gebhart/patrepeval huggingface dataset:
Adding pharmacogenetics information to drug labels: lessons learned (2006)

The US Food and Drug Administration approved a revised package insert for two cancer drugs to include information about the increased risk of severe adverse events owing to enzyme deficiencies caused by genetic variants. The label revisions stopped short of recommending or requiring pharmacogenetic testing prior to or following an adverse event. Despite (or because of) the lack of specific recommendations, we believe the actions taken by US Food and Drug Administration will have implications for pharmacogenetics research, clinical integration, and other policy considerations. We review the reasons behind the cautious label changes and discuss some of the lessons that can be learned from these experiences.
The bus interface and paging units of the i860 microprocessor (2003)

The i860 microprocessor is a one-million-transistor, high-performance, 64-b RISC (reduced-instruction-set-computer)-based microprocessor. The performance of the i860 at 40 MHz is 83000 Dhrystones, 24 double-precision MWhetstones, and 10 double-precision MFLOPS on the Linpack benchmark. To support this rate of integer and floating-point execution a bus interface unit and paging unit were designed to provide the needed bus bandwidth. The bus and paging units, in conjunction with the internal data and instruction caches, can provide a 960-Mbyte internal instruction and data bus bandwidth, and a 160-Mbyte external bus bandwidth.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Oct-1 and CCAAT/Enhancer-binding Protein (C/EBP) Bind to Overlapping Elements within the Interleukin-8 Promoter (1997)

Interleukin-8 (IL-8), a potent neutrophil chemoattractant, can be expressed at high levels by many different cell types after immune stimulation. In contrast, expression of IL-8 in these same cells is virtually absent in the unstimulated state, demonstrating the tight regulation of the IL-8 gene. Although much is known about how this gene is transcriptionally activated after immune stimulation, little is known about the regulation of the IL-8 promoter in the absence of immune activation. In this study we examine how the IL-8 promoter is transcriptionally regulated in the uninduced state and how these mechanisms are altered in response to immune stimulation by IL-1beta. Electrophoretic mobility shift assay and transfection studies show that the IL-8 promoter is transcriptionally regulated by both positive and negative elements. Although the nuclear factor-kappaB (NFkappaB) element regulates only inducible activity of the IL-8 promoter in response to stimulation with IL-1beta, the AP-1 and CCAAT/Enhancer-binding Protein (C/EBP) elements influence both basal and inducible activities. In contrast to these three positive regulatory elements, the binding of the ubiquitously expressed POU-homeodomain transcription factor, Oct-1, strongly represses transcriptional activity of the IL-8 promoter by binding independently to an element overlapping that of C/EBP.
A dual-tag microarray platform for high-performance nucleic acid and protein analyses (2008)

DNA microarrays serve to monitor a wide range of molecular events, but emerging applications like measurements of weakly expressed genes or of proteins and their interaction patterns will require enhanced performance to improve specificity of detection and dynamic range. To further extend the utility of DNA microarray-based approaches we present a high-performance tag microarray procedure that enables probe-based analysis of as little as 100 target cDNA molecules, and with a linear dynamic range close to 10(5). Furthermore, the protocol radically decreases the risk of cross-hybridization on microarrays compared to current approaches, and it also allows for quantification by single-molecule analysis and real-time on-chip monitoring of rolling-circle amplification. We provide proof of concept for microarray-based measurement of both mRNA molecules and of proteins, converted to tag DNA sequences by padlock and proximity probe ligation, respectively.
A fully integrated microfluidic genetic analysis system with sample-in–answer-out capability (2006)

We describe a microfluidic genetic analysis system that represents a previously undescribed integrated microfluidic device capable of accepting whole blood as a crude biological sample with the endpoint generation of a genetic profile. Upon loading the sample, the glass microfluidic genetic analysis system device carries out on-chip DNA purification and PCR-based amplification, followed by separation and detection in a manner that allows for microliter samples to be screened for infectious pathogens with sample-in-answer-out results in < 30 min. A single syringe pump delivers sample/reagents to the chip for nucleic acid purification from a biological sample. Elastomeric membrane valving isolates each distinct functional region of the device and, together with resistive flow, directs purified DNA and PCR reagents from the extraction domain into a 550-nl chamber for rapid target sequence PCR amplification. Repeated pressure-based injections of nanoliter aliquots of amplicon (along with the DNA sizing standard) allow electrophoretic separation and detection to provide DNA fragment size information. The presence of Bacillus anthracis (anthrax) in 750 nl of whole blood from living asymptomatic infected mice and of Bordetella pertussis in 1 microl of nasal aspirate from a patient suspected of having whooping cough are confirmed by the resultant genetic profile.
Surface light fields for 3D photography (2000)

A surface light field is a function that assigns a color to each ray originating on a surface. Surface light fields are well suited to constructing virtual images of shiny objects under complex lighting conditions. This paper presents a framework for construction, compression, interactive rendering, and rudimentary editing of surface light fields of real objects. Generalization of vector quantization and principal component analysis are used to construct a compressed representation of an object's surface light field from photographs and range scans. A new rendering algorithm achieves interactive rendering of images from the compressed representation, incorporating view-dependent geometric level-of-detail control. The surface light field representation can also be directly edited to yield plausible surface light fields for small changes in surface geometry and reflectance properties.
C5a and Thromboxane Generation Associated with Pulmonary Vaso- and Broncho-constriction during Protamine Reversal of Heparin (1987)

The authors conducted a study in humans to determine the mediators associated with acute pulmonary vaso- and broncho-constriction occurring episodically with protamine reversal of heparin anticoagulation. Of 48 adult patients investigated prospectively after termination of cardiopulmonary bypass, two presented a sudden increase of airway pressure, acute pulmonary hypertension, and systemic hypotension 1-3 min after right atrial protamine injection. In these two subjects, plasma levels of C5a increased from 0.7 and 2.2 to 9.8 and 9.9 ng/ml, respectively, and thromboxane B2 increased from 0.26 and 0.34 to 7.5 and 16.2 ng/ml 1 minute after drug injection. A third subject not identified prospectively had an identical reaction and mediator profile (C5a, 10.2 ng/ml; TxB2, 18.6 ng/ml at 1 min). The plasma levels of these mediators were unchanged in the remaining patients (C5a, 0.7 +/- 1.1 [x +/- S.D.] to 0.6 +/- 0.9 ng/ml; TxB2, 0.16 +/- 0.12 to 0.15 +/- 0.07 ng/ml). Plasma histamine was not involved in this type of reaction, but increased from 0.7-10.4 ng/ml in a fourth patient who became hypotensive without acute pulmonary hypertension, bronchoconstriction, or elevation of C5a or TxB2. The authors' data indicate that the generation of high plasma levels of C5a anaphylatoxins and thromboxane is associated with pulmonary vaso- and broncho-constriction induced by protamine reversal of heparin in humans.
Construction and characterization of a herpes simplex virus type 1 mutant unable to transinduce immediate-early gene expression (1989)

A herpes simplex virus mutant, in1814, possessing a 12-base-pair insertion in the gene encoding the transinducing factor Vmw65 has been constructed. The insertion abolished the ability of Vmw65 to transinduce immediate-early (IE) gene expression and to form a protein-DNA complex with cell proteins and the IE-specific regulatory element TAATGAGAT. Accumulation of IE RNA 1 and 2 was reduced four- to fivefold in in1814-infected cells, but the level of IE RNA 4 was reduced only by twofold, and IE RNA 3 was unaffected. Mutant in1814 had a high particle/PFU ratio, but many of the particles, although unable to form plaques, were capable of normal participation in the early stages of infection at high multiplicity of infection. The defect of in1814 was overcome partially by transfection of a plasmid encoding the IE protein Vmw110 into cells prior to titration and by prior infection with ultraviolet light-inactivated herpes simplex virus. Mutant in1814 was essentially avirulent when injected into mice. The results demonstrate that transinduction of IE transcription by Vmw65 is important at low multiplicity of infection and in vivo but that at high multiplicity of infection the function is redundant.
Protein traffic in human synovial effusions (1987)

Concentrations of 5 marker proteins were measured in synovial fluid and serum samples from knee effusions of 11 patients with rheumatoid arthritis and 9 with osteoarthritis. Indirect determinations of synovial plasma flow and lymphatic drainage were obtained by measuring iodide clearance (ml/minute) and radio-albumin clearance (ml/minute). Together with protein concentrations, these determinations allowed us to calculate: the flux of each marker protein through synovial tissues (mg/minute); the volume of plasma cleared by synovium per unit time (ml/minute); and the fractional extraction per passage through the synovial microcirculation (protein permeance). These measures differed substantially between rheumatoid arthritis and osteoarthritis patient populations and quantified the severity of the microvascular lesion in rheumatoid synovitis.
Tissue disaggregation of human renal cell carcinoma with further isopyknic and isokinetic gradient purification. (1980)

Five different human renal cell carcinomas were disaggregated with three combinations of enzymes. Significant tumor heterogeneity in response to the enzyme disaggregation was observed. A combination of collagenase (0.5 mg/ml) and trypsin (0.25%) was then used for routine disaggregation of 11 additional tumors. The viability of cells in suspension ranged between 63 and 98% with a mean viability of 83.2 +/- 10.7% (S.D.). The mean yield of total viable cells per g of tissue was 17.4 +/- 14.2 x 10(6). Tumor cells were further fractionated in isopyknic and isokinetic gradients. After isokinetic sedimentation, significant heterogeneity among tumors was seen, but lymphocytes were consistently located in Fraction 7 +/- 2, whereas tumor cells were predominantly in Fraction 22 +/- 1. Malignant epithelial cells were enriched to a 85.8 +/- 9.4% (range, 69.5 to 92.5%) purity by isokinetic gradient centrifugation. Lymphocytes could be successfully separated from tumor cells using an isopyknic gradient. Controlled rate freezing of cells provided material for repeated experiments while short-term tissue culture prior to cell separation increased the proportion of viable cells in the suspension. Disaggregation of human renal cell carcinoma and separation of malignant cells from tumor lymphocytes provides the foundation for characterizing these tumors biochemically and for analyzing hormonal responsiveness and the immunological characteristics of these tumors in vitro.
Primary structure of the major allergen of yellow mustard (Sinapis alba L.) seed, Sin a I (1988)

Sin a I, a 2-S albumin from the seeds of yellow mustard, is herein described as the major allergen of these seeds. This protein is composed of two disulfide-linked polypeptide chains of 39 and 88 amino acids, whose primary structures are reported. The Sin a I allergen is found to be related to other low-molecular-mass albumins, such as those isolated from rapeseed, castor bean and Brazil nut. Additional structural similarity has also been found between the glutamine-rich large chain of Sin a I and a proline-rich zein, a gliadin, and trypsin and alpha-amylase inhibitors isolated from the seeds of several monocotyledons. Internal amino acid sequence similarity has been detected at both termini of the small and large chains of Sin a I and involves the location of proline and glycine residues at similar positions in relation to the processing cleavage sites. Prediction of secondary structure, based on the amino acid sequences of the mature chains of the mustard allergen, indicates that the precursor polypeptide is cleaved at regions showing a high beta-turn probability. This is also observed with the amino acid sequence deduced from the rapeseed napin gene nucleotide sequence.
Heat Shock Protein 70 Confers Cardiovascular Protection During Endotoxemia via Inhibition of Nuclear Factor-κB Activation and Inducible Nitric Oxide Synthase Expression in the Rostral Ventrolateral Medulla (2004)

We conclude that HSP70 confers protection against sepsis-related circulatory fatality via inhibition of iNOS gene expression in the RVLM through prevention of NF-kappaB activation in cellular processes that include prevention of IkappaB kinase activation and inhibition of IkappaBalpha degradation.
Disulfide pairings in geographutoxin I, a peptide neurotoxin from Conus geographus (1990)

The three intramolecular disulfide linkages of geographutoxin I, a peptide neurotoxin isolated from the venom of the marine snail Conus geographus, were examined by a novel method for determination of the positions of disulfide linkages in peptides [(1989) Bull. Chem. Soc. Jp. 62, 1986-1994]. The disulfide bridges were found to be between Cys3 and Cys15, Cys4 and Cys20, and Cys21, indicating that geographutoxin I has a rigid conformation consisting of three loops stabilized by these three disulfide linkages.
Centrifugation and capillarity integrated into a multiple analyte whole blood analyser (1995)

A unique clinical chemistry analyser is described which processes 90 mul of whole blood (fingerstick or venous) into multiple aliquots of diluted plasma and reports the results of 12 tests in 14 min. To perform a panel of tests, the operator applies the unmetered sample directly into a single use, 8 cm diameter plastic rotor which contains the required liquid diluent and dry reagents. Using centrifugal and capillary forces, the rotor meters the required amount of blood, separates the red cells, meters the plasma, meters the diluent, mixes the fluids, distributes the fluid to the reaction cuvettes and mixes the reagents and the diluted plasma in the cuvettes. The instrument monitors the reagent reactions simultaneously using nine wavelengths, calculates the results from the absorbance data, and reports the results.
A novel approach to multi-criteria inverse planning for IMRT (2007)

Treatment plan optimization is a multi-criteria process. Optimizing solely on one objective or on a sum of a priori weighted objectives may result in inferior treatment plans. Manually adjusting weights or constraints in a trial and error procedure is time consuming. In this paper we introduce a novel multi-criteria optimization approach to automatically optimize treatment constraints (dose-volume and maximum-dose). The algorithm tries to meet these constraints as well as possible, but in the case of conflicts it relaxes lower priority constraints so that higher priority constraints can be met. Afterwards, all constraints are tightened, starting with the highest priority constraints. Applied constraint priority lists can be used as class solutions for patients with similar tumour types. The presented algorithm does iteratively apply an underlying algorithm for beam profile optimization, based on a quadratic objective function with voxel-dependent importance factors. These voxel-dependent importance factors are automatically adjusted to reduce dose-volume and maximum-dose constraint violations.
Facile Synthesis of 6-Hydroxyindole and 6-Methoxyindole via Regioselective Friedel-Crafts Acylation and Baeyer-Villiger Oxidation (1994)

A facile synthesis of 6-hydroxyindole and 6-methoxyindole starting from indole is described. Regioselective chloroacetylation of 1-pivaloylindole followed by Baeyer-Villiger oxidation offers introduction of an oxygen function into the 6-position of the indole ring. Deacylation of 6-chloroacetyl-1-pivaloylindole gives 6-hydroxyindole which is converted to 6-methoxyindole by methylation. The overall yield of 6-hydroxyindole and 6-methoxyindole from indole is 54 and 37%, respectively.
Real-Time PCR for Diagnosis of Human Bocavirus Infections and Phylogenetic Analysis (2007)

The human bocavirus (hBoV) was first described in 2005 in respiratory tract samples. The clinical relevance of hBoV is still unclear. The aim of our study was to establish a real-time PCR assay for the detection and quantification of hBoV DNA, to apply the real-time assay for the analysis of stool and serum samples for the presence of hBoV DNA, and to perform a phylogenetic analysis of the hBoV positive samples. A total of 834 nasopharyngeal aspirates (NPA), 10 serum samples, and 31 stool samples of children with acute respiratory diseases were retrospectively tested. For phylogenetic analysis, 968 bp of the VP2 gene were sequenced from 69 hBoV-positive NPA samples. The qualitative results of the real-time hBoV PCR were in good agreement with a conventional hBoV PCR. We found that 12% of the NPA were positive for hBoV DNA. The median viral load in the NPA was 4.9 x 10(3) copies/ml (range, 2.7 x 10 degrees to 1.5 x 10(11) copies/ml). There was no difference of the hBoV load in NPA between children with or without known coinfection, but the load was significantly higher in children with bronchitis than in children with the diagnosis of febrile seizures. hBoV DNA was found in 1 of 10 serum samples and in 14 of 31 stool samples. hBoV sequence identity was >99% in the VP2 region. In conclusion, hBoV DNA can be found in NPA samples at very high titers. In addition to being found in the respiratory tract, hBoV was found in stool samples. The clinical relevance of these findings remains to be determined.
Performance of an LDPC-coded frequency-hopping OFDMA system based on resource allocation in the uplink (2005)

An LDPC-coded frequency hopping OFDMA system is proposed for the uplink of cellular systems, where the frequency hopping is based on a resource block (RB) for coherent demodulation. For the system, two different RB types are considered, either for better intercell interference averaging capability or for better channel estimation performance. A turbo receiver with iterative channel estimation and decoding is also proposed to provide better channel estimation performance without boosting the pilot power. The performance is evaluated both in single- and multi-cell environments to investigate the effect of the interference on the overall system performance.
Distal Microcirculatory Protection During Percutaneous Coronary Intervention in Acute ST-Segment Elevation Myocardial Infarction<SUBTITLE>A Randomized Controlled Trial</SUBTITLE> (2005)

A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.
Path Error Measurement and Compensation of Precision Working Table (2008)

Ultra-precision machining is a key technology developed with the process of manufacturing. At the point of micro driving, regulating the accuracy of machine tool with smart materials that can generate micro movement to an extent of nanometer level is often introduced to satisfy the required precision. Aiming at reducing the path error of a precision working table driven by an AC servo motor, the measurement of the dynamical characteristics of the system was carried on by a laser interferometer. Error signal was acquired, decomposed and then analyzed to match with various phenomena, such as backlash, stick-slip and self-excited vibration during the motor processes at different speeds. Based on this, a giant magnetostrictive actuator(GMA) was designed to act as a compensator to minimize the typical path error. The hysteresis nonlinearity of the GMA was controlled effectively by PID control techniques. Experimental results showed great improvements of the tracking accuracy, which proved the feasibility of the proposed method.
A 2.4 GHz single chip transceiver (2002)

A GaAs transceiver circuit that includes all transmit and receive switching, amplification, frequency conversion and level shifting is described. An on-chip oscillator is also provided. Low receive current of 30 mA from a +5-V supply and a standby current of less than 0.5 mA make this an ideal component for battery-powered operation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis of Optically Active 2-Alkyl-3,4-iminobutanoic Acids. β-Amino Acids Containing an Aziridine Heterocycle (2001)

All four stereoisomers of 2-alkyl-3,4-iminobutanoic acid, a novel class of beta-amino acids bearing a chemically versatile aziridine ring, were synthesized starting with aspartic acid. The synthetic strategy involves the introduction of an alkyl group at the beta-position of fully protected optically active aspartic acid followed by the construction of an aziridine ring making use of the alpha-carboxylate and alpha-amino groups. The alpha-carboxylate was reduced to the corresponding alcohol, which was then subjected to cyclization to form an aziridine ring with the N-protected amino group. Removal of the protection groups yielded the target compounds.