gebhart/patrepeval huggingface dataset:
Vesicular Anthracycline Accumulation in Doxorubicin-Selected U-937 Cells: Participation of Lysosomes (1997)

The U-A10 cell line, a doxorubicin-selected variant of human U-937 myeloid leukemia cells, exhibits a redistribution of anthracyclines into a expanded vesicular compartment. The acidic nature of this compartment was confirmed by vital staining with a pH sensitive dye, LysoSensor yellow/blue DND-160. Identification of the vesicular compartment was performed by immunofluorescence analysis. Staining for the LAMP-1 and LAMP-2 antigens showed that the vesicles are enlarged lysosomes that are eccentrically placed near the nucleus of U-A10 cells. By contrast, the expression of the multidrug resistance-associated protein and the P-glycoprotein was observed predominately on the plasma membrane of the drug-resistant cells. The accumulation of daunorubicin into cellular compartments was quantified using radiolabeled drug. Exposing cells to 3[H]-daunorubicin and then isolating intact nuclei showed that nuclei from U-A10 cells accumulated twofold to threefold less anthracycline than nuclei from U-937 cells. However, when nuclei were isolated first and then exposed to 3[H]-daunorubicin, little difference in net nuclear drug accumulation was detected. Cytoplasts prepared from U-A10 and U-937 cells were exposed to 3[H]-daunorubicin to measure cytoplasmic drug accumulation. At external daunorubicin concentrations of 100 ng/mL or higher, cytoplasts from U-A10 cells accumulated significantly more daunorubicin than cytoplasts from U-937 cells. Moreover, studies with the lysosomotropic agent chloroquine showed that U-A10 cells accumulated twofold more chloroquine and showed twofold enhanced sensitivity to this agent as compared with parental U-937 cells. Fluorescence microscopy showed that chloroquine affects vesicular anthracycline sequestration in U-A10 cells with an associated increase in daunorubicin nuclear fluorescence. Although chloroquine did not alter anthracycline cytotoxicity in parental cells, it restored daunorubicin and doxorubicin sensitivity to U-A10 cells. Taken together, these studies demonstrate that U-A10 cells exhibit a redistribution of the lysosomal compartment. The trapping of drug into an expanded acidic vesicular compartment results in decreased nuclear drug accumulation and decreased cytotoxicity. Lysosomotropic agents, such as chloroquine, warrant further study as modulators of this acquired drug-resistance phenotype.
A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (2014)

Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths. (Funded by InterMune; ASCEND ClinicalTrials.gov number, NCT01366209.).
Psychiatric morbidity in psoriasis: A review (2004)

Psoriasis is a common condition, affecting 1.5-2% of the population of industrialized countries. It is important for clinicians to be aware that psoriasis can have a substantial emotional impact on an individual, which is not necessarily related to the extent of skin disease. This review examines current literature addressing the psychological and emotional aspects of psoriasis. A literature search of the MEDLINE (1966-2002) and PsycINFO (1984-2002) computer databases and bibliographies was carried out. Papers selected for the review included English language reviews and all original research relevant to the topic, in the form of randomized controlled trials, cohort studies, case-control studies, cross-over and uncontrolled clinical trials, patient surveys, quality-of-life studies, case series and case reports. Despite significant shortcomings, the available prevalence studies showed uniformly high rates of psychopathology among psoriasis sufferers. The few intervention studies available are summarized and critically discussed. Psoriasis is associated with a variety of psychological problems, including poor self esteem, sexual dysfunction, anxiety, depression and suicidal ideation. The clinical severity of the psoriasis may not reflect the degree of emotional impact of the disease. A number of psychological interventions have shown promise in recent trials. It is important that clinicians consider the psychosocial aspects of this illness.
Febuxostat: a new treatment for hyperuricaemia in gout (2009)

Febuxostat is a new non-purine xanthine oxidase inhibitor that is more potent than allopurinol 300 mg daily. In two Phase III trials, significantly more febuxostat-treated gout patients met the primary endpoint [serum urate (sUA) <6 mg/dl (<360 mumol/l) at the last three visits] (48 and 53% with 80 mg; 65 and 62% with 120 mg), compared with those receiving allopurinol 300 mg (22 and 21%; P < 0.001 in both studies). Febuxostat was more effective than allopurinol in the subset with impaired renal function; no dose adjustment is required in mild-to-moderate renal impairment. Long-term extension studies confirmed the efficacy and tolerability of febuxostat. In patients who achieved the sUA target of 6 mg/dl (360 mumol/l), the incidence of gout flares fell steadily and tophi resolved in many patients. The incidence of adverse events such as dizziness, diarrhoea, headache and nausea with febuxostat was similar to allopurinol. The incidence of cardiovascular side-effects (Antiplatelet Trialists Collaboration events) was numerically higher with febuxostat than with allopurinol, but this was not statistically significant. Co-administration of febuxostat with AZA or 6-mercaptopurine is not recommended. Prophylaxis (colchicine and/or NSAIDs) against acute attacks should be used for at least the first 6 months, since early mobilization flares were observed in the clinical trials. In conclusion, febuxostat is more effective than allopurinol 300 mg daily in reducing sUA levels <6 mg/dl (360 mumol/l), the target recommended by EULAR, and offers a new option for the long-term treatment of gout.
Personal communications by satellite (1992)

Abstract Personal communications (PC) refers to two‐way voice (and possibly data) communications to a small hand‐held unit, capable of being carried by a person and used in various locations. PC via satellite refers to the case where this hand‐held unit communicates directly with a satellite to provide the duplex voice (or data) service. Both geosynchronous earth orbit (GEO) and low earth orbit (LEO) satellites have been considered to provide this service. GEO and LEO satellite systems must compete with existing mobile cellular radio systems both in meeting performance requirements and service costs, if they are to be a significant supplier of PC services. GEO and LEO systems each have unique advantages and disadvantages when used to provide a PC service. While these general characteristics are identified in Section 1 of the paper, a more quantitative comparison is needed. This quantitative comparison is made by comparing a GEO PC satellite system, operating at EHF ( K a ‐band) frequencies with a LEO system operating at UHF ( L ‐band) frequencies, including service costs for both systems. The two systems used in the comparison are examples of realistic GEO and LEO system designs for PC service, and although it is not exhaustive, the comparison points out some of the key differences between GEO and LEO systems that affect service performance and cost.
The Histamine receptor (1991)

Pharmacochemistry of H1-and H2-Receptors Pharmacochemistry of H3-Receptors Reversible Labelling of H1-, H2-and H3-Receptors Biochemical Properties of Histamine Receptors The H1-Receptor and Inositol Phospholipid Hydrolysis Histamine Receptors and Cyclic Nucleotides The H3-Receptor and Control of Histamine Release Electrophysiology of Histamine-Receptors Autoradiographic Visualization of the Three Histamine Receptor Subtypes in the Brain Histamine Receptors in the Digestive System Ligand Binding and Functional Evidence for the Presence of Histamine Type-1 and Type-2 Receptors of Human T Lymphocytes Histamine Receptors in the Respiratory Tract Histamine Receptors in the Central Nervous System.
Chromosomal Signatures of a Subset of High-Grade Premalignant Cervical Lesions Closely Resemble Invasive Carcinomas (2009)

Cervical cancer develops from precancerous high-grade cervical intraepithelial neoplasia (CIN) harboring a transforming infection with high-risk human papillomavirus, which is characterized by p16(INK4a) overexpression. Once such a lesion has developed, progression toward an invasive squamous cell carcinoma (SCC) may take one or more decades, underlining the heterogeneity of these lesions in terms of duration of existence and progression risk. We performed array-based comparative genomic hybridization (array CGH) on 46 p16(INK4a) immunopositive CIN2/3 lesions to determine whether this heterogeneity is reflected in their chromosomal profiles. Chromosomal profiles of CIN2/3 lesions were related to those of invasive cervical SCC and promoter methylation of CADM1, a tumor suppressor gene known to be functionally involved in the tumorigenic phenotype of cervical cancer cells. Frequent alterations found in CIN2/3 lesions included gains located at chromosome 1, 3, 7, and 20 and losses located at 4, 11, 16, 17, and 19. Unsupervised hierarchical clustering identified two subsets of CIN2/3 lesions, chromosomal profiles of one of which closely resembled invasive SCCs. Gains of 1, 3q, and 20 were characteristic for CIN2/3 lesions with chromosomal signatures resembling carcinomas. In addition, dense promoter methylation of the CADM1 gene was significantly more frequent in these CIN2/3 lesions (P = 0.004). No chromosomal alterations were detected in six CIN1 lesions, five of which were completely p16(INK4a) immunonegative. These findings suggest that biomarkers associated with gains at chromosomes 1, 3q, and 20 are potential hallmarks of advanced p16(INK4a)-positive CIN2/3 lesions with a high short-term risk of progression.
Sequence regions of Bacilli metalloproteinases that can affect enzyme thermostability. (1991)

By a computer analysis of the five Bacilli metalloprotease sequences it was found that mesophilic Bacillus amyloliquefaciens and B. subtilis proteases had lost two Ca(2+)-binding sites due to the substitutions Asp----Ser 57, Asp----Thr 59, Asp----Pro 200, in comparison with the thermostable B. thermoproteolyticus thermolysin and B. stearothermophilus protease, which conserved three Ca(2+)-binding sites, and B. cereus protease with the intermediate thermostability, which had presumably lost only one site (Ile----Lys 197 substitution). The multiple substitutions within the sequence regions 91-101, 150-154, and 275-280 of the mesophilic enzymes also corresponded with the decrease in the proteinase thermostability value. On the known X-ray structure of thermolysin these sequence regions are spatially drawn together, being located near the central alpha-helix opposite the active site hole and providing the contact of the N- and C-terminal domains. It may be concluded that to increase the thermostability of the mesophilic Bacilli proteinases it is necessary to substitute the sequence regions 91-101, 150-154, 275-280 for the thermolysin ones and restore the Ca(2+)-binding sites of the enzymes.
Lanepitant, an NK-1 Antagonist, in Migraine Prevention (2001)

Lanepitant, a potent non-peptide neurokinin-1 receptor antagonist, inhibits neurogenic dural inflammation, and may have a role in migraine therapy. This study evaluated the effect of lanepitant taken daily for migraine prevention. Patients with migraine headaches with and without aura by International Headache Society classification criteria were enrolled in a 12-week double-blind, parallel design study comparing the effect of 200 mg qd lanepitant (n = 42) and placebo (n = 42) on reduction of migraine frequency. The primary outcome measure was response rate, i.e. the proportion of patients with a 50% reduction in days of headache. Of the 84 patients enrolled, 90.5% were female. The endpoint response rate for lanepitant-treated patients (41.0%) was not statistically significantly (P = 0.065) greater than that for placebo-treated patients (22.0%). No efficacy variables differed significantly between treatments, except for response rates at month 3 (P = 0.045). Higher plasma concentrations were no more effective than lower concentrations. In this study lanepitant was not effective in preventing migraine, but was well tolerated. These results do not support a role for NK-1 antagonism in migraine prevention.
Coexpression of cyclooxygenase-2 and matrix metalloproteinases in human aortic atherosclerotic lesions (2000)

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study aimed to investigate atherosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n = 4) and dissections (n = 3) by using antibodies to COX-2, MMP-9, MT1-MMP, and TIMP-2. Control tissues were obtained from traumatically dissected aortas (n = 2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expression of COX-2, MMP-9, and MT1-MMP in all aortic layers. Immunoreactivity for COX-2 was predominantly noted in macrophages and smooth muscle cells (SMCs) of the intima including atherosclerotic plaque itself and the medial layer of the plaque base, as well as in SMCs and endothelial lining of the vasa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was found in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrates that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophages and SMCs in atherosclerotic lesions, but also in endothelial lining of the vasa vasorum of human aortas. Thus, vascular inflammatory reactions may influence extracellular matrix remodeling by coactivation of MMPs in the development of atherosclerosis and, in turn, the progression of disease.
Cloning and Expression of a cDNA Encoding an Insoluble Matrix Protein in the Gastroliths of a Crayfish, Procambarus clarkii (1999)

In the crayfish Procambarus clarkii, the gastroliths are formed as a paired structure in the stomach during the premolt period, and contain calcium carbonate and a small amount of an organic matrix. In this investigation, a cDNA encoding an insoluble matrix protein was isolated from P. clarkii. The open reading frame encoded 505 amino acid residues including two unique repeated sequences. The N-terminal half of the amino acid sequence, which included 10-amino-acid repeats, exhibited a high degree of similarity to that of involucrin, a protein synthesized in human keratinocytes. Northern blot analysis revealed that mRNA encoding the matrix protein is specifically expressed in the gastrolith discs during the premolt period in which the gastroliths formed. In the gastrolith discs, levels of expression of this mRNA correlated increases in weights of the gastroliths concomitant with their formation. Organ culture of the gastrolith discs suggested that expression of mRNA in the discs is induced by molting hormone, 20-hydroxyecdysone. These results reinforced the relationship between the matrix protein and formation of the gastroliths. Functional analysis showed that the protein inhibits calcium carbonate crystallization in a solution system, suggesting that the protein plays a role in the calcification of the gastroliths.
FimC is a periplasmic PapD-like chaperone that directs assembly of type 1 pili in bacteria. (1993)

Biogenesis of the type 1 pilus fiber in Escherichia coli requires the product of the fimC locus. We have demonstrated that FimC is a member of the periplasmic chaperone family. The deduced primary sequence of FimC shows a high degree of homology to PapD and fits well with the derived consensus sequence for periplasmic chaperones, predicting that it has an immunoglobulin-like topology. The chaperone activity of FimC was demonstrated by purifying a complex that FimC forms with the FimH adhesion. A fimC1 null allele could be complemented by the prototype member of the chaperone superfamily, PapD, resulting in the production of adhesive type 1 pili. The general mechanism of action of members of the chaperone superfamily was demonstrated by showing that the ability of PapD to assemble both P and type 1 pili was dependent on an invariant arginine residue (Arg-8), which forms part of a conserved subunit binding site in the cleft of PapD. We suggest that the conserved cleft is a subunit binding feature of all members of this protein family. These studies point out the general strategies used by Gram-negative bacteria to assemble adhesins into pilus fibers, allowing them to promote attachment to eukaryotic receptors.
Morphine withdrawal increases metabotropic glutamate 2/3 receptors expression in nucleus accumbens (2008)

We examined the effects of chronic morphine treatment and withdrawal on the expression of metabotropic glutamate (mGlu)1, mGlu5, and mGlu2/3 receptors in the nucleus accumbens and caudate putamen. Rats received a 14-day morphine treatment (escalating doses from 10 to 140 mg/kg). Receptor density was evaluated after chronic treatment and after 1, 3, and 14 days of withdrawal. mGlu1 and mGlu5 expression in the nucleus accumbens and in the caudate putamen was not affected by any of the experimental manipulations. In contrast, mGlu2/3 receptors in the nucleus accumbens, but not in the caudate putamen, increased at day 1, 3, and 14 of withdrawal. We suggest that an increased expression of mGlu2/3 receptors in the nucleus accumbens might contribute to the symptoms of morphine withdrawal.
An Explicit Rate Control Framework for Lossless Ethernet Operation (2008)

In this paper, an explicit rate control framework for Ethernet applications, especially data centers, is described. The framework guarantees zero packet drops at the congested switch and fast convergence to fair and stable state. In order to manage the congestion, design choices on 2-point and 3- point structures, the reactive and proactive signaling, explicit and implicit rate controls are compared. Then the core component of the framework, queue control, is carefully studied. Furthermore, we show that this framework can seamlessly cooperate with IEEE 802.3x PAUSE mechanism to recover from severe congestion scenarios. Numerical results are provided to support the claims.
Hemopoietic stem cell transplantation using mouse bone marrow and spleen cells fractionated by lectins. (1978)

Mouse bone marrow and spleen cells were fractionated with the aid of soybean agglutinin and peanut agglutinin. A test for spleen colony-forming units in the isolated fractions showed that the hemopoietic stem cells are agglutinated by both of these lectins. The capacity of the agglutinated fractions to reconstitute lethally irradiated allogeneic mice was investigated. A sequential fractionation of splenocytes from SWR donors by soybean agglutinin and peanut agglutinin, or a single fractionation by soybean agglutinin of splenocytes from BALB/c donors, afforded a cell fraction that successfully reconstituted lethally irradiated (BALB/c X C57BL/6)F1 mice, without complications due to graft-versus-host reaction.
An Arabidopsis Mutant Defective in the Plastid General Protein Import Apparatus (1998)

Elaborate mechanisms have evolved for the translocation of nucleus-encoded proteins across the plastid envelope membrane. Although putative components of the import apparatus have been identified biochemically, their role in import remains to be proven in vivo. An Arabidopsis mutant lacking a new component of the import machinery [translocon at the outer envelope membrane of chloroplasts (Toc33), a 33-kilodalton protein] has been isolated. The functional similarity of Toc33 to another translocon component (Toc34) implies that multiple different translocon complexes are present in plastids. Processes that are mediated by Toc33 operate during the early stages of plastid and leaf development. The data demonstrate the in vivo role of a translocon component in plastid protein import.
Intradermal administration of bivalent and monovalent influenza vaccines. (1977)

Intradermal (ID) administration of 0.1 ml of a bivalent influenza vaccine containing 40 CCA units each of influenza A/New Jersey (Hswine 1N1) and A/Victoria (H3N2) virus antigens and of a monovalent vaccine containing 100 CCA units of influenza B/Hong Kong virus to 70 adult volunteers produced no serious reactions and only 7% bothersome side effects. Excluding persons with high (1:64 or greater) initial antibody titers, then 90% and 85% of persons had fourfold or greater rises in HAI antibodies to A/New Jersey and B/Hong Kong antigens, whereas 53% had rises to A/Victoria. The authors feel the ID route deserves further consideration for giving killed influenza vaccines to adults. However, an influenza virus type that was prevalent for many years may fail to give sufficient rise in HAI to consider the patient protected.
Enhanced detection of cell paths in spatiotemporal plots for noninvasive microscopy of the human retina (2010)

Spatiotemporal (ST) plots have been used for studying cell motion in the microcirculation. However, ST plots are typically applied to invasive imaging methods. Noninvasive video microscopy of the human retinal capillaries can be performed using an Adaptive Optics Scanning Laser Ophthalmoscope, but direct implementation of ST plots is difficult due to low contrast and high noise. We introduce motion contrast enhancement to enhance detection of cell paths, and enable ST plot analysis. Using features generated by the motion contrast enhancement, a method for automatic extraction of cell paths was developed. Our results show that motion contrast is an important precursor step to ST plot analysis for videos with low signal to noise ratios.
Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells (2011)

Engineered biological systems that integrate multi-input sensing, sophisticated information processing, and precisely regulated actuation in living cells could be useful in a variety of applications. For example, anticancer therapies could be engineered to detect and respond to complex cellular conditions in individual cells with high specificity. Here, we show a scalable transcriptional/posttranscriptional synthetic regulatory circuit--a cell-type "classifier"--that senses expression levels of a customizable set of endogenous microRNAs and triggers a cellular response only if the expression levels match a predetermined profile of interest. We demonstrate that a HeLa cancer cell classifier selectively identifies HeLa cells and triggers apoptosis without affecting non-HeLa cell types. This approach also provides a general platform for programmed responses to other complex cell states.
Fractal Surface Finish (1988)

Surface finish measurements are usually fitted to models of the finish correlation function which are parametrized in terms of root-mean-square roughnesses, &sigma;, and correlation lengths, <i>l</i>. Highly finished optical surfaces, however, are frequently better described by fractal models, which involve inverse power-law spectra and are parametrized by spectral strengths, Kn, and spectral indices, n. Analyzing measurements of fractal surfaces in terms of &sigma; and <i>l</i> gives results which are not intrinsic surface parameters but which depend on the bandwidth parameters of the measurement process used. This paper derives expressions for these pseudo-parameters and discusses the errors involved in using them for the characterization and specification of surface finish.