gebhart/patrepeval huggingface dataset:
Structural modeling of the distamycin A-d(CGCGAATTCGCG)2 complex using 2D NMR and molecular mechanics (1988)

The structure of the distamycin A-d(CGCGAATTCGCG)2 complex has been determined through a combination of SKEWSKY and NOESY 2D NMR experiments and molecular mechanics calculations. NMR data provided upper bounds on many proton-proton pairs. The advantage of the SKEWSKY/NOESY method is that small groups of strongly coupled spins can be treated accurately as isolated systems. The AMBER molecular mechanics package, modified to include the NMR constraints, was used in energy refinements. Distamycin A fits snugly into the 5'-AATT-3' minor-groove binding site. Structural analysis revealed van der Waals contacts between A5, A6, and A18 C2H and drug H3 protons, potential three-center hydrogen bonding between drug amide protons and adenine N3 and thymine O2 atoms analogous to the spine of hydration in the crystal structure of the free DNA, and stacking of the sugar O1' atoms of A6-C21, T7-T20, and, T8-T19, over drug pyrrole rings 1, 2, and 3, respectively. In addition to hydrophobic effects, hydrogen bonding, and electrostatic interactions proposed by others, it is suggested that stacking interactions between DNA sugar O1' atoms and the three drug pyrrole rings contribute to the stability of the complex.
Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial (2013)

A previous pilot study with rituximab, gemcitabine and oxaliplatin showed promising activity in patients with refractory/relapsed B-cell lymphoma. We, therefore, conducted a phase II study to determine whether these results could be reproduced in a multi-institutional setting. This phase II study included 49 patients with refractory (n=6) or relapsing (n=43) diffuse large B-cell lymphoma. The median age of the patients was 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplantation in 17 (35%) patients. International Prognostic Index at enrollment was >2 in 34 patients (71%). The primary endpoint was overall response rate after four cycles of treatment. Patients were planned to receive eight cycles if they reached at least partial remission after four cycles. After four cycles 21 patients (44%) were in complete remission and 8 (17%) in partial remission, resulting in an overall response rate of 61%. Factors significantly affecting overall response rate were early (<1 year) progression/relapse (18% versus 54%; P=0.001) and prior exposure to rituximab (23% versus 65%; P=0.004). Five-year progression-free and overall survival rates were 12.8% and 13.9%, respectively. Rituximab, gemcitabine and oxaliplatin were well tolerated with grade 3-4 infectious episodes in 22% of the cycles. These results are the first confirmation from a multicenter study that rituximab, gemcitabine and oxaliplatin provide a consistent response rate in patients with refractory/relapsed diffuse large B-cell lymphoma. This therapy can now be considered as a platform for new combinations with targeted treatments. This trial was registered at clinicaltrial.gov under #NCT00169195.
Theory of borehole stability when drilling through salt formations (2006)

Abstract We present a mathematical analysis of borehole stability when drilling through rock salt. First, we consider an elastic transversely isotropic medium and find the optimal mud weight as a function of the vertical overburden and horizontal tectonic stresses. Then, the Zener and Maxwell mechanical models are used to model the effects of transient and steady-state creep flow, respectively, in isotropic media. Under certain conditions such as the absence of dilatational anelasticity, the Burger model can be used to describe the steady-state flow, including transient creep effects. The type of creep is regulated by critical octahedral-stress values that depend on temperature and pressure. A typical drilling results in conditions of plane strain, whose solution is given by Kirsch's equations. In this case, the borehole is subject to minimum and maximum horizontal stresses, which differ from the vertical stress. The analysis provides expressions for the shape of the borehole-cross section, the borehole-wall closure time, and the optimal mud weight to avoid wall collapse or expansion. It is shown that an anisotropic state of tectonic stress may require mud pressures exceeding the overburden stress and that the calculation should consider the joint optimization of the shape and area of the borehole cross section.
Canine Model and Genomic Structural Organization of Glycogen Storage Disease Type Ia (GSD Ia) (2001)

A canine model of glycogen storage disease Ia (GSD Ia), similar clinically, biochemically, and pathologically to the human disease, was established by crossbreeding Maltese and Beagle dogs carrying a mutated, defective glucose-6-phosphatase (G-6-Pase) gene. Ten puppies were born in three litters from these crossbreedings. Six were homozygous for the previously described M121I GSD Ia mutation. Of these six affecteds, two were stillborn, and one died at 2, 32, and 60 days of life, respectively (puppies A, B, C, D, E), while one is alive at age 15 months (puppy F). Affected puppies exhibited tremors, weakness, and neurologic signs when hypoglycemic. They had postnatal growth retardation and progressive hepatomegaly. Biochemical abnormalities included fasting hypoglycemia, hyperlactacidemia, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Microscopic examination of tissues from affected puppies showed diffuse, marked hepatocellular vacuolation, with distended clear hepatocytes and central to marginally located rounded nuclei. In the kidneys of puppies D and E, there was segmental glomerular sclerosis and vacuolation of proximal convoluted tubular epithelium. Biochemical analysis revealed increased liver glycogen content and isolated markedly reduced G-6-Pase enzyme activity in liver and kidney. The canine G-6-Pase gene was characterized by screening a canine genomic library. It spans approximately 11.8 kb and consists of five exons with >90% amino acid sequence homology to the derived human sequence. The first 1.5 kb of the 5' region was sequenced and contains several putative response element motifs homologous to the human 5' region. Establishment of this canine colony of GSD Ia that closely resembles human disease and isolation of the canine genomic gene provides an excellent model for studying pathophysiology and long-term complications and an opportunity to develop novel therapeutic approaches such as drug and gene therapy.
Topological quantum computing with a very noisy network and local error rates approaching one percent (2013)

A scalable quantum computer could be built by networking together many simple processor cells, thus avoiding the need to create a single complex structure. The difficulty is that realistic quantum links are very error prone. A solution is for cells to repeatedly communicate with each other and so purify any imperfections; however prior studies suggest that the cells themselves must then have prohibitively low internal error rates. Here we describe a method by which even error-prone cells can perform purification: groups of cells generate shared resource states, which then enable stabilization of topologically encoded data. Given a realistically noisy network (≥10% error rate) we find that our protocol can succeed provided that intra-cell error rates for initialisation, state manipulation and measurement are below 0.82%. This level of fidelity is already achievable in several laboratory systems.
The Time Course of Tumor Necrosis Factor-α, Inducible Nitric Oxide Synthase and Vascular Endothelial Growth Factor Expression in an Experimental Model of Chronic Myocardial Infarction in Rats (2001)

An injury to the heart due to myocardial infarction may progress to heart failure. Among the cytokines and growth factors whose interactions promote remodeling of the heart, increased expression of tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) has been found. However, little is known about the sequence of gene expression during the progression of heart injury. In the present study, male Sprague-Dawley rats were used for experimental myocardial infarction performed by ligation of the left anterior descending coronary artery. TNF-alpha, iNOS and VEGF expression was assessed by reverse transcription polymerase chain reaction. Localization of TNF-alpha, VEGF and iNOS protein was assessed by immunohistochemistry. An in vitro proliferation (BrdU incorporation) and differentiation (tube formation) assay of human umbilical vein endothelial cells was performed. The expression of TNF-alpha, iNOS, VEGF(164) and VEGF(188) was observed during the whole period after myocardial infarction (on days 1, 4, 11, 28 and 40), whereas VEGF(120) was found only on day 1 and 4. The most intense immunostaining for TNF-alpha was observed at the border zone. The iNOS immunostaining was initially located in the endothelium, whereas later it was also present in the walls of larger vessels. The VEGF protein was present in the border zone. No gene expression or immunostaining was detected in sham-operated rats. The in vitro experiments showed both proangiogenic (low TNF-alpha concentration, short period of incubation) and antiangiogenic (high TNF-alpha concentration, long period of incubation) effects of TNF-alpha. The expression of TNF-alpha and iNOS genes with the concomitant occurrence of a decrease in VEGF(120), VEGF(188) and VEGF(164) protein could be related to insufficient angiogenesis and may suggest the possible involvement of these events in remodeling after myocardial infarction.
Ruby laser-induced linear dichroism of F A(II) centers in KCl:Li crystals (1991)

The FA(II) color centers of KCl:Li crystals were observed to reorientate at room temperature under the exposure of a ruby laser. The linear dichroism of the centers, induced by ruby laser light, is presented here.
A Comparison of GLC and HPLC Methods for Determining Fatty Acid Composition of Evening Primrose and Soybean Oil (1983)

The composition of the fatty acids of the oil from the seeds of the evening primrose (Oenothera biennis) was studied by capillary and packed-column gas-liquid chromatography (GLC). The major constituents were found to be: 16:0,6%; 18:0, 2%; 18:1ω9, 11.3%; 18:2ω6, 72.3%; and 18:3ω6, 8.9%. Capillary GLC gave better separation of isomeric linolenic acids. Similar results were obtained by analysis of the free fatty acids or methyl esters using reversed-phase high-performance liquid chromatography (RP-HPLC), but GLC is preferred to distinguish evening primrose oil from soybean oil. The 18:3ω6 component could not be readily distinguished from the 18:3ω3 component by RP-HPLC. Analysis of the free fatty acids by RPHPLC gave a higher proportion of 18:3 fatty acids than did analysis of the methyl esters.
Recent advances in the treatment of non-alcoholic fatty liver disease (2005)

Non-alcoholic steatohepatitis is a liver disease strongly associated with features of the metabolic syndrome. It is part of the disease spectrum of non-alcoholic fatty liver disease, which is now thought to be the most common cause of chronic liver disease in the US and other Western countries. Initially this condition was considered innocuous but it is now recognised as having the potential to progress to cirrhosis and its complications. The role of insulin resistance and oxidative stress in its pathogenesis is increasingly accepted. Current investigations are directed towards a better understanding of the natural history, pathogenesis and development of treatment strategies. Several therapeutic modalities, including antioxidants, insulin-sensitising agents and lipid-lowering agents, have been evaluated for the treatment of these patients, mostly in small clinical trials. Despite promising results, no therapy has demonstrated a proven benefit.
A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells (2011)

Previous studies have established a role of vascular-disrupting agents as anti- cancer agents. Plinabulin is a novel vascular-disrupting agent that exhibits potent interruption of tumor blood flow because of the disruption of tumor vascular endothelial cells, resulting in tumor necrosis. In addition, plinabulin exerts a direct action on tumor cells, resulting in apoptosis. In the present study, we examined the anti-multiple myeloma (MM) activity of plinabulin. We show that low concentrations of plinabulin exhibit a potent antiangiogenic action on vascular endothelial cells. Importantly, plinabulin also induces apoptotic cell death in MM cell lines and tumor cells from patients with MM, associated with mitotic growth arrest. Plinabulin-induced apoptosis is mediated through activation of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase cleavage. Moreover, plinabulin triggered phosphorylation of stress response protein JNK, as a primary target, whereas blockade of JNK with a biochemical inhibitor or small interfering RNA strategy abrogated plinabulin-induced mitotic block or MM cell death. Finally, in vivo studies show that plinabulin was well tolerated and significantly inhibited tumor growth and prolonged survival in a human MM.1S plasmacytoma murine xenograft model. Our study therefore provides the rationale for clinical evaluation of plinabulin to improve patient outcome in MM.
Graphene at the Edge: Stability and Dynamics (2009)

Although the physics of materials at surfaces and edges has been extensively studied, the movement of individual atoms at an isolated edge has not been directly observed in real time. With a transmission electron aberration-corrected microscope capable of simultaneous atomic spatial resolution and 1-second temporal resolution, we produced movies of the dynamics of carbon atoms at the edge of a hole in a suspended, single atomic layer of graphene. The rearrangement of bonds and beam-induced ejection of carbon atoms are recorded as the hole grows. We investigated the mechanism of edge reconstruction and demonstrated the stability of the "zigzag" edge configuration. This study of an ideal low-dimensional interface, a hole in graphene, exhibits the complex behavior of atoms at a boundary.
Palladium-Catalyzed Direct C–H Silylation and Germanylation of Benzamides and Carboxamides (2014)

A palladium-catalyzed regioselective activation of C(sp(2))-H and C(sp(3))-H bonds of benzamides and carboxamides, followed by coupling with disilanes to afford organosilanes in moderate to high yields, with the aid of 8-aminoquinoline as a directing group, is reported. Catalytic C(sp(2))-H germanylation of benzamides also proceeds under the same palladium catalysis. The reaction tolerates a wide variety of functional groups and is scalable without yield reduction. The bidentate directing group is readily removed and recovered by the reaction with a hydrazine, with concominant generation of an acyl hydrazide.
GNSS Threat Monitoring and Reporting: Past, Present, and a Proposed Future (2017)

Vulnerability of satellite-based navigation signals to intentional and unintentional interference calls for a high-level overview of Global Navigation Satellite System (GNSS) threats occurring globally to understand the magnitude and evolution of the problem. Therefore, a mechanism needs to be developed whereby disparate monitoring systems will be capable of contributing to a common entity of basic information about the threat scenarios they experience. This paper begins with a literature survey of 37 state-of-the-art GNSS threat monitoring systems, which have been analysed based on their respective operational features - constellations monitored and whether they possess the capability to perform interference-type classification, spoofing detection, and interference localisation. Also described is a comparative analysis of four GNSS threat reporting formats in use today. Based on these studies, the paper describes the Horizon2020 Standardisation of GNSS Threat Reporting and Receiver Testing through International Knowledge Exchange, Experimentation and Exploitation (STRIKE3) proposed integrated threat monitoring demonstration system and related standardised threat reporting message, to enable a high-level overview of the prevailing international GNSS threat scenarios and its evolution over time.
Triple band planar inverted F antennas for handhelddevices (2000)

Two novel triple band planar inverted F antennas (PIFAs) are presented. The first antenna is realised by housing a dual frequency L-shaped spur line loaded PIFA element within the lower resonance PIFA element. The second antenna is realised by embedding two single element PIFAs within a quarter-wave patch. For both antennas, an isolation of better than –15 dB between the feed ports and a good agreement between simulation and measurement results was obtained.
Getty's Synoname™ and its cousins: A survey of applications of personal name-matching algorithms (1992)

The study reported in this article was commissioned by the Getty Art History Information Program (AHIP) as a background investigation of personal name-matching programs in fields other than art history, for purposes of comparing them and their approaches with AHIP's Synoname™ project. We review techniques employed in a variety of applications, including art history, bibliography, genealogy, commerce, and government, providing a framework of personal name characteristics, factors in selecting matching techniques, and types of applications. Personal names, as data elements in information systems, vary for a wide range of legitimate reasons, including cultural and historical traditions, translation and transliteration, reporting and recording variations, as well as typographical and phonetic errors. Some matching applications seek to link variants, while others seek to correct errors. The choice of matching techniques will vary in the amount of domain knowledge about the names that is incorporated, the sources of data, and the human and computing resources required. Personal name-matching techniques may be included in name authority work, information retrieval, or duplicate detection, with some applications matching on name only, and others combining personal names with other data elements in record linkage techniques. We discuss both phonetic- and pattern-matching techniques, reviewing a range of implemented and proposed name-matching techniques in the context of these factors. © 1992 John Wiley & Sons, Inc.
Pharmacokinetics of Recombinant Factor VIIa in the Rat – A Comparison of Bio-, Immuno- and Isotope Assays (1993)

Recombinant human factor VIIa (rFVIIa) is an activated coagulation factor for intravenous use as a haemostatic agent in haemophiliacs who generate antibodies against factor VIII or IX. Plasma kinetic studies are important for the understanding of the action of rFVIIa which is exerted in the vascular compartment of the body, more specifically on the vessel walls at the site of injury. In the present study, rats were dosed 100 or 500 micrograms/kg 125I-rFVIIa i.v., without any side effects being observed, and the plasma profile of rFVIIa was studied by 3 different assays that were shown to correlate well at early times post-dose: trichloroacetic acid (TCA)-precipitable drug-related radioactivity, rFVIIa antigen determination by ELISA technique, and the assay of clot activity which is the only clinically applicable assay. The plasma concentration curve could be resolved into 1-3 exponentials, depending on the FVIIa detection principle that was employed. Initially, there was a short (ca. 10 min) phase of increasing concentrations before the attainment of Cmax. This was followed by a plasma recovery (Cmax x plasma volume/dose) in the vicinity of one half of the administered dose. The initial volume of distribution (V1) corresponded to the vascular compartment whereas the volume of distribution at steady state (Vss) was somewhat larger. Whole body clearance (CL-B) of rFVIIa was approx. 1 ml/min per kg, and mean residence time (MRT) and the half-life assumed to be associated with the loss of biological activity was approx. 1 h and 20-45 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Advanced Biotelemetry Systems for Space Life Sciences: PH Telemetry (1995)

The SENSORS 2000! (S2K!) program at NASA's Ames Research Center is currently developing a biotelemetry system for monitoring pH and temperature in unrestrained subjects. This activity is part of a broader scope effort to provide an Advanced Biotelemetry System (ABTS) for use in future space life sciences research. Many anticipated research endeavors will require biomedical and biochemical sensors and related instrumentation to make continuous inflight measurements in a variable-gravity environment. Since crew time is limited, automated data acquisition, data processing, data storage, and subject health monitoring are required. An automated biochemical and physiological data acquisition system based on non invasive or implantable biotelemetry technology will meet these requirements. The ABTS will ultimately acquire a variety of physiological measurands including temperature, biopotentials (e.g. ECG, EEG, EMG, EOG), blood pressure, flow and dimensions, as well as chemical and biological parameters including pH. Development activities are planned in evolutionary, leveraged steps. Near-term activities include 1) development of a dual channel pH/temperature telemetry system, and 2) development of a low bandwidth, 4-channel telemetry system, that measures temperature, heart rate, pressure, and pH. This abstract describes the pH/temperature telemeter.
Induction of human serum amyloid A in Hep 3B cells by IL-6 and IL-1 beta involves both transcriptional and post-transcriptional mechanisms. (1995)

Previous studies of murine serum amyloid A (SAA) regulation during inflammatory states or following exposure to macrophage-conditioned medium have raised the possibility that both post-transcriptional and transcriptional mechanisms participate in induction of this family of proteins. Since IL-6 and IL-1 have been shown to induce SAA in human hepatoma cell lines, we explored the possibility that these cytokines might induce human SAA through post-transcriptional as well as transcriptional mechanisms. In kinetic studies, we found that continuous exposure of Hep 3B cells to either IL-6 or IL-1 beta alone caused only minimal increases in SAA mRNA and marginal increases in transcription (as measured by nuclear runon). In contrast, the combination of these cytokines led to a 23-fold increase in transcription, maximal at 12 h, with continuing increase in mRNA, achieving levels more than 1,000-fold greater than baseline by 72 h. This massive disparity between increases in mRNA and in transcription rate strongly supports the participation of post-transcriptional mechanisms in SAA induction by (IL-6 + IL-1 beta), whereas the lag between peaks of transcription and mRNA abundance reflects a relatively slow degradation rate of SAA mRNA. As observed by other workers, mean size of SAA mRNA decreased progressively over the course of incubation. Simultaneous kinetic studies of complement factors B and C3, haptoglobin, and alpha-1 protease inhibitor revealed several different patterns of response to IL-6 and IL-1 beta.
Serum Interleukin-6 Levels Correlate with Malnutrition and Survival in Patients with Advanced Non-Small Cell Lung Cancer (2004)

IL-6 secretion may play a role in the pathophysiology of malnutrition in advanced lung cancer. Results show a relation between elevated IL-6 serum levels and malnutrition, poor performance status, acute phase response and shorter survival in patients affected by advanced non-small cell lung cancer.