positif dan signifikan terhadap prokrastinasi salat fardu pada siswa ditunjukkan dengan nilai thitung > ttabel yaitu 3,352 > 2,034 dan nilai signifikansi lebih rendah dari 0,05 yaitu 0,002 < 0,05. Nilai dari Adjusted R Square sebesar 0,254 = 25,4%. Hal ini berarti kemampuan variabel bebas dalam menjelaskan variabel terikat adalah sebesar 25,4% dan sisanya 74,6%, dijelaskan oleh variabel lain yang tidak dibahas pada penelitian ini

Microbiota Modification with Probiotics Induces Hepatic Bile Acid Synthesis via Downregulation of the Fxr-Fgf15 Axis in Mice

Gut microbiota influences host health status by providing trophic, protective, and metabolic functions, including bile acid (BA) biotransformation. Microbial imprinting on BA signature modifies pool size and hydrophobicity, thus contributing to BA enterohepatic circulation. Microbiota-targeted therapies are now emerging as effective strategies for preventing and/or treating gut-related diseases. Here, we show that gut microbiota modulation induced by VSL#3 probiotics enhances BA deconjugation and fecal excretion in mice. These events are associated with changes in ileal BA absorption, repression of the enterohepatic farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis, and increased hepatic BA neosynthesis. Treatment with a FXR agonist normalized fecal BA levels in probiotic-administered mice, whereas probiotic-induced alterations in BA metabolism are abolished upon FXR and FGF15 deficiency. Our data provide clear in vivo evidence that VSL#3 probiotics promote ileal BA deconjugation with subsequent fecal BA excretion and induce hepatic BA neosynthesis via downregulation of the gut-liver FXR-FGF15 axis

A new method for discovering disease-specific miRNA-target regulatory networks

Genes and their expression regulation are among the key factors in the comprehension of the genesis and development of complex diseases. In this context, microRNAs (miRNAs) are post-transcriptional regulators that play an important role in gene expression since they are frequently deregulated in pathologies like cardiovascular disease and cancer. In vitro validation of miRNA - targets regulation is often too expensive and time consuming to be carried out for every possible alternative. As a result, a tool able to provide some criteria to prioritize trials is becoming a pressing need. Moreover, before planning in vitro experiments, the scientist needs to evaluate the miRNA-target genes interaction network. In this paper we describe the miRable method whose purpose is to identify new potentially relevant genes and their interaction networks associate to a specific pathology. To achieve this goal miRable follows a system biology approach integrating together general-purpose medical knowledge (literature, Protein-Protein Interaction networks, prediction tools) and pathology specific data (gene expression data). A case study on Prostate Cancer has shown that miRable is able to: 1) find new potential miRNA-targets pairs, 2) highlight novel genes potentially involved in a disease but never or little studied before, 3) reconstruct all possible regulatory subnetworks starting from the literature to expand the knowledge on the regulation of miRNA regulatory mechanisms