gebhart/patrepeval huggingface dataset:
Immunoregulatory effects of a nutritional preparation containing bovine lactoferrin taken orally by healthy individuals. (1998)

The aim of this study was to monitor several immune parameters in 17 healthy volunteers taking orally commercially available capsules containing bovine lactoferrin (BLFT) for 10 days (40 mg of BLFT daily). We determined leukocyte number and content of main blood cell types, spontaneous and phytohemagglutinin A (PHA)-induced proliferation of lymphocytes, plasma levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) as well as spontaneous and lipopolysaccharide (LPS)-induced production of these cytokines in peripheral blood cell cultures. All measurements were performed before, one day and 14 days following cessation of BLFT treatment. We established some, transient drop in the percentage of neutrophils accompanied by an opposite phenomenon with regard to lymphocyte levels. More profound changes were registered in the percentage of other cell types, for example a 100% increase in the level of immature cell forms (bands) was noted. At the same time the percentages of eosinophils and monocytes declined significantly. All these changes were, however, more individual and regulatory, the direction of these changes depended on initial picture of blood cells. Although the proliferative response of lymphocytes showed, on average, a transient decrease, differentiated effects of BLFT treatment were observed depending on initial ability of lymphocytes to proliferate. TNF-alpha serum levels showed a tendency to decrease during the monitoring time, the changes of IL-6 levels were, however, not significant. As in the case of the proliferative response, the treatment with BLFT was regulatory with respect to serum TNF-alpha levels. When we analyzed spontaneous and LPS-induced cytokine production in cell cultures we found that mainly the mean spontaneous response was affected (inhibition). We also observed a typical, regulatory action of BLFT on the level of spontaneously produced IL-6. This kind of regulatory action of BLFT was also found in the case of spontaneously produced TNF-alpha in cell cultures. The influence of other ingredients such as selenium or vitamins, contained in the capsules, cannot be excluded, although our latest data showed that orally taken bovine lactoferrin alone can induce identical changes as BLFT. Taken together, we revealed regulatory effects of oral treatment with commercially available capsules, containing BLFT. The results indicate that oral administration on BLFT-containing capsules may regulate some immune parameters in healthy individuals. In addition, the data suggest that bovine lactoferrin may be applied in clinic to improve the immune status of patients.
Molecular Characterization of Ste20p, a Potential Mitogen-activated Protein or Extracellular Signal-regulated Kinase Kinase (MEK) Kinase Kinase from Saccharomyces cerevisiae (1995)

The Ste20p protein kinase was immunopurified from yeast cells and analyzed in an in vitro assay system. Ste20p immune complexes exhibited autophosphorylating activity at serine and threonine residues and specifically phosphorylated a bacterially expressed glutathione S-transferase (GST) fusion of Ste11p (a mitogen-activated protein or extracellular signal-regulated kinase kinase (MEK) kinase homologue) at serine and threonine residues. In contrast, GST fusions either of Ste7p (a MEK homologue) or the beta-subunit of the mating response G-protein and immunoprecipitated Ste5p were not phosphorylated by the Ste20p immune complexes. Myelin basic protein was identified as an excellent in vitro substrate, whereas histone H1 was only poorly phosphorylated. Evidence was obtained that autophosphorylation might play a regulatory role for the in vitro kinase activity. The in vitro activity was found to be Ca(2+)-independent. Both the in vivo and in vitro activities were abolished by mutational changes of either the conserved lysine residue 649 within the ATP binding site or threonine 777 between the catalytic subdomains VII and VIII. Wild-type Ste20p and the catalytically inactive T777A mutant were identified as phosphoproteins in vivo. The phosphorylation occurred at serine and threonine residues independent of pheromone stimulation. Based on the genetically determined significance of Ste20p in pheromone signal transduction and on our in vitro studies, we propose the model that Ste20p represents a yeast MEK kinase kinase whose function is to link G-protein-coupled receptors through G beta gamma to a mitogen-activated protein kinase module.
Noninvasive molecular biomarkers for the detection of colorectal cancer (2008)

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, noninvasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.
Induction of Type I Diabetes by Kilham's Rat Virus in Diabetes-Resistant BB/Wor Rats (1991)

Type I diabetes mellitus is an autoimmune disease resulting from the interaction of genetic and environmental factors. A virus that was identified serologically as Kilham's rat virus (KRV) was isolated from a spontaneously diabetic rat and reproducibly induced diabetes in naive diabetes-resistant (DR) BB/Wor rats. Viral antigen was not identified in pancreatic islet cells, and beta cell cytolysis was not observed until after the appearance of lymphocytic insulitis. KRV did not induce diabetes in major histocompatibility complex-concordant and discordant non-BB rats and did not accelerate diabetes in diabetes-prone BB/Wor rats unless the rats had been reconstituted with DR spleen cells. This model of diabetes may provide insight regarding the interaction of viruses and autoimmune disease [corrected]
Silibinin decreases prostate-specific antigen with cell growth inhibition via G 1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention (1999)

Reduction in serum prostate-specific antigen (PSA) levels has been proposed as an endpoint biomarker for hormone-refractory human prostate cancer intervention. We examined whether a flavonoid antioxidant silibinin (an active constituent of milk thistle) decreases PSA levels in hormone-refractory human prostate carcinoma LNCaP cells and whether this effect has biological relevance. Silibinin treatment of cells grown in serum resulted in a significant decrease in both intracellular and secreted forms of PSA concomitant with a highly significant to complete inhibition of cell growth via a G1 arrest in cell cycle progression. Treatment of cells grown in charcoal-stripped serum and 5alpha-dihydrotestosterone showed that the observed effects of silibinin are those involving androgen-stimulated PSA expression and cell growth. Silibinin-induced G1 arrest was associated with a marked decrease in the kinase activity of cyclin-dependent kinases (CDKs) and associated cyclins because of a highly significant decrease in cyclin D1, CDK4, and CDK6 levels and an induction of Cip1/p21 and Kip1/p27 followed by their increased binding with CDK2. Silibinin treatment of cells did not result in apoptosis and changes in p53 and bcl2, suggesting that the observed increase in Cip1/p21 is a p53-independent effect that does not lead to an apoptotic cell death pathway. Conversely, silibinin treatment resulted in a significant neuroendocrine differentiation of LNCaP cells as an alternative pathway after Cip1/p21 induction and G1 arrest. Together, these results suggest that silibinin could be a useful agent for the intervention of hormone-refractory human prostate cancer.
Wnt modulators in the biotech pipeline (2009)

The purpose of this review is to provide a better understanding for the LRP co-receptor-mediated Wnt pathway signaling. Using proteomics, we have also subdivided the LRP receptor family into six sub-families, encompassing the twelve family members. This review includes a discussion of proteins containing a cystine-knot protein motif (i.e., Sclerostin, Dan, Sostdc1, Vwf, Norrin, Pdgf, Mucin) and discusses how this motif plays a role in mediating Wnt signaling through interactions with LRP.
Oxidized Alkyl Phospholipids Are Specific, High Affinity Peroxisome Proliferator-activated Receptor γ Ligands and Agonists (2001)

Synthetic high affinity peroxisome proliferator-activated receptor (PPAR) agonists are known, but biologic ligands are of low affinity. Oxidized low density lipoprotein (oxLDL) is inflammatory and signals through PPARs. We showed, by phospholipase A(1) digestion, that PPARgamma agonists in oxLDL arise from the small pool of alkyl phosphatidylcholines in LDL. We identified an abundant oxidatively fragmented alkyl phospholipid in oxLDL, hexadecyl azelaoyl phosphatidylcholine (azPC), as a high affinity ligand and agonist for PPARgamma. [(3)H]azPC bound recombinant PPARgamma with an affinity (K(d)((app)) approximately 40 nm) that was equivalent to rosiglitazone (BRL49653), and competition with rosiglitazone showed that binding occurred in the ligand-binding pocket. azPC induced PPRE reporter gene expression, as did rosiglitazone, with a half-maximal effect at 100 nm. Overexpression of PPARalpha or PPARgamma revealed that azPC was a specific PPARgamma agonist. The scavenger receptor CD36 is encoded by a PPRE-responsive gene, and azPC enhanced expression of CD36 in primary human monocytes. We found that anti-CD36 inhibited azPC uptake, and it inhibited PPRE reporter induction. Results with a small molecule phospholipid flippase mimetic suggest azPC acts intracellularly and that cellular azPC accumulation was efficient. Thus, certain alkyl phospholipid oxidation products in oxLDL are specific, high affinity extracellular ligands and agonists for PPARgamma that induce PPAR-responsive genes.
Understanding Corporate Social Irresponsibility on Sports Organizations (2012)

For this study, we sought to understand the conceptualization of sports organizations in the CSR context from the customer perspective. Previous studies have mainly focused on the positive effect of CSR and neglected the negative effect of irresponsible behaviors. The associations on these entities are often treated discretely, whereas the interrelatedness of the associations are overlooked. This research employs the brand concept map (BCM) method to elucidate the complex and interconnected associations of how a sports organization is perceived, and presents these findings in a graphical network structure. The aggregated network of associations in people’s memory, consisting of performance, setting, and auxiliary elements, constitutes the core (brand) images and relevant patronage values of an organization. This research contributes to the understanding of sports brand on the association and network levels. This study identifies useful individual associations such as baseball, players, mascots, related products and corporations, CSR-related behaviors, and the interconnection patterns between elements. These identified factors are useful in detecting and developing patronage and in identifying incongruence in the conceptualization of brand and organization image. The interconnectivity and network structure of people’s associations are considered by the employed in this methodology in this study. This study identifies the framework of relevant associations, elements, values, and interconnection patterns, which not only provide comprehensive information in understanding complex conceptual perceptions, but might also be leveraged and focused on by marketers for an enhanced creative marketing and communication strategy.
Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer (2019)

<b>Background:</b> Triple-negative breast cancer (TNBC) represents about 10-20% of all invasive breast cancers and is associated with a poor prognosis. The nectin cell adhesion protein 4 (Nectin-4) is a junction protein involved in the formation and maintenance of cell junctions. Nectin-4 has previously shown to be expressed in about 60% of TNBC as well as in TNBC metastases, but to be absent in normal breast tissue, which makes it a potential specific target for TNBC therapy. Previous studies have shown an association of Nectin-4 protein expression with worse prognosis in TNBC in a small patient cohort. The aim of our study was to explore the role of Nectin-4 in TNBC and confirm its impact on survival in a larger TNBC patient cohort. <b>Material and Methods:</b> We performed immunohistochemical staining for Nectin-4 on a tissue microarray encompassing 148 TNBC cases with detailed clinical annotation and outcomes data. <b>Results:</b> A high expression of Nectin-4 was present in 86 (58%) of the 148 TNBC cases. In multivariate survival analysis, high expression of Nectin-4 was associated with a significantly better overall survival when compared with low expression of Nectin-4 (<i>p</i> < 0.001). Nectin-4-high expression was also significantly associated with a lower tumor stage (<i>p</i> = 0.025) and pN0 lymph node stage (<i>p</i> = 0.034). <b>Conclusion:</b> Our results confirm that expression of Nectin-4 serves as a potential prognostic marker in TNBC and is associated with a significantly better overall survival. In addition, Nectin-4 represents a potential target in TNBC, and its role in molecular defined breast cancer subtype should be investigated in larger patient cohorts.
Controlling Data Quality and Reproducibility of a High-Sensitivity Immunoassay Using Isotachophoresis in a Microchip (2008)

This report describes a method of controlling the sensitivity and reproducibility of a microchip-based immunoassay by using isotachophoresis to preconcentrate the antigen and antibody prior to binding. Gel electrophoresis separation is coupled to the preconcentration step to separate the immunocomplex products formed. The system employs a quartz-based LabChip that automates the metering, preconcentration, reaction, separation, and detection. The system also uses a handoff mechanism that switches the immunocomplex from the stacking mode to the separation mode. We show that the handoff timing affects the data quality and repeatability of the electropherograms, and we demonstrate an automatic handoff mechanism to precisely control the signal intensity and separation of peaks of interest. In so doing, the automatic handoff mechanism also improves the reproducibility of the assay. When applied to the homogeneous liquid-phase detection of alpha-fetoprotein, a common tumor marker, the system shows a greater than 200-fold stacking of specific analytes of interest.
Mps1/TTK: a novel target and biomarker for cancer (2016)

Monopolar spindle1 (Mps1, also known as TTK) is the core component of the spindle assembly checkpoint, which functions to ensure proper distribution of chromosomes to daughter cells. Mps1 is hardly detectable in normal organs except the testis and placenta. However, high levels of Mps1 are found in many types of human malignancies, including glioblastoma, thyroid carcinoma, breast cancer, and other cancers. Several Mps1 inhibitors can inhibit the proliferation of cancer cells and exhibit demonstrable survival benefits. Mps1 can be utilized as a new immunogenic epitope, which is able to induce potent cytotoxic T lymphocyte activity against cancer cells while sparing normal cells. Some clinical trials have validated its safety, immunogenicity and clinical response. Thus, Mps1 may be a novel target for cancer therapy. Mps1 is differentially expressed between normal and malignant tissues, indicating its potential as a molecular biomarker for diagnosis. Meanwhile, the discovery that it clearly correlates with recurrence and survival time suggests it may serve as an independent prognostic biomarker as well.
A motion-adaptive de-interlacing method (1992)

The authors describe an improved motion-adaptive de-interlacing method that incorporates the missing lines of interlaced fields from pixels of the same field or adjacent fields after motion compensation. Some improvements were obtained by suppressing the effect of false motion caused by interpolation error in the searched field, and by interpolation filtering based on the characteristics of moving objects. Experimental data show that the proposed method resulted in smaller interpolation error than conventional de-interlacing methods.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Femtosecond Optical Frequency Comb: Principle, Operation, and Applications (2005)

Over the last few years, there has been a remarkable convergence among the fields of ultrafast optics, optical frequency metrology, and precision laser spectroscopy. This convergence has enabled unprecedented advances in control of the electric field of the pulses produced by femtosecond mode-locked lasers. The resulting spectrum consists of a comb of sharp spectral lines with well-defined frequencies. These new techniques and capabilities are generally known as "femtosecond comb technology." They have had dramatic impact on the diverse fields of precision measurement and extreme nonlinear optical physics. This book provides an introductory description of mode-locked lasers, the connection between time and frequency descriptions of their output and the physical origins of the electric field dynamics, together with an overview of applications of femtosecond comb technology. Individual chapters go into more detail on mode-locked laser development, spectral broadening in microstructure fiber, optical parametric amplification, optical frequency metrology, optical atomic clocks, ultrasensitive sensors, carrier-envelope phase dynamics, high field ionization of atoms and generation of attosecond high-harmonic radiation. To provide readers with the most recent, direct, and comprehensive information, the chapters are written by the international researchers who have led the development of this field. This book provides an introduction to those new to the field and is at the same time a resource for experts.
Room-temperature CW operation of InGaAsP lasers on Si fabricated by wafer bonding (1996)

1.3-μm InGaAsP-InP lasers have been successfully fabricated on Si substrates by wafer bonding with heat treatment at 400/spl deg/C. A pressure of 4 kg/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> has been applied on the wafers before the heat treatment and this pressure application has enabled us to achieve bonding strength required for the device fabrication even when the bonding temperature is as low as 400/spl deg/C. Room-temperature continuous-wave operation with threshold current of 49 mA has been achieved for 7-μm-wide mesa lasers.
Functional Anatomy of the Autonomic Nervous System (1993)

The autonomic nervous system (ANS) via its sympathetic and parasympathetic divisions influences the function of nearly all organ systems. Via autonomic reflexes, the ANS is responsible for maintaining homeostasis of the internal environment. This is achieved by a rather complex integration of autonomic sensory information, somatic sensory information, and descending influences from higher central nervous system centers.
The Linguistic Simplification of Presidential Rhetoric (2008)

This chapter proposes anti-intellectualism as the unifying critique of the contemporary presidency and begins a debate on how to redirect the attention toward the quality, rather than just the quantity, of presidential rhetoric. Then, it presents evidence of the transformed—syntactically truncated and semantically shortened—structure of presidential rhetoric. It specifically reports the evidence of the relentless linguistic (syntactic and semantic) simplification of presidential rhetoric that occurred between 1789 and 2006. In addition, it takes off from the less ambitious proposition that there can be no plausible case for a thoroughgoing anti-intellectualism, which is operationally defined for this chapter as the relentless semantic and syntactic simplification of presidential rhetoric, because at some point simplification becomes oversimplification, and the drastically truncated structure of such language will fail to convey the minimum amount of information required as the basis for competent civic judgments. It can be concluded that the presidential rhetorical simplification across the last two centuries is real and demonstrable, and it cannot endorse the virtue of rhetorical simplicity indefinitely, because at some point simplification becomes oversimplification.
A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13 (2003)

The MCM8 protein from HeLa cells, a new member of the MCM family, co-isolates through several steps with MCM6 and MCM7, and MCM8 co-immunoprecipitates with MCM4, MCM6 and MCM7, proteins reportedly forming a helicase complex involved in initiation of DNA replication. MCM8 mRNA is expressed in placenta, lung and liver, but is also significantly expressed in adult heart, a tissue with a low percentage of proliferating cells. The MCM8 gene, consisting of 19 exons, is located contrapodal to a gene, consisting of 11 exons, encoding a homolog of the yeast GCD10 gene product. The region between these two transcription units, comprising as few as 62 bp, is TATA-less and highly GC-rich, containing multiple CpG units. MCM8 expression is altered in certain forms of neoplasia. In a case of choriocarcinoma MCM8 mRNA is aberrant, leading to expression of a protein lacking 16 amino acids. In several cases of colon adenocarcinoma MCM8 expression is greatly reduced relative to matched non-cancerous tissue. The potential helicase domain of MCM8 is different from those of other MCM proteins in that it is more homologous to canonical ATP-binding domains of other known helicases. Results suggest that MCM8 may interact with other MCM proteins to alter the function of the replicative MCM protein complex.