gebhart/patrepeval huggingface dataset:
A Neural Stimulator Output Stage for Dodecapolar Electrodes (2008)

This paper describes the output stage of a multipurpose ASIC designed to be used for electrical stimulation with a dodecapolar electrode. The circuit is developed within the context of the DEMAR project which aims to provide a palliative solution for nervous system dysfunctions thanks to functional electrical stimulation (FES). The output stage of the stimulator is in charge of amplifying and distributing the current among the poles of the electrode. The proposed structure offers several benefits such as the ability to switch the stimulation sites from cathode to anode configuration and to perform either synchronous, sequential or asynchronous stimulations on every channel.
Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer (1997)

Clinical follow-up data of 276 colorectal adenocarcinoma patients treated in Kuopio University Hospital between 1976 and 1986 and followed up for a mean of 14 years were analysed. The clinical findings were correlated with tumour-infiltrating lymphocytes (TILs) and with histological and quantitative factors including nuclear parameters and volume-corrected mitotic index. In univariate survival analysis, TNM classification, Dukes' stage, histological grade, and TILs were significant predictors of survival. TNM classification, Dukes' stage, and TILs also predicted recurrence-free survival. In multivariate analysis, TILs were an independent prognostic factor of survival in all cases, as well as in patients with T1-4N0-3M0 and T1-4N1-3M1. TILs also independently predicted recurrence-free survival. TILs can provide important prognostic information in colorectal cancer to be used in evaluating for adjuvant therapy in different tumour stages.
Domain-specific search strategies for the effective retrieval of healthcare and shopping information (2002)

An increasing number of users are performing searches on the Web in unfamiliar domains such as healthcare. However, because many users lack domain-specific search knowledge, their searches are often ineffective. An important remedy is to make domain-specific search knowledge in these new domains explicit and available. Towards that goal, healthcare and online shopping experts were observed while they performed search tasks within and outside their domains of expertise. The study: (1) identified domain-specific search strategies in each domain; (2) demonstrated that such knowledge is not automatically acquired from using general-purpose search engines. These results suggest that users should benefit from Strategy Portals that provide domain-specific knowledge to perform searches in unfamiliar domains.
7th European Congress on Intensive Care Medicine Innsbruck, June 14–17, 1994 East and West—A Common Future (1994)

Inlroduction;; Mortality prediction in critically ill patients is an every day routine in ICUs. Our aim is to evaluate prognostic accuracy of SAPS II as compared with the predictive capabilities of its predecesor SAPS 1, and with the one of APACHE II, probably the most used prognostic method of the available ones. Patients and S~tting; 568 patients admitted in two medical-surgical ICUs of two Hospitals (III -A-and II -B-level) were consecutively admitted (A: 358 and B: 210 patients) and prospectively admitted in the study. Methodology: All patients outcome were predicted by SAPS I and SAPS, as well as APACHE II, using the worst values availables during the first 24 h of stay in ICU. For APACHE II diagnostic grouping according original description was also considered. In all cases, procedence, type of patient (surgical or not, emergency admission or not), sex, age, length of stay (LOS) and other epidemiological data were also collected. Mortality was considered at the end of the hospitalary stay. Non paired Student T test, Chi square test, and Regression methods were used in tha analysis. Overall performance of prognostic methods were compared by means of the calculation of the areas under ROC curves. Significative differences were associated to p < 0.05. Results; Mortality in the study was 21% (p NS A vs B) and there were not significant differences in LOS. SAPS I and SAPS II revealed significant differences in severity when studying A and B populations (p < 0.014 and p < 10 .4) and risk of death evaluation was greater in B population when using SAPS II. For the whole sample and at probability level of 50 %, accuracy of prediction was 83 % for SAPS I and 80 % for SAPS II. At probability level of 90 %, accuracies of prediction for both methods were respectively 79 % and 82 %.. When using APACHE II, accuracies were 82% and 80 %. There were not signinficant differences, at any of the considered probability levels (50, 70 and 90 %), between real mortality and predicted mortality when any of the three methodologies were utilized, Facing the evidence that SAPS II do not represent, in our population, predictive advantages in front of SAPS I, a regression equation has been developed between SAPS II and SAP I (SAPS II = 10.53 + 2.28 SAPS I, R: 0,76, SEE 10.54, F: 791, p < 10 .4), Conclusion: SAPS II do not represent predictive advantages in front of SAPS I, about critically ill patients outcome evaluation ICUs Dpts.
Organic Transistor Circuits for Application to Organic Light-Emitting-Diode Displays (2003)

Organic thin-film transistor circuits based on the small molecule, copper phthalocyanine, have been demonstrated for application to an active-matrix display with organic light-emitting diodes. The circuit consists of two organic thin-film transistors and one storage capacitor which provide continuous current under pulsed operation. The transistors for the circuit have been designed on the basis of the current characteristics of the individual transistors. Continuous output current has been obtained under pulsed voltage operation by using the organic transistor circuit.
KDM4A, KDM4B and KDM4C in non-small cell lung cancer. (2015)

KDM4A, KDM4B and KDM4D are lysine demethylases which demethylate H3 at lysine K9 and K36 sites, additionally KDM4D also the H1.4 linker histone at K26 lysine. Lysine methylation changes can repress or induce gene expression at specific sites thus influencing cellular functions. We analysed the immunohistochemical expression of KDM4A, KDM4B and KDM4D in a clinical material of 188 patients with lung carcinomas. There were 132 (70%) squamous cell carcinomas, 53 (28%) adenocarcinomas and 3 (2%) large cell carcinomas in the study. Additionally, the trimethylated state of chromatin was detected with an antibody to trimethylated H3K9 residue. Nuclear KDM4A and KDM4D were associated with the presence of lymph node metastases in tumors. Cytoplasmic KDM4A was associated with poor survival of the patients (P = 0.015) and with a shorter recurrence free interval (P = 0.028). KDM4A and KDM4D appear to have a significant role in the metastatic spread of lung carcinomas. The findings are also in line with their proposed involvement in mechanisms associated with cell proliferation, apoptosis and DNA repair.
MMP-9 Responsive PEG Cleavable Nanovesicles for Efficient Delivery of Chemotherapeutics to Pancreatic Cancer (2014)

Significant differences in biochemical parameters between normal and tumor tissues offer an opportunity to chemically design drug carriers which respond to these changes and deliver the drugs at the desired site. For example, overexpression of the matrix metalloproteinase-9 (MMP-9) enzyme in the extracellular matrix of tumor tissues can act as a trigger to chemically modulate the drug delivery from the carriers. In this study, we have synthesized an MMP-9-cleavable, collagen mimetic lipopeptide which forms nanosized vesicles with the POPC, POPE-SS-PEG, and cholesteryl-hemisuccinate lipids. The lipopeptide retains the triple-helical conformation when incorporated into these nanovesicles. The PEG groups shield the substrate lipopeptides from hydrolysis by MMP-9. However, in the presence of elevated glutathione levels, the PEG groups are reductively removed, exposing the lipopeptides to MMP-9. The resultant peptide-bond cleavage disturbs the vesicles' lipid bilayer, leading to the release of encapsulated contents. These PEGylated nanovesicles are capable of encapsulating the anticancer drug gemcitabine with 50% efficiency. They were stable in physiological conditions and in human serum. Effective drug release was demonstrated using the pancreatic ductal carcinoma cells (PANC-1 and MIAPaCa-2) in two-dimensional and three-dimensional "tumor-like" spheroid cultures. A reduction in tumor growth was observed after intravenous administration of the gemcitabine-encapsulated nanovesicles in the xenograft model of athymic, female nude mice.
[Therapy refractory depression]. (1999)

Patients who fail in an adequate trial of a standard antidepressant drug (corresponding to 150 mg/d imipramine over a minimal period of 4 weeks) are defined as treatment resistant. According to these guidelines a substantial number of patients is not sufficiently treated and, thus, should be reassessed for dosage and length of antidepressant medications. If patients fail to a sufficient treatment a response may be achieved if they are switched to an alternative drug and/or if biochemically differently acting antidepressants are combined. Furthermore, an increasingly popular approach to handle treatment resistance is the use of augmentation strategies. Among these, lithium and thyroid T3 are the most well studied with the most consistently positive results. As non-pharmacological augmentation approach partial sleep deprivation has proved to be effective in combination with antidepressant medication. Finally, patients who had no or only a partial response to several treatments with antidepressants may benefit from electroconvulsive therapy.
Immunogenicity of somatic mutations in human gastrointestinal cancers (2015)

It is unknown whether the human immune system frequently mounts a T cell response against mutations expressed by common epithelial cancers. Using a next-generation sequencing approach combined with high-throughput immunologic screening, we demonstrated that tumor-infiltrating lymphocytes (TILs) from 9 out of 10 patients with metastatic gastrointestinal cancers contained CD4(+) and/or CD8(+) T cells that recognized one to three neo-epitopes derived from somatic mutations expressed by the patient's own tumor. There were no immunogenic epitopes shared between these patients. However, we identified in one patient a human leukocyte antigen-C*08:02-restricted T cell receptor from CD8(+) TILs that targeted the KRAS(G12D) hotspot driver mutation found in many human cancers. Thus, a high frequency of patients with common gastrointestinal cancers harbor immunogenic mutations that can potentially be exploited for the development of highly personalized immunotherapies.
3-(4-Aroyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-alkylamides as a New Class of Synthetic Histone Deacetylase Inhibitors. 1. Design, Synthesis, Biological Evaluation, and Binding Mode Studies Performed through Three Different Docking Procedures (2003)

Recently we reported a novel series of hydroxamates, called 3-(4-aroyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides (APHAs), acting as HDAC inhibitors (Massa, S.; et al. J. Med. Chem. 2001, 44, 2069-2072). Among them, 3-(4-benzoyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide 1 was chosen as lead compound, and its binding mode into the modeled HDAC1 catalytic core together with its histone hyperacetylation, antiproliferative, and cytodifferentiating properties in cell-based assays were investigated (Mai, A.; et al. J. Med. Chem. 2002, 45, 1778-1784). Here we report the results of some chemical manipulations performed on (i) the aroyl portion at the C4-pyrrole position, (ii) the N(1)-pyrrole substituent, and (iii) the hydroxamate moiety of 1 to determine structure-activity relationships and to improve enzyme inhibitory activity of APHAs. In the 1 structure, pyrrole N(1)-substitution with groups larger than methyl gave a reduction in HDAC inhibiting activity, and replacement of hydroxamate function with various non-hydroxamate, metal ion-complexing groups yielded poorly active or totally inactive compounds. On the contrary, proper substitution at the C4-position favorably affected enzyme inhibiting potency, leading to 8 (IC50 = 0.1 micro M) and 9 (IC50 = 1.0 micro M) which were 38- and 3.8-fold more potent than 1 in in vitro anti-HD2 assay. Against mouse HDAC1, 8 showed an IC50 = 0.5 micro M (IC50 of 1 = 4.9 micro M), and also in cell-based assay, 8 was endowed with higher histone hyperacetylating activity than 1, although it was less potent than TSA and SAHA. Such enhancement of inhibitory activity can be explained by the higher flexibility of the pyrrole C4-substituent of 8 which accounts for a considerably better fitting into the HDAC1 pocket and a more favorable enthalpy ligand receptor energy compared to 1. The enhanced fit allows a closer positioning of 8 hydroxamate moiety to the zinc ion. These findings were supported by extensive docking studies (SAD, DOCK, and Autodock) performed on both APHAs and reference drugs (TSA and SAHA).
Hollow Carbon Nanofiber-Encapsulated Sulfur Cathodes for High Specific Capacity Rechargeable Lithium Batteries (2011)

Sulfur has a high specific capacity of 1673 mAh/g as lithium battery cathodes, but its rapid capacity fading due to polysulfides dissolution presents a significant challenge for practical applications. Here we report a hollow carbon nanofiber-encapsulated sulfur cathode for effective trapping of polysulfides and demonstrate experimentally high specific capacity and excellent electrochemical cycling of the cells. The hollow carbon nanofiber arrays were fabricated using anodic aluminum oxide (AAO) templates, through thermal carbonization of polystyrene. The AAO template also facilitates sulfur infusion into the hollow fibers and prevents sulfur from coating onto the exterior carbon wall. The high aspect ratio of the carbon nanofibers provides an ideal structure for trapping polysulfides, and the thin carbon wall allows rapid transport of lithium ions. The small dimension of these nanofibers provides a large surface area per unit mass for Li(2)S deposition during cycling and reduces pulverization of electrode materials due to volumetric expansion. A high specific capacity of about 730 mAh/g was observed at C/5 rate after 150 cycles of charge/discharge. The introduction of LiNO(3) additive to the electrolyte was shown to improve the Coulombic efficiency to over 99% at C/5. The results show that the hollow carbon nanofiber-encapsulated sulfur structure could be a promising cathode design for rechargeable Li/S batteries with high specific energy.
A Structurally Variable Hinged Tetrahedron Framework from DNA Origami (2011)

Nanometer-sized polyhedral wire-frame objects hold a wide range of potential applications both as structural scaffolds as well as a basis for synthetic nanocontainers. The utilization of DNA as basic building blocks for such structures allows the exploitation of bottom-up self-assembly in order to achieve molecular programmability through the pairing of complementary bases. In this work, we report on a hollow but rigid tetrahedron framework of 75 nm strut length constructed with the DNA origami method. Flexible hinges at each of their four joints provide a means for structural variability of the object. Through the opening of gaps along the struts, four variants can be created as confirmed by both gel electrophoresis and direct imaging techniques. The intrinsic site addressability provided by this technique allows the unique targeted attachment of dye and/or linker molecules at any point on the structure's surface, which we prove through the superresolution fluorescence microscopy technique DNA PAINT.
Major Histocompatibility.Complex Molecule Expression in the Human Central Nervous System: Immunohistochemical Analysis of 40 Patients (1988)

To determine factors affecting major histocompatibility complex (MHC) molecule expression in situ in the human central nervous system (CNS) cryostat tissue sections from 36 autopsies and four biopsies were stained by immunoperoxidase with antibodies to class I (HLA-alpha chain, beta-2 microglobulin), class II (HLA-DR, HLA-DQ) MHC, lymphocyte, and macrophage antigens and Factor VIII-related antigen (VIII-RA). Stained cells and vessels/mm2 were counted in gray and white matter of four CNS anatomic levels. Class I molecules were found on parenchymal and endothelial cells (approximately 50% of VIII-RA + vessels) but not neurons, and were more abundant in gray than white matter (p less than 0.02). Class I molecules were absent in infants, but in adults expression was unaffected by age, sex, postmortem interval, presence of CNS lesions, or systemic illnesses. Expression of HLA-alpha chain and beta-2 microglobulin were the same. Class II molecules were usually absent but were found on parenchymal and endothelial cells in older adults, most frequently in association with macrophage infiltrates and spinal cord tract degenerations, but not with systemic illnesses. Expression of HLA-DR was greater than that of HLA-DQ. In the human CNS, regulation regulation of expression of MHC molecules is complex, can be affected by age, regional anatomy, and by local or remote CNS lesions, and may influence patterns and degrees of T cell immune responses.
Automatic Seizure Detection using Inter Quartile Range (2012)

The statistical properties of seizure EEG are found to be different from that of the normal EEG. This paper ascertains the efficacy of inter quartile range (IQR), a median based measure of statistical dispersion, as a discriminating feature that can be used for the classification of EEG signals into normal, interictal and ictal classes. IQR along with variance and entropy are calculated for each frame of EEG. To reduce the feature vector size, standard statistical features such as mean, minimum, maximum and standard deviation were evaluated and were given as input to a linear classifier. Without resorting to any kind of transformation, the proposed method reduces the computational complexity and achieves a classification accuracy of 100%.
Atropisomerism of Aromatic Carbamates (2010)

ortho-Haloarylcarbamates like 1-4 show a high rotational barrier about the N--aryl bond of up to 91.6 kJ mol(-1) as found for 1, which was determined by 2D exchange NMR spectroscopy (EXSY). It was further demonstrated that the height of the barrier not only depends on the substituents at the axis of chirality, but is also influenced by electronic effects.
Mutations in G proteins and G protein-coupled receptors in endocrine disease. (1996)

Naturally occurring mutations in the G protein Gs-α subunit and in a number of G protein-coupled receptors (GPCRs) have been identified in human diseases. Such mutations may lead to loss or gain of function of the encoded protein. Study of such naturally occurring, disease-causing mutations offers unique insights into G protein and GPCR structure and function. In general, diseases caused by GPCR loss-of-function mutations are inherited in autosomal recessive fashion, and those caused by gain-of-function mutations are inherited in autosomal dominant fashion. Endocrine gland dysfunction is the most frequently recognized consequence of GPCR mutation. Loss-of- function mutations in GPCRs for various hormones lead to hormone resistance, manifested as hypofunction of the gland expressing the affected GPCR. Conversely, GPCR gain-of-function mutations lead to hormone-independent activation and hyperfunction of the involved gland.
Interconversion and tissue distribution of pentoxifylline and lisofylline in mice (2006)

The aim of this study was to assess the interconversion pharmacokinetics and tissue distribution of pentoxifylline and the active (R)-enantiomer of its metabolite M1, lisofylline in male CD-1 mice. Both compounds were administered intravenously at a dose of 50 mg/kg on two separate occasions. Serum and tissues were collected at different time points following drug administration. In addition, the (S)-enantiomer of M1 was administered to a group of mice and serum samples were obtained. Analyte concentrations were measured by chiral HPLC. All serum concentration versus time data were fitted simultaneously to a pharmacokinetic model incorporating interconversion processes of parent drug and metabolites. The estimated conversion clearance of (-)-(R)-M1 to pentoxifylline (CL21) was six times greater than that for the reverse process (CL12). The interconversion of pentoxifylline and (+)-(S)-M1 was faster as reflected by the values of conversion clearances CL13 and CL31 which were approximately 16 and 7 times greater in comparison with the corresponding clearances for the interconversion of pentoxifylline and (-)-(R)-M1. When fitting pharmacokinetic data of both parent compounds to a one-compartment model, the values of elimination clearances assessed were close to those obtained on the basis of the interconversion model. After administration of pentoxifylline, tissue-to-serum AUC ratios ranged from 0.1 for liver and lungs to 0.32 for brain tissue. Serum levels of its metabolite, (-)-(R)-M1 were very low, whereas its tissue levels exceeded serum concentrations. The highest value of metabolite-to-parent AUC ratio (4.98) was observed in lungs. When (-)-(R)-M1 was given as a parent drug, tissue-to-serum AUC ratios in liver, kidney, and lungs were very close and ranged from 0.64 to 0.72. At the same time, levels of its metabolite, pentoxifylline were relatively low both in serum and all tissues studied. In consequence, metabolite-to-parent AUC ratios did not exceed the value of 0.27. In conclusion, reversible metabolism plays a modest role in the disposition of pentoxifylline and (-)-(R)-M1. It seems that pentoxifylline has less favourable pharmacokinetic properties than (-)-(R)-M1 due to lower concentrations attained in target organs. High levels of (-)-(R)-M1 observed after pentoxifylline administration in certain tissues such as liver or lungs suggest that pentoxifylline may constitute an effective prodrug for (-)-(R)-M1 in these organs.
Epitope Mapping of Human Recombinant Interferon Alpha Molecules by Monoclonal Antibodies (2007)

The epitopes of six recombinant human interferon alpha (IFN alpha) subtypes have been analysed using 22 monoclonal antibodies (MAbs) obtained from different sources. The IFN alpha subtype specificity of each MAb was determined by a combined immunoprecipitation-bioassay. Eight different epitopes were identified; the number of epitopes on a given IFN alpha subtype varied between four and eight. Each subtype possessed a unique combination of epitopes. Using the best pair of monoclonal antibodies, predicted from epitope mapping studies, subtype-specific two-site (tandem) assays were developed. It was observed that some non-cross-reactive MAbs influenced each other's binding, indicating the flexible nature of IFN molecules. Competitive radioimmunoassay and the combined immunoprecipitation-bioassay were used to identify a common epitope, present on IFN alpha-A, B, C, F and J but not on IFN alpha-D. In neutralization studies, all MAbs that identified this common epitope inhibited the antiviral activity of all IFN alpha molecules tested. It was concluded that the epitope is located within the receptor-binding region of IFN molecules and is important for biological activity. A tentative localization of the common epitope and the other identified epitopes is proposed.
Preshaping photoresist for refractive microlens fabrication (1994)

Refractive microlenses are fabricated by the preshaped photoresist refractive optics by melting (P<sup>2</sup>ROM) process. A polar coordinate HeCd laser beam lithography system (laser writer) is used to directly expose a continuous spheroidal profile into photoresist to fabricate 200-μm-diam microlenses with speeds between <i>f</i>/1.5 and <i>f</i>/5. Interferometric surlace measurements, used to determine the optical quality of the preshaped microlenses, indicate reduced spherical aberration in slow lenses fabricated by the P<sup>2</sup>ROM method.