gebhart/patrepeval huggingface dataset:
VEGF165 mediates glomerular endothelial repair (1999)

VEGF 165 , the most abundant isoform in man, is an angiogenic cytokine that also regulates vascular permeability. Its function in the renal glomerulus, where it is expressed in visceral epithelial and mesangial cells, is unknown. To assess the role of VEGF 165 in glomerular disease, we administered a novel antagonist -a high-affinity, nuclease-resistant RNA aptamer coupled to 40-kDa polyethylene glycol (PEG) -to normal rats and to rats with mesangioproliferative nephritis, passive Heymann nephritis (PHN), or puromycin aminonucleoside nephrosis (PAN). In normal rats, antagonism of VEGF 165 for 21 days failed to induce glomerular pathology or proteinuria. In rats with mesangioproliferative nephritis, the VEGF 165 aptamer (but not a sequence-scrambled control RNA or PEG alone) led to a reduction of glomerular endothelial regeneration and an increase in endothelial cell death, provoking an 8-fold increase in the frequency of glomerular microaneurysms by day 6. In contrast, early leukocyte influx and the proliferation, activation, and matrix accumulation of mesangial cells were not affected in these rats. In rats with PHN or PAN, administration of the VEGF 165 aptamer did not influence the course of proteinuria using various dosages and administration routes. These data identify VEGF 165 as a factor of central importance for endothelial cell survival and repair in glomerular disease, and point to a potentially novel way to influence the course of glomerular diseases characterized by endothelial cell damage, such as various glomerulonephritides, thrombotic microangiopathies, or renal transplant rejection.
Multisensor MELPe using parameter substitution (2004)

The estimation of speech parameters and the intelligibility of speech transmitted through low-rate coders, such as MELP (mixed excitation linear prediction), are severely degraded when there are high levels of acoustic noise in the speaking environment. The application of nonacoustic and nontraditional sensors, which are less sensitive to acoustic noise than the standard microphone, is being investigated as a means to address this problem. Sensors being investigated include the general electromagnetic motion sensor (GEMS) and the physiological microphone (P-mic). As an initial effort in this direction, a multisensor MELPe coder (MELP coder with the addition of a noise preprocessor) using parameter substitution has been developed, where pitch and voicing parameters are obtained from GEMS and P-Mic sensors, respectively, and the remaining parameters are obtained as usual from a standard acoustic microphone. This parameter substitution technique is shown to produce significant and promising DRT (diagnostic rhyme test) intelligibility improvements over the standard 2400 bps MELPe coder in several high-noise military environments. Further work is in progress aimed at utilizing the nontraditional sensors for additional intelligibility improvements and for more effective lower-rate coding in noise.
Lipid trafficking between the endoplasmic reticulum and the chloroplast (2006)

The photosynthetic (thylakoid) membrane of plants is one of the most extensive biological cell membrane systems found in Nature. It harbours the photosynthetic apparatus, which is essential to life on Earth as carbon dioxide is fixed and atmospheric oxygen released by photosynthesis. Lipid biosynthetic enzymes of different subcellular compartments participate in the biogenesis of the thylakoid membrane system. This process requires the extensive exchange of lipid precursors between the chloroplast and the ER (endoplasmic reticulum). The underlying lipid trafficking phenomena are not yet understood at the mechanistic level, but genetic mutants of the model plant Arabidopsis thaliana with disruptions in lipid trafficking between the ER and the chloroplast have recently become available. Their study has led to the identification of components of the lipid transfer machinery at the inner chloroplast envelope.
Specific Activation of the p38 Mitogen-activated Protein Kinase Signaling Pathway and Induction of Neurite Outgrowth in PC12 Cells by Bone Morphogenetic Protein-2 (1999)

Bone morphogenetic protein (BMP)-2 has the capacity to induce the neuronal differentiation of PC12 cells. Unlike nerve growth factor, however, BMP-2 failed to induce the activation of the 41-/43-kDa mitogen-activated protein (MAP) kinase pathway in these cells. In contrast, BMP-2 characteristically induced the sustained activation of the p38 MAP kinase pathway. Pretreatment of PC12 cells with SB203580 inhibited the BMP-2-induced neurite outgrowth formation in a dose-dependent manner; this inhibition coincided well with the ability of SB203580 to inihibit the BMP-2-induced activation of the p38 MAP kinase pathway. Overexpression in PC12 cells of wild-type MAP kinase kinase (MKK)-6 enhanced the BMP-2-induced activation of p38 MAP kinase, whose activation correlated well with the ability of these cells to induce neurite outgrowth in response to BMP-2. Transient expression of kinase-negative forms of MKK3/6 inhibited the formation of neurite outgrowth in response to BMP-2. Furthermore, expression of constitutively active forms of MKK3/6 induced neurite outgrowth without BMP-2 stimulation, and SB203580 inhibited this induction. These results clearly indicate that activation of the p38 MAP kinase pathway is necessary for BMP-2-induced neuronal differentiation of PC12 cells. Our results also suggest that activation of the p38 MAP kinase pathway alone can induce the neuronal differentiation of PC12 cells.
A polarization maintaining, dispersion managed, femtosecond figure-eight fiber laser (2006)

We demonstrate a polarization maintaining, figure-eight erbium-doped fiber laser with a dispersion managed cavity. The laser was passively modelocked and produced pulses that were de-chirped to 427 fs pulses outside the laser cavity. An intra-cavity amplitude modulator was used to initiate the pulses, but the modulator was turned off during femtosecond pulse operation.
The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation (2007)

The physiological regulation of the immune system encompasses comprehensive anti-inflammatory mechanisms that can be harnessed for the treatment of infectious and inflammatory disorders. Recent studies indicate that the vagal nerve, involved in control of heart rate, hormone secretion and gastrointestinal motility, is also an immunomodulator. In experimental models of inflammatory diseases, vagal nerve stimulation attenuates the production of proinflammatory cytokines and inhibits the inflammatory process. Acetylcholine, the principal neurotransmitter of the vagal nerve, controls immune cell functions via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). From a pharmacological perspective, nicotinic agonists are more efficient than acetylcholine at inhibiting the inflammatory signaling and the production of proinflammatory cytokines. This 'nicotinic anti-inflammatory pathway' may have clinical implications as treatment with nicotinic agonists can modulate the production of proinflammatory cytokines from immune cells. Nicotine has been tested in clinical trials as a treatment for inflammatory diseases such as ulcerative colitis, but the therapeutic potential of this mechanism is limited by the collateral toxicity of nicotine. Here, we review the recent advances that support the design of more specific receptor-selective nicotinic agonists that have anti-inflammatory effects while eluding its collateral toxicity.
The CD40–CD154 system in anti-infective host defense (1997)

Research in the past few years has documented significant advances in our understanding of the CD40-CD40 ligand (CD154) system in diverse immune functions. This system influences many T cell mediated inflammatory immune responses and effector functions, unmasking a previously unexpected role for CD40-CD154 in cell mediated immunity. Manipulation of CD154 in animal models of infection by the use of CD154-deficient mice or anti-CD154 antibodies has shown the importance of this system in the initiation of the inflammatory response, in the activation of antigen-presenting cells and in resistance to infections.
Genetic vaccination against the melanocyte lineage-specific antigen gp100 induces cytotoxic T lymphocyte-mediated tumor protection. (1998)

Melanocyte lineage-specific antigens, such as gp100, have been shown to induce both cellular and humoral immune responses against melanoma. Therefore, these antigens are potential targets for specific antimelanoma immunotherapy. A novel approach to induce both cellular and humoral immunity is genetic vaccination, the injection of antigen-encoding naked plasmid DNA. In a mouse model, we investigated whether genetic vaccination against the human gp100 antigen results in specific antitumor immunity. The results demonstrate that vaccinated mice were protected against a lethal challenge with syngeneic B16 melanoma-expressing human gp100, but not control-transfected B16. Both cytotoxic T cells and IgG specific for human gp100 could be detected in human gp100-vaccinated mice. However, only adoptive transfer of spleen-derived lymphocytes, not of the serum, isolated from protected mice was able to transfer antitumor immunity to nonvaccinated recipients, indicating that CTLs are the predominant effector cells. CTI, lines generated from human gp100-vaccinated mice specifically recognized human gp100. Interestingly, one of the CTL lines cross-reacted between human and mouse gp100, indicating the recognition of a conserved epitope. However, these CTLs did not appear to be involved in the observed tumor protection. Collectively, our results indicate that genetic vaccination can result in a potent antitumor response in vivo and constitutes a potential immunotherapeutic strategy to fight cancer.
Modulation of Antigen‐Antibody Complexations by Immunoglobulins (1995)

In this investigation, the modulating effects of non-immune human IgG and rheumatoid factors (RFs) on antigen-antibody complexations were studied. Non-immune human IgG, as well as RF, were found to inhibit the binding of antigen to specific antibodies of both human and rabbit origin. In addition, human immunoglobulins were also able to modify the composition of preformed antigen-antibody complexes. The effects were detected by immunological methods in two different antigen-antibody systems (human serum albumin-rabbit anti-HSA and tetanus toxoid-human anti-TT). Changes in biological activities could be followed by employing enzymes (glucose-6-phosphate dehydrogenase and human placental alkaline phosphatase) as antigens. The outcome of the effects was found to be dependent on the ratio of antigen to antibody, the antigen-binding properties of the antibody and its origin, and on the properties of the immunoglobulins added. The observed changes could not be explained only by the presence of specific antibodies in the immunoglobulin preparations. The ability of immunoglobulins to modulate antigen-antibody complexations may provide a rationale for the large amounts of non-specific immunoglobulins in the circulation by preventing premature precipitation and promoting the elimination of antigenic molecules.
Development and Characterization of Recombinant Adenoviruses Encoding Human p53 for Gene Therapy of Cancer (1994)

We have constructed recombinant human adenoviruses that express wild-type human p53 under the control of either the Ad 2 major late promoter (MLP) or the human cytomegalovirus (CMV) immediate early gene promoter. Each construct replaces the Ad 5 E1a and E1b coding sequences necessary for viral replication with the p53 cDNA and MLP or CMV promoter. These p53/Ad recombinants are able to express p53 protein in a dose-dependent manner in infected human cancer cells. Tumor suppressor activity of the expressed p53 protein was assayed by several methods. [3H]Thymidine incorporation assays showed that the recombinant adenoviruses were capable of inhibiting DNA synthesis in a p53-specific, dose-dependent fashion. Ex vivo treatment of Saos-2 tumor cells, followed by injection of the treated cells into nude mice, led to complete tumor suppression using the MLP/p53 recombinant. Following a single injection of CMV/p53 recombinant adenovirus into the peritumoral space surrounding an in vivo established tumor derived from a human small cell lung carcinoma cell line (NIH-H69), we were able to detect p53 mRNA in the tumors at 2 and 7 days post-injection. Continued treatment of established H69 tumors with MLP/p53 recombinant led to reduced tumor growth and increased survival time compared to control treated animals. These results indicate that recombinant adenoviruses expressing wild-type p53 may be useful vectors for gene therapy of human cancer.
Inhibition of erbB receptor (HER) tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer. (2001)

It has been proposed that binding of ligand to the estrogen receptor (ER) releases its association with transcriptional corepressors, allowing the ER to recruit coactivators, which possess histone acetylase activity, and induce transcription of gene promoters containing estrogen response elements. It has also been proposed that the antiestrogen tamoxifen recruits transcriptional corepressors to the AF-2 region of the hormone-binding domain of the ER, thus blocking ER-mediated transcription. The ER cross-talks with a number of mitogenic signaling pathways and second messengers, like the epidermal growth factor receptor, the insulin-like growth factor-I receptor, mitogen-activated protein (MAP) kinase, phosphatidylinositol-3 kinase/Akt, dopamine, and cyclic AMP. Some of these molecules may: (a) support ligand-independent ER transcription; (b) increase the association of ER with coactivators of transcription; and/or (c) reduce the antiestrogen-induced association of ER with corepressors. These events either alone or in combination may result in hormone independence and/or antiestrogen resistance. We have examined whether signaling by HER2/neu (erbB-2) receptor tyrosine kinase, which can induce antiestrogen resistance, can also disrupt the tamoxifen-induced interaction of ER with transcriptional corepressors. Notably, tamoxifen-induced association of ER with the transcriptional corepressors N-CoR or SMRT was reduced in HER2-overexpressing breast tumor cells but not in cells with low HER2 levels. Small molecule inhibitors of the HER2 kinase or MAP extracellular signal-regulated kinase 1/2 or dominant-negative MAP extracellular signal-regulated kinase 1/2 constructs restored the inhibitory effect of tamoxifen on both ER-mediated transcription and tumor cell proliferation. Treatment with both tamoxifen and the small molecule HER1/2 kinase inhibitor AG1478 reduced mitogen-activated protein kinase activity and markedly reduced growth of established MCF-7/HER2 xenografts in athymic nude mice. Similar results have been obtained with ZD1839 ("Iressa"), an epidermal growth factor receptor (HER1) tyrosine kinase inhibitor. Taken together, these data suggest that exogenous inhibitors of the HER-signaling network and other mitogenic pathways can abrogate or delay the emergence of antiestrogen resistance, thus providing an evaluable therapeutic strategy in human breast carcinoma.
Heat-transfer microstructures for integrated circuits (1984)

Abstract : The design of high-speed integrated circuits and systems is often constrained by thermal considerations. As late as 1981 it was authoritatively predicted that the maximum achievable power flux for liquid-cooled, densely-packed integrated circuits (ICs) would be about 20 W/sq cm. Convective heat-transfer theory indicates that well over 1000 W/sq cm can be compactly removed from ICs at normal operating temperatures, provided microscopic (e.g., 50-microns wide) extended-surface structures are used. The difficulty of constructing high-conductance, low-stress thermal interfaces between ICs and heat sinks suggests the use of an integral heat sink. Accordingly, IC microfabrication techniques were employed to design, fabricate, and test novel, ultracompact water-cooled, laminar-flow, optimized plate-fin and pin-fin heat sinks directly within standard-thickness silicon substrates. Worst-case thermal resistances as low as 0.083 deg C/W were measured from 1-sq cm thin-film resistors (e.g., a 108 deg C temperature rise at 1309 W), in good agreement with predictions. Further increases in heat transfer are achievable. The use of integral liquid-cooled heat sinks in multichip systems presents potential yield, reliability, cost and packaging problems. Attachment of unmodified ICs to micro-heat sinks seems a more attractive approach. A novel die-attachment technique has been developed which avoids the problems of conventional attachments. In this technique, a liquid partially fills an array of micron-wide repentant capillaries in the heat sink substrate, so that surface tension holds the polished back of an IC in intimate thermal contact with the heat sink. The bond is void-free, virtually stress-free, long-lived, and allows repeated detachment and replacement of ICs without damaging the heat sink substrate. The repentant grooves were fabricated by a novel process using electroless plating of nickel onto vertical silicon microgrooves.
Reversible Near-Infrared Light Directed Reflection in a Self-Organized Helical Superstructure Loaded with Upconversion Nanoparticles (2014)

Adding external, dynamic control to self-organized superstructures with desired functionalities is an important leap necessary in leveraging the fascinating molecular systems for applications. Here, the new light-driven chiral molecular switch and upconversion nanoparticles, doped in a liquid crystal media, were able to self-organize into an optically tunable helical superstructure. The resulting nanoparticle impregnated helical superstructure was found to exhibit unprecedented reversible near-infrared (NIR) light-guided tunable behavior only by modulating the excitation power density of a continuous-wave NIR laser (980 nm). Upon irradiation by the NIR laser at the high power density, the reflection wavelength of the photonic superstructure red-shifted, whereas its reverse process occurred upon irradiation by the same laser but with the lower power density. Furthermore, reversible dynamic NIR-light-driven red, green, and blue reflections in a single thin film, achieved only by varying the power density of the NIR light, were for the first time demonstrated.
Ligand Effects on Optical Properties of CdSe Nanocrystals (2005)

We report effects of various organic and inorganic ligands on optical properties of CdSe nanocrystals (NCs) by changes in their photoluminescence and absorbance spectra. Surface ligand loss occurring during dilution and purification of solutions of CdSe NCs leads to a decrease of photoluminescence intensity. The complex of trioctylphosphine with Se atoms on the surface of CdSe NCs is found responsible for the trap emission band that is red-shifted relative to the photoluminescence band edge.
Clot contraction: compression of erythrocytes into tightly packed polyhedra and redistribution of platelets and fibrin (2013)

Contraction of blood clots is necessary for hemostasis and wound healing and to restore flow past obstructive thrombi, but little is known about the structure of contracted clots or the role of erythrocytes in contraction. We found that contracted blood clots develop a remarkable structure, with a meshwork of fibrin and platelet aggregates on the exterior of the clot and a close-packed, tessellated array of compressed polyhedral erythrocytes within. The same results were obtained after initiation of clotting with various activators and also with clots from reconstituted human blood and mouse blood. Such close-packed arrays of polyhedral erythrocytes, or polyhedrocytes, were also observed in human arterial thrombi taken from patients. The mechanical nature of this shape change was confirmed by polyhedrocyte formation from the forces of centrifugation of blood without clotting. Platelets (with their cytoskeletal motility proteins) and fibrin(ogen) (as the substrate bridging platelets for contraction) are required to generate the forces necessary to segregate platelets/fibrin from erythrocytes and to compress erythrocytes into a tightly packed array. These results demonstrate how contracted clots form an impermeable barrier important for hemostasis and wound healing and help explain how fibrinolysis is greatly retarded as clots contract.
Soft robotics (2008)

In this article, we gave an overview on the DLR activities related to two approaches for the realization of soft robotics: actively torque-controlled LWRs and VSA. On the basis of our experience with torque-controlled robots, we presented an analysis on expected advantages and also disadvantages of VSA actuators. Furthermore, two VSA joint designs motivated by this analysis were presented. Torque-controlled robots currently represent a technology mature enough for the market, but we believe that impressive research progress can be expected in the area of VSA-actuated robots in the next decade.
Über Pterinchemie. 65 Mitteilung [1]. Herstellung von (6 R, S)‐5,6,7,8‐Tetrahydro‐L‐biopterin, 7,8‐Dihydro‐L‐biopterin, L‐Sepiapterin, Deoxysepiapterin, (6 R, S)‐5,6‐Dihydrodeoxysepiapterin und 2′‐Deoxybiopterin (1978)

Preparation of (6 R , S )‐5,6,7,8‐tetrahydro‐ L ‐biopterine, 7,8‐dihydro‐ L ‐biopterine, L ‐sepiapterine, deoxysepiapterine, (6 R , S )‐5,6‐dihydrodeoxysepiapterine and 2′‐deoxybiopterine We describe the preparation of (6 R , S )‐5,6,7,8‐tetrahydro‐ L ‐biopterine (II) by catalytic‐ (reported in our short communication [2]) and natriumdithionite reduction of L ‐biopterine (I) and a preparation of 7,8‐dihydro‐ L ‐biopterine (IV) by treatment of L ‐biopterine (I) with natriumdithionite. Whereas oxidation of tetrahydrobiopterine II in the presence of oxygen leads to L ‐sepiapterine (III), dihydrobiopterine IV in acetic acid without oxygen gives deoxysepiapterine (VII), 5,6‐dihydro‐deoxysepiapterine (VI) and 2′‐deoxybiopterine (V) by a disproportionation reaction.
The Varkud satellite ribozyme (2004)

The VS ribozyme is the largest nucleolytic ribozyme, for which there is no crystal structure to date. The ribozyme consists of five helical sections, organized by two three-way junctions. The global structure has been determined by solution methods, particularly FRET. The substrate stem-loop binds into a cleft formed between two helices, while making a loop-loop contact with another section of the ribozyme. The scissile phosphate makes a close contact with an internal loop (the A730 loop), the probable active site of the ribozyme. This loop contains a particularly critical nucleotide A756. Most changes to this nucleotide lead to three-orders of magnitude slower cleavage, and the Watson-Crick edge is especially important. NAIM experiments indicate that a protonated base is required at this position for the ligation reaction. A756 is thus a strong candidate for nucleobase participation in the catalytic chemistry.