gebhart/patrepeval huggingface dataset:
IL-4 controls the selective endothelium-driven transmigration of eosinophils from allergic individuals (1992)

Abstract The mechanism leading to selective accumulation of eosinophils in allergic inflamed tissue is still unknown. In this article, transendothelial migration of circulating eosinophils from normal and allergic individuals is characterized by means of human umbilical vein endothelial cells cultivated on extracellular matrix from human fibroblasts. IL-4 pretreatment of these vascular constructs induced adherence and impressive layer penetration of eosinophils but not of neutrophils. For layer penetration, blood eosinophils from nonallergic donors needed in vitro priming by granulocyte/macrophage-CSF, IL-3, or IL-5. In contrast, freshly isolated blood eosinophils from a group of patients with atopic dermatitis spontaneously penetrated IL-4-activated vascular constructs. The here described selective pathway of eosinophil transmigration was 1) specifically induced by IL-4; 2) inhibited by the IL-4 specific, neutralizing mAb 8F12; and 3) dependent upon endothelial mRNA synthesis. Both eosinophil adherence and transmigration were present at an IL-4 concentration of 1 U/ml. The effect of endothelial preincubation with IL-4 culminated at 16 h and persisted up to 48 h. A linear increase of subendothelial accumulating eosinophils was observed within 2 h, reaching almost 100% after 4 h of coincubation. From inhibition experiments using different mAb, we conclude that the integrins CD11a/CD18, CD11b/CD18, and very late Ag-4 (CDw49d/CD29) are involved in this selective pathway of eosinophil transmigration. Taken together, this study demonstrates a novel mechanism which allows in vitro or in vivo primed eosinophils to leave the vascular compartment without influencing emigration of neutrophils.
The effect of a synthetic 7‐thiaprostaglandin E1 derivative, TEI‐6122, on monocyte chemoattractant protein‐1 induced chemotaxis in THP‐1 cells (1995)

1 The ability of various prostaglandins (PGs) to inhibit monocyte chemotaxis induced by monocyte chemoattractant protein-1 (MCP-1) was investigated with a human monocytic leukaemia cell line, THP-1. Moreover, to investigate the mechanism of the inhibitory action of PGs the involvement of either intracellular adenosine 3': 5'-cyclic monosphosphate (cyclic AMP) accumulation or intracellular Ca2+ mobilization was studied. 2 TEI-6122, a synthetic 7-thia-PGE1 derivative, inhibited chemotaxis of THP-1 cells induced by MCP-1 with an IC50 of 1.5 pM. Its inhibitory activity was 1000 fold more than that of PGE1 and PGE2 (IC50 = 2.8 nM and 0.9 nM, respectively), which were more potent than other PGs such as PGA1, PGA2, PGF2 alpha and PGI2 (IC50 > or = 1 microM). 3 With respect to the effect on intracellular cyclic AMP accumulation in THP-1 cells, TEI-6122 was as potent as PGE1 and PGE2, which were approximately 100 to 1000 fold more potent than the other PGs such as PGA1, PGA2 and PGI2. The minimum concentration of TEI-6122 required to increase intracellular cyclic AMP accumulation in THP-1 cells was 1 nM. 4 TEI-6122 and PGE1 (4 microM) transiently increased intracellular calcium levels in THP-1 cells. When added prior to MCP-1, both PGs partially suppressed the increased in Ca2+ caused by this cytokine. There were no significant differences between the activity of TEI-6122 and PGE1 in either respect. 5 It is concluded that TEI-6122, a synthetic 7-thia-PGE1 derivative is a much more potent inhibitor of MCP-1-induced THP-1 cell chemotaxis than PGEI and PGE2 which are the best inhibitors among the natural PGs tested, while neither intracellular cyclic AMP accumulation nor effects on Ca2+ mobilization account for the extremely potent inhibitory activity of TEI-6122. Thus, either a novel PGE2 receptor (EPreceptor) or a novel intracellular signal transduction system may be involved in the extremely potent chemotaxis inhibitory activity of TEI-6122.
Solution-Phase Monitoring of the Structural Evolution of a Molybdenum Blue Nanoring (2012)

The inorganic host-guest complex Na(22){[Mo(VI)(36)O(112)(H(2)O)(16)]⊂[Mo(VI)(130)Mo(V)(20)O(442)(OH)(10)(H(2)O)(61)]}·180H(2)O ≡ {Mo(36)}⊂{Mo(150)}, compound 1, has been isolated in its solid crystalline state via unconventional synthesis in a custom flow reactor. Carrying out the reaction under controlled flow conditions selected for the generation of {Mo(36)}⊂{Mo(150)} as the major product, allowing it to be reproducibly isolated in a moderate yield, as opposed to traditional "one-pot" batch syntheses that typically lead to crystallization of the {Mo(36)} and {Mo(150)} species separately. Structural and spectroscopic studies of compound 1 and the archetypal Molybdenum Blue (MB) wheel, {Mo(150)}, identified compound 1 as a likely intermediate in the {Mo(36)} templated synthesis of MB wheels. Further evidence illustrating the template effect of {Mo(36)} to MB wheel synthesis was indicated by an increase in the yield and rate of production of {Mo(150)} as a direct result of the addition of preformed {Mo(36)} to the reaction mixture. Dynamic light scattering (DLS) techniques were also used to corroborate the mechanism of formation of the MB wheels through observation of the individual cluster species in solution. DLS measurement of the reaction solutions from which {Mo(36)} and {Mo(150)} crystallized gave particle size distribution curves averaging 1.9 and 3.9 nm, consistent with the dimensions of the discrete clusters, which allowed the use of size as a possible distinguishing feature of these key species in the reduced acidified molybdate solutions and to observe the templation of the MB wheel by {Mo(36)} directly.
Efficient Ex Vivo Engineering and Expansion of Highly Purified Human Hematopoietic Stem and Progenitor Cell Populations for Gene Therapy (2017)

Ex vivo gene therapy based on CD34<sup>+</sup> hematopoietic stem cells (HSCs) has shown promising results in clinical trials, but genetic engineering to high levels and in large scale remains challenging. We devised a sorting strategy that captures more than 90% of HSC activity in less than 10% of mobilized peripheral blood (mPB) CD34<sup>+</sup> cells, and modeled a transplantation protocol based on highly purified, genetically engineered HSCs co-infused with uncultured progenitor cells. Prostaglandin E<sub>2</sub> stimulation allowed near-complete transduction of HSCs with lentiviral vectors during a culture time of less than 38 hr, mitigating the negative impact of standard culture on progenitor cell function. Exploiting the pyrimidoindole derivative UM171, we show that transduced mPB CD34<sup>+</sup>CD38<sup>-</sup> cells with repopulating potential could be expanded ex vivo. Implementing these findings in clinical gene therapy protocols will improve the efficacy, safety, and sustainability of gene therapy and generate new opportunities in the field of gene editing.
Combination of multiple light paths in pulse oximetry: the finger ring example (2007)

When pulse oximetry is required at other body locations than the finger tip new strategies for optical setups and signal handling are required. In this paper we present a combination of short and long light paths that succeeded in resolving the problems associated to the development of a finger ring SpO2 sensor.
Effect of selective PKC isoform activation and inhibition on TNF‐α‐induced injury and apoptosis in human intestinal epithelial cells (2003)

(1) We have investigated the effects of specific PKC isoforms in TNF-alpha mediated cellular damage using a human intestinal cell line (SCBN). (2) TNF-alpha treatment induced a decrease in the extent of intestinal cellular viability as determined by a formazan-based assay and an increase in the apoptotic index as assessed by immunohistology. These changes in cellular integrity were found to be related to the degradation of I-kappaBalpha, mobilization of NF-kappaB and release of mitochondrial cytochrome c. (3) TNF-alpha treatment also induced the activation of selective PKC isoforms which were associated with the decrease in cellular viability and an increase of cellular apoptosis. (4) Nonselective PKC antagonists, such as GF109203X and Gö6976 as well as isoform-selective PKC-inhibiting peptides would reverse the cellular injury as well as reduce the degradation of I-kappaBalpha and mitochondrial cytochrome c release. These effects were most highly correlated with changes in PKCdelta and epsilon primarily. (5) Intestinal cellular injury could be induced by treating cells with agonists selective for PKCdelta and epsilon mainly. (6) In conclusion, this study has shown that TNF-alpha treatment can induce the activation of PKCdelta and epsilon in the human intestinal cell line, SCBN, and this response is closely associated with an increase in cellular damage and apoptosis. PKCdelta and epsilon primarily mediate the release of mitochondrial cytochrome c and degradation of I-kappaBalpha and hence mobilization of NF-kappaB, which are responsible for the pathway leading to cell injury.
Genetics of Endospore Formation in Bacillus subtilis (1986)

We have made rapid progress in recent years in identifying the genetic causes of many human diseases. However, despite this recent progress, our mechanistic understanding of these diseases is often incomplete. This is a problem because it limits our ...Read More
Prefrontal cortical minicolumn: from executive control to disrupted cognitive processing (2014)

The prefrontal cortex of the primate brain has a modular architecture based on the aggregation of neurons in minicolumnar arrangements having afferent and efferent connections distributed across many brain regions to represent, select and/or maintain behavioural goals and executive commands. Prefrontal cortical microcircuits are assumed to play a key role in the perception to action cycle that integrates relevant information about environment, and then selects and enacts behavioural responses. Thus, neurons within the interlaminar microcircuits participate in various functional states requiring the integration of signals across cortical layers and the selection of executive variables. Recent research suggests that executive abilities emerge from cortico-cortical interactions between interlaminar prefrontal cortical microcircuits, whereas their disruption is involved in a broad spectrum of neurologic and psychiatric disorders such as autism, schizophrenia, Alzheimer's and drug addiction. The focus of this review is on the structural, functional and pathological approaches involving cortical minicolumns. Based on recent technological progress it has been demonstrated that microstimulation of infragranular cortical layers with patterns of microcurrents derived from supragranular layers led to an increase in cognitive performance. This suggests that interlaminar prefrontal cortical microcircuits are playing a causal role in improving cognitive performance. An important reason for the new interest in cortical modularity comes from both the impressive progress in understanding anatomical, physiological and pathological facets of cortical microcircuits and the promise of neural prosthetics for patients with neurological and psychiatric disorders.
Molecular and Functional Characterization of the Melastatin-related Cation Channel TRPM3 (2003)

Proteins of the mammalian TRP (transient receptor potential) family form a heterogenous group of cation channels important for cellular Ca2+ signaling and homeostasis. Here we present the full-length sequence of TRPM3, a member of the melastatin-like subfamily (TRPM) of TRP channels. TRPM3 expression was found in human kidney and brain. HEK293 cells transiently transfected with TRPM3 showed a constitutive Ca2+ and Mn2+ entry. Whole-cell patch clamp experiments confirmed the spontaneous activity of TRPM3 and revealed permeability ratios PCa/PNa of 1.57 and PNa/PCs of 0.75. In cell-attached patches, spontaneous inward and outward currents were observed. At negative membrane potentials and in the presence of either 140 mm Cs+, 140 mm Na+, or 100 mm Ca2+ in the pipette solution, the single channel conductance levels were 133, 83, and 65 pS, respectively. The Ca2+ entry in TRPM3-expressing HEK293 cells increased during treatment with hypotonic extracellular solution. The reduction of extracellular osmolarity was accompanied by cell swelling, suggesting volume-regulated activity of TRPM3. From its function and expression in human kidney, we propose a role of TRPM3 in renal Ca2+ homeostasis.
The extraordinary ligand binding properties of human serum albumin (2005)

Human serum albumin (HSA), the most prominent protein in plasma, binds different classes of ligands at multiple sites. HSA provides a depot for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders potential toxins harmless transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and acts as a NO-carrier. The globular domain structural organization of monomeric HSA is at the root of its allosteric properties which are reminiscent of those of multimeric proteins. Here, structural, functional, biotechnological, and biomedical aspects of ligand binding to HSA are summarized.
Optimal thermal design of air cooled forced convection finned heat sinks-experimental verification (1992)

D.B. Tuckerman and R.F.W. Pease (1981) showed that microchannels with water flow could be used to cool VLSI systems. Their work required the flow to be laminar, and the channel system, or fin array, was optimized analytically. Recently, it has been shown that, for some geometries and fluid pressure drops, a lower thermal resistance can be found if the channels are designed to allow turbulent flow. The current work uses the optimization scheme developed by R.W. Knight et al. (1991 and in this issue) to design three air-cooled aluminum finned arrays, which were built and tested experimentally. The thermal performances of the fin array designs, one containing 5 fins, one with 11 fins, and one with the predicted optimum of 8 fins, are compared. All arrays had turbulent flow and pressure drop across them, and all fins were the same length and width. The best thermal performance was obtained with the design predicted to be optimal. The scheme can be applied to a variety of heat sink design applications, including water-cooled microchannels.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Adaptive active contour algorithms for extracting and mapping thick curves (2002)

Two new adaptive active contour algorithms for the extraction and mapping of the skeleton of a thick curve are described. They are based on conditions which guarantee uniqueness and fidelity of the solution. Both algorithms modify the regularization constant K/sub o/ in an attempt to maintain convexity of the energy function while simultaneously improving the fidelity of the result. The first algorithm changes K/sub o/ over time while the second adapts K/sub o/ spatially. Both algorithms are evaluated on experiments with synthetic curves; both demonstrate an improved performance compared to a fixed-parameter active contour algorithm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Can the Sidewalls of Single-Wall Carbon Nanotubes Be Ozonized? (2002)

Ozonization of the sidewalls of single-wall carbon nanotubes (SWNT) has been investigated by means of 2-layered ONIOM(B3LYP/6-31G*:AM1) calculations. The theoretical calculations reveal that the 1,3-dipolar cycloaddition (1,3-DC) of ozone (O3) onto the sidewalls of a (5,5) carbon nanotube is site-selective and facile with a small activation barrier of 1.4 kcal/mol. The desorption of ozone from the thus-formed ozonide was found to be favorable over the decomposition process that gives rise to epoxy adduct and O2 upon thermal activation. This work implies the possibility of functionalizing the sidewalls of SWNTs by means of 1,3-dipolar cycloadditions of 1,3-dipolar molecules.
Prodomains of Transforming Growth Factor β (TGFβ) Superfamily Members Specify Different Functions (2010)

The specific functions of the prodomains of TGFβ superfamily members are largely unknown. Interactions are known between prodomains of TGFβ-1-3 and latent TGFβ-binding proteins and between prodomains of BMP-2, -4, -7, and -10 and GDF-5 and fibrillins, raising the possibility that latent TGFβ-binding proteins and fibrillins may mediate interactions with all other prodomains of this superfamily. This possibility is tested in this study. Results show that the prodomain of BMP-5 interacts with the N-terminal regions of fibrillin-1 and -2 in a site similar to the binding sites for other bone morphogenetic proteins. However, in contrast, the prodomain of GDF-8 (myostatin) interacts with the glycosaminoglycan side chains of perlecan. The binding site for the GDF-8 prodomain is likely the heparan sulfate chain present on perlecan domain V. These results support and extend the emerging concept that TGFβ superfamily prodomains target their growth factor dimers to extracellular matrix macromolecules. In addition, biochemical studies of prodomain·growth factor complexes were performed to identify inactive complexes. For some members of the superfamily, the prodomain is noncovalently associated with its growth factor dimer in an inactive complex; for others, the prodomain·growth factor complex is active, even though the prodomain is noncovalently associated with its growth factor dimer. Results show that the BMP-10 prodomain, in contrast to BMP-4, -5, and -7 prodomains, can inhibit the bioactivity of the BMP-10 growth factor and suggest that the BMP-10 complex is like TGFβ and GDF-8 complexes, which can be activated by cleavage of the associated prodomain.
Design of High Frequency Integrated Analogue Filters (2002)

* Chapter 1: Architectures and design of OTA/gm-C filters * Chapter 2: The MOSFET-C technique * Chapter 3: Active filters using integrated inductors * Chapter 4: Log domain filters * Chapter 5: Low voltage techniques for switched-current filters * Chapter 6: Analogue adaptive filters * Chapter 7: On-chip automatic tuning of filters
Interactive privacy via the median mechanism (2010)

We define a new interactive differentially private mechanism --- the median mechanism --- for answering arbitrary predicate queries that arrive online. Given fixed accuracy and privacy constraints, this mechanism can answer exponentially more queries than the previously best known interactive privacy mechanism (the Laplace mechanism, which independently perturbs each query result). With respect to the number of queries, our guarantee is close to the best possible, even for non-interactive privacy mechanisms. Conceptually, the median mechanism is the first privacy mechanism capable of identifying and exploiting correlations among queries in an interactive setting.
T-Helper 1-Type Immunity to Trophoblast in Women With Recurrent Spontaneous Abortion (1995)

Whereas TH1-type immunity to trophoblast is associated with URA and may play a role in reproductive failure, TH2-type immunity may be a natural response to trophoblast contributing to successful pregnancy.
Two Distinct Pathways of Immuno-Modulation Improve Potency of p53 Immunization in Rejecting Established Tumors (2004)

The p53 gene product is overexpressed by almost 50% of cancers, making it an ideal target for cancer immunotherapy. We previously demonstrated rejection of established p53-overexpressing tumors without stimulating autoimmunity by immunization with modified vaccinia Ankara-expressing murine p53 (MVAp53). Tumor rejection was enhanced through antibody-mediated CTL-associated antigen 4 (CTLA-4) blockade. We examined the role of synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine-phosphate-guanine (CpG) motifs (CpG ODN) in enhancing MVAp53-mediated tumor rejection. CpG ODN with MVAp53 resulted in tumor rejection in BALB/c mice bearing poorly immunogenic 11A-1 murine mammary carcinomas or Meth A sarcomas and C57Bl/6 mice bearing MC-38 colon carcinomas. The effect was similar to that seen in tumor-bearing mice treated with MVAp53 along with CTLA-4 blockade. Monoclonal antibody depletion experiments demonstrated that the adjuvant effects of CpG ODN and CTLA-4 blockades were CD8 dependent. CpG ODN were partially natural killer cell dependent and ineffective in Toll-like Receptor 9(-/-) and interleukin 6(-/-) mice, whereas CTLA-4 blockade was partially CD4 dependent and functional in Toll-like Receptor 9(-/-) and interleukin 6(-/-) mice. In addition, when administered with MVAp53, both adjuvants enhanced p53-specific cytotoxicity and demonstrated an additive effect when combined. The combination of CpG ODN and CTLA-4 blockade worked synergistically to reject palpable 11A-1 and MC-38 tumors. These experiments demonstrate the potential for augmenting MVAp53-mediated antitumor immunity using CpG ODN and CTLA-4 blockade. This cell-free immunotherapy approach is a candidate for evaluation in cancer patients.
Recognition and Ubiquitination of Notch by Itch, a Hect-type E3 Ubiquitin Ligase (2000)

Genetic studies identified Itch, which is a homologous to the E6-associated protein carboxyl terminus (Hect) domain-containing E3 ubiquitin-protein ligase that is disrupted in non-agouti lethal mice or Itchy mice. Itch-deficiency results in abnormal immune responses and constant itching in the skin. Here, Itch was shown to associate with Notch, a protein involved in cell fate decision in many mammalian cell types, including cells in the immune system. Itch binds to the N-terminal portion of the Notch intracellular domain via its WW domains and promotes ubiquitination of Notch through its Hect ubiquitin ligase domain. Thus, Itch may participate in the regulation of immune responses by modifying Notch-mediated signaling.
Automated rapid seizure detection in the human ECoG (2002)

Summary form only given. Automated seizure detection with high specificity and sensitivity is a highly desirable but elusive goal. The failure to develop a reliable system despite decades of effort is due in part to the non-stationary and noise in the EEG/ECoG signals, as well as to the rudimentary mathematical treatment it has received. We have developed a method of automated seizure detection based on a combination of linear and nonlinear filtering techniques, including the discrete wavelet transform. To minimize noise, this method was first developed for intracranial signals, then later adapted to scalp recordings. Preliminary results indicate that this new method may be the fastest and most reliable to date. The generic algorithm has been tested on 5 patients and a total of 20 seizure segments and 7 interictal segments recorded form intracranial electrodes. We have also compared the method to expert visual analysis, performed through a review of polygraph tracings of the signals, and have found our method to be both fast and highly accurate. We are generally able to detect the electrographic seizure within a second of the time marked by the EEGer. The method is also highly adaptable-it automatically accounts for signal changes over time, and has a number of parameters which may be tuned to further improve accuracy for a given individual patient or for a particular signal or group of signals being monitored. The algorithm has been implemented and now allows real-time monitoring and detection on a 486/DX 33 MHz PC.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>