The prion-like RNA-processing protein HNRPDL forms inherently toxic amyloid-like inclusion bodies in bacteria

BACKGROUND: The formation of protein inclusions is connected to the onset of many human diseases. Human RNA binding proteins containing intrinsically disordered regions with an amino acid composition resembling those of yeast prion domains, like TDP-43 or FUS, are being found to aggregate in different neurodegenerative disorders. The structure of the intracellular inclusions formed by these proteins is still unclear and whether these deposits have an amyloid nature or not is a matter of debate. Recently, the aggregation of TDP-43 has been modelled in bacteria, showing that TDP-43 inclusion bodies (IBs) are amorphous but intrinsically neurotoxic. This observation raises the question of whether it is indeed the lack of an ordered structure in these human prion-like protein aggregates the underlying cause of their toxicity in different pathological states. RESULTS: Here we characterize the IBs formed by the human prion-like RNA-processing protein HNRPDL. HNRPDL is linked to the development of limb-girdle muscular dystrophy 1G and shares domain architecture with TDP-43. We show that HNRPDL IBs display characteristic amyloid hallmarks, since these aggregates bind to amyloid dyes in vitro and inside the cell, they are enriched in intermolecular β-sheet conformation and contain inner amyloid-like fibrillar structure. In addition, despite their ordered structure, HNRPDL IBs are highly neurotoxic. CONCLUSIONS: Our results suggest that at least some of the disorders caused by the aggregation of human prion-like proteins would rely on the formation of classical amyloid assemblies rather than being caused by amorphous aggregates. They also illustrate the power of microbial cell factories to model amyloid aggregation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0284-7) contains supplementary material, which is available to authorized users

Survey and benchmark of fully integrated switching power converters: switched-capacitor versus inductive approach

This paper surveys and discusses the state-of-the-art of integrated switched-capacitor and inductive power converters. After introducing applications that drive the need for integrated switching power converters, implementation issues to be addressed for integrated switched-capacitor and inductive converters are given, as well as design examples. At the end of this paper, a comprehensive set of integrated power converters are compared in terms of the main specifications and performance metrics, thereby allowing a categorization and providing application-oriented design guidelines

A 1W 8-ratio switched-capacitor boost power converter in 140nm CMOS with 94.5% efficiency, 0.5mm thickness and 8.1mm2 PCB area

This paper presents a boost switched-capacitor power converter (SCPC) in 140nm CMOS converting a wide input voltage range (2.6V to 4.2V) to an output voltage of 5V at 1W output power. It achieves the highest applicable number of conversion ratios with the lowest number of floating capacitors to date. With 8 conversion ratios and only 4 small floating capacitors, a high peak efficiency of 94.5%, a very small PCB area of 8.1mm2, and a low thickness of 0.5mm are achieved

GAMBARAN FAKTOR YANG MEMPENGARUHI PEMERIKSAAN DIRI KE PELAYANAN KESEHATAN PADA PENDERITA KANKER PAYUDARA

Kanker payudara merupakan salah satu jenis kanker yang sangat menakutkan bagi perempuan diseluruh dunia, salah satunya di Indonesia. Kanker payudara menduduki urutan pertama penyebab kematian di dunia dan di Indonesia. Pencegahan yang dapat dilakukan yaitu dengan cara menghindari faktor risiko dan SADARI agar dapat terdeteksi lebih awal dan tingkat kesembuhan tinggi 80-90%. Beberapa hal dalam penggunaan pelayanan kesehatan, diantaranya karakteristik predisposisi, karakteristik pendukung dan karakteristik kebutuhan. Tujuan penelitian ini adalah untuk membatu tim pelayanan kesehatan dalam membuat perencanaan dalam melakukan pendidikan kesehatan bagi masyarakat agar dapat mengenali sedini mungkin tanda dan gejala kanker payudara sehingga tidak terjadi keterlambatan diagnosis dan penanganan kanker payudara. Penelitian ini merupakan penelitian observasional deskriptif dengan desain cross sectional. Pengambilan sampel menggunakan teknik consecutive sampling sejumlah 110 responden yang sesuai kriteria dengan instrumen penelitian kuesioner. Variabel penelitian terdiri dari keadaan ekonomi, perilaku SADARI, keluhan awal, keluhan saat melakukan pemeriksaan, periksa ke pelayanan kesehatan, rentang waktu dan stadium kanker. Hasil penelitian didapatkan bahwa 42,7% responden dengan keadaan ekonomi rendah, 86,4% tidak pernah melakukan SADARI, 83,6% keluhan awal adalah benjolan payudara, 44,5% keluhan utama penyebab periksa adalah benjolan payudara baru di temukan, 63,6% stadium kanker pertama kali pada locally advanced, 52,7% rentang waktu periksa adalah kurang dari satu bulan dan 46,4% tempat periksa pertama kali adalah rumah sakit daerah setempat, Hampir setengahnya responden dalam keadaan ekonomi rendah, perilaku SADARI dalam satu tahun terakhir serta gejala awal hampir seluruhnya tidak pernah melakukan SADARI dan terdapat benjolan payudara. Keluhan saat periksa berupa benjolan payudara baru ditemukan, sebagian besar diagnosis awal pada locally advanced, sebagian besar rentang waktu antara keluhan awal hingga pemeriksaan pertama kali kurang dari satu bulan, jenis pelayanan kesehatan yang dikunjungi pertama kali berupa rumah sakit daerah. Diharapkan untuk meningkatkan peran tenaga kesehatan dalam sosialisasi deteksi dini kanker payudara dengan SADARI

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This paper discusses the state-of-the-art of integrated switched-capacitor and inductive power converters. After introducing applications that drive the need for integrated switching power converters, implementation issues to be addressed for integrated switched-capacitor and inductive converters are given, as well as design examples. At the end of the paper, various integrated power converters are compared in terms of the main specifications