gebhart/patrepeval huggingface dataset:
In Search of a Mission (2017)

This chapter explores a 25-year kaleidoscopic history of confused and competing United States (US) approaches that are implemented through our bilateral development assistance, channeled through multilateral institutions and translated through diplomatic and military engagements in geographies deemed strategically important. One clear lesson that the nigh-forgotten incident provides is that it is not possible to separate the policies and programs of US overseas engagements from the centuries-long domestic experiences of managing water within our own borders. The first international water treaty involving the US government was signed with Mexico in 1906 in response to years of contentious border incidents in which users on both sides of the Rio Grande and Colorado River lodged claims against each other. During the George W. Bush administration, the battle for control over international water policy swung between Congress and the Department of State amid the larger budgetary and policy fights.
A small molecule virulence factor suppresses plant immune response (2018)

Natural products play important roles in the chemical interactions between bacteria and their host. Thousands of biosynthetic gene clusters for natural products have been identified through genomic analyses, but most of them are uncharacterized (“cryptic” gene clusters). Our goal is to identify the natural products encoded by these cryptic gene clusters and investigate their functions in bacteria‐host interaction. Using transcriptomics, we identified a cryptic gene cluster that is upregulated in Pseudomonas syringe during plant infection. This gene cluster is widely distributed in plant pathogens that cause worldwide crop damage. To identify the natural product encoded by this gene cluster, we develop an approach that combines heterologous expression and metabolomics with in vitro reconstitution of enzyme activity. We identify a novel natural product, phevamine, which harbors a distinct chemical structure that partly resembles spider and wasp toxins. We discover that phevamine is a virulence factor that suppresses plant immune response. The biosynthesis of phevamine involves ATP‐Grasp type amide ligases. Our work identifies a new virulence factor that pathogens use to invade plant defense. Our work also highlights amide ligases as an important and growing class of biosynthetic enzymes for natural products. Support or Funding Information This work was supported by Rita Allen Foundation (B.L.), National Institutes of Health (R00 GM099904, B.L.), NSF‐IOS‐1343020 INSPIRE Track 2 (J.D.), and DOE‐BER‐0000217779 (J.D.). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Systematic Identification of Cellular Signals Reactivating Kaposi Sarcoma–Associated Herpesvirus (2007)

The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.
Bisphosphonates Inhibit Expression of p63 by Oral Keratinocytes (2011)

Osteonecrosis of the jaw (ONJ), a side-effect of bisphosphonate therapy, is characterized by exposed bone that fails to heal within eight weeks. Healing time of oral epithelial wounds is decreased in the presence of amino-bisphosphonates; however, the mechanism remains unknown. We examined human tissue from individuals with ONJ and non-bisphosphonate-treated control individuals to identify changes in oral epithelium and connective tissue. Oral and intravenous bisphosphonate-treated ONJ sites had reduced numbers of basal epithelial progenitor cells, as demonstrated by a 13.8±1.1% and 31.9±5.8% reduction of p63 expression, respectively. No significant differences in proliferation rates, vessel density, or macrophage number were noted. In vitro treatment of clonal and primary oral keratinocytes with zoledronic acid (ZA) inhibited p63, and expression was rescued by the addition of mevalonate pathway intermediates. In addition, both ZA treatment and p63 shRNA knock-down impaired formation of 3D Ex Vivo Produced Oral Mucosa Equivalents (EVPOME) and closure of an in vitro scratch assay. Analysis of our data suggests that bisphosphonate treatment may delay oral epithelial healing by interfering with p63-positive progenitor cells in the basal layer of the oral epithelium in a mevalonate-pathway-dependent manner. This delay in healing may increase the likelihood of osteonecrosis developing in already-compromised bone.
PIasma-Mediated Leukemia Cell Destruction: Concentration and Purification of the Antileukemia Factor (1977)

Selective destruction of leu-kemic cells has been observed in AKR mice following infusion of normal serum, plasma, or whole blood. Heparinized plasma has significantly greater antileukemia activity than serum, and the active factor can be concentrated and purified by heparin precipitation or adsorption onto a calcium phosphate gel.
A model selection criterion for classification: application to HMM topology optimization (2004)

This paper proposes a model selection criterion for classification problems. The criterion focuses on selecting models that are discriminant instead of models based on the Occam's razor principle of parsimony between accurate modeling and complexity. The criterion, dubbed discriminative information criterion (DIC), is applied to the optimization of hidden Markov model topology aimed at the recognition of cursively-handwritten digits. The results show that DIC-generated models achieve 18% relative improvement in performance from a baseline system generated by the Bayesian information criterion (BIC).
Transcription Factor IID Mutants Defective for Interaction with Transcription Factor IIA (1992)

Transcription factor IID (TFIID) recognizes the TATA element of promoters transcribed by RNA polymerase II (RNAPII) and serves as the base for subsequent association by other general transcription factors and RNAPII. The carboxyl-terminal domain of TFIID is highly conserved and contains an imperfect repetition of a 60-amino acid sequence. These repeats are separated by a region rich in basic amino acids. Mutagenesis of the lysines in this region resulted in a conditioned phenotype in vivo, and the mutant proteins were defective for interactions with transcription factor IIA in vitro. Binding of TFIID to DNA was unaffected. These results suggest that the basic domain of TFIID is important for protein-protein interactions.
Less CO2 and Fine Dust Emissions in Automotive (2020)

Abstract There is increasing pressure on the automotive industry for further reduction of CO 2 and particulate (PM10, PM2.5) emissions. One of the main issues is the fine dust resulting from the wear of the brake disc/brake pads, which is considered to be a major source of non‐exhaust traffic‐related emissions, particularly in urban locations. Carbide coatings are the state‐of‐art solution for controlling rotor wear. The challenge of cost‐effective serial production for automotive applications can be mastered by high power laser cladding.
High-Speed EMT Modeling of MMCs With Arbitrary Multiport Submodule Structures Using Generalized Norton Equivalents (2017)

In order to improve features, such as fault current blocking and capacitor voltage balancing, modular multilevel converter (MMC) topologies incorporating multiport submodules (SMs) are being considered as candidates for HVdc transmission applications. This paper presents high-speed and accurate electromagnetic transient (EMT) models for MMCs composed of such multiport SMs. The approach uses the Schur's complement technique to recursively eliminate internal nodes of the converter structure to create a multiport Norton equivalent that connects to the external network. Thus, the final admittance matrix seen by the EMT solver has a dimension orders of magnitude smaller than that of the unreduced structure. As with previously developed approaches for MMCs with single-port SMs, all internal information, such as individual SM capacitor voltages, is preserved and can be output by the program if needed. This increases the bookkeeping effort, but the overall reduction in matrix size more than compensates for any resulting time penalty. Approximately two to three orders of magnitude speedup over a straightforward implementation in an EMT program is achieved.
Activation of the Prolyl Hydroxylase Oxygen-sensor Results in Induction of GLUT1, Heme Oxygenase-1, and Nitric-oxide Synthase Proteins and Confers Protection from Metabolic Inhibition to Cardiomyocytes (2003)

Recently an oxygen-sensing/transducing mechanism has been identified as a family of O2-dependent prolyl hydroxylase domain-containing enzymes (PHD). In normoxia, PHD hydroxylates a specific proline residue that directs the degradation of constitutively synthesized hypoxia-inducible factor-1alpha. During hypoxia, the cessation of hydroxylation of this proline results in less degradation and thus increases hypoxia-inducible factor-1alpha protein levels. In this study we have examined the consequences of activating the PHD oxygen-sensing pathway in cultured neonatal myocytes using ethyl-3,4 dihydroxybenzoate and dimethyloxalylglycine, inhibitors that, similar to hypoxia, inhibit this family of O2-dependent PHD enzymes. Increased glucose uptake and enhanced glycolytic metabolism are classical cellular responses to hypoxia. Ethyl-3,4 dihydroxybenzoate treatment of cardiomyocyte cultures for 24 h increased [3H]deoxy-4-glucose uptake concurrent with an induction of GLUT1 protein. In addition, ethyl-3,4 dihydroxybenzoate, dimethyloxalylglycine, and hypoxia treatments were found to induce protein levels of nitricoxide synthase-2 and heme oxygenase-1, two important cardioregulatory proteins whose expression in response to hypoxic conditions is poorly understood. In conjunction with these changes in gene expression, activation of the PHD oxygen-sensing mechanism was found to preserve myocyte viability in the face of metabolic inhibition with cyanide and 2-deoxyglucose. These results point to a key role for the PHD pathway in the phenotypic changes that are observed in a hypoxic myocyte and may suggest a strategy to pharmacologically induce protection in heart.
Vedolizumab for the Treatment of Moderately to Severely Active Ulcerative Colitis (2015)

Ulcerative colitis is a chronic, idiopathic, inflammatory bowel disease characterized by a relapsing and remitting course. A substantial proportion of patients fail conventional therapies despite therapy with immunosuppressives and tumor necrosis factor antagonists. Accordingly, newer therapeutic agents that target disease-specific inflammation and minimize adverse events are required. Central to the pathogenesis of ulcerative colitis is an aberrant host response to commensal microorganisms with a resultant dysregulation of gut immune homeostasis and lymphocyte trafficking. Recently, a newer biologic, vedolizumab, which blocks lymphocyte trafficking, has been developed for use in moderate to severe ulcerative colitis. The efficacy of this agent has been demonstrated to be similar to that of other currently available biologics, and the selectivity of this agent in blocking lymphocyte migration to the gut has substantially reduced treatment-related adverse events. The drug has now been approved for use in the United States and Europe, and, although the exact positioning of this biologic in clinical practice is yet to be defined, it represents an important new chapter in our armamentarium of treatment options for this population. In this review, we will highlight key considerations to be made by providers when using this agent in clinical practice.
Durable Control of HIV-1 Using a Staphylococcus aureus Cas9-Expressing Lentivirus Co-Targeting Viral Latency and Host Susceptibility (2020)

ABSTRACT CRISPR/Cas9 gene editing has the potential to revolutionize the clinical management of HIV-1 infection, and may eliminate the need for antiretroviral therapy (ART). Current gene therapies attempt to either excise HIV-1 provirus or target HIV-1 entry receptors to prevent infection of new cells. Using a viral dynamic model, we determined that combining these two interventions, in the presence or absence of ART, significantly lowers the gene editing efficacy thresholds required to achieve an HIV-1 cure. To implement this dual-targeting approach, we engineered a single lentiviral vector that simultaneously targets multiple highly-conserved regions of the provirus and the host CXCR4 coreceptor, and developed a novel coculture system enabling real-time monitoring of latent infection, viral reactivation, and infection of new target cells. Simultaneous dual-targeting depleted HIV-1-infected cells with significantly greater potency than vectors targeting either virus or host independently, highlighting its potential as an HIV-1 cure strategy.
An Ultra-Low Phase Noise Class-F 2 CMOS Oscillator With 191 dBc/Hz FoM and Long-Term Reliability (2015)

In this paper, we propose a new class of operation of an RF oscillator that minimizes its phase noise. The main idea is to enforce a clipped voltage waveform around the LC tank by increasing the second-harmonic of fundamental oscillation voltage through an additional impedance peak, thus giving rise to a class-F 2 operation. As a result, the noise contribution of the tail current transistor on the total phase noise can be significantly decreased without sacrificing the oscillator's voltage and current efficiencies. Furthermore, its special impulse sensitivity function (ISF) reduces the phase sensitivity to thermal circuit noise. The prototype of the class-F 2 oscillator is implemented in standard TSMC 65 nm CMOS occupying 0.2 mm 2 . It draws 32-38 mA from 1.3 V supply. Its tuning range is 19% covering 7.2-8.8 GHz. It exhibits phase noise of -139 dBc/Hz at 3 MHz offset from 8.7 GHz carrier, translated to an average figure-of-merit of 191 dBc/Hz with less than 2 dB variation across the tuning range. The long term reliability is also investigated with estimated >10 year lifetime.
Integrated photonic platform based on semipolar InGaN/GaN multiple section laser diodes (2017)

The challenges to realizing Ill-nitride photonic integrated circuit (PIC) are discussed. Utilizing InGaN-based multi-section laser diode (LD) on semipolar GaN substrate, the seamless on-chip integration of III-nitride waveguide photodetector (WPD) in the visible regime has been demonstrated.
Design and Characterization of Enhanced Angle Sensitive Pixels (2015)

Stacks of metal gratings placed above a photodiode have been demonstrated to show a strong sinusoidal response to angle. Although these devices, called angle sensitive pixels (ASPs), enable new imaging modalities on CMOS, such as light field capture, their optical sensitivity is limited by the metallic gratings. In this paper, we provide a detailed characterization of the angular response of ASPs and report on a new set of optically efficient structures for angle detection. By analyzing the properties of the Talbot effect, we present a quantitative model for the angular sensitivity, β, of an ASP and qualitatively describe the dependence of modulation depth, m, on the grating parameters. We then describe structures that employ phase gratings and interleaved diffusion diodes to provide angle sensitivity while improving the quantum efficiency by 4×. A post-CMOS process flow for the fabrication of phase gratings is described. Finally, we show that ASPs that use p <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> diffusion diodes embedded in an n-well diode improve their modulation efficiency by over 50% compared with interleaved diodes that share the p-substrate.
Towards MEMS-Tunable Phase Matching and Mode Conversion in Nanophotonic Waveguides (2020)

The advent of interconnected devices, sensors, and systems requires increasingly large data transmission rates. Optical communications has met these bandwidth needs due to the large information-carrying capacity of light, although new modulation and multiplexing approaches are required to keep up with increasing demand. To this end, mode-division multiplexing (MDM), in which light propagates in on-chip waveguides with distinct and orthogonal spatial mode shapes, may offer a promising solution. To date, however, most chip-scale MDM devices have relied on (de)multiplexing on-chip of fixed optical modes as opposed to tunable mode conversion. In this Letter we demonstrate a new approach to mode conversion and mode-division multiplexing (MDM) that takes advantage of MEMS-tunable optical phase matching. We show via simulations that the approach enables mode conversion with high purity. Measurements on fabricated devices demonstrate the feasibility of this new MEMS index perturbation and phase matching approach for on-demand and dynamic mode conversion for MDM data/communications links. [2020-0107].
Exploring the Interplay Between Colorectal Cancer Subtypes Genomic Variants and Cellular Morphology: A Deep-Learning Approach (2023)

Molecular subtypes of colorectal cancer (CRC) significantly influence treatment decisions. While convolutional neural networks (CNNs) have recently been introduced for automated CRC subtype identification using H&amp;E stained histopathological images, the correlation between CRC subtype genomic variants and their corresponding cellular morphology expressed by their imaging phenotypes is yet to be fully explored. The goal of this study was to determine such correlations by incorporating genomic variants in CNN models for CRC subtype classification from H&amp;E images. We utilized the publicly available TCGA-CRC-DX dataset, which comprises whole slide images from 360 CRC-diagnosed patients (260 for training and 100 for testing). This dataset also provides information on CRC subtype classifications and genomic variations. We trained CNN models for CRC subtype classification that account for potential correlation between genomic variations within CRC subtypes and their corresponding cellular morphology patterns. We assessed the interplay between CRC subtypes' genomic variations and cellular morphology patterns by evaluating the CRC subtype classification accuracy of the different models in a stratified 5-fold cross-validation experimental setup using the area under the ROC curve (AUROC) and average precision (AP) as the performance metrics. Combining the CNN models account for variations in CIMP and SNP further improved classification accuracy (AUROC: 0.847$\pm$0.01 vs. 0.787$\pm$0.03, p$=$0.01, AP: 0.68$\pm$0.02 vs. 0.64$\pm$0.05).
Ergebnisse und Diskussion (1980)

Durch potentiometrische Titration von Calciumchlorid mit gereinigtem STP mit Hilfe einer ionenspezifischen Elektrode wurden zwei Wendepunkte erhalten, die Calcium/TriphosphatMolverhältnissen von 2,5: 1 und 1: 1 entsprechen. (Abb. 1). Visuell konnte im Verlauf der Titration mit zunehmender STP-Zugabe zunächst eine Trübung festgestellt werden, die sich mit Erreichen des äquimolaren Verhältnisses auflöste.
Making and Unmaking of Puget Sound (2021)

The Puget Sound is a complex fjord-estuary system in Washington State that is connected to the Pacific Ocean by the Juan de Fuca Strait and surrounded by several large population centers. The watershed is enormous, covering nearly 43,000 square kilometers with thousands of rivers and streams. Geological forces, volcanos, Ice Ages, and changes in sea levels make the Sound a biologically dynamic and fascinating environment, as well as a productive ecosystem. Human activity has also influenced the Sound. Humans built several major cities, such as Seattle and Tacoma, have dramatically affected the Puget Sound. This book describes the natural history and evolution of Puget Sound over the last 100 million years through the present and into the future. Key Features Summarizes a complex geological, geographical, and ecological history Reviews how the Puget Sound has changed and will likely change in the future Examines the different roles of various drivers of the Sound’s ecosystem function Includes the role of humans—both first people and modern populations. Explores Puget Sound as an example of general bay ecological and environmental issues
Electron impact excitation out of the 2{sup 3}S metastable level of He (1996)

Using a hollow cathode discharge as a source of He, the authors have measured absolute cross sections for electron excitation out of the 2S level of He into the n=2, 3, 4, and 5 triplet levels for energies up to 20 eV. Their results show a pattern of sharply peaked excitation functions into the n = 3, 4, and 5 {sup 3}S and {sup 3}P levels, and comparatively broad excitation functions into the {sup 3}D levels. The 2{sup 3}P level has a remarkably broad excitation function, and its peak direct cross section is over 10 times the size of the next largest peak cross section observed. For energies above 20 eV, the authors use charge exchange of a fast He{sup +} beam with cesium to produce a primarily He target. This allows them to extend their measurements for selected triplet levels out to 1 keV. Their data indicate that even at this energy the excitations into the 3{sup 3}S, 3{sup 3}D, 4{sup 3}D have not yet entered the Born regime. Comparisons with other theoretical calculations at low energies will be made.
Nonlinear control of static systems with unsupervised learning of the initial conditions (2003)

We propose an algorithm for adaptive control of nonlinear multiple-input, multiple-output (MIMO) static systems. The advantage of the proposed method lies in its easy on-line implementation and reliable performance that is due to an intelligent algorithm for handling the initial conditions. We represent the nonlinear system with a piecewise linear model-a variable matrix of first order changes (i.e. the Jacobian matrix). In order to achieve global optimality for different initial conditions, an enhanced method involving on-line learning a fuzzy rule-base for determining a set of "good" initial conditions is developed. The knowledge in the rule-base (so as to determine a "good" initial input change) is extracted by on-line analyzing the relationship between the error signal, and the controller response. The algorithm continuously evaluates this information, and updates the rule-base model by using an unsupervised learning scheme. The rule-base provides the "optimal" estimates for the Jacobian and initial control settings anytime the control algorithm starts from new initial conditions.