gebhart/patrepeval huggingface dataset:
Stem cells in the biology of normal urothelium and urothelial carcinoma (2012)

Urothelium is a special type of stratified epithelium that lines the distal portion of the urinary tract. For a long time, basal urothelial cells have been suspected to include a population of urothelial stem cells. Recent experiments identifying label-retaining cells as well as lineage tracing analyses corroborate this notion. There are striking morphological and antigenic similarities between basal or differentiated urothelial cells and the corresponding cells in some urothelial carcinomas. In this respect, basal cell-specific markers provide good candidates to identify urothelial carcinoma stem cells, e.g. specific cytokeratins (CK5, CK14, CK17) or adhesion molecules (specific integrin subspecies, CD44). Common properties of the stem cells of normal urothelium and urothelial cancer have thus emerged. Both are characterized by a remarkable plasticity and both rely on reciprocal interactions with stromal fibroblasts. However, the stem cells of individual urothelial carcinomas appear to differ considerably and may contribute to the heterogeneity of this disease. The presence, quantity, and particular biological nature of urothelial carcinoma stem cells in each case may thus carry important clinical information that might allow a rationale stratification of urothelial cancer patients for treatment in the near future.
Tucaresol increases oxygen affinity and reduces haemolysis in subjects with sickle cell anaemia (1996)

The primary pathophysiological event in sickling is the intracellular polymerization of deoxygenated haemoglobin S. Tucaresol (589C80;4[2-formyl-3-hydroxyphenoxymethyl] benzoic acid), a substituted benzaldehyde, was designed to interact with haemoglobin to increase oxygen affinity and has been shown to inhibit sickling in vitro. We administered tucaresol to sickle cell patients in the steady state to examine the anti-sickling effect in vivo. Oral doses of tucaresol or placebo were given to nine stable sickle cell patients (aged 17-39 years; tucaresol, six; placebo, three) for 10 d. The first two patients on tucaresol were scheduled to receive a loading dose of 800 mg or 1200 mg (depending on bodyweight) for the first 4 d, followed by maintenance doses of 200 or 300 mg for the next 6 d. Due to concerns over the sharp rise in haematocrit in one patient, subsequent cohorts received 300 mg tucaresol daily throughout the dosing period. The oxygen affinity of haemoglobin S was increased in all patients receiving tucaresol, with between 10% and 24% of the haemoglobin modified, dependent on dose. In all patients on tucaresol, haemolysis was reduced with rises in haemoglobin of 0.9- 3.7 g/dl (mean 2.2 g/dl), falls in lactate dehydrogenase of 16-52%, and a halving of the irreversibly sickled cell counts. These effects were apparent within a few days and persisted for 1-2 weeks following discontinuation of the drug. Three of the six patients on tucaresol developed fever and cervical lymphadenopathy, with onset between days 7 and 11 from start of drug. Further evaluation of the tolerability and efficacy of tucaresol in sickle cell patients is necessary.
Evaluating software deployment languages and schema: an experience report (2002)

Software distribution is evolving from a physical media approach to one where it is practical and advantageous to leverage the connectivity of networks. Network distribution of software systems provides timeliness and continuity of evolution not possible with physical media distribution methods. To support network-based software distribution, companies and organizations such as Microsoft, Marimba, and the Desktop Management Task Force (DMTF) are strengthening their efforts to package software systems in a way that is conducive to network distribution and management. The result of these efforts has led to the creation of software description languages and schema such as the Open Software Description format created by Microsoft and Marimba and the Management Information Format created by DMTF. While these efforts are steps in the right direction, they do not address deployment issues in a complete and systematic fashion. The contribution of this paper is to evaluate these leading software description technologies.
Synthesis of a perylenediimide-viologen dyad (PDI-2V) and its electrochromism in a layer-by-layer self-assembled multilayer film with PEDOT:PSS (2012)

A new electrochromic molecule, perylenediimide-viologen dyad (PDI-2V), was synthesized and used in the fabrication of layer-by-layer (LBL) self-assembled multilayer films with poly(3,4-ethylenedioxythiophene)–poly(styrenesulfonate) (PEDOT:PSS). Since PDI-2V is a tetracationic organic molecule with high molecular weight, it showed strong electrostatic adhesion to negatively charged PEDOT:PSS. When the electrochromic behaviour of the resulting LBL film was investigated with a single type electrochromic device, the PDI-2V showed a three-stage color change from red to blue to violet under the reduction potential range. A dual type electrochromic device was also fabricated with P3HT spin-coated ITO as a counter electrode. This device exhibited a sharp color change between deep red and dark blue when the applied potential was switched from +2.0 V to −2.0 V.
Role of different pathways of the complement cascade in experimental bullous pemphigoid (2006)

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease associated with autoantibodies directed against the hemidesmosomal proteins BP180 and BP230 and inflammation. Passive transfer of antibodies to the murine BP180 (mBP180) induces a skin disease that closely resembles human BP. In the present study, we defined the roles of the different complement activation pathways in this model system. Mice deficient in the alternative pathway component factor B (Fb) and injected with pathogenic anti-mBP180 IgG developed delayed and less intense subepidermal blisters. Mice deficient in the classical pathway component complement component 4 (C4) and WT mice pretreated with neutralizing antibody against the first component of the classical pathway, C1q, were resistant to experimental BP. These mice exhibited a significantly reduced level of mast cell degranulation and polymorphonuclear neutrophil (PMN) infiltration in the skin. Intradermal administration of compound 48/80, a mast cell degranulating agent, restored BP disease in C4(-/-) mice. Furthermore, C4(-/-) mice became susceptible to experimental BP after local injection of PMN chemoattractant IL-8 or local reconstitution with PMNs. These findings provide the first direct evidence to our knowledge that complement activation via the classical and alternative pathways is crucial in subepidermal blister formation in experimental BP.
Transposition of Tn1545-delta 3 in the pathogenic Neisseriae: a genetic tool for mutagenesis (1991)

The ability to study the virulence of pathogenic Neisseria spp. has been greatly limited by the absence of genetic tools which allow the construction of defined mutants. We have engineered a transposon system which allows random mutagenesis of the Neisseria genome at relatively high frequency. Tn1545-delta 3 is a 3.4-kb derivative of the gram-positive transposon Tn1545 encoding resistance to kanamycin. Tn1545-delta 3 was subcloned into an erythromycin-resistant derivative of the mobilizable shuttle vector pLES2 to yield the plasmid pMGC20. This latter plasmid was introduced by conjugation from Escherichia coli S17-1 into Neisseria meningitidis 8013N and Neisseria gonorrhoeae 15063G. Kanamycin-resistant 8013N and 15063G transconjugants appeared at frequencies of 10(-5) and 10(-6), respectively. Restriction enzyme analysis and Southern blot hybridization of these transconjugants showed that, in Neisseria spp., the transposon excised spontaneously from pMGC20 and integrated into chromosomal DNA. Our studies revealed that (i) transposition of Tn1545-delta 3 was in numerous, apparently distinct sites, (ii) in most cases, for each transconjugant a single copy of Tn1545-delta 3 was integrated into the chromosome, and (iii) several passages on selective media did not induce secondary transposition. The kanamycin resistance marker expressed by the transconjugants was subsequently transformed into a parental background without change in the chromosomal location of the transposon. To assess the role of the general recombination system in the transposition of Tn1545-delta 3, the recA gene of N. meningitidis has been cloned and a rec derivative of 8013N has been engineered. Similar results were obtained when this latter strain was used as recipient, suggesting that recA function were not required for Tn1545-delta 3 transposition in N. meningitidis. Transposition with Tn1545-delta 3 may be an important technique for mutagenesis of the pathogenic neisseriae.
The engineering, structure, and DNA binding properties of a novel His4-type zinc finger peptide (2000)

We have created a novel His4-type zinc finger protein (H4Sp1) engineered by Cys-->His mutations of the Cys2His2-type zinc finger in transcription factor Sp1. The CD and NMR studies reveal that the His4 domain has Zn(II)-dependent folding properties and similar secondary structures to wild-type Cys2His2 domain. The DNA binding experiments demonstrate that H4Sp1 can bind DNA in a specific way. The present artificial peptide H4Sp1 will provide valuable information about the interaction between a metallopeptide and DNA.
Piezoactuators for ‘real world' applications. Can they deliver sufficient displacement? (2000)

Piezoelectric actuators can develop large forces very quickly and with high efficiency. The need for high-voltage power supplies has been overcome with stack or multilayer actuators, but the available displacements are still minute. This has limited their use to specialist optical and micro-positioning systems. In order to obtain useful strokes for more general engineering applications, their output displacement must (and can) be amplified. One way of achieving this is by direct mechanical amplification-typically using flexure hinged structures or hydraulic amplifiers. This method is described in the paper.
A Selective Irreversible Inhibitor Targeting a PDZ Protein Interaction Domain (2003)

Irreversible inhibitors of proteases have proven themselves useful tools for determining which proteases are active under given conditions in tissues or cells and for studying the functional role that a protease plays in physiological processes. The application of such techniques to the study of the activity and function of protein-protein interactions has been hindered by the lack of guiding principles for the mechanistic design of irreversible inhibitors targeting the "active site" of a protein interaction. We report herein the first example of a mechanism-based irreversible inhibitor of a protein interaction that has been specifically targeted to one member of the PDZ family of protein interaction domains: the second PDZ domain of the membrane-associated guanylate kinase MAGI3. This inhibitor was designed using rationally directed computational evaluation to take advantage of a conserved histidine in the PDZ domain by introducing an ionizable group that will be held in close proximity to that nucleophile during binding. The novel compound exhibits all of the characteristics of an irreversible inhibitor of the interaction of the tumor suppressor PTEN with MAGI3 in in vitro models. In cells, the inhibitor can be shown to release PTEN from sequestration by MAGI3 and consequently upregulate the PKB signaling pathway.
Bacterial Urease and its Role in Long-Lasting Human Diseases (2012)

Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. The presence of ureolytic activity is an important marker of a number of bacterial infections. Urease is also an immunogenic protein and is recognized by antibodies present in human sera. The presence of such antibodies is connected with progress of several long-lasting diseases, like rheumatoid arthritis, atherosclerosis or urinary tract infections. In bacterial ureases, motives with a sequence and/or structure similar to human proteins may occur. This phenomenon, known as molecular mimicry, leads to the appearance of autoantibodies, which take part in host molecules destruction. Detection of antibodies- binding motives (epitopes) in bacterial proteins is a complex process. However, organic chemistry tools, such as synthetic peptide libraries, are helpful in both, epitope mapping as well as in serologic investigations. In this review, we present a synthetic report on a molecular organization of bacterial ureases - genetic as well as structural. We characterize methods used in detecting urease and ureolytic activity, including techniques applied in disease diagnostic processes and in chemical synthesis of urease epitopes. The review also provides a summary of knowledge about a toxic effect of bacterial ureases on human body and about occurrence of anti-urease antibodies in long-lasting diseases.
Intermolecular Zirconium-Catalyzed Hydrophosphination of Alkenes and Dienes with Primary Phosphines (2014)

Catalytic hydrophosphination of terminal alkenes and dienes with primary phosphines (RPH2; R = Cy, Ph) under mild conditions has been demonstrated using a zirconium complex, [κ(5)-N,N,N,N,C-(Me3SiNCH2CH2)2NCH2CH2NSiMe2CH]Zr (1). Exclusively anti-Markovnikov functionalized products were observed, and the catalysis is selective for either the secondary or tertiary phosphine (i.e., double hydrophosphination) products, depending on reaction conditions. The utility of the secondary phosphine products as substrates for further elaboration was demonstrated with a platinum-catalyzed asymmetric alkylation reaction.
MULTI‐DOCUMENT SUMMARIZATION OF EVALUATIVE TEXT (2012)

In many decision‐making scenarios, people can benefit from knowing what other people's opinions are. As more and more evaluative documents are posted on the Web, summarizing these useful resources becomes a critical task for many organizations and individuals. This paper presents a framework for summarizing a corpus of evaluative documents about a single entity by a natural language summary. We propose two summarizers: an extractive summarizer and an abstractive one. As an additional contribution, we show how our abstractive summarizer can be modified to generate summaries tailored to a model of the user preferences that is solidly grounded in decision theory and can be effectively elicited from users. We have tested our framework in three user studies. In the first one, we compared the two summarizers. They performed equally well relative to each other quantitatively, while significantly outperforming a baseline standard approach to multidocument summarization. Trends in the results as well as qualitative comments from participants suggest that the summarizers have different strengths and weaknesses. After this initial user study, we realized that the diversity of opinions expressed in the corpus (i.e., its controversiality) might play a critical role in comparing abstraction versus extraction. To clearly pinpoint the role of controversiality, we ran a second user study in which we controlled for the degree of controversiality of the corpora that were summarized for the participants. The outcome of this study indicates that for evaluative text abstraction tends to be more effective than extraction, particularly when the corpus is controversial. In the third user study we assessed the effectiveness of our user tailoring strategy. The results of this experiment confirm that user tailored summaries are more informative than untailored ones.
Inhibitory RNA in epilepsy: Research tools and therapeutic perspectives (2010)

Since its discovery a decade ago, RNA interference (RNAi) has been developed not only into powerful experimental tools but also into promising novel therapeutics. In contrast to conventional antiepileptic drugs (AEDs) that target specific proteins such as ion channels or receptors, RNAi-based therapeutics exploit an endogenous regulatory mechanism of gene expression and thereby are poised to prevent or reverse pathogenetic mechanisms involved in seizure development. Therapeutic RNAi has been widely explored for dominant targets involved in neurodegenerative diseases; however, their use for epilepsy therapy has received less attention. This review discusses potential RNAi-based targets that are of interest for epilepsy therapy, including adenosine kinase (ADK), the key negative regulator of the brain's endogenous anticonvulsant adenosine. Overexpression of ADK, and the resulting adenosine deficiency, are pathologic hallmarks of the sclerotic epileptic brain, and have been implicated in seizure generation. Therefore, RNAi-strategies aimed at reducing ADK (and increasing adenosine) are based on a direct neurochemical rationale that has recently been explored experimentally using ex vivo and in vivo gene therapy approaches. Technical issues and challenges remain before those promising tools can be developed into future therapeutics for epilepsy.
Chronic Lymphocytic Leukemia: Recent Advances in Diagnosis and Treatment (2006)

Chronic lymphocytic leukemia (CLL) is a low-grade B-lineage lymphoid malignancy but may have more heterogeneity than previously thought. Many cases require no treatment at all because of an indolent course, while other patients become symptomatic or develop signs of rapid progression. Treatment is usually noncurative and is directed at reducing the symptoms. Some molecular risk features may help delineate, at initial diagnosis, which patients will have a more aggressive course. Newer CLL treatment regimens incorporating purine nucleoside analogues and monoclonal antibodies have increased the rate of molecular complete remissions, which may lead to better survival times. Reduced intensity allogeneic transplant conditioning regimens have made the potentially curative modality more widely available. All these treatments have significant risks for infectious complications, which must be carefully weighed against the risks posed by the underlying disease. A proposed risk-based treatment algorithm is discussed.
A low-density DNA microarray for analysis of markers in breast cancer (2002)

Breast cancer remains a major cause of death in women from Western countries. In the near future, advances in both nucleic acids technology and tumor biology should be widely exploited to improve the diagnosis, prognosis, and outcome prediction of this disease. The DNA microarray, also called biochip, is a promising tool for performing massive, simultaneous, fast, and standardized analyses of multiple molecular markers in tumor samples. However, most currently available microarrays are expensive, which is mainly due to the amount (several thousands) of different DNA capture sequences that they carry. While these high-density microarrays are best suited for basic studies, their introduction into the clinical routine remains hypothetical. We describe here the principles of a low-density microarray, carrying only a few hundreds of capture sequences specific to markers whose importance in breast cancer is generally recognized or suggested by the current medical literature. We provide a list of about 250 of these markers. We also examine some potential difficulties (homologies between marker and/or variant sequences, size of sequences, etc.) associated with the production of such a low-cost microarray.
The application of solid dispersion technique in the preparation of therapeutic tablets. Part 1: Paracetamol, amylobarbitone, and caffeine tablets. (1978)

A trial was made to study the possibility of preparing high-quality therapeutic tablets by direct compression of the solidified drugcarrier melt via solid dispersion technique. Paracetamol-mannitol, amylobarbitone-urea and caffeine-nicotinamide systems were investigated. Phase diagrams of the first two systems were found to be of the simple eutectic type, while that of the third system was a peritectic type. Solubility studies were also carried out. Dissolution rate studies showed that the fused mannitol/paracetamol (80:20), urea/amylobarbitone (80:20) and nicotinamide/caffeine (50:50 and 70:30) solid dispersions exhibited better rates of dissolution than those of the pure drugs. Comparative studies were carried on with tablets prepared by direct compression of the drug-carrier solidified melt exhibiting the highest dissolution rate and by slugging the pure drug and the drug-carrier physical mixture of corresponding composition. The physical properties and dissolution rate data showed the superiority of the tablets prepared by the solid dispersion technique. The drug release from these tablets was 4.5, 7.6 and 3.7 times greater than that from tablets prepared from pure paracetamol, amylobarbitone and caffeine respectively.
High fidelity fabrication of microlens arrays by nanoimprint using conformal mold duplication and low-pressure liquid material curing (2007)

The authors present a novel hyperfidelity fabrication method for microlens arrays. The method consists of the steps of (a) fabrication of a sacrificial master mold of a microlens array in a soft polymer by photolithography and thermal reflow, (b) conformal duplication of a daughter mold of complementary patterns in a hard material by dispensing an UV-curable material liquid on top of the polymer mold, planarizing the liquid with a flat quartz substrate, and curing the material, and (c) fabrication of microlens array using the hard daughter mold and nanoimprinting with an UV-curable lens material. This method has several advantages over conventional fabrication methods of microlens arrays including hyperfidelity, low cost, and high throughput.
Genome-Scale Genotype-Phenotype Matching of Two Lactococcus lactis Isolates from Plants Identifies Mechanisms of Adaptation to the Plant Niche (2007)

Lactococcus lactis is a primary constituent of many starter cultures used for the manufacturing of fermented dairy products, but the species also occurs in various nondairy niches such as (fermented) plant material. Three genome sequences of L. lactis dairy strains (IL-1403, SK11, and MG1363) are publicly available. An extensive molecular and phenotypic diversity analysis was now performed on two L. lactis plant isolates. Diagnostic sequencing of their genomes resulted in over 2.5 Mb of sequence for each strain. A high synteny was found with the genome of L. lactis IL-1403, which was used as a template for contig mapping and locating deletions and insertions in the plant L. lactis genomes. Numerous genes were identified that do not have homologs in the published genome sequences of dairy L. lactis strains. Adaptation to growth on substrates derived from plant cell walls is evident from the presence of gene sets for the degradation of complex plant polymers such as xylan, arabinan, glucans, and fructans but also for the uptake and conversion of typical plant cell wall degradation products such as alpha-galactosides, beta-glucosides, arabinose, xylose, galacturonate, glucuronate, and gluconate. Further niche-specific differences are found in genes for defense (nisin biosynthesis), stress response (nonribosomal peptide synthesis and various transporters), and exopolysaccharide biosynthesis, as well as the expected differences in various mobile elements such as prophages, plasmids, restriction-modification systems, and insertion sequence elements. Many of these genes were identified for the first time in Lactococcus lactis. In most cases good correspondence was found with the phenotypic characteristics of these two strains.