gebhart/patrepeval huggingface dataset:
Music Emotion Detection Using Hierarchical Sparse Kernel Machines (2014)

For music emotion detection, this paper presents a music emotion verification system based on hierarchical sparse kernel machines. With the proposed system, we intend to verify if a music clip possesses happiness emotion or not. There are two levels in the hierarchical sparse kernel machines. In the first level, a set of acoustical features are extracted, and principle component analysis (PCA) is implemented to reduce the dimension. The acoustical features are utilized to generate the first-level decision vector, which is a vector with each element being a significant value of an emotion. The significant values of eight main emotional classes are utilized in this paper. To calculate the significant value of an emotion, we construct its 2-class SVM with calm emotion as the global (non-target) side of the SVM. The probability distributions of the adopted acoustical features are calculated and the probability product kernel is applied in the first-level SVMs to obtain first-level decision vector feature. In the second level of the hierarchical system, we merely construct a 2-class relevance vector machine (RVM) with happiness as the target side and other emotions as the background side of the RVM. The first-level decision vector is used as the feature with conventional radial basis function kernel. The happiness verification threshold is built on the probability value. In the experimental results, the detection error tradeoff (DET) curve shows that the proposed system has a good performance on verifying if a music clip reveals happiness emotion.
Purine-rich exon sequences are not necessarily splicing enhancer sequence in the dystrophin gene. (2001)

Purine-rich sequences within exons are proposed to promote proper splicing as splicing enhancers. In order to test this supposition in the dystrophin gene, which is characterized by the large size of its introns, purine-rich sequences from three exons (exons 43, 46 and 53) were examined for their splicing enhancer activity by using a Drosophila doublesex pre-mRNA. The most powerful activating effect on upstream intron splicing was seen with a sequence from exon 43. A sequence from exon 53 showed relatively low activity, whilst that from exon 46 had little effect. To characterize the splicing enhancer sequences in exons 53 and 46 further, entire exons were divided into 30nt fragments that were examined separately for their splicing enhancer activity. In exon 53, two fragments located at the 5' and 3' ends, respectively, had strong splicing enhancer activity, although they were not the most purine-rich regions of the exon. In contrast, all of the fragments derived from exon 46 had little activity. These results suggest that different exons in the dystrophin transcript are subject to different mechanisms of control by the splicing machinery.
Development of Catheter-Based Procedures for Transducing the Isolated Rabbit Liver with Plasmid DNA (2002)

Rapid systemic injection of naked plasmid DNA (pDNA) in a large volume into a mouse tail vein has been shown to result in a high level of gene expression in the liver. However, the potential therapeutic benefit to humans embodied in hydrodynamic transfection of the liver cannot be realized until a clinically viable method for gene delivery is developed. In light of this fact, we have devised and evaluated several methods for delivering pDNA to the isolated rabbit liver using minimally invasive catheter-based techniques. Using a lobar technique, pDNA was delivered hydrodynamically to an isolated hepatic lobe using a balloon occlusion balloon catheter to occlude a selected hepatic vein. A whole organ technique was used wherein the entire hepatic venous system was isolated and the pDNA solution injected hydrodynamically into the vena cava between two balloons used to block hepatic venous outflow. Lobar delivery of a plasmid encoding a secreted alkaline phosphatase (SEAP) reporter gene resulted in significant levels of transgene product in the serum. A nonsecreted transgene product, chloramphenicol acetyltransferase (CAT), showed the highest levels of expression in the injected lobe distal to the injection site. Compared to lobar delivery, whole organ delivery yielded much higher serum levels of SEAP expression and a significantly broader hepatic parenchymal distribution of CAT expression. These preliminary studies suggest that catheter-mediated hydrodynamic delivery of pDNA to the isolated liver may provide a method for human gene therapy that is both therapeutically significant and clinically practicable.
Llama-derived Single Variable Domains (Nanobodies) Directed against Chemokine Receptor CXCR7 Reduce Head and Neck Cancer Cell Growth in Vivo (2013)

The chemokine receptor CXCR7, belonging to the membrane-bound G protein-coupled receptor superfamily, is expressed in several tumor types. Inhibition of CXCR7 with either small molecules or small interference (si)RNA has shown promising therapeutic benefits in several tumor models. With the increased interest and effectiveness of biologicals inhibiting membrane-bound receptors we made use of the "Nanobody platform" to target CXCR7. Previously we showed that Nanobodies, i.e. immunoglobulin single variable domains derived from naturally occurring heavy chain-only camelids antibodies, represent new biological tools to efficiently tackle difficult drug targets such as G protein-coupled receptors. In this study we developed and characterized highly selective and potent Nanobodies against CXCR7. Interestingly, the CXCR7-targeting Nanobodies displayed antagonistic properties in contrast with previously reported CXCR7-targeting agents. Several high affinity CXCR7-specific Nanobodies potently inhibited CXCL12-induced β-arrestin2 recruitment in vitro. A wide variety of tumor biopsies was profiled, showing for the first time high expression of CXCR7 in head and neck cancer. Using a patient-derived CXCR7-expressing head and neck cancer xenograft model in nude mice, tumor growth was inhibited by CXCR7-targeting Nanobody therapy. Mechanistically, CXCR7-targeting Nanobodies did not inhibit cell cycle progression but instead reduced secretion of the angiogenic chemokine CXCL1 from head and neck cancer cells in vitro, thus acting here as inverse agonists, and subsequent angiogenesis in vivo. Hence, with this novel class of CXCR7 inhibitors, we further substantiate the therapeutic relevance of targeting CXCR7 in head and neck cancer.
Buffer Management in a Packet Switch (1978)

Consider a single packet switch with a finite number of packet buffers shared between several output queues. An arriving packet is lost if no free buffer is available, as in the CIGALE network. It has been observed by simulation that if load increases too much, congestion may occur, i.e., throughput declines; it appears that the busiest link's queue tends to hog the buffers. Therefore, we will limit the queue length and when the queue is full the packet will be dropped. We expect that this restricted buffer sharing policy will avoid congestion under conditions of heavy load. A queueing model of a packet switch is defined and solved by local balance. Loss probability is evaluated, and values of queue limit to minimize loss are found; they depend on load. A Square-Root rule is introduced to make the choice of queue limit independent of load. For a sample switch, with three output links, a comparison is made between performance under different buffer sharing policies; it is shown that restricted sharing prevents congestion by making throughput an increasing function of load.
Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport deficiency (2012)

Cerebral folate transport deficiency is an inherited brain-specific folate transport defect that is caused by mutations in the folate receptor 1 gene coding for folate receptor alpha (FRα). This genetic defect gives rise to a progressive neurological disorder with late infantile onset. We screened 72 children with low 5-methyltetrahydrofolate concentrations in the cerebrospinal fluid and neurological symptoms that developed after infancy. We identified nucleotide alterations in the folate receptor 1 gene in 10 individuals who shared developmental regression, ataxia, profound cerebral hypomyelination and cerebellar atrophy. We found four novel pathogenic alleles, one splice mutation and three missense mutations. Heterologous expression of the missense mutations, including previously described mutants, revealed minor decrease in protein expression but loss of cell surface localization, mistargeting to intracellular compartments and thus absence of cellular binding of folic acid. These results explain the functional loss of folate receptor alpha for all detected folate receptor 1 mutations. Three individuals presenting a milder clinical phenotype revealed very similar biochemical and brain imaging data but partially shared pathogenic alleles with more severely affected patients. Thus, our studies suggest that different clinical severities do not necessarily correlate with residual function of folate receptor alpha mutants and indicate that additional factors contribute to the clinical phenotype in cerebral folate transport deficiency.
Advanced Components of Microfluidic Systems for Bioanalytical Applications. (2009)

The need for detailed understanding of fundamental and advanced components towards the widespread use of microfluidic systems are addressed in this dissertation. First, to understand mixing in microfluidic lab-on-a-chip systems, discrete droplet mixing in microchannels was examined using mathematical modeling, simulations, and experiments. The microfluidic mixing occurs in three distinct regimes (diffusion-dominated, dispersion-dominated, and convection-dominated) depending on the Péclet number and the droplet dimensions. Using mathematically developed asymptotic curves, it was possible to predict the mixing time and required channel distance for any Péclet numbers. The mixing of typical drops (~3000um long) in microchannels (100~500um) resulted in mixing times of 0.001~10000 seconds depending on the drop velocity. Simulations and experiments of the mixing of two discrete drops agreed well with the theoretical limits. Second, novel microfluidic components for discrete drop mixing and routing in lab-on-a-chip systems have been developed. The membranous air bypass valve (MBV) in PDMS allows air to pass through but stops liquid. Using two-dimensional and three-dimensional MBVs, the trapped air between discrete drops was rapidly removed at the aspiration rate of ~65nL/s. MBVs with semicircular membranes could also act as fluidic diodes that allow only unidirectional flow at operating pressures of 12~24kPa. Complex drop routing was possible with multiple fluidic diodes embedded. Third, a user-friendly device construction methodology using prefabrication of microfluidic assembly blocks in PDMS was introduced to allow users to build custom microfluidic systems without any fabrication expertise. Complete sealing was done by applying adhesive materials such as the PDMS curing agent and UV-curable glues between blocks. Using the square blocks of the size of 16mm2, we demonstrated common microfluidic applications including laminar flow development, valve control, and cell culturing. Finally, digital pneumatic microprocessors have been developed as universal on-chip control platforms to multiplex a single pneumatic input. Logic components such as AND, NOR, flip-flops, and shift-registers were constructed and linked to compute, store, and parallelize serially-encoded input signals. The resulting parallel outputs were used to control multiple valves, pumps, channels, and chambers, independently. By significantly reducing the need for external controllers, digital pneumatic microprocessors could facilitate the widespread use of microfluidic systems.
Induction of apoptosis in multidrug-resistant and radiation-resistant acute myeloid leukemia cells by a recombinant fusion toxin directed against the human granulocyte macrophage colony-stimulating factor receptor. (1997)

Multiagent chemotherapy regimens fail to cure more than one-half of the patients with acute myeloid leukemia (AML) because of the emergence of dominant multidrug-resistant subclones of leukemia cells. We have developed a recombinant diphtheria toxin-human granulocyte macrophage colony-stimulating factor chimeric fusion protein (DTctGMCSF) that specifically targets GMCSF receptor-positive AML cells. This novel biotherapeutic agent induced rapid apoptotic cell death of chemotherapy-resistant AML cell lines and primary leukemic cells from treatment-refractory AML patients. Our results suggest that DTctGMCSF may be useful in the treatment of AML patients whose leukemia has recurred and developed resistance to contemporary chemotherapy programs.
RNase L dimerization in a mammalian two-hybrid system in response to 2',5'-oligoadenylates (1998)

RNase L, a key enzyme in the anti-viral activity of interferons, requires activation by 2',5'-linked oligoadenylates (2-5A) to cleave viral and cellular single-stranded RNA. Here we demonstrate that 2-5A causes formation of stable dimers of RNase L in intact human cells as measured with a mammalian two-hybrid system. Hybrid proteins consisting of the GAL4 DNA binding domain fused to RNase L and the VP16 transactivation domain fused to RNase L were able to associate and drive transcription of a reporter gene, but only after cells were transfected with 2-5A. Several functional forms of 2-5A, such as p3A2'p5'A2'p5'A, were capable of activating transcription in human HeLa cells. In contrast, p3A2'p5'A, which can neither activate nor dimerize RNase L, did not induce gene expression. Evidence for the involvement of the C-terminal region of RNase L in dimerization was obtained by expressing truncated forms of RNase L. These findings describe a convenient, high-throughput screening method for RNase L activators which could lead to the discovery of novel anti-viral and anti-cancer agents.
Polymer‐supported dinitrogen complexes of manganese. Coordination of molecular nitrogen in solid‐gas phase reaction under mild conditions (1982)

Abstract A copolymer ( PC‐1 ) was synthesized from a mixture of 1,2‐and 1,3‐isomers of tricarbonyl‐(methylvinylcyclopentadienyl)manganese ( 1 ) and styrene (St) crosslinked with 1,4‐divinylbenzene, and a membrane ( PM–1 ) consisting of the 1 /St copolymer. A polymer‐supported dinitrogen complex ( PC‐4 ) was prepared from the tetrahydrofuran (THF) complex of PC‐1 and molecular nitrogen in a solid‐gas phase reaction under moderate conditions. The dinitrogen complex membrane ( PM–4 ) was readily obtained directly from PM‐1 by a “one‐step reaction” on UV light irradiation under normal pressure of nitrogen at room temperature. A prominent feature of polymer‐supported dinitrogen complexes, PC‐4 and PM‐4 , is their high stability as compared with the corresponding low molecular weight analogues. The coordinated nitrogen can be substituted by carbon monoxide in a PC‐4 /THF mixture. The mechanism of nitrogen co‐ordination to PC‐1 and PM‐1 was investigated by means of IR and/or absorption spectrometry.
Endoplasmic reticulum stress: cell life and death decisions (2005)

Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response, which is aimed initially at compensating for damage but can eventually trigger cell death if ER dysfunction is severe or prolonged. The mechanisms by which ER stress leads to cell death remain enigmatic, with multiple potential participants described but little clarity about which specific death effectors dominate in particular cellular contexts. Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.
Infection of human endothelial cells with Epstein-Barr virus. (1995)

Interleukin-6 (IL-6) promotes growth and tumorigenicity of Epstein-Barr virus (EBV)-immortalized B cells, and is abnormally elevated in the serum of solid organ transplant recipients who develop EBV-positive posttransplant lymphoproliferative disease (PTLD), but not in control transplant recipients. Endothelial cells derived from PTLD lesions were found to secrete spontaneously high levels of IL-6 in vitro for up to 4 mo. We examined possible mechanisms for sustained IL-6 production by endothelial cells. Here, we show that EBV can infect endothelial cells in vitro. After 3-4 wk incubation with lethally irradiated EBV-positive, but not EBV-negative cell lines, a proportion of human umbilical cord-derived endothelial cells (HUVECs) expressed in situ the EBV-encoded small RNAs (EBER). Southern blot analysis after polymerase chain reaction showed EBV DNA in HUVEC that had been incubated with lethally irradiated EBV-positive cells, but not in the controls. Exposure of HUVECs to lethally irradiated EBV-positive but not EBV-negative cell lines induced IL-6 production that was sustained for up to 120 d of culture. These studies identify endothelial cells as targets for EBV infection and raise the possibility that this infection may be important in the life cycle and pathology of EBV.
Apoptosis signaling by death receptors (1998)

Death receptors have been recently identified as a subgroup of the TNF-receptor superfamily with a predominant function in induction of apoptosis. The receptors are characterized by an intracellular region, called the death domain, which is required for the transmission of the cytotoxic signal. Currently, five different such death receptors are known including tumor necrosis factor (TNF) receptor-1, CD95 (Fas/APO-1), TNF-receptor-related apoptosis-mediated protein (TRAMP) and TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 and -2. The signaling pathways by which these receptors induce apoptosis are rather similar. Ligand binding induces receptor oligomerization, followed by the recruitment of an adaptor protein to the death domain through homophilic interaction. The adaptor protein then binds a proximal caspase, thereby connecting receptor signaling to the apoptotic effector machinery. In addition, further pathways have been linked to death receptor-mediated apoptosis, such as sphingomyelinases, JNK kinases and oxidative stress. These pro-apoptotic signals are counteracted by several mechanisms which inhibit apoptosis at different levels. This review summarizes the current and rapidly expanding knowledge about the biological functions of death receptors and the mechanisms to trigger or to counteract cell death.
Differential regulation of the ER stress response by long-chain fatty acids in the pancreatic β-cell (2008)

Recent evidence indicates that treatment of pancreatic beta-cells with long chain fatty acids can lead to the development of an ER (endoplasmic reticulum) stress response. This is manifest as the activation of some components of the PERK [RNA-dependent protein kinase-like ER eIF2alpha (eukaryotic initiation factor 2alpha) kinase]-dependent arm of ER stress and is seen most dramatically when cells are treated with long-chain saturated fatty acids (e.g. palmitate). By contrast, the equivalent mono-unsaturates (e.g. palmitoleate) are much less effective and they can even attenuate the ER stress response to palmitate. This may be due to the regulation of eIF2alpha phosphorylation in cells exposed to mono-unsaturates. The present review discusses the differential effects of saturated and mono-unsaturated fatty acids on ER stress in beta-cells and considers the extent to which regulation of this pathway may be involved in mediating their effects on viability.
Interaction of Ipa proteins of Shigella flexneri with alpha5beta1 integrin promotes entry of the bacteria into mammalian cells. (1996)

Shigella is a genus of highly adapted bacterial pathogens that cause bacillary dysentery in humans. Bacteria reaching the colon invade intestinal epithelial cells by a process of bacterial-directed endocytosis mediated by the Ipa proteins: IpaB, IpaC, and IpaD of Shigella. The invasion of epithelial cells is thought to be a receptor-mediated phenomenon, although the cellular components of the host that interact with the Ipa proteins have not yet been identified. We report here that in a Shigella flexneri invasive system and Chinese hamster ovary (CHO) cell monolayers, the Ipa proteins were capable of interacting directly with alpha5beta1 integrin. The invasive capacity of S. flexneri for CHO cells increased as levels of alpha5beta1 integrin were elevated. When CHO cells were infected with S. flexneri, the tyrosine phosphorylation both of pp 125FAK, an integrin-regulated 125 K focal adhesion kinase, and of paxillin was stimulated. In contrast, an isogenic strain of S. flexneri that was defective in invasion owing to a mutation in its spa32 gene failed to induce such phosphorylation. Under in vitro and in vivo conditions, the released IpaB, IpaC, and IpaD proteins bound to alpha 5 beta 1 integrin in a manner different from that of soluble fibronectin but similar to that of the tissue form of fibronectin. At the site of attachment of S. flexneri to CHO cells, alpha5beta1 integrin converged with polymerization of actin. These data thus suggest that the capacity of Ipa proteins to interact with alpha5beta1 integrin may be an important Shigella factor in triggering the reorganization of actin cytoskeletons.
Rendering synthetic objects into real scenes (2008)

We present a method that uses measured scene radiance and global illumination in order to add new objects to light-based models with correct lighting. The method uses a high dynamic range image-based model of the scene, rather than synthetic light sources, to illuminate the new objects. To compute the illumination, the scene is considered as three components: the distant scene, the local scene, and the synthetic objects. The distant scene is assumed to be photometrically unaffected by the objects, obviating the need for reflectance model information. The local scene is endowed with estimated reflectance model information so that it can catch shadows and receive reflected light from the new objects. Renderings are created with a standard global illumination method by simulating the interaction of light amongst the three components. A differential rendering technique allows for good results to be obtained when only an estimate of the local scene reflectance properties is known.