gebhart/patrepeval huggingface dataset:
Mechanism of action of vitamin C in sepsis: Ascorbate modulates redox signaling in endothelium (2009)

Circulating levels of vitamin C (ascorbate) are low in patients with sepsis. Parenteral administration of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of sepsis, intravenous ascorbate injection increases survival and protects several microvascular functions, namely, capillary blood flow, microvascular permeability barrier, and arteriolar responsiveness to vasoconstrictors and vasodilators. The effects of parenteral ascorbate on microvascular function are both rapid and persistent. Ascorbate quickly accumulates in microvascular endothelial cells, scavenges reactive oxygen species, and acts through tetrahydrobiopterin to stimulate nitric oxide production by endothelial nitric oxide synthase. A major reason for the long duration of the improvement in microvascular function is that cells retain high levels of ascorbate, which alter redox-sensitive signaling pathways to diminish septic induction of NADPH oxidase and inducible nitric oxide synthase. These observations are consistent with the hypothesis that microvascular function in sepsis may be improved by parenteral administration of ascorbate as an adjuvant therapy.
Clinical pharmacology and toxicology of dichloroacetate. (1998)

Dichloroacetate (DCA) is a xenobiotic of interest to both environmental toxicologists and clinicians. The chemical is a product of water chlorination and of the metabolism of various drugs and industrial chemicals. Its accumulation in groundwater and at certain Superfund sites is considered a potential health hazard. However, concern about DCA toxicity is predicated mainly on data obtained in inbred rodent strains administered DCA at doses thousands of times higher than those to which humans are usually exposed. In these animals, chronic administration of DCA induces hepatotoxicity and neoplasia. Ironically, the DCA doses used in animal toxicology experiments are very similar to those used clinically for the chronic or acute treatment of several acquired or hereditary metabolic or cardiovascular diseases. As a medicinal, DCA is generally well tolerated and stimulates the activity of the mitochondrial pyruvate dehydrogenase enzyme complex, resulting in increased oxidation of glucose and lactate and an amelioration of lactic acidosis. By this mechanism, the drug may also enhance cellular energy metabolism. DCA is dehalogenated in vivo to monochloroacetate and glyoxylate, from which it can be further catabolized to glycolate, glycine, oxalate, and carbon dioxide. It remains to be determined whether important differences in its metabolism and toxicology exist in humans between environmentally and clinically relevant doses.
Biological Activity of Cloned Rat Endogenous C-type Virus DNA Transferred by Microinjection (1982)

The biological activity of a molecularly cloned DNA of a rat endogenous C-type leukaemia helper virus, RHHV, was assessed by intranuclear microinjection into normal rat kidney cells (NRK153). Release of rat C-type leukaemia helper viruses by the microinjected cells was examined by superinfection of Kirsten-transformed non-producer cells (K-NRK). Immediate release of helper leukaemia viruses at a very low level was observed only in the NRK153 m3 . 5/cir cells microinjected with the supercoiled form of RHHV DNA in toto, suggesting that the circular form of the virus DNA might have expedited the replication and expression of virus particles. Genome rescue experiments were also performed by co-cultivating the microinjected NRK153 m cells carrying various linear RHHV DNAs, in toto or of subgenomic sizes, with K-NRK cells. The results indicated that both the total and the 5.8 to 6.2 kb DNA fragment proximal to the 5' terminus of the cloned RHHV 8.8 kb DNA were able to rescue successfully a transforming replication-competent pseudotype virus. Subgenomic DNA fragments derived from the centre or the 3' end of the RHHV DNA were ineffective in the genome rescue experiments.
Lipid Digestion as a Trigger for Supersaturation: Evaluation of the Impact of Supersaturation Stabilization on the in Vitro and in Vivo Performance of Self-Emulsifying Drug Delivery Systems (2012)

The generation of supersaturation in the gastrointestinal (GI) tract is an increasingly popular means of promoting oral absorption for poorly water-soluble drugs. The current study examined the impact of changes to the quantities of medium-chain (MC) lipid (Captex 300:Capmul MCM), surfactant (Cremophor EL) and cosolvent (EtOH), and the addition of polymeric precipitation inhibitors (PPI), on supersaturation during the dispersion and digestion of MC self-emulsifying drug delivery systems (SEDDS) containing danazol. The data suggest that digestion acts as a "trigger" for enhanced supersaturation and that solubilization/precipitation behavior is correlated with the degree of supersaturation on dispersion (S(M)DISP) or digestion (S(M)DIGEST). The ability of the formulation to maintain solubilization in vitro decreased as the S(M) of the formulation increased. PPI significantly increased supersaturation stabilization and precipitation was inhibited where S(M)DISP < 3.5 and S(M)DIGEST < 4. In the presence of polymer, some degree of supersaturation was maintained up to S(M)DIGEST ∼ 8. Differentiation in the ability of SEDDS to maintain drug solubilization stems from the ability to stabilize supersaturation and for MC SEDDS, utilization of lower drug loads, higher surfactant levels (balanced against increases in S(M)DISP), lower cosolvent and the addition of PPI enhanced formulation performance. In vivo studies confirmed the ability of PPI to promote drug exposure at moderate drug loads (40% of saturated solubility in the formulation). At higher drug loads (80% saturation) and in lipid-free SEDDS, this effect was lost, suggesting that the ability of PPIs to stabilize supersaturation in vitro may, under some circumstances, overestimate utility in vivo.
Short Communication: Effects of Lactobacillus helveticus-Fermented Milk on the Differentiation of Cultured Normal Human Epidermal Keratinocytes (2006)

Effects of Lactobacillus helveticus-fermented milk whey on the differentiation of normal human epidermal keratinocytes were studied. Analysis using real-time reverse transcription-polymerase chain reaction revealed that addition of Lactobacillus helveticus-fermented milk whey to the culture medium enhanced mRNA expression of keratin 10, an early differentiation marker, as well as involucrin, a late differentiation marker. Whey of artificially acidified milk, prepared by the addition of dl-lactic acid to milk instead of fermentation, also promoted expression of both markers, but Lactobacillus helveticus-fermented milk whey was more effective in increasing expression of those markers. These results indicate that milk whey has the potential to induce multiple stages of keratinocyte differentiation and that fermentation with Lactobacillus helveticus increases that activity. Furthermore, we examined the expression of profilaggrin, which increases with epidermal terminal differentiation, and found that Lactobacillus helveticus-fermented milk whey enhanced expression of profilaggrin mRNA in a dose-dependent manner. Expression also occurred to a greater extent than with artificially acidified milk whey or other whey samples prepared with several lactic acid bacterial species. Because the proteolytically processed form of profilaggrin, filaggrin, is very important for normal epidermal hydration and flexibility, our results indicate that Lactobacillus helveticus-fermented milk whey has the potential to enhance the production of filaggrin-related natural moisturizing factor, because of its effect on the induction of epidermal differentiation, and is expected to be a useful skin moisturizing agent.
The stress-enhanced diffusion of boron in silicon (1978)

The stress effect on diffusion of impurities in the fabrication of silicon avalanche photodiodes was found when thick diffusion masks of SiO2 were used. The observation of the avalanche multiplication profile showed that nonuniform diffusion occurs over the window area of the mask. From the qualitative analysis, it is concluded that the diffusion coefficient is represented by the sum of the zero-stress term and the stress-induced term.
Comprehensive Analysis of Chemotactic Factors for Bone Marrow Mesenchymal Stem Cells (2007)

To understand which growth factors/cytokines can affect migration of mesenchymal stem cells (MSCs) to injured tissues, we compared the effects of many (26) growth factors/cytokines on the migration activity of rabbit and human MSCs using a microchemotaxis chamber. Among them, platelet-derived growth factor (PDGF)-BB, PDGF-AB, epidermal growth factor (EGF), HB-EGF, transforming growth factor (TGF-alpha), insulin growth factor (IGF-I), hepatocyte growth factor (HGF), fibroblast growth factor (FGF-2), and thrombin consistently enhanced the migration of rabbit and human MSCs at appropriate concentrations. PDGF-BB showed the greatest effect on migration. Various combinations of these factors further enhanced the migration of MSCs, whereas combinations of factors that shared common cell-surface receptors did not induce the additive stimulation. On the other hand, some combinations, including that of FGF-2 or thrombin with PDGF-BB, suppressed the migration activity of MSCs. These findings suggest that combinations of growth factors are important to eliciting the maximal chemotactic effect. The factors that induced the migration of MSCs also enhanced their proliferation, suggesting that migration and proliferation can take place simultaneously. The above factors were also effective in stimulating the migration of fibroblasts, but thrombin alone selectively enhanced the migration of MSCs, suggesting that thrombin is useful to stimulate migration of MSCs without migration of fibroblasts.
Identification of Protective Epitopes on Ebola Virus Glycoprotein at the Single Amino Acid Level by Using Recombinant Vesicular Stomatitis Viruses (2002)

Ebola virus causes lethal hemorrhagic fever in humans, but currently there are no effective vaccines or antiviral compounds for this infectious disease. Passive transfer of monoclonal antibodies (MAbs) protects mice from lethal Ebola virus infection (J. A. Wilson, M. Hevey, R. Bakken, S. Guest, M. Bray, A. L. Schmaljohn, and M. K. Hart, Science 287:1664-1666, 2000). However, the epitopes responsible for neutralization have been only partially characterized because some of the MAbs do not recognize the short synthetic peptides used for epitope mapping. To identify the amino acids recognized by neutralizing and protective antibodies, we generated a recombinant vesicular stomatitis virus (VSV) containing the Ebola virus glycoprotein-encoding gene instead of the VSV G protein-encoding gene and used it to select escape variants by growing it in the presence of a MAb (133/3.16 or 226/8.1) that neutralizes the infectivity of the virus. All three variants selected by MAb 133/3.16 contained a single amino acid substitution at amino acid position 549 in the GP2 subunit. By contrast, MAb 226/8.1 selected three different variants containing substitutions at positions 134, 194, and 199 in the GP1 subunit, suggesting that this antibody recognized a conformational epitope. Passive transfer of each of these MAbs completely protected mice from a lethal Ebola virus infection. These data indicate that neutralizing antibody cocktails for passive prophylaxis and therapy of Ebola hemorrhagic fever can reduce the possibility of the emergence of antigenic variants in infected individuals.
Assessing seizure dynamics by analysing the correlation structure of multichannel intracranial EEG (2006)

Epileptic seizures are commonly characterized as 'hypersynchronous states'. This habit is doubly misleading, because seizures are not necessarily synchronous and are not unchanging 'states' but dynamic processes. Here the temporal evolution of the correlation structure in the course of 100 focal onset seizures of 60 patients recorded by intracranial multichannel EEG was assessed. To this end a multivariate method was applied that at its core consists of computing the eigenvalue spectrum of the zero-lag correlation matrix of a short sliding window. Our results show that there are clearly observable and statistically significant changes of the correlation structure of focal onset seizures. Specifically, these changes indicate that the zero-lag correlation of multi-channel EEG either remains approximately unchanged or-especially in the case of secondary generalization-decreases during the first half of the seizures. Then correlation gradually increases again before the seizures terminate. This development was qualitatively independent of the anatomical location of the seizure onset zone and therefore seems to be a generic property of focal onset seizures. We suggest that the decorrelation of EEG activity is due to the different propagation times of locally synchronous ictal discharges from the seizure onset zone to other brain areas. Furthermore we speculate that the increase of correlation during the second half of the seizures may be causally related to seizure termination.
Parametric Photonic Channelized RF Receiver (2011)

A new class of photonic channelized radio-frequency (RF) receiver is proposed and demonstrated. The new device relies on generation of high fidelity signal copies by wavelength multicasting in a self-seeded, two-pump parametric mixer. Signal copying to widely spaced wavelengths enables channelization of the full RF bandwidth using a single periodic filter. The channelization uses freely tunable frequencies of newly generated copies and eliminates the need for construction of a dense, narrowband filter bank. The new concept is demonstrated by channelization of four subcarrier channels with 1-GHz spacing and greater than 20-dB extinction ratio between extracted channels.
Biofilms and Device-Related Infections (2014)

The study of bacterial biofilms is more advanced in the engineering field than in the medical field, but the simple realization that biofilms are involved in chronic infections opens the way for a massive transfer of valuable information from the engineering realm to the medical realm and for its application to the treatment of infectious diseases. Pseudomonas aeruginosa first came to the attention of biofilm microbiologists because it predominates in cold alpine streams and grows predominantly (99.99%) in biofilms in this natural habitat. The Center for Biofilm Engineering (CBE) has established the fact that most biofilms assume this microcolony and water channel structure, including all biofilms formed by the few grampositive species examined to date, and the most significant consequence of this new observation is that we must now explain how these elaborate structures are established and maintained. If we try to imagine the bacterial survival strategies that would have been effective in the earliest stages of the development of life on this planet, growth in stationary biofilms that were protected from unfavorable conditions would prevent bacteria from being swept into acid or boiling downstream pools and from surges of threatening water from upstream sources. The role of host defenses in controlling biofilm infections is discussed in the chapter. There is a growing conviction that antibiotics are losing their ability to control bacterial infections because the bacteria have mobilized all of their survival strategies in the face of this frontal attack.
Cumulant-based approach to harmonic retrieval and related problems (1991)

A frequently encountered problem in signal processing is that of estimating the frequencies and amplitudes of harmonics observed in additive colored Gaussian noise. In practice, the observed signals are contaminated with spatially and temporally colored noise of unknown power spectral density. A cumulant-based approach to these problems is proposed. The cumulants of complex processes are defined, and it is shown that specific 1-D slices of the fourth-order cumulant of the noisy signal for the direction of arrival (DOA) and retrieval of harmonics in noise (RHN) problems are identical to the autocorrelation of a related noiseless signal. Hence correlation-based high-resolution methods may be used with fourth-order cumulants as well. The effectiveness of the proposed methods is demonstrated through standard simulation examples.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Preparation of CdS Nanoparticles in Salt-Induced Block Copolymer Micelles (2001)

A novel preparation method of CdS nanoparticles with controllable size and stability is presented. Poly(styrene-block-2-vinylpyridine) (PS-b-P2VP) and cadmium ions form aggregates of single micelles called compound micelles, upon addition of the cadmium acetate salt into a solution of the block copolymer in tetrahydrofuran. The growth of CdS nanoparticles is confined to the core of single micelles after introduction of hydrogen sulfide gas into the solution. UV−visible spectroscopy, fluorescence spectroscopy, and transmission electron microscopy were employed to characterize the prepared nanoparticles. UV−visible absorption spectra show that larger nanoparticles are produced at lower 2VP:Cd2+ molar ratio. UV−visible absorption spectra and fluorescence spectra both indicate that with a decrease of block copolymer concentration in tetrahydrofuran, the size of the CdS nanoparticles decreases. The stability of the CdS nanoparticles and micelles was also investigated. UV−visible results show that the prepared CdS nanoparticles have good colloidal stability.
Self-healing polymers based on thermally reversible Diels–Alder chemistry (2012)

The development of self-healing materials has received much research attention in the last two decades. This review paper gathers recent publications on the self-healing polymeric materials with thermally reversible Diels–Alder (DA) chemistry. The DA reaction is a [4 + 2] cycloaddition involving a diene and a dienophile. The self-healing polymers employing the furan group as a diene and the maleimide group as a dienophile have been widely studied. Multifunctional furan and maleimide compounds construct thermally reversible crosslinked networks showing removability and remendability. Self-healing materials have also been utilized as healing agents for conventional thermosets like epoxy resins. Other diene–dienophile pairs, such as anthracene–maleimide and cyclopentadiene–dicyclopentadiene, have also been utilized for the development of thermally induced self-healing materials. Photo-induced self-healing polymers and some novel applications based on DA reactions have been discussed in this review. Moreover, self-healing polymer systems based on other thermally triggered and assisted reactions are also discussed. The discussed publication has provided promising molecular designs and synthetic strategies for the development of high performance self-healing polymers.
Molecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors (2006)

Different molecular mechanisms are responsible for primary and secondary imatinib resistance in GISTs. These findings have implications for future approaches to the growing problem of imatinib resistance in patients with advanced GISTs.
Involvement of Valosin-containing Protein, an ATPase Co-purified with IκBα and 26 S Proteasome, in Ubiquitin-Proteasome-mediated Degradation of IκBα (1998)

The inactivation of the prototype NF-kappaB inhibitor, IkappaBalpha, occurs through a series of ordered processes including phosphorylation, ubiquitin conjugation, and proteasome-mediated degradation. We identify valosin-containing protein (VCP), an AAA (ATPases associated with a variety of cellular activities) family member, that co-precipitates with IkappaBalpha immune complexes. The ubiquitinated IkappaBalpha conjugates readily associate with VCP both in vivo and in vitro, and this complex appears dissociated from NF-kappaB. In ultracentrifugation analysis, physically associated VCP and ubiquitinated IkappaBalpha complexes sediment in the 19 S fractions, while the unmodified IkappaBalpha sediments in the 4.5 S fractions deficient in VCP. Phosphorylation and ubiquitination of IkappaBalpha are critical for VCP binding, which in turn is necessary but not sufficient for IkappaBalpha degradation; while the N-terminal domain of IkappaBalpha is required in all three reactions, both N- and C-terminal domains are required in degradation. Further, VCP co-purifies with the 26 S proteasome on two-dimensional gels and co-immunoprecipitates with subunits of the 26 S proteasome. Our results suggest that VCP may provide a physical and functional link between IkappaBalpha and the 26 S proteasome and play an important role in the proteasome-mediated degradation of IkappaBalpha.
PD‐L1 co‐stimulation contributes to ligand‐induced T cell receptor down‐modulation on CD8 + T cells (2011)

T cell receptor (TCR) down-modulation after antigen presentation is a fundamental process that regulates TCR signal transduction. Current understanding of this process is that intrinsic TCR/CD28 signal transduction leads to TCR down-modulation. Here, we show that the interaction between programmed cell death 1 ligand 1 (PD-L1) on dendritic cells (DCs) and programmed death 1 (PD-1) on CD8 T cells contributes to ligand-induced TCR down-modulation. We provide evidence that this occurs via Casitas B-lymphoma (Cbl)-b E3 ubiquitin ligase up-regulation in CD8 T cells. Interference with PD-L1/PD-1 signalling markedly inhibits TCR down-modulation leading to hyper-activated, proliferative CD8 T cells as assessed in vitro and in vivo in an arthritis model. PD-L1 silencing accelerates anti-tumour immune responses and strongly potentiates DC anti-tumour capacities, when combined with mitogen-activated kinase (MAPK) modulators that promote DC activation.
Expression of muscarinic receptor subtype mRNA in the human ciliary muscle. (1995)

These studies show that the human ciliary muscle definitely expresses the mRNA of subtypes m2, m3, and m5, and may also express the mRNA of m1 and m4. Although the expression of mRNA for the m2, m3, and m5 subtypes differed between the circular and longitudinal portions of the ciliary muscle, the strong expression of all three subtypes of muscarinic receptors by both portions demonstrates that the differential distribution of muscarinic subtypes probably is not responsible for the dissociation between outflow facility and accommodation that can occur under certain conditions.
Measuring total corneal power before and after laser in situ keratomileusis with high-speed optical coherence tomography (2006)

Keratometry using the traditional index of 1.3375 overestimated the total power in preoperative corneas and underestimated LASIK-induced refractive change. Measuring both corneal surfaces using a combination of OCT and Placido ring topography provided a better measure of total corneal power that closely tracked the refractive change in post-LASIK eyes.