1,031 research outputs found
Epigenetic-based therapies for Friedreich ataxia
No full textThis article has been made available through the Brunel Open Access Publishing Fund.Friedreich ataxia (FRDA) is a lethal autosomal recessive neurodegenerative disorder caused primarily by a homozygous GAA repeat expansion mutation within the first intron of the FXN gene, leading to inhibition of FXN transcription and thus reduced frataxin protein expression. Recent studies have shown that epigenetic marks, comprising chemical modifications of DNA and histones, are associated with FXN gene silencing. Such epigenetic marks can be reversed, making them suitable targets for epigenetic-based therapy. Furthermore, since FRDA is caused by insufficient, but functional, frataxin protein, epigenetic-based transcriptional re-activation of the FXN gene is an attractive therapeutic option. In this review we summarize our current understanding of the epigenetic basis of FXN gene silencing and we discuss current epigenetic-based FRDA therapeutic strategies. © 2014 Sandi, Sandi, Anjomani Virmouni, Al-Mahdawi and Pook
Analisis Terhadap Kesaksian Polisi (Studi Kasus Putusan Mahkamah Agung Nomor 1531 K/pid.Sus/2010 / oleh Willy Sandi Subakti
No full textabstrak (A) Nama: Willy Sandi Subakti (B) NIM : 205090124 (C) Judul Skripsi: Analisis Terhadap Kesaksian Polisi (Studi Kasus Putusan Mahkamah Agung Nomor 1531 K/pid.Sus/2010 (D) Halaman:vi + 109 + 3 Daftar pustaka + lampiran; 2013 (E) Kata Kunci:Keterangan Saksi Polisi, Ganti Rugi Putusan Bebas (F) Isi: Saksi memegang peranan penting dalam upaya pembuktian kesalahan terdakwa di depan sidang pengadilan selain dari keyakinan hakim. Saksi merupakan alat pembuktian yang paling utama dalam hukum pidana. Saksi dalam Pasal 1 angka 2 KUHAP adalah orang yang dapat memberikan keterangan guna kepentingan penyidikan, penuntutan dan peradilan tentang suatu perkara pidana yang mendengar sendiri, melihat sendiri dan mengalami sendiri. Ket San seorang yang didakwa dan diputus oleh Pengadilan Negeri Sambas (Kalimantan Barat) dan Pengadilan Tinggi Pontianak dengan Undang-Undang Psikotropika telah dinyatakan bersalah melakukan tindak pidana secara tanpa hak memiliki dan membawa psikotropika golongan I jenis ekstasi melanggar unsur pasal 59 ayat (1) UU Psikotropika secara tanpa hak memiliki, menyimpan, dan/atau membawa psikotropika golongan I. Tetapi putusan tersebut kemudian dibatalkan oleh putusan Mahkamah Agung, Ket San dinyatakan tidak bersalah dan dibebaskan dari seluruh dakwaan. Mengapa Hakim Mahkamah Agung dalam Putusan Nomor 1531 K/Pid.Sus/2010 tidak dapat menerima dan meragukan kebenaran keterangan saksi Polisi? Dan Upaya yang dapat dilakukan Ket San yang diputus tidak terbukti secara sah dan meyakinkan melakukan tindak pidana psikotropika? Dapat menuntut ganti rugi baik melalui perdata berdasarkan pasal 1365 dan pasal 95 KUHAP. Dalam penulisan ini menggunakan metode penelitian hukum normatif yang didukung dengan hasil wawancara. Kesimpulan dari hasil penelitian adalah pihak kepolisian mempunyai kepentingan terhadap perkara tidak dapat menjadi saksi di pengadilan, karena keterangannya pasti memberatkan, menyudutkan atau merekayasa. Saran bagi pemerintah gugatan ganti kerugian terhadap terdakwa yang diputus bebas dalam proses peradilan pidana tidak memberikan keadilan jika melihat pada ketentuan jumlah ganti kerugian untuk direvisi. (G) Acuan: 27 (1982-2009) (H) Pembimbing: Sugandi Ishak, S.H., M.H. (I) Penulis: Willy Sandi Subakt
Sandi: A System for Accountability and Applications in Direct Communication
No full textWe construct a system, Sandi, to bring trust in online communication through
accountability. Sandi is based on a unique "somewhat monotone" accountability
score, with strong privacy and security properties. A registered sender can
request from Sandi a cryptographic tag encoding its score. The score measures
the sender's trustworthiness based on its previous communications. The tag is
sent to a receiver with whom the sender wants to initiate a conversation and
signals the sender's "endorsement" for the communication channel. Receivers can
use the sender's score to decide how to proceed with the sender. If a receiver
finds the sender's communication inappropriate, it can use the tag to report
the sender to Sandi, thus decreasing the sender's score.
Sandi aims to benefit both senders and receivers. Senders benefit, as
receivers are more likely to react to communication on an endorsed channel.
Receivers benefit, as they can make better choices regarding who they interact
with based on indisputable evidence from prior receivers.
Receivers do not need registered accounts. Neither senders nor receivers are
required to maintain long-term secret keys. Sandi provides a score integrity
guarantee for the senders, a full communication privacy guarantee for the
senders and receivers, a reporter privacy guarantee to protect reporting
receivers, and an unlinkability guarantee to protect senders. The design of
Sandi ensures compatibility with any communication system that allows for small
binary data transfer.
Finally, we provide a game-theoretic analysis for the sender. We prove that
Sandi drives rational senders towards a strategy that reduces the amount of
inappropriate communication
Packing chromatic vertex-critical graphs
No full textThe packing chromatic number of a graph is the smallest
integer such that the vertex set of can be partitioned into sets ,
, where vertices in are pairwise at distance at least .
Packing chromatic vertex-critical graphs, -critical for short, are
introduced as the graphs for which
holds for every vertex of . If , then is
--critical. It is shown that if is -critical,
then the set can be almost
arbitrary. The --critical graphs are characterized, and
--critical graphs are characterized in the case when they
contain a cycle of length at least which is not congruent to modulo
. It is shown that for every integer there exists a
--critical tree and that a --critical
caterpillar exists if and only if . Cartesian products are also
considered and in particular it is proved that if and are
vertex-transitive graphs and , then is -critical
Proposal of Setting Up a Joint ESC / EAEE Working (Task) Group on Updating of the Concept of Seismic Intensity and of the Seismic Intensity Scales
No full textThe proposal presented subsequently was forwarded by the author, in August 2010, on the eve of the 14th European Conference on Earthquake Engineering, to:- Prof. Atilla Ansal, Secretary General, EAEE;- Dr. Mariano García-Fernández, Secretary General, ESC.This proposal was to a high extent a follow up of the project “Quantification of seismic action on structures” (2005-2008), in which research groups of institutes of Romania (coordination), Russian Federation and Republic Moldova were involved. A summary outcome of the project referred to is represented by the volume [Sandi & al., 2010a]. A brief presentation of the volume referred to is given in its foreword, reproduced in Annex II. The correspondence related to the submission of the proposal is reproduced in Annex III. A paper on this subject, [Sandi & al., 2010b], presented at the 14th European Conference on Earthquake Engineering, is also reproduced in this issue of the journal
Valutazione di produttività e misure di efficienza con applicazioni al settore del trasporto pubblico
No full textGeneration and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models
No full textThis article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al
Soma and Neurite Density MRI (SANDI) of the in-vivo mouse brain and comparison with the Allen Brain Atlas
No full textDiffusion MRI (dMRI) provides unique insights into the neural tissue milieu by probing interactions between diffusing molecules and tissue microstructure. Most dMRI techniques focus on white matter (WM) tissues, nevertheless, interest in gray matter characterizations is growing. The Soma and Neurite Density MRI (SANDI) methodology harnesses a model incorporating water diffusion in spherical objects (assumed to be associated with cell bodies) and in impermeable “sticks” (assumed to represent neurites), which potentially enables the characterization of cellular and neurite densities. Recognising the importance of rodents in animal models of development, aging, plasticity, and disease, we here employ SANDI for in-vivo preclinical imaging and provide a first validation of the methodology by comparing SANDI metrics with cellular density reflected by the Allen mouse brain atlas. SANDI was implemented on a 9.4T scanner equipped with a cryogenic coil, and in-vivo experiments were carried out on N = 6 mice. Pixelwise, ROI-based, and atlas comparisons were performed, magnitude vs. real-valued analyses were compared, and shorter acquisitions with reduced the number of b-value shells were investigated. Our findings reveal good reproducibility of the SANDI parameters, including the sphere and stick fractions, as well as sphere size (CoV < 7%, 12% and 3%, respectively). Additionally, we find a very good rank correlation between SANDI-driven sphere fraction and Allen mouse brain atlas contrast that represents cellular density. We conclude that SANDI is a viable preclinical MRI technique that can greatly contribute to research on brain tissue microstructure
Evaluation report for the Healthier Oregon outreach and healthcare system navigation grant program
No full textauthored by the OSU Evaluation Team : Sandi Cleveland Phibbs, PhD, MPH, Haley Delgado, MPH, Daniela Aguilar, MPH, Araceli Mendez, MPH, Oralia Mendez, MPH, Katherine McLaughlin, PhD.This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Includes bibliographical references.Mode of access: Internet from the Oregon Government Publications Collection.Text in English
Rising tides, rising gates: The complex ecogeomorphic response of coastal wetlands to sea-level rise and human interventions
No full textDepartment of Hydraulics and Research Council of National University of Rosario (CIUNR), Rosario 2000, ArgentinaFil: Sandi, Steven. School of Engineering, The University of Newcastle; AustraliaFil: Rodriguez, Jose F. Centre for Water Security and Environmental Sustainability, The University of Newcastle; AustraliaFil: Saintilan, Neil. Department of Environmental Sciences, Macquarie University; AustraliaFil: Riccardi, Gerardo A. Department of Hydraulics and Research Council of National University of Rosario (CIUNR); ArgentinaFil: Saco, Patricia M. Department of Hydraulics and Research Council of National University of Rosario (CIUNR); Argentin
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