gebhart/patrepeval huggingface dataset:
Applications of Fluorescent Polymer Superquenching to High Throughput Screening Assays for Protein Kinases (2004)

Protein kinases are involved in the regulation of cellular metabolism, growth, differentiation, and proliferation. Aberrations in their function can lead to diseases such as cancer and inflammation. Protein kinases are therefore possible targets for drug therapies. To address the need for high throughput screening of potential inhibitors, QTL has developed a homogeneous and robust kinase assay for use in multiwell plate format. The QTL Lightspeed fluorescence superquenching-based kinase assays do not require specialized equipment, nor do they involve the use of radioactive hazardous materials or antibodies. QTL Lightspeed kinase assays directly measure the enzymatic activity of the target and do not involve secondary (detector) enzyme. In this article, we compare QTL Lightspeed protein kinase assays using Protein Kinase A, Protein Kinase Balpha/Akt1, and ribosomal S6 kinase-2 as examples with other commercially available kinase kits. Our data show that QTL Lightspeed kinase assays offer significant advantages over the current commercial kits in terms of both sensitivity and performance. The QTL Lightspeed kinase assay also offers a kinetic assay mode where the substrate phosphorylation can be monitored in real-time.
Characterization of a Functional NF-κB Site in the Human Interleukin 1β Promoter: Evidence for a Positive Autoregulatory Loop (1993)

The -300 region of the interleukin 1 beta (IL-1 beta) promoter contains a functional NF-kappa B binding site composed of the decamer sequence 5'-GGGAAAATCC-3'. Probes representing the -300 region or the NF-kappa B site alone interacted with NF-kappa B proteins present in phorbol myristate acetate-, lipopolysaccharide-, or Sendai virus-induced myeloid cell extracts as well as recombinant NFKB1 (p50) and RelA (p65); furthermore, NF-kappa B protein-DNA complex formation was dissociated in vitro by the addition of recombinant I kappa B alpha. Mutation of the NF-kappa B site in the context of the IL-1 beta promoter reduced the responsiveness of the IL-1 beta promoter to various inducers, including phorbol ester, Sendai virus, poly(rI-rC), and IL-1 beta. A 4.4-kb IL-1 beta promoter fragment linked to a chloramphenicol acetyltransferase reporter gene was also preferentially inducible by coexpression of individual NF-kappa B subunits compared with a mutated IL-1 beta promoter fragment. When multiple copies of the IL-1 beta NF-kappa B site were linked to an enhancerless simian virus 40 promoter, this element was able to mediate phorbol ester- or lipopolysaccharide-inducible gene expression. In cotransfection experiments, RelA (p65) and c-Rel (p85) were identified as the main subunits responsible for the activation of the IL-1 beta NF-kappa B site; also, combinations of NFKB1 (p50) and RelA (p65) or c-Rel and RelA were strong transcriptional activators of reporter gene activity. The presence of a functional NF-kappa B binding site in the IL-1 beta promoter suggests that IL-1 positively autoregulates its own synthesis, since IL-1 is a strong inducer of NF-kappa B binding activity. Thus, the IL-1 beta gene may be considered as an important additional member of the family of cytokine genes regulated in part by the NF-kappa B/rel family of transcription factors.
<title>Progress in planarized vertical-cavity surface-emitting laser devices and arrays</title> (1991)

We report batch-processed, totally planar, vertical-cavity top surface emitting GaAs/AlGaAs laser devices and arrays. Different size devices are studied experimentally. We measure continuous-wave threshold currents down to 1.7 mA and output powers > 3.7 mW at room temperature. We also discuss interesting characteristics such as differential quantum efficiencies exceeding unity and multi-transverse mode behavior. An array having 64 X 1 individually-accessed elements is characterized and shown to have uniform room-temperature continuous-wave operating characteristics in threshold current approximately equals 2.1 +/- 0.1 mA, wavelength approximately equals 849.4 +/- 0.8 nm, and output power approximately equals 0.5 +/- 0.1 mW.
Selectivity and Tolerance (“Invariance”) Both Increase as Visual Information Propagates from Cortical Area V4 to IT (2010)

Our ability to recognize objects despite large changes in position, size, and context is achieved through computations that are thought to increase both the shape selectivity and the tolerance ("invariance") of the visual representation at successive stages of the ventral pathway [visual cortical areas V1, V2, and V4 and inferior temporal cortex (IT)]. However, these ideas have proven difficult to test. Here, we consider how well population activity patterns at two stages of the ventral stream (V4 and IT) discriminate between, and generalize across, different images. We found that both V4 and IT encode natural images with similar fidelity, whereas the IT population is much more sensitive to controlled, statistical scrambling of those images. Scrambling sensitivity was proportional to receptive field (RF) size in both V4 and IT, suggesting that, on average, the number of visual feature conjunctions implemented by a V4 or IT neuron is directly related to its RF size. We also found that the IT population could better discriminate between objects across changes in position, scale, and context, thus directly demonstrating a V4-to-IT gain in tolerance. This tolerance gain could be accounted for by both a decrease in single-unit sensitivity to identity-preserving transformations (e.g., an increase in RF size) and an increase in the maintenance of rank-order object selectivity within the RF. These results demonstrate that, as visual information travels from V4 to IT, the population representation is reformatted to become more selective for feature conjunctions and more tolerant to identity preserving transformations, and they reveal the single-unit response properties that underlie that reformatting.
ConNexus to awarenex (2001)

We explored the use of awareness information to facilitate communication by developing a series of prototypes. The ConNexus prototype integrates awareness information, instant messaging, and other communication channels in an interface that runs on a desktop computer. The Awarenex prototype extends that functionality to wireless handheld devices, such as a Palm. A speech interface also enables callers to make use of the awareness information over the telephone. While the prototypes offer similar functionality, the interfaces reflect the different design affordances and use context of each platform. We discuss the design implications of providing awareness information on devices with varying interface and network characteristics.
Clinical trial of a laser device called fractional photothermolysis system for acne scars (2006)

Ablative laser resurfacing is an effective treatment for acne scars. However, edema and prolonged erythema are common. Additionally, scarring and hyperpigmentation are often induced. A new concept of laser called fractional photothermolysis has been designed to create microscopic thermal wounds to achieve skin rejuvenation without significant side-effects. We treated 10 patients with acne scars using this laser system (Reliant Fraxel SR Laser). All the patients were successfully treated with minimal adverse effects. The fractional photothermolysis system represents an optional method for the treatment of acne scars.
The 40‐kilodalton allergen of Candida albicans is an alcohol dehydrogenase: molecular cloning and immunological analysis using monoclonal antibodies (1991)

To characterize the 40-kilodalton (kD) major allergen of Candida albicans (C. albicans), six monoclonal antibodies (MoAbs) against this allergen were generated. In SDS-polyacrylamide gel electrophoresis and immunoblot analysis, these MoAbs showed four different reaction patterns to antigens of six different Candida species. With the exception of one MoAb, other MoAbs were resistant to periodate treatment indicating non-carbohydrate epitopes were probably being recognized by these MoAbs. These MoAbs were used in the molecular cloning and immunological analysis of the gene coding for the 40-kD allergen. Nucleotide sequence determination of the two lambda gt11 cDNA clones obtained showed that the 40-kD allergen is an alcohol dehydrogenase (ADH) which shares a 70% amino acid sequence homology with the ADH isozyme I of Saccharomyces cerevisiae. This finding was confirmed by positive immunological response of the lysates of the clones obtained and a preparation of ADH of Saccharomyces cerevisiae to various MoAbs and to IgE antibodies in sera of allergic patients.
Multilevel microstructure fabrication using single-step 3D photolithography and single-step electroplating (1998)

We developed a useful method to obtain multilevel microstructures simply by single-step 3D photolithography followed by single-step electroplating. By varying UV exposure depth with multiple photomasks in a single-coated conventional thick photoresist, we form multilevel photoresist molds in a single lithography step. After the 3D mold patterning, metal electroplating is performed on it until 3D metallic microstructures are obtained. The critical issue in this process, the exposure depth control, was carefully examined by observing the exposure time versus development characteristic of the resist, in the film thickness range of 40 to 90 micrometer. We proposed a simple method to reproducibly obtain the resist thickness of each level as designed. Using the unique overplating feature in electroplating process, we demonstrated two utmost practical examples: a unified Orifice Plate Assembly (OPA), which has orifice, channel, and reservoirs in a single body, for high-resolution inkjet printhead, and an electroplated Solenoid-type Integrated Inductor (SI<SUP>2</SUP>). Both were fabricated using a single-coated 80 micrometer-thick photoresist with only two photomasks, and have many advantages in productivity and performance. This method does not stack planar layer vertically to make 3D microstructures as in the conventional ways, therefore, is a simple, low-cost, and high-yield process. And also, it is IC compatible due to its low process temperature and monolithic process.
The Propeptide Domain of Lysyl Oxidase Induces Phenotypic Reversion of Ras-transformed Cells (2004)

Lysyl oxidase is an extracellular enzyme critical for the normal biosynthesis of collagens and elastin. In addition, lysyl oxidase reverts ras-mediated transformation, and lysyl oxidase expression is down-regulated in human cancers. Since suramin inhibits growth factor signaling pathways and induces lysyl oxidase in ras-transformed NIH3T3 cells (RS485 cells), we sought to investigate the effects of suramin on the phenotype of transformed cells and the role of lysyl oxidase in mediating these effects. Suramin treatment resulted in a more normal phenotype as judged by growth rate, cell cycle parameters, and morphology. beta-aminopropionitrile, the selective inhibitor of lysyl oxidase enzyme activity, was remarkably unable to block suramin-induced reversion. By contrast, ectopic antisense lysyl oxidase demonstrated that lysyl oxidase gene expression mediated phenotypic reversion. Since lysyl oxidase is synthesized as a 50 kDa precursor and processed to a 30 kDa active enzyme and 18 kDa propeptide, the effects of these two products on the transformed phenotype of RS485 cells were then directly assessed in the absence of suramin. Here we report, for the first time, that the lysyl oxidase propeptide, and not the lysyl oxidase enzyme, inhibits ras-dependent transformation as determined by effects on cell proliferation assays, growth in soft agar, and Akt-dependent induction of NF-kappaB activity. Thus, the lysyl oxidase propeptide, which is released during extracellular proteolytic processing of pro-lysyl oxidase, functions to inhibit ras-dependent cell transformation.
Differential downregulation of vascular endothelial growth factor by dexamethasone in normoxic and hypoxic rat glioma cells (1999)

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is a mitogen and chemotactic factor for endothelial cells in vitro and an angiogenesis and vascular permeability factor in vivo. Due to its properties, VEGF is a candidate for both angiogenesis and vascular permeability/oedema induction which typically occur in glioblastomas. In this study we test the hypothesis that the antioedema effect of dexamethasone is mediated by downregulation of VEGF or VEGF receptor expression. VEGF mRNA and protein levels of two rat glioma cells lines, C6 and GS-9L, were determined after incubation with dexamethasone under normoxic and hypoxic conditions. In normoxic C6 and GS9L cells, we observed 50-60% downregulation of VEGF mRNA by dexamethasone (P=0.015 and P=0. 01, respectively). This effect was dependent on glucocorticoid-receptor (GR) function. The inhibitory effect of dexamethasone on VEGF gene expression by tumour cells was markedly reduced by hypoxia which suggests that the upregulation of VEGF driven by hypoxia overcomes the effect of the dexamethasone. Dexamethasone did not alter VEGFR-2 mRNA levels in human umbilical endothelial cells. In a subcutaneous glioma tumour model, we observed only a 15% decrease in VEGF mRNA expression in dexamethasone treated animals (n = 12) compared with controls animals (P = 0.24). We conclude that dexamethasone may decrease brain tumour-associated oedema by reduction of VEGF expression in tumour cells. However, the highly reduced activity on hypoxic tumour cells suggests that dexamethasone efficacy may be limited by hypoxia in rapidly growing tumours.
Comparison of receptors required for entry of Leishmania major amastigotes into macrophages (1993)

We investigated the mechanisms of entry of amastigotes of Leishmania major from two different sources into macrophages by comparing their use of the Fc receptor (FcR), complement receptor type 3 (CR3), and mannose-fucose receptor (MFR). Amastigotes were obtained from BALB/c mice and SCID mice. FcR involvement was examined by opsonizing L. major with parasite-specific immunoglobulin G (IgG). Antiparasite IgG did not alter the uptake of amastigotes from BALB/c mice since these amastigotes had antibody bound to their surface: IgG1 was the most predominant antibody, followed by IgG2b, IgM, and IgG2a. However, opsonization with antiparasite IgG enhanced the entry of amastigotes that lacked antibody on their surface, namely, amastigotes obtained from SCID mice or from macrophages infected in vitro. These results indicate that the FcR is important for amastigote entry into macrophages. Down-modulation of FcRs onto immune complexes, however, did not reduce the entry of amastigotes containing surface-bound IgG into macrophages. Monoclonal antibodies against the CR3 inhibited the entry of amastigotes from either BALB/c or SCID mice into J774A.1 macrophage-like cells. Simultaneous blocking of FcR and CR3 further increased the inhibition of phagocytosis. Treatment of macrophages with soluble mannan or down-modulating the MFR onto mannan-coated coverslips had no effect on the entry of amastigotes from BALB/c or SCID mice. Thus, the MFR does not appear to be used by amastigotes of L. major. We show that ingestion of amastigotes appears to occur primarily through the FcR and CR3; however, additional receptors may also participate in the uptake of amastigotes.
Amyloid β protein (Aβ) deposition: Aβ42(43) precedes Aβ40 in down Syndrome (1995)

The chronological relationship regarding deposition of amyloid beta protein (A beta) species, A beta 40 and A beta 42(43), was investigated in 16 brains from Down syndrome patients aged 31 to 64 years. The frontal cortex was probed with two end-specific monoclonals that recognize A beta 40 or A beta 42(43). All senile plaques detected with an authentic beta monoclonal were also A beta 42(43) positive, but only a varying proportion was A beta 40 positive. In young (< or = 50 years old) brains there were many A beta 42(43)-positive, A beta 40-negative diffuse plaques, but only few A beta 40-positive senile plaques (mean, 6.3% of total number of senile plaques). The 2 youngest Down syndrome brains showed only diffuse plaques that were all A beta 42(43) positive but A beta 40 negative. Old (> 50 years old) brains contained many mature senile plaques with amyloid cores in addition to diffuse and immature plaques and the proportion of A beta 40-positive senile plaques was increased (mean, 42% of total). Cerebral amyloid angiopathy was more abundant in old Down syndrome brains and was positive for both A beta 40 and A beta 42(43). In cerebral amyloid angiopathy, A beta 40 predominated over A beta 42(43) in both staining intensity and number of positive vessels. These results indicate that (1) the A beta species initially deposited in the brain as senile plaques is A beta 42(43) and A beta 40 only appears a decade later, and (2) in cerebral amyloid angiopathy A beta 40 appears as early as A beta 42(43).
CD20‐depleting therapy in autoimmune diseases: from basic research to the clinic (2009)

The B lymphocyte-associated antigen CD20 is becoming an important immunotherapy target for autoimmune diseases, although its biological function has not been defined. Besides rheumatoid arthritis, growing experience with B cell-depleting therapy indicates that it may be effective in Sjögren's syndrome, dermatomyositis-polymyositis, systemic lupus erythematosus and some types of vasculitides. However, controlled clinical trials are still lacking for some of these indications. Infection has not been seen as a major limitation to this therapy, but reports of progressive multifocal leukoencephalopathy in an extremely small number of patients are of concern. Here, we review the therapeutic actions of anti-CD20 antibodies, and the recent and ongoing clinical trials with CD20-depleting therapy in autoimmune diseases.
Frequent value locality and value-centric data cache design (2000)

By studying the behavior of programs in the SPECint95 suite we observed that six out of eight programs exhibit a new kind of value locality, the frequent value locality , according to which a few values appear very frequently in memory locations and are therefore involved in a large fraction of memory accesses. In these six programs ten distinct values occupy over 50% of all memory locations and on an average account for nearly 50% of all memory accesses during program execution. This observation holds for smaller blocks of consecutive memory locations and the set of frequent values remains quite stable over the execution of the program.In the six benchmarks with frequent value locality, on an average 50% of all cache misses occur during the reading or writing of the ten most frequently accessed values. We propose a new data cache structure, the frequent value cache (FVC), which employs a value-centric approach to caching data locations for exploiting the frequent value locality phenomenon. FVC is a small direct-mapped cache which is dedicated to holding only frequently occurring values. The value-centric nature of FVC enables us to store data in a compressed form where the compression is achieved by encoding the frequent values using a few bits. Moreover this simple compression scheme preserves the random access to data values in a cache line.Our experiments demonstrate that by augmenting a direct mapped cache (DMC) with a direct mapped FVC of size no more than 3 Kbytes we can obtain reductions in miss rates ranging from 1% to 68%. In fact we observed that higher reductions in miss rates can be achieved by augmenting a DMC with a small FVC as opposed to doubling the size of DMC for the 124.m88ksim and 134.perl benchmarks.
SCN1Amutations and epilepsy (2005)

SCN1A is part of the SCN1A-SCN2A-SCN3A gene cluster on chromosome 2q24 that encodes for α pore forming subunits of sodium channels. The 26 exons of SCN1A are spread over 100 kb of genomic DNA. Genetic defects in the coding sequence lead to generalized epilepsy with febrile seizures plus (GEFS+) and a range of childhood epileptic encephalopathies of varied severity (e.g., SMEI). All published mutations are collated. More than 100 novel mutations are spread throughout the gene with the more debilitating usually de novo. Some clustering of mutations is observed in the C-terminus and the loops between segments 5 and 6 of the first three domains of the protein. Functional studies so far show no consistent relationship between changes to channel properties and clinical phenotype. Of all the known epilepsy genes SCN1A is currently the most clinically relevant, with the largest number of epilepsy related mutations so far characterized. Hum Mutat 25:535–542, 2005. © 2005 Wiley-Liss, Inc.
Mechanisms of Degranulation in Neutrophils (2006)

Neutrophils are critical inflammatory cells that cause tissue damage in a range of diseases and disorders. Being bone marrow-derived white blood cells, they migrate from the bloodstream to sites of tissue inflammation in response to chemotactic signals and induce inflammation by undergoing receptor-mediated respiratory burst and degranulation. Degranulation from neutrophils has been implicated as a major causative factor in pulmonary disorders, including severe asphyxic episodes of asthma. However, the mechanisms that control neutrophil degranulation are not well understood. Recent observations indicate that granule release from neutrophils depends on activation of intracellular signalling pathways, including beta-arrestins, the Rho guanosine triphosphatase Rac2, soluble NSF attachment protein (SNAP) receptors, the src family of tyrosine kinases, and the tyrosine phosphatase MEG2. Some of these observations suggest that degranulation from neutrophils is selective and depends on nonredundant signalling pathways. This review focuses on new findings from the literature on the mechanisms that control the release of granule-derived mediators from neutrophils.
Adapted wavelet analysis from theory to software (1994)

This detail-oriented text is intended for engineers and applied mathematicians who must write computer programs to perform wavelet and related analysis on real data. It contains an overview of mathematical prerequisites and proceeds to describe hands-on programming techniques to implement special programs for signal analysis and other applications. From the table of contents: - Mathematical Preliminaries - Programming Techniques - The Discrete Fourier Transform - Local Trigonometric Transforms - Quadrature Filters - The Discrete Wavelet Transform - Wavelet Packets - The Best Basis Algorithm - Multidimensional Library Trees - Time-Frequency Analysis - Some Applications - Solutions to Some of the Exercises - List of Symbols - Quadrature Filter Coefficients
A discrete-time localization method for capsule endoscopy based on on-board magnetic sensing (2011)

Recent achievements in active capsule endoscopy have allowed controlled inspection of the bowel by magnetic guidance. Capsule localization represents an important enabling\n\ntechnology for such kinds of platforms. In this paper, the authors present a localization\n\nmethod, applied as first step in time-discrete capsule position detection, that is useful for establishing a magnetic link at the beginning of an endoscopic procedure or for re-linking the capsule in the case of loss due to locomotion. The novelty of this approach consists in using magnetic sensors on board the capsule whose output is combined with pre-calculated magnetic\n\nfield analytical model solutions. A magnetic field triangulation algorithm is used for obtaining the position of the capsule inside the gastrointestinal tract. Experimental validation has demonstrated that the proposed procedure is stable, accurate and has a wide localization range in a volume of about 18 × 103 cm3. Position errors of 14 mm along the X direction, 11 mm\n\nalong the Y direction and 19 mm along the Z direction were obtained in less than 27 s of\n\nelaboration time. The proposed approach, being compatible with magnetic fields used for locomotion, can be easily extended to other platforms for active capsule endoscopy.