gebhart/patrepeval huggingface dataset:
Use of Spin Traps in Intact Animals Undergoing Myocardial Ischemia/Reperfusion: A New Approach to Assessing the Role of Oxygen Radicals in Myocardial “Stunning” (1990)

Numerous studies have indirectly suggested that oxygen-derived free radicals play an important pathogenetic role in the prolonged depression of contractile function observed in myocardium reperfused after reversible ischemia (myocardial "stunning"). In order to provide direct evidence for the oxy-radical hypothesis of stunning, we administered the spin trap, alpha-phenyl N-tert-butyl nitrone (PBN), to open-chest dogs undergoing a 15-min coronary artery occlusion followed by reperfusion. Plasma of local coronary venous blood was analyzed by electron paramagnetic resonance (EPR) spectroscopy. EPR signals characteristic of radical adducts of PBN appeared during ischemia and increased dramatically in the first few minutes after reperfusion. After this initial burst, the production of adducts abated but did not cease, persisting up to 3 h after reflow. The production of PBN adducts after reperfusion was inversely related to collateral flow during ischemia. PBN itself enhanced recovery of contractile function, indicating that the radicals trapped may play a pathogenetic role in myocardial stunning. Superoxide dismutase plus catalase attenuated PBN adduct production and, at the same time, improved recovery of contractile function. Antioxidant therapy given 1 min before reperfusion suppressed PBN adduct production and improved contractile recovery; however, the same therapy given 1 min after reperfusion did not suppress early radical production and did not attenuate contractile dysfunction. After i.v. administration, the elimination half-life of PBN was estimated to be approximately 4-5 h. The results demonstrate that 1) free radicals are produced in the stunned myocardium in intact animals; 2) inhibition of free radical production results in improved contractile recovery; and 3) the free radicals important in causing dysfunction are produced in the first few minutes of reperfusion. Taken together, these studies provide cogent evidence supporting the oxy-radical hypothesis of stunning in open-chest dogs. It is now critical to determine whether these results can be reproduced in conscious animal preparations.
Expression of the alpha, beta II, and gamma protein kinase C isozymes in the baculovirus-insect cell expression system. Purification and characterization of the individual isoforms. (1990)

Detailed in vitro comparisons of the biochemical characteristics of three protein kinase C isozymes were performed. As an alternative to earlier uncertain separation methods and expression schemes, highly purified and genetically distinct protein kinase C enzymes were produced using the baculovirus expression system. The baculovirus expression system yielded approximately 200-300 micrograms of the purified isozyme from 3 x 10(8) (100 ml of culture medium) baculovirus-infected insect cells. Biochemical characterization of the expressed isozymes indicated that the three isozymes had virtually indistinguishable Ca2+, Mg2+, and ATP dependencies. However, in certain critical functional characteristics such as phosphatidylserine dependencies, phospholipid and substrate preferences, and arachidonic acid activation, the gamma isozyme exhibited distinctive properties when compared with both the alpha and beta II subtypes. In addition, the activity of the beta II subtype was more dependent upon diacylglycerol or phorbol esters for activation than either the alpha or gamma isoforms. The alpha isozyme, unlike the beta II and gamma forms, was totally dependent on Ca2+ for activation in the presence of free arachidonic acid. These studies provide definitive characterizations of the pure isoforms; many of the findings were consistent with earlier enzymatic observations using hydroxyapatite-purified isoforms. Thus, the distinctive biochemical properties of the protein kinase C isozymes are consistent with the hypothesis that each isoform may have distinct roles in signal transduction processes.
Review of the use of topotecan in ovarian carcinoma (2004)

Ovarian cancer is the fifth leading cause of cancer deaths in women. The majority of patients present with advanced disease and relapse after first-line platinum-based chemotherapy; therefore, many proceed to treatment with salvage chemotherapy. Currently available treatment options are generally no longer curative in the relapse setting; hence, the emphasis of treatment is towards disease control and palliation of symptoms. There are several agents available for the treatment of relapsed ovarian carcinoma, of which topotecan is one of the most widely studied and characterised. This review aims to evaluate the role of topotecan in the management of this disease by considering the properties of the compound, the clinical efficacy in Phase II and III studies, its role in first- and second-line treatment and alternative dosing strategies to overcome toxicity.
Unusual Reverse Transcriptases (1995)

Reverse transcriptase (RTase), 1 rather than being unique to retroviruses as once appeared likely, is encoded in many DNA genomes (1, 2). RTase genes occur within 1) the retrovirus-like class I retrotransposons that have long terminal repeats (e.g. Ty of yeast), 2) class II (or LINE-like) retrotransposons that lack terminal repeats of any kind and typically have a dA-rich stretch at the 3′-end of the sense DNA strand, and 3) unusual retroelements of chromosomal and organellar origin. Telomerase is also an RTase(3).
AIDS - Can nurses meet the challenge? (1988)

Acquired Immune Deficiency Syndrome presents us with many questions, for which, at present, there are few answers. No one truly knows where the virus appeared from, or how it spread so rapidly throughout the world. It would sometimes seem as though there are as many theories about this as there are people researching the condition. Groups in society or whole countries or continents have been identified as the source, but as yet there is still little real evidence to support such theories.
Enriching the earth: Fritz Haber, Carl Bosch, and the transformation of world food production (2001)

Vaclav Smil admits in the postscript of this book that he had planned originally to write a biography of Fritz Haber.He does in fact include a summary of both Haber's and Carl Bosch's lives in the postscript, but the book itself is dedicated to the discovery, marketing, and consequences of the synthesis of ammonia.The book is interdisciplinary; with individual chapters being of interest to specific groups, but with its historical overview will appeal to a wide group of readers.
Phagocytosis by human monocyte-derived macrophages. Independent function of receptors for C3b (CR1) and iC3b (CR3). (1984)

Human monocytes and monocyte-derived macrophages were examined for their ability to bind and ingest C3-coated sheep erythrocytes (E). Greater than 90% of monocytes and macrophages formed rosettes with EC3b and EC3bi prepared with 15,000-20,000 molecules of C3 per E. Binding of EC3b to the monocyte or macrophage surface was inhibited by rabbit anti-C3b receptor (CR1), but was not inhibited by two different monoclonal anti-C3bi receptor (CR3) antibodies. EC3bi rosette formation was inhibited by monoclonal anti-CR3, but not by anti-CR1. Monocytes and macrophages did not form rosettes with similarly prepared EC3d,g or EC3d. Macrophages cultured for 7 days, but not freshly isolated monocytes, phagocytosed both EC3b and EC3bi. This ability was a consequence of macrophage maturation, as no external stimuli were present during in vitro culture. Experiments directed to determine if EC3b was converted to EC3bi before ingestion suggested that macrophage CR1 and CR3 mediated phagocytosis independently. No evidence was obtained that during the phagocytosis assay, macrophage factor I converted EC3b to EC3bi. The number of E bound or ingested by monocytes and macrophages was dependent on the number of molecules of C3b or iC3b bound per E. Monocytes and macrophages did not require the presence of either Ca++ or Mg++ for rosette formation with EC3b, whereas both divalent cations were required for optimum rosette formation with EC3bi. The presence of divalent cations was required for macrophage phagocytosis of EC3b and EC3bi. For ingestion of EC3b, Mg++ alone was sufficient, and the addition of Ca++ did not increase the number of EC3b ingested. For ingestion of EC3bi, both Ca++ and Mg++ were required for optimal phagocytosis, and their effect was concentration dependent and additive.
Biology of interleukin 1 (1988)

Interleukin 1 (IL 1) is a polypeptide that is produced after infection, injury, or antigenic challenge. Although the macrophage is a primary source of IL 1, epidermal, epithelial, lymphoid, and vascular tissues synthesize IL 1. When IL 1 gains access to the circulation, it acts like a hormone and induces a broad spectrum of systemic changes in neurological, metabolic, hematologic, and endocrinologic systems. Some of the IL 1 that is synthesized remains associated with the plasma membrane and induces changes in local tissues without producing systemic responses. IL 1 affects mesenchymal tissue remodeling where it contributes to both destructive and repair processes. IL 1 activates lymphocytes and plays an important role in the initiation of the immune response. Receptors for IL 1 have been identified, but receptors are scarce and their affinities often do not match the potency of the biological response. The most consistent property of IL 1 is up-regulation of cellular metabolism and increased expression of several genes coding for biologically active molecules. IL 1 is a highly inflammatory molecule and stimulates the production of arachidonic acid metabolites. IL 1 also acts synergistically with other cytokines, particularly tumor necrosis factor. The multitude of biological responses to IL 1 is an example of the rapid adaptive changes that take place to increase the host's defensive mechanisms.
Eliminating synchronization-related atomic operations with biased locking and bulk rebiasing (2006)

The Java™ programming language contains built-in synchronization primitives for use in constructing multithreaded programs. Efficient implementation of these synchronization primitives is necessary in order to achieve high performance.Recent research [9, 12, 10, 3, 7] has focused on the run-time elimination of the atomic operations required to implement object monitor synchronization primitives. This paper describes a novel technique called store-free biased locking which eliminates all synchronization-related atomic operations on uncontended object monitors. The technique supports the bulk transfer of object ownership from one thread to another, and the selective disabling of the optimization where unprofitable, using epoch-based bulk rebiasing and revocation. It has been implemented in the production version of the Java HotSpot™VM and has yielded significant performance improvements on a range of benchmarks and applications. The technique is applicable to any virtual machine-based programming language implementation with mostly block-structured locking primitives.
Evolving role of monoclonal antibodies in the treatment of chronic lymphocytic leukemia (2007)

Recognition of cancer-specific antigens resulted in development of monoclonal antibodies as treatments for various neoplasms including chronic lymphocytic leukemia (CLL). Two monoclonal antibodies, alemtuzumab and rituximab, have been extensively studied, as monotherapy or in combination, in patients with various clinical stages of CLL. Alemtuzumab, particularly when combined with fludarabine-based chemotherapy, sequentially or concomitantly, represents a promising therapeutic approach that results in improved efficacy by further reducing levels of residual disease in previously untreated or relapsed/refractory CLL. On the other hand, single-agent rituximab has limited activity by itself, even at very high doses, and seldom induces complete remissions. However, rituximab is feasible to combine with conventional chemotherapies such as purine analogs, alkylating chemotherapy and/or alemtuzumab. Newer monoclonal antibodies are already showing activity in relapsed/refractory CLL and will eventually be evaluated in combinations with conventional chemotherapy, or with already established antibodies. Modern definitions for assessment of responses such as minimal residual disease negativity (MRD negativity) are emerging and, consequently, development of assays capable of measuring such responses. MRD negativity should become the primary objective of clinical trials when evaluating treatment interventions in patients with CLL. The future of monoclonal antibodies for treatment of CLL is bright.
Large Enhancement of Functional Activity of Active Site-Inhibited Factor VIIa Due to Protein Dimerization:  Insights into Mechanism of Assembly/Disassembly from Tissue Factor (2005)

Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.
Structural determinants for binding to CGRP receptors expressed by human SK‐N‐MC and Col 29 cells: studies with chimeric and other peptides (1998)

Structure-activity relationships for the binding of human alpha-calcitonin gene-related peptide 8-37 (halphaCGRP8-37) have been investigated at the CGRP receptors expressed by human SK-N-MC (neuroblastoma) and Col 29 (colonic epithelia) cells by radioligand binding assays and functional assays (halphaCGRP stimulation of adenylate cyclase). On SK-N-MC cells the potency order was halphaCGRP8-37 > halphaCGRP19-37 = AC187 > rat amylin8-37 > halpha[Tyr0]-CGRP28-37 (apparent pKBs of 7.49+/-0.25, 5.89+/-0.20, 6.18+/-0.19, 5.85+/-0.19 and 5.25+/-0.07). The SK-N-MC receptor appeared CGRP1-like. On Col 29 cells, only halphaCGRP8-37 of the above compounds was able to antagonize the actions of halphaCGRP (apparent pKB=6.48+/-0.28). Its receptor appeared CGRP2-like. halpha[Ala11,18]-CGRP8-37, where the amphipathic nature of the N-terminal alpha-helix has been reduced, bound to SK-N-MC cells a 100 fold less strongly than halphaCGRP8-37. On SK-N-MC cells, halphaCGRP8-18,28-37 (M433) and mastoparan-halphaCGRP28-37 (M432) had apparent pKBs of 6.64+/-0.16 and 6.42+/-0.26, suggesting that residues 19-27 play a minor role in binding. The physico-chemical properties of residues 8-18 may be more important than any specific side-chain interactions. M433 was almost as potent as halphaCGRP8-37 on Col 29 cells (apparent pKB=6.17+/-0.20). Other antagonists were inactive.
[Vacuum treatment in the surgical management of suppurative wounds]. (1986)

Vacuum treatment was used in 116 patients with purulent wounds. It was established that the vacuum treatment of purulent wounds was effective but after surgical treatment. It considerably decreased the amount of microbes in wound tissues, had no harmful effects and improved clinical results of healing the wounds after putting early sutures.
Fast Resampling of Three-Dimensional Point Clouds via Graphs (2017)

To reduce the cost of storing, processing, and visualizing a large-scale point cloud, we propose a randomized resampling strategy that selects a representative subset of points while preserving application-dependent features. The strategy is based on graphs, which can represent underlying surfaces and lend themselves well to efficient computation. We use a general feature-extraction operator to represent application-dependent features and propose a general reconstruction error to evaluate the quality of resampling; by minimizing the error, we obtain a general form of optimal resampling distribution. The proposed resampling distribution is guaranteed to be shift-, rotation- and scale-invariant in the three-dimensional space. We then specify the feature-extraction operator to be a graph filter and study specific resampling strategies based on all-pass, low-pass, high-pass graph filtering and graph filter banks. We validate the proposed methods on three applications: Large-scale visualization, accurate registration, and robust shape modeling demonstrating the effectiveness and efficiency of the proposed resampling methods.
Consequences of stratified sampling in graphics (1996)

Antialiased pixel values are often computed as the mean of N point samples. Using uniformly distributed random samples, the central limit theorem predicts a variance of the mean of O(N -1 ). Stratified sampling can further reduce the variance of the mean. This paper investigates how and why stratification effects the convergence to mean value of image pixels, which are observed to converge from N -2 to N -1 , with a rate of about N -3/2 in pixels containing edges. This is consistent with results from the theory of discrepancy. The result is generalized to higher dimensions, as encountered with distributed ray tracing or form-factor computation.
RHAMM is differentially expressed in the cell cycle and downregulated by the tumor suppressor p53 (2008)

The receptor for hyaluronan-mediated motility RHAMM exerts different functions in the cell as well as on the cell membrane. RHAMM can be exported to the cell surface where it binds hyaluronic acid (HA) and interacts with the HA receptor CD44. Processes like cell motility, wound healing and invasion are modulated by RHAMM. Intracellularly, RHAMM is associated with the cytoskeleton, microtubules, centrosomes and the mitotic spindle. It participates in the control of mitotic spindle stability and integrity. Furthermore, RHAMM is overexpressed in several cancer tissues. We found that RHAMM expression is differentially regulated during the cell cycle and that cell cycle-dependent synthesis of RHAMM is controlled by its promoter on the transcriptional level. RHAMM protein levels follow mRNA expression in the early phases of the cell cycle. However, they already peak in S phase and decrease before the maximum of RHAMM mRNA expression is reached in G(2)/M. Furthermore, RHAMM expression is downregulated by the tumor suppressor p53. This regulation is observed in a transgenic p53-inducible cell system as well as in cells with wild-type p53 treated with nutlin-3, doxorubicin or paclitaxel. Reporter assays demonstrated that the repression by p53 is regulated on the transcriptional level by the RHAMM promoter also comprising the first exon and the first intron of the gene. In general, our data support a role of RHAMM already in S phase. Additionally, p53-dependent downregulation is consistent with an oncogenic function of RHAMM and the recently reported tumor-suppressive function of CD44 transcriptional repression by p53.
Pharmacologic and Bacteriologic Properties of SCH‐27899 (Ziracin), an Investigational Antibiotic from the Everninomicin Family (1999)

SCH-27899 is an investigational antibiotic from the everninomicin family, a group of oligosaccharide antibiotics produced by Micromonospora carbonacea. Information regarding the pharmacology, pharmacodynamics, pharmacokinetics, efficacy, and toxicity of this agent was obtained from a MEDLINE search and a review of abstracts presented at recent scientific meetings. SCH-27899 has in vitro bacteriostatic activity against a wide variety of gram-positive organisms, including highly resistant organisms such as methicillin-resistant Staphylococcus aureus, vancomycin-intermediate-sensitivity S. aureus, Streptococcus pneumoniae (both penicillin-susceptible and -nonsusceptible), and vancomycin-resistant enterococci. In vitro data, animal studies, and preliminary human studies indicate that it is effective and fairly well tolerated. Its place in therapy remains to be determined, and clinical trials continue.
Realtime photoacoustic microscopy in vivo with a 30-MHz ultrasound array transducer (2008)

We present a novel high-frequency photoacoustic microscopy system capable of imaging the microvasculature of living subjects in realtime to depths of a few mm. The system consists of a high-repetition-rate Q-switched pump laser, a tunable dye laser, a 30-MHz linear ultrasound array transducer, a multichannel high-frequency data acquisition system, and a shared-RAM multi-core-processor computer. Data acquisition, beamforming, scan conversion, and display are implemented in realtime at 50 frames per second. Clearly resolvable images of 6-microm-diameter carbon fibers are experimentally demonstrated at 80 microm separation distances. Realtime imaging performance is demonstrated on phantoms and in vivo with absorbing structures identified to depths of 2.5-3 mm. This work represents the first high-frequency realtime photoacoustic imaging system to our knowledge.
V599EB-RAF is an Oncogene in Melanocytes (2004)

The oncogenic version of B-RAF, (V599E)B-RAF, is found in approximately 70% of human melanomas. However, the role that this oncogene plays in melanoma is unclear because (V559E)B-RAF is also found in approximately 80% of benign nevi. We have examined the role of oncogenic B-RAF in the early stages of melanoma by expressing (V599E)B-RAF in cultured melanocytes. In these cells, (V599E)B-RAF induced constitutive mitogen activated ERK-activating kinase (MEK) and extracellular signal-regulated kinase (ERK) signaling, 12-O-tetradecanoylphorbol-13-acetate-independent growth, and tumorigenicity in nude mice. Intriguingly, in RAS-transformed melanocytes, B-RAF depletion did not block MEK-ERK signaling or cell cycle progression. Similarly, B-RAF depletion blocked MEK-ERK signaling in human melanoma cells harboring oncogenic B-RAF, but not in melanoma cells harboring oncogenic RAS. Thus, although B-RAF can act as a potent oncogene in the early stages of melanoma by signaling through MEK and ERK, it is not required for this signaling in RAS-transformed melanocytes due to innate redundancy within the pathway. These findings have important implications for future therapeutic strategies.