gebhart/patrepeval huggingface dataset:
Replacement of His23 by Cys in a zinc finger of HIV‐1 NCp7 led to a change in 1H NMR‐derived 3D structure and to a loss of biological activity (1993)

The nucleocapsid protein NCp7 of human immunodeficiency virus type 1 (HIV-1), which is necessary for the formation of infectious virions, contains two zinc fingers of the Cys-X2-Cys-X4-His-X4-Cys form. To elucidate the importance of this particular motif, well conserved in retroviruses and retroelements, we substituted the histidine residue by a cysteine in the first zinc binding domain 13VKCFNCGKEGHTARNCRA30. The structures of the mutated and native zinc complexed peptides were studied by two-dimensional 600 MHz 1H nuclear magnetic resonance (NMR) in aqueous solution. The nuclear Overhauser effects were used as constraints to determine the solution structures using DIANA software followed by AMBER energy refinement. The results show that native and mutant peptides fold into non-identical three-dimensional structures, probably accounting for the loss of retrovirus infectivity following the His-Cys point mutation.
Levels of normal and abnormally phosphorylated tau in different cellular and regional compartments of Alzheimer disease and control brains (1994)

Microtubule associated protein tau is abnormally phosphorylated in Alzheimer disease (AD) brain. In the present study we investigated (i) whether tau is axonal or both axonal and somatodendritic, (ii) whether tau is a marker of Alzheimer neurofibrillary pathology, and (iii) whether the levels of tau in the cytosol (100,000 x g supernate) from AD brain are altered. Frozen autopsied tissue from 20 AD, 17 normal aged and 15 neurological control cases obtained 3-8 h postmortem were analyzed. Levels of normal, total, and abnormally phosphorylated tau were determined by a radioimmunoslot-blot assay using mAb Tau-1 as the primary antibody. Both frontal gray matter homogenate and cytosol from normal brains had 30-45% higher levels of normal tau than the corresponding fractions from the white matter. In AD frontal and temporal cortices, the total tau levels were 6- to 7-fold higher than in cerebellar cortex (P < 0.01 and P < 0.02). Furthermore, tau levels of cerebellar cortex, an area of the brain unaffected with Alzheimer neurofibrillary changes, were indistinguishable between AD and control groups. The levels of normal tau in cytosol from both frontal gray and white matters in AD were reduced by approximately 40% (P < 0.05). The levels of total tau in AD frontal and temporal cortex were 4- to 5-fold higher than in the corresponding tissue from control cases (P < 0.01) and this increase was in the form of abnormally phosphorylated tau. These studies suggest (i) that there is probably at least as much tau in the somatodendritic compartment as in the axonal compartment, (ii) that the abnormally phosphorylated tau is a biochemical marker of the neurofibrillary pathology in AD, and (iii) that the levels of normal tau are significantly reduced in the 100,000 x g brain supernate from AD cases.
Mechanism of Clay Tactoid Exfoliation in Epoxy-Clay Nanocomposites (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism of Clay Tactoid Exfoliation in Epoxy-Clay NanocompositesTie LanTie LanMore by Tie Lan, Padmananda D. KaviratnaPadmananda D. KaviratnaMore by Padmananda D. Kaviratna, and Thomas J. PinnavaiaThomas J. PinnavaiaMore by Thomas J. PinnavaiaCite this: Chem. Mater. 1995, 7, 11, 2144–2150Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November 1995https://pubs.acs.org/doi/10.1021/cm00059a023https://doi.org/10.1021/cm00059a023research-articleACS PublicationsRequest reuse permissionsArticle Views2541Altmetric-Citations698LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Results of E1496: A phase III trial of CVP with or without maintenance rituximab in advanced indolent lymphoma (NHL) (2004)

6502 Background: Despite high overall response rates, indolent NHL is characterized by continuous relapse. E1496 evaluated the ability of two years (yr) of maintenance rituximab to prolong progression-free survival (PFS, progression or death) after chemotherapy. Methods: Eligible patients (pt) included stage III-IV follicular grade 1 and 2 (small cleaved, mixed) and small lymphocytic NHL. 516 pt were randomized to CVP (cyclophosphamide 1 g/m2 d 1, vincristine 1.4 mg/m2 d 1, prednisone 100 mg/m2 d 1–5) or CF (CYC 1 g/m2 d 1, fludara 20 mg/m2 d 1–5) stratified by age, histology, B symptoms, and tumor burden (low v high). CF (115 pt) was discontinued 9/01 for toxicity (ASCO 2002). 401 CVP pt were treated to maximum response (6–8 cycles); 9% progressed. Of stable/responding pt, 322 were randomized to rituximab (375 mg/m2 weekly x 4) q 6 months x 4 cycles or observation, stratified by residual disease (minimal v greater) and histology. Results: The study was terminated early as the O'Brien-Fleming boundary for PFS was crossed with 303 of 322 randomized pt assessable (one-sided p=0.00008). The rituximab (n=154) and observation (n=149) pt were respectively balanced for age (59, 56 yr), residual disease (58%, 55% minimal), histology (77%, 77% follicular) & tumor burden (62%, 67% high) as well as gender, stage, marrow involvement and International Prognostic Index. 31 rituximab and 56 observation pt have progressed or died. For randomized pt, PFS estimates at 2 & 4 yr from maintenance randomization (∼2.5 & 4.5 yr post study entry) were 74% v 42% and 58% v 34% for rituximab and observation pt, respectively. PFS was significantly longer after rituximab regardless of histology (p<0.02) or residual disease (p<0.008); pt with high tumor burden (p=0.00005) also had significantly longer PFS after rituximab. With 17 (6%) deaths and median follow-up of 1.2 year among survivors, estimated 2 yr survival from maintenance randomization was 95% for rituximab v 91% for observation pt. Conclusion: Maintenance rituximab significantly prolongs PFS after CVP chemo in pt with advanced indolent NHL. Extended follow-up will determine whether longer PFS translates into improved survival. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; Genetech Biooncology Genentech
Nanobiotechnology-Based Strategies for Crossing The Blood–Brain Barrier (2012)

The blood-brain barrier (BBB) is meant to protect the brain from noxious agents; however, it also significantly hinders the delivery of therapeutics to the brain. Several strategies have been employed to deliver drugs across this barrier and some of these may do structural damage to the BBB by forcibly opening it to allow the uncontrolled passage of drugs. The ideal method for transporting drugs across the BBB should be controlled and should not damage the barrier. Among the various approaches that are available, nanobiotechnology-based delivery methods provide the best prospects for achieving this ideal. This review describes various nanoparticle (NP)-based methods used for drug delivery to the brain and the known underlying mechanisms. Some strategies require multifunctional NPs combining controlled passage across the BBB with targeted delivery of the therapeutic cargo to the intended site of action in the brain. An important application of nanobiotechnology is to facilitate the delivery of drugs and biological therapeutics for brain tumors across the BBB. Although there are currently some limitations and concerns for the potential neurotoxicity of NPs, the future prospects for NP-based therapeutic delivery to the brain are excellent.
Influence of correct secondary and tertiary RNA folding on the binding of cellular factors to the HCV IRES (2000)

Structural integrity of the hepatitus C virus (HCV) 5' UTR region that includes the internal ribosome entry site (IRES) element is known to be essential for efficient protein synthesis. The functional explanation for this observation has been provided by the recent evidence that binding of several cellular factors to the HCV IRES is dependent on the conservation of its secondary structure. In order to better define the relationship between IRES activity, protein binding and RNA folding of the HCV IRES, we have focused our attention on its major stem-loop region (domain III) and the binding of several cellular factors: two subunits of eukaryotic initiation factor eIF3 and ribosomal protein S9. Our results show that binding of eIF3 p170 and p116/p110 subunits is dependent on the ability of the domain III apical stem-loop region to fold in the correct secondary structure whilst secondary structure of hairpin IIId is important for the binding of S9 ribosomal protein. In addition, we show that binding of S9 ribosomal protein also depends on the disposition of domain III on the HCV 5' UTR, indicating the presence of necessary inter-domain interactions required for the binding of this protein (thus providing the first direct evidence that tertiary folding of the HCV RNA does affect protein binding).
Amino Acid-stimulated Ca2+ Oscillations Produced by the Ca2+-sensing Receptor Are Mediated by a Phospholipase C/Inositol 1,4,5-Trisphosphate-independent Pathway That Requires G12, Rho, Filamin-A, and the Actin Cytoskeleton (2005)

The G protein-coupled Ca(2+)-sensing receptor (CaR) is an allosteric protein that responds to two different agonists, Ca(2+) and aromatic amino acids, with the production of sinusoidal or transient oscillations in intracellular Ca(2+) concentration ([Ca(2+)](i)). Here, we examined whether these differing patterns of [Ca(2+)](i) oscillations produced by the CaR are mediated by separate signal transduction pathways. Using real time imaging of changes in phosphatidylinositol 4,5-biphosphate hydrolysis and generation of inositol 1,4,5-trisphosphate in single cells, we found that stimulation of CaR by an increase in the extracellular Ca(2+) concentration ([Ca(2+)](o)) leads to periodic synthesis of inositol 1,4,5-trisphosphate, whereas l-phenylalanine stimulation of the CaR does not induce any detectable change in the level this second messenger. Furthermore, we identified a novel pathway that mediates transient [Ca(2+)](i) oscillations produced by the CaR in response to l-phenylalanine, which requires the organization of the actin cytoskeleton and involves the small GTPase Rho, heterotrimeric proteins of the G(12) subfamily, the C-terminal region of the CaR, and the scaffolding protein filamin-A. Our model envisages that Ca(2+) or amino acids stabilize unique CaR conformations that favor coupling to different G proteins and subsequent activation of distinct downstream signaling pathways.
Polymorphism analysis and gene detection by minisequencing on an array of gel-immobilized primers (1999)

Two procedures, multibase and multiprimer, have been developed for single nucleotide extension of primers immobilized within polyacrylamide gel pads on a microchip. In the multibase assay, a primer is next to a polymorphic nucleotide; the nucleotide is identified by the specificity with which the primer incorporates fluorescently labeled dideoxyribo-nucleoside triphosphates. In the multiprimer assay, several primers containing different 3'-terminal nucleotides overlapping the variable nucleotide in DNA are used. The polymorphic nucleotide is identified according to the primer that is extended. The methods were compared for diagnosis of beta-thalassemia mutations. Isothermal amplification of the fluorescent signal was achieved by performing both assays at elevated temperature. Anthrax toxin genes were identified in a model system using this amplification method.
Dynamic modeling of inter-instruction effects for execution time estimation (2001)

The market for embedded applications is facing a growing interest in power consumption issues: this work is intended to provide a new model to estimate software-level power consumption of 32-bit microprocessors. This model extends previous ones by considering dynamic inter-instruction effects that take place during code execution, providing a static means to characterize their energy consumption. The model is formally sound: it is conceived for a generic architecture and it has been preliminary validated on the Intel486™ architectur.
Design and Fabrication of a Locomotive Mechanism for Capsule-Type Endoscopes Using Shape Memory Alloys (SMAs) (2005)

Endoscopes are medical devices to diagnose various kinds of diseases throughout the whole gastrointestinal tracks. Generally, they are divided into conventional push-type endoscopes and more recently developed wireless capsule-type endoscopes. The conventional endoscopes cannot reach the small intestines and generate pain and discomfort to patients due to the stiffness of their body. Such disadvantages do not exist in wireless capsule-type endoscopes. However, commercialized capsule-type endoscopes move passively by peristaltic waves (and the gravity), which makes it impossible for doctors to diagnose the areas of his or her interest more thoroughly and actively. To address this problem of passivity, a locomotive mechanism is proposed for wireless capsule-type endoscopes. Prototypes with micro brushless dc motors, ionic polymer metal composite actuator, and shape memory alloy (SMA) wires are designed and fabricated for preliminary tests. Based on the tests, spring-type SMA actuators are selected to be microactuators for capsule endoscopes. Thus, two-way linear actuators using a pair of SMA springs are developed based on a static analysis on them. Moreover, a simple and effective clamping device is developed based on biomimetic approach. A prototype endoscope with four pairs of SMA springs and four clampers was developed. It has 13 mm in diameter and 33 mm in total length, with a hollow space of 7.6 mm in diameter to house other parts that are needed for endoscopy such as a camera, an RF module, sensors, e.g., for endoscopic ultrasound, and a battery. A sequential control of the four actuators improves the efficiency of locomotion up to four times. To validate the performance of the proposed locomotive mechanism, a series of experiments were carried out including in-vitro tests. The results of the experiments indicate that the proposed locomotion mechanism is effective to be used for micro capsule-type endoscopes.
Reaction of the Antitumor Antibiotic CC-1065 with DNA: Structure of a DNA Adduct with DNA Sequence Specificity (1984)

Sequence-dependent variations in DNA revealed by x-ray crystallographic studies have suggested that certain DNA-reactive drugs may react preferentially with defined sequences in DNA. Drugs that wind around the helix and reside within one of the grooves of DNA have perhaps the greatest chance of recognizing sequence-dependent features of DNA. The antitumor antibiotic CC-1065 covalently binds through N-3 of adenine and resides within the minor groove of DNA. This drug overlaps with five base pairs for which a high sequence specificity exists.
High-power diode lasers and their direct industrial applications (1995)

The paper summarizes activities of the two Fraunhofer-Institutes ILT and IPT concerning the development of high-power laser-diode stacks and their direct industrial applications. With microchannel coolers in copper technology and ultra-precision machined micro-optics a stack of 330 - 400 W total power with a maximum intensity of the focused beam of 2 10<SUP>4</SUP> W/cm<SUP>2</SUP> has been built and tested in first applications. By further improvements of the lens-fabrication and -alignment technology as well as increase of the number of stacked diodes an output power in the kW-range and intensities up to about 10<SUP>5</SUP> W/cm<SUP>2</SUP> shall be achieved in the near future. Applications of such laser sources in surface technology, in the processing of plastics, in laser-assisted machining and in brazing are discussed.
Upsampling Algorithms for Autoencoder Segmentation Neural Networks: A Comparison Study (2019)

This paper compares nine different upsampling methods used in convolutional neural networks in terms of accuracy and processing speed. The process of image segmentation using autoencoder neural networks consists of the image downsampling in the encoder and correspondingly of image upsampling in the decoder part of the network to achieve original image resolution. This paper focuses on the upsampling process in the decoder part of the standard U-Net neural network. Three different interpolations are compared with and without subsequent lxl convolution layers and three transpose convolution layers for image upsampling using different size convolutional cores. The experiment has shown that the best practical results were achieved using simple nearest neighbor interpolation upsampling taking into consideration the computational time needed. The network using nearest neighbor interpolation upsampling achieved pixel accuracy of 99.47% and has shown fast training time and convergence in comparison with other networks using different upsampling methods. The data used in this work consist of a lumbar CT spine segmentation dataset.
Membrane‐associated guanylate kinase dynamics reveal regional and developmental specificity of synapse stability (2016)

Fast excitatory transmission in the brain requires localization of glutamate receptors to synapses. The membrane-associated guanylate kinase (MAGUK) family of synaptic scaffolding proteins is critical for localization of glutamate receptors to synapses. Although the MAGUKs are well-studied in reduced preparations and young animals, few data exist on their role in adult animals. Here, we present a detailed developmental study of the role of the MAGUKs during rat development. We first confirmed by knockdown experiments that MAGUKs are essential for glutamatergic transmission in young animals and cultured slices, and an increase in postsynaptic density protein 95 (PSD-95) by overexpression caused correlated increases in glutamatergic transmission. We found that CA1 synapses in adults, in contrast, were largely unaffected by overexpression of MAGUKs, and although adult CA1 synapses required MAGUKs to the same degree as synapses in young animals, this was only apparent over long time scales of knockdown. We additionally showed that overexpression of MAGUKs is likely to function to accelerate the developmental strengthening of excitatory transmission. Finally, we showed that adult dentate gyrus appears similar to immature CA1, demonstrating regional and developmental control of MAGUK dynamics. Together, these results demonstrate a period of juvenile instability at CA1 synapses, followed by a period of adult stability in which synapses are acutely unaffected by changes in MAGUK abundance.
Isolation and Characterization of a Capsular Polysaccharide Adhesin from Staphylococcus epidermidis (1988)

We isolated a polysaccharide adhesin from Staphylococcus epidermidis strain RP-62A. The adhesin was composed of a complex mix of monosaccharides (with galactose and glucosamine predominating), bound well to silastic catheter tubing, inhibited adherence of strain RP-62A to catheters, and elicited antibodies that both blocked adherence and stabilized an extracellular structure (visualized by transmission electron microscopy) that appeared to be a capsule. Two of three heterologous, highly adherent strains of coagulase-negative staphylococci also produced this adhesin, and their adherence to catheters was inhibited by both purified adhesin and antibody to adhesin. In contrast, the adherence of one highly adherent and two poorly adherent heterologous strains was unaffected by the RP-62A purified adhesin or antibody, a result suggesting the expression of alternate adhesins by these strains. We conclude that the capsular polysaccharide of some strains of coagulase-negative staphylococci is an important factor in adherence to catheter tubing.
Resistance to Heterologous Isolates of Tomato Spotted Wilt Virus in Transgenic Tobacco Expressing Its Nucleocapsid Protein Gene (1992)

The nucleocapsid protein (NP) gene of the lettuce isolate of tomato spotted wilt virus (TSWV-BL), from the L serogroup, was synthesized and cloned into a plant expression cassette using polymerase chain reaction. Transgenic tobacco plant lines were obtained via Agrobacterium tumefaciens-mediated leaf disk transformation, and their progenies were tested for their ability to resist infections by TSWV isolates belonging to the L and I serogroups (...)
Key Metalloproteinases Are Expressed by Specific Cell Types in Experimental Autoimmune Encephalomyelitis (2004)

Metalloproteinases (MPs) include matrix metalloproteinases (MMPs) and metalloproteinase-disintegrins (ADAMs). Their physiological inhibitors are tissue inhibitor of metalloproteinases (TIMPs). MPs are thought to be mediators of cellular infiltration in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). We used real-time RT-PCR to profile the expression of all 22 known mouse MMPs, seven ADAMs, and all four known TIMPs in spinal cord from SJL/J mice and mice with adoptively transferred myelin basic protein (MBP)-specific EAE. A significant and >3-fold alteration in expression was observed for MMP-8, MMP-10, MMP-12, ADAM-12, and TIMP-1, which were up-regulated, and for MMP-15, which was down-regulated. Expression levels correlated with disease course, with all but ADAM-12 returning toward control levels in remission. To examine potential cellular sources of these strongly affected proteins in the inflamed CNS, we isolated macrophages, granulocytes, microglia, and T cells by cell sorting from the CNS of mice with EAE and analyzed their expression by real-time RT-PCR. This identified macrophages as a major source of MMP-12 and TIMP-1. Granulocytes were a major source of MMP-8. ADAM-12 was expressed primarily by T cells. Cellular localization of MMP-10, TIMP-1, and ADAM-12 in perivascular infiltrates was confirmed by immunostaining or in situ hybridization. Microglia from control mice expressed strong signal for MMP-15. Strikingly, the expression of MMP-15 by microglia was significantly down-regulated in EAE, which was confirmed by immunostaining. Our study identifies the cellular sources of key MPs in CNS inflammation.
Thickness Considerations in Direct Silicon Wafer Bonding (1995)

A simple approximate analytical expression based on an elastic deflection principle is suggested as a design guideline for direct bonding of blank or patterned Si or dissimilar materials of various thicknesses. To achieve the high flatness requirement of the mating surfaces for thick wafer bonding, optical polishing must be employed. With a surface flatness variation of 0.1 wavelength (∼630 Å), two 20 mm thick Si pieces of 100 mm in diam were spontaneously bonded at room temperature. On the other hand, the gaps designed to be formed by patterned surfaces may collapse during the bonding process if the pattern dimensions are not properly selected.