gebhart/patrepeval huggingface dataset:
Evidence of Endotoxins in the Rumen Bacteria of Cattle Fed Hay or Grain (1978)

The rumen bacterial fraction obtained from rumen fluids of cattle fed hay or grain was subjected to phenol-water or aqueous ether extraction procedures. The purified and lyophilized extract was endotoxic based on the following characteristics: 1. Proved lethal to mice and chick embryos. Toxicity in mice was potentiated by actinomycin D. 2. Enhanced susceptibility to streptococcal infection in mice. 3. Induced biphasic fever and leukocyte response in rabbits. 4. Elicited local Schwartzman reaction in rabbits. 5. Caused (in nanogram quantities) gelation of limulus lysate. A parallel study with commercial endotoxins of Escherichia coli or Salmonella typhosa showed that endotoxins from them were several times more endotoxic than those from rumen bacteria. This may be due to the presence of contaminating bacterial polysaccharides or to an inherently low endotoxicity of rumen bacteria.
Time Course of Inhibition of Hypertension by Antisense Oligonucleotides Targeted to AT1 Angiotensin Receptor mRNA in Spontaneously Hypertensive Rats (1997)

Antisense oligodeoxynucleotides (AS-ODN) can be designed to provide inhibition of a specific protein. Since angiotensin receptors are involved in blood pressure regulation we constructed AS-ODN to angiotensin II type-1 receptor (AT1) mRNA. When given centrally, the AS-ODN reduces blood pressure in spontaneously hypertensive rats (SHR) 24 h after injection. To study the time course of a single AS-ODN injection on blood pressure and heart rate, groups of SHR were injected intracerebroventricularly (icv) with either single dose of AS-ODN or scrambled (SC) ODN and blood pressure was recorded through implanted catheters daily for up to 9 days. Blood pressure decreased significantly in the AS-ODN treated rats compared to the SC-ODN rats for up to 7 days. The maximum decrease (38 mm Hg) occurred at 3 days. There appeared to be no toxic reaction or side effects and the blood pressure level had recovered by days 8 and 9. Heart rate was not altered by AS-ODN treatment. To test that the ODN was entering the brain tissue, fluorescein-isothiocyanate labelled (FITC) ODN was injected in Sprague-Dawley rats and the fluorescence detected 1 h later by confocal microscopy. Within 1 h there was rapid uptake into cells close to the site of injection and into brain parenchyma around the third and lateral ventricles. To test that the AS-ODN had reduced AT1 receptors, binding studies were carried out on membranes from hypothalamic tissue. There was a modest (approximately 20%) but significant (P < .05) decrease in the AT1 receptor binding after 25 microm or 50 microm AS-ODN. AT2 receptors were not altered by the AS-ODN, indicating its specificity for the AT1 receptor. The small decrease in receptor binding, relative to its large effect on blood pressure, is discussed in terms of the AT1 receptor life cycle. The mechanism for the long action of a single AS-ODN injection is hypothesized as resulting from the persistence of AS-ODN in the nucleus, preventing transport of the mRNA into the cytoplasm.
Smoothing spline ANOVA for exponential families, with application to the Wisconsin Epidemiological Study of Diabetic Retinopathy : the 1994 Neyman Memorial Lecture (1995)

Let $y_i, i = 1, \dots, n$, be independent observations with the density of $y_i$ of the form $h(y_i, f_i) = \exp{y_i f_i - b(f_i) + c(y_i)]$, where b and c are given functions and b is twice continuously differentiable and bounded away from 0. Let $f_i = f(t(i))$, where $t = (t_1, \dots, t_d) \epsilon \mathsf{T}^{(1)} \otimes \dots \otimes \mathsf{T}^{(d)} = \mathsf{T}$, the $\mathsf{T}^{(\alpha)}$ are measurable spaces of rather general form and f is an unknown function on $\mathsf{T}$ with some assumed "smoothness" properties. Given ${y_i, t(i), i = 1, \dots, n}$, it is desired to estimate $f(t)$ for t in some region of interest contained in $\mathsf{T}$. We develop the fitting of smoothing spline ANOVA models to this data of the form $f(t) = C + \sum_{\alpha} f_{\alpha}(t_{\alpha}) + \sum_{\alpha < \beta} f_{\alpha \beta} (t_{\alpha}, t_{\beta}) + \dots$. The components of the decomposition satisfy side conditions which generalize the usual side conditions for parametric ANOVA. The estimate of f is obtained as the minimizer, in an appropriate function space, of $\mathsf{L}(y, f) + \sum_{\alpha} \lambda_{\alpha} J_{\alpha}(f_{\alpha}) + \sum_{\alpha <\beta} \lambda_{\alpha \beta} J_{\alpha \beta}(f_{\alpha \beta}) + \dots$, where $\mathsf{L}(y, f)$ is the negative log likelihood of $y = (y_1, \dots, y_n)'$ given f, the $J_{\alpha}, J_{\alpha \beta}, \dots$ are quadratic penalty functionals and the ANOVA decomposition is terminated in some manner. There are five major parts required to turn this program into a practical data analysis tool: (1) methods for deciding which terms in the ANOVA decomposition to include (model selection), (2) methods for choosing good values of the smoothing parameters $\lambda_{\alpha}, \lambda_{\alpha \beta}, \dots$, (3) methods for making confidence statements concerning the estimate, (4) numerical algorithms for the calculations and, finally, (5) public software. In this paper we carry out this program, relying on earlier work and filling in important gaps. The overall scheme is applied to Bernoulli data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy to model the risk of progression of diabetic retinopathy as a function of glycosylated hemoglobin, duration of diabetes and body mass index. It is believed that the results have wide practical application to the analysis of data from large epidemiological studies.
Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum (2012)

Antibody-based drugs such as infliximab (IFX) are effective for the treatment of inflammatory bowel disease (IBD) and other immune-mediated disorders. The development of antibodies against these drugs may result in unfavorable consequences, including the loss of drug efficacy, hypersensitivity reactions, and other adverse events. Therefore, accurate monitoring of serum drug and anti-drug antibody levels should be an important part of therapy for patients being treated with an antibody-based drug. Current methods for the assessment of anti-drug antibodies and drug levels, involving various bridging ELISA and radioimmunoassay techniques, are limited by their sensitivity, interference, and/or complexity. To overcome these limitations, we have developed a non-radiolabeled homogeneous mobility shift assay (HMSA) to measure the antibodies-to-infliximab (ATI) and IFX levels in serum samples. Full method validation was performed on both the ATI- and IFX-HMSA, and the clinical sample test results were also compared with those obtained from a bridging ELISA method to evaluate the difference in performance between the two assays. Validation of the ATI-HMSA revealed a lower limit of quantitation of 0.012 μg/mL in serum. The linear range of quantitation was 0.029-0.54 μg/mL. The intra- and inter-assay precision was less than 20% of coefficient of variation (CV), and the accuracy (% error) of the assay was less than 20%. In serum samples, ATI as low as 0.036 μg/mL can be measured, even in the presence of 60 μg/mL of IFX in the serum. Sera from 100 healthy subjects were tested to determine the cut point of the assay. ATI-positive samples that had been previously analyzed by using a bridging ELISA from 100 patients were also measured by the new method. There was a high correlation between the two methods for ATI levels (p<0.001). Significantly, the new method identified five false-positive samples from the bridging ELISA method. Validation of the mobility shift IFX assay also showed high assay sensitivity, precision and accuracy. The HMSA method may also be applied to other protein-based drugs to accurately detect serum drug and anti-drug antibody levels.
Cancer statistics, 1998 (1998)

The Surveillance Research Program of the American Cancer Society's Department of Epidemiology and Surveillance reports its 32nd annual compilation of cancer incidence, mortality, and survival data for the United States and around the world.
Very-high-efficiency double-heterostructure copper phthalocyanine/C60 photovoltaic cells (2001)

We demonstrate an external power conversion efficiency of (3.6±0.2)% under AM1.5 spectral illumination of 150 mW/cm2 (1.5 suns) with vacuum-deposited copper phthalocyanine/C60 thin-film double-heterostructure photovoltaic cells incorporating an exciton-blocking layer (EBL). We show that the anode work function influences the photocarrier collection characteristics through the built-in electric field. The cell parameters are less sensitive to the cathode work function, which is attributed to cathode-induced defect states in the EBL energy gap. The presence of these defect states also explains the surprisingly low resistance of the EBL to electron transport. We anticipate significant further improvements in power conversion efficiency by employing optimal structures in light-trapping geometries.
Drug Therapy for Parkinson's Disease (2007)

The fundamental concepts of the medical treatment of Parkinson's disease are simple, and remain based on the enhancement of dopaminergic transmission by means of levodopa and dopamine agonists. Recently published practice parameters from the American Academy of Neurology and an evidence-based review under the auspices of the Movement Disorder Society provide guidance on motor complications and also cognitive and psychiatric issues associated with Parkinson's disease. The choices of medications are increasing as are the routes of administration, with the arrival of injectable and transdermal dopamine agonists and a monoamine inhibitor absorbed via the buccal mucosa. Although simple conceptually, the actual care of patients with Parkinson's disease is often complex, requiring consideration of potential future complications and individualized medication regimens, and minimizing the adverse effects of medications that range from unpleasant to seriously disturbing.
Stable lasers: progress and applications (1985)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text J. L. HALL, D. HILS, C. SALOMON, and M. RAYMAN, "Stable lasers: progress and applications," in Conference on Lasers and Electro-Optics, A. Gara, C. Giuliano, D. Auston, and R. Jacobs, eds., OSA Technical Digest (Optica Publishing Group, 1985), paper FM3. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
MIP-1α and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as Th1/Th2 lymphoctye differentiation (1997)

Chemokines are a family of small-molecular-weight cytokines that induce chemotaxis and chemokinesis of leukocytes. These molecules are ligands for seven-transmembrane, G-protein-linked receptors and are known to activate integrins on the surface of leukocytes and other cells as well as induce a number of signaling events. They play a significant role in the migration of leukocytes from blood into tissue during inflammatory processes. We tested the role of chemokines in experimental autoimmune encephalomyelitis (EAE) and found that macrophage inflammatory protein-1alpha (MIP-1alpha) correlated with acute disease development, whereas monocyte chemotactic protein-1 (MCP-1) did not. In contrast, MCP-1 production in the central nervous system correlated with relapsing EAE development. Moreover, anti-MIP-1alpha, but not anti-MCP-1, inhibited development of acute but not relapsing EAE, whereas anti-MCP-1 significantly reduced the severity of relapsing EAE. To test the effects of chemokines on the differentiation of naive T cells, TCR transgenic splenic T cells (Tg+ T cells) from DO11.10 OVA TCR transgenic mice were used as a source of Th0 cells and were stimulated with specific anti-clonotypic monoclonal antibodies in the presence of MIP-1alpha, MCP-1, or controls. MIP-1alpha drove Th0 cells to differentiate to Th1, whereas MCP-1 drove Th0 cells to differentiate to Th2. Similarly, MCP-1, but not MIP-1alpha significantly inhibited the adoptive transfer of EAE when included in in vitro activation cultures, further suggesting a regulatory anti-inflammatory property. These results suggest a differential role for CC chemokines in the development and activation of T cells during autoimmune inflammatory diseases.
Inhibition of Subsets of G Protein-coupled Receptors by Empty Mutants of G Protein α Subunits in Go, G11, and G16 (2000)

We previously reported that the xanthine nucleotide binding G(o)alpha mutant, G(o)alphaX, inhibited the activation of G(i)-coupled receptors. We constructed similar mutations in G(11)alpha and G(16)alpha and characterized their nucleotide binding and receptor interaction. First, we found that G(11)alphaX and G(16)alphaX expressed in COS-7 cells bound xanthine 5'-O-(thiotriphosphate) instead of guanosine 5'-O-(thiotriphosphate). Second, we found that G(11)alphaX and G(16)alphaX interacted with betagamma subunits in the presence of xanthine diphosphate. These experiments demonstrated that G(11)alphaX and G(16)alphaX were xanthine nucleotide-binding proteins, similar to G(o)alphaX. Third, in COS-7 cells, both G(11)alphaX and G(16)alphaX inhibited the activation of G(q)-coupled receptors, whereas only G(16)alphaX inhibited the activation of G(i)-coupled receptors. Therefore, when in the nucleotide-free state, empty G(11)alphaX and G(16)alphaX appeared to retain the same receptor binding specificity as their wild-type counterparts. Finally, we found that G(o)alphaX, G(11)alphaX, and G(16)alphaX all inhibited the endogenous thrombin receptors and lysophosphatidic acid receptors in NIH3T3 cells, whereas G(11)alphaX and G(16)alphaX, but not G(o)alphaX, inhibited the activation of transfected m1 muscarinic receptor in these cells. We conclude that these empty G protein mutants of G(o)alpha, G(11)alpha, and G(16)alpha can act as dominant negative inhibitors against specific subsets of G protein-coupled receptors.
Phytochrome degradation (1997)

ABSTRACT Plants actively modulate the levels of the various phyto‐chrome isoforms during their life cycle to optimize light absorption and perception. For phytochrome A (phyA), one of the most influential methods of control is selective turnover of the photoreceptor upon photoconversion from the red‐absorbing form (Pr) to the far‐red‐absorbing form (Pfr). Whereas the Pr form has a half‐life of approximately 1 week, the Pfr form is rapidly degraded with a half‐life of 1–2 h. The ubiquitin/26S proteasome pathway has been implicated in phyA breakdown. In this proteolytic pathway, multiple ubiquitins are covalently attached to proteins committed for degradation; these ubiquitin‐protein conjugates then serve as intermediates in the breakdown of the target protein by the 26S proteasome, a multi‐subunit proteolytic complex. In several plant species, ubiquitin‐phyA conjugates have been detected in vivo following Pfr formation that show accumulation and decay kinetics expected for Pfr degradation intermediates. Analyses of phyA mutants and phyA/phyB chimeras expressed in transgenic plants have been particularly useful in mapping domains within the chromoprotein that are necessary for Pfr degradation. Several domains have been identified within both the N‐ and C‐terminal portions of the photoreceptor that presumably serve as recognition and/or acceptor sites for ubiquitination
Multi-site model and simulation of trunking systems (2002)

We consider the case where a number of geographically distributed mobile stations in a trunking system wish to communicate with all other mobile stations belonging to the same group by transmitting messages over a single channel. If the system comprises all these stations, the problem is reduced to allocating every incoming call among the available channels. A multi-site model of trunking systems is proposed and simulated using queuing theory concepts. The results on the performance of this model reveal that its behavior improves if there is the possibility of some unaccessible users in the system. The proposed model requires new call-related parameters: the number of radio units per fleet, the probability distribution vector and the required maximum percentage of unaccessible users per call in progress. For simplicity, we consider a family of fleets and all the users of any fleet uniformly distributed over the sites.
High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy (2005)

Two extended haplotypes exist across the tau gene-H1 and H2-with H1 consistently associated with increased risk of progressive supranuclear palsy (PSP). Using 15 haplotype tagging SNPs (htSNPs), capturing >95% of MAPT haplotype diversity, we performed association analysis in a US sample of 274 predominantly pathologically confirmed PSP patients and 424 matched control individuals. We found that PSP risk is associated with one of two major ancestral H1 haplotypes, H1B, increasing from 14% in control individuals to 22% in PSP patients (P<0.001). In young PSP patients, the H1B risk could be localized to a 22 kb regulatory region in intron 0 (P<0.001) and could be fully explained by one SNP, htSNP167, creating a LBP-1c/LSF/CP2 site, shown to regulate the expression of genes in other neurodegenerative disorders. Luciferase reporter data indicated that the 182 bp conserved regulatory region, in which htSNP167 is located, is transcriptionally active with both alleles differentially influencing expression. Further, we replicated the htSNP167 association in a second, independently ascertained US PSP patient-control sample. However, the htSNP association showed that H1 risk alone could not explain the overall differences in H1 and H2 frequencies in PSP patients and control individuals. Thus, risk variants on different H1 htSNP haplotypes and protective variants on H2 contribute to population risk for PSP.
Nonlinear acoustic echo cancellation based on volterra filters (2003)

This paper describes a nonlinear acoustic echo cancellation algorithm, mainly focused on loudspeaker distortions. The proposed system is composed of two distinct modules organized in a cascaded structure: a nonlinear module based on polynomial Volterra filters models the loudspeaker, and a second module of standard linear filtering identifies the impulse response of the acoustic path. The tracking of the overall system model is achieved by a modified normalized-least mean square algorithm for which equations are derived. Stability conditions are given, and particular attention is placed on the transient behavior of cascaded filters. Finally, results of real data recorded with Alcatel GSM material are presented.
Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial (2017)

Over the past decade, vectors derived from adeno-associated virus (AAV) have established themselves as a powerful tool for in vivo gene transfer, allowing long-lasting and safe transgene expression in a variety of human tissues. Nevertheless, clinical trials demonstrated how B and T cell immune responses directed against the AAV capsid, likely arising after natural infection with wild-type AAV, might potentially impact gene transfer safety and efficacy in patients. Seroprevalence studies have evidenced that most individuals carry anti-AAV neutralizing antibodies that can inhibit recombinant AAV transduction of target cells following in vivo administration of vector particles. Likewise, liver- and muscle-directed clinical trials have shown that capsid-reactive memory CD8<sup>+</sup> T cells could be reactivated and expanded upon presentation of capsid-derived antigens on transduced cells, potentially leading to loss of transgene expression and immune-mediated toxicities. In celebration of the 25th anniversary of the European Society of Gene and Cell Therapy, this review article summarizes progress made during the past decade in understanding and modulating AAV vector immunogenicity. While the knowledge generated has contributed to yield impressive clinical results, several important questions remain unanswered, making the study of immune responses to AAV a priority for the field of in vivo transfer.
Effective Production of Dehydro Cyclic Dipeptide Albonoursin Exhibiting Pronuclear Fusion Inhibitory Activity. II. Biosynthetic and Bioconversion Studies. (2000)

Albonoursin production was greatly enhanced when cyclo (L-Leu-L-Phe) (CFL), a tetrahydro derivative of albonoursin, was added to the 2-day culture of an albonoursin-producing actinomycete, Streptomyces albulus KO-23. The increase in albonoursin production paralleled the amount of CFL added. Furthermore, the resting cells of the strain catalyzed the bioconversion of CFL to albonoursin. The optimum pH and temperature for the conversion were found to be pH 10.0 and 50 degrees C. The feeding experiments and the resting-cell reactions revealed that albonoursin is biosynthesized by dehydrogenation of CFL in the actinomycete. This is the first report for a dehydrogenation of amino acid residues at the alpha,beta-positions in cyclic dipeptides.
Functional Expression and Cellular Localization of a Mouse Epidermal Lipoxygenase (1996)

Three distinct murine lipoxygenase genes have been functionally characterized: 5-lipoxygenase (Chen, X.-S., Naumann, T. A., Kurre, U. , Jenkins, N. A., Copeland, N. G., and Funk, C. D. (1995) J. Biol. Chem. 270, 17993-17999), platelet-type 12-lipoxygenase and leukocyte-type 12-lipoxygenase (Chen, X.-S., Kurre, U., Jenkins, N. A., Copeland, N. G., and Funk, C. D. (1994) J. Biol. Chem. 269, 13979-13987). Here, we describe the cloning and functional characterization of a fourth lipoxygenase gene in mice. Using a polymerase chain reaction-based approach together with partial sequence information from a genomic clone, we isolated a novel lipoxygenase cDNA from the RNA of 3-6-day-old mouse epidermis. The open reading frame predicts a 662-amino acid lipoxygenase that displays 60% identity with both murine 12-lipoxygenase isozymes and 40% identity to 5-lipoxygenase; the sequence is identical to a genomic sequence reported recently (van Dijk, K. W., Steketee, K., Havekes, L., Frants, R., and Hofker, M. (1995) Biochim. Biophys. Acta 1259, 4-8). A full-length clone was expressed in human embryonic kidney 293 cells and homogenates from disrupted cells produced 12-hydroxyeicosatetraenoic acid (12-HETE) and minor amounts of 15-HETE from arachidonic acid. Chiral phase analysis indicated that the 12-HETE is exclusively the 12S enantiomer. In situ hybridization revealed highly specific expression of epidermal lipoxygenase in differentiated keratinocytes of the epidermis and in restricted regions of the root sheath and bulb of hair follicles. High expression was also detected in conjunctiva of the eyelid and in cells of Meibomian and preputial (sebaceous) glands. A 2. 4-kilobase mRNA was detected in mouse epidermis by Northern blot analysis and its abundance was not affected by phorbol ester treatment. The epidermal lipoxygenase gene (Aloxe) resides on mouse chromosome 11 closely linked with the two 12-lipoxygenase genes (Alox12p and Alox12l).