gebhart/patrepeval huggingface dataset:
Molecular and Ionic Recognition with Imprinted Polymers (1998)

The concepts of chemical imprinting of polymeric materials and recognition of molecular and ionic species with imprinted polymers are introduced. Following a brief description of the two general methodologies for the preparation of imprinted polymers, applications are outlined for their use in chromatographic separations, as artificial antibodies in drug and pesticide analysis, in selective sorption of molecular and ionic species, in sensors and membranes, and as artificial enzymes. Recent advances in molecular imprinting as described in the twenty-one contributed chapters are highlighted.
Androgen-Induced Growth Inhibition of Androgen Receptor Expressing Androgen-Independent Prostate Cancer Cells Is Mediated by Increased Levels of Neutral Endopeptidase (2000)

Androgen-mediated growth repression of androgen-independent prostate cancer (AIPC) cells has been reported in androgen-independent PC-3 cells overexpressing the androgen receptor, and in androgen-independent derivatives of LNCaP cells that develop following prolonged culture in androgen-free media. Using two models of AIPC, PC3/AR cells and LNCaP-OM1 cells, a subclone of LNCaP cells derived by prolonged culturing in charcoal-stripped media, we investigated whether expression of neutral endopeptidase 24.11 (NEP), a cell-surface peptidase that cleaves and inactivates neuropeptides implicated in the growth of AIPC, is induced by androgen, and whether NEP contributes to the observed androgen-mediated growth repression. These cell lines each express high levels of androgen receptor. Culturing in dihyrotestosterone (DHT) resulted in a 30–56% (PC3) and 35–43% (LNCaP-OM1) decrease in cell number over 7 days concomitant with a significant increase in NEP enzyme specific activity. Northern analysis detected an increase in NEP transcripts following DHT treatment in PC3/AR cells. The addition of the NEP enzyme inhibitor phosphoramidon to PC3 and LNCaP-OM1 or the NEP competitive inhibitor CGS 24592 to LNCaP-OM1 blocked the increase in NEP enzyme activity and reversed the DHT-induced growth inhibition. Neither phosphoramidon or CGS 24592 alone inhibited cell growth. Furthermore, the reversal of growth inhibition in LNCaP-OM1 cells was dose dependent on the concentration of CGS 24592. These data indicate that androgen-induced growth repression of AIPC cells PC3 and LNCaP-OM1 results in part from androgen-induced expression of NEP in these cells.
Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value. (1997)

Cyclin D1 overexpression, detected by standard immunohistochemistry, was correlated with other prognostic variables and its prognostic value was evaluated in a group of 148 invasive breast cancers with long-term follow-up. Overexpression of cyclin D1 (59% of cases) was negatively correlated (chi 2 test) with histological grade (P = 0.0001), mean nuclear area (P = 0.004), mean nuclear volume (P = 0.02), and mitotic activity (P = 0.03) and positively correlated with estrogen receptor (P = 0.0001). There was a strong correlation between cyclin D1 overexpression and histological type (P = 0.0001). Positive cyclin D1 staining was seen in 11 of 13 tubular carcinomas, 3 of 3 mucinous carcinomas, 4 of 4 invasive cribriform carcinomas, and 17 of 20 lobular carcinomas. Of 102 ductal cancers, 52 were positive, and all 6 medullary carcinomas were negative. There were no significant correlations with lymph node status, tumor size, or DNA ploidy. In survival analysis, cyclin D1 overexpression did not provide significant univariate or multivariate prognostic value. In conclusion, cyclin D1 is mainly overexpressed in the well differentiated and lobular types of invasive breast cancer and is strongly associated with estrogen receptor positivity. It is negatively correlated with the proliferation marker mitoses count and with the differentiation markers nuclear area and nuclear volume. However, cyclin D1 overexpression does not seem to have prognostic value in invasive breast cancer when no adjuvant treatment is given.
Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: role of tumour necrosis factor alpha. (1994)

Neutrophil adherence within the gastric microcirculation is thought to be a major step in the pathogenesis of gastric mucosal damage induced by indomethacin. Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations. Rats were treated with 20 mg/kg oral indomethacin, pretreated with vehicle or with four different doses of pentoxifylline intraperitoneally, and killed after three hours. The gross gastric mucosal injury, neutrophil margination into the gastric microcirculation, mucosal concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha), and PGE2 and serum TNF alpha values were measured. Whether the pentoxifylline induced protection involved nitric oxide mediated pathways or gastric acid secretion was evaluated. The data indicate that pentoxifylline reduces indomethacin induced mucosal damage and neutrophil margination in a dose dependent manner without exerting any effect on gastric mucosal prostaglandin concentrations. The maximally effective dose (200 mg/kg) of pentoxifylline reduced gastric damage by 90% and slightly stimulated acid secretion. The effect of pentoxifylline was not affected by pretreatment with the nitric oxide inhibitor. Pentoxifylline prevented the indomethacin induced increase in TNF alpha concentrations in a dose dependent fashion. Serum TNF alpha values were 30.5 (7.0) IU/ml (mean (SEM)) in rats treated with indomethacin alone and 5.0 (2.5) IU/ml (p < 0.01) in rats treated with indomethacin plus 200 mg/kg pentoxifylline. Pentoxifylline, therefore, prevents the acute gastric mucosal damage and neutrophil margination induced by indomethacin and reduces indomethacin induced release of TNF alpha.
Does Exposure to Rubella Virus Generate Endocrine Autoimmunity? (1990)

Rubella virus is a possible environmental agent which may be involved in triggering autoimmunity to pancreatic islet cells, leading to Type 1 diabetes. Autoantibody responses were determined in 239 10-year-old girls who received live attenuated rubella vaccine, of whom 61 (26%) had no pre-existing rubella immunity. Islet cell antibodies (ICA greater than 5 Juvenile Diabetes Foundation (JDF) units) were present in seven (2.9%) girls before vaccination, and they appeared in three more 6 weeks after vaccination (4.2%). However, the ICA levels were low in all cases and of the three girls who developed ICA greater than 5 JDF units 6 weeks post-vaccination, none had detectable ICA 18 months later. IgG-insulin autoantibodies were present in 17 (7.1%) girls before vaccination, and their prevalence decreased after vaccination (5.4%). Thyroid antibodies (thyroglobulin and microsomal) were present in 2% and 1%, respectively, of the girls before vaccination and none appeared afterwards. Thus, rubella vaccination did not elicit widespread endocrine autoantibody production and viral triggering of endocrine autoimmunity in susceptible subjects remains an open question.
Advances and challenges in biosensor-based diagnosis of infectious diseases (2014)

Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings.
Phenotypic variation in Actinobacillus actionmycetemcomitans during laboratory growth: implications for virulence (1999)

This study examined alteration of specific virulence traits associated with phenotypic changes seen when a low-passage disease-associated and well maintained parent strain of Actinobacillus actinomycetemcomitans was compared to a laboratory-grown spontaneous variant/mutant. Clinical isolates of A. actinomycetemcomitans recovered from periodontitis patients typically grow as rough, adherent colonies on primary culture but undergo transformation to smooth, non-adherent colonies following repeated passage in vitro. The relationship of these phenotypic changes to the virulence of the organism or to the processes that underlie this transformation are not understood. A fresh clinical isolate, designated strain CU1000, was obtained from the first molar site of a patient with classical signs of localized juvenile periodontitis and used as the parent strain to study virulence-related phenotypes. Following several passages of CU1000 on selective agar, a spontaneous variant that demonstrated smooth, opaque, non-adherent colonies was isolated and designated strain CU1060. This study compared the properties of these two strains with respect to colony morphology, autoaggregation, surface appendages, adherence to saliva-coated hydroxyapatite (SHA), LPS chemotype and activity, induction of fibroblast proteinase activity and antigenic properties. CU1000 demonstrated rough, raised, star-positive colonies which upon electron microscopic examination revealed the presence of large, flexible, bundled fibrils. In addition, CU1000 showed adherence to SHA, several unique protein antigens and elevated endotoxin and fibroblast proteinase activity. CU1060, on the other hand, showed minimal adherence to SHA and fewer reactive proteins compared to the fresh clinical isolates. This strain formed smooth, opaque colonies on agar, showed minimal fibril formation and limited endotoxin and fibroblast-proteinase-inducing activity. These findings demonstrate that clinical isolates of A. actinomycetemcomitans undergo significant virulence-reducing phenotypic alterations during in vitro passage and support the need to study this organism in its clinical form.
Establishment and characterization of human B-cell lymphoma cell lines using B-cell growth factor (1990)

B-cell non-Hodgkin's lymphomas (NHL-B) have been difficult to establish in long-term cell culture using standard techniques. We report the establishment of five representative cell lines from high grade NHL-B using B-cell growth factor (BCGF). The five NHL-B cell lines display the morphologic, immunophenotypic, genotypic, and biologic characteristics of the lymphoma cells present in the original diagnostic specimen. The cell lines showed at least a sevenfold dose- dependent increase in proliferation in vitro over background in the presence of BCGF. Other putative B-cell growth-stimulating cytokines showed no significant proliferative activity or were inhibitory in some cases. NHL-B cell lines secreted growth factor(s) into culture supernatants that mediated at least a fivefold dose-dependent increase in cell proliferation in autochthonous lymphoma cells and a 10-fold or greater stimulation in growth factor-dependent normal B cell lines in vitro. The cell lines show monoclonal rearrangements of IgH genes and nonrandom chromosomal abnormalities characteristic of NHL-B, while the expression of Epstein-Barr virus associated antigen (EBNA-I) is present in two of the five cell lines. The studies show that lineage-specific growth factors may be used to establish neoplastic B cell lines in vitro, which are important experimental systems for cellular and molecular studies in the NHL-B.
Why Metallic Surfaces with Grooves a Few Nanometers Deep and Wide May Strongly Absorb Visible Light (2008)

It is theoretically shown that nanometric silver lamellar gratings present very strong visible light absorption inside the grooves, leading to electric field enhancement of several orders of magnitude. It is due to the excitation of quasistatic surface plasmon polaritons with particular small penetration depth in the metal. This may explain the abnormal optical absorption observed a long time ago on almost flat Ag films. Surface enhanced Raman scattering in rough metallic films could also be due to the excitation of such quasistatic plasmon polaritons in grain boundaries or notches of the films.
Staphylococcus aureus leucocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo (2011)

Bloodstream infection with Staphylococcus aureus is common and can be fatal. However, virulence factors that contribute to lethality in S. aureus bloodstream infection are poorly defined. We discovered that LukED, a commonly overlooked leucotoxin, is critical for S. aureus bloodstream infection in mice. We also determined that LukED promotes S. aureus replication in vivo by directly killing phagocytes recruited to sites of haematogenously seeded tissue. Furthermore, we established that murine neutrophils are the primary target of LukED, as the greater virulence of wild-type S. aureus compared with a lukED mutant was abrogated by depleting neutrophils. The in vivo toxicity of LukED towards murine phagocytes is unique among S. aureus leucotoxins, implying its crucial role in pathogenesis. Moreover, the tropism of LukED for murine phagocytes highlights the utility of murine models to study LukED pathobiology, including development and testing of strategies to inhibit toxin activity and control bacterial infection.
Imaging of large-scale integrated circuits using laser-terahertz emission microscopy (2005)

We present the redesign and improved performance of the laser terahertz emission microscope (LTEM), which is a potential tool for locating electrical failures in integrated circuits. The LTEM produces an image of the THz waves emitted when the circuit is irradiated by a femtosecond laser; the amplitude of the THz emission is proportional to the local electric field. By redesigning the optical setup and improving the spatial resolution of the system to below 3 microm, we could extend its application to examining of large-scale integration circuits. As example we show the THz emission pattern of the electric field in an 8-bit microprocessor chip under bias voltage.
Possibilities and limitations of thromboelastometry/thromboelastography (2006)

Summary Thromboelastometry/thromboelastography provides information about clot strength and stability. Modified procedures have improved the standardisation and increased the diagnostic power of these test systems. Heparinase- modified thromboelastometry/thromboelastography allows assessment of the heparin effect. The introduction of FIBTEM on the ROTEM® also makes it possible to differentiate between disorders of the plasma and platelet components of clot strength. This may be of interest in the perioperative setting, as our clinical data show that elevated levels of D-dimer have no predictive value for hyperfibrinolysis. However, disorders of primary haemostasis such as von Willebrand’s disease cannot be determined with thromboelastometry/ thromboelastography, nor do the effects of acetyl salicylic acid and clopidogrel on platelets influence the results. Only platelet aggregation inhibitors which affect the glycoprotein IIb/IIIa receptors, such as ReoPro®, may reduce clot strength at high doses. A similar effect is to be expected with severe Glanzmann’s thrombasthenia. Coagulation times in thromboelastometry/thromboelastography (measured as CT/r value) show poor correlation with conventional coagulation parameters because of the different activators used. The introduction of rotation thromboelastometry (ROTEM®) provides a stable system suitable for near patient testing.
Insulin-like Growth Factor Receptor Inhibitors: Baby or the Bathwater? (2012)

The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response, larger randomized phase III trials have not shown clear clinical benefit of targeting this pathway in combination with conventional strategies. These disappointing results have resulted in the discontinuation of several anti-IGF1R programs. However, the conduct of these trials has brought to the forefront several important factors that need to be considered in the conduct of future clinical trials. The need to develop biomarkers, a clearer understanding of insulin receptor function, and defining rational combination regimens all require further consideration. In this commentary, the current state of IGF1R inhibitors in cancer therapy is reviewed.
Self‐Oscillating Gels Driven by the Belousov–Zhabotinsky Reaction as Novel Smart Materials (2010)

So far stimuli-responsive polymer gels and their application to smart materials have been widely studied; this research has contributed to progress in gel science and engineering. For their development as a novel biomimetic polymer, studies of polymers with an autonomous self-oscillating function have been carried out since the first reports in 1996. The development of novel self-oscillating polymers and gels have been successful utilizing the oscillating reaction, called the Belousov-Zhabotinsky (BZ) reaction, which is recognized as a chemical model for understanding several autonomous phenomena in biological systems. The self-oscillating polymer is composed of a poly(N-isopropylacrylamide) network in which the catalyst for the BZ reaction is covalently immobilized. In the presence of the reactants, the polymer undergoes spontaneous cyclic soluble-insoluble changes or swelling-deswelling changes (in the case of gel) without any on-off switching of external stimuli. Potential applications of the self-socillating polymers and gels include several kinds of functional material systems, such as biomimetic actuators and mass transport surface.
Evidence for the functional binding in vivo of tumor rejection antigens to antigen-presenting cells in tumor-bearing hosts (1991)

Spleen cells of BALB/c mice bearing a syngeneic CSA1M fibrosarcoma were treated with anti-Thy-1.2 antibody plus C, yielding a T cell-depleted, APC-containing fraction. The APC-containing fraction was first tested for its capacity to present exogenous modified-self or another tumor (Meth A) Ag after in vitro pulsing. The results showed comparable Ag-presenting capacities to those obtained by APC-containing fraction from normal spleen cells, indicating that APC function is not affected in tumor-bearing mice. We next examined whether APC from CSA1M-bearing mice bind endogenously generated CSA1M tumor Ag onto its surfaces to stimulate tumor-specific T cells. Five rounds of inoculation of APC-containing fraction from CSA1M-bearing mice without further in vitro pulsing resulted in the induction of potent anti-CSA1M immune resistance. The involvement of anti-CSA1M T cells in the induction of anti-CSA1M immunity was excluded by the fact that the in vivo immunity was excluded by the fact that the in vivo immunity was delivered by Thy-1+ cell-depleted, but not by Thy-1+ cell-enriched fractions of spleen cells from CSA1M-bearing mice. Moreover, the failure of Sephadex G10-passed spleen cells to deliver anti-CSA1M resistance demonstrated the absolute requirement of APC for inducing the in vivo immunity. Finally, this in vivo resistance was found to be tumor specific, because APC fractions from CSA1M-bearing and Meth A-bearing BALB/c mice induced immune resistance selective against the corresponding tumor cell challenge. These results indicate that APC from tumor-bearing hosts can not only exert unaffected APC function against exogenous Ag, but also function to present tumor Ag generated endogenously in the tumor-bearing state and to produce tumor-specific immunity in vivo.
Development and validation of IMMUNO-COV™: a high-throughput clinical assay for detecting antibodies that neutralize SARS-CoV-2 (2020)

We here describe the development and validation of IMMUNO-COV™, a high-throughput clinical test to quantitatively measure SARS-CoV-2-neutralizing antibodies, the specific subset of anti-SARS-CoV-2 antibodies that block viral infection. The test measures the capacity of serum or purified antibodies to neutralize a recombinant Vesicular Stomatitis Virus (VSV) encoding the SARS-CoV-2 spike glycoprotein. This recombinant virus (VSV-SARS-CoV-2-S-Δ19CT) induces fusion in Vero cell monolayers, which is detected as luciferase signal using a dual split protein (DSP) reporter system. VSV-SARS-CoV-2-S-Δ19CT infection was blocked by monoclonal α-SARS-CoV-2-spike antibodies and by plasma or serum from SARS-CoV-2 convalescing individuals. The assay exhibited 100% specificity in validation tests, and across all tests zero false positives were detected. In blinded analyses of 230 serum samples, only two unexpected results were observed based on available clinical data. We observed a perfect correlation between results from our assay and 80 samples that were also assayed using a commercially available ELISA. To quantify the magnitude of the anti-viral response, we generated a calibration curve by adding stepped concentrations of α-SARS-CoV-2-spike monoclonal antibody to pooled SARS-CoV-2 seronegative serum. Using the calibration curve and a single optimal 1:100 serum test dilution, we reliably measured neutralizing antibody levels in each test sample. Virus neutralization units (VNUs) calculated from the assay correlated closely (p < 0.0001) with PRNT <sub>EC50</sub> values determined by plaque reduction neutralization test against a clinical isolate of SARS-CoV-2. Taken together, these results demonstrate that the IMMUNO-COV™ assay accurately quantitates SARS-CoV-2 neutralizing antibodies in human sera and therefore is a potentially valuable addition to the currently available serological tests. The assay can provide vital information for comparing immune responses to the various SARS-CoV-2 vaccines that are currently in development, or for evaluating donor eligibility in convalescent plasma therapy studies.