166 research outputs found
Histone dynamics in DNA damage and repair
The overall perspective of my PhD project was to uncover the mechanisms that generate DNA damage-dependent chromatin mobility and to identify the players implicated in this process. To tackle this problem, I investigated the physical characteristics and composition of chromatin under DNA damaging conditions. I see my PhD project divided into two mayor themes: (I) Identifying physical chromatin changes under DNA damaging conditions (mainly using microscopic assays) (II) Addressing changes in chromatin protein composition upon DNA damage and DNA damage checkpoint activation (using Western blot analysis, genome-wide nucleosome mapping, microscopy and quantitative mass spectrometry
Ultrafast Photo-Induced Charge Transfer Unveiled by Two-Dimensional Electronic Spectroscopy
The interaction of exciton and charge transfer (CT) states plays a central
role in photo-induced CT processes in chemistry, biology and physics. In this
work, we use a combination of two-dimensional electronic spectroscopy (2D-ES),
pump-probe measurements and quantum chemistry to investigate the ultrafast CT
dynamics in a lutetium bisphthalocyanine dimer in different oxidation states.
It is found that in the anionic form, the combination of strong CT-exciton
interaction and electronic asymmetry induced by a counter-ion enables CT
between the two macrocycles of the complex on a 30 fs timescale. Following
optical excitation, a chain of electron and hole transfer steps gives rise to
characteristic cross-peak dynamics in the electronic 2D spectra, and we monitor
how the excited state charge density ultimately localizes on the macrocycle
closest to the counter-ion within 100 fs. A comparison with the dynamics in the
radical species further elucidates how CT states modulate the electronic
structure and tune fs-reaction dynamics. Our experiments demonstrate the unique
capability of 2D-ES in combination with other methods to decipher ultrafast CT
dynamics.Comment: 14 pages, 11 figures, and Supporting informatio
The Lantern Vol. 27, No. 3, Fall 1960
• Thoughts in DaVinici\u27s Coffeehouse • Kinesiology Class • No One is Named Alistair • The Beat Generation • The Super Highway Blues • Panic and the Mountain Peak • The Lake • Later • Ares • The Light • The Room • Thoughts After Three-Thirty • Critique • There • Organized Religion - Pro • Organized Religion - Con • Longing • Apologies to Francois Villon • The Fortune Teller • At Twilight • The Ledge • Waiting at Evening for the Sky to Fall • In Memory of a Friend • The Gentleman • Consumption • Post-Panegyric • The Everglades • Awareness • The Art of Two-Timing • Meditations of an Egyptologist • Sonnet to Mao Tse-Tung • A Strange Affair • With Us Tonight • The Form in Fronthttps://digitalcommons.ursinus.edu/lantern/1078/thumbnail.jp
The spectrum of BPS branes on a noncompact Calabi-Yau
We begin the study of the spectrum of BPS branes and its variation on lines
of marginal stability on O_P^2(-3), a Calabi-Yau ALE space asymptotic to
C^3/Z_3. We show how to get the complete spectrum near the large volume limit
and near the orbifold point, and find a striking similarity between the
descriptions of holomorphic bundles and BPS branes in these two limits. We use
these results to develop a general picture of the spectrum. We also suggest a
generalization of some of the ideas to the quintic Calabi-Yau.Comment: harvmac, 45 pp. (v2: added references
Effectiveness of physiotherapy exercise following hip arthroplasty for osteoarthritis: a systematic review of clinical trials
Background: Physiotherapy has long been a routine component of patient rehabilitation following hip joint replacement. The purpose of this systematic review was to evaluate the effectiveness of physiotherapy exercise after discharge from hospital on function, walking, range of motion, quality of life and muscle strength, for osteoarthritic patients following elective primary total hip arthroplasty.
Methods: Design: Systematic review, using the Cochrane Collaboration Handbook for Systematic Reviews of Interventions and the Quorom Statement. Database searches: AMED, CINAHL, EMBASE, KingsFund, MEDLINE, Cochrane library (Cochrane reviews, Cochrane Central Register of Controlled Trials, DARE), PEDro, The Department of Health National
Research Register. Handsearches: Physiotherapy, Physical Therapy, Journal of Bone and Joint Surgery (Britain)
Conference Proceedings. No language restrictions were applied.
Selection: Trials comparing physiotherapy exercise versus usual/standard care, or comparing two types of relevant exercise physiotherapy, following discharge from hospital after elective primary total hip replacement for osteoarthritis were reviewed.
Outcomes: Functional activities of daily living, walking, quality of life, muscle strength and range of hip joint
motion. Trial quality was extensively evaluated. Narrative synthesis plus meta-analytic summaries were performed to summarise the data.
Results: 8 trials were identified. Trial quality was mixed. Generally poor trial quality, quantity and diversity prevented explanatory meta-analyses. The results were synthesised and meta-analytic summaries were used where possible to provide a formal summary of results. Results indicate that physiotherapy exercise after discharge following total hip replacement has the potential to benefit patients.
Conclusion: Insufficient evidence exists to establish the effectiveness of physiotherapy exercise following primary hip replacement for osteoarthritis. Further well designed trials are required to determine the value of post discharge exercise following this increasingly common surgical procedure
Gravel-bed river floodplains are the ecological nexus of glaciated mountain landscapes
Sherpa Romeo green journal: open accessGravel-bed river floodplains in mountain landscapes disproportionately concentrate diverse habitats, nutrient
cycling, productivity of biota, and species interactions. Although stream ecologists know that river channel and
floodplain habitats used by aquatic organisms are maintained by hydrologic regimes that mobilize gravel-bed
sediments, terrestrial ecologists have largely been unaware of the importance of floodplain structures and processes
to the life requirements of a wide variety of species. We provide insight into gravel-bed rivers as the
ecological nexus of glaciated mountain landscapes. We show why gravel-bed river floodplains are the primary
arena where interactions take place among aquatic, avian, and terrestrial species from microbes to grizzly bears
and provide essential connectivity as corridors for movement for both aquatic and terrestrial species. Paradoxically,
gravel-bed river floodplains are also disproportionately unprotected where human developments are
concentrated. Structural modifications to floodplains such as roads, railways, and housing and hydrologicaltering
hydroelectric or water storage dams have severe impacts to floodplain habitat diversity and
productivity, restrict local and regional connectivity, and reduce the resilience of both aquatic and terrestrial
species, including adaptation to climate change. To be effective, conservation efforts in glaciated mountain
landscapes intended to benefit the widest variety of organisms need a paradigm shift that has gravel-bed rivers
and their floodplains as the central focus and that prioritizes the maintenance or restoration of the intact structure
and processes of these critically important systems throughout their length and breadth.Ye
The next detectors for gravitational wave astronomy
This paper focuses on the next detectors for gravitational wave astronomy
which will be required after the current ground based detectors have completed
their initial observations, and probably achieved the first direct detection of
gravitational waves. The next detectors will need to have greater sensitivity,
while also enabling the world array of detectors to have improved angular
resolution to allow localisation of signal sources. Sect. 1 of this paper
begins by reviewing proposals for the next ground based detectors, and presents
an analysis of the sensitivity of an 8 km armlength detector, which is proposed
as a safe and cost-effective means to attain a 4-fold improvement in
sensitivity. The scientific benefits of creating a pair of such detectors in
China and Australia is emphasised. Sect. 2 of this paper discusses the high
performance suspension systems for test masses that will be an essential
component for future detectors, while sect. 3 discusses solutions to the
problem of Newtonian noise which arise from fluctuations in gravity gradient
forces acting on test masses. Such gravitational perturbations cannot be
shielded, and set limits to low frequency sensitivity unless measured and
suppressed. Sects. 4 and 5 address critical operational technologies that will
be ongoing issues in future detectors. Sect. 4 addresses the design of thermal
compensation systems needed in all high optical power interferometers operating
at room temperature. Parametric instability control is addressed in sect. 5.
Only recently proven to occur in Advanced LIGO, parametric instability
phenomenon brings both risks and opportunities for future detectors. The path
to future enhancements of detectors will come from quantum measurement
technologies. Sect. 6 focuses on the use of optomechanical devices for
obtaining enhanced sensitivity, while sect. 7 reviews a range of quantum
measurement options
Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates
Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy.
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files.
This article is open access.The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1.Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1.Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product.Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability.The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine.info:eu-repo/grantAgreement/EC/FP7/20187
Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts
Background
Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear.
Methodology/Principal Findings
In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration.
Conclusion
We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.National Institutes of Health (U.S.) (grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense (CDMRP Program in TBI, W81XWH-09-1-0514)United States. Air Force Office of Scientific Research (FA9950-04-1-0079
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