gebhart/patrepeval huggingface dataset:
Experimental phasing with SHELXC/D/E: combining chain tracing with density modification (2010)

The programs SHELXC, SHELXD and SHELXE are designed to provide simple, robust and efficient experimental phasing of macromolecules by the SAD, MAD, SIR, SIRAS and RIP methods and are particularly suitable for use in automated structure-solution pipelines. This paper gives a general account of experimental phasing using these programs and describes the extension of iterative density modification in SHELXE by the inclusion of automated protein main-chain tracing. This gives a good indication as to whether the structure has been solved and enables interpretable maps to be obtained from poorer starting phases. The autotracing algorithm starts with the location of possible seven-residue alpha-helices and common tripeptides. After extension of these fragments in both directions, various criteria are used to decide whether to accept or reject the resulting poly-Ala traces. Noncrystallographic symmetry (NCS) is applied to the traced fragments, not to the density. Further features are the use of a 'no-go' map to prevent the traces from passing through heavy atoms or symmetry elements and a splicing technique to combine the best parts of traces (including those generated by NCS) that partly overlap.
Gene therapy for retinitis pigmentosa. (2000)

Retinitis pigmentosa (RP) is a group of retinal degenerative diseases in which there is a slow and progressive loss of photoreceptors. There is no cure for RP and photoreceptor loss leads ultimately to blindness. There has been tremendous progress in the last decade in delineating the molecular basis of RP. Simultaneously, gene transfer experiments have demonstrated that it is possible to deliver transgenes to the retina in vivo in a stable and efficient fashion with minimal toxicity. Proof-of-principle for gene therapy for RP has been established in a number of different animal models. While much more progress needs to be made before moving from the laboratory to the clinic, gene therapy now holds much promise for slowing or even preventing blindness due to RP.
Precision In-Plane Hand Assembly of Bulk-Microfabricated Components for High-Voltage MEMS Arrays Applications (2009)

This paper reports the design and experimental validation of an in-plane assembly method for centimeter-scale bulk-microfabricated components. The method uses mesoscaled deep-reactive-ion-etching (DRIE)-patterned cantilevers that deflect and lock into small v-shaped notches as a result of the hand-exerted rotation between the two components of the assembly. The assembly method is intended for MEMS arrays that necessitate a 3-D electrode structure because of their requirement for low leakage currents and high voltages. The advantages of the assembly method include the ability to decouple the process flow of the components, higher overall device yield, modularity, reassembly capability, and tolerance to differential thermal expansion. Both tapered and untapered cantilevers were studied. Modeling of the cantilever set shows that the springs provide low stiffness while the assembly process is in progress and high stiffness once the assembly is completed, which results in a robust assembly. In addition, analysis of the linearly tapered cantilever predicts that the optimal linearly tapered beam has a cantilever tip height equal to 37% of the cantilever base height, which results in more than a threefold increase in the clamping force for a given cantilever length and deflection, compared to the untapered case. The linear taper profile achieves 80% of the optimal nonlinear taper profile, which would be impractical to fabricate. Analysis of the experimental data reveals a biaxial assembly precision of 6.2-mum rms and a standard deviation of 0.6 mum for assembly repeatability. Electrical insulation was investigated using both thin-film coatings and insulating substrates. Leakage currents less than 1 nA at 2 kV were demonstrated. Finally, this paper provides selected experimental data of a gated MEMS electrospray array as an example of the application of the assembly method.
Expression of Interleukin 9 in the Lungs of  Transgenic Mice Causes Airway Inflammation, Mast Cell Hyperplasia, and Bronchial Hyperresponsiveness (1998)

Interleukin (IL)-9, a pleiotropic cytokine produced by the Th2 subset of T lymphocytes has been proposed as product of a candidate gene responsible for asthma. Its wide range of biological functions on many cell types involved in the allergic immune response suggests a potentially important role in the complex pathogenesis of asthma. To investigate the contributions of IL-9 to airway inflammation and airway hyperresponsiveness in vivo, we created transgenic mice in which expression of the murine IL-9 cDNA was regulated by the rat Clara cell 10 protein promoter. Lung selective expression of IL-9 caused massive airway inflammation with eosinophils and lymphocytes as predominant infiltrating cell types. A striking finding was the presence of increased numbers of mast cells within the airway epithelium of IL-9-expressing mice. Other impressive pathologic changes in the airways were epithelial cell hypertrophy associated with accumulation of mucus-like material within nonciliated cells and increased subepithelial deposition of collagen. Physiologic evaluation of IL-9-expressing mice demonstrated normal baseline airway resistance and markedly increased airway hyperresponsiveness to inhaled methacholine. These findings strongly support an important role for IL-9 in the pathogenesis of asthma.
Treatment for Radiation-Induced Pulmonary Late Effects: Spoiled for Choice or Looking in the Wrong Direction? (2010)

Due to the radiosensitivity of the lung, toxic endpoints, in the form of radiation pneumonitis and pulmonary fibrosis, are relatively frequent outcomes following radiation treatment of thoracic neoplasms. Because of the potential lethal nature of these normal tissue reactions, they not only lead to quality-of-life issues in survivors, but also are deemed dose-limiting and thereby compromise treatment. The mitigation and treatment of lung normal tissue late effects has therefore been the goal of many investigations; however, the complexity of both the organ itself and its response to injury has resulted in little success. Nonetheless, current technology allows us to propose likely targets that are either currently being researched or should be considered in future studies.
Effect of Hyperosmolar Stimuli and Coeliac Disease on the Permeability of the Human Gastrointestinal Tract (1978)

1. Oral loads have been used to assess the permeability of the human gastrointestinal tract, with lactulose (mol. wt. 342), raffinose (mol. wt. 504), stachyose (mol. wt. 666) and a fluoresceinlabelled dextran (mol. wt. 3000) as marker substances. Timed urinary recovery of these substances, which are not metabolized, was measured by quantitative paper chromatography and direct fluorimetry, and the results were used as an indication of passive intestinal permeability. 2. Results in healthy adults showed that permeability to these markers was dependent on molecular size, even after correction for aqueous diffusion differences, such that a profile of restricted permeability could be described for this range of markers. Interpretation in terms of conventional pore theory suggested the presence of more than one population of pores. 3. Ingestion of solutions made hyperosmotic by inclusion of glycerol resulted in a large increase in permeability, in a pattern that suggested an increase in either the size or frequency of a range of smaller pores. 4. A similar increase in permeability and alteration in the profile of restriction was found in patients with coeliac disease. 5. The possible location of such pores in the gastrointestinal mucosa is discussed in relation to the cell membrane, the intercellular junction, and the sites of cell exfoliation.
Chemical vapor deposition of metals: Part 1. An overview of CVD processes (1995)

Abstract The chemical vapor deposition (CVD) of metals is a rapidly developing area in which metal‐containing compounds are being synthesized as new precursors. This article reviews this area and discusses precursor design, reaction pathways, reactor types, and the influence of reactor operating conditions on film growth. We have gathered recent results for precursor design and CVD chemistry and show how analysis of results from CVD experiments can be used to assist in the development of new CVD precursors.
Immune Mechanisms in the Pathogenesis of Pulmonary Tuberculosis (1989)

The pathogenesis of pulmonary tuberculosis and the beneficial and detrimental effects of the host's cell-mediated immune response in this disease are reviewed. Tubercle bacilli are hardly facultative intracellular pathogens that live and multiply in nonactivated macrophages. Before tubercle bacilli can be destroyed by macrophages, these cells must be activated by T lymphocytes and their lymphokines. Such activation is the essence of cell-mediated immunity. Cell-mediated immunity also has a detrimental component, called delayed-type hypersensitivity. This component causes caseous necrosis of host tissues whenever the bacillary antigens reach high levels. Such levels occur intracellularly in macrophages of highly susceptible hosts and extracellularly in liquefied caseous foci of resistant hosts. Vaccines containing antigens that create more cell-mediated immunity and less delayed-type hypersensitivity are greatly needed.
Endothelial Membrane Remodeling Is Obligate for Anti-Angiogenic Radiosensitization during Tumor Radiosurgery (2010)

These studies show that angiogenic factors fail to suppress apoptosis if ceramide remains elevated while anti-angiogenic therapies fail without ceramide elevation, defining a ceramide rheostat that determines outcome of single dose radiotherapy. Understanding the temporal sequencing of anti-angiogenic drugs and radiation enables optimized radiosensitization and design of innovative radiosurgery clinical trials.
MicroRNA-125b may function as an oncogene in lung cancer cells (2014)

The present study aimed to investigate the biofunctions of microRNA (miR)‑125b on lung cancer cells. A miR genechip array was used to examine the differential expression of miRs between 95D lung cancer cells and 16 human bronchial epithelial (HBE) cells. Overexpression of miR‑125b was observed in the cell lines and in the lung carcinoma tissues compared with the adjacent tissues, confirmed using reverse transcription quantitative polymerase chain reaction. Bioinformatic analysis of miR‑125b was also performed, including target prediction, gene ontology and pathway analysis. MTT, flow cytometry and Transwell assays were also used to examine the effect of downregulated miR‑125b on the proliferation, apoptosis, invasive ability and cell cycle of 95D cells. Significant differences were observed in the expression of 45 miRs in the 95D cells compared with those in 16HBE cells and the expression of miR‑125b was significantly higher in 95D cells compared with that in 16HBE cells as well as in lung tumor tissues compared with that in adjacent tissues. In addition, inhibition of the expression of miR‑125b in 95D cells induced apoptosis, G1/S phase arrest and reduction of their invasive ability. In addition, bioinformatics software predicted that miR‑125b was involved in the regulation of several pathways associated with cancer, including the transforming growth factor‑β, Wnt and mitogen‑activated protein kinase signaling pathways. These data indicated for the first time, to the best of our knowledge, that miR‑125b may function as an oncogene in lung cancer.
Joule heating induced stream broadening in free‐flow zone electrophoresis (2017)

Abstract The use of an electric field in free‐flow zone electrophoresis (FFZE) automatically leads to Joule heating yielding a higher temperature at the center of the separation chamber relative to that around the channel walls. For small amounts of heat generated, this thermal effect introduces a variation in the equilibrium position of the analyte molecules due to the dependence of liquid viscosity and analyte diffusivity on temperature leading to a modification in the position of the analyte stream as well as the zone width. In this article, an analytic theory is presented to quantitate such effects of Joule heating on FFZE assays in the limit of small temperature differentials across the channel gap yielding a closed form expression for the stream position and zone variance under equilibrium conditions. A method‐of‐moments approach is employed to develop this analytic theory, which is further validated with numerical solutions of the governing equations. Interestingly, the noted analyses predict that Joule heating can drift the location of the analyte stream either way of its equilibrium position realized in the absence of any temperature rise in the system, and also tends to reduce zone dispersion. The extent of these modifications, however, is governed by the electric field induced temperature rise and three Péclet numbers evaluated based on the axial pressure‐driven flow, transverse electroosmotic and electrophoretic solute velocities in the separation chamber. Monte Carlo simulations of the FFZE system further establish a time and a length scale over which the results from the analytic theory are valid.
Deniable password snatching: on the possibility of evasive electronic espionage (1997)

Cryptovirology has recently been introduced as a means of mounting active viral attacks using public key cryptography. It has been shown to be a tool for extortion attacks and "electronic warfare", where attacks are mounted against information resources. The natural question to ask is whether Cryptovirology is also useful in the area of spying via malware. We demonstrate that Cryptovirology does help in "electronic espionage" and allows the spy to conceal his or her identity (as well as past collected information). Specifically, we present an attack that can be mounted by a cryptotrojan that allows the attacker to gather information (passwords) from a system in such a way that the attacker cannot be proven guilty beyond reasonable doubt. That is, even if the attacker is under surveillance on the local machine from when he first attacks the target machine, to when he obtains the passwords, and even if the leaked information is made available to the attacker exclusively, he still cannot be caught. The threat is made possible by the combination of public key cryptography, probabilistic encryption, and the use of public information (I/O or communication) channels which together form a "secure receiver-anonymous channel". The machine can be standalone or networked. What we learn from the attack is extracted as general tools and basic principles for "espionage attacks".
Squaric Acid Mediated Synthesis and Biological Activity of a Library of Linear and Hyperbranched Poly(Glycerol)–Protein Conjugates (2012)

Polymer-protein conjugates generated from side chain functional synthetic polymers are attractive because they can be easily further modified with, for example, labeling groups or targeting ligands. The residue specific modification of proteins with side chain functional synthetic polymers using the traditional coupling strategies may be compromised due to the nonorthogonality of the side-chain and chain-end functional groups of the synthetic polymer, which may lead to side reactions. This study explores the feasibility of the squaric acid diethyl ester mediated coupling as an amine selective, hydroxyl tolerant, and hydrolysis insensitive route for the preparation of side-chain functional, hydroxyl-containing, polymer-protein conjugates. The hydroxyl side chain functional polymers selected for this study are a library of amine end-functional, linear, midfunctional, hyperbranched, and linear-block-hyperbranched polyglycerol (PG) copolymers. These synthetic polymers have been used to prepare a diverse library of BSA and lysozyme polymer conjugates. In addition to exploring the scope and limitations of the squaric acid diethylester-mediated coupling strategy, the use of the library of polyglycerol copolymers also allows to systematically study the influence of molecular weight and architecture of the synthetic polymer on the biological activity of the protein. Comparison of the activity of PG-lysozyme conjugates generated from relatively low molecular weight PG copolymers did not reveal any obvious structure-activity relationships. Evaluation of the activity of conjugates composed of PG copolymers with molecular weights of 10000 or 20000 g/mol, however, indicated significantly higher activities of conjugates prepared from midfunctional synthetic polymers as compared to linear polymers of similar molecular weight.
<title>Rapid optical figuring of aspherical surfaces with plasma-assisted chemical etching</title> (1992)

Programmed motion of a tool which removes material by plasma assisted chemical etching (PACE) gives controlled, deterministic figuring. The process has been automated to correct arbitrary figure errors on aspheric surfaces directly from the measured surface data. A system is now operating for figuring aspheric surfaces up to 0.5 m diameter. PACE can greatly reduce the time and cost of figuring large optics by its rapid convergence to the final figure requiring only two to three measurement/figuring cycles to reach 1/50 wave surfaces. PACE intrinsically smooths high frequency roughness with material removal leaving a surface free of subsurface damage
Specific and Potent Inhibition of NAD+-dependent DNA Ligase by Pyridochromanones (2003)

Pyridochromanones were identified by high throughput screening as potent inhibitors of NAD+-dependent DNA ligase from Escherichia coli. Further characterization revealed that eubacterial DNA ligases from Gram-negative and Gram-positive sources were inhibited at nanomolar concentrations. In contrast, purified human DNA ligase I was not affected (IC50 > 75 microm), demonstrating remarkable specificity for the prokaryotic target. The binding mode is competitive with the eubacteria-specific cofactor NAD+, and no intercalation into DNA was detected. Accordingly, the compounds were bactericidal for the prominent human pathogen Staphylococcus aureus in the low microg/ml range, whereas eukaryotic cells were not affected up to 60 microg/ml. The hypothesis that inhibition of DNA ligase is the antibacterial principle was proven in studies with a temperature-sensitive ligase-deficient E. coli strain. This mutant was highly susceptible for pyridochromanones at elevated temperatures but was rescued by heterologous expression of human DNA ligase I. A physiological consequence of ligase inhibition in bacteria was massive DNA degradation, as visualized by fluorescence microscopy of labeled DNA. In summary, the pyridochromanones demonstrate that diverse eubacterial DNA ligases can be addressed by a single inhibitor without affecting eukaryotic ligases or other DNA-binding enzymes, which proves the value of DNA ligase as a novel target in antibacterial therapy.
Robust trapped-ion quantum logic gates by continuous dynamical decoupling (2012)

We introduce a scheme that combines phonon-mediated quantum logic gates in trapped ions with the benefits of continuous dynamical decoupling. We demonstrate theoretically that a strong driving of the qubit decouples it from external magnetic-field noise, enhancing the fidelity of two-qubit quantum gates. Moreover, the scheme does not require ground-state cooling, and is inherently robust to undesired ac Stark shifts. The underlying mechanism can be extended to a variety of other systems where a strong driving protects the quantum coherence of the qubits without compromising the two-qubit couplings.
Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals (1995)

Cells from diverse tissues detect mechanical load signals by similar mechanisms but respond differently. The diversity of responses reflects the genotype of the cell and the mechanical demands of the resident tissue. We hypothesize that cells maintain a basal equilibrium stress state that is a function of the number and quality of focal adhesions, the polymerization state of the cytoskeleton, and the amount of extrinsic, applied mechanical deformation. A load stimulus detected by a mechano-electrochemical sensory system, including mechanically sensitive ion channels, integrin-cytoskeleton machinery, and (or) a load-conformation sensitive receptor or nonreceptor tyrosine kinase, may activate G proteins, induce second messengers, and activate an RPTK or JAK/STAT kinase cascade to elicit a response. We propose the terms autobaric to describe a self-loading process, whereby a cell increases its stress state by contracting and applying a mechanical load to itself, and parabaric, whereby a cell applies a load to an adjacent cell by direct contact or through the matrix. We predict that the setpoint for maintaining this basal stress state is affected by continuity of incoming mechanical signals as deformations that activate signalling pathways. A displacement of the cytoskeletal machinery may result in a conformational change in a kinase that results in autophosphorylation and cascade initiation. pp60Src is such a kinase and is part of a mechanosensory protein complex linking integrins with the cytoskeleton. Cyclic mechanical load induces rapid Src phosphorylation. Regulation of the extent of kinase activation in the pathway(s) may be controlled by modulators such as G proteins, kinase phosphorylation and activation, and kinase inhibitors or phosphatases. Intervention at the point of ras-raf interaction may be particularly important as a restriction point.
Acyclic stereoselection. 46. Stereochemistry of the Michael addition of N,N-disubstituted amide and thioamide enolates to .alpha.,.beta.-unsaturated ketones (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcyclic stereoselection. 46. Stereochemistry of the Michael addition of N,N-disubstituted amide and thioamide enolates to .alpha.,.beta.-unsaturated ketonesDavid A. Oare, Mark A. Henderson, Mark A. Sanner, and Clayton H. HeathcockCite this: J. Org. Chem. 1990, 55, 1, 132–157Publication Date (Print):January 1, 1990Publication History Published online1 May 2002Published inissue 1 January 1990https://doi.org/10.1021/jo00288a027RIGHTS & PERMISSIONSArticle Views3483Altmetric-Citations111LEARN 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 InReddit PDF (3 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts