gebhart/patrepeval huggingface dataset:
Lipoprotein Lipase: Recent Contributions from Molecular Biology (1992)

Lipoprotein lipase (LPL) is a glycoprotein enzyme that is produced in several cells and tissues. LPL belongs to a large lipase gene family that includes, among others, hepatic lipase and pancreatic lipase. After secretion, LPL becomes anchored on the luminal surface of the capillary endothelial cells. There it hydrolyzes triglycerides in triglyceride-rich lipoproteins, generating free fatty acids that can serve either as a direct energy source or can be stored. Through this action LPL plays a pivotal role both in energy and in lipoprotein metabolism. LPL production is regulated in a tissue-specific fashion by developmental, hormonal, and nutritional factors. The recent availability of the regulatory sequences of the LPL gene will greatly facilitate these regulatory studies in the future. In man, several mutations resulting in familial LPL deficiency have been delineated at a molecular level. The study of these mutations is not only very beneficial from a clinical point of view but also contributes in a major way to our understanding of the structure-function relationship of LPL and other lipases. In this review major attention is given to molecular studies relating to the regulation of LPL production, to the defects underlying LPL deficiency, and to structure-function relationship of the lipases.
ATF6 Signaling Is Required for Efficient West Nile Virus Replication by Promoting Cell Survival and Inhibition of Innate Immune Responses (2012)

West Nile virus strain Kunjin (WNV(KUN)) is an enveloped, positive-sense RNA virus within the virus family Flaviviridae. Many flaviviruses have been shown to manipulate multiple signaling pathways, including autophagic, innate immune, and stress responses, in order to benefit replication. In particular, we have demonstrated that WNV(KUN) regulates the unfolded protein response (UPR), skewing the downstream effectors toward chaperone expression and Xbp-1 activation while preventing PERK-mediated translation attenuation and C/EBP homologous protein (CHOP) upregulation. WNV(KUN)-regulated UPR signaling can then be hijacked in order to affect type I interferon (IFN) responses, preventing IFN-mediated STAT1 phosphorylation and nuclear translocation. To extend our previous observations, we aimed to investigate the contribution of ATF6- and IRE1-mediated signaling during WNV(KUN) replication and how the two sensors contribute to the inhibition of IFN signaling. ATF6-deficient cells infected with WNV(KUN) showed decreased protein and virion production. These cells also demonstrated increased eIF2α phosphorylation and CHOP transcription, absent in infected matched control cells. Thus, we propose that in the absence of ATF6, WNV(KUN) is incapable of manipulating the PERK-mediated response to infection. In contrast, infection of IRE1(-/-) knockout cells showed no discernible differences compared to IRE1(+/+) cells. However, both ATF6 and IRE1 were required for WNV(KUN)-induced inhibition of STAT1 phosphorylation. We suggest that the combination of abhorrent UPR signaling, promotion of cell death, and increased innate immune responses contributes to the replication defects in ATF6-deficient cells, thus demonstrating the dual importance of ATF6 in maintaining cell viability and modulating immune responses during WNV(KUN) infection.
Purification, Some Properties and the Complete Primary Structures of Two Protease Inhibitors (DE‐3 and DE‐4) from <i>Macrotyloma axillare</i> Seed (1979)

The Macrotyloma axillare plant, belonging to the Leguminosae family, is a perennial climbing or trailing herb 0.2--3.5 m long. The plant is indigenous to South Africa and it occurs in the warm dry northern parts of the Transvaal. It has been introduced into Australia, where the seed are used as animal food. Two protease inhibitors, DE-3 and DE-4, were purified from Macrotyloma axillare seed by gel filtration on Sephadex G-50 followed by ion-exchange chromatography on DEAE-cellulose. They each comprise 76 amino acid residues including 14 half-cystine residues. The complete primary structures of the two protease innibitors have been elucidated and their sequences are 67% identical. The inhibitor specificities, the sequences, the invariant amino acid residues and the reactive inhibitor sites of protease inhibitors DE-3 and DE-4 resemble the corresponding properties of the Bowman-Birk double-headed protease inhibitor group. The cysteine residues are in similar locations to those in protease inhibitors of known structure so they are presumed to link similarly.
Diosgenin--a growth stimulator of mammary gland of ovariectomized mouse. (1992)

Estrogenic action of diosgenin on the mammary epithelium of ovariectomized (OVX) mouse has been reported. Diosgenin when administered (sc) at the dose levels of 20 and 40 mg/kg body weight for a period of 15 days stimulated the growth of mammary epithelium. This was indicated by the increase in DNA content, increase in number of ducts and appearance of terminal endbuds. There was a significant increase in the mammary development scores in the presence of diosgenin. Concomitant treatment of estrogen and diosgenin showed augmentation of estrogenic effect of diosgenin especially at the higher dose level (40 mg/kg body wt). Diosgenin showed a lack of progesterogenic action as was apparent from the absence of alveolar development even in the presence of exogenous estrogen.
Catalytic Oxidation of <i>α</i>-Carbon of Ethers Utilizing Binuclear Copper(II) Complex of 7-Azaindole (1996)

Abstract Treatment of benzyl ethyl ether with a catalytic amount of binuclear copper(II) complex of 7-azaindole 1 under oxygen atmosphere at 80 °C produced ethyl benzoate in 10400% yield based on the catalyst. This reaction could be also applied to other ethers (e.g., alkyl benzyl ethers and dialkyl ethers) to give α-oxygenated products catalytically.
IL-4 and IL-13, But Not IL-10, Protect Human Synoviocytes from Apoptosis (2001)

Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the ability of IL-4 and other Th2 cytokines to protect human synovial cells from apoptosis. Human synoviocytes or synovial explants were pretreated with IL-4, IL-10, and IL-13 before exposure to NO donor sodium-nitro-prusside (SNP). Apoptosis was evaluated by microscopy, annexin V-FITC, 3-(4,5-dimethylthiazol-2-gl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl-2H: tetrazolium inner salt (MTS) test, pulse field gel electrophoresis, and a method proposed in this study based on (32)P Klenow end labeling of high m.w. DNA. Pretreatment by IL-4 or IL-13, but not IL-10, protected human synoviocytes from apoptosis induced by SNP. Even at doses as high as 2 mM SNP, up to 86% and 56% protection was achieved, after IL-4 and IL-13 treatment, respectively. Cell survival was dependent on IL concentration. IL-4 and IL-13 also had antiapoptotic effects on SNP-treated human synovial explants. Effects of IL-4 and IL-13 varied in the presence of phosphatidylinositol-3 kinase and protein kinase C inhibitors, implying the involvement of these pathways in antiapoptotic signaling. Antiapoptotic effects were dramatically inhibited by LY294002, and partially by the protein kinase C inhibitor Gö 6976, while insulin-like growth factor increased synoviocyte survival. The possibility that IL-4 and IL-13 may enhance synovial expansion in vivo by their antiapoptotic effects is discussed.
IL-2 is necessary for the progression of leishmaniasis in susceptible murine hosts (1993)

BALB/c mice are highly susceptible to disseminated infection with the intracellular protozoa Leishmania major. Progression of disease requires in vivo expansion of Th2 CD4+ lymphocytes and is reversed by treatment with anti-IL-4 monoclonal antibody. Inasmuch as IL-2 may be necessary for both the production of IL-4 and differentiation of Th2 cells, the possible contribution of IL-2 to progressive infection was examined. Four weekly injections of anti-IL-2 mAb (S4B6) cured more than 80% of BALB/c mice infected with L. major, as determined by diminished footpad swelling and decreased numbers of parasites in infected tissues. Multiple doses of S4B6 were necessary for benefit; a single dose given at the time of infection was ineffective. The anti-IL-2R mAb PC61 demonstrated a similar protective effect when administered twice weekly for 4 wk. Anti-IL-2-mediated cure of cutaneous leishmaniasis was associated with increased IFN-gamma and decreased IL-4 production by regional lymph node cells compared to untreated BALB/c mice with progressive illness. Both CD4+ and CD8+ T lymphocytes contributed to the increased expression of IFN-gamma mRNA in cured mice. These data suggest that levels of IL-2 suboptimal for Th2 expansion in vivo do not inhibit Th1 CD4+ and CD8+ T cell activation and IFN-gamma synthesis. Other cytokines or activation pathways that are either IL-2-independent or synergistic with low levels of IL-2 may account for the appearance of curative T cell responses during treatment with anti-IL-2 antibodies.
SKN1 and KRE6 define a pair of functional homologs encoding putative membrane proteins involved in beta-glucan synthesis. (1993)

KRE6 encodes a predicted type II membrane protein which, when disrupted, results in a slowly growing, killer toxin-resistant mutant possessing half the normal level of a structurally wild-type cell wall (1-->6)-beta-glucan (T. Roemer and H. Bussey, Proc. Natl. Acad. Sci. USA 88:11295-11299, 1991). The mutant phenotype and structure of the KRE6 gene product, Kre6p, suggest that it may be a beta-glucan synthase component, implying that (1-->6)-beta-glucan synthesis in Saccharomyces cerevisiae is functionally redundant. To examine this possibility, we screened a multicopy genomic library for suppression of both the slow-growth and killer resistance phenotypes of a kre6 mutant and identified SKN1, which encodes a protein sharing 66% overall identity to Kre6p. SKN1 suppresses kre6 null alleles in a dose-dependent manner, though disruption of the SKN1 locus has no effect on killer sensitivity, growth, or (1-->6)-beta-glucan levels. skn1 kre6 double disruptants, however, showed a dramatic reduction in both (1-->6)-beta-glucan levels and growth rate compared with either single disruptant. Moreover, the residual (1-->6)-beta-glucan polymer in skn1 kre6 double mutants is smaller in size and altered in structure. Since single disruptions of these genes lead to structurally wild-type (1-->6)-beta-glucan polymers, Kre6p and Skn1p appear to function independently, possibly in parallel, in (1-->6)-beta-glucan biosynthesis.
Perovskite solar cells with an MoS<sub>2</sub> electron transport layer (2019)

MoS<sub>2</sub> thin films are directly synthesized over FTO/glass substrate in a one-step process and used as an efficient electron transport layer (ETL) for perovskite solar cells (PSCs).
Borna Disease Virus Phosphoprotein Represses p53-Mediated Transcriptional Activity by Interference with HMGB1 (2003)

Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that has a broad host range in warm-blooded animals, probably including humans. Recently, it was demonstrated that a 24-kDa phosphoprotein (P) of BDV directly binds to a multifunctional protein, amphoterin-HMGB1, and inhibits its function in cultured neural cells (W. Kamitani, Y. Shoya, T. Kobayashi, M. Watanabe, B. J. Lee, G. Zhang, K. Tomonaga, and K. Ikuta, J. Virol. 75:8742-8751, 2001). This observation suggested that expression of BDV P may cause deleterious effects in cellular functions by interference with HMGB1. In this study, we further investigated the significance of the binding between P and HMGB1. We demonstrated that P directly binds to the A-box domain on HMGB1, which is also responsible for interaction with a tumor suppression factor, p53. Recent works have demonstrated that binding between HMGB1 and p53 enhances p53-mediated transcriptional activity. Thus, we examined whether BDV P affects the transcriptional activity of p53 by interference with HMGB1. Mammalian two-hybrid analysis revealed that p53 and P competitively interfere with the binding of each protein to HMGB1 in a p53-deficient cell line, NCI-H1299. In addition, P was able to significantly decrease p53-mediated transcriptional activation of the cyclin G promoter. Furthermore, we showed that activation of p21(waf1) expression was repressed in cyclosporine-treated BDV-infected cells, as well as p53-transduced NCI-H1299 cells. These results suggested that BDV P may be a unique inhibitor of p53 activity via binding to HMGB1.
Omalizumab therapy in three patients with chronic autoimmune urticaria (2010)

Chronic urticaria is a common skin disease. In about 45% of patients the cause is an autoantibody directed at the α-subunit of the high-affinity IgE receptor (chronic autoimmune urticaria; CAU). Omalizumab is a monoclonal anti-IgE antibody that has a proven role in the treatment of various allergic diseases. We gave omalizumab once every month for 16 weeks to three patients that were refractory to standard treatment, including high doses of antihistamines, leukotriene receptor antagonist, and corticosteroid. There was dramatic improvement in the primary efficacy variable--the change in mean urticaria activity score (UAS) from baseline (i.e., the average over the first 4-week period before omalizumab) to the final 4-week period of omalizumab treatment. There was improvement in the secondary efficacy variables, which included change from baseline in interference with sleep, interference with daily activities, daily diary record of urticaria signs and symptoms based on a scoring system, and rescue medication use. These improvements persisted for 12 weeks after discontinuation of the drug. Omalizumab may have a role in treating refractory cases of CAU.
Differentiation Induction In Acute Myeloid Leukemia Using Site-Specific DNA-Targeting (2013)

Abstract Hoxa9 and Meis1 are overexpressed in >70% of acute myeloid leukemia (AML) and associated with poor prognosis and survival. Hoxa9 and Meis1 interact with DNA and PBX to achieve transcription of differentiation-blocking genes. We tested transcriptional repression at Hoxa9-PBX-Meis1 genomic binding sites to induce differentiation in a model of human AML We designed a DNA-recognition strategy based on the known structure of the Hoxa9-PBX-DNA complex by fusing the DNA binding helices of Hoxa9 and PBX to create concise homeodomain fusion proteins that target the Hoxa9-PBX DNA recognition sequence. To confer transcription-repressing properties to the proteins, we attached a transcriptional repressor (sin3 interacting) domain and ectopically expressed this protein in Hoxa9-Meis1 immortalized murine progenitors. Introduction of this transcription repressor protein significantly enabled cell differentiation versus control (51.2% Mac-1high Gr-1high cells versus 11.3% for control). Multiple gene transcripts indicative of differentiation, such as GCSFR, myeloperoxidase, neutrophil elastase, and the calcium binding protein, S100A8, were also elevated in repressor-expressing cells. Furthermore, direct transcriptional targets of Hoxa9 (e.g. SOX2, CD34, FOXP1, FLT3R, DNAJC10) were down regulated in repressor-expressing cells. Importantly, a mutant repressor lacking the DNA-interacting amino acids did not affect transcription of Hoxa9 targets, demonstrating on-target specificity. Repressor-expressing cells also exhibited lower surface expression of c-Kit and Flt3 receptors and when transplanted into mice resulted in a significant increase in disease latency with a 94 day median latency versus 62 day latency for the control group (p value = 0.002). Our results demonstrate that site-specific DNA-targeting using homeodomain fusion proteins can enable AML cell differentiation and significantly increase disease latency. Disclosures: Scadden: Fate Therapeutics: Consultancy, Equity Ownership.
Polyrotaxanes: Molecular composites derived by physical linkage of cyclic and linear species (1993)

Molecular composites consisting of cyclic molecules whose cavities have been pierced by linear molecules (see Figure) were discussed as early as 1910. However, recently interest in these molecules, which are known as rotaxanes, and their polymeric derivatives has intensified due to their unique property profiles which cannot be compared with those their components. Progress with rotaxanes and related compounds such as catenanes is reviewed. magnified image
Inhibition of Fumarate Reductase in <i>Leishmania major</i> and <i>L. donovani</i> by Chalcones (2001)

Our previous studies have shown that chalcones exhibit potent antileishmanial and antimalarial activities in vitro and in vivo. Preliminary studies showed that these compounds destroyed the ultrastructure of Leishmania parasite mitochondria and inhibited the respiration and the activity of mitochondrial dehydrogenases of Leishmania parasites. The present study was designed to further investigate the mechanism of action of chalcones, focusing on the parasite respiratory chain. The data show that licochalcone A inhibited the activity of fumarate reductase (FRD) in the permeabilized Leishmania major promastigote and in the parasite mitochondria, and it also inhibited solubilized FRD and a purified FRD from L. donovani. Two other chalcones, 2,4-dimethoxy-4'-allyloxychalcone (24m4ac) and 2,4-dimethoxy-4'-butoxychalcone (24mbc), also exhibited inhibitory effects on the activity of solubilized FRD in L. major promastigotes. Although licochalcone A inhibited the activities of succinate dehydrogenase (SDH), NADH dehydrogenase (NDH), and succinate- and NADH-cytochrome c reductases in the parasite mitochondria, the 50% inhibitory concentrations (IC(50)) of licochalcone A for these enzymes were at least 20 times higher than that for FRD. The IC(50) of licochalcone A for SDH and NDH in human peripheral blood mononuclear cells were at least 70 times higher than that for FRD. These findings indicate that FRD, one of the enzymes of the parasite respiratory chain, might be the specific target for the chalcones tested. Since FRD exists in the Leishmania parasite and does not exist in mammalian cells, it could be an excellent target for antiprotozoal drugs.
Distribution of Labeled Antibiotics in Different Components of Milk Following Intramammary and Intramuscular Administrations (1975)

In crossover trials, four lactating goats were given intramammary infusions and intramuscular injections of radioactivelabeled benzylpenicillin, spiramycin, chloramphenicol, dihydrostreptomycin, and tetracycline. Milk was collected after each treatment and the antibiotic contents in whole milk, skim milk, and whey were determined microbiologically and radiochemically and in cream and casein by radiochemical assay methods. Uptake of antibiotics by cream and casein was highly dependent on drug concentration, increasing with the decrease in antibiotic content in whole milk. Lipophilic chloramphenicol and tetracycline were concentrated in cream to a higher degree than the less lipophilic benzylpenicillin and dihydrostreptomycin. Antibiotic uptake by cream separated from whole milk after intramuscular injection was higher than after intramammary infusion. Antibiotic uptake by casein was independent of the route of administration and was highest for dihydrostreptomycin and tetracycline and lowest for benzylpenicillin.
OmniDet: Surround View Cameras Based Multi-Task Visual Perception Network for Autonomous Driving (2021)

Surround View fisheye cameras are commonly deployed in automated driving for 360 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">°</sup> near-field sensing around the vehicle. This work presents a multi-task visual perception network on unrectified fisheye images to enable the vehicle to sense its surrounding environment. It consists of six primary tasks necessary for an autonomous driving system: depth estimation, visual odometry, semantic segmentation, motion segmentation, object detection, and lens soiling detection. We demonstrate that the jointly trained model performs better than the respective single task versions. Our multi-task model has a shared encoder providing a significant computational advantage and has synergized decoders where tasks support each other. We propose a novel camera geometry based adaptation mechanism to encode the fisheye distortion model both at training and inference. This was crucial to enable training on the WoodScape dataset, comprised of data from different parts of the world collected by 12 different cameras mounted on three different cars with different intrinsics and viewpoints. Given that bounding boxes is not a good representation for distorted fisheye images, we also extend object detection to use a polygon with non-uniformly sampled vertices. We additionally evaluate our model on standard automotive datasets, namely KITTI and Cityscapes. We obtain the state-of-the-art results on KITTI for depth estimation and pose estimation tasks and competitive performance on the other tasks. We perform extensive ablation studies on various architecture choices and task weighting methodologies. A short video at https://youtu.be/xbSjZ5OfPes provides qualitative results.
Singularity-consistent path tracking: a null space based approach (2002)

In this paper we develop further the recently proposed null-space method for path tracking at and around kinematic singularities. We consider two types of singularities known as ordinary singularities and bifurcation/isolated-point singularities. A closed-loop kinematic control scheme is introduced, which is able to keep precisely the direction of the specified end-effector path passing arbitrary close to kinematic singularities. The desired velocity magnitude can be maintained at regular points of the kinematic mapping. In the vicinity of singularities, the maximum available joint velocity specified from hardware limits can be applied. Several advantages of the proposed singularity-consistent approach are pointed out when compared with other well-known methods.
Honest-Sender Commitment and Honest-Receiver Commitment (2011)

摘要: 诚实发送者承诺是为了构造非交互的非延展承诺而引入的。该文给出了两个诚实发送者承诺：第1个是诚实发送者统计绑定的，第2个是完全隐藏的。这两个协议都不是承诺方案。这说明诚实发送者承诺是弱于承诺方案的密码学原语。此外，该文定义了诚实接收者承诺，并给出了两个构造：第1个构造具有统计绑定性质，第2个构造具有诚实接收者完全隐藏性质。这两个方案都不是承诺方案，从而说明了诚实接收者承诺是弱于承诺方案的密码学原语。 关键词: 密码学 / 承诺方案 / 诚实发送者承诺 / 诚实接收者承诺
Optical-fibre-bundle holographic coupler (1978)

The difficulty of realising effective couplers for single-mode fibres imposes a significant obstacle to their application. The paper is concerned with the use of a holographic element, which substantially reduces the sensitivity to tolerance errors in the manufacture of such a coupler. The approach is based on the use of a hologram output window for the cable end, the coupling between the two windows proceeding by means of pseudoplane waves. The effect is to transfer the need for precision to the factory, the coupler to be assembled in the field being relatively undemanding. The system is applicable to bundles of fibres; preliminary experimental results for the coupling between one pair of fibres to another pair are described.
Replication termination for staphylococcal plasmids: plasmids pT181 and pC221 cross-react in the termination process (1988)

We present data which indicate that (i) the origin of replication of plasmids pT181 and pC221 can also function as termination signals; (ii) termination of replication occurs when a round of replication initiated either by RepC at the pT181 origin or by RepD at the pC221 origin reaches either of these origins, proving that the two plasmids cross-react for termination of replication; and (iii) the replication initiated at the origin of another staphylococcal plasmid, pE194, does not terminate at the origin of pT181 or pC221, indicating the existence of a specific relationship between the initiation and termination of a replication event.