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Article ; Online: Biophysics and the Genomic Sciences.

Schwartz, David C

2019 Volume 117, Issue 11, Page(s) 2047–2053

Abstract: It is now rare to find biological, or genetic investigations that do not rely on the tools, data, and thinking drawn from the genomic sciences. Much of this revolution is powered by contemporary sequencing approaches that readily deliver large, genome- ... ...

Abstract	It is now rare to find biological, or genetic investigations that do not rely on the tools, data, and thinking drawn from the genomic sciences. Much of this revolution is powered by contemporary sequencing approaches that readily deliver large, genome-wide data sets that not only provide genetic insights but also uniquely report molecular outcomes from experiments that biophysicists are increasingly using for potentiating structural and mechanistic investigations. In this perspective, I describe a path of how biophysical thinking greatly contributed to this revolution in ways that parallel advancements in computer science through discussion of several key inventions, described as "foundational devices." These discussions also point at the future of how biophysics and the genomic sciences may become more finely integrated for empowering new measurement paradigms for biological investigations.
MeSH term(s)	Biophysics ; Genomics ; Lab-On-A-Chip Devices
Language	English
Publishing date	2019-07-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2019.07.038
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Article ; Online: 'Gel-Stacks' gently confine or reversibly immobilize arrays of single DNA molecules for manipulation and study.

Calle-Casteñeda, Susana / Winden, Eamon / Vasquez-Echeverri, Alejandro / Schickling, Matthew / Browning, Evelyn / Hernandez Ortiz, Juan Pablo / Schwartz, David C

BioTechniques

2024

Abstract: Large DNA molecules (>20 kb) are difficult analytes prone to breakage during serial manipulations and cannot be 'rescued' as full-length amplicons. Accordingly, to present, modify and analyze arrays of large, single DNA molecules, we created an easily ... ...

Abstract	Large DNA molecules (>20 kb) are difficult analytes prone to breakage during serial manipulations and cannot be 'rescued' as full-length amplicons. Accordingly, to present, modify and analyze arrays of large, single DNA molecules, we created an easily realizable approach offering gentle confinement conditions or immobilization via spermidine condensation for controlled delivery of reagents that support live imaging by epifluorescence microscopy termed 'Gel-Stacks.' Molecules are locally confined between two hydrogel surfaces without covalent tethering to support time-lapse imaging and multistep workflows that accommodate large DNA molecules. With a thin polyacrylamide gel layer covalently bound to a glass surface as the base and swappable, reagent-infused, agarose slabs on top, DNA molecules are stably presented for imaging during reagent delivery by passive diffusion.
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	48453-2
ISSN	1940-9818 ; 0736-6205
ISSN (online)	1940-9818
ISSN	0736-6205
DOI	10.2144/btn-2023-0123
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Article: Trench field-effect transistors integrated in a microfluidic channel and design considerations for charge detection.

Park, Dong-Wook / Tsvid, Gene / Hernandez-Ortiz, Juan P / Schwartz, David C / Ma, Zhenqiang

Applied physics letters

2022 Volume 120, Issue 19, Page(s) 192102

Abstract: Field-effect transistors (FETs) combined with a microfluidic system allow for the electrical detection of charged materials moving in a microfluidic channel. Here, we demonstrate trench-shaped silicon FETs with the combination of a microfluidic channel ... ...

Abstract	Field-effect transistors (FETs) combined with a microfluidic system allow for the electrical detection of charged materials moving in a microfluidic channel. Here, we demonstrate trench-shaped silicon FETs with the combination of a microfluidic channel that can be used for simultaneous electrical and optical detection of charged fluorescent beads. The n-channel silicon trench FETs have a maximum transconductance of 1.83 × 10
Language	English
Publishing date	2022-05-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1469436-0
ISSN	1077-3118 ; 0003-6951
ISSN (online)	1077-3118
ISSN	0003-6951
DOI	10.1063/5.0084758
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Article ; Online: A database of restriction maps to expand the utility of bacterial artificial chromosomes.

Winden, Eamon / Vasquez-Echeverri, Alejandro / Calle-Castañeda, Susana / Lian, Yumin / Hernandez Ortiz, Juan Pablo / Schwartz, David C

GigaByte (Hong Kong, China)

2023 Volume 2023, Page(s) gigabyte93

Abstract: While Bacterial Artificial Chromosomes libraries were once a key resource for the genomic community, they have been obviated, for sequencing purposes, by long-read technologies. Such libraries may now serve as a valuable resource for manipulating and ... ...

Abstract	While Bacterial Artificial Chromosomes libraries were once a key resource for the genomic community, they have been obviated, for sequencing purposes, by long-read technologies. Such libraries may now serve as a valuable resource for manipulating and assembling large genomic constructs. To enhance accessibility and comparison, we have developed a BAC restriction map database. Using information from the National Center for Biotechnology Information's cloneDB FTP site, we constructed a database containing the restriction maps for both uniquely placed and insert-sequenced BACs from 11 libraries covering the recognition sequences of the available restriction enzymes. Along with the database, we generated a set of Python functions to reconstruct the database and more easily access the information within. This data is valuable for researchers simply using BACs, as well as those working with larger sections of the genome in terms of synthetic genes, large-scale editing, and mapping.
Language	English
Publishing date	2023-09-20
Publishing country	China
Document type	Journal Article
ISSN	2709-4715
ISSN (online)	2709-4715
DOI	10.46471/gigabyte.93
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Article ; Online: A simple dialysis device for large DNA molecules.

Krerowicz, Samuel Jw / Hernandez-Ortiz, Juan P / Schwartz, David C

BioTechniques

2019 Volume 66, Issue 2, Page(s) 93–95

Abstract: The potential of genomic DNA is realized when new modalities are invented that manipulate large DNAs with minimal breakage or loss of sample. Here, we describe a polydimethylsiloxane-polycarbonate membrane device to remove small molecules from a sample ... ...

Abstract	The potential of genomic DNA is realized when new modalities are invented that manipulate large DNAs with minimal breakage or loss of sample. Here, we describe a polydimethylsiloxane-polycarbonate membrane device to remove small molecules from a sample while retaining large DNAs. Dialysis rates dramatically change as DNA size in kb (M) increases and DNA dimensions become comparable to pore size, and chain characteristics go from rod-like to Gaussian. Consequently, we describe empirical rates of dialysis, R, as a function of M as falling into two regimes: DNAs ≤ 1 kb show R(M) ∼e
MeSH term(s)	DNA/chemistry ; DNA/isolation & purification ; Dimethylpolysiloxanes/chemistry ; Humans ; Membranes, Artificial ; Polycarboxylate Cement/chemistry ; Single Molecule Imaging/methods
Chemical Substances	Dimethylpolysiloxanes ; Membranes, Artificial ; Polycarboxylate Cement ; polycarbonate (25766-59-0) ; baysilon (63148-62-9) ; DNA (9007-49-2)
Language	English
Publishing date	2019-02-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	48453-2
ISSN	1940-9818 ; 0736-6205
ISSN (online)	1940-9818
ISSN	0736-6205
DOI	10.2144/btn-2018-0133
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Article ; Online: In silico evidence for sequence-dependent nucleosome sliding.

Lequieu, Joshua / Schwartz, David C / de Pablo, Juan J

Proceedings of the National Academy of Sciences of the United States of America

2017 Volume 114, Issue 44, Page(s) E9197–E9205

Abstract: Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA ... ...

Abstract	Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. These processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nucleosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces and the corresponding dynamics of nucleosome repositioning. The mechanism of nucleosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.
MeSH term(s)	Chromatin/genetics ; Chromatin Assembly and Disassembly/genetics ; Computer Simulation ; DNA/genetics ; Gene Silencing/physiology ; Genome/genetics ; Histones/genetics ; Models, Molecular ; Nucleosomes/genetics
Chemical Substances	Chromatin ; Histones ; Nucleosomes ; DNA (9007-49-2)
Language	English
Publishing date	2017-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1705685114
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Article ; Online: Microscale Objects via Restructuring of Large, Double-Stranded DNA Molecules.

Krerowicz, Samuel J W / Hernandez-Ortiz, Juan P / Schwartz, David C

ACS applied materials & interfaces

2018 Volume 10, Issue 48, Page(s) 41215–41223

Abstract: As the interest in DNA nanotechnology increases, so does the need for larger and more complex DNA structures. In this work, we describe two methods of using large, double-stranded (ds) DNA to self-assemble sequence-specific, nonrepetitive microscale ... ...

Abstract	As the interest in DNA nanotechnology increases, so does the need for larger and more complex DNA structures. In this work, we describe two methods of using large, double-stranded (ds) DNA to self-assemble sequence-specific, nonrepetitive microscale structures. A model system restructures T7 DNA (40 kb) through sequence-specific biotinylation followed by intramolecular binding to a 40 nm diameter neutravidin bead to create T7 "rosettes". This model system informed the creation of "nodal DNA" where "nodes" with single-stranded DNA flaps are attached to a large dsDNA insert so that a complementary oligonucleotide "strap" bridges the two nodes for restructuring to form a DNA "bolo". To do this in high yield, several methodologies were developed, including a protection/deprotection scheme using RNA/RNase H and dialysis chambers, which remove excess straps while retaining large DNA molecules. To assess these restructuring processes, the DNA was adsorbed onto supported lipid bilayers, allowing for a visual assay of their structure using single-molecule fluorescence microscopy. Good agreement between the expected and observed fluorescence intensity measurements of the individual features of restructured DNA for both the DNA rosettes and bolos gives us a high degree of confidence that both processes give sequence-specific restructuring of large, dsDNA molecules to create microscale objects.
MeSH term(s)	DNA, Single-Stranded/chemistry ; Lipid Bilayers/chemistry ; Models, Molecular ; Nanostructures/chemistry ; Nucleic Acid Conformation
Chemical Substances	DNA, Single-Stranded ; Lipid Bilayers
Language	English
Publishing date	2018-11-19
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.8b18157
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Article: Maligner: a fast ordered restriction map aligner

Mendelowitz, Lee M / Schwartz, David C / Pop, Mihai

Bioinformatics. 2016 Apr. 01, v. 32, no. 7

2016

Abstract: Motivation: The Optical Mapping System discovers structural variants and potentiates sequence assembly of genomes via scaffolding and comparisons that globally validate or correct sequence assemblies. Despite its utility, there are few publicly available ...

Abstract	Motivation: The Optical Mapping System discovers structural variants and potentiates sequence assembly of genomes via scaffolding and comparisons that globally validate or correct sequence assemblies. Despite its utility, there are few publicly available tools for aligning optical mapping datasets. Results: Here we present software, named ‘Maligner’, for the alignment of both single molecule restriction maps (Rmaps) and in silico restriction maps of sequence contigs to a reference. Maligner provides two modes of alignment: an efficient, sensitive dynamic programming implementation that scales to large eukaryotic genomes, and a faster indexed based implementation for finding alignments with unmatched sites in the reference but not the query. We compare our software to other publicly available tools on Rmap datasets and show that Maligner finds more correct alignments in comparable runtime. Lastly, we introduce the M-Score statistic for normalizing alignment scores across restriction maps and demonstrate its utility for selecting high quality alignments. Availability and implementation: The Maligner software is written in C ++ and is available at https://github.com/LeeMendelowitz/maligner under the GNU General Public License. Contact: mpop@umiacs.umd.edu
Keywords	bioinformatics ; computer software ; data collection ; dynamic programming ; genome ; restriction mapping
Language	English
Dates of publication	2016-0401
Size	p. 1016-1022.
Publishing place	Oxford University Press
Document type	Article
ZDB-ID	1468345-3
ISSN	1460-2059 ; 1367-4811 ; 1367-4803
ISSN (online)	1460-2059 ; 1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btv711
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Article: Microscale Objects via Restructuring of Large, Double-Stranded DNA Molecules

Krerowicz, Samuel J. W / Hernandez-Ortiz, Juan P / Schwartz, David C

ACS applied materials & interfaces. 2018 Nov. 07, v. 10, no. 48

2018

Abstract	As the interest in DNA nanotechnology increases, so does the need for larger and more complex DNA structures. In this work, we describe two methods of using large, double-stranded (ds) DNA to self-assemble sequence-specific, nonrepetitive microscale structures. A model system restructures T7 DNA (40 kb) through sequence-specific biotinylation followed by intramolecular binding to a 40 nm diameter neutravidin bead to create T7 “rosettes”. This model system informed the creation of “nodal DNA” where “nodes” with single-stranded DNA flaps are attached to a large dsDNA insert so that a complementary oligonucleotide “strap” bridges the two nodes for restructuring to form a DNA “bolo”. To do this in high yield, several methodologies were developed, including a protection/deprotection scheme using RNA/RNase H and dialysis chambers, which remove excess straps while retaining large DNA molecules. To assess these restructuring processes, the DNA was adsorbed onto supported lipid bilayers, allowing for a visual assay of their structure using single-molecule fluorescence microscopy. Good agreement between the expected and observed fluorescence intensity measurements of the individual features of restructured DNA for both the DNA rosettes and bolos gives us a high degree of confidence that both processes give sequence-specific restructuring of large, dsDNA molecules to create microscale objects.
Keywords	RNA ; biotinylation ; dialysis ; fluorescence ; fluorescence microscopy ; lipid bilayers ; models ; nanotechnology ; oligonucleotides ; ribonucleases ; single-stranded DNA
Language	English
Dates of publication	2018-1107
Size	p. 41215-41223.
Publishing place	American Chemical Society
Document type	Article
ISSN	1944-8252
DOI	10.1021/acsami.8b18157
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Maligner: a fast ordered restriction map aligner.

Mendelowitz, Lee M / Schwartz, David C / Pop, Mihai

Bioinformatics (Oxford, England)

2015 Volume 32, Issue 7, Page(s) 1016–1022

Abstract	Motivation: The Optical Mapping System discovers structural variants and potentiates sequence assembly of genomes via scaffolding and comparisons that globally validate or correct sequence assemblies. Despite its utility, there are few publicly available tools for aligning optical mapping datasets. Results: Here we present software, named 'Maligner', for the alignment of both single molecule restriction maps (Rmaps) and in silico restriction maps of sequence contigs to a reference. Maligner provides two modes of alignment: an efficient, sensitive dynamic programming implementation that scales to large eukaryotic genomes, and a faster indexed based implementation for finding alignments with unmatched sites in the reference but not the query. We compare our software to other publicly available tools on Rmap datasets and show that Maligner finds more correct alignments in comparable runtime. Lastly, we introduce the M-Score statistic for normalizing alignment scores across restriction maps and demonstrate its utility for selecting high quality alignments. Availability and implementation: The Maligner software is written in C ++ and is available at https://github.com/LeeMendelowitz/maligner under the GNU General Public License. Contact: mpop@umiacs.umd.edu.
MeSH term(s)	Algorithms ; Computer Simulation ; Genome ; Restriction Mapping ; Sequence Alignment ; Sequence Analysis, DNA ; Software
Language	English
Publishing date	2015-12-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btv711
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