gebhart/patrepeval huggingface dataset:
Real-Time Detection of Nucleic Acid Interactions by Total Internal Reflection Fluorescence (2003)

This paper describes the development of an optical readout system for the real-time analysis of fluorescent-labeled DNA microarrays is described. The system is targeted toward research applications in genomics, agriculture, and life sciences, where the end-point detection of state-of-the-art readout systems does not provide sufficient information on the hybridization process. The hybridization progress of molecules from the liquid phase in a flow cell to immobilized oligonucleotides on a transducer surface can be observed. The excitation of fluorochromes is realized by a semiconductor laser, and the fluorescence emission is collected by a cooled CCD camera. Quantitative data can be extracted from the images for analysis of the microarray. For the signal transduction, the principle of total internal reflection is used. With a multiple internal reflection arrangement, the sensor chip was adapted to the standard microscope slide format and a homogeneous evanescent illumination of the active area of the sensor surface was achieved. An application measurement was carried out with this readout system. The hybridization of Cy5-labeled 30-mer single-stranded oligonucleotides to fully complementary immobilized strands was observed in real time. A kinetic analysis was demonstrated with the recorded data. Melting curves of a 140-mer PCR product from a hemochromatosis patient sample hybridized to immobilized wild-type mutant 15- and 17-mer oligonucleotides were recorded and single-point mutations could be detected.
Clonal Polymorphism of Borrelia burgdorferi Strain B31 MI: Implications for Mutagenesis in an Infectious Strain Background (2002)

A major obstacle to studying the functions of particular gene products in the mouse-tick infectious cycle of Borrelia burgdorferi has been an inability to knock out genes in pathogenic strains. Here, we investigated conditions for site-directed mutagenesis in B31 MI, the low-passage-number, infectious B. burgdorferi strain whose genome was sequenced. We inactivated several plasmid and chromosomal genes in B31 MI and determined that clones carrying these mutations were not infectious for mice. However, we found extensive heterogeneity among clones and mutants derived from B31 MI based on colony phenotype, growth rate, plasmid content, protein profile, and transformability. Significantly, several B31 MI clones that were not subjected to mutagenesis but that lacked particular plasmids also exhibited defects at various stages in the infectious cycle. Therefore, the high degree of clonal polymorphism within B31 MI complicates the assessment of the contributions of individual genes to the observed phenotypes of the mutants. Our results indicate that B31 MI is not an appropriate strain background for genetic studies in infectious B. burgdorferi, and a well-defined isogenic clone is a prerequisite for targeted mutagenesis. To this end, we derived several wild-type clones from B31 MI that were infectious for mice, and gene inactivation was successful in one of these clones. Due to the instability of the genome with in vitro propagation, careful monitoring of plasmid content of derived mutants and complementation of inactivated genes will be crucial components of genetic studies with this pathogen.
The human mast cell: functions in physiology and disease (2001)

Mast cells are multifunctional, tissue-dwelling cells capable of secreting a wide variety of mediators. They develop from bone marrow-derived progenitor cells, primed with stem cell factor (SCF), which mediates its actions by interacting with the SCF receptor or c-kit on the cell surface. Mast cells continue their maturation and differentiation in peripheral tissue, developing into two well described subsets of cells, MCT and MCTC cells, varying in content of tryptase and chymase as well as in immunobiology. Mast cells are activated by numerous stimuli, including antigen (acting via the high affinity IgE receptor, Fc?RI), superoxides, complement proteins, neuropeptides and lipoproteins resulting in activation and degranulation. Following activation, these cells express mediators such as histamine, leukotrienes and prostanoids, as well as proteases, and many cytokines and chemokines, pivotal to the genesis of an inflammatory response. Recent data suggests that mast cells may play an active role in such diverse diseases as atherosclerosis, malignancy, asthma, pulmonary fibrosis and arthritis. Mast cells directly interact with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been demonstrated to have inhibitory effects on mast cell degranulation or mediator release.
G Protein-coupled Receptors (1998)

Nearly 2000 G protein-coupled receptors (GPCRs)1 have been reported since bovine opsin was cloned in 1983 (1) and the β-adrenergic receptor in 1986 (2). They are classified into over 100 subfamilies according to the sequence homology, ligand structure, and receptor function. A substantial degree of amino acid homology is found among members of a particular subfamily, but comparisons between subfamilies show significantly less or no similarity.
Use of proline mutants to help solve the NMR solution structure of type III antifreeze protein (1993)

To help understand the structure/function relationships in antifreeze proteins (AFP), and to define the motifs required for ice binding, a Type III AFP suitable for two-dimensional (2D) NMR studies was produced in Escherichia coli. A synthetic gene for one of the Type III AFP isoforms was assembled in a T7 polymerase-directed expression vector. The 67-amino acid-long gene product differed from the natural AFP by inclusion of an N-terminal methionine but was indistinguishable in activity. The NMR spectra of this AFP were complicated by cis-trans proline isomerization from the C-terminal sequence YPPA. Substitution of this sequence by YAA eliminated isomer signals without altering the activity or structure of the mutant AFP. This variant (rQAE m1.1) was selected for sequential assignment and the secondary structure determination using 2D 1H NMR spectroscopy. Nine beta-strands are paired to form two triple-stranded antiparallel sheets and one double-stranded antiparallel sheet. Two further proline replacements, P29A and P33A, were made to delineate the role of conserved prolines in Type III AFP. These mutants were valuable in clarifying ambiguous NMR spectral assignments amongst the remaining six prolines of rQAE m1.1. In contrast to the replacement of the C-terminal prolyl residues, the exchange of P29 and P33 caused some structural changes and significantly decreased protein solubility and antifreeze activity.
ErbB-2 and Met Reciprocally Regulate Cellular Signaling via Plexin-B1 (2007)

Sema4D-induced activation of plexin-B1 has been reported to evoke different and sometimes opposing cellular responses. The mechanisms underlying the versatility of plexin-B1-mediated effects are not clear. Plexin-B1 can associate with the receptor tyrosine kinases ErbB-2 and Met. Here we show that Sema4D-induced activation and inactivation of RhoA require ErbB-2 and Met, respectively. In breast carcinoma cells, Sema4D can have pro- and anti-migratory effects depending on the presence of ErbB-2 and Met, and the exchange of the two receptor tyrosine kinases is sufficient to convert the cellular response to Sema4D from pro- to anti-migratory and vice versa. This work identifies a novel mechanism by which plexin-mediated signaling can be regulated and explains how Sema4D can exert different biological activities through the differential association of its receptor with ErbB-2 and Met.
On-chip decoupling capacitor design to reduce switching-noise-induced instability in CMOS/SOI VLSI (2002)

The supply noise from the packaging of CMOS/SOI circuits can cause performance degradation, reliability reduction and even loss of circuit functionality due to the device latch-up problem. By properly adding on-chip decoupling capacitors in the proximity of the circuitry, we can effectively alleviate the switching noise problem and improve the performance of CMOS/SOI circuits.
Investigation of the staggered herringbone mixer with a simple analytical model (2004)

An analytical model is presented for the three-dimensional flow in the recently introduced staggered herringbone mixer for microchannels. In this model, the flow in the cross-section of the channel is treated as a lid-driven cavity flow. The model is shown to reproduce the advection patterns that were observed experimentally in the staggered herringbone mixer. The model is then used to study the quality of mixing in this flow as a function of geometry. Analysis is performed with Poincaré maps, mixing simulations, and residence time distributions. A range of optimal geometries is identified.
Autophagy in Adipose Tissue (2012)

The possible involvement of the evolutionarily conserved process of autophagy (selfeating) in the pathogenesis of human diseases has been increasingly appreciated in recent years. However, at present, many fundamental questions remain to be answered before autophagy can be considered as a therapeutic target: The biological consequences of activating or inhibiting the process are very much cell type-specific and overall biological context-dependent. Consequently, the same manipulation can yield opposing effects, such as enhanced cell survival versus cellular death, or augmented versus attenuated cellular stress responses. In this brief perspective editorial, we highlight the current knowledge on the role of autophagy in adipose tissue (AT). We first address the putative role of autophagy in AT development, and then discuss how AT autophagy is altered in obesity as well as the possible causes for such alteration. Next, we raise outstanding questions on the role altered AT autophagy might play in the context of obesity, and the potential to manipulate adipose autophagy for therapeutic purposes.
Why do so many people drop out from auto-injection therapy for impotence? (1989)

Although intracavernous injection of vasoactive substances has been shown to be a reasonable and reliable method of reversing impotence, studies assessing patient acceptance of this new technology are lacking. By prospectively following patients and willing partners over a 2-year period, this study sought to document patient utilization rates and the reasons why patients decline or discontinue injection therapy. The cumulative dropout rate was 46%, with patients being most at risk for leaving the program after evaluation or during the trial dose phase. Patients decline treatment because they are unable to accept the idea of injecting themselves or because of potential side effects. Patients discontinue treatment because of perceived lack of efficacy. Patient and programatic obstacles to utilization of self-injection therapy are analyzed.
sel-10, a negative regulator of lin-12 activity inCaenorhabditis elegans, encodes a member of the CDC4 family of proteins (1997)

Mutations that influence lin-12 activity in Caenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a member of the CDC4 family of proteins and has a potential human ortholog. Coimmunoprecipitation data indicate that C. elegans SEL-10 complexes with LIN-12 and with murine Notch4. We propose that SEL-10 promotes the ubiquitin-mediated turnover of LIN-12/Notch proteins, and discuss potential roles for the regulation of lin-12/Notch activity by sel-10 in cell fate decisions and tumorigenesis.
Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia (2019)

During the treatment of CLL, ibrutinib was not associated with significantly higher risks of anemia, thrombocytopenia, or neutropenia compared to the control group. However, abdominal manifestations were significantly higher with ibrutinib. Advanced phase trials should further confirm this hypothesis.
High-Performance Semiconducting Nanotube Inks: Progress and Prospects (2011)

While the potential for high mobility printed semiconducting nanotube inks has been clear for over a decade, a myriad of scientific and technological issues has prevented commercialization and practical use. One of the most challenging scientific problems has been to understand the relationship between the pristine, individual nanotube mobility (known to be in the 10,000 cm(2)/V·s range) and the as-deposited random network mobility (recently demonstrated in the 100 cm(2)/V·s range). An additional significant scientific hurdle has been to understand, manage, and ultimately eliminate the effects of metallic nanotubes on the network performance, specifically the on/off ratio. Additional scientific progress is important in understanding the dependence of nanotube length, diameter, and density on device performance. Finally, the development of ink formulations that are of practical use in manufacturing is of paramount importance, especially with regard to drying time and uniformity, and ultimately, the issue of scalability and cost must be addressed. Many of these issues have recently been investigated from a phenomenological point of view, and a comprehensive understanding is beginning to emerge. In this paper, we present an overview of solution-based printed carbon nanotube devices and discuss long-term technology prospects. While significant technical challenges still remain, it is clear that the prospects for the use of nanotube ink in a myriad of systems is feasible given their unmatched mobility and compatibility with heterogeneous integration into a variety of applications in printed and flexible electronics.
Role of CD47 in Erythroid Cells and in Autoimmunity (2004)

The cell surface glycoprotein CD47 (Integrin-associated protein/IAP) was originally identified as a regulator of integrin-dependent responses to extracellular matrix proteins. However, CD47 is ubiquitously expressed, also by cells that do not express integrins. Thus, during the last few years, it has been shown that CD47 has several important functions besides assisting integrin activation. This review will focus on the role of CD47 in erythrocytes. In these cells, CD47 was found to be an important link in the interaction between the band 3 complex and the Rh complex in the maintenance of erythrocyte membrane integrity. CD47 can also function as a marker of self on erythrocytes, and likely also on other cells, by binding to the inhibitory receptor SIRPalpha. In this way, SIRPalpha-expressing cells, like macrophages and dendritic cells, are less likely to phagocytose an autoimmune sensitized cell with CD47 on its surface than a CD47-deficient cell where this inhibitory mechanism will not be engaged. The interaction between CD47 and SIRPalpha seems to be important to limit destruction of host cells in autoimmune diseases like autoimmune hemolytic anemia (AIHA), where macrophages destroy antibody or complement opsonized cells.
Cardiotonic agents. 6. Histamine analogs as potential cardiovascular selective H2 agonists (1990)

Twenty-six alkyl and aralkyl histamine analogues were prepared as potential cardiotonic agents. Compounds were designed to allow interaction with a putative secondary aryl binding site at the H2 receptor, the presence of which was inferred from the structure of cyprohepatadine, which is known to have H2-antagonist properties. The compounds were examined for inotropic activity in ferret papillary muscle. Potent inotropic activity was generally found in N-alkyl- and N,N-dialkylimidazole-4-ethanamines, whereas N-(amidoalkyl)imidazole-4-ethanamines and N-alkylimidazole-4-propanamines were at best weakly active. Five compounds were examined in screens designed to assess hemodynamic effects and gastric acid secretion in vivo. Two of these compounds, alpha-(3-phenyl-2-transpropenyl)-1H-imidazole-4-ethanamine and N-heptyl-1H-imidazole-4-ethanamine, showed positive inotropic activity with minimal effects on heart rate and mean arterial pressure in vivo; however, both compounds were found to stimulate gastric acid secretion. These results demonstrate that selectivity between various H2-receptor-mediated activities can be obtained with substituted histamine analogues.
Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. (1993)

We have explored the therapeutic effects of anti-epidermal growth factor receptor monoclonal antibodies (MAbs) 225 and 528 on well established A431 epidermoid carcinoma xenografts, approximately 400 mm3 (1 cm in diameter) at the start of treatment. In previous reports we demonstrated that MAbs 225 and 528 prevented the growth of A431 cell xenografts in nude mice when treatment was begun on the day of tumor cell inoculation. Since anti-epidermal growth factor receptor MAb therapy of well established tumors was unable to retard growth, we explored combination therapy with MAb plus the chemotherapeutic agent cis-diamminedichloroplatinum (cis-DDP). Additive and concentration-dependent growth-inhibitory effects of MAb with cis-DDP were observed in cultures of A431 cells. Neither intensive treatment with 225 MAb (1 mg/mouse, i.p. on day 8 after tumor inoculation, and twice weekly for 4 weeks) nor a maximally tolerated single dose of cis-DDP [150 micrograms/25 g (6 mg/kg) mouse weight, i.p. on day 8] had significant effects on tumor growth. However, the two treatments in combination resulted in substantial xenograft growth inhibition, compared with both an untreated control group and animals treated with a single modality. When a second dose of cis-DDP (150 micrograms/25 g) was added after 10 days, combination therapy with 225 MAb produced striking antitumor effects. At the end of 1 month tumor xenografts had disappeared in all but one mouse, and no tumor relapses occurred during 6 months of observation. Identical results were obtained with anti-epidermal growth factor receptor MAb 528 in combination with cis-DDP. The results of these studies provide a novel approach to the treatment of well established tumor xenografts, which may have application in the therapy of human malignancies.
Electrical impedance spectroscopy and the diagnostic accuracy for malignant melanoma (2011)

The results suggest that electrical impedance spectra can distinguish between malignant melanoma and benign skin lesions. Although it is indicated that the accuracy of the device is clinically promising, the overall performance, and the sensitivity to thin malignant melanomas, must be improved and thoroughly validated before the instrument can be used as a routine stand-alone diagnostic decision support tool. The technique is under revision to further improve the reproducibility, specificity and sensitivity.
Combining Biochemical and Imaging Markers to Improve Diagnosis and Characterization of Mild Traumatic Brain Injury in the Acute Setting: Results from a Pilot Study (2013)

Blood biomarkers and advanced MRI may correlate or complement each other in different aspects of mTBI detection and characterization. GFAP might have potential to serve as a clinical screening tool for intracranial bleeding. UCH-L1 complements MRI in injury detection. Impairment at WM tracts may account for the patients' neurocognitive symptoms.
Local and systemic changes in glucosinolates in Chinese and European cultivars of oilseed rape (Brassica nap us L.) after inoculation with Sclerotinia sclerotiorum (stem rot) (1999)

Summary Four Chinese Brassica napus lines, generated through a breeding programme to identify Sclerotinia sclerotiorum tolerant and susceptible lines, and three European varieties were analysed for changes in glucosinolates (qualitative and quantitative), and general host reactions, after localised inoculation with a UK S. sclerotiorum isolate. Plants at the fifth leaf stage were either singly inoculated (third leaf) or were inoculated once (third leaf) and then challenged a second time (seventh leaf) 7 days after the first inoculation. The results showed very distinct reactions in the different lines and cultivars to the fungus, both locally and systemically. Of the European lines B. napus cv. Bienvenu showed good resistance (small lesions and less host damage) both 3 and 7 days post‐inoculation. Capricorn was the most susceptible followed by Cobra; the third leaves of these cultivars were showing strong chlorotic and necrotic reactions by day 3 and lesions were well developed. By day 7 the third leaves of Capricorn were completely rotten whilst Cobra still had a little healthy tissue. Inoculation of the four Chinese lines showed that two had moderate resistance (014 and 020 — slightly less resistant than Bienvenu) and two were very susceptible (016 and 024 — similar reactions to Capricorn and Cobra), based on lesion size and host tissue damage. Glucosinolate induction in line 014 was good both locally and systemically, with clear local and systemic induction of indolylglucosinolates and 2‐phenylethylglucosinolate both 3 and 7 days post‐inoculation. Line 020 did not show no particular increases in glucosinolates after inoculation either locally or systemically. In line 016 there was a small local increase and a large systemic reduction in total glucosinolates. Inoculation of line 024 caused no major local changes in glucosinolates and again a big reduction in glucosinolates systemically. The dual inoculation system, with lines 014 and 016, produced comparable results, with line 014 showing good local and systemic induction of glucosinolates (after the first inoculation) and a further local and systemic induction after the second inoculation. This induction in pre‐inoculated line 014 plants was associated with a reduction in lesion size of the second inoculum. Line 016 responded poorly both locally and systemically, and there were no real decrease in the lesion size of the second inoculum. It appears that in line 014 glucosinolate induction may be an important part of resistance, whereas in line 020 there are clearly other non‐glucosinolate factors involved. The poor local and systemic induction of glucosinolates in lines 016 and 024, and subsequent susceptibility, implies that glucosinolate induction may be an important marker of resistance to S. sclerotiorum in oilseed rape.
Remission of refractory gestational trophoblastic disease with high-dose paclitaxel (1996)

High-risk metastatic gestational trophoblastic disease (GTD) in patients who have failed primary chemotherapy has a very poor prognosis. About 25% of women with high-risk metastatic disease become refractory to EMA-CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide and vincristine) and fall to achieve a complete remission. Currently, there is no standard salvage chemotherapeutic regime for EMA-CO failure. Paclitaxel, a taxane analog extracted from the bark of the western yew (Taxus brevlfolla), has shown antitumor activity in a variety of cancer cell lines. High in vivo efficacy was confirmed in phase II trials, especially for breast and epithelial ovarian cancer patients. Recently, two in vitro studies have shown that paclitaxel is a highly effective antineoplastic agent in choriocarcinoma cell lines. We present the first clinical report of a serologic remission with high-dose paclitaxel (250 mg/m2 i.v. infusion over 24 h every 3 weeks) of a highly refractory GTD in a patient who developed brain metastasis after multiple combined chemotherapeutic regimens. The patient tolerated paclitaxel with granulocyte colony stimulating factor support very well. The remission with paclitaxel in this patient confirms its preclinical activity in high-risk, refractory GTD.