A STUDY ON THE FUNCTION OF 14-3-3SIGMA IN REGULATING CANCER ENERGY METABOLISM

Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates c-Myc-induced metabolic target genes expression. Therefore, 14-3-3σ remarkably blocks glycolysis, decreases glutaminolysis and diminishes mitochondrial mass of cancer cells both in vitro and in vivo, thereby severely suppressing cancer bioenergetics and metabolism. As a result, a high level of 14-3-3σ in tumors is strongly associated with increased breast cancer patients’ overall and metastasis-free survival as well as better clinical outcomes. Thus, this study reveals a new role for 14-3-3s as a significant regulator of cancer bioenergetics and a promising target for the development of anti-cancer metabolism therapies

Nuclear quantum effects in water exchange around lithium and fluoride ions

We employ classical and ring polymer molecular dynamics simulations to study the effect of nuclear quantum fluctuations on the structure and the water exchange dynamics of aqueous solutions of lithium and fluoride ions. While we obtain reasonably good agreement with experimental data for solutions of lithium by augmenting the Coulombic interactions between the ion and the water molecules with a standard Lennard-Jones ion-oxygen potential, the same is not true for solutions of fluoride, for which we find that a potential with a softer repulsive wall gives much better agreement. A small degree of destabilization of the first hydration shell is found in quantum simulations of both ions when compared with classical simulations, with the shell becoming less sharply defined and the mean residence time of the water molecules in the shell decreasing. In line with these modest differences, we find that the mechanisms of the exchange processes are unaffected by quantization, so a classical description of these reactions gives qualitatively correct and quantitatively reasonable results. We also find that the quantum effects in solutions of lithium are larger than in solutions of fluoride. This is partly due to the stronger interaction of lithium with water molecules, partly due to the lighter mass of lithium, and partly due to competing quantum effects in the hydration of fluoride, which are absent in the hydration of lithium.Comment: 12 pages, 8 figure

Pengaruh Kepuasan pada Gaji dan Loyalitas Karyawan pada Kinerja Karyawan PT Remaja Service di Kupang

Penelitian ini dilakukan agar, dapat melihat bagaimana pengaruh kepuasan pada gaji, loyalitas karyawan, pada kinerja karyawan PT Remaja Service. Pengumpulan dilakukan dengan cara menyebar angket bagi para responden yang merupakan karyawan PT Remaja Service, penelitian ini mengambil jumlah sampel sebanyak 44 responden. Jenis penelitian yang digunakan adalah penelitian kuantitatif dengan adanya teknik analisis regresi berganda.Hasil dari penelitian ini menunjukan bahwa, terdapat pengaruh signifikan kepuasan pada gaji, loyalitas karyawan, pada kinerja karyawan PT Remaja Service

Yukawa potentials in systems with partial periodic boundary conditions II : Lekner sums for quasi-two dimensional systems

Yukawa potentials may be long ranged when the Debye screening length is large. In computer simulations, such long ranged potentials have to be taken into account with convenient algorithms to avoid systematic bias in the sampling of the phase space. Recently, we have provided Ewald sums for quasi-two dimensional systems with Yukawa interaction potentials [M. Mazars, {\it J. Chem. Phys.}, {\bf 126}, 056101 (2007) and M. Mazars, {\it Mol. Phys.}, Paper I]. Sometimes, Lekner sums are used as an alternative to Ewald sums for Coulomb systems. In the present work, we derive the Lekner sums for quasi-two dimensional systems with Yukawa interaction potentials and we give some numerical tests for pratical implementations. The main result of this paper is to outline that Lekner sums cannot be considered as an alternative to Ewald sums for Yukawa potentials. As a conclusion to this work : Lekner sums should not be used for quasi-two dimensional systems with Yukawa interaction potentials.Comment: 25 pages, 5 figures and 1 tabl

Kinderdoding gevolgd door een ernstige poging tot zelfdoding

Het doden van kinderen is een dramatische gebeurtenis. Deze dodingen krijgen een versterkt dramatisch karakter als de dader ook nog zichzelf doodt of een poging daartoe doet. In deze studie wordt onderzocht of kinderdoding gevolgd door een ernstige poging tot zelfdoding een variatie op doding vormt, een variatie op zelfdoding vormt, of als een aparte categorie van dodelijk geweld moet worden beschouwd. Suïcidale ouders die hun kinderen doodden, verschillen in sociaaldemografische, individuele en daadgebonden karakteristieken van niet-suïcidale ouders die hun kind doodden, en van suïcidale ouders die hun kind(eren) niet doodden. Deze verschillen zijn zodanig, dat kinderdoding gevolgd door (een ernstige poging tot) zelfdoding als aparte groep kan worden beschouwd

Violent encounters

Security and Global Affair

Punishment for Homicide in Europe: Research Challenges and a Roadmap for Progress

This study examines punishments for homicide in Europe by compiling national-level data and presenting a descriptive account of variation. We present original data collected from various European data sources and individual researchers and highlight the problems associated with cross-national data on homicide and the limitations this poses for research. Based on available data, we offer some preliminary observations regarding regional trends in homicide and incarceration rates for homicide. Finally, we provide some suggestions for how these problems might be overcome moving forward.Criminal Justice: Legitimacy, accountability, and effectivit

Human pharmacology of current and new treatments for schizophrenia

The studies in this thesis together show different ways of studying human pharmacology, give an impression of the current drug development in schizophrenia, and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers. The investigated compounds show that the main pharmacological focus in this area has shifted from psychosis to improvement of individual negative or cognitive symptom complexes, from direct receptor inhibition to indirect receptor modulation, and from single drug strategies to combination therapies, each targeted at different symptoms. We have tried to create a pharmacological fingerprint of the investigated compounds by making use of an intensive CNS test battery to measure effects in different functional domains of the brain and additional 'tools' (i.e. positive controls, dose escalation, PK-PD modeling and pharmacological challenge tests) to improve the reliability of the tests. This diversity of drug development strategies and range of neurotransmitters in schizophrenia reflects the increasing complexity of neuropharmacological hypotheses in this field. Despite these difficulties, incremental changes in drug characteristics and treatment strategies may well lead to the introduction of new classes or combinations of drugs in the future.The publication of this thesis was financially supported by the foundation Centre for Human Drug Research (CHDR), Leiden, the NetherlandsUBL - phd migration 201

Asuhan kebidanan berkelanjutan pada Ny.E.N di Puskesmas Lilana tanggal 30 APRIL S/D 30 JUNI 2019

Latar Belakang: Asuhan kebidanan berkelanjutan merupakan asuhan yang menyeluruh diberikan sejak kehamilan, persalinan, nifas dan bayi baru lahir. Data puskesmas Lilana tidak ada kematian bayi dan tidak ada kematian ibu dalam 1 tahun terakhir. Ibu hamil yang melakukan pemeriksaan 4 bulan terakhir adalah 135 orang dengan anemia ringan sebanyak 10 orang, sedang sebanyak 6. Jumlah persalinan sebesar 66 orang. Jumlah kunjungan nifas sebanyak 66 orang, serta jumlah Bayi Baru Lahir sebanyak 66 orang dimana 1 orang bayi yang mengalami kejadian BBLR dan salah satu bayi merupakan bayi dari ibu yang menderita anemia. Tujuan : Mampu memberikan asuhan kebidanan berkelanjutan pada Ny.E.N di Puskesmas Lilana. Metode Laporan : Laporan Tugas Akhir ini dilakukan menggunakan metode studi penelahaan kasus (case study). Lokasi di Puskesmas Lilana, subyek Ny. Lilana. menggunakan format asuhan kebidanan pada ibu hamil sampai nifas dengan menggunakan metode tujuh langkah Varney, teknik pengumpulan data menggunakan data primer dan data sekunder. Hasil penelitian : Berdasarkan asuhan yang telah diberikan, diperoleh keadaan ibu dan bayi baik, bayi masih aktif menyusu, Hb Postpartum 12 gr%,menyarankan ibu untuk mengunnakan KB Imlanp. Kesimpulan : asuhan kebidanan berkelanjutan yang diberikan kepada Ny. E.N sebagian besar telah dilakukan dengan baik dan sistematis, serta ibu dan bayi sehat hingga masa nifas