gebhart/patrepeval huggingface dataset:
Porous Zero-Mode Waveguides for Picogram-Level DNA Capture (2018)

We have recently shown that nanopore zero-mode waveguides are effective tools for capturing picogram levels of long DNA fragments for single-molecule DNA sequencing. Despite these key advantages, the manufacturing of large arrays is not practical due to the need for serial nanopore fabrication. To overcome this challenge, we have developed an approach for the wafer-scale fabrication of waveguide arrays on low-cost porous membranes, which are deposited using molecular-layer deposition. The membrane at each waveguide base contains a network of serpentine pores that allows for efficient electrophoretic DNA capture at picogram levels while eliminating the need for prohibitive serial pore milling. Here, we show that the loading efficiency of these porous waveguides is up to 2 orders of magnitude greater than their nanopore predecessors. This new device facilitates the scaling-up of the process, greatly reducing the cost and effort of manufacturing. Furthermore, the porous zero-mode waveguides can be used for applications that benefit from low-input single-molecule real-time sequencing.
Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration (2010)

Defects in biogenesis or function(s) of primary cilia are associated with numerous inherited disorders (called ciliopathies) that may include retinal degeneration phenotype. The cilia-expressed gene RPGR (retinitis pigmentosa GTPase regulator) is mutated in patients with X-linked retinitis pigmentosa (XLRP) and encodes multiple protein isoforms with a common N-terminal domain homologous to regulator of chromosome condensation 1 (RCC1), a guanine nucleotide exchange factor (GEF) for Ran GTPase. RPGR interacts with several ciliopathy proteins, such as RPGRIP1L and CEP290; however, its physiological role in cilia-associated functions has not been delineated. Here, we report that RPGR interacts with the small GTPase RAB8A, which participates in cilia biogenesis and maintenance. We show that RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange. Disease-causing mutations in RPGR diminish its interaction with RAB8A and reduce the GEF activity. Depletion of RPGR in hTERT-RPE1 cells interferes with ciliary localization of RAB8A and results in shorter primary cilia. Our data suggest that RPGR modulates intracellular localization and function of RAB8A. We propose that perturbation of RPGR-RAB8A interaction, at least in part, underlies the pathogenesis of photoreceptor degeneration in XLRP caused by RPGR mutations.
A Prospective Study of Dietary Calcium and Other Nutrients and the Risk of Symptomatic Kidney Stones (1993)

A high dietary calcium intake decreases the risk of symptomatic kidney stones.
Protection of Mice from Lethal Infection with Aujeszky's Disease Virus by Immunization with Purified gVI (1988)

Virus envelope glycoprotein gVI (gp50) of Aujeszky's disease virus (ADV) was purified from a Nonidet P40-solubilized lysate of ADV-infected Vero cells by immunoaffinity chromatography using a monoclonal antibody against gVI. Mice immunized by the purified gVI produced virus-neutralizing antibody and were successfully protected against subsequent challenge with ADV.
Monoclonal Antibodies That Block the Activity of Leukocyte Function-associated Antigen 1 Recognize Three Discrete Epitopes in the Inserted Domain of CD11a (1995)

The epitopes recognized by eight independently isolated monoclonal antibodies to the alpha chain of human and murine leukocyte function-associated antigen 1 (LFA-1), all able to inhibit receptor function, were identified. Initial localization of epitopes was accomplished using chimeric proteins constructed by splicing fragments of cDNAs encoding the alpha subunit of LFA-1 (CD11a) and the alpha subunit of the closely related leukocyte integrin, Mac-1 (CD11b). Antibody binding to CD11a/CD11b chimeras, expressed in the 293 human kidney cell line, demonstrated that the epitopes recognized by six monoclonal antibodies to human CD11a were located in a approximately 200-amino acid sequence found in all beta 2-integrin alpha subunits, termed the inserted (I) domain. Three distinct epitopes within the I domain (IdeA, IdeB, and IdeC) were identified using a series of mutants in which sequences from murine CD11a were substituted into human CD11a. A series of mutants incorporating single amino acid substitutions was used to identify individual amino acids essential for antibody binding. The location of these residues accounts for the binding specificity of LFA-1-blocking antibodies and identifies particular conserved sequences (residues 126-150) in the I domain of CD11a and homologous sequences in other beta 2-integrin alpha subunits that may be important for ligand binding.
pH-Dependent Fluorescence Spectra of 3-Substituted Umbelliferones (1977)

Abstract Fluorescence data of 3-ethoxycarbonyl-, 3-acetyl-, 3-phephyl-, 4-methyl-3-phenyl-, 3-(2-benzothiazolyl) -and 3-cyanosubstituted 7-hydroxycoumarines are reported as a function of acidity (p H 0 - 9). Unlike umbelliferone or its 4-methyl derivative they do not exhibit significant photoautomerism in acidified solutions, but with the exception of the benzothiazolyl derivative. This behaviour can be interpreted in terms of a) steric hindrance by the substituent and b) enhanced charge delocalisation in the first excited singlet state, leading to lower basicities at the ring carbonyl oxygen.
Role of cyclic plastic deformation in the wear of UHMWPE acetabular cups (1995)

The mechanisms of wear in ultra-high-molecular-weight polyethylene (UHMWPE) acetabular cups were investigated on both laboratory simulator-tested cups and a clinically retrieved component. Two different levels of wear process were identified: one characterized by the formation and detachment of platelet-like flakes from initial machining marks, and the other by the formation of fine ripple and fibrils by repeated passes of microscopic asperities on the femoral head. Both wear processes could be described by a criterion of critical plastic strain. A theoretical model was developed to account for the generation of the microscopic wear particles based on such a critical strain criterion. Its predictions of the dependence of the UHMWPE wear rate on surface roughness and applied load were in excellent agreement with previously published experimental correlations.
Nucleotide Sequence of a Human Immunoglobulin Cγ4 Gene (1981)

We report the nucleotide sequence of a gene encoding the constant region of a human immunoglobulin gamma 4 heavy chain (C gamma 4). These data represent the first complete sequence determination of a human CH gene. As expected from structural studies of mouse C gamma genes, the coding sequences for the CH domains and hinge segment are separated from one another by intervening DNA sequences. Comparison with genomic sequences of the mouse C gamma 1, C gamma 2a, and C gamma 2b genes shows conservation of the sequences in the constant region domains and the 3' untranslated region surrounding the presumed site of poly(A) addition.
In situ analysis of lignins in transgenic tobacco reveals a differential impact of individual transformations on the spatial patterns of lignin deposition at the cellular and subcellular levels (2001)

Using tobacco transgenic lines altered in the monolignol biosynthetic pathway and which differ in their lignin profiles we have evaluated lignin deposition at the cellular and subcellular levels using several microanalytical techniques. Surprisingly, whereas a Cinnamoyl CoA reductase (CCR) down-regulated line with a strong decrease in lignin content exhibited an overall reduction in lignin deposition in the walls of the different xylem cell types, this reduction was selectively targeted to the fibers in a double transformant (down-regulated for both CCR and Cinnamyl alcohol dehydrogenase (CAD)) displaying a similar degree of global lignin content decrease. Fiber and vessel secondary walls of the transgenic tobacco line homozygous for the ccr antisense gene (CCR.H) down-regulated plants were dramatically destructured, particularly in the S2 sublayer, whereas the deposition of lignins in the S1 sublayer was not significantly modified. In contrast, cell wall organization was slightly altered in xylem cells of the double transformant. The relative distribution of non-condensed and condensed units in lignin, evaluated microscopically with specific antibodies, was differentially affected in the transgenics studied and, in a general way, a drop in non-condensed lignin units (beta- 0-4 interunit linkages) was associated with a loss of cohesion and extensive disorganization of the secondary wall. These results demonstrate that lignification is tightly and independently regulated in individual cell types and cell wall sublayers. They also show that down-regulation of specific genes may induce targeted changes in lignin structure and in spatial deposition patterns of the polymer.
Interface surfaces for protein-protein complexes (2004)

Protein-protein interactions, which form the basis for most cellular processes, result in the formation of protein interfaces. Believing that the local shape of proteins is crucial, we take a geometric approach and present a definition of an interface surface formed by two or more proteins. We also present an algorithm and study the geometric and topological properties of these surfaces, thus paving the way for future biochemical studies of protein-protein interactions.
Toward Fulfilling the Promise of Molecular Medicine in Fragile X Syndrome (2010)

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and a leading known cause of autism. It is caused by loss of expression of the fragile X mental retardation protein (FMRP), an RNA-binding protein that negatively regulates protein synthesis. In neurons, multiple lines of evidence suggest that protein synthesis at synapses is triggered by activation of group 1 metabotropic glutamate receptors (Gp1 mGluRs) and that many functional consequences of activating these receptors are altered in the absence of FMRP. These observations have led to the theory that exaggerated protein synthesis downstream of Gp1 mGluRs is a core pathogenic mechanism in FXS. This excess can be corrected by reducing signaling by Gp1 mGluRs, and numerous studies have shown that inhibition of mGluR5, in particular, can ameliorate multiple mutant phenotypes in animal models of FXS. Clinical trials based on this therapeutic strategy are currently under way. FXS is therefore poised to be the first neurobehavioral disorder in which corrective treatments have been developed from the bottom up: from gene identification to pathophysiology in animals to novel therapeutics in humans. The insights gained from FXS and other autism-related single-gene disorders may also assist in identifying molecular mechanisms and potential treatment approaches for idiopathic autism.
High-quality audio compression using an adaptive wavelet packet decomposition and psychoacoustic modeling (1998)

This paper presents a technique to incorporate psychoacoustic models into an adaptive wavelet packet scheme to achieve perceptually transparent compression of high-quality (34.1 kHz) audio signals at about 45 kb/s. The filter bank structure adapts according to psychoacoustic criteria and according to the computational complexity that is available at the decoder. This permits software implementations that can perform according to the computational power available in order to achieve real time coding/decoding. The bit allocation scheme is an adapted zero-tree algorithm that also takes input from the psychoacoustic model. The measure of performance is a quantity called subband perceptual rate, which the filter bank structure adapts to approach the perceptual entropy (PE) as closely as possible. In addition, this method is also amenable to progressive transmission, that is, it can achieve the best quality of reconstruction possible considering the size of the bit stream available at the encoder. The result is a variable-rate compression scheme for high-quality audio that takes into account the allowed computational complexity, the available bit-budget, and the psychoacoustic criteria for transparent coding. This paper thus provides a novel scheme to marry the results in wavelet packets and perceptual coding to construct an algorithm that is well suited to high-quality audio transfer for Internet and storage applications.
A comparative study of a class of full bridge zero-voltage-switched PWM converters (2002)

Four implementations of a full-bridge zero-voltage-switched PWM power converter are discussed. The merits and limitations of each implementation are reviewed and their key features and characteristics are compared. In addition, experimental performance comparisons of the four power converters were performed on 1 kW/400 V laboratory prototypes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The fifth domain of beta 2-glycoprotein I contains a phospholipid binding site (Cys281-Cys288) and a region recognized by anticardiolipin antibodies. (1994)

We have identified a phospholipid binding site in the fifth domain of beta 2-glycoprotein I (beta 2-GPI). Using synthetic peptides spanning the fifth domain of beta 2-GPI, we have shown that the presence of the sequence Glu274-Cys288 caused a decrease in the binding of purified anticardiolipin (aCL) antibodies in a modified cardiolipin (CL)-ELISA by inhibiting the binding of beta 2-GPI to CL. This peptide bound to and could be eluted from a CL affinity column in a manner similar to native beta 2-GPI. Peptides corresponding to other regions of the fifth domain had no inhibitory effect. The inhibitory activity was restricted to the sequence Cys281-Lys-Asn-Lys-Glu-Lys-Lys-Cys288. Peptides in which the two flanking cysteine residues were deleted or substituted with serine residues possessed no inhibitory activity, indicating that the conformation of this highly positively charged sequence may be critical for phospholipid binding. aCL antibodies purified from patients with autoimmune disease were shown to bind directly to wells coated with native beta 2-GPI but not to wells coated with a preparation of beta 2-GPI cleaved between Lys317 and Thr318. The integrity of this sequence is therefore critical for these antibodies to recognize beta 2-GPI, and the putative epitope for aCL antibodies is most likely to be in this region.
Liver Cirrhosis Is Reverted by Urokinase-Type Plasminogen Activator Gene Therapy (2000)

Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans.
Identification of p53 Gene Mutations in Bladder Cancers and Urine Samples (1991)

Although bladder cancers are very common, little is known about their molecular pathogenesis. In this study, invasive bladder cancers were evaluated for the presence of gene mutations in the p53 suppressor gene. Of 18 tumors evaluated, 11 (61 percent) were found to have genetic alterations of p53. The alterations included ten point mutations resulting in single amino acid substitutions, and one 24-base pair deletion. In all but one case, the mutations were associated with chromosome 17p allelic deletions, leaving the cells with only mutant forms of the p53 gene products. Through the use of the polymerase chain reaction and oligomer-specific hybridization, p53 mutations were identified in 1 to 7 percent of the cells within the urine sediment of each of three patients tested. The p53 mutations are the first genetic alterations demonstrated to occur in a high proportion of primary invasive bladder cancers. Detection of such mutations ex vivo has clinical implications for monitoring individuals whose tumor cells are shed extracorporeally.
The response of left ventricular regional function to afterload stress in patients with old myocardial infarction and ventricular aneurysm. (1991)

The functional response of the left ventricle with scar to increased afterload, was examined in 15 patients with old myocardial infarction and left ventricular aneurysm (OMI). Interventional cine left ventriculography during elevating left ventricular pressure with methoxamine. Wall motion was assessed by the radial and the centerline method. Augmented afterload didn't change ejection fraction in patients with OMI, but normalized wall motion (Z) increased in the aneurysmal region and decreased in the remote region in both methods. In the remote region in patients with OMI, afterload stress shortened left ventricular pressure-radial length (P-L) loops along length axis, and reduced percent systolic radial shortening (SS). In the aneurysmal region, P-L loops showed systolic elongation of length at rest and the slope of end-diastolic point to end-systolic point became steeper with increased afterload, resulting in a decrease of aneurysmal expansion. In summary, with increasing afterload, wall motion decreased in non-infarcted regions and increased in aneurysmal regions, in left ventricles with aneurysm. This mechanism may be interpreted as afterload-induced shifts of P-L loops in each region.
Guided navigation of virtual environments (1995)

This paper presents a new methodology for navigating virtual environments called “The River Analogy.” This analogy provides a new way of thinking about the user's relationship to the virtual environment; guiding the user's continuous and direct input within both space and time allowing a more narrative presentation. The paper then presents the details of how this analogy was applied to a VR experience that is now part of the permanent collection at the Chicago Museum of Science and Industry.
The effects of segmentation and feature choice in a translation model of object recognition (2003)

We work with a model of object recognition where words must be placed on image regions. This approach means that large scale experiments are relatively easy, so we can evaluate the effects of various early and midlevel vision algorithms on recognition performance. We evaluate various image segmentation algorithms by determining word prediction accuracy for images segmented in various ways and represented by various features. We take the view that good segmentations respect object boundaries, and so word prediction should be better for a better segmentation. However, it is usually very difficult in practice to obtain segmentations that do not break up objects, so most practitioners attempt to merge segments to get better putative object representations. We demonstrate that our paradigm of word prediction easily allows us to predict potentially useful segment merges, even for segments that do not look similar (for example, merging the black and white halves of a penguin is not possible with feature-based segmentation; the main cue must be "familiar configuration"). These studies focus on unsupervised learning of recognition. However, we show that word prediction can be markedly improved by providing supervised information for a relatively small number of regions together with large quantities of unsupervised information. This supervisory information allows a better and more discriminative choice of features and breaks possible symmetries.
[Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist. (1990)

Two types of binding sites have previously been described for 36-amino acid neuropeptide Y (NPY), called Y1 and Y2 receptors. Y2 receptors can bind long C-terminal fragments of NPY-e.g., NPY-(13-36)-peptide. In contrast, Y1 receptors have until now only been characterized as NPY receptors that do not bind such fragments. In the present study an NPY analog is presented, [Leu31, Pro34]NPY, which in a series of human neuroblastoma cell lines and on rat PC-12 cells can displace radiolabeled NPY only from cells that express Y1 receptors and not from those expressing Y2 receptors. The radiolabeled analog, [125I-Tyr36] monoiodo-[Leu31, Pro34]NPY, also binds specifically only to cells with Y1 receptors. The binding of this analog to Y1 receptors on human neuroblastoma cells is associated with a transient increase in cytoplasmic free calcium concentrations similar to the response observed with NPY. [Leu31, Pro34]NPY is also active in vivo as it is even more potent than NPY in increasing blood pressure in anesthetized rats. It is concluded that [Leu31, Pro34]NPY is a specific Y1 receptor agonist and that the analog or variants of it can be useful in delineating the physiological importance of Y1 receptors.
Muscle Protein Synthesis in the Elderly Following Ingestion of Whey Protein or its Corresponding Essential Amino Acid Content (2006)

Essential amino acids (EAA) are primarily responsible for the stimulation of muscle protein synthesis following ingestion of a mixture of EAA and non-essential amino acids. PURPOSE: To determine if ingestion of whey protein provides extra benefit in the stimulation of muscle protein synthesis in elderly individuals compared to ingestion of its EAA content alone. METHODS: Nine elderly (5F, 4M; 68 ± 2 yr; 76 ± 3 kg; mean ± SE) ingested 15 g of whey protein and another ten subjects (3F, 7M; 67 ± 2 yr; 82 ± 4 kg) ingested the corresponding EAA content (∼ 7 g) in the whey protein. Primed constant L-[ring−2H5]phenylalanine infusion and muscle biopsies were used to determine muscle protein metabolism. The net phenylalanine balance, based on femoral arterio-venous blood samples, as well as the fractional synthetic rate (FSR), before and 3.5 hrs following the protein/EAA ingestion, were used to determine the leg muscle protein response. RESULTS: The area under the curve (AUC) representing net phenylalanine uptake, a measure of muscle protein accretion, was greater in the whey protein group than the EAA group (23 ± 5 mg/leg vs 10 ± 4; P <0.05). The mean change from basal FSR was greater in the whey protein group than the EAA group (0.029 ± 0.009 %/h vs 0.008 ± 0.006 %/h: P <0.05). The ingestion of whey protein appeared to be more effective in stimulating insulin secretion, as calculated using the AUC, than ingestion of the EAA (803 ± 283 uIU/ml/3.5 hrs vs 287 ± 73 uIU/ml/3.5 hrs: P = 0.06). CONCLUSION: These results suggest that muscle protein synthesis is stimulated to a greater extent by ingestion of 15 g of whey protein than ingestion of its essential amino acid content, which is probably in part due to a greater stimulation of insulin secretion.