gebhart/patrepeval huggingface dataset:
Interaction of endosialin/TEM1 with extracellular matrix proteins mediates cell adhesion and migration (2007)

Endosialin/TEM1 was originally discovered as a human embryonic fibroblast-specific antigen and was later found to be differentially expressed in tumor stroma and endothelium. Endosialin/TEM1 overexpression has been observed in many cancers of various tissue origin, including colon, breast, pancreatic, and lung. The knockout (KO) mouse model showed the absence of endosialin/TEM1 expression reduced growth, invasion, and metastasis of human tumor xenografts. In addition, lack of endosialin/TEM1 led to an increase in small immature blood vessels and decreased numbers of medium and large tumor vessels. This abnormal angiogenic response could be responsible for the reduced tumor growth and invasion observed in endosialin/TEM1 KO mice, suggesting a role for endosialin/TEM1 in controlling the interaction among tumor cells, endothelia, and stromal matrix. Here we report the identification of fibronectin (FN) and collagen types I and IV as specific ligands for endosialin/TEM1. More importantly, cells expressing endosialin/TEM1 exhibit enhanced adhesion to FN as well as enhanced migration through matrigel, although these properties could be blocked by a humanized antibody directed against human endosialin/TEM1. Our results pinpoint to a molecular mechanism by which expression of endosialin/TEM1 in the tumor stroma and endothelium may support tumor progression and invasion.
Synthesis of 3-Hydroxypyrimidine-2,4-diones. Addition of Anilines to Benzyloxy Isocyanate Synthons to GiveN-Hydroxyureas (1994)

A new method, the addition of N-benzyloxychloroformate to methyl anthranilate followed by base-catalyzed cyclization, has been employed to synthesize the N-hydroxyquinazolinedione 1 and heterocyclic derivatives. N-Benzyloxycarbonylimidazole is a useful synthon to prepare N-hydroxyureas.
The 19-kD antigen and protective immunity in a murine model of tuberculosis (2000)

The 19-kD antigen is a cell wall-associated lipoprotein present in Mycobacterium tuberculosis and in bacille Calmette-Guérin (BCG) vaccine strains. Expression of the 19-kD antigen as a recombinant protein in two saprophytic mycobacteria-M. vaccae and M. smegmatis-resulted in abrogation of their ability to confer protection against M. tuberculosis in a murine challenge model, and in their ability to prime a DTH response to cross-reactive mycobacterial antigens. Induction of an immune response to the 19-kD antigen by an alternative approach of DNA vaccination had no effect on subsequent M. tuberculosis challenge. These results are consistent with a model in which the presence of the 19-kD protein has a detrimental effect on the efficacy of vaccination with live mycobacteria. Targeted inactivation of genes encoding selected antigens represents a potential route towards development of improved vaccine candidates.
삶의 참된 끝맺음, 웰엔딩(Well-ending)에 관한 이해 -유가사상을 중심으로 (2012)

최근에 부각되고 있는 현대인들의 관심사 중 하나는 죽음의 질적 차원을 드높이는 데있다. 이는 삶을 어떻게 살아가는지에 대한 관심이 아니라, 죽음을 어떻게 맞이할지에 관한 고려로부터 비롯된다. ‘웰다잉(Well-dying)’, 또는 ‘웰엔딩(Well-ending)’이라는 문화 운동코드의 출현은 삶의 질 못지않게 죽음의 질까지도 고려하고자 하는 관심이 반영된 것이다. 유행처럼 번졌던 웰빙 운동처럼, 이들 구호는 사람들의 시선을 끌만큼 충분히 매력적이다. 하지만 이러한 매력적인 구호가 지닌 취지에 비해 아직까지 실천을 진지하게 유발시킬 만큼의 견고한 이론적 토대가 마련되지 않은 것은 사실이다. 유가 사상의 죽음관은 이러한 이론 내용들 중 하나일 수 있다. 특히, ‘웰엔딩’의 뜻을 엄밀하게 이해해 본다면, 유가 사상에서 파악하는 좋은 죽음과의 부합점을 찾을 수 있다. 이는 군자의 죽음을 끝맺음의 ‘종(終)’이라 지칭하는 점에서 드러난다. 이렇게 지칭하는 이유는 유가 사상이 죽음을 삶의 끝맺음과 완성으로 간주하기 때문이다. 하지만, 주목해야 할 부분은 이러한 끝맺음이 단순한 육체적 생명의 시간적인 끝맺음을 가리키는 것이 아니라, 정신적 삶의 가치가 완성됨을 지시한다는 점에 있다. 다시 말하면, ‘인(仁)’으로 상징되는 인간다움의 완성, ‘성인(成仁)’을 의미한다. 이를 일종의 사명처럼 여겨 완수하고자 노력한 이후에 맞이하는 죽음이 바로 ‘종(終)’이라 지칭할 수 있으며, 바로 이러한 관점에서 삶의 참된 끝맺음이라 해석할 수 있는 ‘웰엔딩’과의 접목 지점을 찾을수 있다.
Differentiation and tropic/trophic effects of exogenous neural precursors in the adult spinal cord (2004)

The fate of exogenous neural stem cells (NSCs) in the environment of the adult nervous system continues to be a matter of debate. In the present study, we report that cells of the murine NSC clone C17.2, when grafted into the lumbar segments of the spinal cord of adult rats, survive and undergo partial differentiation. C17.2 cells migrate avidly toward axonal tracts and nerve roots and differentiate into nonmyelinating ensheathing cells. Notably, C17.2 cells induce the de novo formation of host axon tracts aiming at graft innervation. Differentiation and inductive properties of C17.2 cells are independent of the presence of lesions in the spinal cord. The tropic/trophic interactions of C17.2 NSCs with host axons, the avid C17.2 cell-host axon contacts, and the ensheathing properties of these cells are related to their complex molecular profile, which includes the expression of trophic cytokines and neurotrophins such as glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor, glial growth factor receptors such as ErbB-2; and PASK, the mammalian homologue of the fray gene that is involved in axon ensheathment. These results show that NSCs might not only play a critical supportive role in repairing axonal injury in the adult spinal cord but also can be used as probes for exploring the molecular underpinnings of the regenerative potential of the mature nervous system after injury.
Modulation of doxorubicin resistance in P388/ADR cells by Ro44-5912, a tiapamil derivative. (1995)

We describe here investigations into the ability of a tiapamil derivative, Ro44-5912 to overcome multidrug resistance (MDR) in doxorubicin (ADR)-resistant murine leukemic P388 cells. This compound has the formula: C27H39NO4S2.1:2C6H8O6, a M. W. of 858 and is structurally similar to verapamil, an established inhibitor of P-glycoprotein (PGP). We have compared the MDR modulating properties of Ro44-5912 with verapamil in P388ADR cells. Doxorubicin concentration required to achieve 50% inhibition of growth (IC50) for P388ADR cells was found to be 24 microM. In contrast, treatment of P388ADR cells with Doxorubicin and 3 microM verapamil decreased the IC50 value to 2.5 microM. A further decrease was observed with 3 microM Ro44-5912 treatment, where an IC50 value of 1.1 microM was obtained. Doxorubicin accumulation was also determined by flow cytometry in order to determine whether the increased levels of chemosensitivity observed for Ro44-5912 were reflected by increased cellular drug uptake. The results revealed that Ro44-5912, at equivalent concentration, increased doxorubicin accumulation in P388ADR cells beyond that obtained with verapamil whereas no effects were seen with the parental P388 cells. The effect of Ro44-5912 on the binding of C219 monoclonal antibody to PGP in MDR cells was also studied and found not to decrease C219 expression on P388ADR cells.
Direct Analysis of the Dynamics of the Intestinal Mucosa CD8 T Cell Response to Systemic Virus Infection (2001)

The CD8 T cell response to vesicular stomatitis virus infection was characterized in the spleen and intestinal mucosa using MHC tetramers. Surprisingly, the primary response persisted in the lamina propria long after the splenic response had declined. Furthermore, the response was characterized by a protracted effector phase in which cytolytic activity in the lamina propria, but not in the spleen, was maintained. The appearance of Ag-specific cells in the intestinal mucosa was largely, though not exclusively, a result of beta(7) integrin-mediated migration. Infection with Listeria monocytogenes or with vaccinia virus also led to sustained mucosal responses. After reinfection of vesicular stomatitis virus-primed mice with a serotypically distinct virus, a sustained recall response was detected in all tissues. In CD40(-/-) mice, the mucosal, but not the splenic, response was compromised, resulting in diminished mucosal memory. The recall response was CD40 independent and correlated with memory levels, indicating that the mucosal and systemic responses operated independently. These findings illustrated the integrated yet distinct nature of systemic vs mucosal immune responses.
Comparative sequence analysis of human cytomegalovirus strains (1991)

Three regions of DNA from five low-passage clinical isolates of human cytomegalovirus were amplified by polymerase chain reaction. The DNA sequences as well as the predicted amino acid sequences were compared with those of the laboratory strains AD169 and Towne. The genomic regions consisted of (i) three regions from the major glycoprotein (gp58/116, unique long [UL]55), (ii) three regions from the integral membrane protein (IMP, UL100), and (iii) a region from the major immediate-early 1 and 2 (IE-1/2) enhancer/promoter. Homologies ranged from 75.8 to 100.0% on the nucleotide level and from 47 to 100% on the amino acid level. The following two patterns were observed. (i) There are regions with a high degree of conservation with few scattered point mutations (mainly in the IE-1/2 enhancer/promoter and in the IMP gene). (ii) There are clusters of highly variable regions (parts of the gp58/116 gene and of the IMP gene). Within the areas of high variability, the strains could be classified into a limited number of subtypes.
Modulations of VEGF and iNOS in the rat heart by low level laser therapy are associated with cardioprotection and enhanced angiogenesis (2006)

It is concluded that VEGF and iNOS expression in the infarcted rat heart is markedly upregulated by LLLT and is associated with enhanced angiogenesis and cardioprotection.
The 3′ Region of the Chicken Hypersensitive Site-4 Insulator Has Properties Similar to Its Core and Is Required for Full Insulator Activity (2009)

Chromatin insulators separate active transcriptional domains and block the spread of heterochromatin in the genome. Studies on the chicken hypersensitive site-4 (cHS4) element, a prototypic insulator, have identified CTCF and USF-1/2 motifs in the proximal 250 bp of cHS4, termed the "core", which provide enhancer blocking activity and reduce position effects. However, the core alone does not insulate viral vectors effectively. The full-length cHS4 has excellent insulating properties, but its large size severely compromises vector titers. We performed a structure-function analysis of cHS4 flanking lentivirus-vectors and analyzed transgene expression in the clonal progeny of hematopoietic stem cells and epigenetic changes in cHS4 and the transgene promoter. We found that the core only reduced the clonal variegation in expression. Unique insulator activity resided in the distal 400 bp cHS4 sequences, which when combined with the core, restored full insulator activity and open chromatin marks over the transgene promoter and the insulator. These data consolidate the known insulating activity of the canonical 5' core with a novel 3' 400 bp element with properties similar to the core. Together, they have excellent insulating properties and viral titers. Our data have important implications in understanding the molecular basis of insulator function and design of gene therapy vectors.
Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors (2000)

Neuropeptide Y (NPY) has been shown to participate in the cardiovascular response mediated by the sympathetic system. In this report, we investigate the growth factor properties of NPY on cardiac myocytes. Mitogen-activated protein kinases (MAPK) are key signaling molecules in the transduction of trophic signals. Therefore, the role of NPY in inducing MAPK activation was studied in mouse neonatal cardiomyocytes. Exposure of neonatal cardiomyocytes to either NPY, phenylephrine, or angiotensin II induces a rapid phosphorylation of the extracellular responsive kinase, the c-jun N-terminal kinase, and the p38 kinase as well as an activation of protein kinase C (PKC). Moreover, NPY potentiates phenylephrine-induced MAPK and PKC stimulation. In contrast, NPY has no synergistic effect on angiotensin II-stimulated MAPK phosphorylation or PKC activity. NPY effects are pertussis toxin-sensitive and calcium-independent and are mediated by NPY Y5 receptors. Taken together, these results suggest that NPY, via G(i) protein-coupled NPY Y5 receptors, could participate in the development of cardiac hypertrophy during chronic sympathetic stimulation by potentiating alpha-adrenergic signals.
Steinitz theorems for orthogonal polyhedra (2010)

We define a simple orthogonal polyhedron to be a three-dimensional polyhedron with the topology of a sphere in which three mutually-perpendicular edges meet at each vertex. By analogy to Steinitz's theorem characterizing the graphs of convex polyhedra, we characterize the graphs of simple orthogonal polyhedra: they are exactly the 3-regular bipartite planar graphs in which the removal of any two vertices produces at most two connected components. We also characterize two subclasses of these polyhedra: corner polyhedra, which can be drawn by isometric projection in the plane with only one hidden vertex, and xyz polyhedra, in which each axis-parallel line through a vertex contains exactly one other vertex. Based on our characterizations we find efficient algorithms for constructing orthogonal polyhedra from their graphs
Consistent Production of Transgenic Chickens Using Replication-Deficient Retroviral Vectors and High-Throughput Screening Procedures (2002)

We have developed a novel method of DNA extraction combined with a high-throughput method of gene detection allowing thousands of potentially transgenic chicks to be screened quickly and reliably. By using this method and a replication-deficient retroviral vector based on avian leukosis virus (ALV), we have demonstrated germline transmission of three different transgenes. Several generations of chickens carrying intact transgenes were produced, validating the use of the ALV retroviral vectors for large-scale production of transgenic flocks. Fourth-generation chicks that were nontransgenic, hemizygous, or homozygous for the transgene were identified with the combined genetic screening methods.
Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice (1997)

The severe combined immune deficiency (SCID) mouse was reported as an animal model for human immune deficiency. Through the course of several studies, the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) gene came to be considered a candidate for the SCID-responsible gene. We isolated an ORF of the murine DNA-PKcs gene from SCID mice and their parent strain C.B-17 mice and determined the DNA sequences. The ORF of the murine DNA-PKcs gene contained 4128-aa residues and had 78.9% homology with the human DNA-PKcs gene. A particularly important finding is that a T to A transversion results in the substitution of termination codon in SCID mice for the Tyr-4046 in C.B-17 mice. No other mutation was detected in the ORF of the gene. The generality of this transversion was confirmed using four individual SCID and wild-type mice. The substitution took place in the phosphatidylinositol 3-kinase domain, and the mutated gene encodes the truncated products missing 83 residues of wild-type DNA-PKcs products. Furthermore, the quantity of DNA-PKcs transcript in wild-type and SCID cells was almost equal. These observations indicate that the DNA-PKcs gene is the SCID-responsible gene itself and that the detected mutation leads to the SCID aberration.
Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24week, double-blind, randomized Phase 3 trial (2014)

Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.
Treatment of Leber Congenital Amaurosis Due to RPE65 Mutations by Ocular Subretinal Injection of Adeno-Associated Virus Gene Vector: Short-Term Results of a Phase I Trial (2008)

Leber congenital amaurosis (LCA) is a group of autosomal recessive blinding retinal diseases that are incurable. One molecular form is caused by mutations in the RPE65 (retinal pigment epithelium-specific 65-kDa) gene. A recombinant adeno-associated virus serotype 2 (rAAV2) vector, altered to carry the human RPE65 gene (rAAV2-CBSB-hRPE65), restored vision in animal models with RPE65 deficiency. A clinical trial was designed to assess the safety of rAAV2-CBSB-hRPE65 in subjects with RPE65-LCA. Three young adults (ages 21-24 years) with RPE65-LCA received a uniocular subretinal injection of 5.96 x 10(10) vector genomes in 150 microl and were studied with follow-up examinations for 90 days. Ocular safety, the primary outcome, was assessed by clinical eye examination. Visual function was measured by visual acuity and dark-adapted full-field sensitivity testing (FST); central retinal structure was monitored by optical coherence tomography (OCT). Neither vector-related serious adverse events nor systemic toxicities were detected. Visual acuity was not significantly different from baseline; one patient showed retinal thinning at the fovea by OCT. All patients self-reported increased visual sensitivity in the study eye compared with their control eye, especially noticeable under reduced ambient light conditions. The dark-adapted FST results were compared between baseline and 30-90 days after treatment. For study eyes, sensitivity increases from mean baseline were highly significant (p < 0.001); whereas, for control eyes, sensitivity changes were not significant (p = 0.99). Comparisons are drawn between the present work and two other studies of ocular gene therapy for RPE65-LCA that were carried out contemporaneously and reported.
Protocol: a versatile, inexpensive, high-throughput plant genomic DNA extraction method suitable for genotyping-by-sequencing (2018)

This versatile, scalable and simple protocol yields high molecular weight genomic DNA suitable for restriction enzyme digestion and next-generation sequencing applications including GBS and long-read sequencing platforms such as PacBio. The low cost, high-throughput, and extraction of high quality gDNA from a range of fresh and dried source plant material makes this method suitable for many sequencing and genotyping applications including large-scale sample screening underpinning breeding programmes.
Eradication of established renal cell carcinoma by a combination of 5‐fluorouracil and anti‐4‐1BB monoclonal antibody in mice (2008)

Renal cell carcinoma (RCC), one of the most incurable malignancies, is highly resistant to chemotherapy and radiotherapy. Cytokine immunotherapy has been the standard approach, but the overall response rate is still very low. Administration of agonistic anti-4-1BB monoclonal antibody (mAb) has been shown to induce regression of several animal tumors but its effect on RCC is unknown. We show here that monotherapy with either anti-4-1BB mAb or the cytotoxic drug, 5-fluorouracil (5-FU), has little effect on established RCC, Renca tumors, but combination therapy with anti-4-1BB mAb and 5-FU eradicates the tumors in more than 70 % of mice. The regressing tumor tissues from mice receiving the combination therapy contained more apoptotic tumor cells and tumor infiltrating lymphocytes than tumor tissues from mice receiving 5-FU or anti-4-1BB mAb monotherapy. The number of lymphocytes in the spleens and tumor- draining lymph nodes (TDLNs) of the combination therapy mice was greatly increased compared to that of control or 5-FU monotherapy mice. Mice that had recovered due to the combination therapy rapidly rejected rechallenge with the tumor, pointing to the establishment of long-lasting tumor-specific memory. Our results indicate that targeting tumors with 5-FU, and immune cells with 4-1BB stimulation, could be a useful strategy for treating incurable RCC.
Automated Whitebox Fuzz Testing. (2008)

Fuzz testing is an effective technique for finding security vulnerabilities in software. Traditionally, fuzz testing tools apply random mutations to well-formed inputs of a program and test the resulting values. We present an alternative whitebox fuzz testing approach inspired by recent advances in symbolic execution and dynamic test generation. Our approach records an actual run of the program under test on a well-formed input, symbolically evaluates the recorded trace, and gathers constraints on inputs capturing how the program uses these. The collected constraints are then negated one by one and solved with a constraint solver, producing new inputs that exercise different control paths in the program. This process is repeated with the help of a code-coverage maximizing heuristic designed to find defects as fast as possible. We have implemented this algorithm in SAGE (Scalable, Automated, Guided Execution), a new tool employing x86 instruction-level tracing and emulation for whitebox fuzzing of arbitrary file-reading Windows applications. We describe key optimizations needed to make dynamic test generation scale to large input files and long execution traces with hundreds of millions of instructions. We then present detailed experiments with several Windows applications. Notably, without any format-specific knowledge, SAGE detects the MS07-017 ANI vulnerability, which was missed by extensive blackbox fuzzing and static analysis tools. Furthermore, while still in an early stage of development, SAGE has already discovered 30+ new bugs in large shipped Windows applications including image processors, media players, and file decoders. Several of these bugs are potentially exploitable memory access violations. 1
Effect of solanine on the membrane potential of mitochondria in HepG2cells and [Ca2+]iin the cells (2006)

Solanine opens up the PT channels in the membrane by lowering the membrane po-tential, leading to Ca(2+) being transported down its concentration gradient, which in turn leads to the rise of the concentration of Ca(2+) in the cell, turning on the mechanism for apoptosis.
Large mode area fibers with asymmetric bend compensation (2011)

Fibers with asymmetrical bend compensation offer to completely remove the tradeoff between mode area and single-modedness, with potentially huge impact on high-power amplification. These fibers would be difficult to fabricate, but are the only fundamental-mode strategy that can remove the bend-distortion limitations on mode-area scaling. Here, we show that even imperfect fibers can achieve essentially complete HOM suppression for areas of 2000 square microns or larger. Ultimate performance limits due to finite cladding size and fabrication imperfections are calculated.
A Chirp Transform Algorithm for Processing Squint Mode FMCW SAR Data (2007)

Frequency-modulated continuous-wave (FMCW) synthetic aperture radar (SAR) is a lightweight cost-effective high-resolution airborne imaging radar. In squint case, the frequency scaling algorithm, which is suitable for processing nonchirped raw data, cannot be used directly in FMCW SAR data processing because of low system sampling frequency. On the other hand, the continuous antenna motion of FMCW SAR can cause serious distortions in the reconstructed images. In this letter, an improved algorithm called the chirp transform algorithm is proposed. When the effects of the residual video phase are negligible, the algorithm uses a chirp transform to perform the time scaling operation to alleviate the sampling frequency problem. It requires only fast Fourier transforms and multiplications. The range cell migration introduced by the continuous motion is also compensated completely in range-Doppler domain. The algorithm performances are analyzed and are supported by point target simulation experiments.
A novel therapeutic cytomegalovirus DNA vaccine in allogeneic haemopoietic stem-cell transplantation: a randomised, double-blind, placebo-controlled, phase 2 trial (2012)

Vical and US National Institute of Allergy and Infectious Diseases.