gebhart/patrepeval huggingface dataset:
Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK (2009)

Th17 cells play an important role in mediating autoimmune diseases, but the molecular mechanism underlying Th17 differentiation is incompletely understood. We show here that NF-kappaB-inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Th17 cells. NIK-deficient naive CD4 T cells are attenuated in the differentiation to Th17 cells, although they are competent in committing to the other effector lineages. Consistently, NIK knockout mice are resistant to experimental autoimmune encephalomyelitis, a disease model that involves the function of Th17 cells. This phenotype was also detected in Rag2 knockout mice reconstituted with NIK-deficient T cells, confirming a T-cell intrinsic defect. We further show that NIK mediates synergistic activation of STAT3 by T-cell receptor and IL-6 receptor signals. NIK deficiency attenuates activation of STAT3 and induction of STAT3 target genes involved in Th17-commitment program. These findings establish NIK as an important signaling factor that regulates Th17 differentiation and experimental autoimmune encephalitis induction.
β2-microglobulin–deficient Mice Are Resistant to Bullous Pemphigoid (1997)

Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases. We proposed that beta2-microglobulin (beta2m)-deficient mice have been protected from systemic lupus erythematosis (SLE)-like syndromes because they lack the beta2m-associated IgG protection receptor (FcRn) and therefore catabolize IgG, including pathogenic IgG autoantibodies, considerably more rapidly than normal mice. Such an hypothesis would predict that beta2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane. To test this hypothesis, we administered pathogenic rabbit antibody directed toward the hemidesmosome to beta2m-deficient mice and to normal control mice, both intraperitoneally and intradermally, and assessed the mice clinically, histologically, and immunologically for manifestations of skin disease. We found that the beta2m-deficient mice were protected when the antibody was given intraperitoneally whereas intradermal administration resulted in blisters only slightly less severe than those seen in normal mice. These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.
The Efficacy of Surgical Modifications of the Upper Airway in Adults With Obstructive Sleep Apnea Syndrome (1996)

This paper, which has been reviewed and approved by the Board of Directors of the American Sleep Disorders Association, provides the background for the Standards of Practice Committee's parameters for the practice of sleep medicine in North America. The intent of this paper is to provide an overview of the surgical treatment of obstructive sleep apnea syndrome, to provide the basis for the American Sleep Disorders Association's practice parameters on this subject and to share our findings of metanalysis of previously published studies regarding uvulopalatopharyngoplasty. We searched MEDLINE from January 1966 through April 1993, with an update in February 1995, to provide a review of the application of surgical modifications of the upper airway to treat adults with obstructive sleep apnea syndrome. Operations to treat obstructive sleep apnea syndrome include nasal septal reconstruction; uvulopalatopharyngoplasty; uvulopalatopharyngoglossoplasty; laser midline glossectomy; lingualplasty; inferior sagittal mandibular osteotomy and genioglossal advancement, with hyoid myotomy and suspension (the entire process is referred to as GAHM); maxillomandibular osteotomy and advancement, and tracheotomy. Papers included in metanalysis provided preoperative and postoperative polysomnographic data on at least nine patients treated with uvulopalatopharyngoplasty for their obstructive sleep apnea. Analysis of the uvulopalatopharyngoplasty papers revealed that this procedure is, at best, effective in treating less than 50% of patients with obstructive sleep apnea syndrome. The site of pharyngeal narrowing or collapse, although identified by different and unvalidated methods, has a marked effect on the probability of success of uvulopalatopharyngoplasty. Patients who achieve a favorable response with uvulopalatopharyngoplasty tend to have less severe obstructive sleep apnea than those who do not. For patients who demonstrate retrolingual narrowing or collapse, other surgical modifications have been described, such as lingualplasty, GAHM, and maxillomandibular osteotomy and advancement. The studies to support the use of the surgical treatment of obstructive sleep apnea syndrome contain biases related to small sample size, limited follow-up and patient selection.
A Phase I Open-Label, Dose-Escalation, Multi-Institutional Trial of Injection with an E1B-Attenuated Adenovirus, ONYX-015, into the Peritumoral Region of Recurrent Malignant Gliomas, in the Adjuvant Setting (2004)

ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The NABTT CNS Consortium conducted a dose-escalation trial of intracerebral injections of ONYX-015. Cohorts of six patients at each dose level received doses of vector from 10(7) plaque-forming units (pfu) to 10(10) pfu into a total of 10 sites within the resected glioma cavity. Adverse events were identified on physical exams and testing of hematologic, renal, and liver functions. Efficacy data were obtained from serial MRI scans. None of the 24 patients experienced serious adverse events related to ONYX-015. The maximum tolerated dose was not reached at 10(10) pfu. The median time to progression after treatment with ONYX-015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months (range 1.3 to 28.0 + months). One patient has not progressed and 1 patient showed regression of interval-increased enhancement. With more than 19 months of follow-up, 1/6 recipients at a dose of 10(9) and 2/6 at a dose of 10(10) pfu remain alive. In 2 patients who underwent a second resection 3 months after ONYX-015 injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection of ONYX-015 into glioma cavities is well tolerated at doses up to 10(10) pfu.
A randomized controlled trial comparing autologous radiolabeled in vivo platelet (PLT) recoveries and survivals of 7‐day‐stored PLT‐rich plasma and buffy coat PLTs from the same subjects (2011)

We were unable to demonstrate that single-unit BC-PLTs stored for 7 days have superior poststorage viability compared to PRP-PLTs. Failure to meet the minimum FDA criteria for poststorage PLT viability raises questions regarding the acceptance thresholds of these metrics.
Autologous fibrin tissue adhesive: Factors influencing bonding power (1988)

Bonding power of Autologous Fibrin Tissue Adhesive (AFTA) is directly related to its fibrinogen concentration. By increasing the ammonium sulfate concentration 100% during fibrinogen precipitation, the bonding power of two glued 1-cm2 pieces of human dura almost doubled. No relationship between blood fibrinogen level and bonding power was demonstrated. Comparing AFTA with Fibrin Sealant, the commercial fibrin tissue adhesive, shearing strength between two glued pieces of human dura with AFTA was less 10 minutes and greater 30 minutes after gluing. Gluing a TORP (Richards) to a 1-cm2 piece of human dura yielded generally somewhat greater bonding power when using Fibrin Sealant. Autologous Fibrin Tissue Adhesive provides bonding power adequate for middle-ear surgery, eliminates transmission of viral diseases and, unlike Fibrin Sealant, AFTA is available in the United States.
Defining Affinity with the GABAAReceptor (1998)

At nicotinic and glutamatergic synapses, the duration of the postsynaptic response depends on the affinity of the receptor for transmitter (Colquhoun et al., 1977;Pan et al., 1993). Affinity is often thought to be determined by the ligand unbinding rate, whereas the binding rate is assumed to be diffusion-limited. In this view, the receptor selects for those ligands that form a stable complex on binding, but binding is uniformly fast and does not itself affect selectivity. We tested these assumptions for the GABAA receptor by dissecting the contributions of microscopic binding and unbinding kinetics for agonists of equal efficacy but of widely differing affinities. Agonist pulses applied to outside-out patches of cultured rat hippocampal neurons revealed that agonist unbinding rates could not account for affinity if diffusion-limited binding was assumed. However, direct measurement of the instantaneous competition between agonists and a competitive antagonist revealed that binding rates were orders of magnitude slower than expected for free diffusion, being more steeply correlated with affinity than were the unbinding rates. The deviation from diffusion-limited binding indicates that a ligand-specific energy barrier between the unbound and bound states determines GABAA receptor selectivity. This barrier and our kinetic observations can be quantitatively modeled by requiring the participation of movable elements within a flexible GABA binding site.
Isoform-Selective Interaction of Cyclooxygenase-2 with Indomethacin Amides Studied by Real-Time Fluorescence, Inhibition Kinetics, and Site-Directed Mutagenesis (2002)

Conversion of carboxylate-containing nonsteroidal antiinflammatory drugs, such as indomethacin, to esters or amides provides potent and selective inhibitors of cyclooxygenase-2 (COX-2) [Kalgutkar et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 925-930]. Synthesis of cinnamyl- or coumarinyl-substituted ethanolamide derivatives of indomethacin produced fluorescent probes of inhibitor interaction with COX-2 and COX-1. Binding of either derivative to apoCOX-2 or apoCOX-1 resulted in a rapid, reversible enhancement of fluorescence. Following this rapid phase, a slow additional increase in fluorescence was observed with apoCOX-2 but not with apoCOX-1. The slow, COX-2-specific increase in fluorescence was prevented or reversed by addition of the nonfluorescent COX inhibitor (S)-flurbiprofen. Detailed kinetic studies of the interaction of the coumarinyl derivative with COX-2 showed that the observed changes in fluorescence could be described by two sequential equilibria, the first of which is rapid, reversible, and bimolecular in the forward direction. The second equilibrium is slower, reversible, and unimolecular in both directions. The forward rate constant for the slow equilibrium determined by fluorescence enhancement [(3.1 +/- 0.6) x 10(-3) s(-1)] corresponded closely to the forward rate constant for inhibition of COX-2 activity [(6.8 +/- 2.3) x 10(-3) s(-1)], suggesting that the slow fluorescence enhancement is associated with selective COX-2 inhibition. Site-directed mutagenesis indicated that residues in the carboxylate-binding region of the COX-2 active site (Arg-120, Tyr-355, and Glu-524) are critical for the binding of the indomethacin conjugates that leads to slow fluorescence enhancement and cyclooxygenase inhibition. The indomethacin conjugates described herein represent powerful tools for the investigation of a novel class of selective inhibitors of COX-2.
Tetrazine Assists Reduction of Water by Phosphines: Application in the Mitsunobu Reaction (2016)

Reaction of 3,6-disubstituted-1,2,4,5-tetrazines with water and PEt<sub>3</sub> forms the corresponding 1,4-dihydrotetrazine and OPEt<sub>3</sub> . Thus PEt<sub>3</sub> , as a stoichiometric reductant, reduces water, and the resulting two reducing equivalents serve to doubly hydrogenate the tetrazine. A variety of possible initial interactions between electron-deficient tetrazine and electron-rich PR<sub>3</sub> , including a charge transfer complex, were evaluated by density functional calculations which revealed that the energy of all these make them spectroscopically undetectable at equilibrium, but one of these is nevertheless suggested as the intermediate in the observed redox reaction. The relationship of this to the Mitsunobu reaction, which absorbs the components of water evolved in the conversion of alcohol and carboxylic acid to ester, with desirable inversion at the alcohol carbon, is discussed. This enables a modified Mitsunobu reaction, with tetrazine replacing EtO<sub>2</sub> CN=NCO<sub>2</sub> Et (DEAD), which has the advantage that dihydrotetrazine can be recycled to tetrazine by oxidation with O<sub>2</sub> , something impossible with the hydrogenated DEAD. For this tetrazine version, a betaine-like intermediate is undetectable, but its protonated form is characterized, including by X-ray structure and NMR spectroscopy.
The Functional Neuroanatomy of Target Detection: An fMRI Study of Visual and Auditory Oddball Tasks (1999)

The neuronal response patterns that are required for an adequate behavioural reaction to subjectively relevant changes in the environment are commonly studied by means of oddball paradigms, in which occasional 'target' stimuli have to be detected in a train of frequent 'non-target' stimuli. The detection of such task-relevant stimuli is accompanied by a parietocentral positive component of the event-related potential, the P300. We performed EEG recordings of visual and auditory event-related potentials and functional magnetic resonance imaging (fMRI) when healthy subjects performed an oddball task. Significant increases in fMRI signal for target versus non-target conditions were observed in the supramarginal gyrus, frontal operculum and insular cortex bilaterally, and in further circumscribed parietal and frontal regions. These effects were consistent over various stimulation and response modalities and can be regarded as specific for target detection in both the auditory and the visual modality. These results therefore contribute to the understanding of the target detection network in human cerebral cortex and impose constraints on attempts at localizing the neuronal P300 generator. This is of importance both from a neurobiological perspective and because of the widespread application of the physiological correlates of target detection in clinical P300 studies.
RNA Silencing of Dengue Virus Type 2 Replication in Transformed C6/36 Mosquito Cells Transcribing an Inverted-Repeat RNA Derived from the Virus Genome (2002)

Double-stranded RNA (dsRNA) initiates cellular posttranscriptional responses that are collectively called RNA silencing in a number of different organisms, including plants, nematodes, and fruit flies. In plants, RNA silencing has been associated with protection from virus infection. In this study, we demonstrate that dsRNA-mediated interference also can act as a viral defense mechanism in mosquito cells. C6/36 (Aedes albopictus) cells were stably transformed with a plasmid designed to transcribe an inverted-repeat RNA (irRNA) derived from the genome of dengue virus type 2 (DEN-2) capable of forming dsRNA. Clonal cell lines were selected with an antibiotic resistance marker and challenged with DEN-2. The cell lines were classified as either susceptible or resistant to virus replication, based on the percentage of cells expressing DEN-2 envelope (E) antigen 7 days after challenge. Eight out of 18 (44%) cell lines designed to express irRNA were resistant to DEN-2 challenge, with more than 95% of the cells showing no DEN-2 antigen accumulation. One of the DEN-2-resistant cell lines, FB 9.1, was further characterized. DEN-2 genome RNA failed to accumulate in FB 9.1 cells after challenge. Northern blot hybridization detected transcripts containing transgene sequences of both sense and antisense polarity, suggesting that DEN-2-specific dsRNA was present in the cells. In addition, a class of small RNAs 21 to 25 nucleotides in length was detected that specifically hybridized to labeled sense or antisense DEN-2 RNA derived from the target region of the genome. These observations were consistent with RNA silencing as the mechanism of resistance to DEN-2 in transformed mosquito cells.
Opportunities for immunotherapy in microsatellite instable colorectal cancer (2016)

Microsatellite instability (MSI), the somatic accumulation of length variations in repetitive DNA sequences called microsatellites, is frequently observed in both hereditary and sporadic colorectal cancer (CRC). It has been established that defects in the DNA mismatch repair (MMR) pathway underlie the development of MSI in CRC. After the inactivation of the DNA MMR pathway, misincorporations, insertions and deletions introduced by DNA polymerase slippage are not properly recognized and corrected. Specific genomic regions, including microsatellites, are more prone for DNA polymerase slippage and, therefore, more susceptible for the introduction of these mutations if the DNA MMR capacity is lost. Some of these susceptible genomic regions are located within the coding regions of genes. Insertions and deletions in these regions may alter their reading frame, potentially resulting in the transcription and translation of frameshift peptides with c-terminally altered amino acid sequences. These frameshift peptides are called neoantigens and are highly immunogenic, which explains the enhanced immunogenicity of MSI CRC. Neoantigens contribute to increased infiltration of tumor tissue with activated neoantigen-specific cytotoxic T lymphocytes, a hallmark of MSI tumors. Currently, neoantigen-based vaccination is being studied in a clinical trial for Lynch syndrome and in a trial for sporadic MSI CRC of advanced stage. In this Focussed Research Review, we summarize current knowledge on molecular mechanisms and address immunological features of tumors with MSI. Finally, we describe their implications for immunotherapeutic approaches and provide an outlook on next-generation immunotherapy involving neoantigens and combinatorial therapies in the setting of MSI CRC.
A New Comprehensive Approach of Surround Sound Recording (2003)

This convention paper has been reproduced from the author&amp;apos;s advance manuscript, without editing, corrections, or consideration by the Review Board. The AES takes no responsibility for the contents. Additional papers
Modified Rapid DNA Extraction Protocol for High Throughput Microsatellite Analysis in Wheat (2002)

ABSTRACT New technology is allowing marker‐assisted selection to fulfill the promise of increasing efficiency of cultivar development. However, these techniques depend upon the ability to extract DNA from large populations of plants. The objective of this project was to develop a high‐throughput DNA extraction procedure without the need for greenhouse space or growing wheat ( Triticum aestivum L.) plants. A sodium hydroxide rapid DNA extraction was modified for a 96‐well format to reduce costs. Seeds were germinated in 8‐well tissue culture plates, and 4‐d‐old seedling tissue was used to extract DNA by means of sodium hydroxide methodology. Approximately 1 μg of genomic DNA per 10 mg of tissue was isolated at a cost of about $0.10. The DNA quality was verified by amplification of microsatellite markers. Results were consistent with either fresh or stored tissue extracts. This technique allows one person to extract nearly 1000 storage‐stable DNA samples daily, while keeping costs at a minimum.
Automated flaw detection in aluminum castings based on the tracking of potential defects in a radioscopic image sequence (2002)

Presents a method for inspecting aluminum castings automatically from a sequence of radioscopic images taken at different positions of the casting. The classic image-processing methods for flaw detection of aluminum castings use a bank of filters to generate an error-free reference image. This reference image is compared with the real radioscopic image, and flaws are detected at the pixels where the difference between them is considerable. However, the configuration of each filter depends strongly on the size and shape of the structure of the casting under inspection. A two-step technique is proposed to detect flaws automatically and that uses a single filter. First, the method identifies potential defects in each image of the sequence, and second, it matches and tracks them from image to image. The key idea of the paper is to consider as false alarms those potential defects which cannot be tracked in the sequence. The robustness and reliability of the method have been verified on both real data in which synthetic flaws have been added and real radioscopic image sequences recorded from cast aluminum wheels with known defects. Using this method, the real defects can be detected with high certainty. This approach achieves good discrimination from false alarms.
A method for robust segmentation of arbitrarily shaped radiopaque structures in cone‐beam CT projections (2011)

A robust template-based method for segmentation of arbitrarily shaped radiopaque markers in CBCT projections was developed.
A comparison of hardware prefetching techniques for multimedia benchmarks (2002)

Data prefetching is a well known technique for improving cache performance. While several studies have examined prefetch strategies for scientific and commercial applications, no published work has studied the special memory requirements of multimedia applications. This paper presents data for three types of hardware prefetching schemes: stream buffers, stride prediction tables, and a hybrid combination of the two, the stream cache. Use of the stride prediction table is shown to eliminate up to 90% of the misses that would otherwise be incurred in a moderate or large sized cache with no prefetching hardware. The stream cache, proposed for the first time in this paper, has the potential to cut execution times by half with the addition of a relatively small amount of additional hardware.
Prevalence of Antibodies to Lymphadenopathy-Associated Retrovirus in African Patients with AIDS (1984)

The presence of antibodies to lymphadenopathy-associated retrovirus (LAV) was determined by a radioimmunoprecipitation assay and by an enzyme-linked immunosorbent solid assay of sera from Zairian patients with the acquired immune deficiency syndrome (AIDS) in 1983. Thirty-five of 37 patients (94 percent) and 32 of 36 patients (88 percent), respectively, were seropositive by the two tests. In a control group of 26 patients, six (23 percent) showed positive results in these tests. Of these six control patients, five had clinically demonstrable infectious diseases and a low ratio of T4 to T8 lymphocytes. In addition, sera collected from a control group of Zairian mothers in 1980 were positive for LAV in 5 of 100 cases. Other serologic data suggest that LAV was present as early as 1977 in Zaire.
A domain structure common to hemopexin, vitronectin, interstitial collagenase, and a collagenase homolog. (1987)

The sequence of hemopexin consists almost entirely of two homologous domains joined by a short hinge region; the domain structure, with its own characteristic features, is derived from four short tandem repeats. Each repeat contains several alternating clusters of hydrophobic and hydrophilic residues but also has some individual features as a consequence of its position in the domain. Here we present evidence for the presence of a single hemopexin domain in an interstitial collagenase and in a collagenase homolog, as well as of two copies of the domain in vitronectin. The functions of all of these proteins involve binding to various proteins and smaller molecules. We suggest that the presence of this domain may facilitate these binding activities. Our analysis also suggests a tentative identification of substrate-binding and catalytic domains in the collagenase and its homolog.