gebhart/patrepeval huggingface dataset:
The herpes simplex virus ribonucleotide reductase is required for ocular virulence (1991)

We used a herpes simplex virus (HSV) type 1 ribonucleotide reductase (RR) null mutant (ICP6 delta) to study the role of HSV-1 RR in ocular HSV infections. We found that ICP6 delta was unable to induce vascularization of the cornea or stromal keratitis following inoculation into the cornea of BALB/c mice, but was able to induce a transient mild blepharitis. The parental strain (HSV-1 KOS) and a revertant of ICP6 delta, ICP6 delta+3.1, both caused severe ocular disease, indicating that HSV-1 RR is required for ocular virulence in mice. ICP6 delta grew poorly in vitro (Vero and BALB/c 3T3 fibroblasts) and in vivo (eye, trigeminal ganglia and brain) compared to ICP6 delta+3.1 and HSV-1 KOS, suggesting that the avirulence of ICP6 delta is due to poor growth in the host. ICP6 delta also grew less well in primary human corneal fibroblasts, suggesting that RR may be required for virulence in humans. These results indicate that drugs inhibiting the function of RR might be effective in treating ocular HSV infections.
Inhibition of renin–angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine (2010)

The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.
Multivalent Protein−Carbohydrate Interactions. A New Paradigm for Supermolecular Assembly and Signal Transduction (2001)

Many biological recognition processes involve the binding and clustering of ligand-receptor complexes and concomitant signal transduction events. Such interactions have recently been observed in human T cells in which binding and cross-linking of specific glycoprotein counter-receptors on the surface of the cells by an endogenous bivalent carbohydrate binding protein (galectin-1) leads to apoptosis [Pace, K. E., et al. (1999) J. Immunol. 163, 3801-3811]. Importantly, different counter-receptors associated with specific phosphatase or kinase activities were shown to form separate clusters on the surface of the cells as a result of galectin-1 binding to the carbohydrate moieties of the respective glycoproteins. This suggests that the unique separation and organization of signaling molecules that results from galectin-1 binding is involved in delivering the signal to die. The ability of galectin-1 to induce the separation of specific glycoprotein receptors was modeled on the basis of molecular and structural studies of the binding of multivalent carbohydrates to lectins that result in the formation of specific two- and three-dimensional cross-linked lattices. These latter studies have been recently highlighted by X-ray crystallographic results showing that a single tetravalent lectin forms distinct cross-linked complexes with four different bivalent oligosaccharides [Olsen, L. R., et al. (1997) Biochemistry 36, 15073-15080]. In this report, binding and cross-linking of multivalent carbohydrates with multivalent lectins is shown to be a new paradigm for supermolecular assembly and signal transduction in biological systems.
Toll-like Receptor 2 (TLR2) and TLR4 Differentially Activate Human Dendritic Cells (2001)

Toll-like receptors (TLRs) mediate cell activation by various microbial products. Here, we demonstrate that activation of dendritic cells by TLR2 or TLR4 agonists, although it led to comparable activation of NF-kappa B and mitogen-activated protein kinase (MAPK) family members, resulted in striking differences in cytokine and chemokine gene transcription, suggesting that TLR2 and TLR4 signaling is not equivalent. A TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-gamma inducible protein (IP)-10, which is also associated to Th1 responses. In contrast, TLR2 stimulation failed to induce IL-12 p70 and interferon-gamma inducible protein (IP)-10 but resulted in the release of the IL-12 inhibitory p40 homodimer, producing conditions that are predicted to favor Th2 development. TLR2 stimulation also resulted in preferential induction of IL-8 and p19/IL-23. Involvement of phosphatidylinositol 3-kinase and p38 MAPK in the TLR-mediated induction of several cytokine and chemokine messages was demonstrated using specific inhibitors. Thus, TLRs can translate the information regarding the nature of pathogens into differences in the cytokines and chemokines produced by dendritic cells and therefore may contribute to the polarization of the acquired immune response.
Triflavin, an Arg‐Gly‐Asp‐containing Antiplatelet Peptide Inhibits Cell‐substratum Adhesion and Melanoma Cell‐induced Lung Colonization (1992)

Triflavin, an Arg-Gly-Asp (RGD) containing peptide purified from Trimeresurus flavoviridis snake venom, inhibits human platelet aggregation by blocking fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this study, we show that triflavin (1-30 micrograms/mouse) inhibits B16-F10 melanoma cell-induced lung colonization in C57BL/6 mice in a dose-dependent manner. In vitro, triflavin dose-dependently inhibits adhesion of B16-F10 melanoma cells to extracellular matrices (ECMs; i.e., fibronectin, fibrinogen, vitronectin, and collagen type I). Triflavin is approximately 600-800 times more potent than GRGDS at inhibiting cell adhesion. In addition, triflavin dose-dependently inhibits B16-F10 cell-induced platelet aggregation. These results imply that the inhibitory effect of triflavin on the adhesion of tumor cells to ECMs (e.g., fibronectin, vitronectin and collagen type I) and/or tumor cell-induced platelet aggregation may be partially responsible for its antimetastatic activity in C57BL/6 mice.
Algorithms for solid noise synthesis (1989)

A solid noise is a function that defines a random value at each point in space. Solid noises have immediate and powerful applications in surface texturing, stochastic modeling, and the animation of natural phenomena.Existing solid noise synthesis algorithms are surveyed and two new algorithms are presented. The first uses Wiener interpolation to interpolate random values on a discrete lattice. The second is an efficient sparse convolution algorithm. Both algorithms are developed for model-directed synthesis , in which sampling and construction of the noise occur only at points where the noise value is required, rather than over a regularly sampled region of space. The paper attempts to present the rationale for the selection of these particular algorithms.The new algorithms have advantages of efficiency, improved control over the noise power spectrum, and the absence of artifacts. The convolution algorithm additionally allows quality to be traded for efficiency without introducing obvious deterministic effects. The algorithms are particularly suitable for applications where high-quality solid noises are required. Several sample applications in stochastic modeling and solid texturing are shown.
Cytoskeletal Polarization of T Cells Is Regulated by an Immunoreceptor Tyrosine-based Activation Motif–dependent Mechanism (1998)

Binding of a T cell to an appropriate antigen-presenting cell (APC) induces the rapid reorientation of the T cell cytoskeleton and secretory apparatus towards the cell-cell contact site in a T cell antigen receptor (TCR) and peptide/major histocompatibility complex-dependent process. Such T cell polarization directs the delivery of cytokines and cytotoxic mediators towards the APC and contributes to the highly selective and specific action of effector T cells. To study the signaling pathways that regulate cytoskeletal rearrangements in T lymphocytes, we set up a conjugate formation assay using Jurkat T cells as effectors and cell-sized latex beads coated with various antibodies as artificial APCs. Here, we report that beads coated with antibodies specific for the TCR-CD3 complex were sufficient to induce T cell polarization towards the bead attachment site, as judged by reorientation of the microtubule-organizing center (MTOC) and localized actin polymerization. Thus, these cytoskeletal changes did not depend on activation of additional coreceptors. Moreover, single subunits of the TCR complex, namely TCR-zeta and CD3epsilon, were equally effective in inducing cytoskeletal polarization. However, mutagenesis of the immunoreceptor tyrosine-based activation motifs (ITAMs), present three times in TCR-zeta and once in CD3epsilon, revealed that the induction of cytoskeletal rearrangements required the presence of at least one intact ITAM. In agreement with this result, lack of functional Lck, the protein tyrosine kinase responsible for ITAM phosphorylation, abolished both MTOC reorientation and polarized actin polymerization. Both inhibitor and transient overexpression studies demonstrated that MTOC reorientation could occur in the absence of Ras activation. Our results suggest that APC-induced T cell polarization is a TCR-mediated event that is coupled to the TCR by the same signaling motif as TCR-induced gene activation, but diverges in its distal signaling requirements.
Retardation of skeletal muscle fatigue by the two phenylpropanoid glycosides: Verbascoside and Martynoside from Pedicularis plicata Maxim (1999)

The effects of the phenylpropanoid glycosides verbascoside and martynoside from Pedicularis plicata were investigated on muscle contractility in Bufo gastrocnemius muscle electrically stimulated in vitro. The maximum amplitude and maintained time of contraction were mechanically recorded and used as indices of muscle contractility. After 30 min pretreatment of the muscle, verbascoside at 20.0 microM resisted muscle fatigue significantly while martynoside at 80.0 microM improved muscle contractility only slightly. These two glycosides resisted muscle fatigue depending on their antioxidative activities, which is in agreement with the role of reactive oxygen species (ROS) in promoting fatigue in skeletal muscle.
Localization of Mesothelin in Epithelial Ovarian Cancer (2005)

Mesothelin is a cell surface glycoprotein that is present on normal mesothelial cells and overexpressed in several cancers. On immunohistochemical examination of a limited number of ovarian tumors, increased mesothelin expression has been previously noted. The authors evaluated mesothelin expression in 48 patients with ovarian cancer who were screened for participation in phase 1 studies of a recombinant immunotoxin targeting mesothelin. Eligibility criteria for participation in the studies included mesothelin expression by more than 30% of accessible tumor cells. Sections of formalin-fixed paraffin-embedded tumor specimens were evaluated for mesothelin expression by immunohistochemistry using the anti-mesothelin monoclonal antibody K1. Between September 2000 and January 2003, 48 ovarian tumors were analyzed for mesothelin positivity. Mesothelin positivity was noted in 34 of the 48 cases evaluated (71%). These results show that mesothelin is expressed in most epithelial ovarian cancers and that mesothelin expression in ovarian cancers can be evaluated in archival material. Patients whose tumors express mesothelin could be eligible for participation in clinical trials of novel agents targeting mesothelin.
Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget’s disease of bone (2000)

Paget's disease is characterized by highly localized areas of increased osteoclast (OCL) activity. This suggests that the microenvironment in pagetic lesions is highly osteoclastogenic, or that OCL precursors in these lesions are hyperresponsive to osteoclastogenic factors (or both). To examine these possibilities, we compared RANK ligand (RANKL) mRNA expression in a marrow stromal cell line developed from a pagetic lesion (PSV10) with that in a normal stromal cell line (Saka), and expression in marrow samples from affected bones of Paget's patients with that in normal marrow. RANKL mRNA was increased in PSV10 cells and pagetic marrow compared with Saka cells and normal marrow, and was also increased in marrow from affected bones compared with uninvolved bones from Paget's patients. Furthermore, pagetic marrow cells formed OCLs at much lower RANKL concentrations than did normal marrow. Anti-IL-6 decreased the RANKL responsivity of pagetic marrow to normal levels, whereas addition of IL-6 to normal marrow enhanced RANKL responsivity. Thus, RANKL expression and responsivity is increased in pagetic lesions, in part mediated by IL-6. These data suggest that the combination of enhanced expression of RANKL in affected bones and increased RANKL sensitivity of pagetic OCL precursors may contribute to the elevated numbers of OCLs in Paget's disease.
Detection of human papillomavirus 16 transcriptional activity in cervical intraepithelial neoplasia grade III lesions and cervical carcinomas by nested reverse transcription-polymerase chain reaction and in situ hybridization. (1998)

Continued expression of the oncogenes E6 and E7 of human papilloma virus "high risk" type 16 (HPV16) initiates neoplastic transformation and maintenance of the malignant phenotype in cervical carcinoma cells. The transcriptional activity of the HPV16 E6/E7 oncogenes was investigated in HPV16-containing cervical cell lines, cervical carcinomas, and cervical intraepithelial neoplasia grade III lesions using the techniques of reverse transcription-polymerase chain reaction (RT-PCR), Southern blotting, and in situ hybridization. To facilitate detection of the full-length HPV16 E6/E7 oncogene transcript and its characteristic splice products E6*I and E6*II in cervical tissues, a nested RT-PCR (nRT-PCR) assay was designed. Specific detection of HPV E6/E7 oncogene transcripts in clinical specimens was found to be improved by nRT-PCR, being as sensitive as the combination of conventional RT-PCR and subsequent Southern blot hybridization. Regarding the progression of premalignant lesions to cervical cancer, detection of the HPV transcriptional activity by nRT-PCR may provide additional information for risk evaluations. Moreover, improvements in the amplification of HPV oncogene transcripts may also be advantageous for monitoring the activity of HPV before and after transcript-targeted gene therapy of cervical cancer.
Vertical nanotubes connected by a subsurface nanochannel (2010)

We have built an array of vertical nanotubes connected by a subsurface nanofluidic channel. The nanotube system is to be used for cell injections. By culturing cells on top of the nanotubes the cells will be pierced and molecules can enter the cells via the subsurface channel. Several channels can be made on the same sample and different molecules can be injected into different subpopulations of cells. The advantages of our system over similar injection devices include spatial and temporal resolution as well as an increased choice of injected molecules.
Production of bovine alpha-lactalbumin in the milk of transgenic pigs. (1998)

High production of milk and its components are necessary to allow maximal growth of developing pigs. In this study, transgenic pigs were produced containing the alpha-lactalbumin gene, whose product is a potential limiting component in the production of milk. Two lines of transgenic pigs were produced to analyze the effects that overproduction of the milk protein alpha-lactalbumin may have on milk production and piglet growth. Transgenic pigs were produced through microinjection of the bovine alpha-lactalbumin gene. The gene construct contained 2.0 kb of 5' flanking region, the 2.0 kb coding region, and 329 bp of 3' flanking region. Sows hemizygous for the transgene produced as much as .9 g of bovine alpha-lactalbumin per liter of pig milk. The production of the bovine protein caused approximately a 50% increase in the total alpha-lactalbumin concentration of pig milk throughout a lactation. The concentration of bovine alpha-lactalbumin was highest on d 0 and 5 of lactation and decreased as lactation progressed. The ratio of bovine to porcine alpha-lactalbumin changed during the sow's lactation. This ratio was 4.3 to 1 on d 0 of lactation, but by d 20 of lactation the ratio was .43 to 1. This suggested that the bovine transgene and the endogenous porcine gene are under slightly different control mechanisms. The higher level of total alpha-lactalbumin present on d 0 of lactation was correlated with higher lactose percentage on d 0 in transgenic sows (3.8%), compared with controls (2.6%) (P < .01). Although there was also a trend for higher lactose percentage in transgenic sows on d 5 and 10 of lactation, no significant differences were observed. These data suggest that alpha-lactalbumin is limiting early in lactation of swine. Furthermore, higher concentrations of alpha-lactalbumin early in lactation may boost milk output.
Real-time video transmission of ultrasound images to an iPhone (2010)

Abstract Background As point-of-care ultrasound spreads across the globe, there is an increased need for training and supervision of ultrasound studies. Real-time oversight is important, especially in critically ill patients, but often an expert ultrasound over-read is not available on location. Technological advances have improved data transmission so that images and videos can be sent great distances very rapidly. In this study, we examine the feasibility of real-time wireless transmission of ultrasound video to an iPhone. Methods An ultrasound machine was connected via a video converter to a laptop. iCam (SKJM, LLC) software was used to transmit the video across the Atlantic Ocean to an iPhone. Images typical for those performed in an emergency department were sent, in random order by a ‘scanning physician.’ An ‘interpreting physician’ overseas was asked to identify the anatomy, presence or absence of pathology, and comment on the quality, speed, and delay of transmission. Results Rapid image transmission was feasible and the ‘interpreting physician’ was always able to correctly identify the anatomy and orientation. The average delay was minimal (2.7 s), allowing for real-time feedback. The frame rate was markedly slower in the received images as compared to the transmitted images, and was faster when the iPhone was connected via WiFi (1.1 fps) versus a 3G connection (0.4 fps). Conclusion Transmission of real-time ultrasound video to a remote iPhone using inexpensive technology is feasible, with the preservation of image quality and minimal delay. Transmission speed was superior with a WiFi connection than with a 3G connection.
UVT: a unification-based tool for knowledge base verification (1993)

A method for verifying knowledge bases that is based on the unification of rules is discussed. One characteristic that distinguishes this approach from other verification tools is that it infers some of the rules that are not explicitly given in the rule base and considers their effect on the verification process. The method can determine conflicting, redundant, subsumed, circular, and dead-end rules, redundant if conditions in rules, and cycles and contradictions within rules. The method has been implemented in a computer program called UVT (for unification-based verification tool) and tested on sample knowledge bases.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Specific Micro RNA-Regulated TetR-KRAB Transcriptional Control of Transgene Expression in Viral Vector-Transduced Cells (2012)

Precise control of transgene expression in a tissue-specific and temporally regulated manner is desirable for many basic and applied investigations gene therapy applications. This is important to regulate dose of transgene products and minimize unwanted effects. Previously described methods have employed tissue specific promoters, miRNA-based transgene silencing or tetR-KRAB-mediated suppression of transgene promoters. To improve on versatility of transgene expression control, we have developed expression systems that use combinations of a tetR-KRAB artificial transgene-repressor, endogenous miRNA silencing machinery and tissue specific promoters. Precise control of transgene expression was demonstrated in liver-, macrophage- and muscle-derived cells. Efficiency was also demonstrated in vivo in murine muscle. This multicomponent and modular regulatory system provides a robust and easily adaptable method for achieving regulated transgene expression in different tissue types. The improved precision of regulation will be useful for many gene therapy applications requiring specific spatiotemporal transgene regulation.
NY‐ESO‐1 protein expression in primary breast carcinoma and metastases—correlation with CD8+ T‐cell and CD79a+ plasmacytic/B‐cell infiltration (2007)

NY-ESO-1 is a cancer testis antigen expressed in various malignancies and testicular germ cells. Because of its capacity to induce specific humoral and cellular immunity in patients with NY-ESO-1-positive carcinomas, it represents a promising target for cancer immunotherapy. In breast cancer, NY-ESO-1-mRNA was reported in up to 42%, but protein expression has not been determined to larger extent. In the present tissue microarray-based study, primary breast cancers (n = 1,444), in situ lesion (n = 148), recurrences (n = 88), lymph node (n = 525) and distant metastases (n = 91) were studied for NY-ESO-1 expression by immunohistochemistry. NY-ESO-1-protein expression was compared with mRNA expression by real-time PCR. NY-ESO-1-protein was detected in 3.1% (4/128) in situ lesions and in 2.1% (28/1355) invasive breast cancer. There were 1.8% (9/493) NY-ESO-1-positive lymph node and 5.1% (4/78) positive distant metastases. NY-ESO-1 was more frequently expressed in grade 3 (4.9%) than in grade 2 (0.8%) and grade 1 (0.5%) carcinomas (p < 0.0001). Presence of tumor-infiltrating CD8+ T-cells correlated with NY-ESO-1 (p < 0.0001) on the tissue microarray. On randomly selected large sections, 4 out of 9 NY-ESO-1-positive tumors displayed a brisk infiltrate of CD79a+ plasmocytes/B-cells, but none of 10 NY-ESO-1-negative tumors (p < 0.05). NY-ESO-1-mRNA expression was detected in frozen samples of NY-ESO-1-protein positive (n = 6) and negative breast cancers (n = 8) and in normal testis. Comparison between mRNA and protein expression revealed that only breast cancers with NY-ESO-1-mRNA levels comparable or higher than testis expressed NY-ESO-1-protein. These findings suggest that NY-ESO-1-positive breast cancers represent a small subset of poorly differentiated tumors with evidence of cellular and humoral immune response.
[Isolation and analysis of a novel MYC gene from rice]. (2005)

A MYC (Myelocytomatosis) transcription factor gene, OsMYC, was cloned in rice (Oryza sativa L.). The putative protein of the OsMYC gene has a typical DNA binding domain: basic/helix-loop-helix (bHLH) motif at the C-terminus. Its nucleocide sequnce has 78%, 48%, 46% identity with that of the AtMYC2, MYC7E and PG1 genes, respectively. The identity of deduced amino acid between OsMYC and AtMYC2, MYG7E and PG1 is 95%, 84%, and 77% in the bHLH domain, and that is 81%, 54% and 52% in the N-terminus conserved region. The identity is 100% in the nuclear localization signal between them. Phylogenetic comparisons revealed that the OsMYC protein was related to the Arabidopsis AtMYC2, Zea MYC7E and Phaseolus vulgaris PG1. OsMYC gene was expressed at high level in stem, but low level in leaf and root and can be induced by ABA and Fe3+, which is similar to the expression pattern of MYC7E and RAP1 genes. Thus, this gene is a new member of the rice MYC family.