gebhart/patrepeval huggingface dataset:
Membrane-membrane interactions associated with rapid transfer of liposomal bilirubin to microsomal UDP-glucuronyltransferase. Relevance for hepatocellular transport and biotransformation of hydrophobic substrates (1987)

Bilirubin may be transported within intracellular membranes of the hepatocyte and may undergo membrane-membrane transfer to gain access to the conjugating enzyme UDP-glucuronyltransferase in the endoplasmic reticulum. We have demonstrated previously that the lipid composition of liposomal membranes incorporating bilirubin substrate influences the rate of transfer and glucuronidation of bilirubin by hepatic microsomes. To examine the mechanism(s) of substrate transfer, we incorporated radiolabelled bilirubin into small unilamellar model membranes of egg phosphatidylcholine or natural phospholipids in the proportions present in native hepatic microsomes. The rate at which bilirubin was transferred to rat liver microsomes and glucuronidated was then examined in the presence of various endogenous compounds that promote membrane fusion. For bilirubin substrate in membranes of egg phosphatidylcholine, the addition of Ca2+ (2 mM) increased the microsomal glucuronidation rate, whereas retinol enhanced microsomal conjugation rates for bilirubin in membranes of both lipid compositions. When the transfer of [3H]bilirubin from dual-labelled liposomes to microsomes was enhanced by Ca2+ or retinol, there was no associated increase in [14C]phospholipid transfer. Thus it appears likely that bilirubin is transferred to the endoplasmic reticulum by rapid cytosolic diffusion or membrane-membrane collisions, rather than by membrane fusion; this process may be modulated by changes in the lipid microenvironment of the substrate or the effective intracellular concentrations of Ca2+ or retinol. The observation that polymyxin B induced concomitant membrane-membrane transfer of [3H]bilirubin and [14C]phospholipid suggests that under certain circumstances membrane fusion or aggregation may promote the movement of lipophilic substrates in hepatocytes.
HSV Recombinant Vectors for Gene Therapy (2010)

The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), has allowed the development of potential replication-competent and replication-defective vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial. Replication-competent (oncolytic) vectors are becoming a suitable and powerful tool to eradicate brain tumours due to their ability to replicate and spread only within the tumour mass, and have reached phase II/III clinical trials in some cases. The progress in understanding the host immune response induced by the vector is also improving the use of HSV as a vaccine vector against both HSV infection and other pathogens. This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges.
원저 : Helicobacter pylori 감염 진단에서 혈청학적 검사의 타당성 (1994)

To evaluate the efficacy of serologic test in diagnosis of Helicobacter pylori infection, ELISA was used to detect IgG antibody against partially purified H. pylori outer membrane antigen (Bio-RAD GAP test IgG). Endoscopic gastric antral biopsy specimens were also obtained for microscopic examination of the bacteria and rapid urease test(CLO test). Eighty one patients (47 nonulcer dyspepsia patients, 11 benign gastric ulcer patients and 23 duodenal ulcer pa- tients) were enrolled in this study. Detection of H. pylori by microscopy was considered as true positive for H. pylori infection. Absence of H. pylori by microscopy and positive CLO test was considereed as equivocal and these cases were excluded in the analysis of the data. H. pylori infections were detected in 58(77%) of 81 patients, 30(64%) of 47 nonulcer dyspepsia pa- tients, 9(82%) of 11 benign gastric lucer patients and 19(83%) of 23 duodenal ulcer pa- tients). Nineteen of 81 were negative and 4 of 81 were equivocal in H. pylori infection. The sensitivity of the serologic test was 72% and the specificity was 53%. In conclusion, the sensi- tivity and specificity of the serologic test for diagnosis of H. pylori infection is very low, they must be improved to be used clinically. (Korean J Gastroenterol 1994; 26: 631 636)
The future of antiretroviral therapy: challenges and needs (2010)

The introduction of combination antiretroviral therapy (cART) has substantially modified the natural history of HIV infection. At the beginning of the cART era the objective was focused on HIV-1-associated mortality and morbidity, but as this objective was accomplished other issues emerged, including toxicity, resistance and compliance with treatment. Moreover, the participation of other disease mechanisms, such as proinflammatory activity, in the so-called non-AIDS events is becoming increasingly important. To overcome these issues, therapeutic options have dramatically expanded, which has made the management of HIV-1-infected patients increasingly complex. The intense changes seen raise the question of what will be the future of HIV infection and its treatment. A projection into the future may help to reflect on current limitations, needs and research priorities, to optimize patient care. To debate on this topic a group of 38 experts has initiated The HIV 2020 Project, with the aim of reflecting on the future of HIV infection and identifying the needs that should be the attention of research in different areas. This document summarizes the group's conclusions on the future of antiretroviral treatment, presented as 20 relevant questions. Each question includes the current status of the topic and our vision for the future.
A NON-ACTIVATING “HUMANIZED” ANTI-CD3 MONOCLONAL ANTIBODY RETAINS IMMUNOSUPPRESSIVE PROPERTIES IN VIVO (1994)

OKT3, a mouse anti-human CD3 mAb, is a potent immunosuppressive agent used in clinical transplantation to prevent or treat allograft rejection. Associated with this therapy is the systemic release of several cytokines that result in a series of adverse side effects. This release of cytokines is dependent on the cross-linking mediated by OKT3 between T cells and the Fc gamma R-bearing cells. To generate an anti-human CD3 mAb with reduced activating properties as compared with OKT3, we have transferred the complementary determining regions of OKT3 onto human IgG frameworks and then performed point mutations that reduce the affinity of the "humanized" anti-CD3 mAbs for Fc gamma Rs. Initial, in vitro, studies showed that whereas OKT3 and the parental humanized anti-CD3 mAbs activated T cells similarly, a humanized Fc variant failed to do so. Both the Fc variant and the activating anti-CD3 mAbs induced comparable modulation of the TCR and suppression of cytolytic T cell activity, in vitro. In the current study, we exploited an experimental model in which human splenocytes from cadaveric organ donors were inoculated into severe combined immunodeficient mice (hu-SPL-SCID mice) to test the activating and immunosuppressive properties of these anti-human CD3 mAbs in vivo. Unlike injection of OKT3 or of the parental humanized mAb, administration of the Fc variant did not result in T cell activation in vivo, as evidenced by the lack of induction of surface markers of activation, and of systemic human cytokines, including IL-2. Importantly, similar prolongation of human allograft survival was achieved with all anti-CD3 mAbs, indicating that the nonactivating anti-CD3 mAbs retained significant immunosuppressive properties in vivo. Thus, the use of an Fc variant in clinical transplantation should result in fewer side effects than observed with OKT3, while maintaining its clinical efficacy.
Differential Detection of Genetic Loci Underlying Stem and Root Lignin Content in Populus (2010)

In this study, we established a comprehensive genetic map with a large number of progeny from a three-generation hybrid Populus intercross, and phenotyped the lignin content, S/G ratio and 28 cell wall subcomponents both in stems and roots for the mapping individuals. Phenotypic analysis revealed that lignin content and syringyl-to-guaiacyl (S/G) ratio using pyrolysis molecular beam mass spectroscopy (pyMBMS) varied among mapping individuals. Phenotypic analysis revealed that stem lignin content is significantly higher than that in root and the quantified traits can be classified into four distinct groups, with strong correlations observed among components within organs. Altogether, 179 coordinating QTLs were detected, and they were co-localized into 49 genetic loci, 27 of which appear to be pleiotropic. Many of the detected genetic loci were detected differentially in stem and root. This is the first report of separate genetic loci controlling cell wall phenotypes above and below ground. These results suggest that it may be possible to modify lignin content and composition via breed and/or engineer as a means of simultaneously improving Populus for cellulosic ethanol production and carbon sequestration.
Expression profile of transcripts in Alzheimer's disease tangle‐bearing CA1 neurons (2000)

The pathogenesis of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) is poorly understood, but changes in the expression of specific messenger RNAs (mRNAs) may reflect mechanisms underlying the formation of NFTs and their consequences in affected neurons. For these reasons, we compared the relative abundance of multiple mRNAs in tangle-bearing versus normal CA1 neurons aspirated from sections of AD and control brains. Amplified antisense RNA expression profiling was performed on individual isolated neurons for analysis of greater than 18,000 expressed sequence tagged complementary DNAs (cDNAs) with cDNA microarrays, and further quantitative analyses were performed by reverse Northern blot analysis on 120 selected mRNAs on custom cDNA arrays. Relative to normal CA1 neurons, those harboring NFTs in AD brains showed significant reductions in several classes of mRNAs that are known to encode proteins implicated in AD neuropathology, including phosphatases/kinases, cytoskeletal proteins, synaptic proteins, glutamate receptors, and dopamine receptors. Because cathepsin D mRNA was upregulated in NFT-bearing CA1 neurons in AD brains, we performed immunohistochemical studies that demonstrated abundant cathepsin D immunoreactivity in the same population of tangle-bearing CA1 neurons. In addition, levels of mRNAs encoding proteins not previously implicated in AD were reduced in CA1 tangle-bearing neurons, suggesting that these proteins (eg, activity-regulated cytoskeleton-associated protein, focal adhesion kinase, glutaredoxin, utrophin) may be novel mediators of NFT formation or degeneration in affected neurons. Thus, the profile of mRNAs differentially expressed by tangle-bearing CA1 neurons may represent a “molecular fingerprint” of these neurons, and we speculate that mRNA expression profiles of diseased neurons in AD may suggest new directions for AD research or identify novel targets for developing more effective AD therapies. Ann Neurol 2000;48:77–87
Phase recognition during surgical procedures using embedded and body-worn sensors (2011)

In Ubiquitous Computing (Ubicomp) research, substantial work has been directed towards sensor-based detection and recognition of human activity. This research has, however, mainly been focused on activities of daily living of a single person. This paper presents a sensor platform and a machine learning approach to sense and detect phases of a surgical operation. Automatic detection of the progress of work inside an operating room has several important applications, including coordination, patient safety, and context-aware information retrieval. We verify the platform during a surgical simulation. Recognition of the main phases of an operation was done with a high degree of accuracy. Through further analysis, we were able to reveal which sensors provide the most significant input. This can be used in subsequent design of systems for use during real surgeries.
Activation of Eosinophils with Cytokines Produced by Lung Mast Cells (1997)

Here we show that the supernatant from activated lung mast cells induced the release of eosinophil cationic protein (ECP) from eosinophils. Lung mast cells were purified using affinity magnetic selection with monoclonal antibody (mAb) YB5.B8 to achieve a final mast cell purity of 93-99%. Eosinophils were purified by immunomagnetic negative selection (>98.0% pure). The supernatant was obtained from lung mast cells activated for 24 h with 1 microg/ml anti-IgE and 50 ng/ml stem cell factor (SCF). Human eosinophils were incubated with various concentrations of the supernatants for 4 h and ECP released was measured by RIA. Using 4 different donors' supernatant from mast cells, each donor's supernatant caused a dose-dependent release of ECP from eosinophils. The dilutant of 1:2 (v/v) of the supernatant induced 657.5 +/- 55.6 ng/10(6) eosinophils of ECP which is statistically significant (p = 0.008, n = 4) compared with the culture medium alone. Anti-interleukin (IL-5 neutralizing mAb, 10 microg/ml, and anti-tumor necrosis factor-alpha (TNF alpha) neutralizing mAb, 10 microg/ml, significantly inhibited the supernatant-induced ECP release in 79.3 +/- 9.4 and 68.2 +/- 14.1% (mean +/- SEM, n = 6, p < 0.005), respectively. Anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) neutralizing mAb, 50 microg/ml, caused 68.0 +/- 6.1% of inhibition (p = 0.002). The isotype negative control had no measurable inhibitory or stimulatory effect for the stimuli. We confirmed that mast cells produce IL-5, GM-CSF and TNF alpha in response to IgE-dependent stimulation by using RT-PCR, in situ hybridization, ELISA and immunocytochemistry. A million of lung mast cells generated 41.4 pg (7.0-273.6) (median with range) of TNF alpha, 252.6 pg (158.7-3,652) of GM-CSF and 735 pg (< 10-2,750) of IL-5 24 h after activation with SCF and anti-IgE. These findings indicate that the human mast cells may contribute to the chronicity of tissue inflammation.
IMAGE MOTION AND ITS COMPENSATION FOR THE OBLIQUE FRAME CAMERA (1965)

There are three main causes of motion blur in aerial photography: the aircraft velocity, rotations of the aircraft, and vibration. Each of these produces a movement of the image which results in a significant resolution degradation, if not compensated. The image motion from the first two causes is examined in this three part series. The first part consists of an analysis of the image motion arising from the aircraft velocity for the oblique frame camera, with or without image motion compensation. The optimum type of shutter and IMC velocity for the tilted camera are analyzed, and the photographic distortions arising from the use of a focal-plane shutter are examined. Conversion equations from pitch, roll and yaw to tilt, swing and azimuth are included. In the second part, equations for the image-motion from aircraft rotations are derived for the tilted frame camera, from which the resolution loss can be computed. The image-motion equations for the panoramic camera from the aircraft velocity and rotations are derived in part 3. /AUTHOR/
Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin (2000)

Cisplatin is an anticancer drug that has enjoyed remarkable success against testicular tumors, but dose limiting side-effects have limited its application against a broader range of cancers. Previous studies have shown that high-mobility group (HMG) domain proteins such as HMG1 sensitize cells to cisplatin by shielding its major DNA adducts from nucleotide excision repair. Estrogen treatment increases HMG1 mRNA levels in breast cancer MCF-7 cells. Herein, we describe that treatment of human cancer cells having steroid hormone receptors with the appropriate hormone, estrogen and/or progesterone, significantly increases the potency of cisplatin and its analogue carboplatin by causing the overexpression of HMG1. These findings suggest that the proper combination of these drugs, which are already approved by the Food and Drug Administration, could have potential benefit in treating tumors such as ovarian or breast that carry the hormone receptors.
Strategy-Level Separations in Organic Synthesis: From Planning to Practice (1998)

A dirty word in synthesis: separation! The normally unavoidable separation at the end of each reaction finds no friends among synthetic chemists and is often regarded as a technical procedure. However, the need to quickly and cheaply produce pure products is driving the development of new separation and purification techniques. Astonishingly, the modern concepts and techniques for coupling synthesis and separation are rooted in workup procedures that are as old as the art of synthesis itself.
Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A (2014)

Tumor suppressor p53 plays an important role in mediating growth inhibition upon telomere dysfunction. Here, we show that loss of the p53 target gene cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21(WAF1/CIP1)) increases apoptosis induction following telomerase inhibition in a variety of cancer cell lines and mouse xenografts. This effect is highly specific to p21, as loss of other checkpoint proteins and CDK inhibitors did not affect apoptosis. In telomerase, inhibited cell loss of p21 leads to E2F1- and p53-mediated transcriptional activation of p53-upregulated modulator of apoptosis, resulting in increased apoptosis. Combined genetic or pharmacological inhibition of telomerase and p21 synergistically suppresses tumor growth. Furthermore, we demonstrate that simultaneous inhibition of telomerase and p21 also suppresses growth of tumors containing mutant p53 following pharmacological restoration of p53 activity. Collectively, our results establish that inactivation of p21 leads to increased apoptosis upon telomerase inhibition and thus identify a genetic vulnerability that can be exploited to treat many human cancers containing either wild-type or mutant p53.
Introduction (1992)

Abstract Ellen Key announced in 1910 how she believed that the century of the child would rise with the new age. And while asserting a change in the relationships between children and adults, she also wanted to portray a different approach for the West in visualizing not just the future but also the individual, brought about by shifting understanding regarding the notions of class, place, and time. It can be observed, though, that there were already nineteenth century writings that were inspired by the emotionalism expressed during the eighteenth century and by the works of Rousseau that advocated the importance and value of childhood. While this is triggered in almost every generation of adults through pointing out the failures of past generations, there were indeed several responses to childhood during the nineteenth century that addressed such issues as prelinguistic restrictions.
mTOR-blocking agents in advanced renal cancer: an emerging therapeutic option (2009)

Rapamycin derivatives temsirolimus and everolimus have significant clinical activity in patients with advanced-stage RCC. Both parenteral and oral formulations of mTOR inhibitors have shown clinical efficacy and are currently being developed. Combinations of mTOR inhibitors with VEGF/VEGFR-blocking agents are also being studied, in an attempt to further enhance the antineoplastic effect.
Proton pump inhibitory therapy: then and now. (1997)

Proton pump inhibitors (PPIs) have been established as the new "gold standard" for traditional acid-inhibitory treatment of the so called "peptic" diseases. Due to the high antisecretory and ulcer-healing potency of omeprazole, no major improvements of the efficacy in ulcer healing and pain relief can be expected. Pantoprazole, as a further development in PPIs, is characterized by improved pharmacokinetic behavior as well as by higher tissue selectivity and binding specificity and by a very low potential to interact with the cytochrome P450 enzyme system. These characteristics may provide the basis for a low potential for side effects and for a more favorable interaction profile, although the clinical relevance of these potential advantages remains to be proven. Reflux esophagitis will also remain a domain for the traditional use of PPIs in the future. However, in the treatment of gastroduodenal ulcers, the acid inhibitory potential of PPIs will be used mainly to facilitate the eradication of H. pylori.
Fisheye menus (2000)

Article Fisheye menus Share on Author: Benjamin B. Bederson Human-Computer Interaction Lab, Institute for Advanced Computer Studies, Computer Science Department, University of Maryland, College Park, MD Human-Computer Interaction Lab, Institute for Advanced Computer Studies, Computer Science Department, University of Maryland, College Park, MDView Profile Authors Info & Claims UIST '00: Proceedings of the 13th annual ACM symposium on User interface software and technologyNovember 2000 Pages 217–225https://doi.org/10.1145/354401.354782Published:01 November 2000 142citation2,375DownloadsMetricsTotal Citations142Total Downloads2,375Last 12 Months66Last 6 weeks16 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
A 128k 6.5 ns access/5 ns cycle CMOS ECL static RAM (2003)

The authors describe an experimental 128k CMOS ECL-(emitter-coupled-logic)-compatible static RAM which has pipelined architecture and circuit techniques providing 6.5-ns first access and 5-ns cycle operation for fully random read/write. Using an all-CMOS technology, this cycle, combined with the 32-bit data I/O (input/output) capability, offers data bandwidth as high as 6.46 Gb/s. The technology is 1.2- mu m n-well CMOS with 14-nm gate oxide, 0.5- mu m effective channel length, and three levels of metal. The chip features a pin-selectable 32- or 8-bit-wide data I/O interface, transition-rate-controlled data outputs, low standby power, and well-controlled di/dt. To achieve high-speed operation and maximum power distribution efficiency, the chip is partitioned into 32 4k subarrays, organized into four quadrants. Operation using a pipelined chain of self-resetting circuit macros, initiated by a single clock, is shown. Measured waveforms are presented which illustrate the 6.5-ns access time and the 5-ns cycle time for a read '1' followed by a read '0' operation on the same data pin.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>