gebhart/patrepeval huggingface dataset:
Is Mortalin a Candidate Gene for T1DM ? (2004)

Mortalin has been found to be up-regulated by 2D-protein gel analysis in isolated rodent islets exposed to cytokines. In islets from two rat strains with different sensitivity to the toxic effects of cytokines we observed a significant difference in IL-1beta mediated mortalin expression. Constitutive over-expression of rat mortalin in NIH3T3 cells reduced cellular survival in accordance with mortalin being associated to cellular senescence. Hence we consider the gene encoding for mortalin at chromosome 5q31.1 a putative candidate gene in cytokine induced beta-cell destruction. We scanned the human mortalin gene for polymorphisms and identified three novel polymorphisms. Neither the SNPs individually nor as constructed haplotypes showed disease association tested by (E)TDT in a Danish type 1 diabetes (T1DM) population. Furthermore, we tested the D5S500 microsatelite located close to 5q31.1 without finding linkage to (T1DM). In conclusion, the functional data identifying a difference in mortalin expression in IL-1beta stimulated islets between two rat strains and over-expression of mortalin in NIH3T3 cells associated with decreased viability suggests a functional role for mortalin in cytokine mediated beta cell destruction; however, the identified polymorphisms did not reveal any association in the presence of linkage disequilibrium of mortalin to T1DM in the Danish population.
Modular approach to fabrication of three-dimensional microchannel systems in PDMS—application to sheath flow microchips (2001)

A modular approach to fabrication of three-dimensional microchannel systems in polydimethylsiloxane (PDMS) is presented. It is based on building blocks with microstructuring on up to three faces. The assembled 3D-microchip consists of three building blocks in two layers. For assembly of the bottom layer two building blocks are joined horizontally, whereby the side structuring of the first is sealed against the flat side surface of the other. This results in the formation of a vertical interconnection opening between the building blocks to supplement the microstructuring on the lower faces. The 3D microchannel system is completed by placing a third building block, with microstructuring only on its lower face, on top of the assembled layer. While plasma assisted bonding is used between the two building blocks of the bottom layer, inherent adhesion is sufficient between the layers and for attaching the assembled 3D-microchip to a substrate. This modular approach was applied to the fabrication of a 3D-sheath flow microchip. It comprises a 20 microm deep microchannel system with sample inlet, open sensing area and outlet in the bottom layer and sheath flow inlet in the top layer. 100 microM fluorescein at 6 microL min(-1) was used as sample flow and water at increasing flow rates as sheath flow. With ratios of sheath to sample flow up to 20:1 sample layers down to 1 microm thickness could be generated. Sample layer thickness was determined via volume detection on an epi-fluorescence microscope followed by image analysis.
Diagnostic potential of tumor DNA from ovarian cyst fluid (2016)

We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions.
Repair of critical size rat calvarial defects using extracellular matrix protein gels (1995)

In this study the authors examined the capacity of gels of reconstituted basement membrane, laminin, and type I collagen to mediate repair of critical size defects in rat calvaria. Although autografts are widely used to repair bone defects caused by trauma or surgical treatment of congenital malformations, neoplasms, and infections, an adequate quantity of graft is not always available. Allogenic bone is readily available, but its use is associated with an increased incidence of nonunion, fatigue fracture, and rejection. Biologically active, purified components of basement membranes, which have been shown to promote osteogenic differentiation and angiogenesis in vitro and type I collagen (the major constituent of bone extracellular matrix) can be formed into native isotonic space-filling gels. In this study critical size calvarial defects were created in retired male Sprague-Dawley rats. Thirty-six animals were divided into seven groups. Group 1 (control) received no treatment for the defects. Group 2 animals were implanted with methylcellulose. Groups 3, 4, 5, and 6 were implanted with gels of type I collagen, reconstituted basement membrane, or laminin, respectively. The last group of three animals (Group 7) was implanted with 100 micrograms of type I collagen gels (identical to Group 3) and sacrificed at 20 weeks following a single CT scan to determine if complete healing could be obtained with this method given sufficient time. Except for rats in the type I collagen group that was evaluated by multiple computerized tomography (CT) scans biweekly from 2 to 12 weeks, bone repair was evaluated using CT at 12 weeks. Healing was quantified using three-dimensional reconstruction of CT. Following the final CT scan in each experimental group, animals were sacrificed, and a sample of tissues was evaluated by conventional histology. Animals treated with type I collagen gels showed 87.5% repair of the area of the defects at 12 weeks and 92.5% repair by 20 weeks. Increasing the gel volume 1.5 x accelerated complete repair to 3 months. Murine-reconstituted basement membrane and laminin gels induced 55.5% and 46.3% repair, respectively, at 3 months. In untreated control animals 7% repair of the area of the defects showed at 3 months. Histological analysis confirmed new bone formation in partial and completely healed defects. Bioengineered native collagen gels may have wide applicability for bone repair as an alternative bone graft material alone, in combination with autograft or marrow aspirate, or as a delivery system for osteogenic growth factors.
Algorithmic level low-power VLSI design applied to the RGB to HSI conversion (2001)

In the early 90s the first portable computing applications became widely available. At this time, lower performance than the mains dependant counterparts was accepted. However, today user demand small lightweight portable systems with long battery operating times without any compromise in computing performance. To meet these customer demands, a consequent low power approach has to be taken starting at the first design decision. This paper will present the implementation of a low-power real-time image processing circuit for the transformation of a camera signal into the human perception code.
The use of rituximab in the treatment of malignant and nonmalignant plasma cell disorders. (2000)

CD20 is a B-cell-restricted antigen that, for the most part, is expressed from the pre-B-cell to the mature B-cell stage of B-cell differentiation. Several transcription factors regulate CD20 expression during B-cell differentiation, the most important of which appear to be PU.1 and Pip (PU.1 interacting protein). As B cells differentiate to plasma cells, CD20 expression is down-regulated, which coincides with PU.1 downregulation in plasma cells. Analogous to their normal B-cell counterparts, CD20 is expressed on malignant lymphoplasmacytic cells from most patients with Waldenstrom's macroglobulinemia and on malignant plasma cells from a fraction (20%) of multiple myeloma patients. CD20 also is expressed on subpopulations of normal donor plasma cells, which may include autoantibody-secreting plasmacytes. In view of these findings, the anti-CD20 chimeric monoclonal antibody, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA), has been evaluated in the treatment of Waldenstrom's macroglobulinemia and multiple myeloma, as well as in nonmalignant plasma cell disorders including IgM polyneuropathies, immune thrombocytopenias, and autoimmune hemolytic anemias, with reported activity in these entities. An update of these clinical efforts is presented in this report.
Nerve growth factor: two receptors, multiple functions (1998)

Nerve growth factor (NGF) was characterized over 4 decades ago, and like the other neurotrophins subsequently discovered, it is best known for its trophic role, including the prevention of programmed cell death in specific populations of neurones in the peripheral nervous system. This property can be accounted for by the activation of a tyrosine kinase receptor. NGF also regulates neuronal function, as illustrated by its role in pain and inflammation, and in synaptic plasticity. Finally, NGF recently was shown to activate the neurotrophin receptor p75 (p75NTR), a receptor with no intrinsic catalytic activity and with similarities to members of the tumor necrosis factor receptor family. During normal development, the activation of p75NTR by NGF actually kills cells in the central nervous system. One remarkable property of NGF is then that it controls cell numbers in opposite ways in the developing nervous system, a result of its unique ability to activate two different receptor types.
CTLA-1 and CTLA-3 serine esterase transcripts are detected mostly in cytotoxic T cells, but not only and not always. (1987)

We and other investigators previously reported the cloning of CTLA-1 (or CCP-1) and CTLA-3 (or H Factor) serine esterase-related transcripts preferentially expressed in cytolytic T lymphocytes. We extended the survey of the tissue specificity of these molecules. Two main sets of results were obtained. First, both CTLA-1 and CTLA-3 transcripts could be found in the various cytolytic T cells tested, although in widely different amounts, and in some cases just at the threshold of detection. Secondly, these transcripts were not found in most of the other cells tested, including in some natural cytotoxic cells and in activated cytotoxic macrophages; however, they could be detected in mast cells for CTLA-1 and in some noncytotoxic lymphocytes for CTLA-3. Thus, the CTLA-1 and CTLA-3 serine esterase products are most probably not required for macrophage or natural cytotoxicity; their presence cannot be taken as characteristic of cytotoxic T cells; and a discussion about their relevance to T cell-mediated cytotoxicity should take into account their widely different amounts from one cytotoxic T cell to another.
IL-13–induced airway mucus production is attenuated by MAPK13 inhibition (2012)

Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13-driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases.
The survival of brain transplants is enhanced by extracts from injured brain. (1984)

Fragments of rat embryo corpus striatum implanted into wound cavities in the cortex of neonatal rat hosts showed very poor survival when transplantation was performed immediately after the cavity was made. Consistent survival of the transplants was made possible by supplying the implant with extracts from the injured brain of neonatal rats. These extracts also supported in vitro survival of embryonic striatal neurons, suggesting that transplanted cells benefit from injury-induced neuronotrophic factors.
Scanning Polymeric Waveguide Design of a 2-D Display System (2008)

Many small-scale display systems used in head-mounted displays (HMDs) create planar images by beaming light from an optical fiber onto deflectable or rotating mirrors. This mirror-based approach has a critical limitation: the hardware of mirror scanners and grating deflectors must be significantly larger than the light beam diameter to avoid undesirable clipping or diffraction effects. Typically, attempting to reduce the size of a conventional display device reduces pixel count by loss of resolution or field-of-view (FOV) of the device. In this paper, we propose a HMD system utilizing a microfabricated 2D optical scanner controlled by a field-programmable gate array (FPGA) that overcomes the size limitations of other systems while maintaining high resolution.
Enzyme therapy for lysosomal acid lipase deficiency in the mouse (2001)

Lysosomal acid lipase (LAL) is the critical enzyme for the hydrolysis of the triglycerides (TG) and cholesteryl esters (CE) delivered to lysosomes. Its deficiency produces two human phenotypes, Wolman disease (WD) and cholesteryl ester storage disease (CESD). A targeted disruption of the LAL locus produced a null (lal( -/-)) mouse model that mimics human WD/CESD. The potential for enzyme therapy was tested using mannose terminated human LAL expressed in Pichia pastoris (phLAL), purified, and administered by tail vein injections to lal( -/-) mice. Mannose receptor (MR)-dependent uptake and lysosomal targeting of phLAL were evidenced ex vivo using competitive assays with MR-positive J774E cells, a murine monocyte/macrophage line, immunofluorescence and western blots. Following (bolus) IV injection, phLAL was detected in Kupffer cells, lung macrophages and intestinal macrophages in lal( -/-) mice. Two-month-old lal( -/-) mice received phLAL (1.5 U/dose) or saline injections once every 3 days for 30 days (10 doses). The treated lal( -/-) mice showed nearly complete resolution of hepatic yellow coloration; hepatic weight decreased by approximately 36% compared to PBS-treated lal( -/-) mice. Histologic analyses of numerous tissues from phLAL-treated mice showed reductions in macrophage lipid storage. TG and cholesterol levels decreased by approximately 50% in liver, 69% in spleen and 50% in small intestine. These studies provide feasibility for LAL enzyme therapy in human WD and CESD.
Investigation of Fly Ash and Activated Carbon Obtained from Pulverized Coal Boilers (2006)

One of the techniques for Hg capture in coal-fired boilers involves injection of activated carbon (AC) into the boiler downstream of the air preheater. Hg is adsorbed onto the AC particles and fly ash, which are then both removed in an electrostatic precipitator or baghouse. This project addressed the issues of Hg on activated carbon and on fly ash from a materials re-use point of view. It also addressed the possible connection between SCR reactors, fly ash properties and Hg capture. The project has determined the feasibility of separating AC from fly ash in a fluidized bed and of regenerating the separated AC by heating the AC to elevated temperatures in a fluidized bed. The temperatures needed to drive off the Hg from the ash in a fluidized bed have also been determined. Finally, samples of fly ash from power plants with SCR reactors for NO{sub x} control have been analyzed in an effort to determine the effects of SCR on the ash.
Synchronized cyclic capillary electrophores—a novel approach to ion separations in solution (1993)

Abstract A novel concept for repeated column switching in capillary electrophoresis is presented. Theoretical considerations predict high plate numbers per volt. Using micromachining techniques, a planar glass structure has been fabricated, which contains four capillaries of 20 mm length arranged in a square. Laser fluorescence detection gave a cycle time of 70 s for 2.5 kV applied. After five cycles a theoretical plate number of 40,000 was reached.
Versatile Solid-Phase Synthesis of Trisubstituted 1H-Pyrido[2,3-d]pyrimidin-4-ones and Related Heterocycles (2004)

A solid-phase synthesis of trisubstituted 1H-pyrido[2,3-d]pyrimidin-4-ones has been developed. The synthesis utilizes solid-phase bound N-2,6-dichloronicotinoyl-1H-benzotriazole-1-carboximidamides as key intermediates. Sequential substitution of benzotriazole and the two chlorines furnishes the title compounds with regioselectivity and high purity. Application of the method to various disubstituted analogues is also demonstrated.
Functional Analysis of Polyphenol Oxidases by Antisense/Sense Technology (2007)

Polyphenol oxidases (PPOs) catalyze the oxidation of phenolics to quinones, the secondary reactions of which lead to oxidative browning and postharvest losses of many fruits and vegetables. PPOs are ubiquitous in angiosperms, are inducible by both biotic and abiotic stresses, and have been implicated in several physiological processes including plant defense against pathogens and insects, the Mehler reaction, photoreduction of molecular oxygen by PSI, regulation of plastidic oxygen levels, aurone biosynthesis and the phenylpropanoid pathway. Here we review experiments in which the roles of PPO in disease and insect resistance as well as in the Mehler reaction were investigated using transgenic tomato (Lycopersicon esculentum) plants with modified PPO expression levels (suppressed PPO and overexpressing PPO). These transgenic plants showed normal growth, development and reproduction under laboratory, growth chamber and greenhouse conditions. Antisense PPO expression dramatically increased susceptibility while PPO overexpression increased resistance of tomato plants to Pseudomonas syringae. Similarly, PPO-overexpressing transgenic plants showed an increase in resistance to various insects, including common cutworm (Spodoptera litura (F.)), cotton bollworm (Helicoverpa armigera (Hübner)) and beet army worm (Spodoptera exigua (Hübner)), whereas larvae feeding on plants with suppressed PPO activity had higher larval growth rates and consumed more foliage. Similar increases in weight gain, foliage consumption, and survival were also observed with Colorado potato beetles (Leptinotarsa decemlineata (Say)) feeding on antisense PPO transgenic tomatoes. The putative defensive mechanisms conferred by PPO and its interaction with other defense proteins are discussed. In addition, transgenic plants with suppressed PPO exhibited more favorable water relations and decreased photoinhibition compared to nontransformed controls and transgenic plants overexpressing PPO, suggesting that PPO may have a role in the development of plant water stress and potential for photoinhibition and photooxidative damage that may be unrelated to any effects on the Mehler reaction. These results substantiate the defensive role of PPO and suggest that manipulation of PPO activity in specific tissues has the potential to provide broad-spectrum resistance simultaneously to both disease and insect pests, however, effects of PPO on postharvest quality as well as water stress physiology should also be considered. In addition to the functional analysis of tomato PPO, the application of antisense/sense technology to decipher the functions of PPO in other plant species as well as for commercial uses are discussed.
Integrin Targeting for Tumor Optical Imaging (2011)

Optical imaging has emerged as a powerful modality for studying molecular recognitions and molecular imaging in a noninvasive, sensitive, and real-time way. Some advantages of optical imaging include cost-effectiveness, convenience, and non-ionization safety as well as complementation with other imaging modalities such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Over the past decade, considerable advances have been made in tumor optical imaging by targeting integrin receptors in preclinical studies. This review has emphasized the construction and evaluation of diverse integrin targeting agents for optical imaging of tumors in mouse models. They mainly include some near-infrared fluorescent dye-RGD peptide conjugates, their multivalent analogs, and nanoparticle conjugates for targeting integrin αvβ3. Some compounds targeting other integrin subtypes such as α4β1 and α3 for tumor optical imaging have also been included. Both in vitro and in vivo studies have revealed some promising integrin-targeting optical agents which have further enhanced our understanding of integrin expression and targeting in cancer biology as well as related anticancer drug discovery. Especially, some integrin-targeted multifunctional optical agents including nanoparticle-based optical agents can multiplex optical imaging with other imaging modalities and targeted therapy, serving as an attractive type of theranostics for simultaneous imaging and targeted therapy. Continued efforts to discover and develop novel, innovative integrin-based optical agents with improved targeting specificity and imaging sensitivity hold great promises for improving cancer early detection, diagnosis, and targeted therapy in clinic.
Selective Alpha-Particle Mediated Depletion of Tumor Vasculature with Vascular Normalization (2007)

The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy.
ELECTRO-OPTICAL SWITCHING CHARACTERISTICS OF VOLUME HOLOGRAMS IN POLYMER DISPERSED LIQUID CRYSTALS (1996)

Electrically switchable volume holograms lead to the possiblity of real-time electro-optical control of diffractive optic components. We report here on the development of a novel photopolymer-liquid crystal composite material system for writing in a fast single step, high diffraction efficiency volume holograms, capable of switching in applied electric fields of low voltage. Switching of a first-order Bragg diffracted beam into the zero-order with an applied field of ~10 V/µm was observed. With the addition of a surfactant to our pre-polymer syrup, we observed lowering of the switching fields to ~5 V/µm. We report response times for switching and relaxation in the order of microseconds. Low voltage, high resolution scanning electron microscopy studies show that the Bragg gratings formed consist of periodic polymer dispersed liquid crystal planes. The addition of surfactant leads to formation of very uniform small (20–40 nm) nematic droplets. A simple model based on the shape of the liquid crystal droplets was applied to explain the switching fields and response times.