gebhart/patrepeval huggingface dataset:
Allele-Specific Holliday Junction Formation: A New Mechanism of Allelic Discrimination for SNP Scoring (2003)

We report here a new mechanism for allelic discrimination--allele-specific Holliday Junction formation. The Holliday Junction (HJ) is a unique DNA structure that can be formed in a sequence-nonspecific manner by routine PCR. To cause the PCR-based HJ formation to occur in an allele-specific manner, the PCR primers are manipulated such that an extra mismatch next to a SNP of interest is introduced between a target and a reference amplicon and a GC-clamp is added. Based on this new mechanism, novel SNP genotyping methods were developed, including a homogeneous fluorescence polarization (FP) competition assay that requires neither labeled primers/probes nor expensive enzymes/substrates. Using this novel genotyping technology, we were able to convert >95% of SNP sequences into genotyping assays that work well under a universal set of assay conditions and achieved 100% accuracy in clinical samples.
An Apparent Umpolung Reactivity of Indole through [Au]‐Catalysed Cyclisation and Lewis‐Acid‐Mediated Allylation (2020)

The sequential functionalization of indole C2 and C3 in an umpolung fashion was executed with a predesigned substrate and choice of reagents. The developed method comprises gold-catalysed alkynol cycloisomerisation/intramolecular addition of C2 of indole and subsequent BF<sub>3</sub> ⋅OEt<sub>2</sub> -mediated regioselective C3 allylation, resulting in the synthesis of the functionalized indoloisoquinolinone scaffold. The reaction involves 5-endo-alkynol cycloisomerisation and the dearomative addition of indole C2 to the intermediate oxocarbenium cation, which results in two equilibrating fused and spiropentacyclic intermediates, which upon treatment with allyl silane in the presence of BF<sub>3</sub> ⋅OEt<sub>2</sub> , undergo selective indole C3 allylation. Other nucleophiles, such as hydride, azide and indole, were also found to be compatible with this process.
Hybrid modal damping identification for bladed disks and blisks (2012)

Current damping identification methodologies typically require measurements of complex eigenvalues, complex eigenvectors, and the applied force. Also, these methods can be sensitive to measurement noise. Most importantly, only a few current methods can be used for regions of high modal density. Thus, the work herein utilizes the frequency response of a system to identify modal damping in regions of (low and) high modal density. This method does not require knowledge of the absolute forcing, rather only the relative forcing is needed. Results are presented for a mistuned blisk, and the proposed method is compared with an alternative damping identification technique.
Adverse Health Effects of Thirdhand Smoke: From Cell to Animal Models (2017)

The newly identified smoke hazard, thirdhand smoke (THS), has gained public attention in recent years but its health impact and biological effects are largely unknown. THS may be defined by "the four Rs": tobacco chemicals that remain, react, re-emit, and/or are resuspended long after active smoking has ceased. This review summarizes recent research progress in the effects of THS on genotoxicity, metabolism and early life development using cellular and animal models. We first reported that THS generated in laboratory systems caused significant DNA damage in human cell lines. Our finding that THS significantly induces oxidative base lesions has been confirmed in skin wounds of mice models exposed to THS. THS also induced metabolomic changes in human reproductive cell lines. Furthermore, we demonstrated that early exposure to THS not only negatively impacts body weight in both male and female mice, but also induces persistent changes to immunological parameters in peripheral blood in these mice. These results indicate that THS is genotoxic at realistic experimental doses and that there may be a window of susceptibility for some forms of cellular damage induced by THS.
Antioxidant Activity of Fish Protein Hydrolysates in in vitro Assays and in Oil-in-Water Emulsions. (2011)

The aim of this study was to screen different protein hydrolysates with respect to their antioxidative properties in order to select the most promising extracts for further evaluation in oil-in-water emulsions. Three fractions of protein hydrolysates (Crude, >5kDa and 5kDa, 3-5kDa and
Localization of radiolabeled enzyme inhibitors in the adrenal gland. (1976)

Tissue distribution studies were performed in rats and dogs at five time intervals between 10 min and 24 hr after the intravenous injection of one of the following radiolabeled adrenocortical enzyme inhibitors: 3H-amino-glutethimide, 125I-3-iodoaminoglutethimide, 3H-SKF-12185, 125I-3-SKF-12185, 3H-metyrapone. 3H-metyrapol. 3H-amphenone B, and 3H-SU-10603. In rats, 3H-SKF-12185 showed the highest uptake in the whole adrenal (3.5% kg dose/gm at 1 hr). In dogs, 3H-metyrapol showed the highest uptake in the adrenal cortex (9% kg dose/gm at 1 hr), and the peak cortex-to-liver concentration ratio was 57 at 2 hr. These peaks uptakes were comparable to those obtained with the conventional iodocholesterols, but they were reached much earlier, with elimination of most of the adrenal radioactivity by 24 hr. These properties would permit the use of 123I as the label and a higher tracer dose, resulting in a higher photon flux. Thus, the radiolabeled enzyme inhibitors show promise as adrenal-scanning agents, with a markedly shortened scanning procedure, a lower absorbed radiation dose, and better resolution.
Induced Pluripotent Stem Cell-Derived Natural Killer Cells for Treatment of Ovarian Cancer (2015)

Natural killer (NK) cells can provide effective immunotherapy for ovarian cancer. Here, we evaluated the ability of NK cells isolated from peripheral blood (PB) and NK cells derived from induced pluripotent stem cell (iPSC) to mediate killing of ovarian cancer cells in a mouse xenograft model. A mouse xenograft model was used to evaluate the intraperitoneal delivery of three different NK cell populations: iPSC-derived NK cells, PB-NK cells that had been activated and expanded in long-term culture, and overnight activated PB-NK cells that were isolated through CD3/CD19 depletion of PB B and T cells. Bioluminescent imaging was used to monitor tumor burden of luciferase expressing tumor lines. Tumors were allowed to establish prior to administering NK cells via intraperitoneal injection. These studies demonstrate a single dose of any of the three NK cell populations significantly reduced tumor burden. When mice were given three doses of either iPSC-NK cells or expanded PB-NK cells, the median survival improved from 73 days in mice untreated to 98 and 97 days for treated mice, respectively. From these studies, we conclude iPSC-derived NK cells mediate antiovarian cancer killing at least as well as PB-NK cells, making these cells a viable resource for immunotherapy for ovarian cancer. Due to their ability to be easily differentiated into NK cells and their long-term expansion potential, iPSCs can be used to produce large numbers of well-defined NK cells that can be banked and used to treat a large number of patients including treatment with multiple doses if necessary.
Gonadotrophin‐releasing hormone receptor autoantibodies induce polycystic ovary syndrome‐like features in a rat model (2021)

Gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). In the present study, we examined the impact of GnRHR-AAb on reproductive function in GnRHR-immunized female rats. All immunized rats produced high titres of GnRHR-AAb targeting a dominant epitope located in the central region of the second extracellular loop of the GnRHR. Increased pulsatile luteinizing hormone secretion and testosterone concentrations were found in immunized rats. These rats exhibited disrupted oestrous cycles, increased ovarian follicular atresia, and activation of insulin signalling in the pituitary and ovary, as indicated by increased mRNA expressions of insulin receptor substrate, phosphatidylinositol 3-kinase and glucose transporter 1. No significant changes in inflammatory cytokines were detected in the ovarian tissue. These features mimic those observed in humans with PCOS. Our findings support the concept that chronic stimulation of the GnRHR by GnRHR-AAb, with an associated increase in pituitary luteinizing hormone secretion and ovarian androgen overproduction, might represent a new aetiological mechanism for PCOS.
Determination of Optimum Time for the Application of Surface Treatments to Asphalt Concrete Pavements - Phase II (2008)

Significant resources can be saved if reactive type of maintenance activities are replaced by proactive activities that could&#13;\nsignificantly extend the pavements service lives. Due to the complexity and the multitude of factors affecting the pavement&#13;\ndeterioration process, the current guidelines for applying various maintenance treatments are based on empirical observations&#13;\nof the pavement surface condition with time.&#13;\nThis report presents the results of a comprehensive research effort to identify the optimum timing of surface treatment&#13;\napplications by providing a better understanding of the fundamental mechanisms that control the deterioration process of&#13;\nasphalt pavements.&#13;\nBoth traditional and nontraditional pavement material characterization methods were carried out. The nontraditional methods&#13;\nconsisted of X-Ray Photoelectron Spectroscopy (XPS) for quantifying aging, while for microcracks detection, electron&#13;\nmicroprobe imaging test (SEM) and fluorescent dyes for inspection of cracking were investigated. A new promising area, the&#13;\nspectral analysis of asphalt pavements to determine aging, was also presented.&#13;\nTraditional methods, such as Bending Beam Rheometer (BBR), Direct Tension (DTT), Dynamic Shear Rheometer (DSR) and&#13;\nFourier Transform Infrared Spectroscopy (FTIR) for asphalt binders and BBR and Semi-Circular Bending (SCB) for mixtures&#13;\nwere used to determine the properties of the field samples studied in this effort.&#13;\nIn addition, a substantial analysis of measured pavement temperature data from MnROAD and simulations of pavement&#13;\ntemperature using a one-dimensional finite difference heat transfer model were performed.
The Social Impact of STEM, Experienced: Studies With an Engineering Design Concept for Smart Devices (2017)

The government has been allocating multi-billion Dollar budgets to STEM (science, technology, engineering and math) education. Several programs aim to educate girls about STEM and STEAM (STEM and arts). It’s a national goal to create equal opportunities for all genders and increase diversity in STEM fields. We propose that the emerging values and social needs of middle school girls must be considered when creating learning experiences for them, and that appropriate design experiences can make engineering problems engaging and relatable. It has been shown that purposefulness is a critical factor for making engineering attractive to girls. Compared to boys, girls initially perceive engineering to be less socially impactful, yet girls place a higher value on social impact at an earlier age. This paper provides a broad review of relevant literature. It is proposed that creative, innovative engineering activities with perceived social impact may motivate middle and high school girls and build their confidence in the ability to impact people’s lives with technology they create. This work tests this hypothesis using different forms of a design activity that enables students to collaboratively build personal and wearable smart devices. Examples of creations based upon this design toolkit include medical bracelets, physical activity monitoring, and other devices. The paper outlines the development of the toolkit and design activity through various stages of abstraction, and provides novel ways of prototyping design experiences. Three stages of development are implemented and tested with adolescent girls, offering new working methods for the human-centered, iterative process of designing such a toolkit. The first stage of toolkit prototypes consists of sketch models with a physical and digital component; focus groups were used to gain in-depth qualitative data. The second stage of toolkit prototypes consists of cardboard prototypes that allow for interaction mimicking the final design experience. It was used to gather data on design interests of different gender and age groups. The third stage of toolkit prototypes, consisting of computing devices with a simple interface, allowed for conducting experimental workshops to quantitatively investigate participants’ self-efficacy and design and engineering interest both before and after the intervention. A fundamental change in many girls’ mindset was observed in multiple experiments. Findings about requirements for design activities with similar goals are summarized and supported though responses of female middle-school students, who participated in the presented studies. Keywords: Biomedicine, Design, Education, Engineering design, Engineering prototypes, Governments, Mathematics, Paperboard, Science, Technology, Engineering and mathematics, STEAM, Students, Workshops (Work spaces)
Ultra-stable laser clock (1983)

The Air Force has a requirement for a high accuracy Helium-Neon Ring Laser Gyro (RLG) and a high accuracy clock. The author has devised a method (patent applied for) whereby a multi-oscillator RLG can be used simultaneously as a gyro and as a clock. The device uses a multi-frequency laser oscillator with an auxiliary detector to sense a 583 MHz beat frequency and necessary electronics to produce a 5 MHz clock signal. The experiment was conducted at the Sudbury, Massachusetts plant of Raytheon Corporation. The square root of the Allan variance was measured for several different sample times. The best data obtained, for the given times, was 4.6 X 10 to the minus 10th power for 1 msec, 3.4 X 10 to the minus 10th power for 10 msec, 8.7 X 10 to the minus 11th power for 0.1 sec, 1.6 X 10 to the minus 10th power for 1 sec, 4.5 X 10 to the minus 10th power for 10 sec, and 4.8 X 10 to the minus 9th power for 100 sec. The data was quantum limited from 1 msec to 200 msec. The long-term degradation was caused by a drift in the Faraday rotator. A method for correcting the Faraday rotator drift is suggested. (Author)
Abstract Data Machine (2015)

In this paper, we present our ongoing work and formalism of a novel data classification method (Abstract Data Machine) for reliable software systems. Most of the approaches for data classification are based on statistical classification, e.g. machine-learning algorithms that comes with false rates. Another critical problem with such algorithms is that they are not reliable and thus do not ensure any provable assurances. One approach to establish reliability of the algorithms is to classify arbitrary data with an appropriate (pragmatically useful) level of abstraction based on the logical data properties that are amenable to assurances, i.e. a formal proof that data represented by a class indeed respects properties of the class. Furthermore, the formal proofs are fundamental for the security assurance of the applications using the algorithms in general and data security in particular.
An ultra-high-throughput method for measuring biomolecular activities (2022)

Abstract Large datasets of biomolecular activities are crucial for protein engineering, yet their scarcity due to limited experimental throughput hampers progress. We introduce Direct High-throughput Activity Recording and Measurement Assay (DHARMA), an innovative method enabling ultra-high-throughput measurement of biomolecular activities. DHARMA employs molecular recording techniques to link activity directly to editing rates of DNA segments contiguous with the coding sequence of biomolecule of interest. Leveraging a Bayesian inference-based denoising model, we mapped the fitness landscape of TEV protease across 160,000 variants. Using these datasets, we benchmarked popular protein models and showed the impact of data size on model performance. We also developed circuit self-optimization strategies and demonstrated DHARMA’s capability to measure a wide range of biomolecular activities. DHARMA represents a leap forward, offering the machine learning community unparalleled datasets for accurate protein fitness prediction and enhancing our understanding of sequence-to-function relationships. Abstract Figure
A Novel Coreflood Test to Evaluate EOR Potential of Wettability-Altering Surfactants in Oil-Wet Heterogeneous Carbonate Reservoirs (2021)

Abstract Oil-wetness and heterogeneity (i.e., existence of low and high permeability regions) are two main factors that result in low oil recovery by waterflood in carbonate reservoirs. The injected water is likely to flow through high permeability regions and bypass the oil in low permeability matrix. In this study, systematic coreflood tests were carried out in both "homogeneous" cores and "heterogeneous" cores. The heterogeneous coreflood test was proposed to model the heterogeneity of carbonate reservoirs, bypassing in low-permeability matrix during waterfloods, and dynamic imbibition of surfactant into the low-permeability matrix. The results of homogeneous coreflood tests showed that both secondary-waterflood and secondary-surfactant flood can achieve high oil recovery (&amp;gt;50%) from relatively homogenous cores. A shut-in phase after the surfactant injection resulted in an additional oil recovery, which suggests enough time should be allowed while using surfactants for wettability alteration. The core with a higher extent of heterogeneity produced lower oil recovery to waterflood in the coreflood tests. Final oil recovery from the matrix depends on matrix permeability as well as the rock heterogeneity. The results of heterogeneous coreflood tests showed that a slow surfactant injection (dynamic imbibition) can significantly improve the oil recovery if the oil-wet reservoir is not well-swept.
Towards (Really) Safe and Fast Confidential I/O (2023)

Confidential cloud computing enables cloud tenants to distrust their service provider. Achieving confidential computing solutions that provide concrete security guarantees requires not only strong mechanisms, but also carefully designed software interfaces. In this paper, we make the observation that confidential I/O interfaces, caught in the tug-of-war between performance and security, fail to address both at a time when confronted to interface vulnerabilities and observability by the untrusted host. We discuss the problem of safe I/O interfaces in confidential computing, its implications and challenges, and devise research paths to achieve confidential I/O interfaces that are both safe and fast.
Advanced Simulation and Computing Fiscal Year 2011-2012 Implementation Plan, Revision 0 (2010)

The Stockpile Stewardship Program (SSP) is a single, highly integrated technical program for maintaining the surety and reliability of the U.S. nuclear stockpile. The SSP uses past nuclear test data along with current and future non-nuclear test data, computational modeling and simulation, and experimental facilities to advance understanding of nuclear weapons. It includes stockpile surveillance, experimental research, development and engineering (D&E) programs, and an appropriately scaled production capability to support stockpile requirements. This integrated national program requires the continued use of current facilities and programs along with new experimental facilities and computational enhancements to support these programs. The Advanced Simulation and Computing Program (ASC) is a cornerstone of the SSP, providing simulation capabilities and computational resources to support the annual stockpile assessment and certification, to study advanced nuclear weapons design and manufacturing processes, to analyze accident scenarios and weapons aging, and to provide the tools to enable stockpile Life Extension Programs (LEPs) and the resolution of Significant Finding Investigations (SFIs). This requires a balanced resource, including technical staff, hardware, simulation software, and computer science solutions. In its first decade, the ASC strategy focused on demonstrating simulation capabilities of unprecedented scale in three spatial dimensions. In its second decade, ASC is focused on increasing its predictive capabilities in a three-dimensional (3D) simulation environment while maintaining support to the SSP. The program continues to improve its unique tools for solving progressively more difficult stockpile problems (focused on sufficient resolution, dimensionality and scientific details); to quantify critical margins and uncertainties (QMU); and to resolve increasingly difficult analyses needed for the SSP. Moreover, ASC has restructured its business model from one that was very successful in delivering an initial capability to one that is integrated and focused on requirements-driven products that address long-standing technical questions related to enhanced predictive capability in the simulation tools. ASC must continue to meet three objectives: Objective 1 - Robust Tools. Develop robust models, codes, and computational techniques to support stockpile needs such as refurbishments, SFIs, LEPs, annual assessments, and evolving future requirements. Objective 2 - Prediction through Simulation. Deliver validated physics and engineering tools to enable simulations of nuclear weapons performance in a variety of operational environments and physical regimes and to enable risk-informed decisions about the performance, safety, and reliability of the stockpile. Objective 3 - Balanced Operational Infrastructure. Implement a balanced computing platform acquisition strategy and operational infrastructure to meet Directed Stockpile Work (DSW) and SSP needs for capacity and high-end simulation capabilities.
High-throughput chromatin accessibility profiling at single-cell resolution (2018)

Here we develop a high-throughput single-cell ATAC-seq (assay for transposition of accessible chromatin) method to measure physical access to DNA in whole cells. Our approach integrates fluorescence imaging and addressable reagent deposition across a massively parallel (5184) nano-well array, yielding a nearly 20-fold improvement in throughput (up to ~1800 cells/chip, 4-5 h on-chip processing time) and library preparation cost (~81¢ per cell) compared to prior microfluidic implementations. We apply this method to measure regulatory variation in peripheral blood mononuclear cells (PBMCs) and show robust, de novo clustering of single cells by hematopoietic cell type.
Molecular Beam Epitaxy of Wurtzite GaN-Based Magnetic Alloy Semiconductors (2001)

The preparation of hexagonal GaN:Mn and GaN:Fe epilayers has been studied by RF-plasma-assisted molecular beam epitaxy. GaN:Fe epilayers exhibit superparamagnetic behavior, presumably due to ferromagnetic inclusions. GaN:Mn epilayers can be expressed in the form of Ga 1- x Mn x N with x up to 0.02, indicating the successful preparation of the GaN-based magnetic alloy semiconductor for the first time. The epilayers are primarily paramagnetic and highly resistive. For epilayers with very high Mn concentration (∼ 10 21 cm -3 ), analysis of the paramagnetic component has revealed the effective spin number S ≈2.5 together with the positive paramagnetic Curie temperature. This suggests the presence of ferromagnetic spin exchange between Mn ions.
Synthesis and Biological Evaluations of New Pyrrolo[2,3-b]pyrimidine as SDI Analogs (2008)

The synthesis of new pyrrolo [2,3-d]pyrimidines variously substituted on the N-1 and C-2 atoms are described.Access to these compounds, which have modest activity compared with the first inhibitor SDI, involves, as the key step, the formation of a pyrrolopyrimidine skeleton from the 5-amino-2-(methoxymethyl)pyrimidine.we decided to synthesize SDI analogs as expected sorbitol dehydrogenase inhibitory activity.