gebhart/patrepeval huggingface dataset:
Analysis of ligand recognition by the purified alpha 2-macroglobulin receptor (low density lipoprotein receptor-related protein). Evidence that high affinity of alpha 2-macroglobulin-proteinase complex is achieved by binding to adjacent receptors (1991)

The molecular basis for binding of alpha-macroglobulin-proteinase complexes to the human two-chain 500/85-kDa (alpha/beta) alpha 2-macroglobulin (alpha 2M) receptor (alpha 2MR)/low density lipoprotein receptor-related protein was analyzed. Ligand blotting experiments showed that a 40-kDa protein, present in the affinity-purified alpha 2MR preparation, is bound to the alpha 2MR alpha-chain and released by heparin. Removal of the 40-kDa protein resulted in a 3-5-fold increase in binding of alpha 2M-trypsin. Nitrocellulose-immobilized pure two-chain alpha 2MR was incubated with human alpha 2M-trypsin, containing four identical subunits, and two monovalent ligands: rat alpha 1-inhibitor-3-chymotrypsin and the 18-kDa receptor binding fragment of the alpha 2M subunit. Binding of alpha 2M-trypsin to the alpha-chain of immobilized alpha 2MR was composed of a high (Kd = 40 pM at 4 degrees C) and a low (Kd = 2 nM) affinity component. alpha 1-Inhibitor-3-chymotrypsin bound to the same sites but with one component (Kd = 0.4 nM). Competition-inhibition experiments and dissociation experiments, using ligands with different valences, as well as experiments with alpha 2MR immobilized at different densities, led to the following model. The low (Kd = 2 nM) affinity of alpha 2M-proteinase is prevalent when only one of the four domains binds to alpha 2MR, i.e. when the receptor density is low or when neighboring receptors are occupied. The high (Kd = 40 pM) affinity is achieved by binding of at least two domains to adjacent receptors.
High-quality pre-integrated volume rendering using hardware-accelerated pixel shading (2001)

We introduce a novel texture-based volume rendering approach that achieves the image quality of the best post-shading approaches with far less slices. It is suitable for new flexible consumer graphics hardware and provides high image quality even for low-resolution volume data and non-linear transfer functions with high frequencies, without the performance overhead caused by rendering additional interpolated slices. This is especially useful for volumetric effects in computer games and professional scientific volume visualization, which heavily depend on memory bandwidth and rasterization power.We present an implementation of the algorithm on current programmable consumer graphics hardware using multi-textures with advanced texture fetch and pixel shading operations. We implemented direct volume rendering, volume shading, arbitrary number of isosurfaces, and mixed mode rendering. The performance does neither depend on the number of isosurfaces nor the definition of the transfer functions, and is therefore suited for interactive high-quality volume graphics.
Differences between the activities of human monoclonal IgG1 and IgG3 anti-D antibodies of the Rh blood group system in their abilities to mediate effector functions of monocytes. (1988)

Seven IgG1 and seven IgG3 human monoclonal antibodies derived from heterohybridoma or Epstein-Barr virus-transformed lymphocytes and specific for the D antigen of the human Rh blood group system were tested for their ability to bring about red cell attachment to and phagocytosis by monocytes. The antibodies produced by the heterohybridomas were also investigated for their potency to mediate antibody-dependent cellular cytotoxicity (ADCC) by monocytes. When red cells were sensitized with any of the IgG1 anti-D antibodies, most of them were ingested by the phagocytes. By contrast, many of the red cells coated with any of the IgG3 antibodies remained attached to the monocyte surface while only few underwent phagocytosis. Some of the attached red cells remained on the phagocyte exterior for a considerable length of time. The ADCC activities of the IgG3 anti-D antibodies was greater than that of the IgG1 anti-D antibodies. The results mean that in vitro IgG1 anti-D mediates red cell destruction mainly by phagocytosis, while IgG3 anti-D causes their destruction predominantly by prolonged cytolysis. These differences between the effector functions of human monoclonal IgG1 and IgG3 anti-D antibodies might have important implications for their use in the prophylaxis of haemolytic disease of the new-born.
Detection and localization of cytokine immunoreactivity in retro‐ocular connective tissue in Graves' opthalmopathy (1993)

Paracrine interactions between fibroblasts residing in the retro-ocular space and infiltrating lymphocytes/macrophages are thought to be of central importance in the pathogenesis of Graves' ophthalmopathy (GO). Although various roles have been suggested for interferon-gamma (IFN gamma), tumour necrosis factor-alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) in GO, their actual presence in Graves' retro-ocular connective tissue has not been demonstrated. We examined surgical specimens obtained during orbital decompression from patients with severe GO (n = 6), and from normal individuals (n = 5), for the presence of IFN gamma, TNF alpha and IL-1 alpha. We used immunohistochemical methods on frozen tissue sections and primary fibroblast cultures, and sodium dodecylsulfate polyacrylamide-gel electrophoresis of tissue extracts and tissue culture supernatants. In addition, immunohistochemical staining of tissues for characterization of the mononuclear cell infiltrates was performed. Aggregates of mononuclear cells in retro-ocular connective and fatty tissue were found in five of six GO tissue specimens, but in none of the control specimens. We detected immunoreactivity for the three cytokines (IFN gamma, TNF alpha and IL-1 alpha) in the five GO tissue specimens that contained mononuclear cell aggregates. In addition, IL-1 alpha immunoreactivity was demonstrable in primary and subsequent GO fibroblast cultures and in their supernatants. In contrast, no immunoreactivity for any of these cytokines was detected in tissue specimens, primary cultures or culture supernatants derived from normal individuals. The presence of mononuclear cell infiltrates and associated immunoreactivity for IFN gamma, TNF alpha, IL-1 alpha in retro-ocular connective tissue derived from patients with GO suggests that the previously demonstrated in vitro functions of these cytokines may indeed be operative in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Life History and Developmental Processes in the BasidiomyceteCoprinus cinereus (2000)

Coprinus cinereus has two main types of mycelia, the asexual monokaryon and the sexual dikaryon, formed by fusion of compatible monokaryons. Syngamy (plasmogamy) and karyogamy are spatially and temporally separated, which is typical for basidiomycetous fungi. This property of the dikaryon enables an easy exchange of nuclear partners in further dikaryotic-monokaryotic and dikaryotic-dikaryotic mycelial fusions. Fruiting bodies normally develop on the dikaryon, and the cytological process of fruiting-body development has been described in its principles. Within the specialized basidia, present within the gills of the fruiting bodies, karyogamy occurs in a synchronized manner. It is directly followed by meiosis and by the production of the meiotic basidiospores. The synchrony of karyogamy and meiosis has made the fungus a classical object to study meiotic cytology and recombination. Several genes involved in these processes have been identified. Both monokaryons and dikaryons can form multicellular resting bodies (sclerotia) and different types of mitotic spores, the small uninucleate aerial oidia, and, within submerged mycelium, the large thick-walled chlamydospores. The decision about whether a structure will be formed is made on the basis of environmental signals (light, temperature, humidity, and nutrients). Of the intrinsic factors that control development, the products of the two mating type loci are most important. Mutant complementation and PCR approaches identified further genes which possibly link the two mating-type pathways with each other and with nutritional regulation, for example with the cAMP signaling pathway. Among genes specifically expressed within the fruiting body are those for two galectins, beta-galactoside binding lectins that probably act in hyphal aggregation. These genes serve as molecular markers to study development in wild-type and mutant strains. The isolation of genes for potential non-DNA methyltransferases, needed for tissue formation within the fruiting body, promises the discovery of new signaling pathways, possibly involving secondary fungal metabolites.
Digital quantification of gene expression using emulsion PCR (2010)

Abstract Here we describe a single‐molecule quantitative assay of mRNA levels based on mRNA mediate‐ligation and BEAMing (beads, emulsion, amplification, and magnetics) technique, which allows accurate and parallel measurement of multiple genes from a small amount of cells. In this method, a pair of oligos complementary target mRNA was used to probe transcripts for each gene of interest. The ligated products of oligos pair were clonally amplified on beads in millions of parallel compartmentalized droplets in a water‐in‐oil emulsion. The levels of each transcript within a sample were measured by counting the number of the correspondingly amplified beads which were immobilized on a glass surface. To demonstrate its utility, this method has been applied to the quantitation of the mRNA levels for two transcription factors, Klf4 and Sox5 , and a housekeeping gene, Gapdh , in human leukemia K562 cells before and after induction with phorbol 12‐myristate 13‐acetate. Interestingly, we found a significant downregulation of the mRNA level of Sox5 after phorbol 12‐myristate 13‐acetate treatment. The mRNA mediate‐ligation and BEAMing technique provides an accurate and sensitive way to quantify the amount of multiple specific mRNA in a very small number of cells, which may be valuable in the studies requiring precise and parallel quantization of multiple mRNA in the defined cell populations.
Spatial-Random-Access-Enabled Video Coding for Interactive Virtual Pan/Tilt/Zoom Functionality (2011)

High-spatial-resolution videos offer the possibility of viewing an arbitrary region-of-interest (RoI) interactively. Zoom functionality enables watching high-resolution content even on displays of lower spatial resolution. If arbitrary regions corresponding to arbitrary zoom factors can be served to the user, the transmission and/or decoding of the entire high-spatial-resolution video can be avoided. Moreover, if the video content can be encoded such that arbitrary RoIs corresponding to different zoom factors can be simply extracted from the compressed bitstream, we can avoid dedicated video encoding for each user. We propose such a video coding scheme that is vital in allowing the system to scale to large numbers of remote users as well as to encode and store the content for subsequent repeated playback. Apart from generating a multi-resolution representation, our coding scheme uses P slices from H.264/AVC. We study the tradeoff in the choice of slice size. A larger slice size enables higher coding efficiency for representing the entire scene but increases the number of pixels that have to be transmitted. The optimal slice size achieves the best tradeoff and minimizes the expected transmission bitrate. Experimental results confirm the optimality of our predicted slice size for various test cases. Furthermore, we propose an improvement based on background extraction and long-term memory motion-compensated prediction. Experiments indicate up to 85% bitrate reduction while retaining efficient random access capability.
Tachyon: A Gigabit Fibre Channel Protocol Chip (1996)

Relentlessly increasing demands of computer systems continue to stress existing communication architectures to their limits. Even as processor speeds continue to improve dramatically, they are barely keeping up with increasing numbers of concurrently running applications and CPU-intensive applications, such as multimedia, with higher data throughput requirements. Additionally, as the number of interconnects between systems and I/O devices continues to increase, I/O channels become bottlenecks to system performance. A channel such as SCSI (Small Computer Systems Interface), which operates at a maximum throughput of 20 megabytes per second in fast and wide mode, simply cannot keep pace with ever-increasing processor speeds and data rate requirements. Another challenge of contemporary computer systems is the trend to more widely distributed systems, which require greater interface distances. Current parallel bus interconnects between systems and their I/O devices cannot operate over the distances needed for true distributed systems, such as LANs spanning campus areas and high-availability applications requiring remote mirrored disks for disaster recovery. SCSI, for example, is limited to a distance of six meters single-ended (single wire per signal) and 25 meters differential (two wires per signal). Current peripheral interconnect protocols are limited in the number of devices they can interconnect. For example, parallel SCSI can connect eight devices and 16-bit wide SCSI can connect 16 devices. In addition, peripheral connectors are becoming too large to fit into the shrinking footprints of systems and peripherals. Other SCSI limitations include half-duplex operation only, lack of a switching capability, inability to interconnect individual buses, and the need for customized drivers and adapters for various types of attached devices. Computer room real estate also is becoming scarce and expensive, fueled by increasing numbers of racked computers, insufficient room to connect desired numbers of peripheral devices, and more complex cabling. At the same time, data storage requirements are skyrocketing as backups of terabytes of data are becoming commonplace. An additional problem is that ever-increasing amounts of data must be backed up over too-slow LANs, making timely, low-cost backups ever more difficult to accomplish. For all these reasons, today’s parallel bus architectures are reaching their limits. Fibre Channel provides solutions to many of these limitations. Fibre Channel is a forward-thinking solution to future mass storage and networking requirements. Article 11 presents a technical description of Fibre Channel.
Prevalence of PRKDC mutations and association with response to immune checkpoint inhibitors in solid tumors (2020)

Predictive biomarkers of response to immune checkpoint inhibitors (ICI) help to identify cancer patients who will benefit from immunotherapy. Protein kinase, DNA-activated, catalytic subunit (PRKDC) is an important gene for DNA double-strand break (DSB) repair and central T-cell tolerance. We aimed to investigate the association between PRKDC mutations and tumor mutation burden (TMB), tumor microenvironment (TME), and response to ICI. Whole-exome sequencing data of 4023 solid tumor samples from the Cancer Genome Atlas (TCGA) and panel-based sequencing data of 3877 solid tumor samples from Geneplus-Beijing, China, were used to analyze the TMB. The mRNA expression data of 3541 solid tumor samples from TCGA were used to explore the effect of PRKDC mutations on the TME. Four ICI-treated cohorts were analyzed for verifying the correlation between PRKDC mutations and the response to ICI. In both the TCGA and Geneplus datasets, we found that the TMB in PRKDC mutation samples was significantly higher than in PRKDC wild-type samples (P < 0.05 and P < 0.0001, respectively). Further, TCGA datasets showed that PRKDC mutation samples were associated with a significantly increased expression of CD8<sup>+</sup> T cells, NK cells, immune checkpoint, chemokines, etc. compared to PRKDC wild-type samples (P < 0.05). In ICI-treated cohorts, we also found the PRKDC mutations were associated with increased survival (median PFS, not reached vs. 6.8 months, HR, 0.2893; 95% CI, 0.1255-0.6672; P = 0.0650, Hellmann cohort; median OS, 1184 days vs. 250 days, HR, 0.5126; 95% CI, 0.2715-0.9679; P = 0.1020, Allen cohort), and the increase was significant in multivariate analysis (HR, 0.361; 95% CI, 0.155-0.841; P = 0.018, Allen cohort; HR, 0.240 95% CI, 0.058-0.998; P = 0.050, Hellmann cohort). In summary, we found that PRKDC mutation often appeared to co-exist with deficiency in some other DNA damage repair mechanism and is nonetheless one of the important factors associated with increased TMB, inflamed TME, and better response to ICI.
Permissive role of polyamines in the cooperative action of estrogens and insulin or insulin-like growth factor I on human breast cancer cell growth. (1996)

Polyamines have been proposed as specific mediators of estrogen action in breast cancer cells, but their exact role in this process is still controversial. As estrogens cooperatively interact with peptide growth factors in several hormonal responses, the involvement of polyamines in the synergistic effect of 17 beta-estradiol (E2) and insulin or insulin-like-growth factor I (IGF-I) on cell growth, polyamine pools, specific gene induction, and cell cycle progression was examined in estrogen-responsive MCF-7 and ZR-75-1 human breast cancer cells. Spermidine depletion induced by the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), resulted in complete cytostasis and loss of mitogenic response to either E2 or insulin (or IGF-I). In contrast, a steroidal antiestrogen blocked the mitogenic effect of E2, but only partly interfered with the synergistic stimulation of estrogen action by insulin. Whereas antiestrogen-resistant growth in insulin-treated cells was halted by DFMO, the antiestrogen did not further inhibit growth upon prior polyamine depletion. E2 and either IGF-I or insulin induced early increases in putrescine and spermidine, but not spermine, contents in both MCF-7 and ZR-75-1 cells. Moreover, spermidine depletion and decarboxylated S-adenosylmethionine accumulation induced by DFMO required prior mitogenic stimulation by E2 and/or IGF-I. The antiestrogen alone had only a limited effect on polyamine and nucleoside pools. DFMO did not interfere with the coordinate induction of the estrogen- and growth factor-inducible pS2 messenger ribonucleic acid by E2 and insulin even after a 5-day treatment with the drug. On the other hand, DFMO depressed the cycling fraction of E2/IGF-I-stimulated MCF-7 cell population far more dramatically than the antiestrogen and to less than that noted in mitogen-deprived cells. However, in ZR-75-1 cells, which have a much lower spermidine/spermine ratio than MCF-7 cells, specific inhibition of spermine synthase selectively antagonized the effect of E2 compared with that of insulin. These data indicate that spermidine has a permissive role for macromolecular synthesis and cell cycle traverse, but does not qualify as a limiting factor in estrogen receptor-mediated events per se in breast cancer cells. Moreover, polyamine depletion is an efficient complementary strategy to block the mitogenic action of peptide growth factors, which is only partly antagonized by antiestrogens.
Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3 (2004)

Autism is a common neurodevelopmental disorder of complex genetic etiology. Rett syndrome, an X-linked dominant disorder caused by MECP2 mutations, and Angelman syndrome, an imprinted disorder caused by maternal 15q11-q13 or UBE3A deficiency, have phenotypic and genetic overlap with autism. MECP2 encodes methyl-CpG-binding protein 2 that acts as a transcriptional repressor for methylated gene constructs but is surprisingly not required for maintaining imprinted gene expression. Here, we test the hypothesis that MECP2 deficiency may affect the level of expression of UBE3A and neighboring autism candidate gene GABRB3 without necessarily affecting imprinted expression. Multiple quantitative methods were used including automated quantitation of immunofluorescence and in situ hybridization by laser scanning cytometry on tissue microarrays, immunoblot and TaqMan PCR. The results demonstrated significant defects in UBE3A/E6AP expression in two different Mecp2 deficient mouse strains and human Rett, Angelman and autism brains compared with controls. Although no difference was observed in the allelic expression of several imprinted transcripts in Mecp2-null brain, Ube3a sense expression was significantly reduced, consistent with the decrease in protein. A non-imprinted gene from 15q11-q13, GABRB3, encoding the beta3 subunit of the GABAA receptor, also showed significantly reduced expression in multiple Rett, Angelman and autism brain samples, and Mecp2 deficient mice by quantitative immunoblot. These results suggest an overlapping pathway of gene dysregulation within 15q11-q13 in Rett, Angelman and autism and implicate MeCP2 in the regulation of UBE3A and GABRB3 expressions in the postnatal mammalian brain.
China's long-term relations with Southeast Asia: Beyond the pivot (2012)

Extract: Early Chinaâs southward expansion over two millennia from its core zone north of the Yangtze River allowed it to engage nearby states. Regions along the Yangtze and in what is now southern China were gradually absorbed into an enlarging cultural sphere that was eventually integrated into China's imperial domain (basically by the third century B.C.E). Thereafter, when unified, dynastic China engaged Southeast Asia states with a relative but not absolute preponderance of power. China's linkages via diplomacy and trade led to it being at the core of a set of power relations that came to be formalized as the 'tribute system', though China was never an absolute hegemon of Southeast Asia as a whole.2 These perceptions have returned in new forms in the 21st century, with China's economic and military 'rise' being viewed at times as a return to its rightful, historic place, or at least a practical re-balancing of East Asian relations (Harris 2005; Stuart-Fox 2004; Shih 1993).
Effect of dietary supplementation of Bifidobacterium and Lactobacillus strains in Apis mellifera L. against Nosema ceranae (2015)

Nosema ceranae is a widespread microsporidium of European honeybee Apis mellifera L. affecting bee health. The ban of Fumagillin-B (dicyclohexylammonium salt) in the European Union has driven the search for sustainable strategies to prevent and control the infection. The gut microbial symbionts, associated to the intestinal system of vertebrates and invertebrates and its impact on host health, are receiving increasing attention. In particular, bifidobacteria and lactobacilli, which are normal inhabitants of the digestive system of bees, are known to protect their hosts via antimicrobial metabolites, immunomodulation and competition. In this work, the dietary supplementation of gut bacteria was evaluated under laboratory conditions in bees artificially infected with the parasite and bees not artificially infected but evidencing a low natural infection. Supplemented bacteria were selected among bifidobacteria, previously isolated, and lactobacilli, isolated in this work from healthy honeybee gut. Four treatments were compared: bees fed with sugar syrup (CTR); bees fed with sugar syrup containing bifidobacteria and lactobacilli (PRO); bees infected with N. ceranae spores and fed with sugar syrup (NOS); bees infected with N. ceranae and fed with sugar syrup containing bifidobacteria and lactobacilli (NP). The sugar syrup, with or without microorganisms, was administered to bees from the first day of life for 13 days. N. ceranae infection was carried out individually on anesthetised 5-day-old bees. Eight days after infection, a significant (P<0.05) lower level of N. ceranae was detected by real-time PCR in both NP and PRO group, showing a positive effect of supplemented microorganisms in controlling the infection. These results represent a first attempt of application of bifidobacteria and lactobacilli against N. ceranae in honeybees.