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Cohen, David

Publications and source records attributed to Cohen, David.

17 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

SAIGE-GPU: accelerating genome- and phenome-wide association studies using GPUs

Genome-wide association studies (GWAS) at biobank scale are computationally intensive, especially for admixed populations requiring robust statistical models. SAIGE is a widely used method for generalized linear mixed-model GWAS but is limited by its CPU-based implementation, making phenome-wide association studies impractical for many research groups. We developed SAIGE-GPU, a GPU-accelerated version of SAIGE that replaces CPU-intensive matrix operations with GPU-optimized kernels. The core innovation is distributing genetic relationship matrix calculations across GPUs and communication layers. Applied to 2068 phenotypes from 635 969 participants in the Million Veteran Program, including diverse and admixed populations, SAIGE-GPU achieved a 5-fold speedup in mixed model fitting on supercomputing infrastructure and cloud platforms. We further optimized the variant association testing step through multi-core and multi-trait parallelization. Deployed on Google Cloud Platform and Azure, the method provided substantial cost and time savings. Source code and binaries are available for download at https://github.com/saigegit/SAIGE/tree/SAIGE-GPU-1.3.3. A code snapshot is archived at Zenodo for reproducibility (DOI: [10.5281/zenodo.17642591]). SAIGE-GPU is available in a containerized format for use across HPC and cloud environments and is implemented in R/C++ and runs on Linux systems.

Rodriguez, Alex [Argonne National Laboratory (ANL)↗
DOE OSTI2024

Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP)

OBJECTIVE To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011–2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and their characteristics resembled those of individuals with T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low-risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low GRS 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble those of people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.

Yang, Peter K. (ORCID:0000000193796981)↗
DOE OSTI2023

Ectomycorrhizal symbiosis prepares its host locally and systemically for abiotic cue signaling

Tree growth and survival are dependent on their ability to perceive signals, integrate them, and trigger timely and fitted molecular and growth responses. While ectomycorrhizal symbiosis is a predominant tree-microbe interaction in forest ecosystems, little is known about how and to what extent it helps trees cope with environmental changes. We hypothesized that the presence of Laccaria bicolor influences abiotic cue perception by Populus trichocarpa and the ensuing signaling cascade. We submitted ectomycorrhizal or non-ectomycorrhizal P. trichocarpa cuttings to short-term cessation of watering or ozone fumigation to focus on signaling networks before the onset of any physiological damage. Poplar gene expression, metabolite levels, and hormone levels were measured in several organs (roots, leaves, mycorrhizas) and integrated into networks. We discriminated the signal responses modified or maintained by ectomycorrhization. Ectomycorrhizas buffered hormonal changes in response to short-term environmental variations systemically prepared the root system for further fungal colonization and alleviated part of the root abscisic acid (ABA) signaling. Furthermore, the presence of ectomycorrhizas in the roots also modified the leaf multi-omics landscape and ozone responses, most likely through rewiring of the molecular drivers of photosynthesis and the calcium signaling pathway. In conclusion, P. trichocarpa-L. bicolor symbiosis results in a systemic remodeling of the host's signaling networks in response to abiotic changes. In addition, ectomycorrhizal, hormonal, metabolic, and transcriptomic blueprints are maintained in response to abiotic cues, suggesting that ectomycorrhizas are less responsive than non-mycorrhizal roots to abiotic challenges.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Identifying intragenic functional modules of genomic variations associated with cancer phenotypes by learning representation of association networks

Background Genome-wide Association Studies (GWAS) aims to uncover the link between genomic variation and phenotype. They have been actively applied in cancer biology to investigate associations between variations and cancer phenotypes, such as susceptibility to certain types of cancer and predisposed responsiveness to specific treatments. Since GWAS primarily focuses on finding associations between individual genomic variations and cancer phenotypes, there are limitations in understanding the mechanisms by which cancer phenotypes are cooperatively affected by more than one genomic variation. Results This paper proposes a network representation learning approach to learn associations among genomic variations using a prostate cancer cohort. The learned associations are encoded into representations that can be used to identify functional modules of genomic variations within genes associated with early- and late-onset prostate cancer. The proposed method was applied to a prostate cancer cohort provided by the Veterans Administration’s Million Veteran Program to identify candidates for functional modules associated with early-onset prostate cancer. The cohort included 33,159 prostate cancer patients, 3181 early-onset patients, and 29,978 late-onset patients. The reproducibility of the proposed approach clearly showed that the proposed approach can improve the model performance in terms of robustness. Conclusions To our knowledge, this is the first attempt to use a network representation learning approach to learn associations among genomic variations within genes. Associations learned in this way can lead to an understanding of the underlying mechanisms of how genomic variations cooperatively affect each cancer phenotype. This method can reveal unknown knowledge in the field of cancer biology and can be utilized to design more advanced cancer-targeted therapies.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2008

Adaptive MGS Phase Retrieval

Adaptive MGS Phase Retrieval software uses the Modified Gerchberg-Saxton (MGS) algorithm, an image-based sensing method that can turn any focal plane science instrument into a wavefront sensor, avoiding the need to use external metrology equipment. Knowledge of the wavefront enables intelligent control of active optical systems.

Basinger, Scott A.↗
NASA NTRS2007

Ring-Resonator/Sol-Gel Interferometric Immunosensor

A proposed biosensing system would be based on a combination of (1) a sensing volume containing antibodies immobilized in a sol-gel matrix and (2) an optical interferometer having a ring resonator configuration. The antibodies would be specific to an antigen species that one seeks to detect. In the ring resonator of the proposed system, light would make multiple passes through the sensing volume, affording greater interaction length and, hence, greater antibody- detection sensitivity.

Bearman, Gregory↗
NASA NTRS2007

R.F Microphotonics for NASA Space Communications Applications

An RF microphotonic receiver has-been developed at Ka-band. The receiver consists of a lithium niobate micro-disk that enables RF-optical coupling to occur. The modulated optical signal (- 200 THz) is detected by the high-speed photonic signal processing electronics. When compared with an electronic approach, the microphotonic receiver technology offers 10 times smaller volume, smaller weight, and smaller power consumption; greater sensitivity; and optical isolation for use in extreme environments. The status of the technology development will be summarized, and the potential application of the receiver to NASA space communications systems will be described.

Pouch, John↗
NASA NTRS2006

Ring-Interferometric Sol-Gel Bio-Sensor

A biosensor embodying the invention includes a sensing volume having an array of pores sized for immobilizing a first biological entity tending to bind to a second biological entity in such a manner as to change an index of refraction of the sensing volume. The biosensor further includes a ring interferometer, one volumetric section of the ring interferometer being the sensing volume, a laser for supplying light to the ring interferometer, and a photodetector for receiving light from the interferometer.

Bearman, Gregory↗
NASA NTRS2005

Actuated Hybrid Mirror Telescope

The figure depicts the planned Actuated Hybrid Mirror Telescope (AHMT), which is intended to demonstrate a new approach to the design and construction of wide-aperture spaceborne telescopes for astronomy and Earth science. This technology is also appropriate for Earth-based telescopes. The new approach can be broadly summarized as using advanced lightweight mirrors that can be manufactured rapidly at relatively low cost. More specifically, it is planned to use precise replicated metallic nanolaminate mirrors to obtain the required high-quality optical finishes. Lightweight, dimensionally stable silicon carbide (SiC) structures will support the nanolaminate mirrors in the required surface figures. To enable diffraction- limited telescope performance, errors in surface figures will be corrected by use of mirror-shape-control actuators that will be energized, as needed, by a wave-front-sensing and control system. The concepts of nanolaminate materials and mirrors made from nanolaminate materials were discussed in several previous NASA Tech Briefs articles. Nanolaminates constitute a relatively new class of materials that can approach theoretical limits of stiffness and strength. Nanolaminate mirrors are synthesized by magnetron sputter deposition of metallic alloys and/or compounds on optically precise master surfaces to obtain optical-quality reflector surfaces backed by thin shell structures. As an integral part of the deposition process, a layer of gold that will constitute the reflective surface layer is deposited first, eliminating the need for a subsequent and separate reflective-coating process. The crystallographic textures of the nanolaminate will be controlled to optimize the performance of the mirror. The entire deposition process for making a nanolaminate mirror takes less than 100 hours, regardless of the mirror diameter. Each nanolaminate mirror will be bonded to its lightweight SiC supporting structure. The lightweight nanolaminate mirrors and SiC supporting structures will be fabricated from reusable master molds. The mirror-shape-control actuators will be low-power, high-capacitance lead magnesium niobate electrostrictive actuators that will be embedded in the SiC structures. The mode of operation of these actuators will be such that once power was applied, they will change in length and once power was removed, they will maintain dimensional stability to nanometer precision. This mode of operation will enable the use of low-power, minimally complex electronic control circuitry. The wave-front-sensing and control system will be designed and built according to a two-stage architecture. The first stage will be implemented by a Shack- Hartmann (SH) sensor subsystem, which will provide a large capture range. The second, higher-performance stage will be implemented by an image-based wave-front-sensing subsystem that will include a phase-retrieval camera (PRC), and will utilize phase retrieval and other techniques to measure wavefront error directly. Phase retrieval is a process in which multiple images of an unresolved object are iterated to estimate the phase of the optical system that acquired the images. The combination of SH and phase-retrieval sensors will afford the virtues of both a dynamic range of 105 and an accuracy of <10 nm.

Hickey, Gregory↗
NASA NTRS2004

Coronagraphic Notch Filter for Raman Spectroscopy

A modified coronagraph has been proposed as a prototype of improved notch filters in Raman spectrometers. Coronagraphic notch filters could offer alternatives to both (1) the large and expensive double or triple monochromators in older Raman spectrometers and (2) holographic notch filters, which are less expensive but are subject to environmental degradation as well as to limitations of geometry and spectral range. Measurement of a Raman spectrum is an exercise in measuring and resolving faint spectral lines close to a bright peak: In Raman spectroscopy, a monochromatic beam of light (the pump beam) excites a sample of material that one seeks to analyze. The pump beam generates a small flux of scattered light at wavelengths slightly greater than that of the pump beam. The shift in wavelength of the scattered light from the pump wavelength is known in the art as the Stokes shift. Typically, the flux of scattered light is of the order of 10 7 that of the pump beam and the Stokes shift lies in the wave-number range of 100 to 3,000 cm 1. A notch filter can be used to suppress the pump-beam spectral peak while passing the nearby faint Raman spectral lines. The basic principles of design and operation of a coronagraph offer an opportunity for engineering the spectral transmittance of the optics in a Raman spectrometer. A classical coronagraph may be understood as two imaging systems placed end to end, such that the first system forms an intermediate real image of a nominally infinitely distant object and the second system forms a final real image of the intermediate real image. If the light incident on the first telescope is collimated, then the intermediate image is a point-spread function (PSF). If an appropriately tailored occulting spot (e.g., a Gaussian-apodized spot with maximum absorption on axis) is placed on the intermediate image plane, then the instrument inhibits transmission of light from an on-axis source. However, the PSFs of off-axis light sources are formed off axis - that is, away from the occulting spot - so that they become refocused onto the final image plane.

Cohen, David↗
NASA NTRS2003

Demonstration of extreme wavefront sensing performance on the TPF high contrast imaging testbed

The Terrestrial Platet Finder high contrast imaging testbed facilitates the investigation into the diversity of engineering challenges presented by the goal of direct exo-planet detection, for instance, HCIT offers a high-density deformable mirror to control the optical wavefront errors, a configurable coronagraph to control the diffracted light, and translatable cameras for measuring the focal and pupil planes before and after the coronagraph. In this paper, we summarize the measurements that are obtained about the occulter focal plane.

Trauger, John T.↗
NASA NTRS1987

Calculation of skin-stiffener interface stresses in stiffened composite panels

A method for computing the skin-stiffener interface stresses in stiffened composite panels is developed. Both geometrically linear and nonlinear analyses are considered. Particular attention is given to the flange termination region where stresses are expected to exhibit unbounded characteristics. The method is based on a finite-element analysis and an elasticity solution. The finite-element analysis is standard, while the elasticity solution is based on an eigenvalue expansion of the stress functions. The eigenvalue expansion is assumed to be valid in the local flange termination region and is coupled with the finite-element analysis using collocation of stresses on the local region boundaries. Accuracy and convergence of the local elasticity solution are assessed using a geometrically linear analysis. Using this analysis procedure, the influence of geometric nonlinearities and stiffener parameters on the skin-stiffener interface stresses is evaluated.

Cohen, David↗
NASA NTRS1987

Calculation of stresses and forces between the skin and stiffener in composite panels

A methodology for computing the stresses at the interface between the skin and stiffener in stiffened composite panels is described. The methodology is based on finite-element analyses and on elasticity solution. The finite-element analyses are standard, while the elasticity solution is based on eigenvalue expansions of the stress function. The eigenvalue expansions are assumed to be valid in the local region where the stiffener flange terminates. The local elasticity solution is coupled to the global finite-element analysis using collocation on the boundary of the local region. Accuracy and convergence of the method are discussed and several examples of its utility are presented.

Hyer, M. W.↗
NASA NTRS1987

Temperature and deflection data from the asymmetric heating of cross-ply composite tubes

Data generated while heating several cross-ply graphite-epoxy tubes on one side, along their lengths, and cooling them on the other side are presented. This heating arrangement produces a circumferential temperature gradient, and the data show that the gradient can be represented by a cosinusoidal temperature distribution. The thermally induced bending deflections caused by the temperature gradient are also presented.

Hyer, Michael W.↗