gebhart/patrepeval huggingface dataset:
A multivalent recombinant antibody fragment specific for carcinoembryonic antigen (2005)

In the present paper we report the development of a bivalent scFv (single-chain Fv) antibody fragment, starting from a mouse mAb (monoclonal antibody) specific for CEA (carcinoembryonic antigen) that has received approval for in vivo radioimmunodiagnosis in humans. The diabody is well expressed in Escherichia coli, is easily purified by a combination of immobilized metal ion affinity chromatography and gel filtration and exhibits high affinity and specificity for CEA, comparable with those of the original mAb. Biodistribution experiments in athymic nude mice transplanted with human CEA+ cancer cells showed that the 125I-labelled diabody preferentially localizes in the tumour tissue and that retention is still high 48 h after injection. The diabody can be advantageous for some in vivo tumour targeting applications, due to the faster clearance derived from its smaller molecular mass.
A family of concatenated network codes for improved performance with generations (2008)

Random network coding can be viewed as a single block code applied to all source packets. To manage the concomitant high coding complexity, source packets can be partitioned into generations; block coding is then performed on each set. To reach a better performance-complexity tradeoff, we propose a novel concatenated network code which mixes generations while retaining the desirable properties of generation-based coding. Focusing on the code's erasure performance, we show that the probability of successfully decoding a generation on erasure channels can increase substantially for any erasure rate. Using both analysis (for small networks) and simulations (for larger networks), we show how the code's parameters can be tuned to extract best performance. As a result, the probability of failing to decode a generation is reduced by nearly one order of magnitude.
Failure to thrive: the earliest feature of cystic fibrosis in infants diagnosed by neonatal screening (1997)

The benefits of early treatment of nutritional and respiratory problems in the CF infant and of genetic counselling for the parents are widely recognized. However, clinical diagnosis of CF is often delayed despite early onset of symptoms and the usefulness of neonatal population screening as a preventive measure is still under debate. This study analyses the clinical history of CF patients diagnosed exclusively on the basis of positive neonatal screening tests with the aim of identifying the earliest markers of the disease. We studied 103 CF infants born in north-east Italy, diagnosed following neonatal screening: assay of immunoreactive trypsin (IRT) from a heel-prick blood sample followed by a measurement of meconium lactase in cases with raised IRT. Diagnosis was confirmed by sweat test at an average age of 39 days. Eighty-one patients (79%) had symptoms strongly suggestive of CF at diagnosis, and signs and/or symptoms of pancreatic insufficiency were present in 16 of the remaining 22 cases. The most frequent symptom was growth failure (69% of infants) and of these, 44% weighed the same as at birth or less. Pancreatic insufficiency was confirmed by the low level of faecal chymotrypsin found in 85% of cases. IRT was elevated in all cases. CF had not been suspected in any symptomatic infant, although most of the infants had been monitored by a paediatrician. In conclusion, most infants with CF diagnosed by neonatal screening are already symptomatic in the first six weeks of life and the most frequent symptom is failure to thrive; pancreatic insufficiency was already present in most cases. In areas without CF neonatal screening programs, the disease should be excluded by differential diagnosis in all cases with growth failure notwithstanding adequate caloric intake in the first months of life. The high sensitivity, low cost and simple execution of IRT and fecal chymotrypsin tests make them an ideal first step in suspect cases before proceeding to the sweat test, often performed late because of limited availability.
3D sensor algorithms for spacecraft pose determination (2006)

Researchers at the Michigan Aerospace Corporation have developed accurate and robust 3-D algorithms for pose determination (position and orientation) of satellites as part of an on-going effort supporting autonomous rendezvous, docking and space situational awareness activities. 3-D range data from a LAser Detection And Ranging (LADAR) sensor is the expected input; however, the approach is unique in that the algorithms are designed to be sensor independent. Parameterized inputs allow the algorithms to be readily adapted to any sensor of opportunity. The cornerstone of our approach is the ability to simulate realistic range data that may be tailored to the specifications of any sensor. We were able to modify an open-source raytracing package to produce point cloud information from which high-fidelity simulated range images are generated. The assumptions made in our experimentation are as follows: 1) we have access to a CAD model of the target including information about the surface scattering and reflection characteristics of the components; 2) the satellite of interest may appear at any 3-D attitude; 3) the target is not necessarily rigid, but does have a limited number of configurations; and, 4) the target is not obscured in any way and is the only object in the field of view of the sensor. Our pose estimation approach then involves rendering a large number of exemplars (100k to 5M), extracting 2-D (silhouette- and projection-based) and 3-D (surface-based) features, and then training ensembles of decision trees to predict: a) the 4-D regions on a unit hypersphere into which the unit quaternion that represents the vehicle [Q<sub>X</sub>, Q<sub>Y</sub>, Q<sub>Z</sub>, Q<sub>W</sub>] is pointing, and, b) the components of that unit quaternion. Results have been quite promising and the tools and simulation environment developed for this application may also be applied to non-cooperative spacecraft operations, Autonomous Hazard Detection and Avoidance (AHDA) for landing craft, terrain mapping, vehicle guidance, path planning and obstacle avoidance.
Pyrazolo[3,4-b]pyridines: Syntheses, reactions, and nuclear magnetic resonance spectra (1988)

Efficient syntheses of approximately 70 simple substituted representatives of pyrazolo[3,4-b]pyridine 1 are reported from the following: (a) suitably substituted pyridines onto which a pyrazole ring is annelated, and (b) appropriately substituted pyrazoles onto which a pyridine ring is annelated. Selected examples of electrophilic, nucleophilic, and homolytic substitution reactions and group transformations are described, providing regiosynthetic paths to useful intermediate species. Some systematic aspects of substituent chemical shift influences in the 1 H and 13 C nuclear magnetic resonance spectra, aiding in structural assignments, are illustrated.
The Fagerström Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire (1991)

We examine and refine the Fagerström Tolerance Questionnaire (FTQ: Fagerström, 1978). The relation between each FTQ item and biochemical measures of heaviness of smoking was examined in 254 smokers. We found that the nicotine rating item and the inhalation item were unrelated to any of our biochemical measures and these two items were primary contributors to psychometric deficiencies in the FTQ. We also found that a revised scoring of time to the first cigarette of the day (TTF) and number of cigarettes smoked per day (CPD) improved the scale. We present a revision of the FTQ: the Fagerström Test for Nicotine Dependence (FTND).
Curcumin has potent anti‐amyloidogenic effects for Alzheimer's β‐amyloid fibrils in vitro (2004)

Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the destabilization of preformed fAbeta in the central nervous system, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAbeta formation from Abeta(1-40) and Abeta(1-42) and destabilize preformed fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of curcumin (Cur) and rosmarinic acid (RA) on the formation, extension, and destabilization of fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic activities of Cur and RA with NDGA. Cur and RA dose-dependently inhibited fAbeta formation from Abeta(1-40) and Abeta(1-42), as well as their extension. In addition, they dose-dependently destabilized preformed fAbetas. The overall activities of Cur, RA, and NDGA were similar. The effective concentrations (EC(50)) of Cur, RA, and NDGA for the formation, extension, and destabilization of fAbetas were in the order of 0.1-1 microM. Although the mechanism by which Cur and RA inhibit fAbeta formation from Abeta and destabilize preformed fAbeta in vitro remains unclear, they could be a key molecule for the development of therapeutics for AD.
Notch-1 inhibits apoptosis in murine erythroleukemia cells and is necessary for differentiation induced by hybrid polar compounds (1999)

Strikingly increased expression of notch-1 has been demonstrated in several human malignancies and pre-neoplastic lesions. However, the functional consequences of notch-1 overexpression in transformed cells remain unclear. We investigated whether endogenously expressed notch-1 controls cell fate determination in mouse erythroleukemia (MEL) cells during pharmacologically induced differentiation. We found that notch-1 expression is modulated during MEL cell differentiation. Premature downregulation of notch-1 during differentiation, by antisense S-oligonucleotides or by enforced expression of antisense notch-1 mRNA, causes MEL cells to abort the differentiation program and undergo apoptosis. Downregulation of notch-1 expression in the absence of differentiation inducer increases the likelihood of spontaneous apoptosis. We conclude that in MEL cells, endogenous notch-1 expression controls the apoptotic threshold during differentiation and growth. In these cells, notch-1 allows differentiation by preventing apoptosis of pre-committed cells. This novel function of notch-1 may play a role in regulating apoptosis susceptibility in notch-1 expressing tumor cells.
Impact of Chronic Stress Protocols in Learning and Memory in Rodents: Systematic Review and Meta-Analysis (2016)

The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals' strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests' performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments.
Production of functional platelets by differentiated embryonic stem (ES) cells in vitro (2003)

Megakaryocytes and functional platelets were generated in vitro from murine embryonic stem (ES) cells with the use of a coculture system with stromal cells. Two morphologically distinctive megakaryocytes were observed sequentially. Small megakaryocytes rapidly produced proplatelets on day 8 of the differentiation, and large hyperploid megakaryocytes developed after day 12, suggesting primitive and definitive megakaryopoiesis. Two waves of platelet production were consistently observed in the culture medium. A larger number of platelets was produced in the second wave; 104 ES cells produced up to 108 platelets. By transmission electron microscopy, platelets from the first wave were relatively rounder with a limited number of granules, but platelets from the second wave were discoid shaped with well-developed granules that were indistinguishable from peripheral blood platelets. ES-derived platelets were functional since they bound fibrinogen, formed aggregates, expressed P-selectin upon stimulation, and fully spread on immobilized fibrinogen. These results show the potential utility of ES-derived platelets for clinical applications. Furthermore, production of gene-transferred platelets was achieved by differentiating ES cells that were transfected with genes of interest. Overexpression of the cytoplasmic domain of integrin beta3 in the ES-derived platelets prevented the activation of alphaIIbbeta3, demonstrating that this system will facilitate functional platelet studies.
Replication of Atypical Ovine Rotavirus in Small Intestine and Cell Culture (1986)

Colostrum-deprived lambs experimentally infected with an atypical ovine rotavirus isolated from naturally scouring animals, and a naturally infected colostrum-deprived lamb, were examined by immunofluorescence and immunoperoxidase labelling, and electron microscopy. A hyperimmune serum to the virus was produced in a gnotobiotic lamb and used to demonstrate antigen in the villous epithelial cells of the small intestine from infected animals. Scanning and transmission electron microscopy of tissues from infected animals revealed giant multinucleate syncytia composed of fused epithelial cells. Infected cells contained intracytoplasmic virus particles which resembled group A rotaviruses in morphology and morphogenesis. Small numbers of infected cells in MA104 cultures inoculated with ovine atypical rotavirus could be detected by immunofluorescence but virus growth could not be maintained by passage. Virus particles were seen by thin-section electron microscopy but their morphology and morphogenesis were abnormal; they were each composed of a single electron-dense shell, with no core, and were associated with envelopes of smooth membrane rather than rough endoplasmic reticulum.
Combined therapy with RAD001 e BEZ235 overcomes resistance of PET immortalized cell lines to mTOR inhibition (2014)

Pancreatic endocrine tumors (PETs) are characterised by an indolent behaviour in terms of tumor growth. However, most patients display metastasis at diagnosis and no cure is currently available. Since the PI3K/AKT/mTOR axis is deregulated in PETs, the mTOR inhibitor RAD001 represents the first line treatment. Nevertheless, some patients do not respond to treatments and most acquire resistance. Inhibition of mTOR leads to feedback re-activation of PI3K activity, which may promote resistance to RAD001. Thus, PI3K represents a novel potential target for PETs. We tested the impact of three novel PI3K inhibitors (BEZ235, BKM120 and BYL719) on proliferation of PET cells that are responsive (BON-1) or unresponsive (QGP-1) to RAD001. BEZ235 was the most efficient in inhibiting proliferation in PET cells. Furthermore, combined treatment with BEZ235 and RAD001 exhibited synergic effects and was also effective in BON-1 that acquired resistance to RAD001 (BON-1 RR). Analysis of PI3K/AKT/mTOR pathway showed that RAD001 and BEZ235 only partially inhibited mTOR-dependent phosphorylation of 4EBP1. By contrast, combined therapy with the two inhibitors strongly inhibited phosphorylation of 4EBP1, assembly of the translational initiation complex and protein synthesis. Thus, combined treatment with BEZ235 may represent suitable therapy to counteract primary and acquired resistance to RAD001 in PETs.
Late‐Phase 3 EAD. A Unique Mechanism Contributing to Initiation of Atrial Fibrillation (2006)

Early (EAD) and delayed (DAD) afterdepolarizations-induced triggered activity is capable of initiating and maintaining cardiac arrhythmias. EAD-induced triggered responses are traditionally thought to be involved in the generation of ventricular arrhythmias under long QT conditions and are precipitated by bradycardia or long pauses. In contrast, DAD-induced triggered activity commonly underlies arrhythmias precipitated by tachycardia. Spontaneous release of calcium from the sarcoplasmic reticulum (SR) secondary to cellular calcium overload induces DADs and some forms of EADs. Recent studies from our laboratory have uncovered a novel mechanism giving rise to triggered activity, termed "late-phase 3 EAD," which combines properties of both EAD and DAD, but has its own unique character. Late-phase 3 EAD-induced triggered extrasystoles represent a new concept of arrhythmogenesis in which abbreviated repolarization permits "normal SR calcium release" to induce an EAD-mediated closely coupled triggered response, particularly under conditions permitting intracellular calcium loading. This review briefly describes the mechanisms and properties of late-phase 3 EADs, how they differ from conventional EADs and DADs, as well as their role in the initiation of cardiac arrhythmias, such as atrial fibrillation.
Structure of the gene encoding chitinase D of Bacillus circulans WL-12 and possible homology of the enzyme to other prokaryotic chitinases and class III plant chitinases (1992)

The gene (chiD) encoding the precursor of chitinase D was found to be located immediately upstream of the chiA gene, encoding chitinase A1, which is a key enzyme in the chitinase system of Bacillus circulans WL-12. Sequencing analysis revealed that the deduced polypeptide encoded by the chiD gene was 488 amino acids long and the distance between the coding regions of the chiA and chiD genes was 103 bp. Remarkable similarity was observed between the N-terminal one-third of chitinase D and the C-terminal one-third of chitinase A1. The N-terminal 47-amino-acid segment (named ND) of chitinase D showed a 61.7% amino acid match with the C-terminal segment (CA) of chitinase A1. The following 95-amino-acid segment (R-D) of chitinase D showed 62.8 and 60.6% amino acid matches, respectively, to the previously reported type III-like repeating units R-1 and R-2 in chitinase A1, which were shown to be homologous to the fibronectin type III sequence. A 73-amino-acid segment (residues 247 to 319) located in the putative activity domain of chitinase D was found to show considerable sequence similarity not only to other bacterial chitinases and class III higher-plant chitinases but also to Streptomyces plicatus endo-beta-N-acetylglucosaminidase H and the Kluyveromyces lactis killer toxin alpha subunit. The evolutionary and functional meanings of these similarities are discussed.
Role of alpha 5 beta 1 integrin in determining malignant properties of colon carcinoma cells. (1997)

We characterized the expression of alpha 5 beta 1 integrin in two distinct phenotypes of colon carcinoma cell lines. Highly invasive colon cell lines (designated Group I cell lines) expressed higher levels of integrin alpha 5 beta 1 mRNA and protein than did poorly invasive colon cell lines (designated Group III cell lines). The relatively high expression of integrin alpha 5 beta 1 in Group I cell lines resulted in strong enhancement of cell adhesion to fibronectin (FN) tissue culture plates, whereas Group III cell lines showed little or no enhancement of cell adhesion by coating. There was no significant difference between Group I and Group III cell lines with respect to cell adhesion to laminin and collagen IV. Cell adhesion to FN in Group I cells was mainly mediated by integrin alpha 5 beta 1 because a monoclonal anti-alpha 5 subunit antibody could block cell adhesion to FN, whereas anti-alpha 2 and anti-alpha 3 antibodies had no effect on cell adhesion to FN. The divergence of alpha 5 beta 1 expression in these two distinct colon carcinoma phenotypes suggested that high expression of alpha 5 beta 1 might contribute to malignant progression in this model system. To test this hypothesis, GEO cells, a Group III cell line that did not express alpha 5 integrin, were transfected with the alpha 5 subunit. Stable transfection of alpha 5 sense cDNA into a typical GEO-limiting dilution clone led to the expression of alpha 5 subunit mRNA and cell surface alpha 5 beta 1 protein. The alpha 5 sense transfectants showed enhanced attachment to FN-coated plates and were more tumorigenic when the cells were injected into athymic nude mice. These results indicate that inappropriately high alpha 5 beta 1 integrin expression contributes to malignant progression in colon carcinoma.
Design and Characterisation of Poly(lactide-co-glycolide) Small Particulate Systems for the Delivery of Immunostimulant CpG Oligonucleotide (2006)

The aim of this study was to develop and characterize biodegradable small particles of poly(lactide-co-glycolide) (PLGA) as oral vehicle for immunostimulatory oligonucleotide (ODN-CpG). Three different polymers were used as surface stabilizing agents (SSA): polyvinyl alcohol (PVA), hydrophobically modified hydroxyethylcellulose (HMHEC), or polyethylenimine (PEI). Particle surface was characterized as well as ODN-CpG release kinetics. All particles were found to be around 1 microm. Particles of PLGA-PVA and PLGA-HMHEC were spherical in shape with a smooth surface whereas PLGA-PEI particles were porous. The presence of ODN-CpG within the particle matrix was confirmed in all particle type using scanning laser confocal microscopy. Particle surface assayed by XPS, zeta potential analysis, and evaluation of particle surface hydrophobicity suggested that a significant amount of SSA remains associated onto particle surface. Release profiles evidenced that ODN-CpG release was strongly dependent on particle surface properties. 100% of encapsulated ODN-CpG was released from PLGA-PVA and PLGA-HMHEC particles 37 days after incubation in a buffer solution, whereas only 25% were released from PLGA-PEI particles. ODN-CpG can therefore be nicely entrapped in several types of small particles displaying a prolonged and controlled release upon time. In addition, particle surface is not modified by the presence of ODN-CpG.
ChemInform Abstract: Synthesis of Amino Derivatives of 1,3,5‐Triazine Containing Higher Alkyl Radicals. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.