gebhart/patrepeval huggingface dataset:
High expression of urokinase plasminogen activator receptor (UPA-R) in acute myeloid leukemia (AML) is associated with worse prognosis (2005)

Urokinase-type plasminogen activator receptor (UPA-R; CD87) is a membrane protein responsible for plasmin expression on cells facilitating cellular extravasations and tissue invasions. We studied the expression of the UPA-R on bone marrow (BM) cells of 93 patients with acute myeloid leukemia at first diagnosis and 8 healthy probands as controls by FACS analysis using phycoerythrin (PE)-conjugated antibodies. A case was defined as UPA-R-positive (UPA-R+) if >20% of the gated cells expressed UPA-R. Whereas none of the 8 healthy BM samples was positive for the UPA-R, 32 (34%) of the 93 AML samples were UPA-R+. Expression of UPA-R was heterogeneous in different FAB types, however, with the highest expression rates in monocytic subtypes (FAB M4/M5): 18%/19%/30% of UPA-R+ cases were found in M1/M2 or M3, and 58%/80% of cases with M4 or M5 were UPA-R+. Proportions of UPA-R+ cells varied between 1% and 98% of the mononuclear cell fractions, with the highest proportions in M4/M5 subtypes (on average 27%/40% UPA-R+ cells) and the lowest expression in AML M2 (11% UPA-R+ cells). The density of expressed UPA-R, estimated as mean channel fluorescence activity, was highest in cases with AML M1 (mFI: 124) followed by M4 and M5 (mFI: 78/77) and lowest in AML M2 (mFI: 43). In sAML, higher proportions of UPA-R+ cases (8 of 18; 44%) compared to pAML (24 of 75; 32%) were found as well as higher proportions of UPA-R+ cells (27% vs. 19%). Separating our patients' cohort in cytogenetic risk groups, we could not detect significant differences in the UPA-R expression profiles. For evaluations of the clinical course of AML, only patients treated by the AML-CG protocol (n = 65) were included. In the group of patients who did not respond to AML-CG therapy, significantly higher proportions of UPA-R+ cells (31% vs. 14%, P = 0.0015, t-test) were found. By evaluating a cut-off value for the percentage of positive cells that allows the most significant separation and differentiation between cases with shorter or longer relapse-free survival times, we could show that patients with >26.5% UPA-R-positive cells were characterized by a significantly higher risk for relapse compared to cases with <26.5% positive cells (P = 0.05). In summary, our data show a high expression of the UPA-R in AML, especially in (myelo)monocytoid subtypes. Cases with higher proportions of UPA-R+ cells were characterized by a significant lower remission rate after AML-CG therapy and a higher risk for relapse. Although prospective trials are still lacking, UPA-R is a prognostically relevant factor independent from the karyotype. UPA-R positivity may identify subtypes of AML associated with a more aggressive clinical course. Thus due to lower remission probabilities in UPA-R+ cases, a more intensive induction therapy regimen could be considered.
Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. (1992)

We have shown that E1 and E2 proteins of human papillomavirus type 11 (HPV-11) were essential to support the replication of the homologous viral origin (ori) in a transient replication assay, similar to reports on bovine papillomavirus type 1 (BPV-1). Unexpectedly, matched or even mixed combinations of E1 and E2 proteins from HPV-11 or BPV-1 replicated either ori in human, monkey, and rodent cell lines of epithelial or fibroblastic lineage, albeit with varied efficiencies. Either set of viral proteins was also able to initiate replication of ori-containing plasmids from many other human and animal papillomaviruses. Thus the interactions among the cis elements and trans factors of papillomaviruses are more conserved than expected from the other members of the papovavirus family, simian virus 40 and polyomavirus, for which large tumor antigen does not replicate a heterologous ori in either permissive or nonpermissive cells. We infer that the stringent species and tissue specificities observed for papillomaviruses in vivo are not entirely due to direct restrictions on viral DNA replication. Rather, transcriptional control of viral gene expression must play a dominant role.
Emerging genetic therapies to treat Duchenne muscular dystrophy (2009)

These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy.
Abbeymycin, a new anthramycin-type antibiotic produced by a Streptomycete. (1987)

A new antibiotic, abbeymycin, has been isolated from Streptomyces sp. AB-999F-52. The structure of abbeymycin was assigned on the basis of NMR, mass spectrometric and UV spectral data. Abbeymycin has weak activity against a limited number of anaerobic bacteria.
3D-TV Content Creation: Automatic 2D-to-3D Video Conversion (2011)

Three-dimensional television (3D-TV) is the next major revolution in television. A successful rollout of 3D-TV will require a backward-compatible transmission/distribution system, inexpensive 3D displays, and an adequate supply of high-quality 3D program material. With respect to the last factor, the conversion of 2D images/videos to 3D will play an important role. This paper provides an overview of automatic 2D-to-3D video conversion with a specific look at a number of approaches for both the extraction of depth information from monoscopic images and the generation of stereoscopic images. Some challenging issues for the success of automatic 2D-to-3D video conversion are pointed out as possible research topics for the future.
Fibrillar collagen‐biphasic calcium phosphate composite as a bone graft substitute for spinal fusion (1992)

The osteoconductive capacity of fibrillar collagen-biphasic calcium phosphate composition was compared to autogenous bone in a canine spinal fusion model. All animals underwent a standard intervertebral body fusion (L2-L4) with rigid internal fixation and received either autogenous bone alone or a mixture of the ceramic and autogenous bone (3:1) as the graft material. Animals were followed for 12 months and the quality of fusion in each animal assessed by biomechanical testing and histological analysis. The fused L2-L4 segment of each dog was embedded in bone cement and mounted in a specially designed mechanical tester for testing in flexion, extension, and side bending. Overall, the mean rigidity of the fusion mass was not significantly different between the two groups [10.5 +/- 4.1 (SD) for autogenous bone vs. 11.3 +/- 1.7 for the ceramic plus autogenous bone, p greater than 0.05]. Similar findings were obtained for mean bending moment, compressive load, angular deformation, and energy absorbed for the two groups. Histological analysis was performed on transverse nondecalcified specimens. Quantitation of bone ingrowth using back-scattered electron imaging disclosed no significant differences in the amount of new bone formed at the graft site between autogenous bone and the ceramic plus autogenous bone recipients (23.4 +/- 10% vs. 25.8 +/- 8.8%) when correction for the autogenous bone volumes was performed. Light microscopic analysis of toluidine blue-stained transverse sections demonstrated new bone growth around and through the ceramic bone graft material. These results suggest that use of a collagen-biphasic calcium phosphate ceramic and autogenous bone mixture (3:1) provides a suitable osteoconductive alternative to the use of autogenous bone and results in the formation of a mechanically competent fusion mass not significantly different from that obtained with autogenous bone alone.
Canadian Headache Society guideline for migraine prophylaxis. (2012)

There is good evidence from randomized controlled trials for use of a number of different prophylactic medications in patients with migraine. Medication choice for an individual patient requires careful consideration of patient clinical features.
Expansion of a CD8+CD28- cell population in the blood and lung of HIV-positive patients. (1993)

CD8+ cytotoxic T lymphocytes (CTLs) in human immunodeficiency virus (HIV) patients have defects in cytolytic ability and proliferative potential. The surface receptor CD28 is important in regulating antigen-specific responses to T cells. We hypothesized that activated CD8+ CTLs in HIV patients would have altered expression of CD28. We examined surface expression of D44, a CD8+ CTL marker, and of CD28 on T cells from blood and bronchoalveolar lavage from HIV+ patients and normal volunteers. We found no significant difference between normal volunteers and HIV+ individuals in percentage of CD8+D44+ CTLs in blood or the lung. In contrast, CD8+CD28- T cells in the blood of HIV patients constituted 74% of CD8+ cells compared to 25% in normal subjects (p = 0.001), findings exaggerated in both normal and HIV+ lung. CD4+CD28- blood T cells were significantly increased in HIV+ patients compared to normal subjects (24 vs. 1.5%, p = 0.004). The HIV infection itself did not directly downmodulate CD28 expression, demonstrated in the CD28+ SUPT1 cell line. Increased numbers of CD28- T cells may be the result of immunologic activation or of expansion of a preexisting CD28- subset. These findings have immunologic consequences for the antigen-specific response of T cells in HIV+ patients.
In Vivo MRI Detection of Gliomas by Chlorotoxin‐Conjugated Superparamagnetic Nanoprobes (2008)

Converging advances in the development of nanoparticle-based imaging probes and improved understanding of the molecular biology of brain tumors offer the potential to provide physicians with new tools for the diagnosis and treatment of these deadly diseases. However, the effectiveness of promising nanoparticle technologies is currently limited by insufficient accumulation of these contrast agents within tumors. Here a biocompatible nanoprobe composed of a poly(ethylene glycol) (PEG) coated iron oxide nanoparticle that is capable of specifically targeting glioma tumors via the surface-bound targeting peptide, chlorotoxin (CTX), is presented. The preferential accumulation of the nanoprobe within gliomas and subsequent magnetic resonance imaging (MRI) contrast enhancement are demonstrated in vitro in 9L cells and in vivo in tumors of a xenograft mouse model. TEM imaging reveals that the nanoprobes are internalized into the cytoplasm of 9L cells and histological analysis of selected tissues indicates that there are no acute toxic effects of these nanoprobes. High targeting specificity and benign biological response establish this nanoprobe as a potential platform to aid in the diagnosis and treatment of gliomas and other tumors of neuroectodermal origin.
IP "telephony" vs. ATM: what is there to discuss? (2002)

This paper lists a number of issues that need to be addressed to natively support telephony services in an integrated service environment over both ATM and IP infrastructures. It presents the different approaches proposed for the network technologies. It then compares and contrasts the two solutions and concludes that IP networks are not likely to replace public telephone networks. As the current telephone networks evolve to B-ISDN, the role of IP may change from a layer 2 independent routing protocol to an addressing scheme with embedded routing information, similar to current use of E.164 addresses.
Fundamental aspects of contactless conductivity detection for capillary electrophoresis. Part I: Frequency behavior and cell geometry (2004)

A better understanding of the characteristics of the axial contactless conductivity cell could be obtained by carefully studying the effect of the cell geometry on its frequency behavior. A good fit between theoretical and experimental results shows that the axial contactless conductometric detector can effectively be described by the simplest possible equivalent circuitry consisting of a capacitor, resistor, and a second capacitor. The cell constant is largely defined by the length of the gap between the electrodes. The effective electrode size is thus not related to the dimensions of the real electrodes but more closely to the cross-sectional area of the internal diameter of the capillary. Typical experimental values of 20 MOmega and 0.1 pF were obtained for the resistance and capacitances, respectively, of a cell formed by a 2 mm gap between two 4 mm long electrodes fitted with a capillary of 50 microm ID. It could be shown that the diameter of the electrode is not critical and tight coupling of the electrodes to the outer wall of the capillary is not needed. The peak overshoot phenomenon, which has frequently been reported, is an artefact that can be minimized by optimizing the frequency for cell excitation. The frequency setting has to be optimized for each cell design, operational amplifier, electrolyte solution and capillary.
Computer vision in the interface (2004)

There are still obstacles to achieving general, robust, high-performance computer vision systems. The last decade, however, has seen significant progress in vision technologies for human-computer interaction.
Study of single-nucleotide polymorphism in seven genes (GHR, IGFBP3, IGFR1, IRS1, FMN1, ANXA2, TAGLN) in ethnic Russians and patients with prostate cancer (2010)

Using the RT-PCR method for allele discrimination, we examined nine known SNPs in seven genes (GHR, IGFBP3, IGFR1, IRS1, FMN1, ANXA2, TaGLN) in ethnic Russians and in patients with prostate cancer (PC). For Russian population data on genotype distribution in studied SNPs was obtained. It was revealed that six of nine analyzed sites in examined locus were polymorphic. Distributions of alleles and genotypes frequency of polymorphic site 1388 T/C (Leu463Pro) in gene FMN1 (rs2306277) were distinguished between patients and control groups (delta = 0.019; chi2 = 7.884). In particular, correlation of OO genotype with increased risk of PC was observed (OR = 2.1591 95% CI 1.2055-3.8726). Moreover, the analysis of the polymorphic site 2911G/A (Glu917Arg) in gene IRS1 (rs1801278) revealed the accumulation of allele A in cancer group in comparison with control group (chi2 = 4.038; p = 0.044). Thus, the obtained data indicate the possibility of participation of polymorphism in genes FMN1 and IRS1 in formation of predisposition to PC.
LC/MS/MS method for analysis of E2 series prostaglandins and isoprostanes (2011)

15-series prostaglandins (PGE₂s) and isoprostanes (isoPGE₂s) are robust biomarkers of oxidative stress, possess potent biological activity, and may be derived through cyclooxygenase or free radical pathways. Thus, their quantification is critical in understanding many biological processes where PG, isoPG, or oxidative stress are involved. LC/MS/MS methods allow a highly selective, sensitive, simultaneous analysis for prostanoids without derivatization. However, the LC/MS/MS methods currently used do not allow for simultaneous separation of the major brain PGE₂/D₂) and isoPGE₂ without derivatization and multiple HPLC separations. The developed LC/MS/MS method allows for the major brain PGE₂/PGD₂/isoPGE₂ such as PGE₂, entPGE₂, 8-isoPGE₂, 11β-PGE₂, PGD₂, and 15(R)-PGD₂ to be separated and quantified without derivatization. The method was validated by analyzing free and esterified isoPGE₂ in mouse brains fixed with head-focused microwave irradiation before or after global ischemia. Using the developed method, we report for the first time the esterified isoPGE₂ levels in brain tissue under basal conditions and upon global ischemia and demonstrate a nonreleasable pool of esterified isoPG upon ischemia. In addition, we demonstrated that PGE₂s found esterified in the sn-2 position in phospholipids are derived from a free radical nonenzymatic pathway under basal conditions. Our method for brain PG analysis provides a high level of selectivity to detect changes in brain PG and isoPG mass under both basal and pathological conditions.
Human monoclonal IgG isotypes differ in complement activating function at the level of C4 as well as C1q. (1988)

Humanized antibodies are likely to have a major role in therapy and it is important to define their interaction with physiological effectors. By comparing a matched series of chimeric human mAbs we found that igG1 was most efficient in complement lysis, although IgG3 bound more C1q. To resolve this paradox we compared the ability of human IgG1, IgG2, IgG3, IgG4, and IgE and rat IgG2b to cause C1q binding, C1 binding and activation, C4 activation, C4b binding, and C3b binding. Rat IgG2b was included because this isotype has already successfully been used for therapy. Human IgG1 was less efficient than IgG3 and fixing C1q and C1 on the cell surface, but the number of C4 molecules bound per C1 was 10-fold greater for IgG1 than for IgG3. This difference, amplified through later stages of the complement cascade, can account for the superiority of IgG1 for cell lysis. The efficiency of IgG1 in fixing C4 was not due to a favored binding site on the antibody molecule, since virtually all of the bound C4b was attached to the cells. Rather, it appeared that the activation of C4 by C1s was greatly favored by IgG1 compared with IgG3. It should be possible to combine the optimal properties of IgG1 and IgG3 antibodies to produce an improved therapeutic reagent.
Activation of a serine/threonine kinase signaling pathway by transforming growth factor type beta. (1995)

Transforming growth factor type beta (TGF-beta) is a multifunctional factor that regulates proliferation and differentiation of many cell types. TGF-beta mediates its effects by binding to and activating cell surface receptors that possess serine/threonine kinase activity. However, the intracellular signaling pathways through which TGF-beta receptors act remain largely unknown. Here we show that TGF-beta activates a 78-kDa protein (p78) serine/threonine kinase as evidenced by an in-gel kinase assay. Ligand-induced activation of the kinase was near-maximal 5 min after TGF-beta addition to the cells and occurred exclusively on serine and threonine residues. This kinase is distinct from TGF-beta receptor type II, as well as several cytoplasmic serine/threonine kinases of similar size, including protein kinase C, Raf, mitogen-activated protein kinase kinase kinase, and ribosomal S6 kinase. Indeed, these kinases can be separated almost completely from p78 kinase by immunoprecipitation with specific antibodies. Furthermore, using different cell lines, we demonstrate that p78 kinase is activated only in cells for which TGF-beta can act as a growth inhibitory factor. These data raise the interesting possibility that protein serine/threonine kinases contribute to the intracellular relay of biological signals originating from receptor serine/threonine kinases such as the TGF-beta receptors.
Role of Biotransformation in Drug-Induced Toxicity: Influence of Intra- and Inter-Species Differences in Drug Metabolism (2010)

It is now widely appreciated that drug metabolites, in addition to the parent drugs themselves, can mediate the serious adverse effects exhibited by some new therapeutic agents, and as a result, there has been heightened interest in the field of drug metabolism from researchers in academia, the pharmaceutical industry, and regulatory agencies. Much progress has been made in recent years in understanding mechanisms of toxicities caused by drug metabolites, and in understanding the numerous factors that influence individual exposure to products of drug biotransformation. This review addresses some of these factors, including the role of drug-drug interactions, reactive metabolite formation, individual susceptibility, and species differences in drug disposition caused by genetic polymorphisms in drug-metabolizing enzymes. Examples are provided of adverse reactions that are linked to drug metabolism, and the mechanisms underlying variability in toxic response are discussed. Finally, some future directions for research in this field are highlighted in the context of the discovery and development of new therapeutic agents.
The regulatory role of dendritic cells in the immune tolerance (2006)

Immune homeostasis is important for the protection of a host from pathogen aggression, as well as for preventing autoimmunity. Dendritic cells (DCs), the most potent antigen presenting cells, are critical in innate, adaptive immunity and in central tolerance. Recently, their involvement in peripheral tolerance has been shown. Whether DCs induce immunity or tolerance depends on their state of maturation. Different subsets of tolerogenic DCs have been identified in vivo, either in physiological, or pathological conditions, such as tumors, or GVHD. Moreover, tolerogenic DCs can be generated in vitro, by using different culture conditions, such as IL-10 or TGF-beta. In our study, we obtained tolerogenic DCs, by culturing them in the presence of human mesenchymal stem cells (MSCs).
Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages. (1993)

Because fibroblast growth factors (FGFs) modulate important functions of endothelial cells (EC) and smooth muscle cells (SMC), we studied FGF expression in human vascular cells and control or atherosclerotic arteries. All cells and arteries contained acidic (a) FGF and basic (b) FGF mRNA. Northern analysis detected aFGF mRNA only in one of five control arteries but in all five atheroma tested, while levels of bFGF mRNA did not differ among control (n = 3) vs. plaque specimens (n = 6). Immunolocalization revealed abundant bFGF protein in control vessels (n = 10), but little in plaques (n = 14). In contrast, atheroma (n = 14), but not control arteries (n = 10), consistently exhibited immunoreactive aFGF, notably in neovascularized and macrophage-rich regions of plaque. Because macrophages colocalized with aFGF, we tested human monocytoid THP-1 cells and demonstrated accumulation of aFGF mRNA during PMA-induced differentiation. We also examined the expression of mRNA encoding FGF receptors (FGFRs). All cells and arteries contained FGFR-1 mRNA. Only SMC and control vessels had FGFR-2 mRNA, while EC and some arteries contained FGFR-4 mRNA. The relative lack of bFGF in plaques vs. normal arteries suggests that this growth factor may not contribute to cell proliferation in advanced atherosclerosis. However, aFGF produced by plaque macrophages may stimulate the growth of microvessels during human atherogenesis.