1,454 research outputs found
Arm-length stabilisation for interferometric gravitational-wave detectors using frequency-doubled auxiliary lasers
Residual motion of the arm cavity mirrors is expected to prove one of the
principal impediments to systematic lock acquisition in advanced
gravitational-wave interferometers. We present a technique which overcomes this
problem by employing auxiliary lasers at twice the fundamental measurement
frequency to pre-stabilise the arm cavities' lengths. Applying this approach,
we reduce the apparent length noise of a 1.3 m long, independently suspended
Fabry-Perot cavity to 30 pm rms and successfully transfer longitudinal control
of the system from the auxiliary laser to the measurement laser
Hadronic Atoms and Effective Interactions
We examine the problem of hadronic atom energy shifts using the technique of
effective interactions and demonstrate equivalence with the conventional
quantum mechanical approach.Comment: 22 page latex file with 2 figure
Journal of African Christian Biography: v. 4, no. 2
A publication of the Dictionary of African Christian Biography with U.S. offices located at the Center for Global Christianity and Mission at Boston University. This issue focuses on: 1. Tributes to Lamin Sanneh by friends, family, colleagues, scholars, a Bible translator, and an editor. 2. Biographies by Lamin Sanneh in the DACB. 3. A selected bibliography by Lamin Sanneh, compiled by B. Restrick. 4. Book Notes, compiled by B. Restric
Journal of African Christian Biography: v. 4, no. 1
A publication of the Dictionary of African Christian Biography with U.S. offices located at the Center for Global Christianity and Mission at Boston University. This issue focuses on: 1. Introducing African Christian Biography. 2. Modern African Church History and the Streetlight Effect. 3. Both African and Christian. 4. Musicians and Composers in African Christianity. 5. Yared. 6. John Knox Bokwe. 7. Recent Print and Digital Resources Related to Christianity in Africa. 8. Guidelines for Article Contributors. 9. Suggested Interview Guidelines and Questions. 10. Guidelines for Book Reviewers
Stimuli-responsive amphiphilic peptides for biomedical applications
The overarching goal of the present thesis entitled “Stimuli-Responsive Amphiphilic Peptides for Biomedical Applications” was the de novo design and synthesis of responsive and functional amphiphilic peptides as molecular building blocks to self-assemble into smart nanoparticles for biomedical applications. These encompass two functional classes: diagnostic nanoparticles and therapeutic nanoparticles.
In the past decades numerous drug- and gene-delivery carriers have been developed to increase therapeutic efficacy, decrease drug doses, and minimize side effects. While drug delivery carriers for small molecule drugs became well established, noncytotoxic gene delivery remains a major challenge. Additionally, emerging beneficial synergistic effects, combining therapeutic drugs and/or genes created a tremendous demand for sophisticated and responsive codelivery systems. Similarly, current diagnostic nanoparticles still lack high sensitivity and specificity. There is, for instance, a great need for highly sensitive and responsive MRI contrast agents for early diagnosis of diseases.
A first project aimed for the production of peptide nanoparticles for theragnostic purposes, i.e. condensing diagnostic and therapeutic requirements down into one nanoparticle design. Therefore, we created composite peptide–gold nanoparticle superstructures. The high optical density and thermoplasmonic properties of the gold nanoparticles within the self-assemblies allow diagnostic imaging triggered release of entrapped payload upon external stimuli, such as near infrared light. The obtained densely packed gold nanoparticle superstructures contain individual gold nanoparticles separated by a peptide bilayer. We proved that these amphiphilic peptides are capable of serving as scaffolds for gold nanoparticles, highlighting the strong driving forces to self-assemble in aqueous solution. These nanoparticles mighty find application in diagnostics, being used for probing cellular uptake pathways, or for real-time drug delivery imaging.
A second project focused on creating a codelivery carrier for antisense oligonucleotides and small molecule drugs. Such systems are crucial for combined treatments to combat multidrug resistance or to exploit synergistic effects of drug–gene or drug–drug combinations. Therefore, we engineered amphiphilic peptides bearing moieties to condense nucleic acid payloads and/or hydrophilic payloads and a hydrophobic region able to entrap small drugs upon self-assembly. The peptides were further equipped with a reduction-sensitive linker for triggered decomposition and cargo release in physiologic conditions at diseases sites. Straightforward rational design combining desired features within one peptide sequence led to noncytotoxic peptide nanoparticles with sizes optimal for biomedical applications (100–150 nm). The created nanoassemblies were able to carry hydrophilic, nucleic acid, and hydrophobic payloads. Further, they revealed high coloading efficiency and were highly sensitive to reductive trigger releasing both payloads in a fast manner. This novel codelivery system is further characterized by effective cell uptake and high therapeutic efficacy delivering the hydrophilic model drug DoxHCl.
A third project addressed the development of amphiphilic peptides bearing polylysine hydrophilic regions to achieve gene transfection in vitro. The created peptides showed good plasmid DNA condensing abilities and formed nanoparticles in appropriate sizes for biomedical applications. Subsequent transfection experiments revealed high efficiencies. The developed purely peptidic nanoparticles show very promising potential towards highly potent gene transfection agents.
A fourth project aimed at the development of a highly sensitive MRI contrast agent. Therefore, we used an amphiphilic block copolymer bearing a hydrophilic block of heparin, known to possess high affinity to trivalent lanthanides such as gadolinium. Gadolinium is widely used as a positive contrast agent to increase contrast in MRI due to its high paramagnetism. The constructed contrast agent revealed relaxivities of more than one order of magnitude higher (44 mM 1s 1) compared to commercially available contrast agents (~4 mM 1s 1). For achieving triggered contrast enhancement, the copolymer was coassembled with a reduction-responsive amphiphilic peptide. Physiologic amounts of reducing agent resulted in a relaxivity increase from 44 to 54 mM-1s-1, which is about 20%. Important properties such as its nontoxicity, lack of anticoagulation activity, and stability over seven months regarding gadolinium release suggest this reduction-responsive highly sensitive MRI contrast agent as very promising candidate for selective contrast enhancement at disease sites.
The present dissertation demonstrates, that rational design of amphiphilic peptides can lead to multifunctional, biocompatible, and biodegradable nanoarchitectures self-assembled in a well-defined manner. Functionality is introduced by point mutations in the peptide sequence. The projects presented here provide an array of tailor-made amphiphilic peptides, tuned to distinct properties required for their intended applications
Ninja data analysis with a detection pipeline based on the Hilbert-Huang Transform
The Ninja data analysis challenge allowed the study of the sensitivity of
data analysis pipelines to binary black hole numerical relativity waveforms in
simulated Gaussian noise at the design level of the LIGO observatory and the
VIRGO observatory. We analyzed NINJA data with a pipeline based on the Hilbert
Huang Transform, utilizing a detection stage and a characterization stage:
detection is performed by triggering on excess instantaneous power,
characterization is performed by displaying the kernel density enhanced (KD)
time-frequency trace of the signal. Using the simulated data based on the two
LIGO detectors, we were able to detect 77 signals out of 126 above SNR 5 in
coincidence, with 43 missed events characterized by signal to noise ratio SNR
less than 10. Characterization of the detected signals revealed the merger part
of the waveform in high time and frequency resolution, free from time-frequency
uncertainty. We estimated the timelag of the signals between the detectors
based on the optimal overlap of the individual KD time-frequency maps, yielding
estimates accurate within a fraction of a millisecond for half of the events. A
coherent addition of the data sets according to the estimated timelag
eventually was used in a characterization of the event.Comment: Accepted for publication in CQG, special issue NRDA proceedings 200
Benefits of Artificially Generated Gravity Gradients for Interferometric Gravitational-Wave Detectors
We present an approach to experimentally evaluate gravity gradient noise, a
potentially limiting noise source in advanced interferometric gravitational
wave (GW) detectors. In addition, the method can be used to provide sub-percent
calibration in phase and amplitude of modern interferometric GW detectors.
Knowledge of calibration to such certainties shall enhance the scientific
output of the instruments in case of an eventual detection of GWs. The method
relies on a rotating symmetrical two-body mass, a Dynamic gravity Field
Generator (DFG). The placement of the DFG in the proximity of one of the
interferometer's suspended test masses generates a change in the local
gravitational field detectable with current interferometric GW detectors.Comment: 16 pages, 4 figure
Long term study of the seismic environment at LIGO
The LIGO experiment aims to detect and study gravitational waves using ground
based laser interferometry. A critical factor to the performance of the
interferometers, and a major consideration in the design of possible future
upgrades, is isolation of the interferometer optics from seismic noise. We
present the results of a detailed program of measurements of the seismic
environment surrounding the LIGO interferometers. We describe the experimental
configuration used to collect the data, which was acquired over a 613 day
period. The measurements focused on the frequency range 0.1-10 Hz, in which the
secondary microseismic peak and noise due to human activity in the vicinity of
the detectors was found to be particularly critical to interferometer
performance. We compare the statistical distribution of the data sets from the
two interferometer sites, construct amplitude spectral densities of seismic
noise amplitude fluctuations with periods of up to 3 months, and analyze the
data for any long term trends in the amplitude of seismic noise in this
critical frequency range.Comment: To be published in Classical and Quantum Gravity. 24 pages, 15
figure
Stimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles
Ever more emerging combined treatments exploiting synergistic effects of drug combinations demand smart, responsive codelivery carriers to reveal their full potential. In this study, a multifunctional stimuli-responsive amphiphilic peptide was designed and synthesized to self-assemble into nanoparticles capable of co-bearing and -releasing hydrophobic drugs and antisense oligonucleotides for combined therapies. The rational design was based on a hydrophobic l-tryptophan-d-leucine repeating unit derived from a truncated sequence of gramicidin A (gT), to entrap hydrophobic cargo, which is combined with a hydrophilic moiety of histidines to provide electrostatic affinity to nucleotides. Stimuli-responsiveness was implemented by linking the hydrophobic and hydrophilic sequence through an artificial amino acid bearing a disulfide functional group (H3SSgT). Stimuli-responsive peptides self-assembled in spherical nanoparticles in sizes (100–200 nm) generally considered as preferable for drug delivery applications. Responsive peptide nanoparticles revealed notable nucleotide condensing abilities while maintaining the ability to load hydrophobic cargo. The disulfide cleavage site introduced in the peptide sequence induced responsiveness to physiological concentrations of reducing agent, serving to release the incorporated molecules. Furthermore, the peptide nanoparticles, singly loaded or coloaded with boron-dipyrromethene (BODIPY) and/or antisense oligonucleotides, were efficiently taken up by cells. Such amphiphilic peptides that led to noncytotoxic, reduction-responsive nanoparticles capable of codelivering hydrophobic and nucleic acid payloads simultaneously provide potential toward combined treatment strategies to exploit synergistic effects
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