gebhart/patrepeval huggingface dataset:
Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus type 1 (HIV-1): interference with early and late events in HIV-1 replication (1995)

SDZ NIM 811 is a cyclosporin A analog that is completely devoid of immunosuppressive capacity but exhibits potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity. The mechanism of action of SDZ NIM 811 is clearly different from those of all other anti-HIV agents described so far. In cell-free assays, it is not an inhibitor of reverse transcriptase, protease, integrase, and it does not interfere with Rev or Tat function. SDZ NIM 811 does not down-regulate CD4 or inhibit fusion between infected and uninfected, CD4-expressing cells. p24 production from chronically HIV-infected cells is not impaired either. To elucidate the mode of action of SDZ NIM 811, we performed DNA PCR analysis in HIV-1 IIIB-infected MT4 cells in one cycle of virus replication. The effects of SDZ NIM 811 on the kinetics of viral DNA synthesis, appearance of two-long terminal repeat circles (2-LTR circles), and integration of DNA were studied. SDZ NIM 811 inhibited 2-LTR circle formation in a concentration-dependent manner, which is indicative of nuclear localization of preintegration complexes. Half-maximal inhibition was achieved at 0.17 microgram/ml; this concentration is close to the 50% inhibitory concentrations (0.01 to 0.2 microgram/ml) for viral growth inhibition. As expected, integration of proviral DNA into cellular DNA was also inhibited by SDZ NIM 811. Analysis of the viral particles produced by SDZ NIM 811-treated, chronically infected cells revealed amounts of capsid proteins, reverse transcriptase activity, and viral RNA comparable to those of the untreated control. However, these particles showed a dose-dependent reduction in infectivity (50% inhibitory concentration of 0.028 microgram/ml) which indicates that the assembly process is also impaired by SDZ NIM 811. Gag proteins are postulated to play a role not only in assembly but also in early steps of viral replication, e.g., nuclear localization of the preintegration complex. Recently, it was reported that HIV-1 Gag protein binds to cyclophilin A, the intracellular receptor for cyclosporin A. Interference with Gag-cyclophilin interaction may be the molecular basis for the antiviral activity of cyclosporin A and its analogs.
Small-Molecule Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (2003)

The growth and proliferation of cells are usually tightly regulated processes that are activated by stimuli from their environment. Epidermal growth factor (EGF)-related peptides represent a class of molecules that can trigger cell proliferation, among several cellular processes, such as differentiation, migration, and survival. Binding of EGF-like peptides to the EGF receptor (EGFR) at the cell surface leads to a cascade of intracellular reactions that transduce signals to the nucleus, resulting in particular gene expression patterns. However, in many tumor cells, the regulation of EGFR activity is lost, due to increased or aberrant expression of the receptor or its ligands, and this contributes to many processes important for tumor growth, including cell proliferation, survival, angiogenesis, invasion, and metastasis. Many strategies have been developed that specifically target the EGFR and inhibit its activity. Of these, small-molecule tyrosine kinase inhibitors represent one of the most promising classes of anticancer agents. Here, we describe the status of small-molecule EGFR tyrosine kinase inhibitors in preclinical and clinical development.
Seeing the world by hearing: Virtual Acoustic Space (VAS) a new space perception system for blind people. (2006)

Virtual Acoustic Space (VAS) is a research and development project on the perception of space using only sound. A portable electronic prototype that allows blind people to receive spatial information of their surroundings has been developed. This information is perceived via an audible image using Head Related Transfer Function (HRTFs) processed sounds. The main goal is to create for the user the illusion that the surrounding objects are covered by small sound continuously emitting sources in a particular and sustained way. Therefore, a virtual acoustic world is generated, where a physical object emit sounds from all the coordinates of its surface. Our results validate the hypothesis that, it is possible to generate an experience of global and sustained presence of different objects inside the perception field from these stimuli, with the same shape, dimensions and location as the real environment. Our objectives are now focused on: a better delimitation of the observed capabilities, the study of the developed prototype in everyday life conditions, on exploring how blind people learn to use new strategies to improve their perception of the environment and the exploration of the possible cortical brain areas involved in this process, using functional imaging techniques
Biallelic deletion within 16p13.13 including SOCS‐1 in Karpas1106P mediastinal B‐cell lymphoma line is associated with delayed degradation of JAK2 protein (2005)

Activity of Janus kinase 2 (JAK2) in the JAK2/STAT5 signaling pathway is critically controlled by suppressor of cytokine signaling-1 (SOCS-1). We have previously shown that SOCS-1 is biallelically mutated in the primary mediastinal B-cell lymphoma (PMBL) cell line MedB-1, resulting in impaired JAK2 degradation and sustained phospho-JAK2 action. SOCS-1 is frequently mutated in PMBL tumor primaries. Here, we report that the PMBL cell line Karpas1106P has a biallelic deletion of the SOCS-1 region on chromosome 16p13.13. By fluorescence in situ hybridization and microsatellite analysis, this deletion was narrowed down to a range of 650 kb to 1.48 Mb. Like MedB-1, Karpas1106P harbors gains of the JAK2 gene on chromosomal region 9p24 and elevated levels of JAK2 mRNA. Nevertheless, JAK2 protein was not increased but constitutively phosphorylated in Karpas1106P cells. In analogy to MedB-1 cells, Karpas1106P cells exhibited a retarded degradation of de novo synthesized JAK2 protein revealed by pulse/chase experiments. Therefore, we conclude that loss of SOCS-1 function either by mutation or by the complete deletion of the gene plays an important role in the dysregulation of JAK/STAT signaling in Karpas1106P and PMBL.
A morphology-based filter structure for edge-enhancing smoothing (2002)

We introduce the value-and-criterion filter structure, a new framework for designing filters based on mathematical morphology. The value-and-criterion filter structure is more flexible than the morphological structure, because it allows linear and nonlinear operations other than just the minimum and maximum to be performed on the data. One particular value-and-criterion filter, the mean of least variance (MLV) filter, finds the mean over the "subwindow" of data with the smallest variance within an overall window. The ability of the MLV filter to smooth noise while preserving and enhancing edges and corners is demonstrated. An example application of the MLV filter in improving the contrast of magnetic resonance images is also shown.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ordered Mesoporous Silicon through Magnesium Reduction of Polymer Templated Silica Thin Films (2008)

This paper describes the process of making ordered mesoporous silicon (Si) thin films. The process begins with mesoporous silica (SiO 2) thin films that are produced via evaporation induced self-assembly (EISA) using sol-gel silica precursors with a diblock copolymer template. This results in a film with a cubic lattice of 15 nm diameter pores and 10 nm thick walls. The silicon is produced through reduction of the silica thin films in a magnesium (Mg) vapor at 675 degrees C. Magnesium reduction preserves the ordered pore-solid architecture but replaces the dense silica walls with 10-17 nm silicon crystallites. The resulting porous silicon films are characterized by a combination of low and high angle X-ray diffraction, combined with direct SEM imaging. The result is a straightforward route to the production of ordered nanoporous silicon.
The Nucleus of the Intervertebral Disc from Development to Degeneration (2000)

The nucleus of the intervertebral disc in humans shows the most dramatic changes with age of any cartilaginous tissue. It originates from the notochord. In the foetus and infant, the nucleus contains actively dividing and biosynthetically active notochordal cells. The proteoglycans and other matrix components produced have a high osmotic pressure, imbibe water and maintain a hydrated structure which, though it has little mechanical strength, has a high swelling pressure which maintains disc turgor. In some species, the notochordal cells and the mucoid nucleus pulposus persist throughout adult life. However by about 4 yr of age in humans, the notochordal cells have disappeared to be replaced by those of chondrocytic appearance but of unknown origin. These cells continue to produce proteoglycans but also synthesize significant amounts of collagen. The nucleus becomes firmer and less hydrated and loses its transparent appearance. The cell density of the adult nucleus is very low with cells occupying less than 0.5% of tissue volume; each cell thus has to turn over and maintain a large domain of extracellular matrix. The density of living cells decreases with age, possibly because of problems with nutrient supply to this large avascular tissue. Proteoglycan concentration also falls, and nucleus hydration decreases markedly, the disc discolours and in many cases clefts and fissures form. In most adults, the disc nucleus degenerates eventually to a stage where it can no longer fulfil its mechanical role.
Bioluminescent Assays for High-Throughput Screening (2007)

In the development of high throughput screening (HTS) as a central paradigm of drug discovery, fluorescence has generally been adopted as the favored methodology. Nevertheless, luminescence has maintained a prominent position among certain assay formats, most notably genetic reporters. Recently, there has been growing partiality for luminescent assays across a wider range of applications due to their sensitivity, broad linearity, and robustness to library compounds and complex biological samples. This trend has been fostered by the development of several new assay designs for diverse targets such as kinases, cytochrome p450s, proteases, apoptosis, and cytotoxicity. This review addresses recent progress made in the use of bioluminescent assays for HTS, highlighting new detection capabilities brought about by engineering luciferase genes, enzymes, and substrates. In genetic reporter applications, modifications to the luciferase genes have improved assay sensitivity by substantially increasing expression efficiency and enhanced response dynamics by reducing expression lifetime. The performance of assays based on detection of ATP and luciferin has been enhanced by modifications to the luciferase enzyme that increase its chemical and physical stability. Detection of ATP allows rapid analysis of cell metabolism and enzymatic processes coupled to ATP metabolism. Because luciferins are not naturally associated with mammalian physiology, assays for luciferin detection utilize synthetic derivatives designed to yield luminescence only when coupled with specific target enzymes. Finally, new methods for modulating the specific activity of luciferases are leading to the development of intracellular biosensors for dynamic detection of physiological processes.
N-Glycosylation of Cholera Toxin B Subunit: Serendipity for Novel Plant-Made Vaccines? (2015)

The non-toxic B subunit of cholera toxin (CTB) has attracted considerable interests from vaccinologists due to strong mucosal immunomodulatory effects and potential utility as a vaccine scaffold for heterologous antigens. Along with other conventional protein expression systems, various plant species have been used as production hosts for CTB and its fusion proteins. However, it has recently become clear that the protein is N-glycosylated within the endoplasmic reticulum of plant cells-a eukaryotic post-translational modification that is not present in native CTB. While functionally active aglycosylated variants have been successfully engineered to circumvent potential safety and regulatory issues related to glycosylation, this modification may actually provide advantageous characteristics to the protein as a vaccine platform. Based on data from our recent studies, I discuss the unique features of N-glycosylated CTB produced in plants for the development of novel vaccines.
Regulation of the citrate synthase (gltA) gene of Escherichia coli in response to anaerobiosis and carbon supply: role of the arcA gene product (1994)

As an enzyme of the tricarboxylic acid cycle pathway, citrate synthase participates in the generation of a variety of cellular biosynthetic intermediates and in that of reduced purine nucleotides that are used in energy generation via electron transport-linked phosphorylation reactions. It catalyzes the condensation of oxaloacetate and acetyl coenzyme A to produce citrate plus coenzyme A. In Escherichia coli this enzyme is encoded by the gltA gene. To investigate how gltA expression is regulated, a gltA-lacZ operon fusion was constructed and analyzed following aerobic and anaerobic cell growth on various types of culture media. Under aerobic culture conditions, expression was elevated to a level twofold higher than that reached under anaerobic culture conditions. ArcA functions as a repressor of gltA expression under each set of conditions: in a delta arcA strain, gltA-lacZ expression was elevated to levels two- and eightfold higher than those seen in a wild-type strain under aerobic and anaerobic conditions, respectively. This control is independent of the fnr gene product, an alternative anaerobic gene regulator in E. coli. When the richness or type of carbon compound used for cell growth was varied, gltA-lacZ expression varied by 10- to 14-fold during aerobic and anaerobic growth. This regulation was independent of both the crp and fruR gene products, suggesting that another regulatory element in E. coli is responsible for the observed control. Finally, gltA-lacZ expression was shown to be inversely proportional to the cell growth rate. These findings indicate that the regulation of gltA gene expression is complex in meeting the differential needs of the cell for biosynthesis and energy generation under various cell culture conditions.
Computer Abbreviations: Evidence and Synthesis (1985)

This paper examines the experimental data on 11 abbreviation techniques for use with computer systems. The techniques include abbreviations based on intuition, abbreviations derived from formal rules, and military abbreviations. Although the comparison of user performance on the abbreviations produced by these different techniques is complicated by the varying conditions under which they were tested, trends in the data are apparent. This paper presents design recommendations based on this evidence as well as conjecture on how to further improve operator performance.
Poly(thioether) Vitrimers via Transalkylation of Trialkylsulfonium Salts (2017)

Vitrimers are permanently cross-linked organic polymers that can be reshaped, molded, and recycled without loss of network integrity. Herein, we report poly(thioether) networks, prepared through a straightforward thiol-ene photopolymerization, that can be turned into catalyst-free vitrimer materials by partial alkylation of the thioethers (1-10%) to the corresponding trialkylsulfonium salts. Based on a classical S<sub>N</sub>2-type substitution, the resulting polyionic networks can be reshaped upon heating via swift transalkylation reactions. This novel exchange reaction for the design of vitrimers was studied both on low MW model compounds as well as on a material level. In addition, we demonstrated the recycling of these networks without significant loss of mechanical properties.
Price discovery in dynamic power markets with low-voltage distribution-network participants (2014)

We focus on extending Locational Marginal Price (LMP) principles to (i) incorporate marginal costs of real and reactive power, line losses, voltage control, and distribution asset life degradation, and (ii) to enable distribution network connected loads and generators to participate in marginal cost based real and reactive power transactions. To this end, we define a distribution market that can discover spatiotemporal real and reactive power prices dynamically to optimize cost and utility of distributed generation assets, consumers, transformer and other asset life degradation, line losses, and voltage control, while observing full AC load flow constraints. We solve the socially optimal day-ahead market (DAM) clearing problem on a distribution feeder containing industrial, commercial and residential sub-feeders serving conventional non-elastic and flexible reschedulable loads and featuring devices capable of using excess capacity relative to their primary use to provide VAr compensation and voltage support. Numerical results on several DAM clearing scenarios elaborate the value of a fully functional distribution market in providing efficient operation incentives, intertemporal scheduling of demand and optimal location signals to distributed renewable generation and last but not least distribution network rent.
Cell surface expression of class II MHC proteins bound by a single peptide. (1995)

On normal cells, the peptide-binding grooves of class II MHC proteins contain a wide spectrum of peptides. For some purposes, however, it would be helpful to have cells bearing class II proteins engaged by only one peptide species. In an attempt to make such cells we constructed a gene for a MHC class II beta-chain, IA beta b, covalently linked to a peptide, E alpha 52-68, which is known to bind to the peptide-binding groove of IAb. This gene, together with the gene for IA alpha b, was transfected into B lymphoma cells and fibroblasts. The IAb-E alpha complex was expressed on the surfaces of these cells where it could be recognized by a mAb and T cells specific for IAb plus E alpha 52-68. Most of the peptide on fibroblasts remained covalently attached to the IAb beta-chain, but the covalent linker and/or peptide were degraded to some extent on B lymphoma cells. Nearly all of the IAb expressed by transfected fibroblasts was occupied by the E alpha peptide. Of 16 IAb-reactive T cell hybridomas, only 3 could respond to the IAb-E alpha complex on fibroblasts, confirming the idea that recognition of MHC may often involve recognition of the peptides bound to the MHC as well.
Recombinant human IgG1-murine IgE chimeric Ig. Construction, expression, and binding to human Fc gamma receptors. (1990)

We have constructed a set of chimeric Ig by exchanging corresponding H chain C domains between human (hu) IgG1 and murine (m) IgE. We used this set of Ig to dissect the interaction of individual Ig domains with human Fc gamma receptors. Only one of the chimeras, epsilon/C gamma 2,3 (an mIgE with C epsilon 3 and C epsilon 4 replaced by C gamma 2 and C gamma 3 from huIgG1), binds tightly to the human Fc gamma RI on U937 cells. We found that epsilon/C gamma 2,3 has only twofold lower affinity for Fc gamma RI as compared to huIgG1. The gamma/C epsilon 4 (huIgG1 with C epsilon 4 replacing C gamma 3) binds weakly to Fc gamma RI. The other chimeric Ig, epsilon/C gamma 3, epsilon/C gamma 2, and gamma/C epsilon 3, as well as mIgE do not bind detectably to Fc gamma RI. From these data we conclude that the C gamma 2 domain is crucial for binding and contains the majority of the binding site for Fc gamma RI on IgG1. The C gamma 3 domain makes a smaller contribution to the binding, and the C gamma 1 domain and the hinge region have very little effect on the Fc gamma RI-IgG1 interaction. The chimeric epsilon/C gamma 2,3 and huIgG1 both mediate the formation of rosettes between K562 cells and antigen-sensitized E with similar concentration dependences. These results suggest similar ability to bind to Fc gamma RII. The other chimeric Ig do not cause rosettes in this assay system. Hence, both C gamma 2 and C gamma 3 seem to be required for binding to Fc gamma RII, but the C gamma 1-hinge region has no detectable effect.
<em>Ex parte Milligan</em> and the Detainees at Guantanamo Bay: A Legacy Lost (2013)

Justice Steven H. David, Ex parte Milligan and the Detainees at Guantanamo Bay: A Legacy Lost, Indiana Magazine of History, Vol. 109, No. 4, Special Issue—Ex Parte Milligan at 150 (December 2013), pp. 380-394
Topical skin depigmentation agents (1997)

Novel topical dermatologic or cosme-ceutical agents are needed to treat cutaneous hyperpigmentation, since most currently available products typically contain hydroquinone (HQ), which has significant disadvantages. Although most studies have found HQ therapies to be efficacious, this compound is highly toxic and mutagenic to mammalian cells. Skin pigmentation results from the enzymatic conversion of tyrosine into melanin within the melanosomes of melanocytes, followed by transfer of the melanosomes into the keratinocytes of the epidermis. In order to identify novel inhibitors of skin pigmentation based on inhibition of tyrosinase, the key enzyme responsible for initiating melanogenesis, agent screening methods have been developed using both melanocyte cell cultures and cell-free enzymatic assays. An example of an HQ analog that demonstrates the desired activity in these assays is methyl gentisate (MG), which was discovered as an inhibitor of de novo melanogenesis in cultured melanocytes, with significantly reduced cytotoxicity and lack of mutagenic potential compared to HQ. A strategy is summarized for discovering new compounds capable of inhibiting melanogenesis, such as MG, and developing them into dermatologic or cosmeceutical products. In addition, consideration is given to the major differences in product registration requirements in various global markets for topical skin-light-ening agents.
DuploTrack (2012)

We demonstrate a realtime system which infers and tracks the assembly process of a snap-together block model using a Kinect® sensor. The inference enables us to build a virtual replica of the model at every step. Tracking enables us to provide context specific visual feedback on a screen by augmenting the rendered virtual model aligned with the physical model. The system allows users to author a new model and uses the inferred assembly process to guide its recreation by others. We propose a novel way of assembly guidance where the next block to be added is rendered in blinking mode with the tracked virtual model on screen. The system is also able to detect any mistakes made and helps correct them by providing appropriate feedback. We focus on assemblies of Duplo® blocks.