gebhart/patrepeval huggingface dataset:
Enabling Technology:High-throughput genotyping assay approaches (2000)

High-throughput genotyping approaches are being developed to meet the demands of pharmacogenomnics, where numerous individuals are studied with thousands of single nucleotide polymorphism (SNP) markers. All non-gel-based genotyping approaches achieve allelic discrimination by one of four mechanisms: allele-specific hybridisation, allele-specific primer extension, allele-specific oligonucleotide ligation and allele-specific cleavage of a flap probe. By combining one of these allelic discrimination mechanisms with either a homogeneous or solid-phase reaction format and a detection method such as fluorescence intensity, fluorescence polarisation or mass spectrometry, a number of viable high-throughput genotyping methods have been developed and are being readied for routine use. With the biochemistry for robust genotyping in place, good engineering solutions are needed to make high-throughput genotyping a reality.
Procalcitonin as a Marker for the Detection of Bacteremia and Sepsis in the Emergency Department (2011)

Rapid diagnosis of bloodstream infections (BSIs) in the emergency department (ED) is challenging, with turnaround times exceeding the timeline for rapid diagnosis. We studied the usefulness of procalcitonin as a marker of BSI in 367 adults admitted to our ED with symptoms of systemic infection. Serum samples obtained at the same time as blood cultures were available from 295 patients. Procalcitonin levels were compared with blood culture results and other clinical data obtained during the ED visit. Procalcitonin levels of less than 0.1 ng/mL were considered negative; all other levels were considered positive. In 16 patients, there was evidence of BSI by blood culture, and 12 (75%) of 16 patients had a procalcitonin level of more than 0.1 ng/mL. In 186 (63.1%) of 295 samples, procalcitonin values were less than 0.1 ng/mL, and all were culture negative. With a calculated threshold of 0.1475 ng/mL for procalcitonin, sensitivity and specificity for the procalcitonin assay were 75% and 79%, respectively. The positive predictive value was 17% and the negative predictive value 98% compared with blood cultures. Procalcitonin is a useful marker to rule out sepsis and systemic inflammation in the ED.
The anti‐CD20 antibody rituximab augments the immunospecific therapeutic effectiveness of an anti‐CD19 immunotoxin directed against human B‐cell lymphoma (2006)

The chimaeric anti-CD20 antibody rituximab (Rituxan) sensitises lymphoma cells to small molecule cytotoxic drugs and to protein toxins. We have explored the augmentive effect of rituximab on the anti-CD19 immunotoxin BU12-SAPORIN in a model of human lymphoma. Intact rituximab and its F(ab)2 derivative both augmented the immunospecific protein synthesis inhibitory effects of BU12-SAPORIN in a complement-independent manner. A combination of rituximab + BU12-SAPORIN completely abolished the proliferation of Ramos cells in vitro and also induced a significantly greater degree of apoptosis in these cells. Treatment with rituximab, BU12-SAPORIN or a combination of both induced poly(ADPribose) polymerase and caspase 3 cleavage, although this was always consistently greater in combination-treated cells. zVAD almost completely inhibited apoptosis in rituximab- or BU12-SAPORIN-treated cells but only partially in combination-treated cells. In severe combined immunodeficient (SCID)-Ramos mice the combination of rituximab + BU12-SAPORIN was significantly better therapeutically than either single agent. The immunological fidelity of the therapeutic effect because of combination treatment was demonstrated through the failure of rituximab to augment an irrelevant anti-CD7 immunotoxin. The therapeutic efficacy of rituximab and combination treatment was reduced in SCID-Ramos mice depleted of serum complement while natural killer cell depletion failed to show any convincing role for antibody-dependent cellular cytotoxicity. This study shows a clear therapeutic advantage from using rituximab to immunospecifically augment immunotoxin cytotoxicity warranting further investigation.
Exploring interactive curve and surface manipulation using a bend and twist sensitive input strip (1999)

We explore a new input device and a set of interaction techniques to facilitate direct manipulation of curves and surfaces. The input device, called ShapeTapeTM, is a continuous bend and twist sensitive strip that encourages manipulations that use both hands and, at times, all 10 fingers. We explore this input and interaction design space through a set of usage scenarios for creating and editing curves and surfaces as well as consider general interactions such as command access and camera controls. This investigation is carried out by extending Alias|wavefront’s modeling and animation package, Maya. CR
Comparison of preservation media and freezing conditions for storage of specimens of faeces (1989)

To evaluate the long-term recoverability of bacterial enteropathogens, two freezing conditions (deep-freezing at -70 degrees C and liquid nitrogen) and three preservation media (Cary-Blair, Amies, and buffered glycerol-saline) were tested. These were compared with storage in containers with no preservation medium and refrigeration at 4 degrees C. At 4 degrees C, viability of organisms could not be consistently maintained beyond one month; Cary-Blair medium generally gave the best results and storage without preservation medium was the least efficient. Storage in liquid nitrogen and deep-freezing effectively preserved all organisms except Campylobacter jejuni for the entire period of study (12 months). There was no difference between the various preservation media, or between storage with or without medium. Storage in preservation medium was superior to storage without such supplement for C. jejuni. We conclude that most enteropathogens survive in faecal specimens for as long as 12 months when stored at very low temperatures (-70 degrees C) whether or not preservation media are used.
Cloning and nucleotide sequence of a mouse erythrocyte beta-spectrin cDNA (1987)

A rabbit monospecific antibody for mouse beta-spectrin was used to screen a mouse anemic spleen cDNA expression library. A mouse beta- spectrin cDNA clone was isolated and identified by its ability to make mouse beta-spectrin-like antigens in Escherichia coli. This clone was used to probe total RNA from various mouse tissues. Anemic spleen RNA showed two strongly hybridizing RNA species of approximately 6 and 8 kb. Two very faintly hybridizing bands of about 6 kb and 10 kb could also be seen in total mouse brain RNA. All of these bands could be detected after hybridization under both stringent and nonstringent conditions. This suggests that erythroid beta-spectrin may also be expressed in the brain. No bands could be detected in kidney, liver, or spleen RNA. Southern blot analysis of mouse genomic DNA showed a single hybridizing band after digestion with several restriction endonucleases even under nonstringent conditions. Nucleotide sequencing of the cDNA insert revealed almost complete identity between the N-terminus of the deduced amino acid sequence of the cDNA clone and the C-terminal 15 amino acids of a peptide derived from the beta-8 repeat unit of human erythrocyte beta-spectrin. The deduced amino acid sequence contained most of the conserved amino acids characteristic of the 106 amino acid repeat unit first found in human alpha-spectrin and thus provides the first evidence for a complete 106 amino acid repeat unit structure in beta-spectrin.
Relationship between magnetic circumferential orientation and magnetic thermal stability (1999)

Magnetic recording media with a capacity exceeding 40Gbt/in2 must have not only high signal-to-noise ratio (S/Nm) but also magnetic thermal stability.
Fabrication and characterization of poly(methylmethacrylate) microfluidic devices bonded using surface modifications and solvents (2005)

The fabrication of polymer microchips allows inexpensive, durable, high-throughput and disposable devices to be made. Poly(methylmethacrylate) (PMMA) microchips have been fabricated by hot embossing microstructures into the substrate followed by bonding a cover plate. Different surface modifications have been examined to enhance substrate and cover plate adhesion, including: air plasma treatment, and both acid catalyzed hydrolysis and aminolysis of the acrylate to yield carboxyl and amine-terminated PMMA surfaces. Unmodified PMMA surfaces were also studied. The substrate and cover plate adhesion strengths were found to increase with the hydrophilicity of the PMMA surface and reached a peak at 600 kN m(-2) for plasma treated PMMA. A solvent assisted system has also been designed to soften less than 50 nm of the surface of PMMA during bonding, while still maintaining microchannel integrity. The extent to which both surface modifications and solvent treatment affected the adhesion of the substrate to the cover plate was examined using nanoindentation methods. The solvent bonding system greatly increased the adhesion strengths for both unmodified and modified PMMA, with a maximum adhesion force of 5500 kN m(-2) achieved for unmodified PMMA substrates. The bond strength decreased with increasing surface hydrophilicity after solvent bonding, a trend that was opposite to what was observed for non-solvent thermal bonding.
Electronic diaries for monitoring chronic pain: 1-year validation study (2001)

Electronic data collection for monitoring pain has become increasingly popular in clinical research. However, no direct comparison has been made between electronic diaries and self-report paper diaries or phone interviews. We asked 36 patients with chronic low back pain to monitor their pain for 1 year; 20 of them used both a palmtop computer and paper diaries, and 16 used paper diaries alone. All patients were called once a week and asked to rate their pain. Regression analyses with a measurement error model were run on hourly pain scores recorded by both palmtop computer and paper diaries. Ratings of pain intensity were highly reliable between data recorded with a palmtop computer and with data from paper diaries. Patients who monitored their pain with the palmtop computer entered data on average 6.75 times a week and were 89.9% compliant with daily monitoring throughout the year. Two-way messaging available through the palmtop computer seemed to encourage continued use of the device. Internal consistency of reporting and correlations with phone reports and standardized measures were highly significant, suggesting that data from electronic diaries are both reliable and valid. Patients using electronic diaries preferred them to paper diaries and showed much higher rates of compliance and satisfaction over the 1-year trial.
Mitochondrial PKCε and Mitochondrial ATP-Sensitive K + Channel Copurify and Coreconstitute to Form a Functioning Signaling Module in Proteoliposomes (2006)

Mitochondria are key mediators of the cardioprotective signal and the mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) plays a crucial role in originating and transmitting that signal. Recently, protein kinase C epsilon (PKC epsilon) has been identified as a component of the mitoK(ATP) signaling cascade. We hypothesized that PKC epsilon and mitoK(ATP) interact directly to form functional signaling modules in the inner mitochondria membrane. To examine this possibility, we studied K+ flux in liposomes containing partially purified mitoK(ATP). The reconstituted proteins were obtained after detergent extraction of isolated mitochondria, 200-fold purification by ion exchange chromatography, and reconstitution into lipid vesicles. Immunoblot analysis revealed the presence of PKC epsilon in the reconstitutively active fraction. Addition of the PKC activators 12-phorbol 13-myristate acetate, hydrogen peroxide, and the specific PKC epsilon peptide agonist, psi epsilonRACK, each activated mitoK(ATP)-dependent K+ flux in the reconstituted system. This effect of PKC epsilon was prevented by chelerythrine, by the specific PKC epsilon peptide antagonist, epsilonV(1-2), and by the specific mitoK(ATP) inhibitor 5-hydroxydecanoate. In addition, the activating effect of PKC agonists was reversed by exogenous protein phosphatase 2A. These results demonstrate persistent, functional association of mitochondrial PKC epsilon and mitoK(ATP).
Novel strategies for the site-specific covalent labelling of nucleic acids (2008)

To broaden the scope of applications in DNA nano- and biotechnology, material science, diagnostics and molecular recognition the functionalization of DNA is of utmost importance. In the last decade many new methods have been developed to achieve this goal. Apart from the direct chemical synthesis of modified DNA by automated phosphoramidite chemistry incorporation of labelled triphosphates and the post-synthetic labelling approach evolved as valuable methods. New bioorthogonal reactions as Diels-Alder, click and Staudinger ligations pushed forward the post-synthetic approach as new insights into DNA polymerase substrate specificity allowed generation and amplification of labelled DNA strands. These novel developments are summarized herein.
CHEYNE-STOKES RESPIRATION IN PATIENTS WITH CONGESTIVE HEART FAILURE: CAUSES AND CONSEQUENCES (2005)

Cheyne-Stokes respiration is a form of periodic breathing in which central apneas and hypopneas alternate with periods of hyperventilation, producing a waxing and waning pattern of tidal volume. This review focuses on the causes and consequences of Cheyne-Stokes respiration in patients with congestive heart failure, in whom the prevalence is strikingly high and ranges from 30% to 50%. Several factors have been implicated in the genesis of Cheyne-Stokes respiration, including low cardiac output and recurrent hypoxia. The key pathophysiological mechanism triggering Cheyne-Stokes respiration is hyperventilation and low arterial CO2 (PaCO2) that when below the apneic threshold triggers a central apnea. Hyperventilation is associated with pulmonary congestion, and Cheyne-Stokes respiration is more prone to occur during sleep, when the respiratory system is mainly dependent on chemical control. It is associated with recurrent dips in oxygen saturation and arousals from sleep, with oscillations in blood pressure and heart rate, sympathetic activation and increased risk of ventricular tachycardia. Cheyne-Stokes respiration is an independent marker of poor prognosis and may participate in a vicious cycle, further stressing the failing heart.
Exploring the Use of Antisense, Enzymatic RNA Molecules (Ribozymes) as Therapeutic Agents (1991)

Antisense catalytic RNAs that specifically base-pair with and cleave target RNA sequences have potential for use as therapeutic agents against viral as well as endogenous gene expression. With the ultimate goal of developing anti-human immunodeficiency virus type 1 (HIV-1) ribozymes for therapeutic use, we have been exploring ways to improve upon the functional activity of ribozymes in living cells. This is being done by the systematic exploration of parameters that affect antisense, and hence ribozyme, function. These include target accessibility, stability of the catalyst, methods for delivery, and intracellular localization of the ribozyme. In addition, we have been examining the kinetic consequences of having extra, nontargeted sequences appended to the ribozyme flanking sequences. Perhaps the single most important consideration for ribozyme effectiveness in an intracellular environment is the accessibility of the target RNA for cleavage. By exploiting the mechanisms by which naturally occurring antisense RNAs interact with their target sequences, we hope to be able to address this problem of targeting and fully capitalize upon the potential of ribozymes as therapeutic agents.
Cadherin‐like receptor binding facilitates proteolytic cleavage of helix α‐1 in domain I and oligomer pre‐pore formation of Bacillus thuringiensis Cry1Ab toxin (2002)

Cry toxins form lytic pores in the insect midgut cells. The role of receptor interaction in the process of protoxin activation was analyzed. Incubation of Cry1Ab protoxin with a single chain antibody that mimics the cadherin-like receptor and treatment with Manduca sexta midgut juice or trypsin, resulted in toxin preparations with high pore-forming activity in vitro. This activity correlates with the formation of a 250 kDa oligomer that lacks the helix alpha-1 of domain I. The oligomer, in contrast with the 60 kDa monomer, was capable of membrane insertion as judged by 8-anilino-1-naphthalenesulfonate binding. Cry1Ab protoxin was also activated to a 250 kDa oligomer by incubation with brush border membrane vesicles, presumably by the action of a membrane-associated protease. Finally, a model where receptor binding allows the efficient cleavage of alpha-1 and formation of a pre-pore oligomeric structure that is efficient in pore formation, is presented.
Volumetric 3D displays and application infrastructure (2005)

Volumetric displays produce volume-filling three-dimensional imagery. Each volume element or voxel in a 3D scene emits visible light from the region in which it appears. Given their ability to project volume-filling autostereoscopic imagery, these displays are being adopted in fields as diverse as medical imaging, mechanical computer-aided design, and military visualization. The author uses the term autostereoscopic to describe a display property that lets observers experience a 3D effect without requiring any additional eyewear. Vendors are developing software that lowers the barrier to adoption by providing compatibility with new and legacy applications. At least one firm is developing a display-dependent visualization environment with the aim of 3D displays overall. The widespread adoption of volumetric 3D displays requires the ability to integrate tightly into today's visualization software.
A muscle model for animation three-dimensional facial expression (1987)

The development of a parameterized facial muscle process, that incorporates the use of a model to create realistic facial animation is described.Existing methods of facial parameterization have the inherent problem of hard-wiring performable actions. The development of a muscle process that is controllable by a limited number of parameters and is non-specific to facial topology allows a richer vocabulary and a more general approach to the modelling of the primary facial expressions.A brief discussion of facial structure is given, from which a method for a simple modelling of a muscle process that is suitable for the animation of a number of divergent facial types is described.
T4 phage ribonucleotide reductase. Allosteric regulation in vivo by thymidine triphosphate. (1991)

Based upon analyses of purified enzyme preparations, T4 bacteriophage-coded ribonucleotide reductase is considered to be relatively insensitive to control by allosteric inhibition. However, two factors suggest that CDP reduction to dCDP is feedback-controlled by dTTP in infected cells. First, the pool of 5-hydroxymethyldeoxycytidine triphosphate, which expands manyfold upon infection by a dCMP deaminase-deficient T4 mutant, shrinks to near-normal levels as a consequence of dTTP accumulation, and ribonucleotide reductase is the only apparent control point. Second, analysis of mutagenesis by 5-bromodeoxyuridine suggests that most induced mutations result from localized pool depletion of 5-hydroxymethyl-dCTP at replication sites, as if 5-bromo-dUTP were behaving like dTTP in inhibiting the CDP reductase activity of the phage enzyme. We found that CDP reductase activity in crude extracts of T4 phage-infected bacteria is sensitive to inhibition by either dTTP or 5-bromo-dUTP, at concentrations as low as 0.01 mM. However, in partially purified enzyme preparations that sensitivity is lost. Although we don't know the basis for this loss of feedback sensitivity, the results suggest that kinetic properties of enzymes in intact cells are determined by the cellular milieu in ways not apparent from analysis of purified enzymes.
Isolation and amino acid sequence of cyclophilin. (1986)

Cyclophilin, a specific cyclosporin A-binding protein has been purified to homogeneity from human spleen and bovine thymus cytosol. Purification of bovine and human cyclophilin was achieved by large scale molecular filtrations, Matrex Blue A affinity chromatography, preparative isoelectric focusing, phenyl-Sepharose chromatography, and weak cation exchange high performance liquid chromatography. Major and minor bovine and human cyclophilin isoforms were identified and found to have an apparent molecular weight of 17,000 and very similar amino acid compositions. The complete amino acid sequence of the major bovine cyclophilin isoform (163 residues, Mr 17,737) was determined from analysis of peptides derived by endoproteinase lysine C and cyanogen bromide cleavage and an NH2-terminal sequence of the intact protein. The first 72 NH2-terminal residues of the major human cyclophilin isoform were also determined and found to be identical to bovine cyclophilin. A computer search of cyclophilin with the National Biomedical Research Foundation database (3,182 protein sequences) did not detect any significant homologies. Cyclophilin represents a new class of abundant, highly conserved cytosolic proteins that probably play an important role in the regulation of T lymphocyte activation and proliferation.
Diagram Technique for Nonlinear Optical Spectroscopy in the Fast Electronic Dephasing Limit (2000)

Abstract We show that applying the double‐sided Feynman diagrams to systems with fast electronic dephasing opens up new possibilities for using this technique in resonance nonlinear optical spectroscopy. The novel potentials are including non‐perturbative system‐bath interactions (non‐Markovian relaxation) and the summation of diagrams. The last procedure enables us to obtain new equations for a nonperturbative description of the light‐matter interaction.
Combined Transdermal Testosterone Gel and the Progestin Nestorone Suppresses Serum Gonadotropins in Men (2009)

Transdermal NES gel alone had gonadotropin suppression activity. Combined transdermal NES (6 or 8 mg) plus T gel demonstrated safe and effective suppression of gonadotropins, justifying a longer-term study of this combination for suppression of spermatogenesis.