gebhart/patrepeval huggingface dataset:
An adaptive strain estimator for elastography (1998)

Elastography is based on the estimation of strain due to applied tissue compression. In conventional elastography, strain is computed from the gradient of the displacement estimates between gated pre- and postcompression echo signals. Gradient-based estimation methods are known to be susceptible to noise. In elastography, in addition to the electronic noise, a principal source of estimation error is the decorrelation of the echo signal as a result of tissue compression (decorrelation noise). Temporal stretching of postcompression signals previously was shown to reduce the decorrelation noise. In this paper, we introduce a novel estimator that uses the stretch factor itself as an estimator of the strain. It uses an iterative algorithm that adaptively maximises the correlation between the pre- and postcompression echo signals by appropriately stretching the latter. We investigate the performance of this adaptive strain estimator using simulated and experimental data. The estimator has exhibited a vastly superior performance compared with the conventional gradient-based estimator.
Epilepsies in twins: Genetics of the major epilepsy syndromes (1998)

We studied twins to examine the genetics of epilepsy syndromes. We ascertained 358 twin pairs in whom one or both reported seizures. After evaluation, 253 of 358 (71%) had seizure disorders and 105 pairs were false positives. Among the monozygous (MZ) pairs, more were concordant for seizures (48 of 108; casewise concordance = 0.62 +/- 0.05) than among the dizygous (DZ) pairs (14 of 145; casewise concordance = 0.18 +/- 0.04). In 94% of concordant MZ pairs, and 71% of concordant DZ pairs, both twins had the same major epilepsy syndrome. When analyzed according to major epilepsy syndrome, the casewise concordances for generalized epilepsies (MZ = 0.82; DZ = 0.26), both idiopathic (MZ = 0.76; DZ = 0.33) and symptomatic (MZ = 0.83; DZ = 0), were greater than those for partial epilepsies (MZ = 0.36; DZ = 0.05), with intermediate values seen for febrile seizures (MZ = 0.58; DZ = 0.14) and unclassified epilepsies (MZ = 0.53; DZ = 0.18). We conclude that genetic factors are particularly important in the generalized epilepsies but also play a role in the partial epilepsies. The high frequency of concordant MZ pairs with the same major syndrome strongly suggests there are syndrome-specific genetic determinants rather than a broad genetic predisposition to seizures.
Matriconditioning of Vegetable Seeds to Improve Stand Establishment in Early Field Plantings (1992)

A matriconditioning procedure based on the matric properties of Micro-Cel E and expanded vermiculite #5 has proved effective in improving seedling emergence in growth chambers. The major objectives of this study were to examine some physical characteristics of the carriers and their effectiveness as preplant conditioning media in improving stand establishment of vegetable seeds in field plantings. Carrier characteristics included no detectable solute or osmotic potential, low electrical conductivity (0.48-0.04 mmho/cm), high water-retaining capacity (450% to 600%), a pH range of 7.0 to 8.4, and ability to effectively control seed hydration (conditioning) at low matric potential. The seed: carrier: water ratio for seed conditioning ranged from 1:0.3-0.5:1-2 (by weight). In a field trial, conditioning of `Long Imperator' and `Nantes' carrot (Daucus carota var. sativus Hoffm.) seeds reduced the time to 10% of final emergence (T 10 ) by 2.6 to 2.8 days and to 50% of final emergence (T 50 ) by 2.1 to 3.0 days. Conditioning increased the final emergence percentage by 39% in 1-year-old `Long Imperator' compared to 150% in 4-year-old `Nantes' seeds. In another field trial, the effect of conditioning on stand establishment was evaluated in `Jackpot' tomato (Lycopersicon esculentum Mill.), `California Wonder' pepper (Capsicum annuum L.), and `BBL 47' snap bean (Phaseolus vulgaris) seeds. In tomato, conditioning reduced the T 10 by 0.9 day, had no effect on T 50 , and increased the emergence percentage by 86%. In pepper, conditioning reduced the T 10 and T 50 by 1.5 days and increased the percentage emergence by 30%. In snap bean seeds, conditioning in Micro-Ccl E reduced the T 10 and T 50 by 0.8 day but adversely affected the percentage emergence. Further reductions in T 10 and T 50 (1.2 and 1.6 days, respectively) and restoration of percentage emergence to control level occurred upon addition of 0.001 mM GA 3 during conditioning. Fungicides added to carrot, tomato, and pepper seeds, with or without conditioning, showed no additional improvements and, in a few cases, adversely affected emergence. A preplant conditioning in Micro-Ccl E, alone or in combination with GA 3 , smears to be a viable alternative to conditioning! seeds in liquid carriers. Chemical name used: gibberellic acid (GA 3 )
Efficient management of complex elements in physical IC design (2002)

An efficient data structure for the management of complex elements in physical design is described. The data structure is based on the use of low-level algorithms for the management of simple elements, such as rectangles and trapezoids. These algorithms constitute a generalization of those used for the management of the basic corner stitching data structure; the main enhancement is constituted by the possibility of managing simple elements with 45 degrees sides. At a higher level, a hierarchical structure is implemented which is able to manage more complex elements such as generic nonrectilinear polygons. This is performed by providing the user with a complete set of procedures for the creation and management of polygons. The algorithm is based on the decomposition of a polygon into a disjoint set of simple elements, managed through the use of the available low-level procedures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Non-CPAP therapies in obstructive sleep apnoea: mandibular advancement device therapy (2011)

Mandibular advancement devices (MADs) represent the main non-continuous positive airway pressure (non-CPAP) therapy for patients with obstructive sleep apnoea (OSA). The aim of the European Respiratory Society Task Force was to review the evidence in favour of MAD therapy. Effects of tongue-retaining devices are not included in this report. Custom-made MADs reduce apnoea/hypopnoea index (AHI) and daytime sleepiness compared with placebo devices. CPAP more effectively diminishes AHI, while increasing data suggest fairly similar outcomes in relation to symptoms and cardiovascular health from these treatments. Patients often prefer MADs to CPAP. Milder cases and patients with a proven increase in upper airway size as a result of mandibular advancement are most likely to experience treatment success with MADs. A custom-made device titrated from an initial 50% of maximum mandibular advancement has been recommended. More research is needed to define the patients who will benefit from MAD treatment compared with CPAP, in terms of the effects on sleep-disordered breathing and on other diseases related to OSA. In conclusion, MADs are recommended for patients with mild to moderate OSA (Recommendation Level A) and for those who do not tolerate CPAP. The treatment must be followed up and the device adjusted or exchanged in relation to the outcome.
Tobramycin and bicarbonate synergise to kill planktonic Pseudomonas aeruginosa, but antagonise to promote biofilm survival (2016)

Increasing antibiotic resistance and the declining rate at which new antibiotics come into use create a need to increase the efficacy of existing antibiotics. The aminoglycoside tobramycin is standard-of-care for many types of <i>Pseudomonas aeruginosa</i> infections, including those in the lungs of cystic fibrosis (CF) patients. <i>P. aeruginosa</i> is a nosocomial and opportunistic pathogen that, in planktonic form, causes acute infections and, in biofilm form, causes chronic infections. Inhaled bicarbonate has recently been proposed as a therapy to improve antimicrobial properties of the CF airway surface liquid and viscosity of CF mucus. Here we measure the effect of combining tobramycin and bicarbonate against <i>P. aeruginosa</i>, both lab strains and CF clinical isolates. Bicarbonate synergises with tobramycin to enhance killing of planktonic bacteria. In contrast, bicarbonate antagonises with tobramycin to promote better biofilm growth. This suggests caution when evaluating bicarbonate as a therapy for CF lungs infected with <i>P. aeruginosa</i> biofilms. We analyse tobramycin and bicarbonate interactions using an interpolated surface methodology to measure the dose-response function. These surfaces allow more accurate estimation of combinations yielding synergy and antagonism than do standard isobolograms. By incorporating predictions based on Loewe additivity theory, we can consolidate information on a wide range of combinations that produce a complex dose-response surface, into a single number that measures the net effect. This tool thus allows rapid initial estimation of the potential benefit or harm of a therapeutic combination. Software code is freely made available as a resource for the community.
Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma (2015)

Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related death worldwide, and the factors influencing HCC progression are poorly understood. Here we reveal that HCC progression via induction of epithelial-mesenchymal transition (EMT) is closely associated with the expression of CD36/fatty acid translocase and elevated free fatty acid (FFA) levels. Although obesity is manifested as elevated FFA levels, the degree of EMT was not associated with the body mass index of the patients, highlighting the specific roles of CD36 and FFA uptake. Treatment of human liver cancer cell lines with FFAs exacerbated the EMT phenotype, whereas chemical inhibition of CD36 mitigated these effects. Furthermore, the Wnt and TGF-β signaling pathways were activated upon FFA treatment, potentially acting as upstream activators of the EMT program. These results provide the first direct evidence associating CD36 and elevated FFAs with HCC progression.
Physiochemical Aspects of Tubulin-Interacting Antimitotic Drugs (2001)

A diverse group of natural biological compounds bind to microtubules and suppress microtubule dynamics. Here we review the mechanism of microtubule assembly and dynamics as well as structural features that are important for nucleotide binding, GTP hydrolysis and stabilization of longitudinal and lateral protofilament contacts. Specific emphasis is placed upon the polar structure of the microtubule, the exposure of the nucleotide hydrolysis site at the + end and the conformational and configurational plasticity of the microtubule lattice. These features have important implications for the mechanism of dynamic instability and the disruptive action of antimitotic drugs. We then discuss the various classes of tubulin binding drugs emphasizing their site and mode of binding as well as the structural and energetic basis for their effects on microtubule assembly and dynamics. A common feature of tubulin-interacting compounds is a linkage to assembly, either the stabilization of a microtubule lattice by compounds like taxol or epothilone A, or the preferential formation of alternate lattice contacts and polymers at microtubule ends by compounds like colchicine, vinca alkaloids and cryptophycin-52. Finally, we explore the likely possibility that these drugs also disrupt the regulation of microtubule dynamics. Future generations of these compounds may be selectively developed to directly target the proteins that regulate mitotic spindle dynamics.
Contribution of positively charged flanking residues to the insertion of transmembrane helices into the endoplasmic reticulum (2008)

Positively charged residues located near the cytoplasmic end of hydrophobic segments in membrane proteins promote membrane insertion and formation of transmembrane alpha-helices. A quantitative understanding of this effect has been lacking, however. Here, using an in vitro transcription-translation system to study the insertion of model hydrophobic segments into dog pancreatic rough microsomes, we show that a single Lys or Arg residue typically contributes approximately -0.5 kcal/mol to the apparent free energy of membrane insertion (DeltaG(app)) when placed near the cytoplasmic end of a hydrophobic segment and that stretches of 3-6 Lys residues can contribute significantly to DeltaG(app) from a distance of up to approximately 13 residues away.
Protease-Deleted Adenovirus Vectors and Complementing Cell Lines: Potential Applications of Single-Round Replication Mutants for Vaccination and Gene Therapy (2000)

A new kind of versatile adenoviral vector (AdV) has been constructed, one that is completely replication disabled in the absence of Ad-E1 proteins but is capable of a single round of replication when Ad-E1 is present. This was made possible by deletion of the Ad protease gene (PS), which is essential for many steps of the Ad life cycle. The PS-deleted virus can be propagated in 293-derived cell lines engineered to express PS. In these new complementing cells, the PS gene was expressed from a tetracycline-inducible promoter in a dicistronic vector coexpressing the green fluorescent protein (GFP). When induced, the best 293-PS stable clones produced the PS in amounts greater than the level reached after Ad infection. Biological activity was first demonstrated by the ability of 293-PS cells to support the replication of Ad2ts1, a mutant expressing a functionally defective PS. While overexpression of the Ad PS slightly affected cell growth, moderate expression at levels sufficient to fully complement Ad2ts1 was well tolerated in 293 cells. Two PS-deleted mutants, deleted or not deleted for E1/E3, were then generated and characterized. Despite their complete loss of infectivity after a single round of replication in permissive cells, the PS-deleted mutants produced as much viral protein as wildtype Ad. These new vectors should thus be both safer and more efficient for applications in which enhancement of transgene expression is desirable, as in the case of vaccination, in situ therapy for tumors, protein production, or the large-scale production of other viral vectors such as adeno-associated virus (AAV).
The Intelligence of Hydrocephalic Children (1981)

In a group of 78 children with hydrocephalus in the first months of life, the level and pattern of intelligence were considered in relation to various parameters and symptoms of their condition. These included demography (age, sex, handedness); early developmental status; symptoms (visual, motor, and seizure); formative pathology; type of hydrocephalus; site of CSF obstruction; extent and configuration of cortical thinning; and shunt treatment. The common outcome of early hydrocephalus is an uneven growth of intelligence during childhood, with nonverbal intelligence developing less well than verbal intelligence. The origin of this selective cognitive deficit is in neither the hydrocephalic condition itself nor its treatment, but rather in the developmental brain anomalies and symptoms to which the hydrocephalic child is prone: In children with aqueduct blocks and intraventricular hydrocephalus, a selectively thin vertex and occipital lobe; in any hydrocephalic child, ocular abnormalities, motor deficits, and seizures.
Purification, Cloning, and Characterization of the CEL I Nuclease (2000)

CEL I, isolated from celery, is the first eukaryotic nuclease known that cleaves DNA with high specificity at sites of base-substitution mismatch and DNA distortion. The enzyme requires Mg(2+) and Zn(2+) for activity, with a pH optimum at neutral pH. We have purified CEL I 33 000-fold to apparent homogeneity. A key improvement is the use of alpha-methyl-mannoside in the purification buffers to overcome the aggregation of glycoproteins with endogenous lectins. The SDS gel electrophoresis band for the homogeneous CEL I, with and without the removal of its carbohydrate moieties, was extracted, renatured, and shown to have mismatch cutting specificity. After determination of the amino acid sequence of 28% of the CEL I polypeptide, we cloned the CEL I cDNA. Potential orthologs are nucleases putatively encoded by the genes BFN1 of Arabidopsis, ZEN1 of Zinnia, and DSA6 of daylily. Homologies of CEL I with S1 and P1 nucleases are much lower. We propose that CEL I exemplifies a new family of neutral pH optimum, magnesium-stimulated, mismatch duplex-recognizing nucleases, within the S1 superfamily.
MOLECULAR AND CELLULAR BIOLOGY (2007)

1. Introduction to Cell and Molecular Biology 2. A Chemical Background for Cell and Molecular Biology 3. Energy, Enzymes, and Biological Reactions 4. The Structure of Cellular Membranes 5. The Functions of Membranes in Transport 6. The Cell Surface 7. Extracellular Structures of Eurkaryotic Cells: The Extracellular Matrix 8. Provision of Energy for Cell Activities: Cellular Oxidations and the Meitochondrion 9. Photosynthesis and the Chloroplast 10. Microtubules and Cell Motility 11. Microfilament-Generated Cell Motility 12. The Cytoskeleton 13. The Nucleus and Its Molecular Constituents 14. The Transcription and the Processing of Messenger RNA 15. Transcription and Processing of rRNA, tRNA, and sn/scRNAs 16. The Interaction of mRNA, rRNA, and tRNA in Protein Synthesis 17. Transcriptional and Translational Regulation 18. Organization of the Genome and Genetic Rearrangements 19. Programmed Genetic Rearrangements as a Part of Normal Cell Function: The Generation of Antibodies 20. Protein Sorting, Distribution, Secretion, and Endocytosis 21. Transcription and Translation in Mitochondria and Chloroplasts 22. The Cell Cycle and DNA Replication 23. Cell Cycle Regulation and Cancer 24. Nuclear and Cytoplasmic Division 25. Meiosis and Genetic Recombination 26. Gametogenesis, Fertilization, and Early Development 27. The Origins of Cellular Life
CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum (1998)

Cellular stress, particularly in response to toxic and metabolic insults that perturb function of the endoplasmic reticulum (ER stress), is a powerful inducer of the transcription factor CHOP. The role of CHOP in the response of cells to injury associated with ER stress was examined in a murine deficiency model obtained by homologous recombination at the chop gene. Compared with the wild type, mouse embryonic fibroblasts (MEFs) derived from chop -/- animals exhibited significantly less programmed cell death when challenged with agents that perturb ER function. A similar deficit in programmed cells death in response to ER stress was also observed in MEFs that lack CHOP's major dimerization partner, C/EBPbeta, implicating the CHOP-C/EBP pathway in programmed cell death. An animal model for studying the effects of chop on the response to ER stress was developed. It entailed exposing mice with defined chop genotypes to a single sublethal intraperitoneal injection of tunicamycin and resulted in a severe illness characterized by transient renal insufficiency. In chop +/+ and chop +/- mice this was associated with the early expression of CHOP in the proximal tubules followed by the development of a histological picture similar to the human condition known as acute tubular necrosis, a process that resolved by cellular regeneration. In the chop -/- animals, in spite of the severe impairment in renal function, evidence of cellular death in the kidney was reduced compared with the wild type. The proximal tubule epithelium of chop -/- animals exhibited fourfold lower levels of TUNEL-positive cells (a marker for programmed cell death), and significantly less evidence for subsequent regeneration. CHOP therefore has a role in the induction of cell death under conditions associated with malfunction of the ER and may also have a role in cellular regeneration under such circumstances.
Cellulase production by a new mutant strain of Trichoderma reesei MCG77 (1978)

Productivity in a cellulase fermentation can be improved by optimization of media and fermentation conditions and by strain improvement, which enables us to alleviate or circumvent the genetic and metabolic controls that reduce or limit enzyme synthesis. T. reesei is the best organism to use for cellulase production because it produces high levels of a stable and complete cellulase complex. The wild strain produces little cellulase because of the restrictions placed on cellulase synthesis by genetic and metabolic controls. The mutant strains with enhanced cellulase productivity metabolic controls. The mutant strains with enhanced cellulase productivity AM 9414 and NG 14 are also subject to catabolite repression. With these mutants the best yields are attained when growth is good but restrained by substrate limitation or low pH. The results obtained in using new improved strains of T. reesei were discussed. High cellulase productivity was attained by using 6% two-roll milled cotton which contains about 80% fairly susceptible cellulose and about 20% residue that is very resistant to cellulase. The mutant strains grow rapidly on the susceptible portions of the cellulose, producing mostly biomass, and then continue hydrolyzing the resistant fraction of the cellulose with active enzyme production over a 14-day period,more » which results finally in broths containing up to 2% extracellular protein. Strain MCG 77 gives yields similar to the other enhanced mutant strains QM 9414 and NG 14 in regular cellulase fermentations. However, this strain grows rapidly on soluble substrates without subsequent restrictions in celllulase synthesis and has a faster rate of metabolism and enzyme production. 8 figures, 3 tables.« less
New Recombinant Ad5 Vector Overcomes Ad5 Immunity Allowing for Multiple Safe, Homologous Immunizations (2012)

Recombinant viral vectors have been utilized in the settings of gene therapy, vaccination and immunotherapy but have encountered clinical challenges because they are recognized as foreign entities to the host. This recognition leads to an immunologic clearance of the vector and the inserted gene of interest. We have reported on a new viral vector technology that can be utilized as an immunization modality to induce immune responses even in the presence of vector immunity. We have reported immunization and immunotherapy results to infectious diseases and cancers. This improved viral platform, Ad5 [E1-, E2b-], can be utilized in the development of multiple vaccines and immunotherapies.
Tumor necrosis factor-alpha augments pulmonary arterial transendothelial albumin flux in vitro (1990)

Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator of pulmonary vascular endothelial injury. We studied the effect of human recombinant TNF alpha (rTNF alpha) on transfer of 14C-labeled bovine serum albumin (BSA) across cultured bovine pulmonary arterial endothelial cell monolayers. rTNF alpha induced a dose-, time-, and temperature-dependent increment in transendothelial [14C]BSA flux. Only after an incubation time of greater than or equal to 4 h did rTNF alpha significantly (P less than 0.005) increase transendothelial albumin flux. rTNF alpha exposure times as brief as 5 min induced significantly (P less than 0.005) increased albumin transfer at 6 h. Although this initial rTNF alpha-endothelial interaction was not temperature dependent, the subsequent barrier dysfunction could only be generated at 37 degrees C. The rTNF alpha-induced changes could not be ascribed to endothelial cell cytotoxicity and was not blocked by protein synthesis inhibition. The effects of rTNF alpha on endothelial permeability were reversible and not specific for albumin transfer. Therefore, rTNF alpha may influence the movement of macromolecules across the pulmonary vascular endothelial barrier.