gebhart/patrepeval huggingface dataset:
Sorting out the cytokines of asthma. (1996)

Asthma is a complex disorder characterized by intermittent, reversible airway obstruction, and by airway hyperresponsiveness and inflammation. Although its cause(s) remain unknown, we now recognize that asthma is a syndrome whose common pathologic expression is inflammation of the airways. The airways of patients with even mild asthma are inflamed, and some data suggest that the severity of the asthma parallels the degree of inflammation (1-3). The airway inflammation of asthma is unique in that the airway wall is infiltrated by T lymphocytes bearing the T helper type 2 phenotype (4) and by eosinophils and mast ceils (2, 5, 6). Each of these cells is thought to contribute to the physiologic changes that characterize asthma (Fig. 1). The TH2 lymphocytes produce a limited panel ofcytokines including IL-3, IL-4, IL-5, and GM-CSF. Although the primary signals resulting in the infiltration of the asthmatic airways by this lymphocyte subset have not yet been identified, a number of models have been proposed based on the concept that the inflammtory process is triggered by the presentation of a restricted panel of antigens in the presence of appropriate cytokines. The net effect of antigen presentation in this microenvironment is to promote the synthesis of IgE through the actions of IL-4 on Ig isotype switching (7) and to enhance the differentiation, migration, and pathobiologic capacity of eosinophils through the actions of GMCSF, IL-3, and IL-5 (8, 9). The IgE produced in asthmatic airways binds to Fc~RI on mast cells, priming them for activation by antigen. Mast cells arise from bone marrow precursors, enter the circulation as non-metachromatically staining, agranular, CD34 +, c-kit +, and F%I<I + mononuclear leukocytes (10), and localize to mucosal and submucosal sites such as the bronchi. Once localized, these lineage-committed immature mast cells undergo tissue-specific differentiation along with maturation and expansion. Their development and movement involves growth factors and cytokines derived from both structural and hematopoietic cells in their microenvironment. The mast cells that further migrate into the luminal space, and which can be recovered by bronchoalveolar lavage, are primed for an augmented activation response (11). Mast cells also elaborate IL-4 (12, 13), which favors conversion ofT cells to the TH 2 phenotype, and IL-5 (14), which contributes to eosinophilopoiesis and to the priming of eosinophils for augmented responses. Once recruited from the circulation, mature eosinophils, in the presence ofasthmatic cytokines, convert to an autoaggressive phenotype (15, 16), termed hy
Recent advance in immunotherapies for Alzheimer disease, with special reference to DNA vaccination (2009)

Alzheimer disease (AD) is the most common cause of dementia characterized by progressive neurodegeneration. Based on the amyloid cascade hypothesis, several immunotherapies for AD have been developed as curative treatment. In 1999, Schenk et al. reported for the first time that amyloid beta (Abeta) deposits in AD model mice could be reduced by active vaccination with Abeta peptide. Although clinical trials with the Abeta peptide were halted due to the development of meningoencephalitis in some treated patients, the vaccine therapy was judged to be effective on the basis of clinical and pathological analyses. Passive immunization using humanized anti-Abeta monoclonal antibodies is also under clinical trials; however they have some problems to be solved. As other strategies, DNA vaccines have been developed as immunotherapies for AD, which is simple, easily modified and can be administered without adjuvant. DNA vaccines were developed by several groups including our laboratory, which induced Abeta reduction in AD model mice without side effects. DNA vaccination may be open up new avenue of vaccine therapies for AD in the near future.
Reasoning about temporal relations (2003)

Allen's interval algebra is one of the best established formalisms for temporal reasoning. This article provides the final step in the classification of complexity for satisfiability problems over constraints expressed in this algebra. When the constraints are chosen from the full Allen's algebra, this form of satisfiability problem is known to be NP-complete. However, eighteen tractable subalgebras have previously been identified; we show here that these subalgebras include all possible tractable subsets of Allen's algebra. In other words, we show that this algebra contains exactly eighteen maximal tractable subalgebras, and reasoning in any fragment not entirely contained in one of these subalgebras is NP-complete. We obtain this dichotomy result by giving a new uniform description of the known maximal tractable subalgebras, and then systematically using a general algebraic technique for identifying maximal subalgebras with a given property.
Distribution of Amitriptyline and Nortriptyline in Blood (1993)

To interpret blood levels of tricyclic antidepressants, we studied the distributions of amitriptyline and nortriptyline in human blood and explored their control by plasma factors. Each compound (300 ng/ml) was added to whole adult blood and to cord blood with decreased alpha-1-glycoprotein (AGP). Drugs (250 ng/ml) were also added to washed erythrocytes (RBCs) resuspended in autologous plasma or saline (hematocrit = 0.4) with or without AGP, albumin, or tris(2-butoxyethyl) phosphate (TBEP), used to displace AGP-bound drugs. Plasma AGP was determined in all adult blood donors (n = 17). With adult blood, plasma amitriptyline was 393 +/- 52 ng/ml, RBC amitriptyline was 184 +/- 33 ng/ml. Plasma and RBC nortriptyline were 199 +/- 28 and 288 +/- 39 ng/ml, respectively. With saline, cellular amitriptyline and nortriptyline were 81 +/- 10 and 88 +/- 6%, respectively. With plasma, cellular amitriptyline and nortriptyline were 25 +/- 8 and 49 +/- 10%, respectively. The corresponding cord blood values were 52 +/- 12 and 62 +/- 6%. Graded increments of AGP in saline reproduced the distribution pattern seen with increasing concentrations of plasma. Albumin did not influence drug distribution. TBEP markedly increased erythrocyte amitriptyline in adult but not in cord blood. Plasma AGP correlated positively (p = 0.031) with the RBC/plasma ratio of amitriptyline. Amitriptyline is predominantly distributed in plasma, nortriptyline in RBCs. This differential distribution is dose dependent and reflects the higher binding of amitriptyline to AGP when compared with nortriptyline. Interpretation of tricyclic antidepressant blood levels is clarified by obtaining assays from RBCs and plasma.
Isozyme patterns of section Elegans, section Liseola and similar species in the genus Fusarium (1994)

To investigate taxonomical relationships of Fusarium species, , acid phosphatase, malate dehydrogenase, peroxidase and polygalacturonase were extracted and the isozyme patterns were compared by using polyacrylamide gel electrophoretic analysis. Only polygalacturonase was monozyme and the other enzymes showed little differences in banding patterns. Genetic similarities based on the isozyme banding patterns were as follows: the interspecific similarity between F. subglutinans and F. moniliforme in Liseola showed the closest relationship of 74.3% of all species studies. And the similarity between section Elegans and section Liseola was 45.4%. F. napiforme and F. nygamai showed the similarity of 64.7%, similar to the correlation between species in the same section. The similarity of these two species to Liseola and Elegans showed 55.2% and 45.4%, being revealed that they would be closer to Liseola than Elegans. However, these results were similar to those of any other sections. Therefore it suggested that these 2 species should be in a different section from any other sections. And F. graminearum showed the similarity of 28.2% to the other 6 species.
Novel Regulators of Fgf23 Expression and Mineralization in Hyp Bone (2009)

We used gene array analysis of cortical bone to identify Phex-dependent gene transcripts associated with abnormal Fgf23 production and mineralization in Hyp mice. We found evidence that elevation of Fgf23 expression in osteocytes is associated with increments in Fgf1, Fgf7, and Egr2 and decrements in Sost, an inhibitor in the Wnt-signaling pathway, were observed in Hyp bone. beta-Catenin levels were increased in Hyp cortical bone, and TOPflash luciferase reporter assay showed increased transcriptional activity in Hyp-derived osteoblasts, consistent with Wnt activation. Moreover, activation of Fgf and Wnt-signaling stimulated Fgf23 promoter activity in osteoblasts. We also observed reductions in Bmp1, a metalloproteinase that metabolizes the extracellular matrix protein Dmp1. Alterations were also found in enzymes regulating the posttranslational processing and stability of Fgf23, including decrements in the glycosyltransferase Galnt3 and the proprotein convertase Pcsk5. In addition, we found that the Pcsk5 and the glycosyltransferase Galnt3 were decreased in Hyp bone, suggesting that reduced posttranslational processing of FGF23 may also contribute to increased Fgf23 levels in Hyp mice. With regard to mineralization, we identified additional candidates to explain the intrinsic mineralization defect in Hyp osteoblasts, including increases in the mineralization inhibitors Mgp and Thbs4, as well as increases in local pH-altering factors, carbonic anhydrase 12 (Car12) and 3 (Car3) and the sodium-dependent citrate transporter (Slc13a5). These studies demonstrate the complexity of gene expression alterations in bone that accompanies inactivating Phex mutations and identify novel pathways that may coordinate Fgf23 expression and mineralization of extracellular matrix in Hyp bone.
Rapid and preferential activation of the c-jun gene during the mammalian UV response. (1991)

Exposure of mammalian cells to DNA-damaging agents leads to activation of a genetic response known as the UV response. Because several previously identified UV-inducible genes contain AP-1 binding sites within their promoters, we investigated the induction of AP-1 activity by DNA-damaging agents. We found that expression of both c-jun and c-fos, which encode proteins that participate in formation of the AP-1 complex, is rapidly induced by two different DNA-damaging agents: UV and H2O2. Interestingly, the c-jun gene is far more responsive to UV than any other immediate-early gene that was examined, including c-fos. Other jun and fos genes were only marginally affected by UV or H2O2. Furthermore, UV is a much more efficient inducer of c-jun than phorbol esters, the standard inducers of c-jun expression. This preferential response of the c-jun gene is mediated by its 5' control region and requires the TPA response element, suggesting that this element also serves as an early target for the signal transduction pathway elicited by DNA damage. Both UV and H2O2 lead to a long-lasting increase in AP-1 binding activity, suggesting that AP-1 may mediate the induction of other damage-inducible genes such as human collagenase.
Numerical Simulation of Morphology and Microsegregation Evolution during Solidification of Al-Si Alloy (2009)

A stochastic model coupled with transient calculations for the distributions of temperature, solute and velocity during the solidification of binary alloy is presented. The model can directly describe the evolution of both morphology and segregation during dendritic crystal growth. The model takes into account the curvature and growth anisotropy of dendritic crystals. Finite difference method is used to explicitly track the sharp solid liquid (S/L) interface on a fixed Cartesian grid. Two-dimensional mesoscopic calculations are performed to simulate the evolution of columnar and equiaxed dendritic morphologies of an Al-7 wt pct Si alloy. The effects of heat transfer coefficient on the evolution of both the dendrite morphology and segregation patterns during the solidification of binary alloys are analyzed. This model is applied to the solidification of small casting. Columnar-to-equiaxed transition is analyzed in detail. The effects of heat transfer coefficient on final casting structures are also studied. Final casting structures changing from wholly columnar dendrites to wholly equiaxed dendrites are described. The effect of melt flow on the morphological development during Al-7 wt pct Si alloy soilidification is also described.
Physical and Chemical Aspects Related to Substances Released from Polymer Materials in an Aqueous Environment (1995)

Exposure to an aqueous environment will change the physical properties of polymer materials with time. Due to water absorption, surface hardness is reduced and mechanical properties are adversely affected. The composition of polymer dental materials varies greatly. The organic substances are represented by monomers, oligomers, polymers, initiators, activators, inhibitors, anti-oxidants, UV stabilizers, plasticizers, fluorescent compounds, and other additives. The inorganic substances are represented by oxides and glasses (fillers and pigments) of various composition. Both organic and inorganic substances are released into water from composite materials. Combined-HPLC/UVspectroscopy analysis of an aqueous extract from a composite filling material demonstrates that the eluate contains several components. Several inorganic metal-ions released into aqueous solutions have been identified. Only a few of the released organic substances have been identified. Several investigators have determined the quantity of residual monomers in the polymerized materials, and the decrease of such residual monomers with time. Exposure to water, or aqueous salivary enzyme solutions, results in release of degradation products, such as formaldehyde, methacrylic acid, and others.
Serum antibody response to Human papillomavirus (HPV) infections detected by a novel ELISA technique based on denatured recombinant HPV16 L1, L2, E4, E6 and E7 proteins (2006)

This novel ELISA, based on multiple denatured HPV16 antigens, is able to detect antibodies in women infected by HPV16 and it is not genotype-specific, as it detects antibodies also in women infected by other genital HPVs. The assay is easy to perform and has low cost, making it suitable for monitoring the natural history of HPV infections as well as for detecting pre-existing HPV antibodies in women who receive VLP-based HPV vaccination.
B cell depletion: a novel therapy for autoimmune diabetes? (2007)

Autoimmune diabetes is believed to be mediated primarily by T cells. However, B cells have been implicated in the pathogenesis of the disease in NOD mice. Although preclinical studies have been limited by the absence of anti-CD20 reagents that can induce B cell depletion in mice, a clinical trial using the B cell-depleting anti-CD20 monoclonal antibody rituximab (Rituxan) is underway in type 1 diabetes patients. In this issue of the JCI, Hu et al. describe the generation of transgenic NOD mice that express human CD20 on B cells (see the related article beginning on page 3857). They show that anti-CD20 therapy induces B cell depletion in these mice and offers some level of protection against diabetes. Although many questions remain unanswered, this mouse model represents the first opportunity to evaluate the potential value of rituximab as a novel therapy for autoimmune diabetes.
Investigation of a surface-wave line for long distance transmission (1952)

The surface-wave line discussed in this paper is a single conductor with a dielectric coat. The energy is propagated along the surface of the line in a wave mode similar to that in a coaxial line. The phase velocity of this wave is reduced by 1 to 5% from the velocity of light, depending on the thickness of' the dielectric layer. Because of this reduction in phase velocity, no outer conductor is necessary for the return of the current. The conduction current in the outer conductor of a coaxial line is replaced by a displacement current through the air. The experiments demonstrated that the single conductor surface-wave transmission line is practical for long-distance, wide-band communication. They also indicated possible improvements: (a) The use of "copperweld" conductor rather than a conductor with segmental structure in order to reduce the conductivity loss. The ~eat mechanical strength of this cable would permit an increase in the span to at least 250 feet; (b) Avoiding unnecessary curves; (o) Omitting the· messenger wire..
A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS (1970)

SUMMARY A modification of an earlier rating scale for extrapyramidal system disturbance is described, and evidence for the validity and reliability of the scale is presented. The usefulness of the scale in studies of neuroleptic drugs is discussed. By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors.
Codon Usage and Transfer RNA Contents: Organism-specific Codon-choice Patterns in Reference to the Isoacceptor Contents (1983)

The choice of synonymous codons in both prokaryotic and eukaryotic genes is strongly biased. There exist clear similarities in codon usage among different genes of the same or taxonomically related organisms, regardless of the functions of the genes or the dissimilarities among the genes (even among those encoding cognate proteins) of taxonomically distant organisms (Grantham et al. 1980, 1981; Ikemura 1981a,b, 1982).
Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent serine protease. (1989)

The KEX2-encoded endoprotease was overproduced in yeast several hundred-fold and further purified to achieve a 10,000-fold enrichment in specific activity. The enzyme was (i) membrane-bound, but solubilized by detergents; (ii) able to cleave peptide substrates at both Lys-Arg and Arg-Arg sites; (iii) inhibited by EDTA and EGTA (but not o-phenanthroline), but fully reactivated by Ca2+; (iv) unaffected by 5-10 mM phenylmethylsulfonyl fluoride, N alpha-(ptosyl)lysine chloromethyl ketone, or L-1-tosylamido-2-phenylethyl chloromethyl ketone, but inactivated by 1-2 microM Ala-Lys-Arg-chloromethyl ketone; (v) labeled specifically by 125I-labeled Tyr-Ala-Lys-Arg-chloromethyl ketone; and (vi) resistant to trans-epoxysuccinate compounds (which inactivate thiol proteases), but inactivated by diisopropyl fluorophosphate (a diagnostic serine protease inhibitor). Mutant enzyme molecules lacking as many as 200 C-terminal residues still retained Ca2+-dependent protease activity and were labeled by 125I-labeled Tyr-Ala-Lys-Arg-chloromethyl ketone.
Inhibition of human cytomegalovirus in culture by alkenyl guanine analogs of the thiazolo[4,5-d]pyrimidine ring system (1994)

A series of alkyl and alkenyl guanine analogs containing a thiazolo[4,5-d]pyrimidine ring system were prepared by reaction of the appropriate alkyl halide with the sodium salt of the heterocycle. In preliminary antiviral efficacy evaluations against laboratory strains of both human cytomegalovirus (HCMV) and herpes simplex virus types 1 and 2, it was determined that two of the compounds (T70072 and T01132) were more active and less toxic in stationary-phase cell monolayers than were the other derivatives tested. T01132 and T70072, which have 2-pentenyl and 3-methyl-2-butenyl moieties attached to position 3 of the 5-aminothiazolo[4,5-d]pyrimidine-2,7-dione, respectively, were then more extensively evaluated for anti-HCMV activity. The concentrations of T01132 and T70072 required to inhibit HCMV by 50% in plaque reduction assays were approximately 0.5 and 6.8 microM, respectively. These two compounds inhibited the growth of KB, MRC-5, or Vero cells at concentrations of 75 to 150 microM, depending upon the cell line. In bone marrow progenitor cells T01132 was slightly less toxic than ganciclovir (DHPG). The 50% inhibitory concentrations of T01132 against clinical isolates and DHPG-resistant strains of HCMV were approximately the same as those obtained for laboratory strains of HCMV (approximately 0.5 microM). When tested in combination with DHPG, the resultant antiviral activity was determined to be additive but not synergistic. Experiments performed using variations of the viral multiplicity of infection (MOI) demonstrated that T01132 was more active than DHPG at a low MOI (0.002 or 0.02). However, when a higher MOI (0.2 or 2.0) was used, DHPG was more efficacious than T01132. In experiments in which drug was added at various times post-viral infection, T01132 was most effective when added within the first 24 h post-HCMV infection while DHPG was able to protect cells in this assay system when added up to 48 h postinfection, indicating that T01132 is exerting its antiviral effect on events leading up to and possibly including viral DNA synthesis. The data presented in this report suggest that the antiviral activity of alkenyl-substituted thiazolopyrimidine derivatives may represent a mechanism of action against herpesviruses alternative to that of classical nucleoside analogs such as acyclovir or DHPG.
ChemInform Abstract: Indolocarbazoles as Anti‐Cancer Agents (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Application of enzymes in food processing (1996)

Enzymes offer potential for many exciting applications for the improvement of foods. There is still, however, a long way to go in realizing this potential. Economic factors such as achievement of optimum yields and efficient recovery of desired protein are the main deterrents in the use of enzymes. Changing values in society with respect to recombinant DNA and protein engineering technologies and the growing need to explore all alternative food sources may in time make enzyme applications more attractive to the food industry. Research is continuing on the commercially viable enzymes in use today to improve various properties such as thermostabilities, specificities, and catalytic efficiencies. New and unique enzymes continue to be developed for use in enzymatic reactions to produce food ingredients by hydrolysis, synthesis, or biocatalysis. An aggressive approach is needed to open new opportunities for enzyme applications that can benefit the food industry.