gebhart/patrepeval huggingface dataset:
Effects of the CYP2D6 Gene Duplication on the Pharmacokinetics and Pharmacodynamics of Tramadol (2008)

The analgesic drug tramadol is bioactivated by CYP2D6 to the opioid receptor agonist O-desmethyltramadol. Case reports indicated that carriers of the CYP2D6 gene duplication may be at high risk for opioid adverse events. However, the effects of the CYP2D6 duplication on kinetics and dynamics of tramadol have not been systematically studied. Pharmacokinetics and effects were monitored after a single dose of 100 mg racemic tramadol in 11 carriers of a CYP2D6 gene duplication allele (ultrarapid metabolizer [UM]) and compared with 11 carriers of 2 active CYP2D6 genes (extensive metabolizer [EM]). Pharmacodynamics was measured by cold pressure test, pupillometry, and standardized adverse event recording. The maximum plasma concentrations of the active metabolite (+)R,R-O-desmethyltramadol were significantly higher in the UM group compared with the EM group (P = 0.005; t test) with a mean difference of 14 ng/mL (95% confidence limit of difference, 2-26 ng/mL). Median (+)R,R-tramadol area under the curve was 786 and 587 mug.h.L in EMs and UMs, and the corresponding median (+)R,R-O-desmethyltramadol area under the curve was 416 and 448 mug.h.L (P = 0.005, t test). There was an increased pain threshold and pain tolerance and a stronger miosis after tramadol in UMs compared with EMs. Almost 50% of the UM group experienced nausea compared with only 9% of the EM group. In conclusion, pharmacokinetic differences between EMs and UMs were smaller than expected; nevertheless, UMs were more sensitive to tramadol than EMs. Therefore, tramadol may frequently cause adverse effects in southern European and Northern African populations with a high proportion of UMs.
Guidelines for the treatment of myelodysplastic syndromes (MDS) in South Africa. (2011)

Correct diagnosis, risk stratification and appropriate therapeutic choices are the cornerstones of success in the management of patients with myelodysplastic syndromes.
Erythrocyte-mediated delivery of phenylalanine ammonia lyase for the treatment of phenylketonuria in BTBR-Pahenu2 mice (2014)

Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by defects in the phenylalanine hydroxylase gene. Preclinical and clinical investigations suggest that phenylalanine ammonia lyase (PAL) could be an effective alternative for the treatment of PKU. The aim of this study is to investigate if erythrocytes loaded with PAL may act as a safe delivery system able to overcome bioavailability issues and to provide, in vivo, a therapeutically relevant concentration of enzyme. Murine erythrocytes were loaded with recombinant PAL from Anabaena variabilis (rAvPAL) and their ability to perform as bioreactors was assessed in vivo in adult BTBR-Pah(enu2) mice, the genetic murine model of PKU. Three groups of mice were treated with a single i.v. injection of rAvPAL-RBCs at three different doses to select the most appropriate one for assessment of efficacy. Repeated administrations at 9-10 day-intervals of the selected dose for 10 weeks showed that the therapeutic effect was persistent and not affected by the generation of antibodies induced by the recombinant enzyme. This therapeutic approach deserves further in vivo evaluation either as a potential option for the treatment of PKU patients or as a possible model for the substitutive enzymatic treatment of other inherited metabolic disorders.
Discovery of Potent Cell Migration Inhibitors through Total Synthesis:  Lessons from Structure−Activity Studies of (+)-Migrastatin (2004)

Synthesis of highly active migrastatin-based tumor migration cell inhibitors has been accomplished. Our flexible and concise total synthesis of migrastatin has allowed us to explore otherwise inaccessible migrastatin-derived structural motifs. This effort has resulted in the discovery of analogues with tumor cell migration inhibitory activity 3 orders of magnitude higher than that of the natural product.
Identification of High Potency Microbial and Self Ligands for a Human Autoreactive Class II–restricted T Cell Clone (1997)

CD4+ class II-restricted T cells specific for self antigens are thought to be involved in the pathogenesis of most human autoimmune diseases and molecular mimicry between foreign and self ligands has been implicated as a possible mechanism for their activation. In this report we introduce combinatorial peptide libraries as a powerful tool to identify cross-reactive ligands for these T cells. The antigen recognition of a CD4+ T cell clone (TCC) specific for myelin basic protein peptide (MBP) (86-96) was dissected by the response to a set of 220 11-mer peptide sublibraries. Based on the results obtained with the libraries for each position of the antigen, artificial peptides were found that induced proliferative responses at much lower concentrations than MBP(86-96). In addition stimulatory ligands derived from protein sequences of self and microbial proteins were identified, some of them even more potent agonists than MBP(86-96). These results indicate that: (a) for at least some autoreactive CD4+ T cells antigen recognition is highly degenerate; (b) the autoantigen used to establish the TCC represents only a suboptimal ligand for the TCC; (c) a completely random and unbiased approach such as combinatorial peptide libraries can decrypt the spectrum of stimulatory ligands for a T cell receptor (TCR).
The Removal of Free Surface Interactions From Three-Component Seismograms (1991)

The effect of the free surface can be removed from three-component seismic recordings to recover the incident upgoing wavefield, if the slowness and azimuth of the current wavefront are known as a function of time. For a single three-component station it is usually possible to estimate an azimuth for an event from the first arriving P-waves, but slowness estimates are less reliable when more than one wavetype is presented in the seismic wavetrain. However, the free surface correction operators are generally slowly varying functions of slowness and so some error in slowness can be tolerated. Effective approximations for the removal of the free surface effects can be made for hard rock sites to cover slowness bands for the main regional phases Pn, Pg, Sn and Lg. By applying these operators in turn over group velocity windows appropriate to the particular phases, the relative amplitude of the P, SV and SH contributions to the wavefield can be estimated. Because the free surface amplification effects have been removed, the amplitudes can be compared directly and provide useful constraints on the radiation characteristics of the source. This procedure is therefore helpful for developing discrimination measures for different classes of sources.
Transesterification of Soybean Oil to Biodiesel by Using Heterogeneous Basic Catalysts (2006)

Biodiesel production has increased greatly in recent years, because of the less-detrimental effects of this fuel on the environment, compared to a conventional diesel obtained from petroleum. This work investigates the possibility of using MgO and calcined hydrotalcites as catalysts for the transesterification of soybean oil with methanol. The achieved experimental data show a correlation not only with the catalysts basicity, but also with its structural texture. However, the structural texture of the examined catalysts is dependent on both the precursor and the preparation method. At least four different types of basic sites have been individuated on the surface of MgO and calcined hydrotalcite catalysts. The strongest basic sites (super-basic) promote the transesterification reaction also at very low temperature (100 °C), while the basic sites of medium strength require higher temperatures to promote the same reaction. Ultimately, all the tested catalysts are resistant to the presence of moisture in the reaction environment.
Immune Complex-Mediated Enhancement of Secondary Antibody Responses (2010)

Immunologic memory is a hallmark of the vertebrate immune system. The first antigenic exposure leads to a slow and modest immune response, whereas repeated exposure, even many years later, leads to a rapid and exaggerated response that is two to three orders of magnitude greater than the primary. In the case of humoral immunity, the increased efficacy of recall responses is due to the production of amplified levels of Ag-specific Ab, as well as the accelerated kinetics of their production. Current thinking suggests that this is due to selective activation of long-lived, Ag-specific memory B cells. A downside of restricting secondary responses solely to memory cells is that the repertoire of the memory B cell pool remains static while pathogens continue to evolve. In this study, we propose that during secondary responses, naive Ag-specific B cells participate alongside memory cells. We show that immune complexes formed in vivo between the Ag and pre-existing Abs from the primary response activate these naive B cells, inducing them to respond with accelerated kinetics and increased magnitude. Thus, the continued recruitment of new B cell clones after each antigenic exposure enables the immune system to stay abreast of rapidly changing pathogens.
Aerosolized immunoglobulin treatment of respiratory syncytial virus infection in infants (1996)

Aerosolized immunoglobulin in the dosage used had no substantial beneficial effect on RSV bronchiolitis. Despite these findings passive immunotherapy for treatment of RSV-induced lower respiratory tract infection deserves further evaluation before being discarded as ineffective.
Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in ambulatory adults over age 60 (1996)

The safety and immunogenicity of purified fusion protein (PFP-2) respiratory syncytial virus (RSV) vaccine was evaluated in a randomized placebo-controlled, double-blind study of 64 healthy adults over age 60. Vaccination was well tolerated with no significant acute side-effects. Twenty-nine of 33 vaccinees (87%) showed a greater than or equal to fourfold rise in serum IgG to the F protein of RSV at 8 weeks post vaccination. Twenty of 33 vaccine recipients (61%) had a greater than or equal to fourfold rise in serum neutralizing titer to group A and/or group B RSV. Response to vaccination was inversely correlated with pre-immunization serum neutralizing titers. Active surveillance throughout the ensuring winter identified three RSV infections in the placebo group and none in the vaccine group. Thus, PFP-2 was found to be safe and immunogenic in healthy older adults.
Arbitrary Analog/RF Spatial Filtering for Digital MIMO Receiver Arrays (2017)

Traditional digital multiple-input multiple-output (MIMO) receivers that feature element-level digitization face high instantaneous dynamic range challenges in the analog/RF domain due to the absence of analog/RF spatial filtering. Existing analog/RF spatial notch filtering techniques are limited in their noise, linearity, and spatial filtering bandwidth performance. More importantly, only single spatial notches have been demonstrated, providing insufficient filtering in practical scenarios. We propose a frequency-translational arbitrary spatial filtering technique that features not only arbitrary spatial filtering response generation at baseband for the protection of the following analog-to-digital converters, but modulated baseband input impedance that can be translated by passive mixers to achieve arbitrary spatial filtering at RF as well. This technique allows the synthesis and independent steering of an arbitrary number of spatial notches, and the independent adjustment of notch depths. Current-mode operation leads to superior linearity performance and ultra-wideband rejection. A four-element 65-nm CMOS 0.1-3.1 GHz prototype MIMO receiver array shows arbitrary spatial response formation, more than 50-dB spatial rejection across all measured directions, and an ultra-wide 320-MHz 20-dB rejection bandwidth for a single-notch setting at 500-MHz local oscillator (LO) frequency. Formation of a single spatial notch only moderately degrades the equivalent single-element double-sideband noise figure from 2.1-3.7 dB to 3.4-5.8 dB. In the notch direction, +34 dBV in-band output-referred IP3 is measured, an improvement of 33 dB compared with outside-notch directions. A wireless demonstration shows the receiver array demodulating a weak spatial signal in the presence of two strong in-band spatial signals, verifying the arbitrary spatial filtering functionality.
Pim kinase inhibitors: a survey of the patent literature (2010)

A greater understanding of pathological mechanisms for Pim kinases has stimulated the recent development of a variety of inhibitor classes with one compound advancing into the clinic earlier this year. Ongoing studies will help define applications for these inhibitors in the treatment of Pim-associated human diseases.
Flt3 Ligand Promotes the Generation of a Distinct CD34+Human Natural Killer Cell Progenitor That Responds to Interleukin-15 (1998)

Interleukin-15 (IL-15) is produced by human bone marrow (BM) stromal cells and can induce CD34(+) hematopoietic progenitor cells (HPCs) to differentiate into CD56(+)CD3(-) natural killer (NK) cells in the absence of stromal cells. IL-15 mediates its effects by signaling through the beta and gammac chains of the IL-2/15 receptor (R). The c-kit ligand (KL), also produced by stromal cells, enhances the expansion of NK cells from CD34(+) HPCs in the presence of IL-15, but alone has no ability to differentiate NK cells. Mice deficient in KL do not appear to have a quantitative deficiency in NK cells, suggesting that other stromal cell factors may contribute to NK cell expansion. Flt3 ligand (FL) is also produced by BM stromal cells and has homology with KL. Furthermore, mice with a targeted disruption of the FL gene have reduced numbers of NK cells. We evaluated here the effects of FL on human NK cell development and expansion from CD34(+) HPCs. Like KL, FL significantly enhanced the expansion of NK cells from CD34(+) HPCs in the presence of IL-15, compared with IL-15 alone. However, FL alone had no effect on NK cell differentiation. We therefore explored the mechanism by which FL promotes IL-15-mediated NK cell development. FL was found to induce IL-2/15Rbeta (CD122) expression on CD34(bright) HPCs. The CD34(bright) CD122(+) cell coexpressed CD38, but lacked expression of CD7, CD56, NK cell receptors (NKRs), or cytotoxic activity in the absence of IL-15. Using limiting dilution analysis in the presence of IL-15 alone, we demonstrated that the FL-induced CD34(bright)CD122(+) HPCs had an NK cell precursor frequency 20- to 60-fold higher than the CD34(dim/neg)CD122(-) HPCs and 65- to 235-fold higher than fresh CD34(+) HPCs. KL had similar effects as FL, but induced a significantly lower percentage of CD34(bright)CD122(+) cells (P </=.01). Both FL and KL also increased IL-15R transcript in CD34(+) HPCs. Culture of CD34(+) HPCs in FL or KL, followed by culture in IL-15 alone, induced expression of both C-type lectin and Ig-superfamily NKRs on CD56(+) cells. These data collectively support a role for FL in early human NK cell development. FL or KL generate a unique CD34(bright) CD122(+)CD38(+) human NK cell intermediate from CD34(+) HPCs that lacks NK features yet is IL-15-responsive. IL-15 is then required for the induction of CD56 and NKRs, LGL morphology, cytotoxic activity, and the ability to produce abundant cytokines and chemokines.
Hemodynamics of failing dialysis grafts. (1993)

Pressures were measured in the graft and the central vein during 104 consecutive angiographic examinations of failing hemodialysis grafts. Stenosis severity greater than 40% led to a statistically significant rise in graft pressure. In grafts in which all stenoses were of 40% or less severity, the systolic pressures in the venous and arterial limbs of the grafts were 31% +/- 16 and 45% +/- 17, respectively, of systemic systolic pressure. In grafts in which the highest grade of stenosis was greater than 40%, pressures in the venous and arterial limbs of the grafts were 53% +/- 25 and 75% +/- 24, respectively, of systemic systolic pressure. Graft thrombosis tended to occur at a higher degree of lumen reduction (but at similar pressures) with central vein stenoses compared with venous anastomotic stenoses. Dialysis graft pressures can help determine the hemodynamic importance of stenoses and the need for intervention. Percutaneous intervention should achieve arterial and venous limb pressures of less than 50% and 33% of systemic pressure, respectively.
Low-Power Far-Field Wireless Powering for Wireless Sensors (2013)

This paper discusses far-field wireless powering for low-power wireless sensors, with applications to sensing in environments where it is difficult or impossible to change batteries and where the exact position of the sensors might not be known. With expected radio-frequency (RF) power densities in the 20-200- μW/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> range, and desired small sensor overall size, low-power nondirective wireless powering is appropriate for sensors that transmit data at low duty cycles. The sensor platform is powered through an antenna which receives incident electromagnetic waves in the gigahertz frequency range, couples the energy to a rectifier circuit which charges a storage device (e.g., thin-film battery) through an efficient power management circuit, and the entire platform, including sensors and a low-power wireless transmitter, and is controlled through a low-power microcontroller. For low incident power density levels, codesign of the RF powering and the power management circuits is required for optimal performance. Results for hybrid and monolithic implementations of the power management circuitry are presented with integrated antenna rectifiers operating in the 1.96-GHz cellular and in 2.4-GHz industrial-scientific-medical (ISM) bands.
Towards a scientific interpretation of the terroir concept: plasticity of the grape berry metabolome (2015)

Our experiments with a single Corvina clone in different vineyards have revealed the existence of a clear terroir-specific effect on the transcriptome and metabolome which persists over several vintages and allows each vineyard to be characterized by the unique profile of specific metabolites.
Isolation and Characterization of a Rhizobacterial Antagonist of Root-Knot Nematodes (2014)

The rhizobacterial strain Jdm2 was isolated from the rhizosphere of the traditional Chinese medicinal herb Trichosanthes kirilowii in Jiangsu province, China, and was identified as Bacillus subtilis. Exposure of cell-free filtrate of the strain to the root-knot nematode Meloidogyne incognita under in vitro conditions caused substantial mortality of the second stage juvenile (J2) and significantly reduced egg hatchability. A greenhouse trial demonstrated that 56 days after treatment with Jdm2, the number of galls associated with M. incognita infection in the tomato (Solanum lycopersicum) roots was significantly reduced compared to controls, and the disease severity of infected plants was lower in treated plants (36%) compared to water control (75%). Consistently, in the field trial, the biocontrol efficacy of Jdm2 reached 69%, 51% and 48% after 30, 60 and 90 days post-transplantation, respectively. As indicated by PCR-DGGE analysis, inoculation with Jdm2 strain had an effect on the bacterial community of the tomato rhizosphere at the first stage, but was not able to imperil the bacterial community stability for long time. The novel bacterial strain Jdm2 enhances plant growth and inhibits nematode activity, and has the potential to be a safe and effective microbial pesticide.
THE SWEDISH HC-9 CIPHERING MACHINE (1989)

The HC-9 ciphering machine was used in Sweden after World War II. It satisfied the need for a simple key-setting process and the requirement of resistance to cryptanalysis by reduction of the risk of error when operated. The machine uses a punched card system instead of pin wheels and a drum with 16 changeable mixed alphabets which interrelated with the card reading mechanism and rotates after each letter is enciphered. The enciphering/deciphering process is described along with the machine's operating principles.
Handbook of Relational Database Design (1990)

Introduction. Why a Handbook of Relational Database Design? Introduction to Logical Data Modeling. Relational Concepts and SQL. Introduction to Relational Database Design. Build Skeletal User Views. Add Keys to User Views. Add Detail to User Views. Validate User Views through Normalization. Determine Additional Attribute Business Rules. Integrate User Views. Translate the Logical Data Structure. Translate the Logical Data Integrity. Tune by Establishing Storage-Related Access Mechanisms. Tune by Adding Indexes. Tune by Introducing Controlled Data Redundancy. Tune by Redefining the Relational Database Structure. Special Design Challenges. Appendix. Bibliography. Index of Design Rules. Index.
Identification of the promoter sequences involved in the interleukin-6 dependent expression of the rat α2-macroglobulin gene (1989)

The 5'-region of the rat alpha 2-macroglobulin gene has been characterized. A 5.6 kb Sal I - Xba I fragment containing the first 4 exons of the alpha 2-macroglobulin gene and 1.3 kb of its 5'-flanking region was sequenced. The putative transcriptional start site was determined by RNase protection and primer extension analysis. TATA- and CAAT-box equivalent sequences were found. A potential glucocorticoid receptor binding site was located on the antisense strand. DNA sequences containing the 5'-flanking region of the rat alpha 2-macroglobulin gene were linked to the gene coding for the bacterial chloramphenicol acetyltransferase and introduced into Hep G2 cells. In these transfected Hep G2 cells CAT activity could be induced by recombinant human interleukin-6. Deletion analyses have shown that the sequences between -852 and -777 as well as between -404 and -165 relative to the cap site, contain regulatory elements involved in the interleukin-6 dependent induction of the alpha 2-macroglobulin gene.
Efficient new cationic liposome formulation for systemic delivery of small interfering RNA silencing tumor necrosis factor α in experimental arthritis (2006)

We demonstrated the efficiency of systemic delivery of siRNA designed to silence TNFalpha in CIA, using a liposome carrier system as a way to address the methodologic limitations in vivo.
Classifying Relations via Long Short Term Memory Networks along Shortest Dependency Paths (2015)

Relation classification is an important research arena in the field of natural language processing (NLP). In this paper, we present SDP-LSTM, a novel neural network to classify the relation of two entities in a sentence. Our neural architecture leverages the shortest dependency path (SDP) between two entities; multichannel recurrent neural networks, with long short term memory (LSTM) units, pick up heterogeneous information along the SDP. Our proposed model has several distinct features: (1) The shortest dependency paths retain most relevant information (to relation classification), while eliminating irrelevant words in the sentence. (2) The multichannel LSTM networks allow effective information integration from heterogeneous sources over the dependency paths. (3) A customized dropout strategy regularizes the neural network to alleviate overfitting. We test our model on the SemEval 2010 relation classification task, and achieve an F 1 -score of 83.7%, higher than competing methods in the literature.
Functional and Cellular Responses in a Novel Rodent Model of Anterior Ischemic Optic Neuropathy (2003)

rAION rapidly results in electrophysiological and histologic changes similar to clinical AION, with reactive responses in primary and supporting neuronal cell layers. The rAION model can enable a detailed analysis of the individual retinal and optic nerve changes that occur after optic nerve stroke, which may be useful in determining possible therapeutic interventions for this disorder.