gebhart/patrepeval huggingface dataset:
Signal transduction driving technology driving signal transduction: Factors in the design of targeted therapies (2001)

A significant number of human diseases can be attributed to defects in cellular signal transduction pathways. Large-scale proteomics projects now in progress seek to better define critical components of signal transduction networks, to enable more intelligent design of therapeutic agents that can specifically correct disease-specific signaling alterations by targeting individual proteins. A complicating factor in this endeavor is the fact that intracellular signaling involves many diverse mechanisms that in sum finely modulate the activity of individual proteins in response to different biological inputs. Ability to develop reagents that selectively correct disease-associated signaling activities, while leaving intact benign or essential activities, encompassed within a single protein requires an intimate knowledge of pathway-specific control mechanisms. To illustrate these points, we provide examples of some of the complex control mechanisms regulating the Cas proteins, which contribute to integrin-dependent biological response. We then discuss issues involved in systematically incorporating information related to complex control mechanisms in proteomic databases. Finally, we describe some recent instances in which protein interaction technologies have been specifically adapted to identify small molecule agents that regulate protein response in physiologically desirable ways, and discuss issues relevant to future drug discovery efforts.
Detection of infliximab in breast milk of nursing mothers with inflammatory bowel disease (2011)

In contrast with prior reports, infliximab can be detected in the breast milk of nursing mothers. The miniscule amounts of infliximab transferred in breast milk are unlikely to result in systemic immune-suppression of the infant. Nonetheless, local effects of this exposure on the neonates' intestine and potential immune sensitization or tolerization towards the drug can not be excluded and merit further investigations.
Upper-Limb Prosthetics (2007)

Future research should focus on continued development of more comfortable and functional prostheses, particularly for individuals with high-level or bilateral limb absence. Improved follow-up, repair, and information services, together with active involvement of clients in the selection of prostheses meeting their specific goals and needs, is recommended.
Glial Expression of the β-Amyloid Precursor Protein (APP) in Global Ischemia (1995)

The beta-amyloid precursor protein (APP) bears characteristics of an acute-phase protein and therefore is likely to be involved in the glial response to brain injury. In the brain, APP is rapidly synthesized by activated glial cells in response to comparatively mild neuronal lesions, e.g., a remote peripheral nerve injury. Perfusion deficits in the brain result largely in neuronal necrosis and are a common condition in elderly patients. This neuronal necrosis is accompanied by a pronounced reaction of astrocytes and microglia, which can also be observed in animal models. We have therefore studied in the rat, immunocytochemically, the induction of APP after 30 min of global ischemia caused by four-vessel occlusion. The postischemic brain injuries were examined at survival times from 12 h to 7 days. From day 3 onward, APP immunoreactivity was strongly induced in the CA1 and CA4 regions of the rat dorsal hippocampus as well as in the dorsolateral striatum. In these areas, the majority of APP-immunoreactive cells were reactive glial fibrillary acidic protein (GFAP)-positive astrocytes, as shown by double-immunofluorescence labeling for GFAP and APP. Additionally, small ramified cells, most likely activated microglia, expressed APP immunoreactivity. In contrast, in the parietal cortex, APP immunoreactivity occurred focally in clusters of activated microglia rather than in astrocytes, as demonstrated by double-immunofluorescence labeling for APP and the microglia-binding lectin Griffonia simplicifolia isolectin B4. In conclusion, following global ischemia, APP is induced in reactive glial cells with spatial differences in the distribution pattern of APP induction in astrocytes and microglia.
SW-ARRAY: a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data (2005)

Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith-Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267-1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides.
Scalable Visual Analytics of Massive Textual Datasets (2007)

This paper describes the first scalable implementation of a text processing engine used in visual analytics tools. These tools aid information analysts in interacting with and understanding large textual information content through visual interfaces. By developing a parallel implementation of the text processing engine, we enabled visual analytics tools to exploit cluster architectures and handle massive datasets. The paper describes key elements of our parallelization approach and demonstrates virtually linear scaling when processing multi-gigabyte data sets such as Pubmed. This approach enables interactive analysis of large datasets beyond capabilities of existing state-of-the art visual analytics tools.
Dysregulation of Chemokine/Chemokine Receptor Axes and NK Cell Tissue Localization during Diseases (2016)

Chemokines are small chemotactic molecules that play key roles in physiological and pathological conditions. Upon signaling <i>via</i> their specific receptors, chemokines regulate tissue mobilization and trafficking of a wide array of immune cells, including natural killer (NK) cells. Current research is focused on analyzing changes in chemokine/chemokine receptor expression during various diseases to interfere with pathological trafficking of cells or to recruit selected cell types to specific tissues. NK cells are a heterogeneous lymphocyte population comprising several subsets endowed with distinct functional properties and mainly representing distinct stages of a linear development process. Because of their different functional potential, the type of subset that accumulates in a tissue drives the final outcome of NK cell-regulated immune response, leading to either protection or pathology. Correspondingly, chemokine receptors, including CXCR4, CXCR3, and CX<sub>3</sub>CR1, are differentially expressed by NK cell subsets, and their expression levels can be modulated during NK cell activation. At first, this review will summarize the current knowledge on the contribution of chemokines to the localization and generation of NK cell subsets in homeostasis. How an inappropriate chemotactic response can lead to pathology and how chemokine targeting can therapeutically affect tissue recruitment/localization of distinct NK cell subsets will also be discussed.
A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. (1991)

The profound influence of glucocorticoid hormones on the inflammatory response includes a rapid and significant reduction in the synthesis of cyclooxygenase (prostaglandin G/H synthase, PGHS), the key enzyme for prostaglandin biosynthesis. In analyzing the glucocorticoid effects on PGHS synthesis in C127 mouse fibroblasts, we detected a novel 4-kilobase (kb) mRNA that is related to a PGHS cDNA cloned from an ovine seminal vesicle library. This RNA is much more prevalent in cycloheximide-treated cells and, based on stringency analysis and preliminary sequence data, arises from a gene distinct from that transcribed into the previously cloned 2.8-kb PGHS cDNA. Furthermore, the 4-kb mRNA encodes a 70-kDa protein that is specifically immunoprecipitated by anti-PGHS serum. The abundance of the 4-kb mRNA is strongly decreased by dexamethasone and increased by serum within 2 h whereas the 2.8-kb PGHS mRNA, which is also seen in these cells, does not consistently change. These changes in the level of the 4-kb mRNA with serum and dexamethasone treatment parallel changes in the level of synthesized PGHS protein detected in both metabolically labeled cells and in in vitro translated mRNAs. This discovery of a cyclooxygenase-related gene that is transcriptionally regulated by serum and glucocorticoid hormones in a manner identical to that reported for cyclooxygenase activity may help clarify issues regarding cyclooxygenase regulation and suggests that two distinct and differentially regulated cyclooxygenase species exist.
Nuclear factor–kB in rheumatoid synovium. Localization of P50 and P65 (1995)

In most RA patients, the p50 and p65 subunits of NF-kappa B were present in the majority of CD14-positive cells within the lining and sublining regions and in a proportion of other cells throughout the synovium, including endothelial cells. NF-kappa B is likely to play an important role in the expression of macrophage-derived cytokines in rheumatoid synovium. Different but overlapping distributions of nuclear p50 and p65 versus Jun and Fos indicate separate or divergent mechanisms for the activation of NF-kappa B and the expression of AP-1 proteins in rheumatoid synovium.
A simple method for the purification of Eimeria tenella sporozoites. (1993)

A rapid, simple and cheap method for the purification of Eimeria tenella sporozoites has been developed using commercially available filter paper (595 filter paper circles, Schleicher & Schuell, 3354 Dassel, Germany, order 311610). Yield and purity are of the same value as by purification with a leukopac column (Bontemps & Yvore 1974). The described method can be used for the purification of Eimeria tenella sporozoites under sterile conditions for subsequent in vitro cultivation.
Growth Hormone Responses to Melatonin in Man (1974)

Oral administration of 1 gram of melatonin caused rapid and significant elevations of serum human growth hormone in eight out of nine normal male subjects. The mean (+/- standard error of the mean) of the peak response by growth hormone was 22.9 +/- 4.6 microunits per milliliter. The increased secretion of growth hormone may be due to interaction of melatonin with hypothalamic serotoninergic receptors.
Simulating long-distance entanglement in quantum spin chains by superconducting flux qubits (2015)

We investigate the performance of superconducting flux qubits for the adiabatic quantum simulation of long distance entanglement (LDE), namely a finite ground-state entanglement between the end spins of a quantum spin chain with open boundary conditions. As such, LDE can be considered an elementary precursor of edge modes and topological order. We discuss two possible implementations which simulate open chains with uniform bulk and weak end bonds, either with Ising or with XX nearest-neighbor interactions. In both cases we discuss a suitable protocol for the adiabatic preparation of the ground state in the physical regimes featuring LDE. In the first case the adiabatic manipulation and the Ising interactions are realized using dc currents, while in the second case microwaves fields are used to control the smoothness of the transformation and to realize the effective XX interactions. We demonstrate the adiabatic preparation of the end-to-end entanglement in chains of four qubits with realistic parameters and on a relatively fast time scale.
Glycogen Synthase Kinase-3β Phosphorylates Bax and Promotes Its Mitochondrial Localization during Neuronal Apoptosis (2004)

Glycogen synthase kinase-3β (GSK-3β) is a critical activator of neuronal apoptosis induced by a diverse array of neurotoxic insults. However, the downstream substrates of GSK-3β that ultimately induce neuronal death are unknown. Here, we show that GSK-3β phosphorylates and regulates the activity of Bax, a pro-apoptotic Bcl-2 family member that stimulates the intrinsic (mitochondrial) death pathway by eliciting cytochrome c release from mitochondria. In cerebellar granule neurons undergoing apoptosis, inhibition of GSK-3β suppressed both the mitochondrial translocation of an expressed green fluorescent protein (GFP)-Bax α fusion protein and the conformational activation of endogenous Bax. GSK-3β directly phosphorylated Bax α on Ser163, a residue found within a species-conserved, putative GSK-3β phosphorylation motif. Coexpression of GFP-Bax α with a constitutively active mutant of GSK-3β, GSK-3β(Ser9Ala), enhanced the in vivo phosphorylation of wild-type Bax α , but not a Ser163Ala mutant of Bax α , in transfected human embryonic kidney 293 (HEK293) cells. Moreover, cotransfection with constitutively active GSK-3β promoted the localization of Bax α to mitochondria and induced apoptosis in both transfected HEK293 cells and cerebellar granule neurons. In contrast, neither a Ser163Ala point mutant of Bax α nor a naturally occurring splice variant that lacks 13 amino acids encompassing Ser163 (Bax σ ) were driven to mitochondria in HEK293 cells coexpressing constitutively active GSK-3β. In a similar manner, either mutation or deletion of the identified GSK-3β phosphorylation motif prevented the localization of Bax to mitochondria in cerebellar granule neurons undergoing apoptosis. Our results indicate that GSK-3β exerts some of its pro-apoptotic effects in neurons by regulating the mitochondrial localization of Bax, a key component of the intrinsic apoptotic cascade.
Roles of key active-site residues in flavocytochrome P450 BM3 (1999)

The effects of mutation of key active-site residues (Arg-47, Tyr-51, Phe-42 and Phe-87) in Bacillus megaterium flavocytochrome P450 BM3 were investigated. Kinetic studies on the oxidation of laurate and arachidonate showed that the side chain of Arg-47 contributes more significantly to stabilization of the fatty acid carboxylate than does that of Tyr-51 (kinetic parameters for oxidation of laurate: R47A mutant, Km 859 microM, kcat 3960 min-1; Y51F mutant, Km 432 microM, kcat 6140 min-1; wild-type, Km 288 microM, kcat 5140 min-1). A slightly increased kcat for the Y51F-catalysed oxidation of laurate is probably due to decreased activation energy (DeltaG) resulting from a smaller DeltaG of substrate binding. The side chain of Phe-42 acts as a phenyl 'cap' over the mouth of the substrate-binding channel. With mutant F42A, Km is massively increased and kcat is decreased for oxidation of both laurate (Km 2. 08 mM, kcat 2450 min-1) and arachidonate (Km 34.9 microM, kcat 14620 min-1; compared with values of 4.7 microM and 17100 min-1 respectively for wild-type). Amino acid Phe-87 is critical for efficient catalysis. Mutants F87G and F87Y not only exhibit increased Km and decreased kcat values for fatty acid oxidation, but also undergo an irreversible conversion process from a 'fast' to a 'slow' rate of substrate turnover [for F87G (F87Y)-catalysed laurate oxidation: kcat 'fast', 760 (1620) min-1; kcat 'slow', 48.0 (44.6) min-1; kconv (rate of conversion from fast to slow form), 4.9 (23.8) min-1]. All mutants showed less than 10% uncoupling of NADPH oxidation from fatty acid oxidation. The rate of FMN-to-haem electron transfer was shown to become rate-limiting in all mutants analysed. For wild-type P450 BM3, the rate of FMN-to-haem electron transfer (8340 min-1) is twice the steady-state rate of oxidation (4100 min-1), indicating that other steps contribute to rate limitation. Active-site structures of the mutants were probed with the inhibitors 12-(imidazolyl)dodecanoic acid and 1-phenylimidazole. Mutant F87G binds 1-phenylimidazole >10-fold more tightly than does the wild-type, whereas mutant Y51F binds the haem-co-ordinating fatty acid analogue 12-(imidazolyl)dodecanoic acid >30-fold more tightly than wild-type.
Diversity control among multiple coders: a simple approach to multiple descriptions (2002)

This paper presents a voice communication arrangement in which multiple coder-decoder (codec) pairs are coordinated to provide diversified descriptions of the source signal. This arrangement allows the system to robustly mitigate channel erasures that may occur while providing the best possible quality in the absence of channel impairments. Since single descriptive systems have been largely deployed in various networks, it is important that diversity systems can maintain backward interoperability. The proposed diversity control strategies achieve this by slightly modifying the legacy encoder, without the need for modifying the legacy decoder.
Universal Epitopes for Human CD4+Cells on Tetanus and Diphtheria Toxins (2000)

Previous studies suggested that tetanus and diphtheria toxoids (TTD and DTD, respectively) contain "universal" epitopes for human CD4+ cells (residues 632-651 and 950-969 of TTD and 271-290, 321-350, 351-370, 411-430, and 431-450 of DTD). To investigate whether CD4+ cells of 100 randomly selected subjects recognized those sequences, the proliferation of CD4+ cell-enriched blood lymphocytes to TTD and DTD and individual synthetic universal epitopes was measured. CD4+ cells of 98 subjects recognized both toxoids, those of 1 subject only TTD, and those of 1 only DTD. The TTD peptides and DTD peptides 271-290 and 331-350 were recognized by >/=80% of the toxoid-sensitized subjects. The other DTD sequences were recognized by 63%-71% of subjects. DR-homozygous subjects recognized several universal epitopes less frequently than did DR-heterozygous subjects. The intensity of responses to the epitope peptides correlated with that to TTD or DTD, consistent with recognition of the peptides by CD4+ cells specific for the cognate toxoid.
Analysis of human tonsil and cancer DNAs and RNAs for DNA sequences of group C (serotypes 1, 2, 5, and 6) human adenoviruses (1979)

Group C human adenoviruses (Ads) of serotypes 1, 2, 5, and 6 infect most children and commonly cause latent infections of lymphoid tissues. Ads transform cells into a malignant-like phenotype; the oncogenic genetic information is in the left 8% of the viral genome, in the HindIII-G DNA fragment. We have investigated the molecular basis for group C Ad latent infections in human tonsils as well as whether these viruses are linked to human cancer. Tonsil or cancer DNAs and RNAs were assayed for Ad sequences by liquid-phase saturation-hybridization with in vitro-labeled Ad5 HindIII-G fragment. About 25% of the 52 tonsils analyzed contained DNA or RNA sequences specific to HindIII-G, indicating that Ad transforming sequences are expressed as RNA in tonsils. Southern blotting analysis of four tonsil DNAs revealed multiple copies of the complete Ad genome in a free state and provided evidence for an unusual form of the Ad genome, possibly Ad DNA integrated into cellular DNA. In assays of human cancers, no Ad sequences were detected in DNAs from 26 squamous cell carcinomas (Cas), 3 adenocarcinomas, 4 oat cell Cas, 5 stomach Cas, 5 small intestine Cas, 15 colon Cas, 6 rectum Cas, 5 Hodgkin and 6 non-Hodgkin lymphomas, and 2 breast Cas. Reconstruction experiments indicated that the HindIII-G probe could detect 1 copy per cell of 0.2-0.3% of the viral genome. No HindIII-G-specific sequences were detected in RNAs from 21 squamous cell Cas, 3 oat cell Cas, 2 stomach Cas, or 18 colon Cas. In six other experiments using the complete Ad2 genome as probe, no Ad sequences were found in DNAs from 6 lung Cas, 12 normal lung tissues, 33 gastrointestinal Cas, 19 normal gastrointestinal tissues, 6 Hodgkin lymphomas, 3 breast Cas, or 4 kidney Cas, at a sensitivity of about 1 copy per tumor cell of 5-10% of the Ad2 genome. All Ad-induced cancer cells should contain at least 1 copy of 1-6% of the viral genome, the minimal size of the transforming region, and probably should contain multiple copies of more of the genome. Therefore, our data are definitive evidence against group C Ads being the cause of the cancers tested, which represent about 50% of the cancer incidence in the United States. Of additional interest, we did not detect Ad2 sequences in RNAs from 7 human placentas, 12 normal lungs, or 19 normal gastrointestinal tissues (nor in 44 cancer or 23 tonsil RNAs). Thus, we did not confirm a recent report of the presence of Ad2 RNA in RNAs from human placentas; the possibility that a small population of cells in placenta expresses group C "related" sequences is not ruled out.
Biological Activities of 'Noninfectious' Influenza A Virus Particles (2014)

Only a small fraction of influenza A virus (IAV) particles within a viral population register as infectious by traditional infectivity assays. Despite constituting the most abundant product of influenza infection, the role that the 'noninfectious' particle fraction plays in the biology of the virus has largely been ignored. This review shines a light on this oft-ignored population by highlighting studies, both old and new, that describe the unique biological activities of these particles, and discussing what this population can tell us about the biology of IAV evolution and disease.
Better region proposals for pedestrian detection with R-CNN (2016)

Region-based convolutional neural networks (R-CNNs) have achieved great success in object detection recently. These deep models depend on region proposal algorithms to hypothesize object locations. In this paper, we combine a special region proposal algorithm with R-CNN, and apply it to pedestrian detection. The special algorithm is used to generate region proposals only for pedestrian class. It is different from the popular region proposal algorithm selective search that detects generic object locations. The experimental results prove that region proposals generated by our method are more applicable than selective search for pedestrian detection. Our method performs faster training and testing than the deep model based on, and it achieves competitive performance compared to the state-of-the-arts in pedestrian detection.
Mitogen-Activated Protein Kinases Regulate Cytokine Gene Expression in Human Airway Myocytes (2000)

The signal transduction pathways regulating smooth-muscle gene expression and production of cytokines in response to proinflammatory mediators are undefined. Cultured human bronchial smooth-muscle cells were treated for 20 h with a cytokine cocktail containing interleukin (IL)-1beta, tumor necrosis factor-alpha, and interferon-gamma. A complementary DNA expression array containing 588 genes was used to follow cytokine-stimulated gene expression. The expression and secretion of the cytokines IL-1beta, IL-6, and IL-8 significantly increased after 20 h of stimulation as measured by relative reverse transcriptase/ polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting techniques. Expression of IL-6 and IL-8 was sensitive to SB203580, the specific inhibitor of p38 mitogen-activated protein (MAP) kinase and PD98059, an inhibitor of MAP kinase kinase. Expression of IL-1beta was sensitive only to PD98059. Together, these results demonstrate that the p38 and extracellular signal-regulated protein kinase MAP kinase pathways are required for proinflammatory mediator- induced cytokine expression in airway myocytes. The generation of chemokines and cytokines in airway smooth muscle also provides evidence that smooth-muscle cells have the ability to contribute to the inflammatory response.