gebhart/patrepeval huggingface dataset:
The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection (2011)

It is estimated that one-third of the world's population is infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is largely ineffective, and ways to enhance its efficacy are being developed. Of note, the candidate booster vaccines currently under clinical development have been designed to improve BCG efficacy but not prevent reactivation of latent infection. Here, we demonstrate that administering a multistage vaccine that we term H56 in the adjuvant IC31 as a boost to vaccination with BCG delays and reduces clinical disease in cynomolgus macaques challenged with M. tuberculosis and prevents reactivation of latent infection. H56 contains Ag85B and ESAT-6, which are two of the M. tuberculosis antigens secreted in the acute phase of infection, and the nutrient stress-induced antigen Rv2660c. Boosting with H56/IC31 resulted in efficient containment of M. tuberculosis infection and reduced rates of clinical disease, as measured by clinical parameters, inflammatory markers, and improved survival of the animals compared with BCG alone. Boosted animals showed reduced pulmonary pathology and extrapulmonary dissemination, and protection correlated with a strong recall response against ESAT-6 and Rv2660c. Importantly, BCG/H56-vaccinated monkeys did not reactivate latent infection after treatment with anti-TNF antibody. Our results indicate that H56/IC31 boosting is able to control late-stage infection with M. tuberculosis and contain latent tuberculosis, providing a rationale for the clinical development of H56.
NASA Fluid Lensing & MiDAR: Next-Generation Remote Sensing Technologies for Aquatic Remote Sensing (2018)

We present two recent instrument technology developments at NASA, Fluid Lensing and MiDAR, and their application to remote sensing of Earth's aquatic systems. Fluid Lensing is the first remote sensing technology capable of imaging through ocean waves in 3D at sub-cm resolutions. MiDAR is a next-generation active hyperspectral remote sensing and optical communications instrument capable of active fluid lensing. Fluid Lensing has been used to provide 3D multispectral imagery of shallow marine systems from unmanned aerial vehicles (UAVs, or drones), including coral reefs in American Samoa and stromatolite reefs in Hamelin Pool, Western Australia. MiDAR is being deployed on aircraft and underwater remotely operated vehicles (ROVs) to enable a new method for remote sensing of living and nonliving structures in extreme environments. MiDAR images targets with high-intensity narrowband structured optical radiation to measure an objectâ€TMs non-linear spectral reflectance, image through fluid interfaces such as ocean waves with active fluid lensing, and simultaneously transmit high-bandwidth data. As an active instrument, MiDAR is capable of remotely sensing reflectance at the centimeter (cm) spatial scale with a signal-to-noise ratio (SNR) multiple orders of magnitude higher than passive airborne and spaceborne remote sensing systems with significantly reduced integration time. This allows for rapid video-frame-rate hyperspectral sensing into the far ultraviolet and VNIR wavelengths. Previously, MiDAR was developed into a TRL 2 laboratory instrument capable of imaging in thirty-two narrowband channels across the VNIR spectrum (400-950nm). Recently, MiDAR UV was raised to TRL4 and expanded to include five ultraviolet bands from 280-400nm, permitting UV remote sensing capabilities in UV A, B, and C bands and enabling mineral identification and stimulated fluorescence measurements of organic proteins and compounds, such as green fluorescent proteins in terrestrial and aquatic organics.
Common Gene Rearrangements in Prostate Cancer (2011)

Prostate cancer is a common heterogeneous disease, and most patients diagnosed in the post prostate-specific antigen (PSA) era present with clinically localized disease, the majority of which do well regardless of treatment regimen undertaken. Overall, those with advanced prostate cancer at time of diagnosis do poorly after androgen withdrawal therapy. Understanding the biologic underpinning of prostate cancer is necessary to best determine the risk of disease progression and would be advantageous for the development of novel therapeutic approaches to impede or prevent disease. This review focuses on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a detailed understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease.
Vitamin E Phosphate Nucleoside Prodrugs: A Platform for Intracellular Delivery of Monophosphorylated Nucleosides (2018)

Vitamin E phosphate (VEP) nucleoside prodrugs are designed to bypass two mechanisms of tumor resistance to therapeutic nucleosides: nucleoside transport and kinase downregulation. Certain isoforms of vitamin E (VE) have shown activity against solid and hematologic tumors and result in chemosensitization. Because gemcitabine is one of the most common chemotherapeutics for the treatment of cancer, it was used to demonstrate the constructs utility. Four different VE isoforms were conjugated with gemcitabine at the 5' position. Two of these were δ-tocopherol-monophosphate (MP) gemcitabine (NUC050) and δ-tocotrienol-MP gemcitabine (NUC052). NUC050 was shown to be able to deliver gemcitabine-MP intracellularly by a nucleoside transport independent mechanism. Its half-life administered IV in mice was 3.9 h. In a mouse xenograft model of non-small cell lung cancer (NSCLC) NCI-H460, NUC050 at a dose of 40 mg/kg IV qwk × 4 resulted in significant inhibition to tumor growth on days 11-31 (<i>p</i> < 0.05) compared to saline control (SC). Median survival was 33 days (NUC050) vs. 25.5 days (SC) ((hazard ratio) HR = 0.24, <i>p</i> = 0.017). Further, NUC050 significantly inhibited tumor growth compared to historic data with gemcitabine at 135 mg/kg IV q5d × 3 on days 14-41 (<i>p</i> < 0.05). NUC052 was administered at a dose of 40 mg/kg IV qwk × 2 followed by 50 mg/kg qwk × 2. NUC052 resulted in inhibition to tumor growth on days 14-27 (<i>p</i> < 0.05) and median survival was 34 days (HR = 0.27, <i>p</i> = 0.033). NUC050 and NUC052 have been shown to be safe and effective in a mouse xenograft of NSCLC.
On Replication Algorithm in P2P VoD (2013)

Traditional video-on-demand (VoD) systems rely purely on servers to stream video content to clients, which does not scale. In recent years, peer-to-peer assisted VoD (P2P VoD) has proven to be practical and effective. In P2P VoD, each peer contributes some storage to store videos (or segments of videos) to help the video server. Assuming peers have sufficient bandwidth for the given video playback rate, a fundamental question is what is the relationship between the storage capacity (at each peer), the number of videos, the number of peers, and the resultant off-loading of video server bandwidth. In this paper, we use a simple statistical model to derive this relationship. We propose and analyze a generic replication algorithm Random with Load Balancing (RLB) that balances the service to all movies for both deterministic and random (but stationary) demand models and both homogeneous and heterogeneous peers (in upload bandwidth). We use simulation to validate our results for sensitivity analysis and for comparisons to other popular replication algorithms. This study leads to several fundamental insights for P2P VoD system design in practice.
Simulating Dysarthric Speech for Training Data Augmentation in Clinical Speech Applications (2018)

Training machine learning algorithms for speech applications requires large, labeled training data sets. This is problematic for clinical applications where obtaining such data is prohibitively expensive because of privacy concerns or lack of access. As a result, clinical speech applications typically rely on small data sets with only tens of speakers. In this paper, we propose a method for simulating training data for clinical applications by transforming healthy speech to dysarthric speech using adversarial training. We evaluate the efficacy of our approach using both objective and subjective criteria. We present the transformed samples to five experienced speech-language pathologists (SLPs) and ask them to identify the samples as healthy or dysarthric. The results reveal that the SLPs identify the transformed speech as dysarthric 65% of the time. In a pilot classification experiment, we show that by using the simulated speech samples to balance an existing dataset, the classification accuracy improves by ~10% after data augmentation.
Isolation in Commodity Multicore Processors (2007)

Resource sharing in modern chip multiprocessors (multicores) provides many cost and performance benefits. However, component sharing also creates drawbacks for fault, performance, and security isolation.Thus, integration of components on a multicore chip should also be accompanied by features that help isolate effects of faults, destructive performance interference, and security breaches.
Delta-like Ligand-4-Notch Signaling Inhibition Regulates Pancreatic Islet Function and Insulin Secretion (2018)

Although Notch signaling has been proposed as a therapeutic target for type-2 diabetes, liver steatosis, and atherosclerosis, its direct effect on pancreatic islets remains unknown. Here, we demonstrated a function of Dll4-Notch signaling inhibition on the biology of insulin-producing cells. We confirmed enhanced expression of key Notch signaling genes in purified pancreatic islets from diabetic NOD mice and showed that treatment with anti-Dll4 antibody specifically abolished Notch signaling pathway activation. Furthermore, we showed that Notch inhibition could drive proliferation of β-islet cells and confer protection from the development of STZ-induced diabetes. Importantly, inhibition of the Dll4 pathway in WT mice increased insulin secretion by inducing the differentiation of pancreatic β-islet cell progenitors, as well as the proliferation of insulin-secreting cells. These findings reveal a direct effect of Dll4-blockade on pancreatic islets that, in conjunction with its immunomodulatory effects, could be used for unmet medical needs hallmarked by inefficient insulin action.
Versatile Strategy To Generate a Rhodamine Triplet State as Mitochondria-Targeting Visible-Light Photosensitizers for Efficient Photodynamic Therapy (2019)

Through the use of a rhodamine-appended chelate, bpy-Rho, a versatile strategy has been demonstrated to readily form mitochondria-targeting photosensitizers via the incorporation of a variety of luminescent transition-metal systems, M-Rho, such as Re(I), Ir(III), Pt(II), and Rh(III). The emission from the rhodamine singlet excited state and the transition-metal triplet excited state is partially quenched by the depopulation of them into the dark rhodamine triplet excited state. The generation of the triplet excited state of a rhodamine moiety endows the complexes with mitochondria-targeting photosensitizing ability to form singlet oxygen (<sup>1</sup>O<sub>2</sub>) for use as a photodynamic therapy (PDT) agent upon visible-light irradiation. The combination of the rhodamine organic dye and luminescent transition-metal centers in such hybrid systems exhibits the synergistic merits for the biological applications, including low dark cytotoxicity, selective tumor cell uptake, high molar absorptivity suitable for low-energy excitation in the visible region, and high photostability. The corresponding in vitro photocytotoxicity and in vivo photo-antitumor efficacy have also been studied to demonstrate the potential PDT application of M-Rho.
Overcoming HLA restriction in clinical trials (2012)

A decade of collective work by tumor immunologists has led to improved large scale generation, maturation, antigen loading and administration of dendritic cells (DCs) to cancer patients, promoting enhanced antitumor activity. We alleviated the HLA-restriction in DC therapy and demonstrated that it is meaningful to treat patients with DCs irrespective of their HLA type.
Scattering optimization synthesis of compact mode converters for waveguides (2002)

Discusses mode converters for overmoded waveguides. Various designs based on periodic PIBU perturbation have previously been demonstrated for conversion from say TE/sub om/ to TE/sub on/ modes in overmoded circular waveguides. These designs demonstrate high conversion efficiencies but their overall length is large compared to the radial dimensions of the waveguide. To resolve the problem of length and also to explore other possibilities, a different approach to the design of mode converters for waveguides is proposed, The method is based on a short forceful perturbation of the field rather than a periodic field disturbance caused by a grating like structure. For designing a mode converter, the problem is formulated as that of finding a scattering surface (formed by varying the transverse dimensions of the waveguide) which can scatter the incoming field in such a way as to convert it from one mode structure to the other. The shape of the required mode converter is found by optimizing the scattered power in the required output mode as a function of the surface profile of the scatterer.
Spacer-drain overlap dependence of subthreshold characteristics for tunnel field-effect transistors based on vertical tunneling (2012)

In this paper, the impact of a spacer-drain overlap on the subthreshold characteristics is studied for a silicon n-channel tunnel field-effect transistor, in which the dominant carrier tunneling occurs in a direction that is in-line with the gate electric-field. It is demonstrated that subthreshold swing is significantly reduced by reducing the impact of fringe-induced barrier lowering by appropriate designing of the drain-side spacer. Short-channel effects, such as drain-induced barrier lowering (DIBL), are also greatly suppressed in it. Results of the investigation on the scaling properties of such devices are also reported.
Microchip device for liquid phase analysis (2000)

The lab-on-a-chip concept has enabled miniature instruments to be developed that allow the rapid execution and automation of fluidic operations such as valving, separation, dilution, mixing, and flow splitting upon the proper application of a motive (driving) force. The integration of these simple operations to perform complete, multiple-step chemical assays is rapidly becoming a reality. Such compact, monolithic devices potentially enjoy advantages in speed, cost, automation, reagent consumption, and waste generation compared to existing laboratory-scale instruments. Initial reports of these microfluidic devices focused on combining various electrokinetically driven separation methods including microchip electrophoresis, gel electrophoresis, micellar electrokinetic chromatography (MEKC) and open channel electrochromatography (OCEC) with fluidic valving to introduce sample plugs into the separation channel. Other operations have quickly been integrated with the separations and fluidic valving on these microchips. For example, integrated devices with mixers/diluters for precolumn and postcolumn analyte derivatization, deoxyribonucleic acid (DNA) restriction digests, enzyme assays, and polymerase chain reaction (PCR) amplification have been added to the basic design. Integrated mixers that can perform solvent programming for both MEKC and OCEC have also been demonstrated. These examples are simple, yet powerful, demonstrations of the potential for lab-on-a-chip devices. In this report, three key areas for improved performance of these devices are described: on-chip calibration techniques, enhanced separative performance, and enhanced detection capabilities.
Abstract 5524: Generation of cellular immune responses to MUC1-C to target the portion of MUC1 that is most biologically relevant to the transformation process (2011)

Abstract MUC1 is overexpressed in diverse human carcinomas and hematological cancers, and therefore serves as a potential target for immunotherapy. The MUC1 molecule has two distinctive subunits, formed by autocleavage with a SEA domain. The N-terminal (MUC1-N) is the large extracellular domain, and the C-terminal (MUC1-C) has three subunits: a small extracellular domain that is covalently bound to MUC1-N, a single transmembrane domain and a cytoplasmic tail. It has been reported by Kufe et al that the MUC1-C subunit transduces signals that confer growth and survival responses. The MUC1-C cytoplasmic tail located downstream of the SEA domain is sufficient for the induction of anchorage independent growth and tumorigenicity. MUC1-C overexpression is also highly associated with poor prognosis in patients with lung cancer and breast cancer. We and others have previously reported on HLA-A2 binding agonist epitopes to MUC1-N. The objective of this investigation is to identify and characterize HLA-A3 binding cytotoxic T-lymphocyte (CTL) epitopes and agonist epitopes of the MUC1-C subunit. The intention is to add these peptides to vaccines against MUC1 positive carcinomas, as well as using them for monitoring patients’ immune responses in clinical MUC1 vaccine trials. The generation of cellular immune responses to MUC1-C would thus target the portion of MUC1 that is most biologically relevant to the transformation process. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5524. doi:10.1158/1538-7445.AM2011-5524
Plasmonic engineering of singlet oxygen generation (2008)

In this article, we report metal-enhanced singlet oxygen generation (ME(1)O2). We demonstrate a direct relationship between the singlet oxygen yield of a common photosensitizer (Rose Bengal) and the theoretical electric field enhancement or enhanced absorption of the photosensitizer in proximity to metallic nanoparticles. Using a series of photosensitizers, sandwiched between silver island films (SiFs), we report that the extent of singlet oxygen enhancement is inversely proportional to the free space singlet oxygen quantum yield. By modifying plasmon coupling parameters, such as nanoparticle size and shape, fluorophore/particle distance, and the excitation wavelength of the coupling photosensitizer, we can readily tune singlet oxygen yields for applications in singlet oxygen-based clinical therapy.
POINT: An Intent-Driven Framework for Integrated Packet-Optical In-Band Network Telemetry (2018)

Emerging packet-optical networks have exposed flexibility and scalability limitations of current network telemetry mechanisms. Recent work in packet networks has explored the possibility of improving network telemetry for devices that have programmable data planes with encouraging results. Extending those mechanisms into optical networks, however, is far from straightforward due to factors such as layering and presence of devices that do not process packets. We introduce a framework that overcomes those challenges for packet-optical networks with constructs to unify telemetry across packet and optical network segments. We demonstrate the utility of the proposed framework with an implementation of use-case examples in packet-optical network telemetry.
Evaluation of Steel Bridges (Volume I): Monitoring the Structural Condition of Fracture-Critical Bridges using Fiber Optic Technology (2007)

This report is divided into two volumes. This volume (Volume I) summarizes a structural health monitoring (SHM) system that was developed for the Iowa DOT to remotely and continuously monitor fatigue critical bridges (FCB) to aid in the detection of crack formation. The developed FCB SHM system enables bridge owners to remotely monitor FCB for gradual or sudden damage formation. The SHM system utilizes fiber bragg grating (FBG) fiber optic sensors (FOSs) to measure strains at critical locations. The strain-based SHM system is trained with measured performance data to identify typical bridge response when subjected to ambient traffic loads, and that knowledge is used to evaluate newly collected data. At specified intervals, the SHM system autonomously generates evaluation reports that summarize the current behavior of the bridge. The evaluation reports are collected and distributed to the bridge owner for interpretation and decision making. Volume II summarizes the development and demonstration of an autonomous, continuous SHM system that can be used to monitor typical girder bridges. The developed SHM system can be grouped into two main categories: an office component and a field component. The office component is a structural analysis software program that can be used to generate thresholds which are used for identifying isolated events. The field component includes hardware and field monitoring software which performs data processing and evaluation. The hardware system consists of sensors, data acquisition equipment, and a communication system backbone. The field monitoring software has been developed such that, once started, it will operate autonomously with minimal user interaction. In general, the SHM system features two key uses. First, the system can be integrated into an active bridge management system that tracks usage and structural changes. Second, the system helps owners to identify damage and deterioration.
Preparative size-exclusion chromatography for separation and purification of water-stable Cd-based quantum dots (2012)

Size-exclusion chromatography (SEC) associated with High Performance Liquid Chromatography (HPLC) is a powerful tool to separate, purify and fractionalize materials based on size. In this paper, we present a SEC method that was developed for the separation of thiol-capped Cd(Se,S) quantum dots (QDs) synthesized in the aqueous phase. A HPLC system with a SEC column and a cascade of three detectors (UV/Vis, FLD and ELSD) was used to analyze the different size fractions of QDs. Nanocrystals–HPLC column interactions were suppressed using thioglycolic acid (TGA) as an ion pair agent. Five fractions, namely F1 to F5, of different sizes and tunable optical properties were isolated from the original QDs sample. The emission peaks for fractions F1 and F2 were red-shifted and the fractions F4 and F5 were blue-shifted compared with the original sample, which suggested the presence of nanocrystals having different sizes. Dynamic Light Scattering (DLS) confirmed that collected fractions exhibited different hydrodynamic diameters ranging from 98.2 nm (fraction F1) to 24.9 nm (fraction F5). Also, fractions F2 and F4 were functionalized with glutathione and analyzed by HPLC-SEC. Glutathione-capped Cd(Se,S) QDs showed an increase in their molecular weight, when compared to bare TGA-capped Cd(Se,S) QDs, without a remarkable change of their crystal size and optical properties. The developed SEC technique allows a fast and reproducible separation of water-stable Cd(Se,S) QDs. Collected fractions with tunable optical properties could have potential applications in the nanotechnology area such as bio-imaging and diagnostics, e.g. cell sorting.