gebhart/patrepeval huggingface dataset:
Resistance to juvenile hormone and an insect growth regulator in Drosophila is associated with an altered cytosolic juvenile hormone-binding protein. (1990)

The Met mutant of Drosophila melanogaster is highly resistant to juvenile hormone III (JH III) or its chemical analog, methoprene, an insect growth regulator. Five major mechanisms of insecticide resistance were examined in Met and susceptible Met+ flies. These two strains showed only minor differences when penetration, excretion, tissue sequestration, or metabolism of [3H]JH III was measured. In contrast, when we examined JH III binding by a cytosolic binding protein from a JH target tissue, Met strains had a 10-fold lower binding affinity than did Met+ strains. Studies using deficiency-bearing chromosomes provide strong evidence that the Met locus controls the binding protein characteristics and may encode the protein. These studies indicate that resistance in Met flies results from reduced binding affinity of a cytosolic binding protein for JH III.
Recognizing action units for facial expression analysis (2001)

Most automatic expression analysis systems attempt to recognize a small set of prototypic expressions, such as happiness, anger, surprise, and fear. Such prototypic expressions, however, occur rather infrequently. Human emotions and intentions are more often communicated by changes in one or a few discrete facial features. In this paper, we develop an Automatic Face Analysis (AFA) system to analyze facial expressions based on both permanent facial features (brows, eyes, mouth) and transient facial features (deepening of facial furrows) in a nearly frontal-view face image sequence. The AFA system recognizes fine-grained changes in facial expression into action units (AUs) of the Facial Action Coding System (FACS), instead of a few prototypic expressions. Multistate face and facial component models are proposed for tracking and modeling the various facial features, including lips, eyes, brows, cheeks, and furrows. During tracking, detailed parametric descriptions of the facial features are extracted. With these parameters as the inputs, a group of action units (neutral expression, six upper face AUs and 10 lower face AUs) are recognized whether they occur alone or in combinations. The system has achieved average recognition rates of 96.4 percent (95.4 percent if neutral expressions are excluded) for upper face AUs and 96.7 percent (95.6 percent with neutral expressions excluded) for lower face AUs. The generalizability of the system has been tested by using independent image databases collected and FACS-coded for ground-truth by different research teams.
Splicing Factor RBM20 Regulates Transcriptional Network of Titin Associated and Calcium Handling Genes in The Heart (2018)

RNA binding motif 20 (RBM20) regulates pre-mRNA splicing of over thirty genes, among which titin is a major target. With RBM20 expression, titin expresses a larger isoform at fetal stage to a smaller isoform at adult resulting from alternative splicing, while, without RBM20, titin expresses exclusively a larger isoform throughout all ages. In addition to splicing regulation, it is unknown whether RBM20 also regulates gene expression. In this study, we employed <i>Rbm20</i> knockout rats to investigate gene expression profile using Affymetrix expression array. We compared wild type to <i>Rbm20</i> knockout at day1, 20 and 49. Bioinformatics analysis showed RBM20 regulates fewer genes expression at younger age and more at older age and commonly expressed genes have the same trends. GSEA indicated up-regulated genes are associated with heart failure. We examined titin binding partners. All titin direct binding partners are up-regulated and their increased expression is associated with dilated cardiomyopathy. Particularly, we found that genes involving calcium handling and muscle contraction are changed by RBM20. Intracellular calcium level measurement with individual cardiomyocytes further confirmed that changes of these proteins impact calcium handling. Selected genes from titin binding partners and calcium handling were validated with QPCR and western blotting. These data demonstrate that RBM20 regulates gene splicing as well as gene expression. Altered gene expression by RBM20 influences protein-protein interaction, calcium releasing and thus muscle contraction. Our results first reported gene expression impacted by RBM20 with heart maturation, and provided new insights into the role of RBM20 in the progression of heart failure.
CD40 is functionally expressed on human thymic epithelial cells (1992)

CD40 is a prominent B cell Ag also found on certain epithelial cells and on carcinomas. In this report, we analyzed CD40 distribution in the human thymus. CD40 was not found on the majority of CD45-positive thymocytes, but was present in a CD45-negative stromal cell population. Immunohistology showed CD40 expression on cortical thymic epithelial cells (TEC), medullary TEC, thymic interdigitating cells, and thymic B cells. CD40 was not found on thymocytes, endothelial cells, or on the fibroblasts of the septae. Expression of CD40 was specifically maintained on cultured TEC and not found on cultured thymic fibroblasts. IL-1 alpha, TNF-alpha, IFN-gamma, but not IL-4, significantly up-regulated the membrane expression of CD40 on cultured TEC. The regulation of CD40 was similar to that of ICAM-1, and contrasted with that of MHC class II Ag, which could only be induced by IFN-gamma but not by IL-1, TNF, or IL-4. Northern blot analysis showed the presence of a 1.4-kb mRNA transcript for CD40 in TEC, which was up-regulated by IL-1 and IFN-gamma. Cross-linking of CD40 at the surface of human TEC in the absence of IL-1 stimulation failed to induce cytokine secretion. Triggering of TEC with anti-CD40 mAb in conjunction with IFN-gamma and IL-1 stimulation increased granulocyte-macrophage CSF secretion in a dose-dependent manner. The effect was visible as early as 24 h after triggering, occurred in the absence of cellular proliferation, and was specific for CD40 since triggering of other TEC membrane Ag such as ICAM-1 or MHC class I molecules had no effect to increase cytokine production in TEC. These data demonstrate that CD40 is expressed and is a functional molecule at the surface of the epithelial cells of the thymus.
Strategies for enzyme/prodrug cancer therapy. (2001)

The selective activation of prodrug(s) in tumor tissues by exogenous enzyme(s) for cancer therapy can be accomplished by several ways, including gene-directed enzyme prodrug therapy (GDEPT), virus-directed enzyme prodrug therapy (VDEPT), and antibody-directed enzyme prodrug therapy (ADEPT). The central part of enzyme/prodrug cancer therapy is to deliver drug-activating enzyme gene or functional protein to tumor tissues, followed by systemic administration of a prodrug. Although each approach (GDEPT, VDEPT, and ADEPT) has been tested in clinical trials, there are some potential problems using the current delivery systems. In this article, disadvantages and advantages associated with each approach (GDEPT, VDEPT, and ADEPT) and future perspective for improving current systems are discussed.
Testis-specific miRNA-469 Up-regulated in Gonadotropin-regulated Testicular RNA Helicase (GRTH/DDX25)-null Mice Silences Transition Protein 2 and Protamine 2 Messages at Sites within Coding Region (2011)

Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), a testis-specific member of the DEAD-box family, is an essential post-transcriptional regulator of spermatogenesis. Failure of expression of Transition protein 2 (TP2) and Protamine 2 (Prm2) proteins (chromatin remodelers, essential for spermatid elongation and completion of spermatogenesis) with preservation of their mRNA expression was observed in GRTH-null mice (azoospermic due to failure of spermatids to elongate). These were identified as target genes for the testis-specific miR-469, which is increased in the GRTH-null mice. Further analysis demonstrated that miR-469 repressed TP2 and Prm2 protein expression at the translation level with minor effect on mRNA degradation, through binding to the coding regions of TP2 and Prm2 mRNAs. The corresponding primary-microRNAs and the expression levels of Drosha and DGCR8 (both mRNA and protein) were increased significantly in the GRTH-null mice. miR-469 silencing of TP2 and Prm2 mRNA in pachytene spermatocytes and round spermatids is essential for their timely translation at later times of spermiogenesis, which is critical to attain mature sperm. Collectively, these studies indicate that GRTH, a multifunctional RNA helicase, acts as a negative regulator of miRNA-469 biogenesis and consequently their function during spermatogenesis.
Effect of Imidazole on the Solubility of a His-Tagged Antibody Fragment (2003)

A number of studies have demonstrated the limited solubility of single-chain Fv antibody fragments and its improvement by genetic engineering. This limits the stability of recombinant protein upon storage and the efficiency of chemical modification. The RAFT3 scFv used in the present work is specific for melanoma-associated proteoglycan and an attractive candidate for clinical radioimaging studies because of its unusual radiolabelling properties. However, when expressed with a c-terminal his(6) IMAC purification tag, the recombinant protein starts to precipitate after column elution and dialysis against PBS and reaches a concentration of soluble protein of approximately 150 microg/mL within a few days upon storage at 4 degrees C. We tested several commonly used buffer modifications (addition of detergents, high salt, amino acids) to improve the solubility and stability of the protein but without any major improvement. However, we found that, when the final dialysis step was omitted and the protein left in IMAC column elution buffer (PBS containing imidazole), it remained soluble. Furthermore, several months old and precipitated protein could be redissolved in this buffer without loss of antigen binding. This observation and the largely pH-independent nature of protein solubility suggest that neither salt bridges formed by the his(6) tail nor cross-linking of his(6) tails mediated by metal ions leached from the column during elution are responsible for the limited solubility of the protein in the absence of imidazole. The presence of imidazole did not interfere with radiolabelling and in vivo tumor targeting in a mouse model. The solubilizing and stabilizing effect of imidazole could be of use for his(6) tagged and poorly soluble recombinant proteins other than scFvs.
Ultra-Dynamic Voltage Scaling (UDVS) Using Sub-Threshold Operation and Local Voltage Dithering (2005)

Local voltage dithering provides near optimum savings when workload varies for fine-grained blocks. Combining this approach with sub-threshold operation permits ultra-dynamic voltage scaling from 1.1 V to below 300 mV for a 90-nm test chip. Operating at 330 mV provides minimum energy per cycle at 9/spl times/ less energy than ideal shutdown for reduced performance scenarios. Measurements from the test chip characterize the impact of temperature on the minimum energy point.
Caenorhabditis elegans neuron degeneration and mitochondrial suppression caused by selected environmental chemicals. (2013)

Mitochondrial alterations have been documented for many years in the brains of Parkinson's disease (PD), a disorder that is characterized by the selective loss of dopamine neurons. Recent studies have demonstrated that Parkinson's disease-associated proteins are either present in mitochondria or translocated into mitochondria in response to stress, further reinforcing the importance of the mitochondrial function in the pathogenesis of Parkinson's disease. Exposure to environmental chemicals such as pesticides and heavy metals has been suggested as risk factors in the development of Parkinson's disease. It has been reported that a number of environmental agents including tobacco smoke and perfluorinated compounds, pesticides, as well as metals (Mn(2+) and Pb(2+)) modulate mitochondrial function. However the exact mechanism of mitochondrial alteration has not been defined in the context of the development and progression of Parkinson's disease. The complexity of the mammalian system has made it difficult to dissect the molecular components involved in the pathogenesis of Parkinson's disease. In the present study we used the nematode Caenorhabditis elegans (C. elegans) model of neuron degeneration and investigated the effect of environmental chemicals on mitochondrial biogenesis and mitochondrial gene regulation. Chronic exposure to low concentration (2 or 4 μM) of pesticide rotenone, resulted in significant loss of dopamine neuron in C. elegans, a classic feature of Parkinson's disease. We then determined if the rotenone-induced neuron degeneration is accompanied by a change in mitochondria biogenesis. Analysis of mitochondrial genomic replication by quantitative PCR showed a dramatic decrease in mitochondrial DNA (mtDNA) copies of rotenone-treated C. elegans compared to control. This decreased mitochondrial biogenesis occurred prior to the development of loss of dopamine neurons, and was persistent. The inhibition of mtDNA replication was also found in C. elegans exposed to another neuron toxicant Mn(2+) at the concentration 50 or 100 mM. We further examined the mitochondrial gene expression and found significant lower level of mitochondrial complex IV subunits COI and COII in C. elegans exposed to rotenone. These results demonstrate that environmental chemicals cause persistent suppression of mitochondrial biogenesis and mitochondrial gene expression, and suggest a critical role of modifying mitochondrial biogenesis in toxicants-induced neuron degeneration in C. elegans model.
The human intraepithelial lymphocyte marker HML‐1 is an integrin consisting of a β7 subunit associated with a distinctive α chain (1992)

Abstract The membrane antigen defined by the monoclonal antibody (mAb) HML‐1 is abundantly expressed on, and largely restricted to, the T cells which populate the intestinal epithelium. We show that the mature form of the antigen is a heterodimer comprising a 150‐kDa α chain and a 120‐kDa β chain. Direct sequencing of tryptic peptides cleaved from the purified β chain identified this polypeptide with the integrin β7 isotype. cDNA clones coding for the β7 chain have recently been isolated from T cell cDNA libraries, but the β7 chain had not been identified at the protein level. No information is available concerning the primary structure of the HML‐1 α chain. We show that this subunit is synthesized as a precursor form that undergoes, like several other integrin α subunits, a post‐translational cleavage of a peptide bond. Among the 11 human integrin α chains previously identified, 10 have biochemical features and/or a distribution different from those of HML‐1 α. One, VLAα4 (CD49d), has a molecular mass of 150 kDa and is expressed on HML‐1 + cells but is not recognized by HML‐1 mAb. We conclude that HML‐1 is a novel member of the integrin family made of the β7 chain and of an as‐yet‐undescribed human α chain characterized by the post‐translational cleavage of a 10‐kDa peptide. HML‐1 is, thus, probably the human counterpart of the mouse antigen M290.
GVHD-associated, inflammasome-mediated loss of function in adoptively transferred myeloid-derived suppressor cells (2015)

Myeloid-derived suppressor cells (MDSCs) are a naturally occurring immune regulatory population associated with inhibition of ongoing inflammatory responses. In vitro generation of MDSCs from bone marrow has been shown to enhance survival in an acute model of lethal graft-versus-host disease (GVHD). However, donor MDSC infusion only partially ameliorates GVHD lethality. In order to improve the potential therapeutic benefit and ultimately survival outcomes, we set out to investigate the fate of MDSCs after transfer in the setting of acute GVHD (aGVHD). MDSCs transferred to lethally irradiated recipients of allogeneic donor hematopoietic grafts are exposed to an intense inflammatory environment associated with aGVHD, which we now show directly undermines their suppressive capacity. Under a conditioning regimen and GVHD inflammatory settings, MDSCs rapidly lose suppressor function and their potential to inhibit GVHD lethality, which is associated with their induced conversion toward a mature inflammasome-activated state. We find even brief in vitro exposure to inflammasome-activating mediators negates the suppressive potential of cultured murine and human-derived MDSCs. Consistent with a role for the inflammasome, donor MDSCs deficient in the adaptor ASC (apoptosis-associated speck-like protein containing a CARD), which assembles inflammasome complexes, conferred improved survival of mice developing GVHD compared with wild-type donor MDSCs. These data suggest the use of MDSCs as a therapeutic approach for preventing GVHD and other systemic inflammatory conditions will be more effective when combined with approaches limiting in vivo MDSC inflammasome activation, empowering MDSCs to maintain their suppressive potential.
Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation (2000)

This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody causes platelet aggregation and granule secretion. A physiological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen. A pathophysiological role for the F11R was revealed by demonstrating the presence of F11R-antibodies in patients with thrombocytopenia. Adhesion of platelets through the F11R resulted in events characteristic of the action of cell adhesion molecules (CAMs). To determine the structure of this protein, we cloned the F11R cDNA from human platelets. The predicted amino acid sequence demonstrated that it is an integral membrane protein and an immunoglobulin superfamily member containing 2 extracellular C2-type domains. The structure of the F11R as a member of a CAM family of proteins and its activity in mediating adhesion confirm each another. We conclude that the F11R is a platelet-membrane protein involved in 2 distinct processes initiated on the platelet surface. The first is antibody-induced platelet aggregation and secretion that are dependent on both the FcgammaRII and the GPIIb/IIIa integrin and that may be involved in pathophysiological processes associated with certain thrombocytopenias. The second is an F11R-mediated platelet adhesion that is not dependent on either the FcgammaRII or the fibrinogen receptor and that appears to play a role in physiological processes associated with platelet adhesion and aggregation. (Blood. 2000;95:2600-2609)
Galectin-3 inhibitors: a patent review (2008–present) (2014)

The lack of commercially available anti-Gal-3 therapeutic reagents and its clear involvement in serious disease, notably cancer, leads to an urgent need for development of inhibitors that specifically target Gal-3. Design of potent and selective carbohydrate inhibitors targeting Gal-3 is challenging due to relative weak protein-carbohydrate interactions along with the high sequence homology in the carbohydrate binding site region among galectins. To date, some chemical scaffolds have been exploited for design of promising effective Gal-3 inhibitors for cancer therapy.
Recent bio-applications of sol–gel materials (2005)

This review is devoted to the most recent developments (2000–2005) of sol–gel materials at the interface with biology. In the context of bioencapsulation in mineral hosts, novel synthetic approaches have been designed, allowing the immobilization of numerous proteins, enzymes and immune molecules as well as poly-saccharides, phospholipids and nucleic acids. These efforts have led to the development of new biosensors and bioreactors. A similar trend was also observed for whole cell encapsulation, survival periods over several weeks now being achieved. This has opened the possibility of designing hybrid hosts for cell-based biosensing and bioproduction, ultimately allowing the development of artificial organs. Indeed, applications of sol–gel processes are not restricted to bioencapsulation, as demonstrated by recent progress in drug release systems and bioactive materials. Finally, the considerable efforts devoted to the biomimetic elaboration of mineral structures suggest that they might be the key for future development of improved sol–gel materials for bio-applications.
Tunable, broad visible range, fibre-based Ramansource (2000)

Nine Raman orders covering a 130 nm bandwidth in the visible range have been generated in an optical fibre using a visible fibre pump source based on a seeded ytterbium amplifier and second harmonic generation in periodically poled KTP. A tunable, compact, fibre-based visible source has been demonstrated.
Inclusive, Balanced, Sustained Growth in the Asia-Pacific (2010)

The recovery of the Asia-Pacific region from the global economic crisis of 2008–2009 is underway but incomplete. Risks range from slow growth and persistent unemployment to re-emerging international imbalances and financial volatility. While early policy responses to the crisis were successful in avoiding a larger calamity, new policy strategies are now needed to resolve imbalances among the United States, China, and other economies, and to build robust demand in the medium term. This report, drafted by an international team of experts for the Pacific Economic Cooperation Council (PECC), provides a policy framework for completing the recovery and achieving sustained growth beyond it. The report identifies priorities for replacing stimulus programmes with structural reforms, and for launching new growth engines to drive investment and employment throughout the Asia-Pacific region. Led by Professor Peter Petri (Brandeis University/East-West Center), the team included eminent scholars from China, Japan, the United States and other countries. The report presents a regional strategy as well as separate, detailed analyses of the challenges facing China, Advanced Asia, Southeast Asia, North America, and South America. It concludes that inclusive, balanced, sustained growth in the region is feasible, but will require structural reforms that change economic relationships within economies and among them, and substantial international cooperation in implementing coherent national policies