gebhart/patrepeval huggingface dataset:
Differential Regulation of Rat Aquaporin-5 Promoter/Enhancer Activities in Lung and Salivary Epithelial Cells (2000)

Aquaporin-5 (AQP5) is a water channel protein that is selectively expressed in respiratory, salivary, and lacrimal tissues. In order to establish the tissue-specific transcriptional programs that underlie its lung- and salivary-specific expression, a 4.5-kilobase pair DNA fragment encompassing the 5'-flanking region of the rat AQP5 gene has been characterized in detail. A major transcription start site utilized in lung and salivary glands has been localized downstream of a TATAA-like motif. Transient transfection assays of -4.3- and -1.7-AQP5-luciferase constructs in AQP5-expressing lung (MLE-15) and salivary (Pa-4) cells and nonexpressing fibroblast (NIH3T3) and epithelial (HeLa) cells demonstrate preferential transcriptional enhancement of reporter activities in MLE-15 and Pa-4 cells. Transient transfection assays of a series of 5' --> 3' deletion constructs of -4.3-AQP5-luciferase suggest that a common salivary and lung enhancer is located between nucleotides -274 and -139, and a lung-specific enhancer is located between nucleotides -894 and -710. There is one putative lung-specific repressor located in the region of nucleotides -1003/-894 and a common lung and salivary repressor located at nucleotides -503/-385. Moreover, 3' --> 5' deletions up to -171 and -127 base pairs almost abolish transcriptional activation in salivary and lung cells, respectively. Together, our findings indicate that the combination of enhancer/repressor elements within the proximal 5'-flanking region of rat AQP5 gene dictates its restricted expression in both lung and salivary cells.
Characterization of a Melanosomal Transport System in Murine Melanocytes Mediating Entry of the Melanogenic Substrate Tyrosine (1996)

In this study, we identify a transport system for tyrosine, the initial precursor of melanin synthesis, in the melanosomes of murine melanocytes. Melanosomes preloaded with tyrosine demonstrated countertransport of 10 microM [3H]tyrosine, indicating carrier-mediated transport. Melanosomal tyrosine transport was saturable, with an apparent Km for tyrosine transport of 54 microM and a maximal velocity of 15 pmol of tyrosine/unit of hexosaminidase/min. Transport was temperature-dependent (Ea = 7.5 kcal/mol) and showed stereospecificity for the l-isomer of tyrosine. Aromatic, neutral hydrophobic compounds (such as tryptophan and phenylalanine), as well as the small, bulky neutral amino acids (such as leucine, isoleucine, and methionine) competed for tyrosine transport. Tyrosine transport was inhibited by the classical system L analogue, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid and by monoiodotyrosine, but not by cystine, lysine, glutamic acid, or 2-(methylamino)-isobutyric acid. Tyrosine transport showed no dependence on Na+ or K+, and did not require an acidic environment or the availability of free thiols. These results demonstrate the existence of a neutral amino acid carrier in murine melanocyte melanosomes which resembles the rat thyroid FRTL-5 lysosomal system h. This transport system is critical to the function of the melanosome since tyrosine is the essential substrate required for the synthesis of the pigment melanin.
Antibody engineering toward high-sensitivity high-throughput immunosensing of small molecules (2010)

Clinical and environmental analyses often require immunochemical detection and quantification of small molecules (haptens) that are available as biomarkers. However, the affinity ceilings of conventional anti-hapten antibodies, which are produced by immunizing animals, prevent subfemtomole-range determinations with competitive immunoassay formats. "Sandwich-type" noncompetitive (immunometric) assays allow for sensitive determinations of macromolecules (subattomole-range) and the direct relationship between analyte amount and signal intensity provides higher accessibility to modern high-throughput sensing systems. Unfortunately, sandwich-type assays require that analytes have at least two epitopes, and thus are not applicable to haptens. Antibody engineering, i.e., genetic manipulation of antibody molecules, could provide artificially improved reagents that enable us to overcome these limitations. In this review, we summarize recent successful developments and applications of engineered antibodies for sensitive and high-throughput hapten sensing.
Asynchronous design/evaluation methods for hypertext technology development (1989)

A process model used in the design and evaluation of hypertext systems is discussed. The model includes asynchronous processes of task analysis, document analysis, literature survey and systems evaluation, interpretation of data, designing and building systems, and collecting data. For each process, experiences with NaviText™ SAM, a hypertext interface to a reference source, are discussed. A variety of new methods for evaluation of experimental systems are presented along with several empirical results.
Coronavirus leader RNA regulates and initiates subgenomic mRNA transcription both in trans and in cis (1994)

Mouse hepatitis virus (MHV), a coronavirus, utilizes a discontinuous transcription mechanism for subgenomic mRNA synthesis. Previous studies (C.-L. Liao and M. C. C. Lai, J. Virol. 68:4727-4737, 1994) have demonstrated that an upstream cis-acting leader sequence serves as a transcriptional enhancer, but the mechanism of transcriptional regulation is not clear. In this study, we constructed a series of defective interfering (DI) RNAs containing the chloramphenicol acetyltransferase (CAT) gene behind a differentially expressed transcription initiation (intergenic) sequence (for mRNA2-1). These DI RNAs had different copy numbers of the UCUAA pentanucleotide sequence at the 3' end of the leader. Transfection of these DI RNA constructs into cells infected with a helper MHV, which contains either two or three UCUAA copies at the 3' end of the leader, resulted in differential expression of CAT activities. We demonstrated that the copy number of UCUAA repeats in the leaders of both helper viral and DI RNAs affected the level of CAT activity, suggesting that MHV leader RNA could regulate both in trans and in cis the transcription of subgenomic mRNAs. The leader RNA of subgenomic mRNAs was derived from either the trans- or the cis-acting leader. Furthermore, insertion of a UA-rich sequence (UUUAUAAAC) immediately downstream of the leader in DI RNA, to match the sequence of helper viral RNA, enhanced the CAT activity by threefold, suggesting that this nine-nucleotide sequence is a cis-acting element. Interestingly, when the nine-nucleotide sequence was absent in DI RNA, the leaders of subgenomic mRNAs were exclusively derived from the helper virus. In contrast, when the nine-nucleotide sequence was present in DI RNA, the leaders were derived from both helper viral and DI RNAs. These results suggest that the nine-nucleotide sequence either is required for the leader RNA to initiate mRNA synthesis or, alternatively, serves as a transcription terminator for the leader RNA synthesis. However, when a constitutively expressed intergenic sequence (for mRNA7) was used, no difference in transcription efficiency was noted, regardless of the copy number of UCUAA in the DI RNA and helper virus. This study thus indicates that MHV subgenomic RNA transcription requires the interaction among the intergenic (promoter) sequence, a trans-acting leader, and a cis-acting leader sequence. A novel model of transcriptional regulation of coronavirus subgenomic mRNAs is presented.
Biomechanical Comparison of Spondylolysis Fixation Techniques (1999)

All four fixation techniques restored the intervertebral rotational displacements under flexion and torsional loading to the intact condition. The screw-rod-hook fixation allowed the least amount of motion across the defect during flexion.
The dependence of ion bombardment induced preferential orientation on the direction of the ion beam (1981)

Abstract Ion bombardment of vacuum-deposited Cu specimens results in a preferential orientation of {110} planes parallel to the surface plane of the specimen. The effect is shown to be dependent on the direction of the incident beam with respect to the surface plane of the specimen. This evidence suggests a channelling mechanism to explain the origin of the effect.
Identification of Novel Adenosine A2A Receptor Antagonists by Virtual Screening (2012)

Virtual screening was performed against experimentally enabled homology models of the adenosine A(2A) receptor, identifying a diverse range of ligand efficient antagonists (hit rate 9%). By use of ligand docking and Biophysical Mapping (BPM), hits 1 and 5 were optimized to potent and selective lead molecules (11-13 from 5, pK(I) = 7.5-8.5, 13- to >100-fold selective versus adenosine A(1); 14-16 from 1, pK(I) = 7.9-9.0, 19- to 59-fold selective).
Charging mechanism in a SiO2 matrix embedded with Si nanocrystals (2006)

One of the applications of a Si nanocrystals (nc-Si) embedded in a SiO2 matrix is in the area of nonvolatile memory devices based on the charge storage in the material system. However, whether the charge trapping mainly occurs at the nc-Si∕SiO2 interface or in the nc-Si is still unclear. In this work, by x-ray photoemission spectroscopy analysis of the Si 2p peaks, the concentrations of both the nc-Si and the Si suboxides that exist at the nc-Si∕SiO2 interface are determined as a function of thermal annealing, and the charging effect is also measured by monitoring the shift of the surface C 1s peak. It is observed that the annealing-caused reduction of the total concentration of the interfacial suboxides is much faster than that of both the C 1s shift and the nc-Si concentration. In addition, the trend of the C 1s shift coincides with that of the nc-Si concentration. The results suggest that the Si nanocrystal, rather than the nc-Si∕SiO2 interface, plays the dominant role in the charging effect.
Lipopolysaccharides from Campylobacter jejuni associated with Guillain-Barré syndrome patients mimic human gangliosides in structure (1994)

Lipopolysaccharides extracted from Campylobacter jejuni serostrains (serotype reference strains) for serotypes O:4 and O:19 were found to have core oligosaccharides with terminal structures resembling human gangliosides GM1 and GD1a. High-molecular-weight molecules that reflected the presence of O chains were shown in immunoblots to be immunologically specific for each serostrain. The O:19 antiserum also reacted strongly with core oligosaccharides of two isolates from patients with Guillain-Barré syndrome (GBS), but the banding patterns and molecular structures were different from those of the O:19 serostrain. A neuraminobiose disaccharide unit is attached to the terminal Gal residue in one isolate, and the other isolate lacked terminal N-acetyl glucosamine and galactose with attached sialic acid so that the sialic acid residues were present in a neuraminobiose unit linked to the only remaining galactose. Analysis of the high-M(r) lipopolysaccharides of the O:19 serostrain and the two isolates from GBS patients revealed the presence of a hyaluronic acid-like polymer with disaccharide-repeating units consisting of beta-D-glucuronic acid amidated with 2-amino-2-deoxyglycerol and N-acetyl glucosamine. The results confirm a potential role for the core oligosaccharides in the etiology of GBS but also suggest that the O-chain polysaccharide may be a contributing factor.
Multi-mode and multi-level technologies for FeRAM embedded reconfigurable hardware (2003)

Programmability of circuit function is one of the most important features of modern-day VLSIs in terms of flexibility for multiple applications and redundancy against design failures. Ferroelectric non-volatile memory (FeRAM) as a novel reconfigurable engine not only allows a fast write time and low power consumption, but also leads to high efficiency of memory usage. The memory in a FeRAM-based reconfigurable hardware can be used for storing the logic configuration data, the instructions for embedded processors, and at the same time serves as a RAM for data accessing. An array of reconfigurable elements based on FeRAM can be arranged where a microprocessor unit (MPU) is located at the center of the chip, while reconfigurable array elements are located around the rest of the chip. The switching elements connect the reconfigurable array elements to each other. A set of multiple configuration data for each array element is stored locally in the FeRAM.
Constancy and diversity in the flavivirus fusion peptide (2008)

The constancy of the canonical fusion peptide sequences in the arthropod-borne flaviviruses contrasts with the high prevalence of mutations in most individual viruses. The discrepancy may be the result of a survival advantage accompanying sequence diversity (quasispecies) involving the fusion peptide. Limited clinical data with yellow fever virus suggest that the presence of fusion peptide mutants is not associated with a decreased case fatality rate. The cell-fusing related agents may have substantial differences from other flaviviruses in their mechanism of viral entry into the host cell.
A forward link performance study of the 1xEV-DO rev. 0 system using field measurements and simulations (2005)

Following the unprecedented growth of voice applications in wireless mobile communication, high-speed wireless data applications have started to proliferate. One system that has attracted considerable attention is the 1×EV-DO high-speed data system. Extensive analyses indicate that the spectral efficiency of a wireless data application can be increased significantly compared to that of a wireless voice application by means of a number innovative techniques, including turbo coding, rate adaptation, early completion, packet scheduling, and receive diversity. In this paper, we offer extensive field measurements to quantify the gains provided by these techniques. We also provide estimates of the throughput and capacity of the 1×EV-DO system that are validated by both field measurements and simulations.
In vitro polyadenylation is stimulated by the presence of an upstream intron. (1990)

The majority of vertebrate pre-mRNAs are both spliced and polyadenylated. To investigate the mechanism whereby processing factors recognize last exons containing both splicing and polyadenylation consensus elements, chimeric precursor RNAs containing a single intron and a poly(A) site were constructed and assayed for in vitro splicing and polyadenylation. Chimeric RNAs underwent splicing and polyadenylation. Both reactions occurred in a single RNA. The presence of an intron enhanced the rate of polyadenylation at a downstream poly(A) site. The extent of stimulation varied from two- to fivefold, depending on the magnesium concentration. Maximal stimulation of polyadenylation by an upstream intron required a 3' splice site but not a 5' splice site, suggesting that the structure of the terminal exon was more important than the presence of a complete upstream intron. We suggest that splicing and polyadenylation factors interact to recognize terminal, poly(A) site-containing exons. Such interaction may explain why all known intron-containing eukaryotic pre-mRNAs generate their 3' ends by polyadenylation.
A monoclonal antibody to Candida albicans enhances mouse neutrophil candidacidal activity (1997)

A monoclonal antibody (MAb) to Candida albicans (MAb B6.1) that protects against candidiasis and the nonprotective MAb B6 were compared for ability to support neutrophil (polymorphonuclear leukocyte [PMN]) candidacidal activity. Both MAbs are immunoglobulin M, and each recognizes distinct C. albicans mannan cell wall determinants. PMN candidacidal activity was assessed by transmission electron microscopy and by an in vitro killing assay. The results indicated that MAb B6.1, but not MAb B6, enhances ingestion and killing of yeast cells by PMN in the presence of serum complement.
Development and validation of receptor occupancy pharmacodynamic assays used in the clinical development of the monoclonal antibody vedolizumab (2015)

Two pharmacodynamic receptor occupancy assays were developed and validated to assess the effect of vedolizumab on peripheral blood cells. The results of these assays demonstrated the practical use of flow cytometry to examine pharmacodynamic response in clinical trials.
Engineering of an Hepatic Organoid to Develop Liver Assist Devices (2010)

Cell-based technologies to support/restore liver function represent one of the most promising opportunities in the treatment of acute liver failure. However, the understanding of the constituent cell types that interact to achieve liver-specific structure and function has not been achieved in the development of liver assist devices (LADs). Here we show that hepatocytes migrated toward and adhered and formed sinusoids-like structures in conjunction with liver nonparenchymal cells, and that this liver organoid formed sophisticated tissue after 7 days in an implanted LAD in rodents. Hepatocytes only or in combination with human nonparenchymal liver cell lines (endothelial, cholangiocytes, and stellate cells) were cultured in Matrigel. Ultrastructural analysis showed that the hepatocyte-decorated endothelial vascular structures resemble in vivo sinusoids containing plate-like structures, bile canaliculi, and lumen. The sinusoid-like structures retained albumin secretion and drug metabolism capabilities. In addition, LADs containing cocultures of human liver nonparenchymal cells were transplanted in animals for a week; the liver tissue formed sophisticated structures resembling the liver. These results demonstrate the importance of nonparenchymal cells in the cellular composition of LADs. The novelty of the culture's sinusoid-like organization and function strongly support the integration of liver nonparenchymal units into hepatocyte coculture-based LADs as a potential destination therapy for liver failure.
Fast Boundary Element Method for Shape Optimization of RPV Nozzles (2011)

Summary A three-dimensional fast boundary element solver is developed for the shape optimization of nozzles of nuclear reactor pressure vessels (RPVs). In a RPV, pressure and mechanical loads may lead to high stress concentration due to the discontinuity of the structure, especially at the inner surface of the cold/hot legs. This work aims to minimize these stress concentrations by optimizing the geometry of the openings using modern shape optimization techniques and fast boundary element method. Shape optimization methods based on the principle of biological adaptive growth are incorporated into a boundary element method program and used to optimize the design of the RPV. The fast multipole method is adopted to accelerate the three-dimensional boundary element solution with large scales. In the numerical examples, the influence of the design variables on the convergence and efficiency is studied. Compared with the conventional design, the stress level at the in the optimized design is reduced significantly.
Rhodium-Catalyzed C–H Amination. An Enabling Method for Chemical Synthesis (2011)

Reaction methods for selective C-H amination are finding ever-increasing utility for the preparation of nitrogen-derived fine chemicals. This brief account highlights the remarkable versatility of dirhodium-based catalysts for promoting oxidation of aliphatic C-H centers in both intra- and intermolecular reaction processes.
Protein fold recognition by sequence threading: tools and assessment techniques (1996)

Protein fold recognition has been approached by threading an amino acid sequence onto a library of folds, calculating a sequence-structure compatibility score, and ranking these scores. Due to imperfections in the empirically derived pairwise potential functions and the necessarily heuristic approach to the sequence-structure alignment problem, the method benefits from the assessment of threaded models to evaluate the most probable structures among the list of possible folds. THREADER and ANALYST, software tools available through the Internet, facilitate the alignment and assessment steps of a threading prediction. No process has been found to be universally reliable for the detection of folds related to the structure of a known input sequence, but several useful steps and approaches are discussed.
Familial Danish Dementia (2005)

Familial Danish dementia is an early onset autosomal dominant neurodegenerative disorder linked to a genetic defect in the BRI2 gene and clinically characterized by dementia and ataxia. Cerebral amyloid and preamyloid deposits of two unrelated molecules (Danish amyloid (ADan) and beta-amyloid (Abeta)), the absence of compact plaques, and neurofibrillary degeneration indistinguishable from that observed in Alzheimer disease (AD) are the main neuropathological features of the disease. Biochemical analysis of extracted amyloid and preamyloid species indicates that as the solubility of the deposits decreases, the heterogeneity and complexity of the extracted peptides exponentially increase. Nonfibrillar deposits were mainly composed of intact ADan-(1-34) and its N-terminally modified (pyroglutamate) counterpart together with Abeta-(1-42) and Abeta-(4-42) in approximately 1:1 mixture. The post-translational modification, glutamate to pyroglutamate, was not present in soluble circulating ADan. In the amyloid fractions, ADan was heavily oligomerized and highly heterogeneous at the N and C terminus, and, when intact, its N terminus was post-translationally modified (pyroglutamate), whereas Abeta was mainly Abeta-(4-42). In all cases, the presence of Abeta-(X-40) was negligible, a surprising finding in view of the prevalence of Abeta40 in vascular deposits observed in sporadic and familial AD, Down syndrome, and normal aging. Whether the presence of the two amyloid subunits is imperative for the disease phenotype or just reflects a conformational mimicry remains to be elucidated; nonetheless, a specific interaction between ADan oligomers and Abeta molecules was demonstrated in vitro by ligand blot analysis using synthetic peptides. The absence of compact plaques in the presence of extensive neuro fibrillar degeneration strongly suggests that compact plaques, fundamental lesions for the diagnosis of AD, are not essential for the mechanism of dementia.
Parameter estimation of finite mixtures using the EM algorithm and information criteria with application to medical image processing (1992)

A method for parameter estimation in image classification or segmentation is studied within the statistical frame of finite mixture distributions. The method models an image as a finite mixture. Each mixture component corresponds to an image class. Each image class is characterized by parameters, such as the intensity mean, the standard deviation, and the number of image pixels in that class. The method uses a maximum likelihood (ML) approach to estimate the parameters of each class and employs information criteria of Akaike (AIC) and/or Schwarz and Rissanen (MDL) to determine the number of classes in the image. In computing the ML solution of the mixture, the method adopts the expectation maximization (EM) algorithm. The initial estimation and convergence of the ML-EM algorithm were studied. The accuracy in determining the number of image classes using AIC and MDL is compared. The MDL criterion performed better than the AIC criterion. A modified MDL showed further improvement.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>