gebhart/patrepeval huggingface dataset:
Identification of Cellular Pathways of “Type 1,” Th17 T Cells, and TNF- and Inducible Nitric Oxide Synthase-Producing Dendritic Cells in Autoimmune Inflammation through Pharmacogenomic Study of Cyclosporine A in Psoriasis (2008)

Therapeutic modulation of psoriasis with targeted immunosuppressive agents defines inflammatory genes associated with disease activity and may be extrapolated to a wide range of autoimmune diseases. Cyclosporine A (CSA) is considered a "gold standard" therapy for moderate-to-severe psoriasis. We conducted a clinical trial with CSA and analyzed the treatment outcome in blood and skin of 11 responding patients. In the skin, as expected, CSA modulated genes from activated T cells and the "type 1" pathway (p40, IFN-gamma, and STAT-1-regulated genes). However, CSA also modulated genes from the newly described Th17 pathway (IL-17, IL-22, and downstream genes S100A12, DEFB-2, IL-1beta, SEPRINB3, LCN2, and CCL20). CSA also affected dendritic cells, reducing TNF and inducible NO synthase (products of inflammatory TNF- and inducible NO synthase-producing dendritic cells), CD83, and IL-23p19. We detected 220 early response genes (day 14 posttreatment) that were down-regulated by CSA. We classified >95% into proinflammatory or skin resident cells. More myeloid-derived than activated T cell genes were modulated by CSA (54 myeloid genes compared with 11 lymphocyte genes), supporting the hypothesis that myeloid derived genes contribute to pathogenic inflammation in psoriasis. In circulating mononuclear leukocytes, in stark contrast, no inflammatory gene activity was detected. Thus, we have constructed a genomic signature of successful treatment of psoriasis which may serve as a reference to guide development of other new therapies. In addition, these data also identify new gene targets for therapeutic modulation and may be applied to wide range of autoimmune diseases.
Cellular and Molecular Neurosurgery: Pathways from Concept to Reality-Part II: Vector Systems and Delivery Methodologies for Gene Therapy of the Central Nervous System (1997)

Different vector systems that have been used and/or specifically developed for central nervous system (CNS) gene transfer studies are briefly discussed along with their advantages and disadvantages with respect to potential clinical application. These include retroviruses, recombinant herpes simplex virus, adenoviruses, adenoassociated viruses, encapsulation of plasmid deoxyribonucleic acid into cationic liposomes, and neural and oliogodendroglial stem cells. Particular attention has been paid to relate the modality of a specific CNS gene therapy to the strategy for adequate delivery of genetic material to the brain for either global or localized CNS neurodegenerative chronic disorder, as well as for CNS tumors and stroke. Techniques to circumvent the "impermeable" blood-brain barrier and how to breach the more versatile blood-brain-tumor barrier to deliver the genetic material to the target CNS cells are reviewed and include the following: 1) local stereotactic CNS injection/infusion of viral vectors, administration of vector producer cells, or cell replacement; 2) local administration of genetic material into the cerebrospinal fluid ventriculocisternal system; 3) osmotic opening of the blood-brain barrier; 4) local intra-arterial infusion; and 5) administration of blood-brain-tumor barrier permeabilizers, such as a bradykinin B2 agonist RMP-7. It is concluded that gene therapy for several brain disorders holds great potential, as suggested mainly by in vitro experiments and, to some extent, by a limited number of animal experiments. However, several drawbacks currently hamper the application of gene therapy under the clinical setting. The problems associated with gene therapy that still present major obstacles are as follows: 1) inefficient transfection of host cells by viral vectors; 2) restricted delivery of genetic material across vascular barriers of the CNS and brain tumors; 3) nonselective expression of the transgene; and 4) in situ CNS regulation of the transgene expression in a therapeutically controlled manner, as imposed by the course and phenotype of the CNS disease.
Privacy transformations for databank systems (1973)

The term databank implies a centralized collection of data to which a number of users have access. A computerized databank system consists of the data files, the associated computer facility, a management structure, and a user community. Several classes of databank systems can be defined on the basis of the nature of the organization supported by the databank, and its activity; the nature of the data and its uses; and the structure of the associated computer facility. Such classifications have been discussed in detail elsewhere.
TRB2, a Mouse Tribbles Ortholog, Suppresses Adipocyte Differentiation by Inhibiting AKT and C/EBPβ (2007)

Adipocyte differentiation is regulated by a complex array of extracellular signals, intracellular mediators and transcription factors. Here we describe suppression of adipocyte differentiation by TRBs, mammalian orthologs of Drosophila Tribbles. Whereas all the three TRBs were expressed in 3T3-L1 preadipocytes, TRB2 and TRB3, but not TRB1, were immediately down-regulated by differentiation stimuli. Forced expression of TRB2 and TRB3 inhibited adipocyte differentiation at an early stage. Akt activation is a key event in adipogenesis and was severely inhibited by TRB3 in 3T3-L1 cells. However, the inhibition by TRB2 was mild compared with severe inhibition by TRB3, though TRB2 suppressed adipogenesis as strongly as TRB3. Interestingly, TRB2 but not TRB3 reduced the level of C/EBPbeta, a transcription factor required for an early stage of adipogenesis, through a proteasome-dependent mechanism. Furthermore, knockdown of endogenous TRB2 by siRNA allowed 3T3-L1 cells to differentiate without full differentiation stimuli. These results suggest that inhibition of Akt activation in combination with degradation of C/EBPbeta is the basis for the strong inhibitory effect of TRB2 on adipogenesis.
Expression of vascular endothelial growth factor (VEGF)‐C and VEGF‐D, and their receptor VEGFR‐3, during different stages of cervical carcinogenesis (2003)

Cervical carcinogenesis has well-defined stages of disease progression including three grades of pre-invasive lesions--cervical intraepithelial neoplasia grades 1-3 (CIN 1-3)--and invasive cervical cancer. However, the biological properties of CIN lesions prone to develop invasive disease are not well defined. Recent observations suggest that early invasive disease spreads to regional lymph nodes in several tumour types and that growth factors (VEGF-C and VEGF-D) involved in new lymphatic vessel formation may play a crucial role in this process. The present study has assessed the expression of VEGF-C and VEGF-D, and their receptor VEGFR-3, in 152 cervical lesions (33 CIN 1, 33 CIN 2, 37 CIN 3, and 49 squamous cell carcinomas) to determine whether expression of lymphangiogenic factors occurs prior to invasion. The presence of lymphatic vessels was determined using LYVE-1 and podoplanin staining, as well as double immunostaining for LYVE-1/CD34 and podoplanin/CD34. In situ hybridization was performed to determine VEGFR-3 mRNA expression. A significant positive correlation was found between VEGF-C, VEGF-D, and VEGFR-3 expression through the different stages of cervical carcinogenesis. Significant differences in protein expression for VEGF-C, VEGF-D, and VEGFR-3 were found between CIN 1-2 and CIN 3 (p<0.001 for all), but not between CIN 3 and cervical cancer. More than 50% of the CIN 3 lesions showed moderate to strong staining for VEGF-C and VEGF-D, whereas most of the early pre-cancerous lesions (CIN 1 and 2) were negative. In cervical cancer, similar observations to those in CIN 3 were found. VEGFR-3 mRNA expression was found in the cytoplasm of epithelial neoplastic cells and VEGFR3 protein expression was found in more than 50% of CIN 3 lesions and cervical cancers, compared with 15% in CIN 1 and 2. These findings suggest an autocrine growth stimulation pattern via VEGFR-3. Adjacent CIN 3 was present in nine cervical cancers and displayed strong expression for VEGF-C, VEGF-D, and VEGFR-3. These results suggest that in cervical carcinogenesis a switch to the lymphangiogenic phenotype may occur at the stage of CIN 3.
Development and pharmacological characterization of a rat model of osteoarthritis pain (2004)

Osteoarthritis (OA) is an age-related joint disease characterized by degeneration of articular cartilage and is associated with chronic pain. Although several experimental models of OA have been employed to investigate the underlying etiologies of the disease, there has been relatively little investigation into development of animal models of OA to study the pain associated with the condition. In the present study, we investigated OA induced by injection of either iodoacetate or papain into the knee joint of rats, and assessed the joint degeneration with radiographic analyses and measured pain behavior using hind limb weight bearing. We found that injection of iodoacetate, but not papain, resulted in a chronic joint degeneration as measured by decreased bone mineral content and bone mineral density, necrosis of articular cartilage and osteophyte formation. These pathological changes were associated with pain that manifested as time- and concentration-dependent alterations in hind limb weight bearing. These alterations in hind limb weight bearing were reversed with morphine, but were not significantly affected by acute administration of either indomethacin or celecoxib. However, administration of 30 mg/kg celecoxib twice daily for 10 days resulted in a significant restoration of hind limb weight bearing. We conclude that the iodoacetate model of OA is a relevant animal model to study pain associated with OA, and can be used to test potential therapeutic agents.
Gesture Registration, Relaxation, and Reuse for Multi-Point Direct-Touch Surfaces (2006)

Freehand gestural interaction with direct-touch computation surfaces has been the focus of significant research activity. While many interesting gestural interaction techniques have been proposed, their design has been mostly ad-hoc and has not been presented within a constructive design framework. In this paper, we develop and articulate a set of design principles for constructing - in a systematic and extensible manner - multi-hand gestures on touch surfaces that can sense multiple points and shapes, and can also accommodate conventional point-based input. To illustrate the generality of these design principles, a set of bimanual continuous gestures that embody these principles are developed and explored within a prototype tabletop publishing application. We carried out a user evaluation to assess the usability of these gestures and use the results and observations to suggest future design guidelines.
Syntheses of 1‐Alkyl‐2‐(substituted‐2‐pyridyl)benzimidazoles. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
The link between infection and cancer: Tumor vasculature, free radicals, and drug delivery to tumors via the EPR effect (2013)

This review focuses primarily on my own research, including pathogenic mechanisms of microbial infection, vascular permeability in infection and tumors, and effects of nitric oxide (NO), superoxide anion radical (O₂⁻), and 8-nitroguanosine in the enhanced permeability and retention (EPR) effect for the tumor-selective delivery of macromolecular agents (nanomedicines). Infection-induced vascular permeability is mediated by activation of the kinin-generating protease cascade (kallikrein-kinin) triggered by exogenous microbial proteases. A similar mechanism operates in cancer tissues and in carcinomatosis of the pleural and peritoneal cavities. Infection also stimulates O₂⁻ generation via activation of xanthine oxidase while generating NO by inducing NO synthase. These chemicals function in mutation and carcinogenesis and promote inflammation, in which peroxynitrite (a product of O₂⁻ and NO) activates MMP, damages DNA and RNA, and regenerates 8-nitroguanosine and 8-oxoguanosine. We showed vascular permeability by using macromolecular drugs, which are not simply extravasated through the vascular wall into the tumor interstitium but remain there for prolonged periods. We thus discovered the EPR effect, which led to the rational development of tumor-selective delivery of polymer conjugates, micellar and liposomal drugs, and genes. Our styrene-maleic acid copolymer conjugated with neocarzinostatin was the first agent of its kind used to treat hepatoma. The EPR effect occurs not only because of defective vascular architecture but also through the generation of various vascular mediators such as kinin, NO, and vascular endothelial growth factor. Although most solid tumors, including human tumors, show the EPR effect, heterogeneity of tumor tissue may impede drug delivery. This review describes the barriers and countermeasures for improved drug delivery to tumors by using nanomedicines.
A nuclear juvenile hormone-binding protein from larvae of Manduca sexta: a putative receptor for the metamorphic action of juvenile hormone. (1994)

A 29-kDa nuclear juvenile hormone (JH)-binding protein from the epidermis of Manduca sexta larvae was purified by using the photoaffinity analog for JH II ([3H]epoxyhomofarnesyldiazoacetate) and partially sequenced. A 1.1-kb cDNA was isolated by using degenerate oligonucleotide primers for PCR based on these sequences. The cDNA encoded a 262-amino acid protein that showed no similarity with other known proteins, except for short stretches of the interphotoreceptor retinoid-binding protein, rhodopsin, and human nuclear protein p68. Recombinant baculovirus containing this cDNA made a 29-kDa protein that was covalently modified by [3H]epoxyhomofarnesyldiazoacetate and specifically bound the natural enantiomer of JH I (Kd = 10.7 nM). This binding was inhibited by the natural JHs but not by methoprene. Immunocytochemical analysis showed localization of this 29-kDa protein to epidermal nuclei. Both mRNA and protein are present during the intermolt periods; during the larval molt, the mRNA disappears but the protein persists. Later when cells become pupally committed, both the mRNA and protein disappear with a transient reappearance near pupal ecdysis. The properties of this protein are consistent with its being the receptor necessary for the antimetamorphic effects of JH.
Bending losses in hollow and dielectric tube leaky waveguides (1981)

A general method is presented of evaluating bending losses in hollow-core waveguides; analytic expressions are obtained for metallic hollow, dielectric hollow, and tube leaky waveguides on the basis of the 2-D slab waveguide model. Numerical examples are given for waveguides made of different kinds of metals, oxide, and dielectric materials at 10.6 microm. It is shown that the dielectric tube leaky waveguide can be bent with a small bending radius compared with a metallic hollow waveguide when the guide material is appropriately selected.
Rethinking Automatic Chord Recognition with Convolutional Neural Networks (2012)

Despite early success in automatic chord recognition, recent efforts are yielding diminishing returns while basically iterating over the same fundamental approach. Here, we abandon typical conventions and adopt a different perspective of the problem, where several seconds of pitch spectra are classified directly by a convolutional neural network. Using labeled data to train the system in a supervised manner, we achieve state of the art performance through this initial effort in an otherwise unexplored area. Subsequent error analysis provides insight into potential areas of improvement, and this approach to chord recognition shows promise for future harmonic analysis systems.
Pixelation effect removal from fiber bundle probe based optical coherence tomography imaging (2010)

A method of eliminating pixelization effect from en face optical coherence tomography (OCT) image when a fiber bundle is used as an OCT imaging probe is presented. We have demonstrated that applying a histogram equalization process before performing a weighted-averaged Gaussian smoothing filter to the original lower gray level intensity based image not only removes the structural artifact of the bundle but also enhances the image quality with minimum blurring of object's image features. The measured contrast-to-noise ratio (CNR) for an image of the US Air Force test target was 14.7dB (4.9dB), after (before) image processing. In addition, by performing the spatial frequency analysis based on two-dimensional discrete Fourier transform (2-D DFT), we were able to observe that the periodic intensity peaks induced by the regularly arrayed structure of the fiber bundle can be efficiently suppressed by 41.0dB for the first nearby side lobe as well as to obtain the precise physical spacing information of the fiber grid. The proposed combined method can also be used as a straight forward image processing tool for any imaging system utilizing fiber bundle as a high-resolution imager.
Biosensor analysis of the interleukin‐2 receptor complex (1999)

Surface plasmon resonance (SPR) biosensor technology has been a significant addition to the evolution and refinement of methods to study macromolecular interactions. Prior to the advent of SPR, we employed a variety of biochemical and biological techniques to study the interleukin-2/interleukin-2 receptor system (IL-2/IL-2R). By combining site-directed mutagenesis, equilibrium and kinetic radioligand binding, and competitive biological assays, we and others had begun to understand many aspects of the structure–activity relationships of the IL-2/IL-2R system. Due to the complexity of the IL-2R, cell-based assays proved limited in their ability to provide quantitative information on the binding characteristics of subclasses of the IL-2 receptor. SPR technology promised to be a new and powerful approach to the quantitative analysis of complex receptor systems. To demonstrate the feasibility of this technology, we employed Biacore® analysis to investigate the ligand binding characteristics of novel, pre-assembled, IL-2R coiled-coil complexes. The results of these studies, although limited by instrumentation and data analysis, clearly established the utility of this method. Subsequently, by incorporating advancements in both of these areas, we have been able to carry out detailed kinetic analyses of the binding properties of individual IL-2R subunits as well as heteromeric complexes on the surface of a biosensor. Therefore, SPR biosensor analysis combined with other established analytical methods has proven to be a powerful tool for the analysis of complex hematopoietic receptor systems. Published in 1999 by John Wiley & Sons, Ltd.
Excited State Symmetry Assignment Through Polarized Two-Photon Absorption Studies of Fluids (1971)

We consider the effect of molecular symmetry on the two-photon absorption constants of a randomly oriented sample of molecules. It is shown that a complete polarization study of an allowed two-photon transition of a fluid generally yields enough information to permit an unequivocal identification of the symmetry species of the excited state. Ambiguities occur in only a few cases. Thus, oriented molecule studies for symmetry assignment will be largely unnecessary in two-photon molecular spectroscopy. Symmetry assignment rules are given for all of the 32 crystallographic point groups and for the two groups of linear molecules. It is shown that certain transitions, which are allowed for two photons of different energies, are forbidden for two photons of the same energy. The application of this formalism to Raman scattering problems is discussed.
Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis (1999)

Tumour cells exposed to hypoxia have been shown to up-regulate the expression of vascular endothelial growth factor (VEGF). The purpose of the present work was to investigate whether hypoxia-induced VEGF up-regulation can result in increased metastatic efficiency of human melanoma cells. Two melanoma lines, one showing high (A-07) and the other showing low (D-12) VEGF secretion under aerobic conditions, were included in the study. Cell cultures were exposed to hypoxia (oxygen concentrations < 10 ppm) in vitro and metastatic efficiency, i.e. lung colonization efficiency, as well as transplantability and angiogenic potential were assessed in BALB/c-nu/nu mice Both cell lines showed significantly increased VEGF secretion under hypoxic conditions as measured by enzyme-linked immunosorbent assay The D-12 cells showed increased metastatic efficiency, transplantability and angiogenic potential following exposure to hypoxia. The metastatic efficiency increased with the duration of the hypoxia treatment and decreased with the time after reoxygenation. The A-07 cells on the other hand showed unchanged metastatic efficiency, transplantability and angiogenic potential following exposure to hypoxia. Both cell lines showed significantly decreased metastatic efficiency and angiogenic potential in mice treated with neutralizing antibody against VEGF. These results suggest that (a) VEGF is a limiting factor for the rate of angiogenesis in low but not in high VEGF-expressing melanomas under normoxic conditions and (b) transient hypoxia might promote the development of metastases in low VEGF-expressing melanomas by upregulating the expression of VEGF and hence enhancing the angiogenic potential of the tumour cells.
Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. (1985)

Recombinant human tumor necrosis factor (TNF) was found to enhance the adherence of human peripheral blood neutrophils to human umbilical vein endothelial (HUVE) cell monolayers in vitro. The enhancement was due to the effects both on neutrophils and HUVE cells. The effect on neutrophils was maximally induced within 5 min and did not require protein or RNA synthesis. By contrast, maximal effects on HUVE cells took 4 hr to develop and required de novo protein and RNA synthesis; however, exposure of HUVE cells to TNF for as little as 5 min was sufficient to initiate changes leading to maximal adherence of neutrophils at 4 hr. Both the effect on neutrophils and that on HUVE cells were blocked by a monoclonal antibody against TNF. TNF also rapidly induced an increased surface expression of neutrophil antigens recognized by monoclonal antibodies directed against epitopes of a glycoprotein required for optimum adherence and for complement component C3bi receptor (CR3) function. Thus, the mechanism of action of TNF may involve the regulation of expression of cell surface molecules. Our observations show that TNF induces a process central to the development of all inflammatory reactions and that both blood neutrophils and endothelial cells are targets of TNF action. The regulation of inflammatory reactions by TNF or antagonists of TNF has wide-ranging clinical implications.
Field Development of Resistance to Bacillus thuringiensis in Diamondback Moth (Lepidoptera: Plutellidae) (1990)

Foliar applications of commercial formulations of the insecticidal spore-crystal protein complex of Bacillus thuringiensis subsp. kUTstaki caused development of resistance in field populations of a major lepidopteran pest of vegetables, diamondback moth, Plutella xylostella (L.). Laboratory bioassays of larvae showed that the LC"" and LC for a field population of diamondback moth treated repeatedly with B. thuTingiensis were 25 to 33 times greater than the respective LC",,'sand LC's for two susceptible laboratory colonies. Mortality at the field rate of B. thuTingiensis was 34-35% in two resistant populations compared with 90-100% in two susceptible laboratory colonies. The results suggest that the potential for resistance development in pest populations is an important consideration for deployment of B. thuTingiensis toxin genes in genetically-engineered crop plants and use of B. thuringiensis in related tactics.