gebhart/patrepeval huggingface dataset:
Functional cooperation between T helper cell determinants (2000)

The immune response to T helper (Th) cell determinants of a variety of antigens is often poor and limits severely the potential efficacy of current therapeutic measures through vaccination. Here, we report that an immunologically silent tumor determinant can be rendered immunogenic if linked with a dominant determinant of a parasite antigen, suggesting the existence of functional Th-Th cooperation in vivo. This phenomenon could be mimicked in part by signaling either through CD40 to the antigen-presenting cells or through OX40 to the tumor-determinant reactive T cells, with maximal effects obtained by combined anti-CD40 and anti-OX40 treatment in vivo. The data suggest that CD4 T cells reactive with a dominant determinant provide help to other CD4 T cells through up-regulating the costimulatory ability of antigen-presenting cells, in much the same way as help for CD8 cells. CD4 help for CD4 T cells represents a new immunological principle and offers new practical solutions for vaccine therapy against cancer and other diseases in which antigenic help is limiting.
Tissue-Specific Expression of the Human CD 19 Gene in Transgenic Mice Inhibits Antigen-Independent B-Lymphocyte Development (1994)

CD19 is a B-cell-specific member of the immunoglobulin superfamily expressed from early pre-B-cell development until plasma cell differentiation. In vitro studies demonstrate that the CD19 signal transduction molecule can serve as a costimulatory molecule for activation through other B-lymphocyte cell surface molecules. However, much remains to be known regarding how CD19 functions in vivo and whether CD19 has different roles at particular stages of B-cell differentiation. Therefore, transgenic mice overexpressing the human CD19 (hCD19) gene were generated to determine whether this transgene would be expressed in a B-lineage-specific fashion and to dissect the in vivo role of CD19 in B-cell development and activation. Expression of the human transgene product was specifically restricted to all B-lineage cells and appeared early in development as occurs with hCD19. In addition, expression of hCD19 severely impaired the development of immature B cells in the bone marrow, with dramatically fewer B cells found in the spleen, peripheral circulation, and peritoneal cavity. The level of hCD19 expressed on the cell surface correlated directly with the severity of the defect in different transgenic lines. These results demonstrate that the hCD19 gene is expressed in a lineage-specific fashion in mice, indicating that the hCD19 gene may be useful for mediating B-lineage-specific expression of other transgene products. In addition, these results indicate an important role for the lineage-specific CD19 molecule during early B-cell development before antigen-dependent activation.
JAK2 in Myeloproliferative Disorders Is Not Just Another Kinase (2005)

Myeloproliferative disorders (MPD) represent a subcategory of hematological malignancies and are characterized by a stem cell-derived clonal proliferation of myeloid cells including erythrocytes, platelets, and leucocytes. Traditionally, the term 'MPD' included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis with myeloid metaplasia (MMM). At present, these four disorders are referred to as 'classic' MPD and are distinguished from a spectrum of other MPD-like clinicopathologic entities that are operationally classified as 'atypical' MPD. The oncogenic mutations(s) in classic MPD are unknown except for CML, which is associated with an activating mutation (Bcr/Abl) of the gene encoding for the Abl cytoplasmic protein kinase (PTK). In the last 3 months, a somatic point mutation of JAK2 (JAK2(V617F)), the gene encoding for another cytoplasmic PTK was reported in the majority of patients with PV and approximately half of those with either ET or MMM. The same mutation was also found in a small number of patients with either atypical MPD or the myelodysplastic syndrome but not in normal controls, germline tissue including T lymphocytes, and patients with secondary erythrocytosis. In vitro, JAK2(V617F) was associated with constitutive phosphorylation of JAK2 and its downstream effectors as well as induction of erythropoietin hypersensitivity in cell lines. In vivo, murine bone marrow transduced with a retrovirus containing JAK2(V617F) induced erythrocytosis in the transplanted mice. Taken together, these observations suggest that JAK2(V617F) is an acquired myeloid lineage-specific mutation that engenders a pathogenetic relevance for the PV phenotype in MPD.
In vitro selection of viral vectors with modified tropism: the adeno-associated virus display (2003)

Improving the efficiency and specificity of gene vectors is critical for the success of gene therapy. In an effort to generate viral mutants with controlled tropism we produced a library of adeno-associated virus (AAV) clones with randomly modified capsids and used it for the selection of receptor-targeting mutants. After several rounds of selection on different cell lines that were resistant to infection by wild-type (wt) AAV, infectious mutants were harvested at high titers. These mutants transduced target cells with an up to 100-fold increased efficiency, in a receptor-specific manner and without interacting with the primary receptor for wt AAV. The results demonstrate for the first time that a combinatorial approach based on a eukaryotic virus library allows one to generate efficient, receptor-specific targeting vectors with desired tropism.
FormCracker (2010)

Filling out document forms distributed by email or hosted on the Web is still problematic and usually requires a printer and scanner. Users commonly download and print forms, fill them out by hand, scan and email them. Even if the document is form-enabled (PDFs with FDF information), to read the file users still have to launch a separate application which may not be available, especially on mobile devices.
Parametric study of antenna with parasitic element for improving the hearing aids compatibility of mobile phones and the Specific absorption rate in the head (2011)

In this paper, we present a design of a planar inverted F antenna (PIFA) mounted on a ground plane with form factor corresponding to a typical candy bar type of mobile phone. A quarter-wavelength parasitic element is introduced with the objective to both decrease the specific absorption rate (SAR) and improve the level of hearing aid compatibility (HAC). By varying the position of the parasitic element we have achieved reduction in the averaged SAR in the order of 20% in the 1900MHz GSM band. However, the improvement of HAC due to electric and magnetic fields has been found only marginal.
Amacrine-Signaled Loss of Intrinsic Axon Growth Ability by Retinal Ganglion Cells (2002)

The central nervous system (CNS) loses the ability to regenerate early during development, but it is not known why. The retina has long served as a simple model system for study of CNS regeneration. Here we show that amacrine cells signal neonatal rat retinal ganglion cells (RGCs) to undergo a profound and apparently irreversible loss of intrinsic axon growth ability. Concurrently, retinal maturation triggers RGCs to greatly increase their dendritic growth ability. These results suggest that adult CNS neurons fail to regenerate not only because of CNS glial inhibition but also because of a loss of intrinsic axon growth ability.
Sequence-Specific Photomodification of DNA by an Oligonucleotide-Phenanthrodihydrodioxin Conjugate (1998)

We introduce a new member of a family of photochemically active oligonucleotide conjugates. A Phenanthrodihydrodioxin (PDHD)-based agent was synthesized and covalently linked to a 5'-end of the 9-mer oligonucleotide via a hexamethylene linker. The conjugate hybridized to a complementary 30-nucleotide-long target and efficiently cleaved it in a sequence specific manner. Up to 67% of target was specifically damaged (51% cross-links and 16% direct cleavage). While the photosensitizer alone nonspecifically damaged only Gs in a single-stranded target, its conjugate cross-linked to and damaged also A, T, and C sites in a target in agreement with duplex and triplex formation.
The features of clearance in recombinant factor IX (BeneFIX<sup>®</sup>) (2015)

The mean CL calculated from IVR and distribution half-life was 4.4 ± 0.4 mL kg(-1) h(-1) (range = 4.0-5.1 mL kg(-1) h(-1) ). The mean CL calculated from IVR and terminal half-life was 2.1 ± 0.5 mL kg(-1) h(-1) (range = 1.7-2.8 mL kg(-1) h(-1) ). The mean CL during CI was 4.9 ± 0.6 mL kg(-1) h(-1) (range = 4.2-5.6 mL kg(-1) h(-1) ). In addition, when we simulated the theoretical CL using a one-compartment model, the adjusted mean CL during CI was 4.8 ± 0.5 mL kg(-1) h(-1) (range = 4.0-5.4 mL kg(-1) h(-1) ). The CL obtained from distribution half-life was comparable to the CL during CI, while the CL calculated from terminal half-life did not reflect actual CL. Further, the rFIX concentrate was characterized by a one-compartment model under certain conditions.
Microbeam-forming methods for synchrotron radiation (1997)

The increasing availability of synchrotron x-ray sources has stimulated the development of advanced hard x-ray (E⩾5 keV) microprobes. It is now possible to achieve intense submicron x-ray beams with a variety of techniques including Fresnel zone plates, Kirkpatrick–Baez mirrors, tapered capillaries and Bragg–Fresnel optics. These synchrotron-based x-ray microprobes can be used for ultra-sensitive elemental detection by x-ray fluorescence/absorption and for microdiffraction to identify phase and strain with submicron resolution. Advanced methods for forming microbeams are reviewed and the relative merits of each approach are discussed. The efficient techniques developed for synchrotron beams can also be used to tailor the beam properties from conventional x-ray sources. © 1997 This article is a US Government work and, as such, is in the public domain in the United States of America
Technique for in situ measurement of calcium in intracellular inositol 1,4,5-trisphosphate-sensitive stores using the fluorescent indicator mag-fura-2. (1993)

Stimulation of cells with calcium-mobilizing agonists frequently results in inositol 1,4,5-trisphosphate (InsP3)-mediated discharge of Ca from an internal store. We report here a technique for directly monitoring Ca within this and other stores in gastric epithelial cells. This technique takes advantage of the propensity of the acetoxymethyl ester derivative of the fluorescent dye mag-fura-2 (which is sensitive to Ca concentrations above 5 microM) to accumulate in subcellular compartments where it can report changes in the free Ca concentration. Intact dye-loaded cells responded to cholinergic stimulation with a decrease in the 350 nm/385 nm excitation ratio, as measured in individual cells with a digital imaging microscope, consistent with reduced Ca concentration in one or more cellular compartments. When cells were permeabilized with digitonin and incubated in an "intracellular buffer," the cytoplasmic dye was released, leaving the mag-fura-2 in the internal store. InsP3 caused the ratio from the trapped indicator to decrease (i.e., Ca was released) in a dose-dependent manner, and this effect was blocked by the InsP3 receptor antagonist heparin. Ca sequestration into the internal store was ATP-dependent, and reuptake into the InsP3-sensitive pool was blocked by thapsigargin, a specific inhibitor of the Ca-ATPase of the internal store. We used this technique to investigate the role of Cl on the release and reloading of the InsP3-sensitive internal store and found that Ca uptake was reduced in Cl-free solutions, suggesting an important function for Cl in the refilling of this pool.
Synthesis and insecticidal activity of benzoheterocyclic analogues of <i>N</i>′‐benzoyl‐<i>N</i>‐(<i>tert</i>‐butyl)benzohydrazide: Part 1. Design of benzoheterocyclic analogues (2002)

The N'-benzoyl group of N-tert-butyl-N'-benzoyl-3,5-dimethylbenzohydrazide (1) was converted to a series of benzoheterocyclecarbonyl groups in order to investigate the potential usefulness of superimposing a hydrazine insecticide on 20-hydroxyecdysone. A series of analogues with benzodioxole, benzodioxane, benzodioxapine, indole, benzoxazole, benzoxazine or benzothiazole instead of the phenyl group of (1) were synthesized and tested for their insecticidal activity against the common cutworm (Spodoptera litura F). N-tert-Butyl-N'-(3,5-dimethylbenzoyl)-1,3-benzodioxole-5-carbohydrazide and N-tert-butyl-N'-(3,5-dimethylbenzoyl)-2,3-dihydro-1,4-benzodioxine-6-carbohydrazide showed high insecticidal activities, superior to that of (1) and equal to that of the commercial insecticide tebufenozide (RH-5992).
Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity. (2003)

Dendritic cells (DCs) were adenovirally engineered to constitutively and durably secrete the potent Th1-biasing cytokines interleukin (IL)-12 (AdIL12DC) and/or IL-18 (AdIL18DC) and evaluated for their ability to promote therapeutic antitumor immunity in murine sarcoma models. Injection of either AdIL12DC or AdIL18DC into day 7 CMS4 or MethA tumors resulted in tumor rejection or slowed tumor growth when compared with control cohorts. Importantly, intratumoral injection with DCs engineered to secrete both IL-12 and IL-18 (AdIL12/IL18DC) resulted in complete and the most acute rejection of any treatment group analyzed. This strategy was also effective in promoting the regression of contralateral, untreated tumors. Both CD4+ and CD8+ T cells were required for tumor rejection. CD8+ splenic T cells from mice treated with AdIL12/IL18DC produced the highest levels of IFN-gamma in response to tumor rechallenge in vitro and displayed the broadest repertoire of Tc1-type reactivity to acid-eluted, tumor-derived peptides among all treatment cohorts. This apparent enhancement in cross-presentation of tumor-associated epitopes in vivo may result from the increased capacity of engineered DCs to kill tumor cells, survive tumor-induced apoptosis, and present immunogenic MHC/tumor peptide complexes to T cells after intratumoral injection. In support of this hypothesis, cytokine gene-engineered DCs expressed higher levels of MHC and costimulatory molecules, as well as Fas ligand and membrane-bound tumor necrosis factor alpha, with the latter markers associated with elevated tumoricidal activity in vitro. Cytokine gene-engineered DCs appeared to have a survival advantage in situ when injected into tumor lesions, to be found in approximation with regions of tumor apoptosis, and to have the capacity to ingest apoptotic tumor bodies. These results support the ability of combined cytokine gene transfer to enhance multiple effector functions mediated by intralesionally injected DCs that may concertedly promote cross-priming and the accelerated immune-mediated rejection of tumors.
Minnesota Agricultural Economist 688 (1997)

ECR : A Revolution in the Retail Food System
Immune Mechanisms in Pulmonary Fibrosis (2016)

Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis, represents a chronic and progressive disease with high mortality and limited therapeutic options. Excessive deposition of extracellular matrix proteins results in fibrotic remodeling, alveolar destruction, and irreversible loss of lung function. Both innate and adaptive immune mechanisms contribute to fibrogenesis at several cellular and noncellular levels. Here, we summarize and discuss the role of immune cells (T cells, neutrophils, macrophages, and fibrocytes) and soluble mediators (cytokines and chemokines) involved in pulmonary fibrosis, pointing toward novel immune-based therapeutic strategies in the field.
Population pharmacokinetics of recombinant factor IX: implications for dose tailoring (2013)

The principles of pharmacokinetic (PK) dose tailoring in clinical practice, using limited blood sampling and Bayesian PK analysis, have been described for factor VIII (FVIII). This study applied the same procedure to recombinant FIX (rFIX), i.e. population PK modelling and the use of a simplified (one-compartment) model to describe only the terminal part of the coagulation factor vs. time curve. Data from a previous study on rFIX in 56 patients (4-56 years, 18-133 kg) were used to define a three-compartment population PK model. The average FIX clearance was 8.4 mL h(-1) kg(-1) . Elimination half-life ranged between 14 and 27 h. Data obtained from 24 h after the infusion were found to define the terminal phase of FIX disposition. Doses to produce a target trough FIX level (set at 0.01 IU mL(-1) ) at 72 h predicted by the Bayesian analysis, with blood sampling at either 24, 48 and 72 h or at only 24 and 48 h, were within -40% to +67% of those predicted using the three-compartment model, and within -57% to +125% for targeting a level at 96 h. These errors were lower than the overall interindividual variance in dose requirements. As three-compartment models are needed to characterize the PK of both plasma-derived FIX and rFIX, simplification to a one-compartment model is less straightforward than for FVIII, and the methodology should be investigated further before clinical application. Limited blood sampling and Bayesian analysis could still, however, be potentially useful for targeting rFIX trough levels during prophylaxis.
Faster cascading menu selections with enlarged activation areas (2006)

Cascading menus are used in almost all graphical user interfaces. Most current cascade widgets implement an explicit delay between the cursor entering/leaving a parent cascade menu item and posting/unposting the associated menu. The delay allows users to make small steering errors while dragging across items, and it allows optimal diagonal paths from parent to cascade items. However, the delay slows the pace of interaction for users who wait for the delay to expire, and it demands jerky discrete movements for experts who wish to pre-empt the delay by clicking. This paper describes Enlarged activation area MenUs (EMUs), which have two features: first, they increase the area of the parent menu associated with each cascade; second, they eliminate the posting and unposting delay. An evaluation shows that EMUs allow cascade items to be selected up to 29% faster than traditional menus, without harming top-level item selection times. They also have a positive smoothing effect on menu selections, allowing continuous sweeping selections in contrast to discrete movements that are punctuated with clicks.
Molecular cloning of the GTP‐cyclohydrolase structural gene <i>RIB1</i> of <i>Pichia guilliermondii</i> involved in riboflavin biosynthesis (1995)

The structural gene of GTP-cyclohydrolase, involved in riboflavin biosynthesis, was cloned from a Pichia guilliermondii genomic library. A 1855 bp genomic DNA fragment complementing the riboflavin auxotrophies of an Escherichia coli ribA mutant, defective in GTP-cyclohydrolase II, and a P. guilliermondii rib1 mutant was isolated and sequenced. An open reading frame with the potential to encode a protein of 344 amino acids with a predicted molecular mass of 38,711 Da was detected. The P. guilliermondii enzyme shows a high degree of homology to GTP-cyclohydrolases type II from E. coli and Baccillus subtilis and to GTP-cyclohydrolase from Saccharomyces cerevisiae. Functional GTP-cyclohydrolase from P. guilliermondii may consist of four identical subunits.
Saturated Red‐Emitting Electrophosphorescent Polymers with Iridium Coordinating to <i>β</i>‐Diketonate Units in the Main Chain (2006)

Abstract Summary: A series of novel copolymers with fluorene‐ alt ‐carbazole segments and β ‐diketonate moieties coordinating to iridium were synthesized by Suzuki polycondensation, and characterized by 1 H NMR, 13 C NMR, and GPC. In the absorption spectra of the copolymers, metal‐to‐ligand charge‐transfer transitions coming from iridium complex increased in intensity with increasing content of Ir complex in copolymers. The photoluminescence spectra of the copolymers were dominated by emission from the iridium complex with peak at ca. 620 nm even at the feed ratio of the complex as low as 0.5 mol‐%. The electrochemical investigation indicated that the incorporation of carbazole and iridium complex units reduce the barrier for both hole and electron injection compared with the polyfluorene. The light‐emitting diodes using the copolymers as emission layer under different device configurations were fabricated. The devices with 2‐(4‐biphenylyl)‐5‐(4‐ tert ‐butylphenyl)‐1,3,4‐oxadiazole (PBD) show significantly higher external quantum efficiencies than those without PBD. A saturated red‐emitting polymer light‐emitting diode with emission peak at 628 nm, the maximum external quantum efficiency of 0.6% at the current density ( J ) of 38.5 mA · cm −2 , and the maximum luminance of 541 cd · m −2 at 15.8 V was achieved from the device ITO/PEDOT/PFCzIrpiq3 + PBD (40%)/Ba/Al. Novel copolymers with fluorene‐ alt ‐carbazole segments and iridium coordinating to β ‐diketonate in the main chain. magnified image Novel copolymers with fluorene‐ alt ‐carbazole segments and iridium coordinating to β ‐diketonate in the main chain.
Cold-sensitive growth and decreased GTP-hydrolytic activity from substitution of Pro17 for Val in Era, an essential Escherichia coli GTPase (1992)

A substitution mutation of Pro17 by Val (P17V) was constructed in the guanine nucleotide binding domain of Era, an essential protein in Escherichia coli. The mutation is analogous to the oncogenic activating allele at position 12 in the GTP-binding domain of p21ras. The phenotype of this mutant was analysed in a strain which exclusively expressed the mutant protein (Era-V17) in null allele chromosomal background (era1: :kan). The strain was found to be cold-sensitive for growth. Mutant Era-V17 purified from the strain was cold-sensitive for GTP-hydrolytic activity, suggesting that the GTPase activity of Era is required for cell growth since the P17V mutation resulted in both cold-sensitive growth of cells and cold-labile GTPase activity of the purified protein.
Microstructure Evolution and Mechanical Behavior of Mg‐10Gd‐3Y‐0.4Zr Alloy Processed by ECAP at High Temperature (2014)

This chapter contains sections titled: Introduction Experiments Results and Discussion Conclusions Acknowledgements
Endogenous steroids and financial risk taking on a London trading floor (2008)

Little is known about the role of the endocrine system in financial risk taking. Here, we report the findings of a study in which we sampled, under real working conditions, endogenous steroids from a group of male traders in the City of London. We found that a trader's morning testosterone level predicts his day's profitability. We also found that a trader's cortisol rises with both the variance of his trading results and the volatility of the market. Our results suggest that higher testosterone may contribute to economic return, whereas cortisol is increased by risk. Our results point to a further possibility: testosterone and cortisol are known to have cognitive and behavioral effects, so if the acutely elevated steroids we observed were to persist or increase as volatility rises, they may shift risk preferences and even affect a trader's ability to engage in rational choice.
Trends in hospitalization for heart failure in Scotland, 1990–1996. An epidemic that has reached its peak? (2001)

Heart failure continues to be a common cause of hospitalization. The previously reported 'epidemic' of increasing rates of hospitalization for heart failure in Scotland and elsewhere between 1980 and 1990, however, seems to have peaked (in about 1993/4).