gebhart/patrepeval huggingface dataset:
Merged remotely sensed data for geomorphological investigations in deserts: examples from central Saudi Arabia (2003)

Image merging has gained acceptance in geological remote sensing, however it has rarely been applied in geomorphology. We report on the usefulness of principal components substitution (PCS) to merge IRS panchromatic data with multispectral Thematic Mapper (TM) imagery, to map commonly encountered desert geomorphological features, and in relative age dating of alluvial surfaces. The merged data were applied to the identification and mapping of geomorphological features along two geolo‐gically different mountain fronts in central Saudi Arabia. Two types of geomorphological maps have been created. A morphogenetic map that distinguishes between aeolian landforms, fluvial landforms, desert pavements, and gypsum crusts. Second, a morphochronological map, which shows the relative age of four geomorphic surfaces developed on an alluvial fan. The construction of the two maps is supported by field observations and laboratory measurements. Using the optimum index factor (OIF), a TM band 1, 5 and 7 image (of 20 merged composites) was found to be the optimum colour composite image for the geomorphological features in this arid environment. We discuss our findings in the context of the spatial and spectral properties required for applied geomorphological remote sensing.
Atypical Fabry's disease. An oligosymptomatic variant. (1996)

Fabry's disease is a rare, inherited, X-linked metabolic storage disease with ceramide hexoside due to alpha-galactosidase A deficiency. Patients with typical Fabry's disease usually present with several clinical manifestations of corneal dystrophy, neurologic abnormalities, cardiovascular disease, heavy proteinuria, and characteristic cutaneous angiokeratoma. However, atypical Fabry's disease with oligosymptomatic phenotype presents with symptoms restricted solely to cardiocytes or kidney and might be diagnosed by chance during a routine endomyocardial or renal biopsy examination. In this article, we report a case of Fabry's disease incidentally diagnosed in a 34-year-old man who presented with intermittent trace or 1(+) proteinuria only. This patient had no history of renal disease in any other family member. A renal biopsy to evaluate trace proteinuria revealed histologic and ultrastructural findings compatible with Fabry's disease. Subsequent to the renal biopsy, a skin biopsy on a few initially unrecognized, scattered, dark-pinkish scrotal papules showed typical angiokeratoma. A biochemical enzymatic assay of alpha-galactosidase in urine and plasma revealed a markedly decreased enzyme level in the hemizygous range.
Hypersensitivity or Development of Antibodies to Asparaginase Does Not Impact Treatment Outcome of Childhood Acute Lymphoblastic Leukemia (2000)

In this setting, in which most patients with allergy were switched to another preparation, there was no adverse prognostic impact of clinical or subclinical allergy to asparaginase.
Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross‐reactive (2010)

Cross-reactive memory T cells induced by primary infection with one of the four serotypes of dengue virus (DENV) are hypothesized to have an immunopathological function in secondary heterologous DENV infection. To define the T-cell response to heterologous serotypes, we isolated HLA-A(*)1101-restricted epitope-specific CD8(+) T-cell lines from primary DENV-immune donors. Cell lines exhibited marked cross-reactivity toward peptide variants representing the four DENV serotypes in tetramer binding and functional assays. Many clones responded similarly to homologous and heterologous serotypes with striking cross-reactivity between the DENV-1 and DENV-3 epitope variants. In vitro-stimulated T-cell lines consistently revealed a hierarchical induction of MIP-1β>degranulation>tumor necrosis factor α (TNFα)>interferon-γ (IFNγ), which depended on the concentration of agonistic peptide. Phosphoflow assays showed peptide dose-dependent phosphorylation of ERK1/2, which correlated with cytolysis, degranulation, and induction of TNFα and IFNγ, but not MIP-1β production. This is the first study to show significant DENV serotype-cross-reactivity of CD8(+) T cells after naturally acquired primary infection. We also show qualitatively different T-cell receptor signaling after stimulation with homologous and heterologous peptides. Our data support a model whereby the order of sequential DENV infections influences the immune response to secondary heterologous DENV infection, contributing to varying disease outcomes.
Diabetes in Friedreich Ataxia (2013)

Diabetes is a common metabolic disorder in patients with Friedreich ataxia. In this Supplement article, we review the clinical data on diabetes in Friedreich ataxia, and the experimental data from rodent and in vitro models of the disease. Increased body adiposity and insulin resistance are frequently present in Friedreich ataxia, but pancreatic β cell dysfunction and death are a conditio sine qua non for the loss of glucose tolerance and development of diabetes. The loss of frataxin function in mitochondria accounts for these pathogenic processes in Friedreich ataxia. Mitochondria are essential for the sensing of nutrients by the β cell and for the generation of signals that trigger and amplify insulin secretion, known as stimulus-secretion coupling. Moreover, in the intrinsic pathway of apoptosis, pro-apoptotic signals converge on mitochondria, resulting in mitochondrial Bax translocation, membrane permeabilization, cytochrome c release and caspase cleavage. How and at which level frataxin deficiency impacts on these processes in β cells is only partially understood. A better understanding of the molecular mechanisms mediating β cell demise in Friedreich ataxia will pave the way for new therapeutic approaches.
Atom-selective imaging and mechanical atom manipulation using the non-contact atomic force microscope (2004)

We succeeded in distinguishing between oxygen and silicon atoms on an oxygen-adsorbed Si(111)7 x 7 surface, and also distinguished between silicon and tin atoms on Si(111)7 x 7-Sn intermixed and Si(111) square root(3) x square root(3)-Sn mosaic-phase surfaces using non-contact atomic force microscopy (NC-AFM) at room temperature. Atom species of individual atoms are specified from the number of each atom in NC-AFM images, the tip-sample distance dependence of NC-AFM images and/or the surface distribution of each atom. Further, based on the NC-AFM method but using soft nanoindentation, we achieved two kinds of mechanical vertical manipulation of individual atoms: removal of a selected Si adatom and deposition of a Si atom into a selected Si adatom vacancy on the Si(111)7 x 7 surface at 78 K. Here, we carefully and slowly indented a Si atom on top of a clean Si tip apex onto a predetermined Si adatom to remove the targeted Si adatom and onto a predetermined Si adatom vacancy to deposit a Si atom, i.e. to repair the targeted Si adatom vacancy. By combining the atom-selective imaging method with two kinds of mechanical atom manipulation, i.e. by picking up a selected atom species and by depositing that atom one by one at the assigned site, we hope to construct nanomaterials and nanodevices made from more than two kinds of atom species in the near future.
Population Pharmacokinetics and Pharmacodynamics of Ciclesonide (2003)

Ciclesonide is a novel glucocorticoid that is converted into ciclesonide--active principle (CIC-AP) in the lung. The study objectives were to identify a structural model for population pharmacokinetic (PK) analysis of CIC-AP using nonlinear mixed-effects modeling, assess the influence of select covariates on PK and/or pharmacodynamic (PD) parameters, and investigate the effects of CIC-AP on endogenous cortisol. Pooled concentration data from nine phase I studies (dose: 400-3600 micrograms) involving healthy and asthmatic patients were included in the PK analysis. There were 151 subjects (3300 observations) for the CIC-AP population PK analysis. Various models examined inter- and intrasubject variability for the PK parameters. Population estimates of the PK parameters of clearance and volume of distribution were 396 L/h (64.8% co-efficient of variation [CV]) and 1190 L (41.2% CV), respectively. Pharmacodynamic population estimates included maximum cortisol release rate, 3140 ng/h (5.4% CV). The EC50 of CIC-AP was 0.88 ng/mL. Ciclesonide is a safe corticosteroid that causes negligible cortisol suppression. The disposition and effect of CIC-AP can be described using mixed-effect modeling. The estimated EC50 is similar to mean Cmax from an 800-micrograms dose, further suggesting CIC-AP has little effect on cortisol suppression.
Amino Acid 49 Polymorphisms of the Human β 1 -Adrenergic Receptor Affect Agonist-Promoted Trafficking (2002)

The signaling impact of a human beta1-adrenergic receptor (beta1 AR) polymorphism at residue 49 of the aminoterminus (Ser-to-Gly substitution) was studied by recombinantly expressing each receptor. The two receptors displayed identical agonist and antagonist binding affinities. Furthermore, basal and agonist-stimulated adenylyl cyclase activities were the same for these receptors as assessed in both cell types. Although short-term agonist exposure resulted in similar degrees of receptor internalization, long-term agonist-promoted downregulation was greater for Gly49 compared with Ser49. The Gly49 receptor underwent a 24 +/- 3% loss of receptor density after exposure to isoproterenol for 18 h, whereas Ser49 underwent no such loss. In studies in which receptor synthesis was inhibited, agonist-promoted downregulation for Gly49 was 55 +/- 3% compared with 36 +/- 5% for Ser49. In the absence of agonist, degradative turnover of each receptor was the same. Immunoblotting revealed that some of the Ser49 receptor exists as a highly N-glycosylated form (approximately 105-kD molecular mass), which is not present with Gly49. Thus the phenotype of the Gly49 polymorphic receptor is that of wild-type coupling with enhanced agonist-promoted downregulation, which is associated with altered N-glycosylation. Based on this cellular phenotype, the beta1 AR Gly49 polymorphism may impart a beneficial effect in chronic heart failure.
Evaluation of the Invader Assay, a Linear Signal Amplification Method, for Identification of Mutations Associated with Resistance to Rifampin and Isoniazid in Mycobacterium tuberculosis (2000)

We evaluated a recently described linear signal amplification method for sensitivity and specificity in detecting mutations associated with resistance to rifampin (RIF) and isoniazid (INH) in Mycobacterium tuberculosis. The assay utilizes the thermostable flap endonuclease Cleavase VIII, derived from Archaeoglobus fulgidus, which cleaves a structure formed by the hybridization of two overlapping oligonucleotide probes to a target nucleic acid strand. This method, termed the Invader assay, can discriminate single-base differences. Nine pairs of probes, encompassing five mutations in rpoB and katG that are associated with resistance to either RIF or INH, as well as the corresponding wild-type (drug-susceptible) alleles, were tested using amplified DNA. Fluorescent-labeled cleavage products, ranging from 4 to 13 nucleotides in length, depending on the genotype of the test sample, were separated by denaturing polyacrylamide (20 to 24%) gel electrophoresis and then detected by scanning. All nine alleles could be identified and differentiated on the basis of product size. Multiple mutations at a specific rpoB nucleotide in target PCR products could be identified, as could mutants that were present at > or =0.5% of the total population of target sequences. The Invader assay is a sensitive screen for some mutations associated with antituberculosis drug resistance in amplified gene regions.
Characterization of a Mouse Multigene Family That Encodes Zinc Finger Structures (1988)

The Drosophila segmentation gene Krüppel encodes multiple tandemly repeated units predicted to form DNA-binding zinc fingers. We have isolated 23 bacteriophages, containing nonoverlapping inserts from a mouse genomic DNA library, on the basis of cross-hybridization under nonstringent conditions to a probe corresponding to the Krüppel finger region. Nucleotide sequence analysis of six phage DNAs indicated that they all contained regions with similarity to Krüppel and potentially encoded zinc finger domains. Within these regions, the level of similarity to Krüppel was particularly high between successive fingers. Northern (RNA) blotting analysis suggested that the mouse sequences belonged to different genes, the expression of some of which was modulated during cell differentiation and development. Hybridization experiments suggested that the similarity between some of the genes extended outside of the finger regions. In conclusion, our data suggest that the mouse genome contains a large family of evolutionarily related genes encoding possible trans-acting factors. These genes are likely to play a regulatory role at the transcriptional level.
CREB-Binding Protein and Histone Deacetylase Regulate the Transcriptional Activity of Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50 (2001)

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) open reading frame 50 (ORF50) encodes a viral transcriptional activator, which binds to the KSHV promoter and stimulates the transcription of viral early and late genes, thus activating the lytic cycle of KSHV. We report here that KSHV ORF50 binds to the cellular proteins CREB-binding protein (CBP) and histone deacetylase (HDAC) and these binding events modulate ORF50-activated viral transcription. Binding of ORF50 to CBP and HDAC activates and represses, respectively, ORF50-mediated viral transcription. KSHV ORF50 was shown to bind to the C/H3 domain and the C-terminal transcriptional activation domain of CBP, while CBP bound to the amino-terminal basic domain and the carboxyl-terminal transactivation domain of ORF50. The LXXLL motif within the transcriptional activation domain of ORF50 is reminiscent of the CBP-binding sequence found in nuclear receptor proteins. The adenovirus E1A protein, which also binds to the C/H3 domain of CBP, repressed the transcriptional activation activity of ORF50. The cellular protein c-Jun, which binds to the kinase-induced activation domain of ORF50, stimulated ORF50-mediated viral transcription. The HDAC1-interacting domain of ORF50 was shown to be a central proline-rich sequence. Our data provide a framework for delineating the regulatory mechanisms used by KSHV to modulate its transcription and replication through interaction with both histone acetyltransferases and HDACs.
Resistance of primary CD8+ cytotoxic T lymphocytes to lysis by cytotoxic granules from cloned T cell lines. (1988)

Recent evidence has shown that cloned, murine CTL cell lines are resistant to the cytotoxic components of the toxic granules they release upon specific interaction with their target cells. Inasmuch as the resistance might be due to selection in culture over many months by repeated exposure to these cytolytic components (which are released repeatedly as a result of the cultured CTL being periodically stimulated by target cells), we asked whether primary CTL are also resistant. The primary CTL were elicited in vivo by i.p. injection of allogeneic tumor cells or in vitro by 5- to 6-day MLC or by 48-h exposure to the lectin Con A. The responding cells were separated into purified CD8+ (i.e., CD4-, CD8+) and purified CD4+ (i.e., CD4+, CD8-) T cell populations that were analyzed for cytolytic activity and for resistance to lysis by toxic secretory granules derived from cloned CTL cell lines. The CD8+ T cells were highly cytolytic and relatively resistant; they retained their cytolytic activity and were lysed to a minimal extent (0 to 10%) by quantities of isolated granules that lysed 80 to 90% of the P815 tumor cell line (tested as a representative standard cell line). The CD4+ T cells, in contrast, had only minimal cytolytic activity and were far more susceptible to granule-mediated lysis. Although the resistance of primary CD8+ T cells is impressive, it is not as pronounced as the resistance of the cloned CTL cell lines, indicating that during long-term culture there is some selection for increased resistance to granule-mediated lysis. In contrast to T cells (especially CD8+ T cells), Ia+ macrophages, isolated from primary immune peritoneal exudates, were highly susceptible to granule-mediated lysis.
Mobile Communication with Virtual Network Address Translation (2002)

Virtual Network Address Translation (VNAT) is a novel architecture that allows transparent migration of end-to-end live network connections associated with various computation units. Such computation units can be either a single process, or a group of processes of an application, or an entire host. VNAT virtualizes network connections perceived by transport protocols so that identification of network connections is decoupled from stationary hosts. Such virtual connections are then remapped into physical connections to be carried on the physical network using network address translation. VNAT requires no modification to existing applications, operating systems, or protocol stacks. Furthermore, it is fully compatible with the existing communication infrastructure; virtual and normal connections can coexist without interfering each other. VNAT functions entirely within end systems and requires no third party proxies. We have implemented a VNAT prototype with the Linux 2.4 kernel and demonstrated its functionality on a wide range of popular real-world network applications. Our performance results show that VNAT has essentially no overhead except when connections are migrated, in which case the overhead of our Linux prototype is less than 7 percent.
A Common Pathogenic Mechanism Linking Type-2 Diabetes and Alzheimer's Disease: Evidence from Animal Models (2011)

The failure of large-scale drug trials targeting the amyloidogenic pathway in Alzheimer's disease (AD) is increasing the need to identify a novel pathogenic mechanism. Studies finding a relationship between sporadic AD and type-2 diabetes mellitus (T2DM) are now receiving more attention. The risk for developing both T2DM and sporadic AD increases exponentially with age, and having T2DM doubles the risk of developing AD. The postmortem brains of AD patients show altered activities of insulin receptors and downstream molecules, as well as reduced protein and mRNA levels of insulin. More-recent laboratory research using animal models has identified mechanisms that are shared by diabetes and AD. Exogenous application of streptozotocin, which disrupts systemic insulin secretion, results in insulin deficiency, increased tau phosphorylation, and cognitive impairments that can be reversed by exogenous insulin supplementation. However, AD pathology is more severe in T2DM animal models exhibiting hyperinsulinemia and insulin resistance, and this is not modulated by insulin. The symptoms of this AD pathology included increased tau phosphorylation at multiple sites, increased tau cleavage, and greater neuronal and synaptic damage, even with increased amyloid β protein production. It has therefore been suggested that hyperinsulinemia and insulin resistance represent major factors underlying AD in T2DM. A recent study involving cross-mating ob/ob and amyloid precursor protein transgenic mice provided evidence that T2DM and AD aggravate each other, and suggested that cerebral vessels constitute an important substrate that is commonly damaged by the two major disorders. Given the evidence provided by animal models, further investigation of the mechanisms underlying T2DM in AD should help to identify potential treatment targets in AD.
A Practical Guide to Monoclonal Antibodies (1991)

Overview of Hybridoma Technology. Tissue Culture Techniques. Immunization. Screening Test Design. Myeloma Cells, Lymphocytes, Fusion. Hybrid Selection and Cloning. Characterization, Purification and Labeling. Human Hybridomas and Engineered Antibodies. Appendices. References. Index.
Cannabinoid Analgesia as a Potential New Therapeutic Option in the Treatment of Chronic Pain (2006)

Cannabinoids provide a potential approach to pain management with a novel therapeutic target and mechanism. Chronic pain often requires a polypharmaceutical approach to management, and cannabinoids are a potential addition to the arsenal of treatment options.
Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells (2000)

Benzene is an established human carcinogen, producing leukemia, hematotoxicity and perhaps lymphoma. Its carcinogenicity is most likely dependent upon its conversion to phenol and hydroquinone, the latter being oxidized to the highly toxic 1,4-benzoquinone in the bone marrow. Exposure of human lymphocytes and cell lines to hydroquinone has previously been shown to cause various forms of genetic damage, including aneusomy and the loss and gain of chromosomes. However, the target cells for leukemogenesis are the pluripotent stem cells or early progenitor cells which carry the CD34 antigen (CD34 + cells). In this study, human cord blood, which is particularly rich in CD34 + cells, was exposed to hydroquinone for 72 h in a medium that favored CD34 + cell survival and growth. CD34 + and CD34 – cells were then isolated. Fluorescence in situ hybridization was employed to determine the level of aneusomy of chromosomes 7 and 8 in both cell types. CD34 + cells were generally more susceptible to aneusomy induction by hydroquinone than CD34 – cells. Increased trisomy and monosomy of chromosomes 7 and 8 were observed in CD34 + cells ( Ptrend < 0.001), whereas in CD34 – cells only an increased level of monosomy 7 was detected ( Ptrend = 0.002). Particularly striking effects of hydroquinone were observed in CD34 + cells on monosomy 7 and trisomy 8, two common clonal aberrations found in myeloid leukemias, suggesting that these aneusomies produced by hydroquinone in CD34 + cells play a role in benzene-induced leukemogenesis.
Quantitative magnetic resonance imaging in the assessment of degenerative disc disease (1998)

Understanding degenerative intervertebral disc diseases hinges on the ability to objectively and noninvasively assess the disc matrix composition and integrity. The potential of quantitative magnetic resonance imaging to meet these demands was evaluated. Analyzing the T1 and T2 signal patterns in the nucleus pulposus with increasing Thompson morphological grade revealed a significant reduction related to grade. This significant decrease in T1 and T2 in the nucleus pulposus with grade 4 degeneration and the corresponding low correlation coefficients with respect to the content of individual matrix molecules suggest that matrix integrity plays an important and distinct role in determining T1 and T2 signal. Similarly, the significant increase in magnetization transfer in the nucleus pulposus observed in grade 4 degeneration did not correlate with the changes in molecular content in these highly degenerated discs. Again, this lack of correlation clearly indicates that the tissue integrity and matrix composition independently contribute to the magnetization transfer signal. This study presents the first clear evidence that quantitative magnetic resonance analysis reflects not only the disc matrix composition, but also the structural integrity of the matrix of the disc.