gebhart/patrepeval huggingface dataset:
Abstract 4504: Targeting cMYC in metastatic castration resistant and neuroendocrine prostate cancer (2023)

Abstract Prostate cancer is the most common cancer in men and the second leading cause of cancer death among men in the United States according to the National Cancer Institute. Current treatment modalities involve prostatectomy, androgen receptor blockade and supportive/palliative care. Despite these treatment options, metastatic castration resistant prostate cancer and neuroendocrine prostate cancer still have very dismal clinical outcomes. Therefore, there is a need to understand the biology of the aggressive prostate cancer subtypes to identify novel targetable molecules. The castration resistant prostate cancer, neuroendocrine prostate cancer and the metastatic prostate cancers that recur have c-MYC amplification. These cancers are not responsive to androgen blockade or deprivation therapy. Attempts to target c-MYC have been difficult due to the intrinsic disordered nature of c-MYC. Various approaches have been attempted to control c-MYC; namely RNAi which has high off target effects, anti-sense oligonucleotides (ASO) which have low cellular penetrance and needs phosphorothioate modification, G-quadruplex inhibitors which are unspecific as they block POLII, the BRD4 and CDK inhibitors which are indirect inhibitors of c-MYC. Only OmoMyc a bHLH domain mutant with enhanced leucine zipper dimerization is in phase 1 trials with limited bioavailability. To explore the possibility of targeting c-MYC in these difficult-to-treat prostate cancers, we transfected C4-2B, a cellular model of metastatic castration resistant prostate cancer, with engineered destabilized 3‘UTR AU rich element of c-MYC. We found that we degraded c-MYC transcript and protein and killed the cancer cells. Taken together, we offer preliminary evidence that we can directly target c-MYC and inhibit these difficult-to-treat cancers. In vivo studies to validate these findings are ongoing. Citation Format: Chidiebere U. Awah, Olorunseun O. Ogunwobi. Targeting cMYC in metastatic castration resistant and neuroendocrine prostate cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4504.
Quantifying the uncertainty of deep learning-based computer-aided diagnosis for patient safety (2019)

Abstract In this work, we discuss epistemic uncertainty estimation obtained by Bayesian inference in diagnostic classifiers and show that the prediction uncertainty highly correlates with goodness of prediction. We train the ResNet-18 image classifier on a dataset of 84,484 optical coherence tomography scans showing four different retinal conditions. Dropout is added before every building block of ResNet, creating an approximation to a Bayesian classifier. Monte Carlo sampling is applied with dropout at test time for uncertainty estimation. In Monte Carlo experiments, multiple forward passes are performed to get a distribution of the class labels. The variance and the entropy of the distribution is used as metrics for uncertainty. Our results show strong correlation with ρ = 0.99 between prediction uncertainty and prediction error. Mean uncertainty of incorrectly diagnosed cases was significantly higher than mean uncertainty of correctly diagnosed cases. Modeling of the prediction uncertainty in computer-aided diagnosis with deep learning yields more reliable results and is therefore expected to increase patient safety. This will help to transfer such systems into clinical routine and to increase the acceptance of machine learning in diagnosis from the standpoint of physicians and patients.
Cross-Domain Generalization Through Memorization: A Study of Nearest Neighbors in Neural Duplicate Question Detection (2020)

Duplicate question detection (DQD) is important to increase efficiency of community and automatic question answering systems. Unfortunately, gathering supervised data in a domain is time-consuming and expensive, and our ability to leverage annotations across domains is minimal. In this work, we leverage neural representations and study nearest neighbors for cross-domain generalization in DQD. We first encode question pairs of the source and target domain in a rich representation space and then using a k-nearest neighbour retrieval-based method, we aggregate the neighbors' labels and distances to rank pairs. We observe robust performance of this method in different cross-domain scenarios of StackExchange, Spring and Quora datasets, outperforming cross-entropy classification in multiple cases.
The aging rhesus macaque as a potential model for Alzheimer's disease/dementia: An <i>in vivo</i> study of [<sup>11</sup>C]PIB, [<sup>11</sup>C]UCB‐j, [<sup>18</sup>F]MK‐6240 and working memory performance (2020)

Abstract Background Nonhuman primates (NHPs) exhibit age‐related cognitive impairments, synaptic loss, and accumulation of tau and amyloid in dorsolateral prefrontal cortex (dlPFC) and entorhinal cortex (ERC). In a cohort of NHPs with longitudinal cognitive data, we perform SV2A ([ 11 C]UCB‐J), amyloid ([ 11 C]PIB), and tau ([ 18 F]MK‐6240) PET. We aim to 1) investigate in vivo relationships and age‐related change in amyloid, tau, and synaptic density (SV2A) and 2) to relate these to cognition in NHPs. Method Middle‐aged (n = 5, 10.4 ± 0.5 y.o.) and old (n = 17, 19.9 ± 2.7 y.o.) NHPs were dynamically PET scanned (FOCUS 220) following i.v . injection of each of [ 18 F]MK‐6240 (173 ± 12 MBq), [ 11 C]PIB (131 ± 52 MBq), and [ 11 C]UCB‐J (105 ± 34 MBq). Structural MR scans were acquired for registering PET to template space. Outcome measures were SUVR 40‐60 for [ 11 C]PIB, SRTM2‐derived DVR for [ 11 C]UCB‐J, and SUVR 90‐110 for [ 18 F]MK‐6240. Cerebellum was used as reference ([ 11 C]PIB, [ 11 C]UCB‐J), and cerebellar gray matter for [ 18 F]MK‐6240. A subset of the old NHPs (n = 15) were tested with the spatial‐delayed response task to assess working memory performance. Outcome measures: number‐of‐wells, time‐delay, and combined score (number‐of‐wells × time‐delay); higher score indicates better memory performance. Result No regional mean differences were observed in amyloid or SV2A between middle‐aged and old NHPs, though old NHPs exhibited higher variance for all tracers; mean tau was elevated in dlPFC ( p = 0.0031) and hippocampus (HC, p = 0.011) in old NHP compared with middle‐aged (Figure 1). In ERC, a positive relationship was found between tau and amyloid), and in HC, a negative correlation was found between tau and SV2A (Figure 2A). Synaptic density displayed a positive relationship with combined score both in dlPFC ( p = 0.0055, R 2 = 0.46) and HC ( p = 0.029, R 2 = 0.32) (Figure 2B). Tau had a negative relationship with number‐of‐wells in dlPFC ( p = 0.05, R 2 = 0.40), and combined score in HC ( p = 0.015, R 2 = 0.40). Conclusion NHPs exhibit age‐related changes in canonical AD biomarkers as seen by PET. PET markers of SV2A, tau, and amyloid in known early‐pathology regions (dlPFC, HC) correlate appropriately with working memory performance. These studies demonstrate the potential of NHPs as a highly useful model for human AD.
Development of near-bamboo and bamboo microstructures in thin-film strips (1992)

A two-dimensional grain growth model is used to study microstructural evolution in thin film strips. We focus on the strip’s transformation to the bamboo structure, in which individual grains transverse the width of the strip. We find that the approach to a fully bamboo structure is exponential, and that the rate of transformation is inversely proportional to the square of the strip width. When the simulation is extended to model grain boundary pinning due to grooving at grain boundary−free surface intersections, we find that there exists a maximum strip width to thickness ratio beyond which the transformation to the bamboo structure does not proceed to completion.
Increased coinfection of Human Herpesviruses 6A (HHV-6A) and HHV-6B in Multiple Sclerosis patients (P7.014) (2015)

Objective: To investigate the incidence of HHV-6A and HHV-6B coinfection in samples from healthy donors and MS patients. Background: Human herpesvirus 6 (HHV-6) is a ubiquitous virus associated with neurologic diseases, notably MS. The two subgroups of HHV-6 were recently reclassified as distinct viral species due to increasing evidence of their biological differences. Importantly, HHV-6A is considered more neurotropic and neurovirulent compared to HHV-6B. Design/Methods: Elevated levels of HHV-6 DNA have been reported in MS patients versus controls, but the frequency of detection varies widely, likely reflecting differences in detection methodologies. Moreover, few studies investigate coinfection of the two viral species. We employed a novel technology called digital droplet PCR (ddPCR) to precisely quantify HHV-6A and HHV-6B coinfection in a multiplex format using blood and saliva from healthy donors and MS patients. Results: In our assessment of healthy donors, we observed a heretofore-underappreciated high frequency of coinfection in PBMC and serum. We observed higher viral loads in saliva compared to blood of healthy donors, and therefore chose this sample type to compare between healthy donors and MS patients; MS PBMC studies are underway. Interestingly, we detected a significantly elevated frequency of coinfection in MS saliva. Such increased detection of HHV-6A in MS patients is consistent with other studies suggesting that this viral species is more prevalent among MS patients. Conclusions: Our data supports the hypothesis that in a population where HHV-6B is the predominant species of childhood infection, an abundance of detectable HHV-6A may be pathophysiologic. Studies of coinfection may prove clinically relevant by enhancing our understanding of the role(s) of each virus in neurologic diseases such as MS.
Accessing the Two‐Electron Charge Storage Capacity of MnO <sub>2</sub> in Mild Aqueous Electrolytes (2020)

Abstract Rechargeable batteries based on MnO 2 cathodes, able to operate in mild aqueous electrolytes, have attracted attention due to their appealing features for the design of low‐cost stationary energy storage devices. However, the charge/discharge mechanism of MnO 2 in such media is still a matter of debate. Here, an in‐depth quantitative spectroelectrochemical analysis of MnO 2 thin‐films provides a set of unrivaled mechanistic insights. A major finding is that charge storage occurs through the reversible two‐electron faradaic conversion of MnO 2 into Mn 2+ in the presence of a wide range of weak Brønsted acids, including the [Zn(H 2 O) 6 ] 2+ or [Mn(H 2 O) 6 ] 2+ complexes present in aqueous Zn/MnO 2 batteries. Furthermore, it is shown that buffered electrolytes loaded with Mn 2+ are ideal to achieve highly reversible conversion of MnO 2 with both high gravimetric capacity and remarkably stable charging/discharging potentials. In the most favorable case, a record gravimetric capacity of 450 mA·h·g −1 is obtained at a high rate of 1.6 A·g −1 , with a Coulombic efficiency close to 100% and a MnO 2 utilization of 84%. Overall, the present results challenge the common view on MnO 2 the charge storage mechanism in mild aqueous electrolytes and underline the benefit of buffered electrolytes for high‐performance rechargeable aqueous batteries.
Efficient runner networks for investment castings (2000)

We present a computational method that finds an efficient runner network for an investment casting, once the gate locations have been established. The method seeks to minimize a cost function that is based on total network volume. The runner segments are restricted to lie in the space not occupied by the part itself. The collection of algorithms has been coded in C and runner designs have been computed for several real parts, demonstrating substantial reductions in rigging volume. Copyright © 2000 John Wiley & Sons, Ltd.
Imaging of test quartz gratings with a photon scanning tunneling microscope Experiment and theory (1995)

We use the differential formalism of the electromagnetic theory of gratings to interpret the images of test sinusoidal or lamellar quartz gratings obtained with a photon scanning tunneling microscope. The period of the grating is 0.5 μm, and the height of the rule is 0.2 μm. It is shown that the images depend strongly on several parameters, such as polarization or angle of incidence, with respect to the ruling direction. A systematic study of the isointensity lines above the gratings as a function of polarization is presented, and it is shown that the image contrast can be increased or decreased depending on the sample–probe distance. To model the interaction of the fiber probe with the electromagnetic field, we consider a second grating facing the grating under study, and by varying the periodicity of the second grating we calculate the intensity of the collected light and compare it with the experimental results.
Efficient Production of Optically Pure <scp>d</scp> -Lactic Acid from Raw Corn Starch by Using a Genetically Modified <scp>l</scp> -Lactate Dehydrogenase Gene-Deficient and α-Amylase-Secreting <i>Lactobacillus plantarum</i> Strain (2008)

In order to achieve direct and efficient fermentation of optically pure D-lactic acid from raw corn starch, we constructed L-lactate dehydrogenase gene (ldhL1)-deficient Lactobacillus plantarum and introduced a plasmid encoding Streptococcus bovis 148 alpha-amylase (AmyA). The resulting strain produced only D-lactic acid from glucose and successfully expressed amyA. With the aid of secreting AmyA, direct D-lactic acid fermentation from raw corn starch was accomplished. After 48 h of fermentation, 73.2 g/liter of lactic acid was produced with a high yield (0.85 g per g of consumed sugar) and an optical purity of 99.6%. Moreover, a strain replacing the ldhL1 gene with an amyA-secreting expression cassette was constructed. Using this strain, direct D-lactic acid fermentation from raw corn starch was accomplished in the absence of selective pressure by antibiotics. This is the first report of direct D-lactic acid fermentation from raw starch.
Challenges in Implementing a Large-Scale PMU System (2006)

Synchronized measurements represent next generation of paradigm-shift technology, enabling improvements in planning and operating electrical grid otherwise not possible. However, implementing a large-scale PMU system presents some unique challenges. Such systems need to transmit and store large amount of data. Deployment of this technology typically involves a large number of entities (utilities in a connected grid, ISOs, regional organizations, regulators). Each owner/operator is responsible for a part of the system. These systems need to support a wide range of applications for their stakeholders, thus need to accommodate diverse requirements of different applications. As many applications are still in the research and development stage and the deployment roadmaps are not fully developed, requirements are not clearly defined. This is one of the main reasons that there is a lack of available products to support large-scale implementation. How to design a system that meets all those diverse requirements under current situation is a major challenge and the key to the deployment success. Ensuring the consistent performance of all PMUs that will be acquired from multiple vendors, and installed, operated and maintained by different entities is another major challenge. This paper discusses key deployment challenges and recommends measures to address them.
Extending haptic augmented reality: Modulating stiffness during two-point squeezing (2012)

This paper is concerned with haptic augmented reality, which allows us to merge virtual haptic stimuli into the real haptic environment. Considering the modulation of real haptic properties as a key functionality, we previously focused on modulating stiffness of a real fixed object constrained at one contact point. In this paper we generalize the approach by enabling a user to grasp, lift, and manipulate an object via two interaction points. Modulated stiffness can be explored by squeezing an object. To this end, two haptic interfaces equipped with force sensors are employed to render the additional virtual forces of the augmentation at the two interaction points. We introduce the required extended algorithms and evaluate the performance in a pilot user study. A longer term goal of our work is the development of a training environment for tumor palpation.
Do microbes have a memory? History-dependent behavior in the adaptation to variable environments (2022)

Microbes are constantly confronted with changes and challenges in their environment. A proper response to these environmental cues is needed for optimal cellular functioning and fitness. Interestingly, past exposure to environmental cues can accelerate or boost the response when this condition returns, even in daughter cells that have not directly encountered the initial cue. Moreover, this behavior is mostly epigenetic and often goes hand in hand with strong heterogeneity in the strength and speed of the response between isogenic cells of the same population, which might function as a bet-hedging strategy. In this review, we discuss examples of history-dependent behavior (HDB) or "memory," with a specific focus on HDB in fluctuating environments. In most examples discussed, the lag time before the response to an environmental change is used as an experimentally measurable proxy for HDB. We highlight different mechanisms already implicated in HDB, and by using HDB in fluctuating carbon conditions as a case study, we showcase how the metabolic state of a cell can be a key determining factor for HDB. Finally, we consider possible evolutionary causes and consequences of such HDB.
Analysis of macerated ticks using Boolean logic gating colorimetric isothermal nucleic acid assays for Lyme Borrelia and Ixodes scapularis ticks (2023)

Lyme disease, one of the most common tickborne diseases, has been rapidly spreading in parallel with the expansion of the range of its tick vector. Better tick surveillance efforts are needed to accurately estimate disease risk and to guide public health and clinical management. We have developed two multiplex loop-mediated isothermal amplification (LAMP) reactions coupled with oligonucleotide strand displacement (OSD) probes to identify the tick host, Ixodes scapularis, and the Lyme disease pathogen, Borrelia burgdorferi, they carry. In each multiplex LAMP-OSD assay the co-presence of two target sequences is computed at the DNA level by linking the two corresponding amplicons and detecting the co-product on colorimetric lateral flow dipsticks. In tests with synthetic DNA, the co-presence of as few as four copies of input DNA could be detected, without producing spurious signals. Most importantly, though, the LAMP-OSD assay is amenable to being carried out directly with macerated tick samples, without any sample preparation. In such field conditions, assays performed robustly and demonstrated 97-100% sensitivity and 100% specificity with both field-collected and lab-raised artificially infected ticks. Such easy-to-use, arthropod and pathogen-specific assays would be well suited to field and near patient use without relying on complex instrumentation or infrastructure.
Dissolution Methods for the Quantification of Metals in Oil Sands Bitumen (2020)

Seven different dissolution methods proposed in the literature to prepare oil samples for metal analysis by inductively coupled plasma optical emission spectrometry (ICP-OES) were evaluated for V, Ni, Fe, and Ca analysis of bitumen. The dissolution methods evaluated were direct dilution, dry ashing, sulfated ashing, ultrasound assisted extraction, extraction induced emulsion breaking, detergentless microemulsification, and acid decomposition in closed vessels. The types of bitumen samples evaluated were raw bitumen, bitumen with emulsified water, and diluted bitumen. Only direct dilution and sulfated ashing could be recommended for the dissolution of all types of bitumen samples to quantify V and Ni content. Of these two methods, only sulfated ashing resulted in samples with good storage stability. Typical values for these elements in raw Athabasca bitumen were 224–226 (±14) μg V/g and 94 (±4) μg Ni/g. No firm recommendation about the most appropriate dissolution methods for analysis of Fe and Ca in bitumen could be made, and the values were typically around 10 μg/g or less for both Fe and Ca. When bitumen was stored as diluted bitumen in a toluene solution, it was found that 40–50% of the V-containing species separated from the bulk solution during a 28 day storage period. Over the same storage period <20% of the Ni-containing species separated from the bulk solution. These observations are relevant to bitumen upgrading, and some implications for metal removal from bitumen were discussed.
Further study on the verification of CD-SEM based monitoring for hyper NA lithography (2008)

In our previous paper*[1], next generation lithography offering improved resolution by use of Hyper-NA and Low-k1, changes in exposure tool focus were seen to influence pattern shape and it was verified that pattern profile variation occurs even when measured CD values are similar. This shows the necessity for process control to include pattern shape information, conventional methods using the CD value alone will be insufficient as process latitudes continue to shrink. In such a situation, to be able to precisely measure the physical dimensions of design features becomes more and more important. In this study, we have investigated improved precision of Process Window (PW) determination by using the MPPC function that allows the pattern profile shape to be quantified. We have also evaluated pattern shape variation by means of Litho-simulation. As a result, it was confirmed that resist loss is the main change in shape that occurs. Therefore, we have focused our attention on resist loss and optimized the MPPC parameters by SEM simulation*[2]. As a consequence, it was possible to precisely detect the resist loss. Using this technique, it was possible to show the possibility for highly precise 3D measurement determination, for use in exposure tool monitoring, by using the MPPC measurement technique.
Dietary Threonine Reduces Plasma Phenylalanine Levels in Patients With Hyperphenylalaninemia (2003)

The data of the present study show that oral THR supplementation has a clear plasma-PHE-reducing effect but they do not allow any conclusion about the mechanisms responsible for the observed effect. Although it seems attractive on the basis of the present data to use THR supplementation in patients with hyperphenylalaninemia, the mechanism of the observed effect should be clarified before introduction of such a treatment in these patients.
Micromachined Amperometric Nitrate Sensor with an Anion Permeable Membrane (2004)

A nitrate-sensing system that consists of a micromachined sensor substrate, anion-permeable membrane, integrated microfluidic channels, and standard fluidic connectors has been designed, fabricated, assembled, and tested. Our microsensor was designed for in-situ monitoring of nitrate concentrations in ground water. A silver electrode was patterned for amperometric nitrate detection. An electrochemically oxidized silver electrode was used as a reference electrode. Microfluidic channels were fabricated as flow paths to the microelectrochemical (MEC) cell for the eluent and ground-water sample. The sensor also incorporates an anion-permeable membrane that is used for selective measurement of nitrate. With standard addition methods, linear calibration curves have been obtained and the detection limit is ~1 Î¼M. To test selectivity, the sensor response to a 100-Î¼M-nitrate solution and a mixture of nitrate and interfering ions (100 Î¼M each of NOââ», POââ»Â², SOââ»Â³, Fâ», and Clâ») were compared. Despite the 400% increase in total ionic concentration, the sensor output only increased 13.9%.