gebhart/patrepeval huggingface dataset:
Protective T-Cell-Based Immunity Induced in Neonatal Mice by a Single Replicative Cycle of Herpes Simplex Virus (2001)

Newborns are very susceptible to infections because their immune systems are not fully developed and react to antigen exposure preferentially with unresponsiveness. UV-inactivated herpes simplex virus type 1 (HSV-1) represents such an antigen and does not induce an immune response in neonates. In contrast, protective T cells were primed in newborn mice by a single replicative cycle of DISC HSV-1 given once within 24 h of birth. Each of the HSV-1-primed CD4(+) or CD8(+) T cells induced in wild-type or interferon-deficient mice conferred resistance to naive animals exposed to a lethal virus challenge. Inactivated HSV-1, injected at variable doses up to 10(4) times that of DISC HSV-1, was ineffective in inducing any detectable immune responses in neonates. Thus, the capacity of HSV-1 to replicate once, but not the number of virus particles per se, was decisive in inducing protective T-cell-associated immunity in newborn mice.
Parkin-deficient Mice Exhibit Nigrostriatal Deficits but Not Loss of Dopaminergic Neurons (2003)

Loss-of-function mutations in parkin are the major cause of early-onset familial Parkinson's disease. To investigate the pathogenic mechanism by which loss of parkin function causes Parkinson's disease, we generated a mouse model bearing a germline disruption in parkin. Parkin-/- mice are viable and exhibit grossly normal brain morphology. Quantitative in vivo microdialysis revealed an increase in extracellular dopamine concentration in the striatum of parkin-/- mice. Intracellular recordings of medium-sized striatal spiny neurons showed that greater currents are required to induce synaptic responses, suggesting a reduction in synaptic excitability in the absence of parkin. Furthermore, parkin-/- mice exhibit deficits in behavioral paradigms sensitive to dysfunction of the nigrostriatal pathway. The number of dopaminergic neurons in the substantia nigra of parkin-/- mice, however, is normal up to the age of 24 months, in contrast to the substantial loss of nigral neurons characteristic of Parkinson's disease. Steady-state levels of CDCrel-1, synphilin-1, and alpha-synuclein, which were identified previously as substrates of the E3 ubiquitin ligase activity of parkin, are unaltered in parkin-/- brains. Together these findings provide the first evidence for a novel role of parkin in dopamine regulation and nigrostriatal function, and a non-essential role of parkin in the survival of nigral neurons in mice.
Inhibition of Six Serine Proteinases of the Human Coagulation System by Mutants of Bovine Pancreatic Trypsin Inhibitor (2000)

A series of 12 bovine pancreatic trypsin inhibitor variants mutated in the P(4) and P(3) positions of the canonical binding loop containing additional K15R and M52L mutations were used to probe the role of single amino acid substitutions on binding to bovine trypsin and to the following human proteinases involved in blood clotting: plasmin, plasma kallikrein, factors X(a) and XII(a), thrombin, and protein C. The mutants were expressed in Escherichia coli as fusion proteins with the LE1413 hydrophobic polypeptide and purified from inclusion bodies; these steps were followed by CNBr cleavage and oxidative refolding. The mutants inhibited the blood-clotting proteinases with association constants in the range of 10(3)-10(10) m(-)(1). Inhibition of plasma kallikrein, factors X(a) and XII(a), thrombin, and protein C could be improved by up to 2 orders of magnitude by the K15R substitution. The highest increase in the association constant for P(3) mutant was measured for factor XII(a); P13S substitution increased the K(a) value 58-fold. Several other substitutions at P(3) resulted in about 10-fold increase for factor X(a), thrombin, and protein C. The cumulative P(3) and P(1) effects on K(a) values for the strongest mutant compared with the wild type bovine pancreatic trypsin inhibitor were in the range of 2.2- (plasmin) to 4,000-fold (factors XII(a) and X(a)). The substitutions at the P(4) site always caused negative effects (a decrease in the range from over 1,000- to 1.3-fold) on binding to all studied enzymes, including trypsin. Thermal stability studies showed a very large decrease of the denaturation temperature (about 22 degrees C) for all P(4) mutants, suggesting that substitution of the wild type Gly-12 residue leads to a change in the binding loop conformation manifesting itself in non-optimal binding to the proteinase active site.
Sorbent therapy of the porphyrias. III. Comparative efficacy of experimental plasma perfusion with several commercial hemoperfusion cartridges. (1984)

The manifestations of the acute attack of an hepatic porphyria may result from the actions of the excessive amounts of delta-aminolevulinic acid (ALA) or porphobilinogen (PBG) that accumulate during the event. Adsorption and removal of these materials by a solid phase sorbent may be an effective rapid treatment of the attack. We have compared the rate at which 5 commercial charcoal hemoperfusion cartridges remove ALA and PBG from an in vitro system, to ascertain if any of these may be useful in the treatment of the porphyric attack. Solutions of ALA (3.0 mg/L in plasma) or PBG (1.5 mg/L in saline) were circulated from a reservoir through the cartridge and back to the reservoir. Clearances (ml/min +/- SD) of ALA or PBG were determined from their concentration in both the reservoir (kept nearly constant by periodic addition of solute) and the cartridge effluent. For ALA, clearances decreased in the order Hemosorba (118 +/- 15), two Detoxyl 2 devices in series (93 +/- 17), one Detoxyl 2 (72 +/- 16), Adsorba 300 C (52 +/- 12), Haemocol 100 (48 +/- 14) and Hemodetoxifier (46 +/- 17). Differences in ALA clearance between the Hemosorba, one or two Detoxyl 2 cartridges and all other cartridges were of high statistical significance. For PBG, clearances decreased in the order Hemosorba (1462 +/- 23), one Detoxyl 2 (719 +/- 89), Adsorba 300 C (477 +/- 131), Hemodetoxifier (376 +/- 75) and Haemocol 100 (48 +/- 13). Differences in PBG clearance among all cartridges were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatic stellate cells uptake of retinol associated with retinol‐binding protein or with bovine serum albumin (2003)

Retinol is stored in liver, and the dynamic balance between its accumulation and mobilization is regulated by hepatic stellate cells (HSC). Representing less than 1% total liver protein, HSC can reach a very high intracellular retinoid (vitamin-A and its metabolites) concentration, which elicits their conversion from the myofibroblast to the fat-storing lipocyte phenotype. Circulating retinol is associated with plasma retinol-binding protein (RBP) or bovine serum albumin (BSA). Here we have used the in vitro model of GRX cells to compare incorporation and metabolism of BSA versus RBP associated [(3)H]retinol in HSC. We have found that lipocytes, but not myofibroblasts, expressed a high-affinity membrane receptor for RBP-retinol complex (KD = 4.93 nM), and both cell types expressed a low-affinity one (KD = 234 nM). The RBP-retinol complex, but not the BSA-delivered retinol, could be dislodged from membranes by treatments that specifically disturb protein-protein interactions (high RBP concentrations). Under both conditions, treatments that disturb the membrane lipid layer (detergent, cyclodextrin) released the membrane-bound retinol. RBP-delivered retinol was found in cytosol, microsomal fraction and, as retinyl esters, in lipid droplets, while albumin-delivered retinol was mainly associated with membranes. Disturbing the clathrin-mediated endocytosis did not interfere with retinol uptake. Retinol derived from the holo-RBP complex was differentially incorporated in lipocytes and preferentially reached esterification sites close to lipid droplets through a specific intracellular traffic route. This direct influx pathway facilitates the retinol uptake into HSC against the concentration gradients, and possibly protects cell membranes from undesirable and potentially noxious high retinol concentrations.
[1992 tumor classification/developments]. (1992)

Surgical oncology must consider some new international and national publications: 1. New fascicles of the 2nd edition of the WHO International Histological Classification of Tumors. 2. The 1992 revision of the 4th edition of the UICC TNM Classification and of the UICC TNM Atlas. 3. The TNM Supplement 1992/93 (UICC), which includes, among other things, explanatory notes for uniform use, proposals for further development, and a compilation of prognostic factors other than TNM and R to be considered in clinical studies. 4. The fully revised and enlarged tumor documentation system of the Working Group of German Cancer Centers (Arbeitsgemeinschaft Deutscher Tumorzentren).
Ultrasonic backscatter coefficient quantitative estimates from high-concentration Chinese hamster ovary cell pellet biophantoms (2011)

Previous work estimated the ultrasonic backscatter coefficient (BSC) from low-concentration (volume density <3%) Chinese Hamster Ovary (CHO, 6.7-μm cell radius) cell pellets. This study extends the work to higher cell concentrations (volume densities: 9.6% to 63%). At low concentration, BSC magnitude is proportional to the cell concentration and BSC frequency dependency is independent of cell concentration. At high cell concentration, BSC magnitude is not proportional to cell concentration and BSC frequency dependency is dependent on cell concentration. This transition occurs when the volume density reaches between 10% and 30%. Under high cell concentration conditions, the BSC magnitude increases slower than proportionally with the number density at low frequencies (ka<1), as observed by others. However, what is new is that the BSC magnitude can increase either slower or faster than proportionally with number density at high frequencies (ka>1). The concentric sphere model least squares estimates show a decrease in estimated cell radius with number density, suggesting that the concentric spheres model is becoming less applicable as concentration increases because the estimated cell radius becomes smaller than that measured. The critical volume density, starting from when the model becomes less applicable, is estimated to be between 10% and 30% cell volume density.
Constitutive activation of phosphatidyl‐inositide 3 kinase contributes to the survival of Hodgkin's lymphoma cells through a mechanism involving Akt kinase and mTOR (2005)

The molecular mechanisms underlying the pathogenesis of the malignant Hodgkin's/Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL) are largely unknown. This study investigates the contribution of phosphatidyl-inositide 3 kinase (PI3-kinase) and demonstrates that Akt, a substrate of PI3-kinase, is constitutively activated in HL-derived cell lines. Several downstream effectors of Akt signalling, including glycogen synthase kinase 3 (GSK-3) alpha and beta and mTOR substrates 4E-BP1 and p70 S6 kinase, were also phosphorylated in HL cells. The mTOR inhibitor, rapamycin, inhibited phosphorylation of these proteins. Furthermore, LY294002 inhibited phosphorylation of p70 S6 kinase and 4E-BP1, suggesting that the phosphorylation of p70 S6 kinase and 4E-BP1 in HL cells is PI3-kinase dependent. Importantly, HRS cells of primary tumour samples not only expressed high levels of activated Akt but also displayed phosphorylation of downstream targets of Akt activation including GSK-3, 4E-BP1, and p70 S6 Kinase. Inhibition of PI3-kinase and mTOR showed only modest effects on cell survival at the lower serum concentrations. However, rapamycin and doxorubicin acted synergistically to reduce HL cell survival. A combination of rapamycin and chemotherapy should be investigated in the treatment of HL.
Interleukin-1 Expression in Different Plaque Types in Alzheimerʼs Disease (1995)

The histologically apparent polymorphism of plaques containing beta-amyloid in Alzheimer's disease is thought to represent different stages in plaque evolution. beta-amyloid-immunopositive plaques were classified according to the pattern of beta-amyloid distribution (diffuse vs dense-core) and the presence or absence of dystrophic beta-amyloid precursor protein-immunopositive (beta-APP+) neurites (neuritic vs non-neuritic). The potential contribution of microglia-derived interleukin-1 (IL-1), an immune response cytokine that induces synthesis and processing of beta-APP, to the possible sequential development of these plaque types was examined through determination of the number of IL-1 alpha+ microglia associated with each of four identified plaque types. Diffuse non-neuritic plaques had the least dense and most widely dispersed beta-amyloid, did not exhibit beta-APP+ dystrophic neurites, but most (78%) contained activated IL-1 alpha+ microglia (2 +/- 0.2/plaque; mean +/- SEM). Diffuse neuritic plaques had more dense, but still widely dispersed beta-amyloid, displayed a profusion of beta-APP+ dystrophic neurites, and had the greatest numbers of associated activated IL-1 alpha+ microglia (7 +/- 0.8/plaque). Dense-core neuritic plaques had both compact and diffuse beta-amyloid and had fewer IL-1 alpha+ microglia (4 +/- 0.4/plaque). Dense-core, non-neuritic plaques had compact beta-amyloid, lacked associated diffuse beta-amyloid, and were devoid of both IL-1 alpha+ microglia and beta-APP+ dystrophic neurites. These results suggest an important immunological component in the evolution of amyloid-containing plaques in Alzheimer's disease and further suggest that IL-1-expressing cells are necessary to initiate dystrophic neurite formation in diffuse beta-amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS)
Physics of electrophotography (1993)

Electrophotography is one means of arranging 100 million pigmented plastic particles on a sheet of paper to faithfully replicate an original. It is based on many diverse phenomena and employs many properties of matter. These include gaseous ionization in the charging step; photogeneration and charge transport through disordered solid-state materials in the latent-image-formation step; triboelectricity in the particle-charging step; mechanical, electrostatic, and magnetic forces to detach particles in the development and transfer steps; and the application and transfer of heat in the fixing step. In addition, it relies on a precise balance of thermorheological, chemical, and mechanical properties of large area films and small particles. This article reviews the physics of the latent-image formation and development steps.
Vitamin B12 responsive homocystinuria and megaloblastic anemia: Heterogeneity in methylcobalamin deficiency (1987)

A male infant with methyl-B12 deficiency (cblE) presented at age 6 weeks with lethargy, staring spells, and vomiting. He later became hypotonic and unresponsive to stimuli and required intubation and ventilation. He had homocystinuria and hypomethioninemia with megaloblastic anemia but normal serum folate and vitamin B12 concentrations. No methylmalonic aciduria was detected. Fibroblasts, cultured from the patient, were unable to grow in medium in which homocysteine replaced methionine and incorporated abnormally small amounts of [14C]-methyl-tetrahydrofolate but normal amounts of [14C]-propionate into protein. Methyl-B12 content of fibroblasts was low, while the adenosyl-B12 content was normal. Methionine synthase activity was decreased when the assay was performed under both optimal and suboptimal reducing conditions, suggesting heterogeneity in the cblE disease. The patient responded dramatically to hydroxocobalamin treatment. Homocystinuria disappeared after 10 days of therapy, and methionine was normalized after 3 weeks. Psychometric testing at age 15 months showed a developmental age of 9 months.
Down‐regulation of GAP‐43 During Oligodendrocyte Development and Lack of Expression by Astrocytes In Vivo: Implications for Macroglial Differentiation (1991)

The discovery of molecular markers which are selectively expressed during the development of specific classes of rat central nervous system macroglia has greatly advanced our understanding of how these cells are related. In particular, it has been shown in tissue culture that oligodendrocytes and some astrocytes (type-2) may be derived from a common progenitor cell (O-2A progenitor). However, the existence of type-2 astrocytes in vivo has yet to be unequivocally established. Recently, it has been reported that the neural-specific growth-associated protein-43 (GAP-43, otherwise known as B-50, F1, pp46 and neuromodulin) may be expressed by cells of the O-2A lineage in vitro. We set out to examine the cellular specificity of GAP-43 in O-2A progenitors and their descendants in vitro and in vivo. Using a polyclonal antiserum against a GAP-43 fusion protein we have shown the presence of immunoreactive GAP-43 in the membranes of bipotential O-2A glial progenitor cells and type-2 astrocytes by Western blotting and immunocytochemistry of cells in culture. In contrast to previous studies, double labelling with mature oligodendrocyte markers showed that GAP-43 is down-regulated during oligodendrocyte differentiation in vitro. Immunohistochemical staining of sections of developing rat brain demonstrated the same developmental regulation of GAP-43, suggesting that oligodendrocytes only express GAP-43 at immature stages. In addition, normal and reactive astrocytes in tissue sections were not labelled with GAP-43.
Influence of Mobile Ions on Nanotube Based FET Devices (2003)

Carbon nanotube field-effect transistors often exhibit a hysteresis effect in the gate-voltage dependence. We report devices fabricated with small hysteresis, and demonstrate a method to introduce this effect controllably by coating nanotube devices with charged polymers. In addition, the hysteresis is sensitive to humidity on sub-second time scales, showing promise as a humidity sensor. The polymer charge is related to the threshold shift observed, proving that the induced hysteresis results from ionic motion.
Spheres Isolated from 9L Gliosarcoma Rat Cell Line Possess Chemoresistant and Aggressive Cancer Stem‐Like Cells (2007)

The rat 9L gliosarcoma is a widely used syngeneic rat brain tumor model that closely simulates glioblastoma multiforme when implanted in vivo. In this study, we sought to isolate and characterize a subgroup of cancer stem-like cells (CSLCs) from the 9L gliosarcoma cell line, which may represent the tumor-initiating subpopulation of cells. We demonstrate that these CSLCs form clonal-derived spheres in media devoid of serum supplemented with the mitogens epidermal growth factor and basic fibroblast growth factor, express the NSC markers Nestin and Sox2, self-renew, and differentiate into neuron-like and glial cells in vitro. More importantly, these cells can propagate and recapitulate tumors when implanted into the brain of syngeneic Fisher rats, and they display a more aggressive course compared with 9L gliosarcoma cells grown in monolayer cultures devoid of mitogens. Furthermore, we compare the chemosensitivity and proliferation rate of 9L gliosarcoma cells grown as a monolayer to those of cells grown as floating spheres and show that the sphere-generated cells have a lower proliferation rate, are more chemoresistant, and express several antiapoptosis and drug-related genes, which may prove to have important clinical implications. Disclosure of potential conflicts of interest is found at the end of this article.
Off-road Path Following using Region Classification and Geometric Projection Constraints (2006)

We describe a realtime system for finding and tracking unstructured paths in off-road conditions. The system was designed as part of the recent Darpa Grand Challenge and was tested over hundreds of miles of off-road driving. The unique feature of our approach is to combine geometric projection used for recovering Pitch and Yaw with Learning approaches for identifying familiar "drivable" regions in the scene. The region-based component segments the image to "path" and "non-path" regions based on texture analysis borne out of a learning-by-examples principle. The boundary-based component looks for the path bounding lines assuming a geometric model of a planar pathway bounded by parallel edges taken by a perspective camera. The combined effect of both sub-systems forms a robust system capable of finding the path even in situations where the vehicle is positioned out of the path - a situation which is not common for human drivers but is relevant for autonomous driving where the vehicle may find itself occasionally veering out of the path.
A Single Amino Acid Interchange Yields Reciprocal CTL Specificities for HIV-1 gp160 (1989)

For the IIIB isolate of human immunodeficiency virus type-1 (HIV-1), the immunodominant determinant of the envelope protein gp160 for cytotoxic T lymphocytes (CTLs) of H-2d mice is in a region of high sequence variability among HIV-1 isolates. The general requirements for CTL recognition of peptide antigens and the relation of recognition requirements to the natural variation in sequence of the HIV were investigated. For this purpose, a CTL line specific for the homologous segment of the envelope from the MN isolate of HIV-1 and restricted by the same class I major histocompatibility (MHC) molecule (Dd) as the IIIB-specific CTLs was raised from mice immunized with MN-env-recombinant vaccinia virus. The IIIB-specific and MN-specific CTLs were completely non-cross-reactive. Reciprocal exchange of a single amino acid between the two peptide sequences, which differed in 6 of 15 residues, led to a complete reversal of the specificity of the peptides in sensitizing targets, such that the IIIB-specific CTLs lysed targets exposed to the singly substituted MN peptide and vice versa. These data indicate the importance of single residues in defining peptide epitopic specificity and have implications for both the effect of immune pressure on selection of viral mutants and the design of effective vaccines.
VARIATIONS IN SUBJECT POOL AS A FUNCTION OF EARLIER OR LATER PARTICIPATION (2000)

Data were obtained from 113 participants in a university subject pool during a 16-wk. semester. Without knowing the purpose of the study, participants self-selected to participate earlier (Weeks 3 and 4: n = 63) or later (Weeks 15 or 16) n = 50). Variations in scores on the NEO Personality Inventory–Revised, the Crowne-Marlowe Social Desirability Scale, the General Expectancy of Success Scale, the Shipley Institute of Living Scale, self-reported SATs and GPAs, and a measure of academic self-efficacy as a function of earlier or later participation were examined. Multivariate analysis of variance indicated that early participants differed significantly from later participants but not in predicted ways. Earlier participants scored higher on NEO PI–R Neuroticism; specifically men (n = 15) and women (n = 48) scored higher on Hostility, and women scored higher on Depression and Self-consciousness. An additional significant difference occurred for self-reported SAT Verbal scores for men, which were significantly higher for later participants. These temporal variations may represent confounds in research using university subject pools.