gebhart/patrepeval huggingface dataset:
Hepatitis Delta Antigen Requires a Flexible Quasi-Double-Stranded RNA Structure To Bind and Condense Hepatitis Delta Virus RNA in a Ribonucleoprotein Complex (2014)

RNA-protein complexes (RNPs) formed by the hepatitis delta virus RNAs and protein, HDAg, perform critical roles in virus replication. Neither the structures of these RNPs nor the RNA features required to form them have been characterized. HDV RNA is unusual in that it forms an unbranched quasi-double-stranded structure in which short base-paired segments are interspersed with internal loops and bulges. We analyzed the role of the HDV RNA sequence and secondary structure in the formation of a minimal RNP and visualized the structure of this RNP using atomic force microscopy. Our results indicate that HDAg does not recognize the primary sequence of the RNA; rather, the principle contribution of unpaired bases in HDV RNA to HDAg binding is to allow flexibility in the unbranched quasi-double-stranded RNA structure. Visualization of RNPs by atomic force microscopy indicated that the RNA is significantly bent or condensed in the complex.
Ultraviolet Light-Induced Pathology in the Eye: Associated Changes in Ocular Aldehyde Dehydrogenase and Alcohol Dehydrogenase Activities (1993)

Adult male C57BL/6J inbred mice were subjected to ultraviolet radiation (UVR) exposure (302-nm peak wavelength; average intensity 282 microW/cm2) for 1 h and monitored for ocular aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) activity changes over a period of 25 days. Dramatic reductions in activities were observed by 4-6 days postexposure, resulting in enzyme levels of 15-16% of control animals. Major decreases in corneal enzyme levels were predominantly responsible for these changes. Ocular morphology was observed throughout using a photoslit-lamp biomicroscope, with maximum corneal clouding occurring at days 4-6. These data support earlier proposals for major roles for these corneal enzymes in assisting the cornea in protecting the eye against UVR-induced tissue damage.
Identification of a novel mutation of PJVK in the Chinese non-syndromic hearing loss population with low prevalence of the PJVK mutations (2015)

In all, we identiﬁed one novel frameshift mutation, c.930_931del AC (p.C312W fsX19), co-segregating with the phenotype in one consanguineous family with a prevalence of 1.5% (1/65). The p.C312W fsX19 mutation was just positioned in the zinc-fingers domain, which was important to the function of pejvakin, and resulted in a stop codon after 19 additional amino acids. It was not identiﬁed in the controls and was considered as the causative mutation of family 804566 with autosomal recessive, non-syndromic, prelingual sensorineural hearing impairment.
A Novel Multiresolution Spatiotemporal Saliency Detection Model and Its Applications in Image and Video Compression (2009)

Salient areas in natural scenes are generally regarded as areas which the human eye will typically focus on, and finding these areas is the key step in object detection. In computer vision, many models have been proposed to simulate the behavior of eyes such as SaliencyToolBox (STB), Neuromorphic Vision Toolkit (NVT), and others, but they demand high computational cost and computing useful results mostly relies on their choice of parameters. Although some region-based approaches were proposed to reduce the computational complexity of feature maps, these approaches still were not able to work in real time. Recently, a simple and fast approach called spectral residual (SR) was proposed, which uses the SR of the amplitude spectrum to calculate the image's saliency map. However, in our previous work, we pointed out that it is the phase spectrum, not the amplitude spectrum, of an image's Fourier transform that is key to calculating the location of salient areas, and proposed the phase spectrum of Fourier transform (PFT) model. In this paper, we present a quaternion representation of an image which is composed of intensity, color, and motion features. Based on the principle of PFT, a novel multiresolution spatiotemporal saliency detection model called phase spectrum of quaternion Fourier transform (PQFT) is proposed in this paper to calculate the spatiotemporal saliency map of an image by its quaternion representation. Distinct from other models, the added motion dimension allows the phase spectrum to represent spatiotemporal saliency in order to perform attention selection not only for images but also for videos. In addition, the PQFT model can compute the saliency map of an image under various resolutions from coarse to fine. Therefore, the hierarchical selectivity (HS) framework based on the PQFT model is introduced here to construct the tree structure representation of an image. With the help of HS, a model called multiresolution wavelet domain foveation (MWDF) is proposed in this paper to improve coding efficiency in image and video compression. Extensive tests of videos, natural images, and psychological patterns show that the proposed PQFT model is more effective in saliency detection and can predict eye fixations better than other state-of-the-art models in previous literature. Moreover, our model requires low computational cost and, therefore, can work in real time. Additional experiments on image and video compression show that the HS-MWDF model can achieve higher compression rate than the traditional model.
Interpretation and Quantification of Immunostains (2001)

Despite the fact that immunohistochemistry is widely used in routine diagnostic work and is a very common part of scientific reports in pathology and cytology, its standardization still lags behind. Interpretation of immunostains should be based on microanatomic distribution of the staining, proportion of positively stained cells, staining intensity, if relevant, and cutoff levels. These parameters should be shown to be reasonably reproducible and should be clearly defined in publications. Uniformity in the setting of thresholds could probably benefit from interlaboratory control materials containing defined amounts of the target antigen. Reliable and precise quantitative immunohistochemistry requires the use of control materials containing defined amounts of the target antigen and processed alongside the specimen combined with automated computer-assisted microspectrophotometry. Application of these suggestions is hoped to improve standardization and to facilitate communication in the field of immunohistochemistry.
Clonazepam treatment of tardive dyskinesia: a practical GABAmimetic strategy (1990)

Because of the efficacy of specific gamma-aminobutyric acid (GABA) agonists in tardive dyskinesia, the authors tested the benzodiazepine clonazepam in a 12-week, double-blind, placebo-controlled, randomized crossover trial in 19 chronically ill patients with tardive dyskinesia who were being treated with neuroleptics. They found a 35% decrease in dyskinesia ratings with clonazepam treatment. The six patients with predominantly dystonic symptoms showed greater benefit than the 13 patients with predominantly choreoathetoid dyskinesias. Tolerance developed to the antidyskinetic effect of clonazepam in the five patients whose long-term use of the drug was followed, but a 2-week clonazepam-free period recaptured its antidyskinetic effect.
Auditory Thalamus Bursts in Anesthetized and Non-Anesthetized States: Contribution to Functional Properties (2004)

Over the last 10 years, high-frequency bursts of action potentials have been the subject of intense researches to understand their potential role in information encoding. Based on recordings from auditory thalamus neurons (n = 302) collected during anesthesia (pentobarbital, urethan, or ketamine/xylazine), waking (W), and slow-wave sleep (SWS), we investigated how bursts participate to frequency tuning, intensity-function, response latency (and latency variability), and stimulus detectability. Although present in all experimental conditions, bursts never dominated the cells mode of discharge: the highest proportion was found during ketamine/xylazine anesthesia (22%), the lowest during waking (4.5%). In all experimental conditions, bursts preferentially occurred at or around the cells best frequency (BF), thus increasing the frequency selectivity. This effect was observed at both the intensities producing the highest and the lowest evoked responses. Testing the intensity-functions indicated that for most of the cells, there was no systematic relationship between burst proportion and responses strength. Under several conditions (W, SWS, and urethan), when cells exhibited bursts >20%, the variability of their response latency was reduced in burst mode compared with single-spike mode. During W, this effect was accompanied by a reduction of the response latency. Finally, a receiver operating characteristic analysis indicated no particular relation between bursts and stimulus detectability. Compared with single-spike mode, which is present for broader frequency ranges, the prominence of bursts at the BF should contribute to filter information reaching the targets of medial geniculate cells at both cortical and subcortical levels.
Introduction of Macromolecules into Bovine Adrenal Medullary Chromaffin Cells and Rat Pheochromocytoma Cells (PC12) by Permeabilization with Streptolysin O: Inhibitory Effect of Tetanus Toxin on Catecholamine Secretion (1989)

Conditions are described for controlled plasma membrane permeabilization of rat pheochromocytoma cells (PC12) and cultured bovine adrenal chromaffin cells by streptolysin O (SLO). The transmembrane pores created by SLO invoke rapid efflux of intracellular 86Rb+ and ATP, and also permit passive diffusion of proteins, including immunoglobulins, into the cells. SLO-permeabilized PC12 cells release [3H]dopamine in response to micromolar concentrations of free Ca2+. Permeabilized adrenal chromaffin cells present a similar exocytotic response to Ca2+ in the presence of Mg2+/ATP. Permeabilized PC12 cells accumulate antibodies against synaptophysin and calmodulin, but neither antibody reduces the Ca2+-dependent secretory response. Reduced tetanus toxin, although ineffective when applied to intact chromaffin cells, inhibits Ca2+-induced exocytosis by both types of permeabilized cells studied. Omission of dithiothreitol, toxin inactivation by boiling, or preincubation with neutralizing antibodies abolishes the inhibitory effect. The data indicate that plasma membrane permeabilization by streptolysin O is a useful tool to probe and define cellular components that are involved in the final steps of exocytosis.
X-ray Structure of Pyruvate Formate-Lyase in Complex with Pyruvate and CoA (2002)

The glycyl radical enzyme pyruvate formate-lyase (PFL) synthesizes acetyl-CoA and formate from pyruvate and CoA. With the crystal structure of the non-radical form of PFL in complex with its two substrates, we have trapped the moment prior to pyruvate cleavage. The structure reveals how the active site aligns the scissile bond of pyruvate for radical attack, prevents non-radical side reactions of the pyruvate, and confines radical migration. The structure shows CoA in a syn conformation awaiting pyruvate cleavage. By changing to an anti conformation, without affecting the adenine binding mode of CoA, the thiol of CoA could pick up the acetyl group resulting from pyruvate cleavage.
Novel Role of Phosphatidylinositol 3-Kinase in CD28-mediated Costimulation (2001)

Ligation of the CD28 surface receptor provides a major costimulatory signal for full scale T cell activation. Despite extensive studies, the intracellular signaling pathways delivered by CD28 ligation are not fully understood. A particularly controversial matter is the role of phosphatidylinositol 3-kinase (PI3K) in CD28-mediated costimulation. It is known that the binding site for PI3K and Grb-2 lies nested within the YMNM motif of the CD28 cytoplasmic domain. To elucidate the role of PI3K during CD28-mediated interleukin-2 (IL-2) production, CD28 YMNM point and deletion mutants were expressed in Jurkat cells. We then measured IL-2 promoter activation after CD28 ligation. Our results showed that the Y189F mutant, which disrupts binding by PI3K, and the YMNM deletion mutant both demonstrated reduced but significant activity for IL-2 promoter activation. In contrast, the N191A mutant, which retains PI3K binding ability, resulted in a complete abrogation of activity, suggesting that PI3K mediates a negative effect upon transcriptional activation of the IL-2 gene. Consistent with this idea, we found that the addition of a PI3K pharmacological inhibitor augmented IL-2 promoter activity, whereas coexpression of a constitutively active form of PI3K reduced this activity. Taken together, these data indicate that PI3K, when associated with the YMNM motif, may act as a negative mediator in CD28-mediated IL-2 gene transcription.
Quantitative molecular virology in patient management (2000)

The detection of viral genome (that is, viral nucleic acid, either DNA or RNA) has gained enormous importance over the last decade in the diagnosis and management of viral infections and diseases (table 1). Nucleic acid testing (NAT) has proven its superiority over more conventional laboratory techniques in several areas, for example:

View this table:

 Table 1 
Detection of viral genome (qualitative): clinical applications 







As well as qualitative analysis, the characterisation of viruses by analysis of the amplified region of the genome allows the detection and identification of viral types or subtypes and mutants. This is now used to monitor patients on highly active antiretroviral therapy (HAART), based on the multitude of resistance associated mutations that have been characterised in HIV infected patients receiving antiretroviral treatment.1 This allows a more rational therapeutic approach. Sequence analysis has also proved to be a valuable epidemiological tool—for example, to investigate possible links between cases of infection, as in outbreaks of hepatitis B2 and hepatitis C infection.3

In addition to qualitative analysis and genome sequencing, methods have been developed for the quantification of viral genomes. While initially largely applied in the research field, quantitative NAT has recently been introduced into routine diagnostic virology. In this review, we will briefly introduce the different methods available for viral genome quantification, define their place in clinical virology, and speculate on the possible future role of quantitative genomic testing for viral infections.

In principle, molecular biological assays that …
The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease (2009)

Mitochondria play critical roles in neuronal function and almost all aspects of mitochondrial function are altered in Alzheimer neurons. Emerging evidence shows that mitochondria are dynamic organelles that undergo continuous fission and fusion, the balance of which not only controls mitochondrial morphology and number, but also regulates mitochondrial function and distribution. In this review, after a brief overview of the basic mechanisms involved in the regulation of mitochondrial fission and fusion and how mitochondrial dynamics affects mitochondrial function, we will discuss in detail our and others' recent work demonstrating abnormal mitochondrial morphology and distribution in Alzheimer's disease (AD) models and how these abnormalities may contribute to mitochondrial and synaptic dysfunction in AD. We propose that abnormal mitochondrial dynamics plays a key role in causing the dysfunction of mitochondria that ultimately damage AD neurons.
Purification of HLA-linked B lymphocyte alloantigens in immunologically active form by preparative sodium dodecyl sulfate-gel electrophoresis and studies on their subunit association. (1977)

The HLA-linked B cell alloantigen (p29,34) is composed of two subunits of 29,000 (p29) and 34,000 (p34) molecular weight. The partially purified HLA-linked B cell alloantigen was purified by a final step of preparative sodium dodecyl sulfate-gel electrophoresis. An antiserum was prepared against p29,34 which specifically lysed B lymphocytes. In sodium dodecyl sulfate at 21 degrees, p29 and p34 remained noncovalently associated and retained immunologic activity; subunit dissociation at higher temperatures correlated with loss of immunologic activity. Although the pI values of p29 and p34 are 6.1 and 5.2, respectively, the subunits co-electrofocus under nondenaturing conditions. In addition, cross-linking studies showed the B cell antigen has a (p29)1(p34)1 subunit structure.
Radiation chemistry of linear low‐density polyethylene. I. Gel formation and unsaturation effects (1983)

Abstract Quenched and annealed samples of linear low‐density polyethylene (LLDPE) were irradiated with 60 Co γ rays in vacuo at room temperature. The data follow rather accurately Charlesby's equation s = k/r , where s is the soluble fraction, r the dose, and k a constant from which G(X) , the G ‐value for crosslinks, was calculated. Crosslinking in the LLDPE is about twice as extensive at equal doses as in LHDPE. Production of vinylene unsaturation was approximately the same in the two types of polyethylene.
Hormone-Dependent Coactivator Binding to a Hydrophobic Cleft on Nuclear Receptors (1998)

The ligand-binding domain of nuclear receptors contains a transcriptional activation function (AF-2) that mediates hormone-dependent binding of coactivator proteins. Scanning surface mutagenesis on the human thyroid hormone receptor was performed to define the site that binds the coactivators, glucocorticoid receptor-interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1). The residues involved encircle a small surface that contains a hydrophobic cleft. Ligand activation of transcription involves formation of this surface by folding the carboxyl-terminal alpha helix against a scaffold of three other helices. These features may represent general ones for nuclear receptors.
BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells (2003)

The BCL6 proto-oncogene encodes a transcriptional repressor required for the development of germinal centers (GCs) and implicated in the pathogenesis of GC-derived B cell lymphoma. Understanding the precise role of BCL6 in normal GC formation and in lymphomagenesis depends on the identification of genes that are direct targets of its transcriptional repression. Here we report that BCL6 directly controls the expression of B7-1/CD80, a costimulatory receptor involved in B-T cell interactions critical for the development of T cell-mediated antibody responses. Upon CD40 signaling, transcription of the CD80 gene is induced by the nuclear factor (NF)-kappaB transcription factor. Our results show that BCL6 prevents CD40-induced expression of CD80 by binding its promoter region in vivo and suppressing its transcriptional activation by NF-kappaB. Consistent with a physiologic role for BCL6 in suppressing CD80, the expression of these two genes is mutually exclusive in B cells, and BCL6-defective mice show increased expression of CD80 in B cells. The results suggest that BCL6 may directly control the ability of B cell to interact with T cells during normal GC development. In addition, these findings imply that T-B cell interactions may be disrupted in B cell lymphoma expressing deregulated BCL6 genes.
Synthesis and antihypertensive activity of 4-(cyclic amido)-2H-1-benzopyrans (1986)

The synthesis and antihypertensive activity of a series of novel 4-(cyclic amido)-2H-1-benzopyran-3-ols, administered orally to conscious spontaneously hypertensive rats, are described. The effects of lactam ring size, the presence of heteroatoms in the lactam ring, substitution at C(2) and C(3), relative stereochemistry at C(3) and C(4), and aromatic substitution pattern on the blood pressure lowering activity of this series have been determined. The key compound 2 from this work [BRL 34915; (+/-)-6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxopyrrolidin-1- yl)-2H-1-benzopyran-3-ol] has been resolved, and antihypertensive activity was found to reside primarily in the (-) enantiomer. The key step in the preparation of this class of compounds is the action of a cyclo amidic anion on an appropriate epoxide. Another approach, involving a cyclization step to the lactam was found to be more convenient in certain cases, particularly in forming the cis analogue of compound 2. Compound 2 has been shown to possess a novel mechanism of action, and it has been selected for progression to the clinic.
Molecular basis of flame inhibition (1973)

The role played by inorganic chemical additives in fire retardancy and flame inhibition is considered. Particular attention is given to the molecular level aspects of commercially important systems containing compounds of antimony, halogens, and phosphorus. The flame inhibiting function of metal containing additives is also discussed.
Chemokines and their role in airway hyper-reactivity (2000)

Airway hyper-reactivity is a characteristic feature of many inflammatory lung diseases and is defined as an exaggerated degree of airway narrowing. Chemokines and their receptors are involved in several pathological processes that are believed to contribute to airway hyper-responsiveness, including recruitment and activation of inflammatory cells, collagen deposition and airway wall remodeling. These proteins are therefore thought to represent important therapeutic targets in the treatment of airway hyper-responsiveness. This review highlights the processes thought to be involved in airway hyper-responsiveness in allergic asthma, and the role of chemokines in these processes. Overall, the application of chemokines to the prevention or treatment of airway hyper-reactivity has tremendous potential.
A Case Study in the Development of a Staff Appraisal Scheme (1997)

Abstract The research reported in this paper is a review of the appraisal scheme at a higher education (HE) college. Questionnaires were used to collect data from appraisees and appraisers in two successive years. Differences in perception of the appraisal process between appraisers and appraisees were revealed. Some positive developments in the nature of the appraisal interview were noted and some suggested modifications to the scheme are put forward.
Six-Helix Bundle and Triangle DNA Origami Insulator-Based Dielectrophoresis (2013)

Self-assembled DNA nanostructures have large potential for nanoelectronic circuitry, targeted drug delivery, and intelligent sensing. Their applications require suitable methods for manipulation and nanoscale assembly as well as adequate concentration, purification, and separation methods. Insulator-based dielectrophoresis (iDEP) provides an efficient and matrix-free approach for manipulation of micro- and nanometer-sized objects. In order to exploit iDEP for DNA nanoassemblies, a detailed understanding of the underlying polarization and dielectrophoretic migration is essential. Here, we explore the dielectrophoretic behavior of six-helix bundle and triangle DNA origamis with identical sequence but large topological difference and reveal a characteristic frequency range of iDEP trapping. Moreover, the confinement of triangle origami in the iDEP trap required larger applied electric fields. To elucidate the observed DEP migration and trapping, we discuss polarizability models for the two species according to their structural difference complemented by numerical simulations, revealing a contribution of the electrophoretic transport of the DNA origami species in the iDEP trapping regions. The numerical model showed reasonable agreement with experiments at lower frequency. However, the extension of the iDEP trapping regions observed experimentally deviated considerably at higher frequencies. Our study demonstrates for the first time that DNA origami species can be successfully trapped and manipulated by iDEP and reveals distinctive iDEP behavior of the two DNA origamis. The experimentally observed trapping regimes will facilitate future exploration of DNA origami manipulation and assembly at the nano- and microscale as well as other applications of these nanoassemblies with iDEP.