gebhart/patrepeval huggingface dataset:
Multiple presentation of foreign peptides on the surface of an RNA-free spherical bacteriophage capsid (1993)

We have produced a plasmid expression vector for the coat protein of RNA bacteriophage MS2. The vector has been modified to introduce a unique KpnI restriction site within the coat protein gene at a site corresponding to the most radially distant feature of the bacteriophage capsid, namely the top of the N-terminal beta-hairpin (between residues 15 and 16). Insertion of DNA oligonucleotides at this site allows the production of chimeric MS2 coat proteins having foreign peptide sequences expressed as the central part of the hairpin. We have produced chimeras with a number of different peptide sequences (up to 24 amino acids in length) chosen because of their known antigenic properties. The chimeric coat proteins self-assemble into largely RNA-free phage-like capsids in Escherichia coli and can be easily disassembled and reassembled in vitro. Such peptide-presenting particles may have a number of biotechnological applications, including use as a cost-effective, synthetic vaccine. We have tested the antigenicity of one such construct in vivo in mice and have shown that these particles are immunogenic and that antibody titres against the inserted peptide epitope can be obtained.
Rapid fabrication of polymer microfluidic systems for the production of artificial lipid bilayers (2005)

A polymer microfluidic device has been fabricated using rapid prototyping techniques. The device was built to allow the formation and subsequent investigation of artificial bilayer lipid membranes (BLMs). A simple dry film photoresist stamp was used to hot emboss microfluidic channels into PMMA films. Laser micromachining was employed to form an aperture through the PMMA channels, across which the BLM was later formed. The dry film photoresist was also used as a simple etch mask for the deep etching of glass substrates in buffered HF solutions, which was used in this work for the production of glass embossing stamps. We show that bilayer films can be successfully produced across laser micromachined apertures in PMMA films.
Design of Selectively Activated Anticancer Prodrugs: Elimination and Cyclization Strategies (2002)

Cancer chemotherapy is associated with severe side effects which may be reduced by selective liberation, at the tumour site, of a cytotoxic agent from a non-toxic prodrug. Several strategies are used to achieve the required selective activation: with enzymes which are present in higher concentration in, or close, to the tumour (beta-glucuronidase, plasmin), with enzymes covalently linked to a macromolecular carrier able to recognize antigen positive cancer cells (ADEPT: Antibody Directed Enzyme Prodrug Therapy) or with reductive processes which are favoured in an hypoxic environment. Most of the prodrugs include a linker (or spacer) between the trigger and the drug (or effector). The design of such linkers is crucial in order to achieve a fast drug liberation under physiological conditions. The linker groups may be classified in two categories based on elimination or cyclization processes. The advantages and the limitations of each strategy are discussed.
Use of geographical meta-data in ASR language and acoustic models (2010)

The query distribution, in the speech recognition applications of directory assistance (DA) and voice-search, depends on the customer's location. This motivates the research on query models conditioned on the user location, here denoted as local models. We describe and test our methods for the estimation of local models with various degrees of spacial “granularity”, for the recognition of city-state (sub-task of DA) and for the recognition of business listings, spoken over iPhones in a nation-wide business-listing voice-search service. Our local language models improve the accuracy of city-state by 2.4% absolute (32% relative error reduction), and of voice-search by 2.2% (7% relative).
Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro (2006)

Human embryonic stem cells (hESCs) have enormous potential as a source of cells for cell replacement therapies and as a model for early human development. In this study we examined the differentiating potential of hESCs into hepatocytes in two- and three-dimensional (2D and 3D) culture systems. Embryoid bodies (EBs) were inserted into a collagen scaffold 3D culture system or cultured on collagen-coated dishes and stimulated with exogenous growth factors to induce hepatic histogenesis. Immunofluorescence analysis revealed the expression of albumin (ALB) and cytokeratin-18 (CK-18). The differentiated cells in 2D and 3D culture system displayed several characteristics of hepatocytes, including expression of transthyretin, alpha-1-antitrypsin, cytokeratin 8, 18, 19, tryptophan-2,3-dioxygenase, tyrosine aminotransferase, glucose-6-phosphatase (G6P), cytochrome P450 subunits 7a1 and secretion of alpha-fetoprotein (AFP) and ALB and production of urea. In 3D culture, ALB and G6P were detected earlier and higher levels of urea and AFP were produced, when compared with 2D culture. Electron microscopy of differentiated hESCs showed hepatocyte-like ultrastructure, including glycogon granules, well-developed Golgi apparatuses, rough and smooth endoplasmic reticuli and intercellular canaliculi. The differentiation of hESCs into hepatocyte-like cells within 3D collagen scaffolds containing exogenous growth factors, gives rise to cells displaying morphological features, gene expression patterns and metabolic activities characteristic of hepatocytes and may provide a source of differentiated cells for treatment of liver diseases.
A Prodrug Nanoparticle Approach for the Oral Delivery of a Hydrophilic Peptide, Leucine5-enkephalin, to the Brain (2012)

The oral use of neuropeptides to treat brain disease is currently not possible because of a combination of poor oral absorption, short plasma half-lives and the blood-brain barrier. Here we demonstrate a strategy for neuropeptide brain delivery via the (a) oral and (b) intravenous routes. The strategy is exemplified by a palmitic ester prodrug of the model drug leucine(5)-enkephalin, encapsulated within chitosan amphiphile nanoparticles. Via the oral route the nanoparticle-prodrug formulation increased the brain drug levels by 67% and significantly increased leucine(5)-enkephalin's antinociceptive activity. The nanoparticles facilitate oral absorption and the prodrug prevents plasma degradation, enabling brain delivery. Via the intravenous route, the nanoparticle-prodrug increases the peptide brain levels by 50% and confers antinociceptive activity on leucine(5)-enkephalin. The nanoparticle-prodrug enables brain delivery by stabilizing the peptide in the plasma although the chitosan amphiphile particles are not transported across the blood-brain barrier per se, and are excreted in the urine.
Genes dependent on zebrafishcyclops function identified by AFLP differential gene expression screen (2000)

Zebrafish cyclops (cyc) encodes a Transforming Growth Factor beta (TGFbeta) signaling factor closely related to mouse Nodal. By comparing amplified fragment length polymorphisms (AFLP) from cyc mutant and wild-type cDNA pools, we devised a differential gene expression screen to isolate genes whose expression is dependent on Cyc signaling. We report two genes not previously described in the zebrafish that were identified using this approach. The first gene, crestin, is expressed predominantly in premigratory and migrating neural crest cells during somitogenesis stages. crestin expression is reduced in cyc mutants initially but recovers by late somitogenesis. The second gene encodes the zebrafish homologue of the calcium-binding protein, calreticulin. Zebrafish calreticulin is highly expressed in the hatching gland and in the floor plate, tissues that are affected in cyc mutants. During gastrulation, calreticulin transcripts are found in the dorsal mesendoderm, in the same cells that express the cyc gene. Expression is reduced in cyc mutants and is abolished by the one-eyed pinhead (oep) mutation that is presumed to prevent Nodal signaling. The identification of calreticulin suggests that a differential screen between wild-type and mutant cDNA is a useful approach to reveal regulation of unexpected gene expression in response to cellular signals. genesis 26:86-97, 2000.
Revisiting concepts of visceral nociception in irritable bowel syndrome (2012)

Alterations in the modulatory balance of pro- and antinociceptive central processing of noxious peripheral input may serve as in integrative hypothesis for explaining visceral hypersensitivity in IBS. Nevertheless, it remains troublesome to estimate the contribution of central and peripheral factors in visceral hypersensitivity, posing a challenge in determining effective therapeutic entities.
Automatic Record Hash Coding and Linkage for Epidemiological Follow-up Data Confidentiality (1998)

A protocol is proposed to allow linkage of anonymous medical information within the framework of epidemiological follow-up studies. The protocol is composed of two steps; the first concerns the irreversible transformation of identification data, using a one-way hash function which is used after spelling processing. To avoid dictionary attacks, two large random files of keys, called pads, are introduced. The second step consists in the linkage of files rendered anonymous. The weight given to each linkage field is estimated by a mixture model, the likelihood of which being maximized with the Expectation and Maximization (EM) algorithm. The performance of this method has been assessed by comparing record linkage, based on exclusive use of the automatic procedure, with a manual linkage, obtained by the Burgundy Registry of Digestive Cancers. The result of the linkage of a file of 2,847 cancers with a file of 388,614 hospitalization stays in the Dijon university hospital showed a sensitivity of 97% and a specificity of 93%.
Image Processing Algorithms for Digital Mammography: A Pictorial Essay (2000)

Digital mammography systems allow manipulation of fine differences in image contrast by means of image processing algorithms. Different display algorithms have advantages and disadvantages for the specific tasks required in breast imaging-diagnosis and screening. Manual intensity windowing can produce digital mammograms very similar to standard screen-film mammograms but is limited by its operator dependence. Histogram-based intensity windowing improves the conspicuity of the lesion edge, but there is loss of detail outside the dense parts of the image. Mixture-model intensity windowing enhances the visibility of lesion borders against the fatty background, but the mixed parenchymal densities abutting the lesion may be lost. Contrast-limited adaptive histogram equalization can also provide subtle edge information but might degrade performance in the screening setting by enhancing the visibility of nuisance information. Unsharp masking enhances the sharpness of the borders of mass lesions, but this algorithm may make even an indistinct mass appear more circumscribed. Peripheral equalization displays lesion details well and preserves the peripheral information in the surrounding breast, but there may be flattening of image contrast in the nonperipheral portions of the image. Trex processing allows visualization of both lesion detail and breast edge information but reduces image contrast.
New Zealand Obstetricians' Management of Hypertension in Pregnancy A Questionnaire Survey (1989)

A questionnaire about the management of hypertension in pregnancy was sent to the 150 members of the Royal New Zealand College of Obstetricians and Gynaecologists. Sixty five out of a total of 77 replies were suitable for analysis. There was a wide variation in the criteria for diagnosis and the outpatient and inpatient investigation and treatment. The commonest drugs prescribed in imminent eclampsia were hydralazine as an anti-hypertensive, and diazepam or phenytoin as anticonvulsants. All clinicians practised aggressive management with induction of delivery if significant proteinuria complicated hypertension in pregnancy. Glucocorticoid therapy for the premature induction of fetal lung maturity in mothers and severe hypertension was considered beneficial by some, yet contraindicated by others.
On-Manifold Preintegration for Real-Time Visual--Inertial Odometry (2016)

Current approaches for visual-inertial odometry (VIO) are able to attain highly accurate state estimation via nonlinear optimization. However, real-time optimization quickly becomes infeasible as the trajectory grows over time; this problem is further emphasized by the fact that inertial measurements come at high rate, hence, leading to the fast growth of the number of variables in the optimization. In this paper, we address this issue by preintegrating inertial measurements between selected keyframes into single relative motion constraints. Our first contribution is a preintegration theory that properly addresses the manifold structure of the rotation group. We formally discuss the generative measurement model as well as the nature of the rotation noise and derive the expression for the maximum a posteriori state estimator. Our theoretical development enables the computation of all necessary Jacobians for the optimization and a posteriori bias correction in analytic form. The second contribution is to show that the preintegrated inertial measurement unit model can be seamlessly integrated into a visual-inertial pipeline under the unifying framework of factor graphs. This enables the application of incremental-smoothing algorithms and the use of a structureless model for visual measurements, which avoids optimizing over the 3-D points, further accelerating the computation. We perform an extensive evaluation of our monocular VIO pipeline on real and simulated datasets. The results confirm that our modeling effort leads to an accurate state estimation in real time, outperforming state-of-the-art approaches.
Efficient Elimination of B-Lineage Lymphomas by Anti-CD20–Auristatin Conjugates (2004)

The anti-CD20 antibody rituximab is useful in the treatment of certain B-cell malignancies, most notably non-Hodgkin's lymphoma. Its efficacy has been increased when used in combination with chemotherapy, yet anti-CD20 monoclonal antibodies (mAbs) directly conjugated with drugs such as doxorubicin (Dox) have failed to deliver drug or to demonstrate antitumor activity. We have produced anti-CD20 antibody-drug conjugates that possess potent antitumor activity by using the anti-mitotic agent, monomethyl auristatin E (MMAE), linked via the lysosomally cleavable dipeptide, valine-citrulline (vc). Two anti-CD20 conjugates, rituximab-vcMMAE and 1F5-vcMMAE, were selectively cytotoxic against CD20(+) B-lymphoma cell lines, with IC(50) values ranging from 50 ng/mL to 1 microg/mL. Unlike rituximab, which showed diffuse surface localization, rituximab-vcMMAE capped and was internalized within 4 hours after binding to CD20(+) B cells. Internalization of rituximab-vcMMAE was followed by rapid G(2)-M phase arrest and onset of apoptosis. Anti-CD20 antibody-drug conjugates prepared with Dox were internalized and localized as with rituximab-vcMMAE, yet these were not effective for drug delivery (IC(50) > 50 microg/mL). Consistent with in vitro activity, rituximab-vcMMAE showed antitumor efficacy in xenograft models of CD20-positive lymphoma at doses where rituximab or rituximab-Dox conjugates were ineffective. These data indicate that anti-CD20-based antibody-drug conjugates are effective antitumor agents when prepared with a stable, enzyme-cleavable peptide linkage to highly potent cytotoxic agents such as MMAE.
A Dynamic Clustering Approach in Wireless Networks with Multi-Cell Cooperative Processing (2008)

Multi-cell cooperative processing (MCP) has recently attracted a lot of attention because of its potential for co-channel interference (CCI) mitigation and spectral efficiency increase. MCP inevitably requires increased signaling overhead and inter-base communication. Therefore in practice, only a limited number of base stations (BSs) can cooperate in order for the overhead to be affordable. The intrinsic problem of which BSs shall cooperate in a realistic scenario has been only partially investigated. In this contribution linear beamforming has been considered for the sum-rate maximisation of the uplink. A novel dynamic greedy algorithm for the formation of the clusters of cooperating BSs is presented for a cellular network incorporating MCP. This approach is chosen to be evaluated under a fair MS scheduling scenario (round-robin). The objective of the clustering algorithm is sum-rate maximisation of the already selected MSs. The proposed cooperation scheme is compared with some fixed cooperation clustering schemes. It is shown that a dynamic clustering approach with a cluster consisting of 2 cells outperforms static coordination schemes with much larger cluster sizes.
El proceso de certificacion ISO 9002 (1995)

La Calidad de una organizacion viene dada por la vision de su Direccion General encaminada hacia el espanol y europeo, cada dia mas competitivo, donde solo perduraran las que mejor sepan resolver, con la competitividad de sus productos y servicios, la demanda del mercado; sin olvidar transmitir entusiasmo, implicacion, apoyo y formacion a su mercado interno: sus colaboradores.
Polymyxin antibiotics for gram-negative infections (2007)

The polymyxins have become a last resort for the treatment of infections caused by multidrug-resistant gram-negative organisms. Recent studies have suggested that the frequency of polymyxin-associated nephrotoxicity and neurotoxicity may not be as high as was once thought. The polymyxins seem to be effective in treating various infections caused by multidrug-resistant gram-negative organisms but should not be used as first-line therapy until more is known about this class of antibiotics.
The Increase in Serum Uric Acid Concentration Caused by Diuretics Might be Beneficial in Heart Failure (2005)

Patients with mild-moderate chronic heart failure (CHF) often have raised levels of serum uric acid (UA). This is due, amongst other factors, to reduced UA excretion by the kidneys, which is partly explained by restriction of sodium intake and treatment with diuretics. The decline in renal function that parallels worsening cardiac function also contributes to elevated serum UA in patients with advanced CHF. However, UA production also appears to be augmented in CHF. Because UA scavenges various reactive oxygen species, diuretic-induced elevations in serum UA could be beneficial in patients with CHF. This concept is supported by the superior performance of antihypertensive therapy with diuretics in preventing heart failure. The present hypothesis may be tested by examining the effects of add-on treatment with a thiazide-type diuretic on morbidity and mortality, or surrogate variables, in asymptomatic patients with left ventricular dysfunction but without fluid retention.
The Docosatriene Protectin D1 Is Produced by TH2 Skewing and Promotes Human T Cell Apoptosis via Lipid Raft Clustering (2005)

Docosahexaenoic acid, a major omega-3 fatty acid in human brain, synapses, retina, and other neural tissues, displays beneficial actions in neuronal development, cancer, and inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatography-tandem mass spectrometry, that (10,17S)-docosatriene/neuroprotectin D1, now termed protectin D1 (PD1), is generated from docosahexaenoic acid by T helper type 2-skewed peripheral blood mononuclear cells in a lipoxygenase-dependent manner. PD1 blocked T cell migration in vivo, inhibited tumor necrosis factor alpha and interferon-gamma secretion, and promoted apoptosis mediated by raft clustering. These results demonstrated novel anti-inflammatory roles for PD1 in regulating events associated with inflammation and resolution.
Transforming information use in preventive medicine: learning to balance technology with the art of caring. (1994)

CompuHx* is an Interactive Health Appraisal System (IHAPS) used in the examining room to record patient information, assist in diagnosis, and provide a legible summary of findings. This paper describes Phase I of a longitudinal study in which 22 examiners (five system users and 17 non-users) responded to detailed surveys and interviews about the system. Findings indicated that both users and non-users had mixed feelings about the system's ease of use and impact on their jobs, but agreed that it would have value for their practice. Underlying their acceptance of the system was a common concern for maintaining a caring relationship with patients and not allowing computer technology to depersonalize the examining room. Examiners also expressed concerns about the implementation process.
Plasma-density measurements by microwave interferometry and Langmuir probes in an rf discharge (1993)

Improvements for two established methods for plasma-density measurements have been developed: (a) microwave interferometry and (b) single Langmuir-probe technique. The new microwave interferometer design allows us to avoid a rigid waveguide as the reference line and therefore results in a high flexibility for the use at plasma chambers with different geometries. The system is operated at 35 GHz and has a bandwidth of 10 MHz. The cylindrical single Langmuir-probe system has been equipped with a new rf-suppression circuit. This allows the application of probes of nearly arbitrary geometrical dimensions in rf-driven plasmas. The circuit is simply mounted outside the vacuum chamber between the probe feedthrough and the dc circuit. The performance of these two developments has been demonstrated and comparative measurements of charge carrier densities in a conventional rf-driven plasma show good agreement between the two methods.
Variations in demethylation of N-methylnaltrexone in mice, rats, dogs, and humans (1989)

1. Rats and mice have a greater capacity than dogs or humans to N-demethylate the quaternary ammonium compound, N-methylnaltrexone. 2. In dogs, following the i.v. administration of N-[14C-methyl]methylnaltrexone, 50% of the radioactivity was excreted in the urine and an additional 30% in the faeces within 120 h. 3. In humans following the i.v. administration of 14C-N-methylnaltrexone, 40-60% of the radioactivity was excreted in the urine within the first 24 h. The plasma radioactivity-time curves indicated a biphasic decay and a short distribution phase between 6 and 9 min. with a longer elimination phase between 238 and 1320 min.
Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups (2010)

Warfarin-dosing algorithms incorporating CYP2C9 and VKORC1 -1639G>A improve dose prediction compared with algorithms based solely on clinical and demographic factors. However, these algorithms better capture dose variability among whites than Asians or blacks. Herein, we evaluate whether other VKORC1 polymorphisms and haplotypes explain additional variation in warfarin dose beyond that explained by VKORC1 -1639G>A among Asians (n = 1103), blacks (n = 670), and whites (n = 3113). Participants were recruited from 11 countries as part of the International Warfarin Pharmacogenetics Consortium effort. Evaluation of the effects of individual VKORC1 single nucleotide polymorphisms (SNPs) and haplotypes on warfarin dose used both univariate and multi variable linear regression. VKORC1 -1639G>A and 1173C>T individually explained the greatest variance in dose in all 3 racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among whites than blacks and Asians. Differences in the percentage of variance in dose explained by VKORC1 across race were largely accounted for by the frequency of the -1639A (or 1173T) allele. Thus, clinicians should recognize that, although at a population level, the contribution of VKORC1 toward dose requirements is higher in whites than in nonwhites; genotype predicts similar dose requirements across racial groups.