gebhart/patrepeval huggingface dataset:
Composition profiling of seized ecstasy tablets by Raman spectroscopy (2000)

Raman spectroscopy with far-red excitation has been investigated as a simple and rapid technique for composition profiling of seized ecstasy (MDMA, N-methyl-3,4-methylenedioxyamphetamine) tablets. The spectra obtained are rich in vibrational bands and allow the active drug and excipient used to bulk the tablets to be identified. Relative band heights can be used to determine drug/excipient ratios and the degree of hydration of the drug while the fact that 50 tablets per hour can be analysed allows large numbers of spectra to be recorded. The ability of Raman spectroscopy to distinguish between ecstasy tablets on the basis of their chemical composition is illustrated here by a sample set of 400 tablets taken from a large seizure of > 50,000 tablets that were found in eight large bags. The tablets are all similar in appearance and carry the same logo. Conventional analysis by GC-MS showed they contained MDMA. Initial Raman studies of samples from each of the eight bags showed that despite some tablet-to-tablet variation within each bag the contents could be classified on the basis of the excipients used. The tablets in five of the bags were sorbitol-based, two were cellulose-based and one bag contained tablets with a glucose excipient. More extensive analysis of 50 tablets from each of a representative series of sample bags have distribution profiles that showed the contents of each bag were approximately normally distributed about a mean value, rather than being mixtures of several discrete types. Two of the sorbitol-containing sample sets were indistinguishable while a third was similar but not identical to these, in that it contained the same excipient and MDMA with the same degree of hydration but had a slightly different MDMA/sorbitol ratio. The cellulose-based samples were badly manufactured and showed considerable tablet-to-tablet variation in their drug/excipient ratio while the glucose-based tablets had a tight distribution in their drug/excipient ratios. The degree of hydration in the MDMA feedstocks used to manufacture the cellulose-, glucose- and sorbitol-based tablets were all different from each other. This study, because it centres on a single seizure of physically similar tablets with the same active drug, highlights the fact that simple physical descriptions coupled with active drug content do not in themselves fully characterize the nature of the seized materials. There is considerable variation in the composition of the tablets within this single seizure and the fact that this variation can be detected from Raman spectra demonstrates that the potential benefits of obtaining highly detailed spectra can indeed translate into information that is not readily available from other methods but would be useful for tracing of drug distribution networks.
In VitroModeling of Human Bocavirus 1 Infection of Polarized Primary Human Airway Epithelia (2013)

Human bocavirus 1 (HBoV1) is an emerging human-pathogenic respiratory virus. We characterized two important features of HBoV1 infection in polarized primary human airway epithelia (HAE). Apical HBoV1 infection of HAE at a low multiplicity of infection causes disruption of the tight junction barrier, loss of cilia, and epithelial cell hypertrophy, which are hallmarks of the airway epithelial damage caused by HBoV1 infection. HBoV1 also infects HAE from the basolateral surface productively, although less efficiently, and this also leads to the characteristic airway epithelial damage.
Evaluation of four CD22 antibodies as ricin a chain‐containing immunotoxins for the in vivo therapy of human B‐cell leukemias and lymphomas (1988)

Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigen, CD22, were prepared from 4 monoclonal antibodies (MAbs) or their Fab' fragments: RFB4, HD6, UV22-I and UV22-2. The ITs were tested for their ability to kill cells from the Burkitt lymphoma line, Daudi, the pre-B-cell leukemia line, NALM-6, and the myeloma cell line, ARH-77. Daudi expresses high levels of CD22, whereas NALM-6 and ARH-77 express low levels of CD22. The IgG-RFB4-A was highly toxic to all 3 cell lines; it killed 50% of the Daudi cells at a concentration of 1.2 x 10(-12) M and 50% of NALM-6 and ARH-77 cells at concentrations of 1.5 to 2.1 x 10(-11) M. IgG-RFB4-A was 10-30 times more toxic to Daudi cells than were the IgG-As constructed from the other 3 CD22 MAbs and 10 times more toxic than ricin itself. IT-As constructed from the Fab' fragments of the 4 CD22 antibodies were 2 to 5 times less toxic to Daudi cells than their IgG-A counterparts. Fab'-RFB4-A was twice as toxic to Daudi cells as ricin, whereas the other Fab'-As were about 7 times less toxic than ricin. Scatchard analyses of the binding of the radio-iodinated antibodies to Daudi cells showed that the intact RFB4 antibody bound 3-10 times more strongly than the other antibodies, whereas the Fab'-RFB4 bound 1.2 to 3.5 times more strongly than the Fab' fragments prepared from the other antibodies. Thus, the potent cytotoxic activity of the RFB4-As appears to derive, in part, from their superior binding affinity. Prior studies have shown that UV22-I and HD6 cross-react with certain normal human tissues lacking cells of B-cell lineage, whereas UV22-2 and RFB4 are B-cell-specific. This fact, together with its superior potency as an IT-A, suggests that RFB4 is the antibody of choice for preparing Fab'-As or IgG-As for in vivo therapy of human B-cell leukemias and lymphomas.
Recombinant human interleukin 10 for induction of remission in Crohn's disease (2010)

Interleukin 10 does not appear to provide any benefit for the treatment of active Crohn's disease. This systematic review shows that interleukin 10 does not increase the number of remissions (complete or clinical), but increases the rate of withdrawal due to adverse events relative to placebo. The quality of the evidence regarding the efficacy of IL-10 is moderate and although further research may have an impact on point estimates of efficacy further randomized trials are unlikely to be undertaken.
Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B (1995)

Human immunodeficiency virus type 1 (HIV-1) vpr inhibits the replication of tumor cell lines and peripheral blood mononuclear cells. Here it is demonstrated that expression of vpr, either in the context of a provirus or from an independent genetic element, induces a discrete cell cycle arrest, with cells containing 4N DNA. Low cyclin B-associated kinase activity, as well as the status of p34cdc2 and cdc25C phosphorylation, indicates that the cascade of reactions which drives the cell into mitosis has not been initiated. The phosphatase inhibitor okadaic acid releases the block, suggesting that Vpr perturbs upstream regulatorsof the G2-M transition. These studies demonstrate that HIV-1 vpr has profound effects on the cellular factors which control entry into mitosis and indicate vpr's potential contribution to the cellular pathology associated with HIV-1 infection.
Tissue microarray‐based studies of patients with lymph node negative breast carcinoma show that met expression is associated with worse outcome but is not correlated with epidermal growth factor family receptors (2003)

The current results indicate that the cytoplasmic domain of Met shows a unique staining pattern and defines a set of patients unique from the set of patients defined by overexpression of HER-2, EGFR, or hormone receptors. Furthermore, this group of patients is associated tightly and independently with worse outcome.
GSK-3α Promotes Oncogenic KRAS Function in Pancreatic Cancer via TAK1–TAB Stabilization and Regulation of Noncanonical NF-κB (2013)

Mutations in KRAS drive the oncogenic phenotype in a variety of tumors of epithelial origin. The NF-κB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. Recently, TGF-β-activated kinase 1 (TAK1), an upstream regulator of IκB kinase (IKK), which controls canonical NF-κB signaling, was shown to be important for chemoresistance in pancreatic cancer and for regulating KRAS-mutant colorectal cancer cell growth and survival. Here, we show that mutant KRAS upregulates glycogen synthase kinase 3α (GSK-3α), leading to its interaction with TAK1 to stabilize the TAK1-TAB complex to promote IKK activity. In addition, GSK-3α is required for promoting critical noncanonical NF-κB signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3 suppresses growth of human pancreatic tumor explants, consistent with the loss of expression of oncogenic genes such as c-myc and TERT. These data identify GSK-3α as a key downstream effector of oncogenic KRAS via its ability to coordinately regulate distinct NF-κB signaling pathways.
CGRP receptor antagonists: a new choice for acute treatment of migraine? (2004)

The neuropeptide calcitonin gene-related peptide (CGRP) is believed to play a central role in the underlying pathology of migraine. Serum levels of CGRP, elevated during a migraine attack, return to normal as pain alleviates. Recently, a causative role for CGRP in migraine has been suggested. Based on these findings, it was proposed that blockade of postsynaptic CGRP receptors, and hence the physiological effects of CGRP, should effectively abort a migraine attack. This review will discuss the therapeutic potential of olcegepant, the first non-peptide CGRP receptor antagonist available for human studies, within the context of current neurovascular theories on migraine pathology.
Stabilization of Enzymes in Silk Films (2009)

Material systems are needed that promote stabilization of entrained molecules, such as enzymes or therapeutic proteins, without destroying their activity. We demonstrate that the unique structure of silk fibroin protein, when assembled into the solid state, establishes an environment that is conducive to the stabilization of entrained proteins. Enzymes (glucose oxidase, lipase, and horseradish peroxidase) entrapped in these films over 10 months retained significant activity, even when stored at 37 degrees C, and in the case of glucose oxidase did not lose any activity. Further, the mode of processing of the silk protein into the films could be correlated to the stability of the enzymes. The relationship between processing and stability offers a large suite of conditions within which to optimize such stabilization processes. Overall, the techniques reported here result in materials that stabilize enzymes to an extent, without the need for cryoprotectants, emulsifiers, covalent immobilization, or other treatments. Further, these systems are amenable to optical applications and characterization, environmental distribution without refrigeration, are ingestible, and offer potential use in vivo, because silk materials are biocompatible and FDA approved, degradable with proteases, and currently used in biomedical devices.
The use of RGD-engineered exosomes for enhanced targeting ability and synergistic therapy toward angiogenesis (2017)

Promoted therapeutic angiogenesis is a major objective in the area of regenerative medicine, and sufficient vascularization of artificial tissues or organs is one of the main difficulties for the realization of tissue engineering methods. The identification of new kinds of pro-angiogenic materials will greatly profit developments in regenerative medicine. The use of exosomes for this intention is a considerably new idea developed in recent years. However, several limitations need to be addressed before their use as clinical therapeutics, including the lack of efficient exosome enrichment and methods to endow exosomes with targeting ability. Herein, we pioneered biomimetic particles with topographic structures for exosome isolation. Using this system, nearly 80% of exosomes were isolated in 30 min. Through a donor cell-assisted membrane modification strategy, the isolated exosomes exhibited increased targeting to blood vessels due to the modified Arg-Gly-Asp (RGD) peptide on the exosome membrane, and simultaneously possessed a synergistic therapeutic angiogenesis effect and angiogenesis imaging attributed to metabolic labeling by click chemistry both in vitro and in vivo. The engineered exosomes represent a potential new therapeutic tool for angiogenesis therapy and imaging in a bio-friendly manner.
Design and simulation of opera lighting and projection effects (1991)

A major problem challenging opera designers is the inability to co-ordinate lighting, projection systems, and set designs in the preliminary planning phase. New computer graphics techniques, which provide the set and lighting designer the opportunity to evaluate, test, and control opera designs prior to the construction of full scale systems are presented. These techniques---light source input, simulation of directional lighting, modeling of scenic projection systems, and full three-dimensional simulation---show the potential for the use of computer graphics in theater design.The light source input component consists of a program for assigning light source attributes with a set of theater lighting icons. This module allows a designer to specify light source characteristics in a way familiar to the discipline and to make preliminary evaluations of the lighting conditions.An extended progressive radiosity method is introduced to simulate the directional lighting characteristics which are specified by the input program.A new projection approach is presented to simulate the optical effects of scenic projectors. In addition, a solution to the distortion problem produced by angular projections is described.The above components are integrated to produce full three-dimensional simulations of the global illumination effects in an opera scene.
Percutaneous Transluminal Coronary Angioplasty in 1985–1986 and 1977–1981 (1988)

In August 1985, the Percutaneous Transluminal Coronary Angioplasty Registry of the National Heart, Lung, and Blood Institute reopened at its previous sites to document changes in angioplasty strategy and outcome. The new registry entered 1802 consecutive patients who had not had a myocardial infarction in the 10 days before angioplasty. Patient selection, technical outcome, and short-term major complications were compared with those of the 1977 to 1981 registry cohort. The new-registry patients were older and had a significantly higher proportion of multivessel disease (53 vs. 25 percent, P less than 0.001), poor left ventricular function (19 vs. 8 percent, P less than 0.001), previous myocardial infarction (37 vs. 21 percent, P less than 0.001), and previous coronary bypass surgery (13 vs. 9 percent, P less than 0.01). The new-registry cohort also had more complex coronary lesions, and angioplasty attempts in these patients involved more multivessel procedures. Despite these differences, the in-hospital outcome in the new cohort was better. Angiographic success rates according to lesion increased from 67 to 88 percent (P less than 0.001), and overall success rates (measured as a reduction of at least 20 percent in all lesions attempted, without death, myocardial infarction, or coronary bypass surgery) increased from 61 to 78 percent (P less than 0.001). In-hospital mortality for the new cohort was 1 percent, and the nonfatal myocardial infarction rate was 4.3 percent. Both rates are similar to those for the old registry. The long-term efficacy of current angioplasty remains to be determined.
Treatment with monoclonal anti-CD3 antibody protects against lethal Sendai virus infection by induction of natural killer cells. (1990)

C57BL/6 mice are protected from a lethal pneumonia caused by Sendai virus when treated with low doses of mAb directed to the CD3 Ag. The protective mechanism is not due to an accelerated Sendai virus-specific Th cell, CTL, or antibody response but to a strong NK cell response via the in vivo induction of lymphokines. Antibodies directed against the NK1.1 and asialo GM1 marker totally reversed the protective effect of anti-CD3 treatment. In vivo treatment with rIL-2 also induced NK activity and induced antiviral protection. Treatment with anti-CD3 protects when given in a narrow time window (1 day before until 1 day after Sendai virus inoculation), indicating that NK activity is protective in the early phase of virus infection.
Seasonal Patterns of Photosystem 2 Photochemical Efficiency in Evergreen Sclerophylls and Drought Semi-Deciduous Shrubs under Mediterranean Field Conditions (1999)

Photochemical efficiency of photosystem 2 (PS2), assessed from in situ chlorophyll (Chl) fluorescence measurements, was seasonally monitored in five evergreen sclerophyll and five malacophyllous drought semi-deciduous species, co-occurring in the same Mediterranean field site. In evergreen sclerophylls, a considerable drop in the variable (Fv) to maximum (Fm) Chl fluorescence ratio coincided with the lowest winter temperatures, indicating low PS2 efficiency during this period. Summer drought caused a comparatively slight decrease in Fv/Fm and only in three of the five evergreen sclerophyll species tested. In drought semi-deciduous shrubs, the winter drop in Fv/Fm was much less conspicuous. During the summer, and in spite of the severe and prolonged desiccation of their malacophyllous leaves, Fv/Fm was maintained high and only in one species the PS2 efficiency was transiently suppressed, when the leaf relative water content became lower than 30 %. Thus evergreen sclerophylls are more prone to photoinhibition by low winter temperatures, while the sensitivity of drought semi-deciduals depends on the extent and duration of summer drought.
Universal Definition of Myocardial Infarction (2007)

Udgivelsesdato: 2007-Nov-27
Stable expression of mammalian beta 1,4-galactosyltransferase extends the N-glycosylation pathway in insect cells (1998)

An established lepidopteran insect cell line (Sf9) was cotransfected with expression plasmids encoding neomycin phosphotransferase and bovine beta 1,4-galactosyltransferase. Neomycin-resistant transformants were selected, assayed for beta 1,4-galactosyltransferase activity, and the transformant with the highest level of enzymatic activity was characterized. Southern blots indicated that this transformed Sf9 cell derivative contained multiple copies of the galactosyltransferase-encoding expression plasmid integrated at a single site in its genome. One-step growth curves showed that these cells supported normal levels of baculovirus replication. Baculovirus infection of the transformed cells stimulated beta 1,4-galactosyltransferase activity almost 5-fold by 12 h postinfection. This was followed by a gradual decline in activity, but the infected cells still had about as much activity as uninfected controls as late as 48 h after infection and they were able to produce a beta 1,4-galactosylated virion glycoprotein during infection. Infection of the transformed cells with a conventional recombinant baculovirus expression vector encoding human tissue plasminogen activator also resulted in the production of a galactosylated end-product. These results demonstrate that stable transformation can be used to add a functional mammalian glycosyltransferase to lepidopteran insect cells and extend their N-glycosylation pathway. Furthermore, stably-transformed insect cells can be used as modified hosts for conventional baculovirus expression vectors to produce foreign glycoproteins with "mammalianized" glycans which more closely resemble those produced by higher eucaryotes.
Automatic URL completion and prediction using fuzzy type-ahead search (2009)

Type-ahead search is a new information-access paradigm, in which systems can find answers to keyword queries "on-the-fly" as a user types in a query. It improves traditional autocomplete search by allowing query keywords to appear at different places in an answer. In this paper we study the problem of automatic URL completion and prediction using fuzzy type-ahead search. That is, we interactively find relevant URLs that contain words matching query keywords, even approximately, as the user types in a query. Supporting fuzzy search is very important when the user has limited knowledge about URLs. We describe the design and implementation of our method, and report the experimental results on Firefox.
L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis (2018)

The results of this review suggest a possible beneficial effect of L-ornithine L-aspartate on mortality, hepatic encephalopathy, and serious adverse events in comparisons with placebo or no-intervention, but, because the quality of the evidence is very low, we are very uncertain about these findings. There was very low quality evidence of a possible beneficial effect of L-ornithine L-aspartate on hepatic encephalopathy, when compared with probiotics, but no other benefits were demonstrated in comparison with other active agents. Additional access to data from completed, but unpublished trials, and new randomised placebo-controlled, double-blind clinical trials are needed.
The pdhR–aceEF–lpd operon of Escherichia coli expresses the pyruvate dehydrogenase complex (1994)

Summary Transcript mapping and studies with lacZ translational fusions have shown that the pdhR gene (formerly genA ) is the proximal gene of the pdhR–aceE–aceF–Ipd operon encoding the pyruvate dehydrogenase (PDH) complex of Escherichia coli. A pdhR–lpd read‐through transcript (7.4 kb) initiating at the pyruvate‐inducible pdh promoter, and a smaller lpd transcript (1.7 kb) initiating at the independent lpd promoter, were identified. Evidence showing that the pdhR gene product negatively regulates the synthesis of the PdhR protein and the PDH complex via the pdh promoter was obtained, with pyruvate (or a derivative) serving as the putative inducing coeffector. The partially purified PdhR protein was also found to specifically retard and protect DNA fragments containing the pdh promoter region. The pdh promoter was not strongly controlled by ArcA, FNR or CRP.
Numerical indices based on circulating tumor DNA for the evaluation of therapeutic response and disease progression in lung cancer patients (2016)

Monitoring of disease/therapeutic conditions is an important application of circulating tumor DNA (ctDNA). We devised numerical indices, based on ctDNA dynamics, for therapeutic response and disease progression. 52 lung cancer patients subjected to the EGFR-TKI treatment were prospectively collected, and ctDNA levels represented by the activating and T790M mutations were measured using deep sequencing. Typically, ctDNA levels decreased sharply upon initiation of EGFR-TKI, however this did not occur in progressive disease (PD) cases. All 3 PD cases at initiation of EGFR-TKI were separated from other 27 cases in a two-dimensional space generated by the ratio of the ctDNA levels before and after therapy initiation (mutation allele ratio in therapy, MART) and the average ctDNA level. For responses to various agents after disease progression, PD/stable disease cases were separated from partial response cases using MART (accuracy, 94.7%; 95% CI, 73.5-100). For disease progression, the initiation of ctDNA elevation (initial positive point) was compared with the onset of objective disease progression. In 11 out of 28 eligible patients, both occurred within ±100 day range, suggesting a detection of the same change in disease condition. Our numerical indices have potential applicability in clinical practice, pending confirmation with designed prospective studies.
High‐dose interleukin‐2 for the treatment of metastatic renal cell carcinoma (2008)

HD IL-2 can induce complete tumor regression in a small number of patients, and many patients have experienced extended disease-free intervals. Given its relative safety, HD IL-2 should still be considered a first-line therapy in patients with metastatic RCC who have an overall good performance status.