gebhart/patrepeval huggingface dataset:
Quantification of murine endothelial cell adhesion molecules in solid tumors (1999)

Coordinated adhesive interactions between lymphocyte receptors and endothelial cell adhesion molecules (CAMs) are a prerequisite for effector cell entry into tumor stroma. Whereas the diminished leukocyte-endothelial cell interactions observed in tumor microvessels have been attributed to a reduced expression of endothelial CAMs, there is no quantitative data bearing on this issue. The dual-radiolabeled monoclonal antibody technique was used to quantify constitutive and tumor necrosis factor (TNF)-alpha-induced expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), ICAM-2, P-selectin, E-selectin, and platelet-endothelial cell adhesion molecule 1 (PECAM-1) in different vascular beds of normal (C57Bl/6) and RM-1 tumor-bearing mice. When corrected for endothelial surface area, the constitutive expression of selectins in tumor vessels was higher than that observed in other vascular beds. Both constitutive and induced expression of endothelial CAMs in peripheral vascular beds did not differ between normal and tumor-bearing mice. Within the tumor, the magnitude of the upregulation of P-selectin, ICAM-1, and VCAM-1 after TNF-alpha was similar to that within other vascular beds. E-selectin expression in tumors was refractory to TNF-alpha, whereas PECAM-1 and ICAM-2 expression were significantly reduced. Our findings suggest that the presence of a solid tumor does not influence endothelial CAM expression in other vascular beds and that the higher density of selectins in nonstimulated tumor vessels may promote the recruitment of rolling leukocytes in this tissue.
Prospective Isolation of Human Eosinophil-Committed Progenitors. (2006)

Abstract Eosinophils play an important role in the pathogenesis of allergic reactions or chronic inflammatory diseases by releasing various types of cytokines and chemical mediators. Recently, we have identified murine eosinophil-committed progenitors (mEoPs) in mouse bone marrow. The expression of receptor for IL-5, a critical cytokine for proliferation and differentiation of eosinophils, was a key marker to isolate mEoPs: mEoP was IL-5Ra+Lineage(lin)-CD34+c-Kitlow population in murine bone marrow (J Exp Med.201, 1891ndash;7, 2005). Here we report that EoPs are prospectively isolatable also in human bone marrow. We analyzed the expression of human IL-5Ra in human stem and progenitor populations, and found that a fraction of common myeloid progenitor (CMP; lin-CD34+CD38+CD45RA-IL-3Ra+) population expressed hIL-5Ra on their surface by using anti-human IL-5Ra monoclonal antibodies. IL-5Ra protein and mRNA were undetectable in hematopoietic stem cells (HSCs; lin-CD34+CD38-), common lymphoid progenitors (CLPs; lin-CD34+CD38+CD10+), megakaryocyte/erythrocyte progenitors (MEPs; lin-CD34+CD38+CD45RA-IL-3Ra-), or granulocyte/monocyte progenitors(GMPs; lin-CD34+CD38+CD45RA+IL-3Ra+) by FACS and RT-PCR, respectively. The IL-5Ra+ cells within the CMP fraction constituted only ~0.04% of steady-state bone marrow mononuclear cells, and gave rise only to pure eosinophil colonies. Thus we termed this population as human EoP (hEoP). Both HSCs and the IL-5Ra- fraction of CMPs gave rise to IL-5Ra+ hEoPs in vitro in the presence of IL-3 and GM-CSF, while MEPs or GMPs never generated hEoPs, indicating that human eosinophil pathway diverges at the CMP stage, and that the eosinophil potential was lost at the GMP or MEP stage. Accordingly, the human eosinophil pathway is different from that in murine hematopoiesis where mEoPs develop from the GMP stage. Strikingly, the number of hEoPs in the bone marrow of patients with hypereosinophilic syndrome was significantly (~4-fold) increased as compared to that in normal bone marrow, suggesting that hEoP represents a critical stage for eosinophilia in vivo. Thus, the hEoP is an attractive candidate for therapeutic target in eosinophil-related allergic and inflammatory disorders. This population might also be very useful to study the molecular mechanism of human eosinophil development.
Kernelized Hashcode Representations for Relation Extraction (2017)

Kernel methods have produced state-of-the-art results for a number of NLP tasks such as relation extraction, but suffer from poor scalability due to the high cost of computing kernel similarities between natural language structures. A recently proposed technique, kernelized locality-sensitive hashing (KLSH), can significantly reduce the computational cost, but is only applicable to classifiers operating on kNN graphs. Here we propose to use random subspaces of KLSH codes for efficiently constructing an explicit representation of NLP structures suitable for general classification methods. Further, we propose an approach for optimizing the KLSH model for classification problems by maximizing an approximation of mutual information between the KLSH codes (feature vectors) and the class labels. We evaluate the proposed approach on biomedical relation extraction datasets, and observe significant and robust improvements in accuracy w.r.t. state-of-the-art classifiers, along with drastic (orders-of-magnitude) speedup compared to conventional kernel methods.
Synthesis and Activities of the Phosphonate Isostere of the Monophosphate of (±)Cyclobut-G (1992)

Abstract Synthesis of the novel phosphonate isostere of the monophosphate of (±)Cyclobut-G and its biological activities against HSV-1 and HSV-2 in Vero cells are reported. The cyclobutane ring was constructed by a [2+2] thermal cycloaddition. The relative stereochemistry of the substituents on the ring was determined by NOE experiments.
Compressed linear algebra for large-scale machine learning (2016)

Large-scale machine learning (ML) algorithms are often iterative, using repeated read-only data access and I/O-bound matrix-vector multiplications to converge to an optimal model. It is crucial for performance to fit the data into single-node or distributed main memory. General-purpose, heavy- and lightweight compression techniques struggle to achieve both good compression ratios and fast decompression speed to enable block-wise uncompressed operations. Hence, we initiate work on compressed linear algebra (CLA), in which lightweight database compression techniques are applied to matrices and then linear algebra operations such as matrix-vector multiplication are executed directly on the compressed representations. We contribute effective column compression schemes, cache-conscious operations, and an efficient sampling-based compression algorithm. Our experiments show that CLA achieves in-memory operations performance close to the uncompressed case and good compression ratios that allow us to fit larger datasets into available memory. We thereby obtain significant end-to-end performance improvements up to 26x or reduced memory requirements.
Multiple factors may contribute to care inequity (2018)

As much as racial and ethnic disparities exist broadly across health care in the United States, it is not surprising to observe this phenomenon in the urologic arena, writes Arthur L. Burnett, II, MD, MBA.
Color difference metrics and surround effects: preliminary results (2002)

Whereas both the CMC color difference metric and CIE94 show a considerable dependence on chroma, our measurements of contrast sensitivity show little or no such dependence. That is, the sensitivity to spatial variations in lightness, chroma and hue do not appear to depend on chroma, at least not to an extent greater than inter-observer variability. A key difference between a contrast sensitivity experiment and a color matching experiment is that the background color is the former is of necessity the mean color of the grating, whereas the background in the latter is typically a neutral gray of specified reflectivity or luminance. Goodman hypothesized that the chroma dependence in CMC and CIE94 may result from distance from background, rather than distance from neutral; the experiments reported here test that hypothesis. Results are only preliminary: a single combination of hue and lightness was used throughout the experiments, however they indicated at least partial agreement with Goodman's hypothesis.
Partonic Flow andϕ-Meson Production inAu+AuCollisions atsNN=200  GeV (2007)

We present first measurements of the phi-meson elliptic flow (v2(pT)) and high-statistics pT distributions for different centralities from radical sNN=200 GeV Au+Au collisions at RHIC. In minimum bias collisions the v2 of the phi meson is consistent with the trend observed for mesons. The ratio of the yields of the Omega to those of the phi as a function of transverse momentum is consistent with a model based on the recombination of thermal s quarks up to pT approximately 4 GeV/c, but disagrees at higher momenta. The nuclear modification factor (R CP) of phi follows the trend observed in the K S 0 mesons rather than in Lambda baryons, supporting baryon-meson scaling. These data are consistent with phi mesons in central Au+Au collisions being created via coalescence of thermalized s quarks and the formation of a hot and dense matter with partonic collectivity at RHIC.
Plasma-mediated transfection of RPE (2006)

A major obstacle in applying gene therapy to clinical practice is the lack of efficient and safe gene delivery techniques. Viral delivery has encountered a number of serious problems including immunological reactions and malignancy. Non-viral delivery methods (liposomes, sonoporation and electroporation) have either low efficiency in-vivo or produce severe collateral damage to ocular tissues. We discovered that tensile stress greatly increases the susceptibility of cellular membranes to electroporation. For synchronous application of electric field and mechanical stress, both are generated by the electric discharge itself. A pressure wave is produced by rapid vaporization of the medium. To prevent termination of electric current by the vapor cavity it is ionized thus restoring its electric conductivity. For in-vivo experiments with rabbits a plasmid DNA was injected into the subretinal space, and RPE was treated trans-sclerally with an array of microelectodes placed outside the eye. Application of 250-300V and 100-200 &#956;s biphasic pulses via a microelectrode array resulted in efficient transfection of RPE without visible damage to the retina. Gene expression was quantified and monitored using bioluminescence (luciferase) and fluorescence (GFP) imaging. Transfection efficiency of RPE with this new technique exceeded that of standard electroporation by a factor 10,000. Safe and effective non-viral DNA delivery to the mammalian retina may help to materialize the enormous potential of the ocular gene therapy. Future experiments will focus on continued characterization of the safety and efficacy of this method and evaluation of long-term transgene expression in the presence of phiC31 integrase.
Clinical challenges in rapidly progressive dementia:lessons learned from an autopsy series (P2.091) (2017)

To describe three patients with rapidly progressive dementia all of whom had a positive autoimmune autoantibody during life, but on autopsy were found to have alternative diagnoses.
Investigating the development of the human visual system with fMRI in awake, behaving infants (2018)

Vision undergoes rapid and dramatic development early in life. These changes have been investigated extensively with behavioral techniques, but there is a dearth of direct neural studies of the developing visual system. This stands in contrast to the adult visual system where a great deal has been learned over two decades by using fMRI, including studies of retinotopy, attention, and perceptual learning. The lack of fMRI studies in infants and toddlers reflects the technical complexity of performing such experiments, including head motion, attention span and fussiness, inability to understand or follow instructions, uncomfortable apparatus, and adult-centric analysis approaches. When infants have been scanned successfully, it has typically been during sleep or sedation, preventing the kinds of cognitive tasks that would allow for comparisons to adults and for benefitting from the tremendous advances in adult cognitive neuroscience. Here we report on our attempts to re-imagine task-based fMRI procedures for early developmental populations. The resulting advances include: projector-based panoramic visual presentation, flexible experiment transitions, within-volume motion artefact detection and functional alignment. With these procedures, we have now scanned 18 participants under the age of 36 months and retained a high percentage of the functional data collected from each participant. These procedures also produce reliable evoked BOLD activity in visual cortex in response to a wide variety of visual stimuli. With these tools in hand, we are now investigating the retinotopic organization, attention networks, and plasticity of the infant visual cortex. Each of these studies presents its own unique challenges, such as the difficulty ensuring fixation during retinotopy. Nevertheless, the hope is to complement the wealth of work on visual development with a detailed understanding of early brain function. Meeting abstract presented at VSS 2018
Say “adios” to the American dream? The interplay between ethnic and national identity among Latino and Caucasian Americans. (2010)

In three studies, implicit and explicit measures were used to examine the interconnections between ethnic and national identities among Latino Americans and Caucasian Americans. Consistently, Latino Americans as a group were conceived of as being less American than Caucasian Americans (Studies 1-3). This effect was exhibited by both Caucasian and Latino participants. Overall, Caucasian participants displayed a stronger national identification than Latino participants (Studies 2 and 3). In addition, ethnic American associations accounted for the strength of national identification for Caucasian participants, but not for Latino participants (Study 2). Finally, ethnic differences in national identification among individuals who exclude Latino Americans from the national identity emerged when persistent ethnic disparities were primed, but not when increasing equalities were stressed (Study 3). In sum, ethnic American associations account for the merging versus dissociation between ethnic and national identifications and reflect a long-standing ethnic hierarchy in American society.
Changes in Global Gene Expression Associated with 3D Structure of Tumors: An Ex Vivo Matrix-Free Mesothelioma Spheroid Model (2012)

Tumor microenvironments present significant barriers to anti-tumor agents. Molecules involved in multicellular tumor microenvironments, however, are difficult to study ex vivo. Here, we generated a matrix-free tumor spheroid model using the NCI-H226 mesothelioma cell line and compared the gene expression profiles of spheroids and monolayers using microarray analysis. Microarray analysis revealed that 142 probe sets were differentially expressed between tumor spheroids and monolayers. Gene ontology analysis revealed that upregulated genes were primarily related to immune response, wound response, lymphocyte stimulation and response to cytokine stimulation, whereas downregulated genes were primarily associated with apoptosis. Among the 142 genes, 27 are located in the membrane and related to biologic processes of cellular movement, cell-to-cell signaling, cellular growth and proliferation and morphology. Western blot analysis validated elevation of MMP2, BAFF/BLyS/TNFSF13B, RANTES/CCL5 and TNFAIP6/TSG-6 protein expression in spheroids as compared to monolayers. Thus, we have reported the first large scale comparison of the transcriptional profiles using an ex vivo matrix-free spheroid model to identify genes specific to the three-dimensional biological structure of tumors. The method described here can be used for gene expression profiling of tumors other than mesothelioma.
Abstract 4334: Identification and elimination of T-cell epitopes in recombinant immunotoxins used to treat cancer. (2013)

Abstract Moxetumomab pasudotox and SS1P are immunotoxins that have been developed in our lab to treat cancer. Moxetumomab pasudotox, which can be given for many treatment cycles, targets CD22 and has produced many complete remissions in drug-resistant hairy cell leukemia. However, SS1P, which targets mesothelin, could only be given for one cycle before ADA (anti drug antibodies) developed and neutralized the protein. We hypothesize that SS1P could be more effective if it were less immunogenic and more treatment cycles could be given. To de-immunize the immunotoxin we sought to identify and remove T cell epitopes. To identify the epitopes we stimulated PBMCs from 50 normal donors with whole immunotoxin for 14 days to expand the T cells and then stimulated the T cells with peptides (15 mers) derived from the toxin, followed by ELISpot to identify the peptides that stimulated the T cells. We found that all 50 donors gave a positive response, which correlates with the frequency of ADAs in patients with normal immune systems. We used alanine-scanning mutagenesis to determine which amino acids in each peptide are important for T cell stimulation. SS1P contains domains II and III of PE. In 46% of the donors we found a single highly immunodominant and promiscuous epitope that is located in domain II. We previously showed we could eliminate almost all of domain II while retaining excellent cytotoxic activity. These data indicate that immunogenicity should be eliminated in 34% of normal individuals donors and diminished in another 42% by deletion of domain II. In domain III we identified 5 peptides that stimulated T cell responses in different donors and also identified alanine mutations within each peptide that eliminated or greatly lowered T cell stimulation in most donors. We are using this information to make immunotoxins with mutations in domain III that should have a further decrease in immunogenicity. We have shown that among many individuals with different HLA alleles there is a dominant T cell epitope in domain II of PE38 and 5 subdominant epitopes in domain III. We plan to use this information to make new immunotoxins in which the large majority of T cell epitopes are silenced resulting in diminished immunogenicity of the immunotoxin. We plan to combine these T cell mutations with B cell mutations previously described to make immunotoxins with very low immunogenicity allowing more treatment cycles to be given and better anti-tumor activity achieved. Citation Format: Ronit Mazor, Aaron N. Vassall, Jaime A. Eberle, Richard Beers, Xiaobo Hu, Itai Benhar, Ira Pastan. Identification and elimination of T-cell epitopes in recombinant immunotoxins used to treat cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4334. doi:10.1158/1538-7445.AM2013-4334
Dynamic Extraction of Spearmint Oil Components by Using Supercritical CO2 (2000)

The effects of various extraction conditions on the dynamic extraction of the essential oil components carvone and limonene from spearmint leaves using SC-CO2 were investigated. The extraction rate increased with increasing pressure or decreasing temperature. An increase of the CO2 flow rate increased the extraction rate but decreased the solvent efficiency of CO2. Ground leaf samples with a smaller particle size showed an enhanced initial extraction rate for carvone as compared to larger particle size leaf samples. The use of an ethanol modifier did not enhance the extraction rate but did cause the coextraction of pigment and waxy substances.
Advances on the Constitutive Characterization of Composites via Multiaxial Robotic Testing and Design Optimization (2014)

The research areas of mutiaxial robotic testing and design optimization have been recently utilized for the purpose of data-driven constitutive characterization of anisotropic material systems. This effort has been enabled by both the progress in the areas of computers and information in engineering as well as the progress in computational automation. Although our efforts have begun three decades ago, in this chapter we are presenting our progress on this synergistic combination of technologies developed in the last five years. Specifically, in this chapter we are reporting on the first successful implementation of our evolving methodology that recently was completed with the first industrial rate campaign of experiments for this purpose. This methodology is motivated by the data-driven requirements of employing design optimization principles for determining the constitutive behavior of composite materials as described in our recent work [1, 2]. Traditionally, the determination of the constitutive characterization of composite materials has been achieved through conventional uniaxial tests, mainly aiming for the estimation of the elastic properties. Typically, extraction of these properties, involve uniaxial tests conducted with specimens mounted on uniaxial testing machines, where the major orthotropic axis of any given specimen is angled relative to the loading direction. In addition, specimens are designed such that a homogeneous state of strain is developed over a well-defined area, which is required for the purpose of measuring stresses and strains through the measurement of the respective reaction forces and displacement [3, 4]. Consequently, the use of uniaxial testing machines imposes requirements of using multiple specimens, griping fixtures, and multiple experiments without the option of studying mutltiaxial effects. The requirement of a homogeneous state of strain frequently imposes restrictions on the sizes and shapes of specimens to be tested. These requirements result in increased cost and time, and to inefficient characterization processes.To address these issues and to extend characterization to multiaxial state of strain in both the linear and non-linear regimes, multi-degree of freedom automated mechatronic testing machines, which are capable of loading specimens multiaxially, in conjunction with energy-based inverse characterization methodologies, were introduced at the Naval Research Laboratory (NRL) [5–7]. This development was the first of its kind and has continued through the present [8–10].
Photochemical and Antimicrobial Properties of Novel C60 Derivatives in Aqueous Systems (2009)

Four novel hexakis C60 derivatives with varying functionalities were synthesized, and their photochemical properties and photodynamic disinfection efficiencies were quantitatively evaluated. All these C. derivatives generated O2 more efficiently than commercial multihydroxylated C60 (fullerol), as assessed by furfuryl alcohol consumption and electron paramagnetic resonance analysis. Despite significant agglomeration/aggregation in the aqueous phase to micrometer-sized particles, nanosecond laser flash photolysis showed that the lifetime of triplet state (a key intermediate for energy transfer responsible for (1)O2 production) was comparable to reported values for pristine C. in organic phase. As a result of facile (1)O2 production, the Co derivatives efficiently inactivated Escherichie coli and MS-2 bacteriophage. Cationic aminofullerene hexakis, which likely exerted electrostatic attraction, exhibited exceptionally rapid virus inactivation even compared to commercial nano-TiO2 photocatalyst These unique photodynamic, hydrophilic and cationic properties may be instrumental for the development of next generation photocatalysts for disinfection applications. The high ROS (reactive oxygen species) production activity and associated cytotoxicity are concerns for potential releases of functionalized Ca to the environment, and require careful assessment apart from other forms of C60 (e.g., nC60) that have been widely studied as model nanomaterials but behave differently.