77 research outputs found
Long-term clinical outcomes of prophylaxis with an rFVIIIFc or rFIXFc in adults aged ≥50 years with hemophilia A or B
No full textLetter from [John Victor Carson], Dominguez Estate Company to Local board No. 279, March 1, 1943
No full textLetter certifies that Mr. Hing Quon, a Chinese farmer, has since April 15, 1942, operated land at 2756 Carson Street in North Long Beach, which was formerly occupied by Japanese tenants
Development of a Time–Height Profile Assimilation Technique for Large-Eddy Simulation
No full textMesoscale-to-microscale coupling (MMC) aims to address the limited scope of traditional large-eddy simulations by driving the microscale flow with information concerning large-scale weather patterns provided by mesoscale models. We present a new offline MMC technique for horizontally homogeneous microscale flow conditions, in which internal forcing terms are computed based on mesoscale time–height profiles of mean-flow quantities. The advantage of such an approach is that it can be used to drive a microscale simulation with either mesoscale or observational data, and that it does not rely on specific terms in the mesoscale budget equations, which are typically not part of the default output of a mesoscale solver. The performance of the proposed profile assimilation technique is assessed based on the simulation of a typical diurnal cycle over the Scaled Wind Farm Technology site in west Texas. Results indicate that simple data assimilation techniques lead to unphysically high levels of shear and turbulence caused by the algorithm’s inability to cope with inaccuracies in the mesoscale time–height profiles. Modifying the algorithm to account for vertical coherence in the mesoscale source terms gives the microscale solver a greater ability to correct the provided mesoscale time–height profiles, leading to improved predictions of shear and turbulence statistics. The resulting turbulence statistics are in good agreement with meteorological tower observations and simulation results obtained with state-of-the-art coupling techniques using mesoscale budget components.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Wind Energ
The role of vitamin D in neuroprotection in multiple sclerosis: an update
No full textMultiple sclerosis (MS) is a complex neurological condition that involves both inflammatory demyelinating and neurodegenerative components. MS research and treatments have traditionally focused on immunomodulation, with less investigation of neuroprotection, and this holds true for the role of vitamin D in MS. Researchers have already established that vitamin D plays an anti-inflammatory role in modulating the immune system in MS. More recently, researchers have begun investigating the potential neuroprotective role of vitamin D in MS. The active form of vitamin D, 1,25(OH)2D3, has a range of neuroprotective properties, which may be important in remyelination and/or the prevention of demyelination. The most notable finding relevant to MS is that 1,25(OH)2D3 promotes stem cell proliferation and drives the differentiation of neural stem cells into oligodendrocytes, which carry out remyelination. In addition, 1,25(OH)2D3 counteracts neurodegeneration and oxidative stress by suppressing the activation of reactive astrocytes and M1 microglia. 1,25(OH)2D3 also promotes the expression of various neuroprotective factors, including neurotrophins and antioxidant enzymes. 1,25(OH)2D3 decreases blood–brain barrier permeability, reducing leukocyte recruitment into the central nervous system. These neuroprotective effects, stimulated by 1,25(OH)2D3, all enhance neuronal survival. This review summarizes and connects the current evidence supporting the vitamin D-mediated mechanisms of action for neuroprotection in MS.Peer reviewedvitamin Dmultiple sclerosisneuroprotectionneurodegeneration1,25(OH)2D
Using observational mean-flow data to drive large-eddy simulations of a diurnal cycle at the SWiFT site
No full textReproducing realistic date- and site-specific unsteady wind conditions in large-eddy simulations is becoming increasingly useful in wind energy. How to run a large-eddy simulation to match observed conditions, however, remains an open research question. One approach that has received considerable attention is mesoscale-to-microscale coupling, in which information about the mesoscale weather, most commonly acquired from a mesoscale numerical weather model, is passed on to a microscale model. In this paper, we demonstrate how the recently developed profile-assimilation technique, a form of mesoscale-to-microscale coupling, can be used to drive large-eddy simulations solely based on observed mean-flow profiles at a single location, bypassing the need for auxiliary mesoscale simulations. The new approach is evaluated for a diurnal cycle at the Scaled Wind Farm Technology site. Observed mean-flow profiles from the ground up to a height of 2 km are reconstructed by aggregating measurements from multiple instruments, and gaps in the data are infilled with natural neighbor interpolation. We perform nine simulations using various forcing approaches to deal with data limitations. The results show that it is indeed possible to drive microscale large-eddy simulation with observations using the profile-assimilation technique, notwithstanding large gaps in virtual potential temperature measurements. However, profile assimilation with vertical smoothing of the error between the desired and actual profiles is required. Without that smoothing, the microscale simulations develop unrealistically high turbulence levels under many situations. Finally, we show that simulated mesoscale data can account for missing observations, although care is needed as both data sources are not necessarily compatible.</p
Miscellaneous Applications of Quons
No full textThis paper deals with quon algebras or deformed oscillator algebras, for which the deformation parameter is a root of unity. We motivate why such algebras are interesting for fractional supersymmetric quantum mechanics, angular momentum theory and quantum information. More precisely, quon algebras are used for (i) a realization of a generalized Weyl-Heisenberg algebra from which it is possible to associate a fractional supersymmetric dynamical system, (ii) a polar decomposition of SU2 and (iii) a construction of mutually unbiased bases in Hilbert spaces of prime dimension. We also briefly discuss (symmetric informationally complete) positive operator valued measures in the spirit of (iii).This paper is a contribution to the Proceedings of the 3-rd Microconference “Analytic and Algebraic Methods III”. Some parts of the material reported here were worked out in collaboration with Mohammed Daoud, Olivier Albouy, and Michel Planat. The present paper is a contribution to the 3rd International Microconference “Analytic and Algebraic Methods in Physics” (June 2007, Villa Lanna, Prague); the author is very indebted to Miloslav Znojil for organizing the conference and for useful comments; thanks are due to Uwe G¨unther, Stefan Rauch-Wojciechowski, Artur Sergyeyev, Petr Sulcp, and Pierguilio Tempesta for interesting discussions. This work was also presented at the workshop “Finite Projective Geometries in Quantum Theory” (August 2007, Astronomical Institute, Tatransk´a Lomnica); the author acknowledges the organizer, Metod Saniga, and the other participants for fruitful interactions
Miscellaneous Applications of Quons
Get PDFThis paper deals with quon algebras or deformed oscillator algebras, for which the deformation parameter is a root of unity. We motivate why such algebras are interesting for fractional supersymmetric quantum mechanics, angular momentum theory and quantum information. More precisely, quon algebras are used for (i) a realization of a generalized Weyl-Heisenberg algebra from which it is possible to associate a fractional supersymmetric dynamical system, (ii) a polar decomposition of SU2 and (iii) a construction of mutually unbiased bases in Hilbert spaces of prime dimension. We also briefly discuss (symmetric informationally complete) positive operator valued measures in the spirit of (iii).This paper is a contribution to the Proceedings of the 3-rd Microconference “Analytic and Algebraic Methods III”. Some parts of the material reported here were worked out in collaboration with Mohammed Daoud, Olivier Albouy, and Michel Planat. The present paper is a contribution to the 3rd International Microconference “Analytic and Algebraic Methods in Physics” (June 2007, Villa Lanna, Prague); the author is very indebted to Miloslav Znojil for organizing the conference and for useful comments; thanks are due to Uwe G¨unther, Stefan Rauch-Wojciechowski, Artur Sergyeyev, Petr Sulcp, and Pierguilio Tempesta for interesting discussions. This work was also presented at the workshop “Finite Projective Geometries in Quantum Theory” (August 2007, Astronomical Institute, Tatransk´a Lomnica); the author acknowledges the organizer, Metod Saniga, and the other participants for fruitful interactions
Coupling Mesoscale Budget Components to Large-Eddy Simulations for Wind-Energy Applications
No full textTo simulate the airflow through a wind farm across a wide range of atmospheric conditions, microscale models (e.g., large-eddy simulation, LES, models) have to be coupled with mesoscale models, because microscale models lack the atmospheric physical processes to represent time-varying local forcing. Here we couple mesoscale model outputs to a LES solver by applying mesoscale momentum- and temperature-budget components from the Weather Research and Forecasting model to the governing equations of the Simulator fOr Wind Farm Applications model. We test whether averaging the budget components affects the LES results with regard to quantities of interest to wind energy. Our study focuses on flat terrain during a quiescent diurnal cycle. The simulation results are compared with observations from a 200-m tall meteorological tower and a wind-profiling radar, by analyzing time series, profiles, rotor-averaged quantities, and spectra. While results show that averaging reduces the spatio-temporal variability of the mesoscale momentum-budget components, when coupled with the LES model, the mesoscale bias (in comparison with observations of wind speed and direction, and potential temperature) is not reduced. In contrast, the LES technique can correct for shear and veer. In both cases, however, averaging the budget components shows no significant impact on the mean flow quantities in the microscale and is not necessary when coupling mesocale budget components to the LES model.</p
Phenomenology and artistic praxis:an application to marine communication
No full textThe author's ecologically informed art praxis can be traced back to her experiences while deep-diving off Tasmania's eastern coast. These provided a plethora of aesthetic sensations, but also images of the appalling degradation wrought upon the marine environment by humans. Her art focuses upon this juxtaposition between natural harmony and ecological dysfunction. The artist/author outlines her views on artistic communication generally and, specifically, on the role of art as ecological communication and discusses the significance of presenting her multimedia and sculptural installations in "general" public contexts. She discusses three of her artworks and possible future projects. ©2005 ISAST
A Phase I Study of the Pan-Notch Inhibitor CB-103 for Patients with Advanced Adenoid Cystic Carcinoma and Other Tumors
Get PDFPan-notch inhibitor CB-103; Advanced adenoid cystic carcinomaInhibidor pan-notch CB-103; Carcinoma adenoide quístic avançatInhibidor pan-notch CB-103; Carcinoma adenoide quístico avanzadoPurpose:
CB-103 selectively inhibits the CSL–NICD (Notch intracellular domain) interaction leading to transcriptional downregulation of oncogenic Notch pathway activation. This dose-escalation/expansion study aimed to determine safety, pharmacokinetics, and preliminary antitumor activity.
Experimental Design:
Patients ≥18 years of age with selected advanced solid tumors [namely, adenoid cystic carcinoma (ACC)] and hematologic malignancies were eligible. CB-103 was dosed orally in cycles of 28 days at escalating doses until disease progression. Notch-activating mutations were required in a dose confirmatory cohort. Endpoints included dose-limiting toxicities (DLT), safety, tumor response, pharmacokinetics, and pharmacodynamics. Exploratory analyses focused on correlates of Notch and target gene expression.
Results:
Seventy-nine patients (64, 12 dose-escalation cohorts; 15, confirmatory cohort) enrolled with 54% receiving two or more lines of prior therapy. ACC was the dominant tumor type (40, 51%). Two DLTs were observed [elevated gamma-glutamyl transferase (GGT), visual change]; recommended phase II dose was declared as 500 mg twice daily (5 days on, 2 days off weekly). Grade 3–4 treatment-related adverse events occurred in 15 patients (19%), including elevated liver function tests (LFTs), anemia, and visual changes. Five (6%) discontinued drug for toxicity; with no drug-related deaths. There were no objective responses, but 37 (49%) had stable disease; including 23 of 40 (58%) patients with ACC. In the ACC cohort, median progression-free survival was 2.5 months [95% confidence interval (CI), 1.5–3.7] and median overall survival was 18.4 months (95% CI, 6.3–not reached).
Conclusions:
CB-103 had a manageable safety profile and biological activity but limited clinical antitumor activity as monotherapy in this first-in-human study.
Significance:
CB-103 is a novel oral pan-Notch inhibitor that selectively blocks the CSL–NICD interaction leading to transcriptional downregulation of oncogenic Notch pathway activation. This first-in-human dose-escalation and -confirmation study aimed to determine the safety, pharmacokinetics, and preliminary antitumor efficacy of CB-103. We observed a favorable safety profile with good tolerability and biological activity but limited clinical single-agent antitumor activity. Some disease stabilization was observed among an aggressive NOTCH-mutant ACC type-I subgroup where prognosis is poor and therapies are critically needed. Peripheral downregulation of select Notch target gene levels was observed with escalating doses. Future studies exploring CB-103 should enrich for patients with NOTCH-mutant ACC and investigate rational combinatorial approaches in tumors where there is limited success with investigational or approved drugs
- …
