gebhart/patrepeval huggingface dataset:
PTEN and phosphatidylinositol 3'-kinase inhibitors up-regulate p53 and block tumor-induced angiogenesis: evidence for an effect on the tumor and endothelial compartment. (2003)

Previous work from our laboratory demonstrated that PTEN regulates tumor-induced angiogenesis and thrombospondin 1 expression in malignant glioma. Herein, we demonstrated the first evidence that the systemic administration of a phosphatidylinositol 3'-kinase (PI3K) inhibitor (LY294002) has antitumor and antiangiogenic activity in vivo. We show that PTEN reconstitution diminished phosphorylation of AKT, induced the transactivation of p53 (7.5-fold induction) and increased the expression of p53 target genes, p21(waf-1) and insulin-like growth factor binding protein 3 in glioma cells. PTEN and LY294002 induced p53 activity in human brain endothelial cells, suggesting that PTEN and PI3K pathways can suppress the progression of cancer through direct actions on tumor and endothelial cells. The capacity of PTEN and LY294002 to inhibit U87MG or U373MG glioma growth was tested in an ectopic skin and orthotopic brain tumor model. LY294002 inhibited glioma tumor growth in vivo, induced tumor regression, decreased the incidence of brain tumors, and blocked the tumor-induced angiogenic response of U87MG cells in vivo. These data provide evidence that both PTEN and PI3K inhibitors regulate p53 function and display in vivo antiangiogenic and antitumor activity. These results provide evidence that the two tumor suppressor genes, PTEN and p53, act together to block tumor progression in vivo. Our data provide the first preclinical evidence for the in vivo efficacy for LY294002 in the treatment of malignant gliomas.
Isolation and characterization of the recA gene of Rhizobium meliloti (1983)

Interspecific complementation of an Escherichia coli recA mutant with plasmids containing a gene bank of Rhizobium meliloti DNA was used to identify a clone which contains the recA gene of R. meliloti. The R. meliloti recA protein can function in recombination and in response to DNA damage when expressed in an E. coli recA host, and hybridization studies have shown that DNA sequence homology exists between the recA gene of E. coli and that of R. meliloti. The isolated R. meliloti recA DNA was used to construct a recA R. meliloti, and this bacterium was not deficient in its ability to carry out symbiotic nitrogen fixation.
A collaborative wearable system with remote sensing (2002)

This paper presents a collaborative wearable system based on the notion of remote sensing. Remote sensing lets users of wearable or stationary computers perceive a remote environment through the sensors of a remote wearable computer. We describe a concrete system with remote sensing capability that is designed to enhance the communication and cooperation of highly mobile computer technicians.
Targeted disruption of the murine Fanconi anemia gene,Fancg/Xrcc9 (2001)

Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and ionizing radiation. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have been cloned, and the encoded FA proteins interact in a common cellular pathway. To further understand the in vivo role of one of these human genes (FANCG), we generated a targeted disruption of murine Fancg and bred mice homozygous for the targeted allele. Similar to the phenotype of the previously described Fancc(-/-) and Fanca(-/-) mice, the Fancg(-/-) mice had normal viability and no gross developmental abnormalities. Primary splenic lymphocytes, bone marrow progenitor cells, and murine embryo fibroblasts from the Fancg(-/-) mice demonstrated spontaneous chromosome breakage and increased sensitivity to mitomycin C and, to a lesser extent, ionizing radiation. Fancg(-/-) lymphocytes had a defect in the FA pathway, based on their failure to activate the monoubiquitination of the downstream Fancd2 protein in response to IR. Finally, Fancg(-/-) mice had decreased fertility and abnormal gonadal histology. In conclusion, disruption of the Fancg gene confirms the role of Fancg in the FA pathway. The Fancg(-/-) mouse may be useful as an animal model for future gene therapy and cancer susceptibility studies.
PK10453, a Nonselective Platelet‐Derived Growth Factor Receptor Inhibitor, Prevents the Progression of Pulmonary Arterial Hypertension (2014)

The platelet-derived growth factor (PDGF) signaling pathway has been found to be activated in human pulmonary arterial hypertension (PAH) and in animal models of the disease. Our study tested the hypothesis that a novel, nonselective inhaled PDGF receptor inhibitor, PK10453, would decrease pulmonary hypertension both in the rat monocrotaline (MCT) model and the rat MCT plus pneumonectomy (MCT+PN) model of PAH. PK10453, delivered by inhalation for 4 (D4)- and 8 (D8)-minute exposures 3 times a day for 2 weeks, decreased right ventricular systolic pressure (RVSP) in both the rat MCT and rat MCT+PN models: RVSP was 80.4 ± 2.6 mmHg in the vehicle MCT group (n = 6), 44.4 ± 5.8 mmHg in the D4 MCT group (n = 6), and 37.1 ± 4.5 mmHg in the D8 MCT group (n = 5; P < 0.001 vs. vehicle); RVSP was 75.7 ± 7.1 mmHg in the vehicle MCT+PN group (n = 9), 40.4 ± 2.7 mmHg in the D4 MCT+PN group (n = 10), and 43.0 ± 3.0 mmHg in the D8 MCT+PN group (n = 8; P < 0.001). In the rat MCT+PN model, continuous telemetry monitoring of pulmonary artery pressures also demonstrated that PK10453 prevented the progression of PAH. Imatinib given by inhalation was equally effective in the MCT model but was not effective in the MCT+PN model. Immunohistochemistry demonstrated increased activation of the PDGFβ receptor compared to the PDGFα receptor in neointimal and perivascular lesions found in the MCT+PN model. We show that imatinib is selective for the PDGFα receptor, whereas PK10453 has a lower half-maximal inhibitor concentration (IC50) for inhibition of kinase activity of both the PDGFα and PDGFβ receptors compared to imatinib. In conclusion, PK10453, when delivered by inhalation, significantly decreased the progression of PAH in the rat MCT and MCT+PN models. Nonselective inhibition of both the PDGFα and PDGFβ receptors may have a therapeutic advantage over selective PDGFα receptor inhibition in PAH.
A Phase I Pharmacokinetic and Pharmacodynamic Study of TKI258, an Oral, Multitargeted Receptor Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors (2008)

The MTD was defined as 125 mg/d. Evidence of antitumor activity in melanoma and gastrointestinal stromal tumors warrants further investigation, and other phase I studies are ongoing. Further pharmacodynamic evaluation is required in these studies to evaluate the biological effects of TKI258.
Retinoic Acid Treatment Induces the Ectopic Exporession of Retinoic Acid Receptor β Gene and Excessive Cell Death in the Embryonic Mouse Face (1992)

Maternal treatment with 100 mg/kg of retinoic acid (RA) on day 9 of gestation in mice caused craniofacial abnormalities of the mandibulofacial dysostosis type. The abnormal morphology was attributed to the excessive cell death in the dorsal aspects of the maxillary and mandibular prominences of the first pharyngeal arch and in the proximal region of the mandibular prominence. To investigate the expression of the RA receptor (RAR) genes in abnormal face morphogenesis, in situ hybridization was performed. The distribution patterns of RAR α and γ transcripts were not altered in the treated embryos. By contrast, the teratogenic dose of RA increased the level of RAR β transcripts, as early as 3 hr after RA-treatment, in the regions where the RAR β expression is at a low level in normal development. The increase of RAR β transcripts was detected by 12 hr, and declined to the low level within 24 hr after the treatment. The regions where ectopic expression of RAR β gene was observed included the areas where the excessive cell death occurred 9-12 hr after RA-treatment. These results suggest that ectopic induction of RAR β by RA may lead to the excessive cell death, threfore may cause abnormal morphogenesis.
Migrants and Motives: Religion and the Settlement of New England, 1630-1640 (1985)

N oman, perhaps, would seem to have been an unlikelier candidate for transatlantic migration than John Bent. He had never shown any particular interest in moving; indeed, in 1638, at the age of forty-one, Bent still lived in Weyhill, Hampshire, where both he and his father before him had been born. Having prospered in the village of his birth, John Bent held enough land to distinguish himself as one of Weyhill's wealthiest inhabitants. One might reasonably expect that Bent's substantial economic stake, combined with his growing familial responsibilities-which by 1638 included a wife and five children-would have provided him with ample incentive to stay put. By embarking on a transatlantic voyage-moving for the first time in his life and over a vast distance-Bent would exchange an economically secure present for a highly uncertain future and venture his family's lives and fortunes no less than his own. Yet in the spring of 1638, Bent returned his Weyhill land to the lord of the manor, gathered his family and possessions, and traveled twenty-five miles to the port of Southampton. There, he and his fam-
Linear modes of gene expression determined by independent component analysis (2002)

Studying cell cycle-related gene expression in yeast, we found that the dominant expression modes could be related to distinct biological functions, such as phases of the cell cycle or the mating response. Analysis of human lymphocytes revealed modes that were related to characteristic differences between cell types. With both data sets, the linear influences of the dominant modes showed distributions with large tails, indicating the existence of specifically up- and downregulated target genes. The expression modes and their influences can be used to visualize the samples and genes in low-dimensional spaces. A projection to expression modes helps to highlight particular biological functions, to reduce noise, and to compress the data in a biologically sensible way.
Eosinophilia in the Ethmoid Mucosa and Its Relationship to the Severity of Inflammation in Chronic Rhinosinusitis (2002)

Eosinophilic mucosal inflammation represents the most severe inflammatory changes of the mucosa. Twenty to forty percent of the patients with chronic rhinosinusitis had no eosinophilic inflammation of the mucosa. The CT-staging system of Lund-Mackay correlated with the extent of mucosal inflammation.
The use of name spaces in Plan 9 (1993)

Plan 9 is a distributed system built at the Computing Sciences Research Center of AT&amp;amp;T Bell Laboratories over the last few years. Its goal is to provide a production-quality system for software development and general computation using heterogeneous hardware and minimal software. A Plan 9 system comprises CPU and file servers in a central location connected together by fast networks. Slower networks fan out to workstation-class machines that serve as user terminals. Plan 9 argues that given a few carefully implemented abstractions it is possible to produce a small operating system that provides support for the largest systems on a variety of architectures and networks. The foundations of the system are built on two ideas: a per-process name space and a simple message-oriented file system protocol.
TP53 mutation‐correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53‐mutated breast cancers (2014)

Breast cancers (BC) carry a complex set of gene mutations that can influence their gene expression and clinical behavior. We aimed to identify genes driven by the TP53 mutation status and assess their clinical relevance in estrogen receptor (ER)-positive and ER-negative BC, and their potential as targets for patients with TP53 mutated tumors. Separate ROC analyses of each gene expression according to TP53 mutation status were performed. The prognostic value of genes with the highest AUC were assessed in a large dataset of untreated, and neoadjuvant chemotherapy treated patients. The mitotic checkpoint gene MPS1 was the most significant gene correlated with TP53 status, and the most significant prognostic marker in all ER-positive BC datasets. MPS1 retained its prognostic value independently from the type of treatment administered. The biological functions of MPS1 were investigated in different BC cell lines. We also assessed the effects of a potent small molecule inhibitor of MPS1, SP600125, alone and in combination with chemotherapy. Consistent with the gene expression profiling and siRNA assays, the inhibition of MPS1 by SP600125 led to a reduction in cell viability and a significant increase in cell death, selectively in TP53-mutated BC cells. Furthermore, the chemical inhibition of MPS1 sensitized BC cells to conventional chemotherapy, particularly taxanes. Our results collectively demonstrate that TP53-correlated kinase MPS1, is a potential therapeutic target in BC patients with TP53 mutated tumors, and that SP600125 warrant further development in future clinical trials.
Beyond the Standard of Care: A Review of Novel Immunotherapy Trials for the Treatment of Lung Cancer (2013)

Recent clinical trials in lung cancer demonstrate the potential of immunotherapeutics to increase overall survival in patients with lung cancer compared with the current standard of care.
Heteromeric Assembly of Acid-sensitive Ion Channel and Epithelial Sodium Channel Subunits (2007)

Amiloride-sensitive ion channels are formed from homo- or heteromeric combinations of subunits from the epithelial Na+ channel (ENaC)/degenerin superfamily, which also includes the acid-sensitive ion channel (ASIC) family. These channel subunits share sequence homology and topology. In this study, we have demonstrated, using confocal fluorescence resonance energy transfer microscopy and co-immunoprecipitation, that ASIC and ENaC subunits are capable of forming cross-clade intermolecular interactions. We have also shown that combinations of ASIC1 with ENaC subunits exhibit novel electrophysiological characteristics compared with ASIC1 alone. The results of this study suggest that heteromeric complexes of ASIC and ENaC subunits may underlie the diversity of amiloride-sensitive cation conductances observed in a wide variety of tissues and cell types where co-expression of ASIC and ENaC subunits has been observed.
Practical automated filter generation to explicitly enforce implicit input assumptions (2005)

Vulnerabilities in distributed applications are being uncovered and exploited faster than software engineers can, patch the security holes. All too often these weaknesses result from implicit assumptions made by an application about its inputs. One approach to defending against their exploitation is to interpose a filter between the input source and the application that verifies that the application's assumptions about its inputs actually hold. However, ad hoc design of such filters is nearly as tedious and error-prone as patching the original application itself. We have automated the filter generation process based on a simple formal description of a broad class of assumptions about the inputs to an application. Focusing on the back-end server application case, we have prototyped an easy-to-use tool that generates server-side filtering scripts. These can then be quickly installed on a front-end webs server (either in concert with the application or., when a vulnerability is uncovered), thus shielding the server application from a variety of existing and exploited, attacks, as solutions requiring changes to the applications are developed and tested. Our measurements suggest that input filtering can be done efficiently and should not be a performance concern for moderately loaded web servers. The overall approach may be generalizable to other domains, such as firewall filter generation and API wrapper filter generation.
Collaborative Editing - distribution and replication of shared versioned objects (1995)

Position paper. We take the starting point in a system for collabora-tive editing in a distributed environment. It includes integrated sup-port for fine-grained version control and configuration management. We describe how such object can be migrated to independent sites, edited, and then merged into one object with several alternatives. We also show that our model is meaningful to understand other applica-tions. 1
The role of graft materials in suture augmentation for tendon repairs and reattachment (2005)

Various biomaterials have been used to augment sutures for the repair and reattachment of tendons. This study examined four different graft materials in a simple and reproducible model using chicken Achilles tendons to determine the strength and mechanism of suture reinforcement of tendon repairs. The graft materials tested were Gore-Tex(R) Soft Tissue Patch, Graftjacket, bovine pericardium, and an experimental graft material from Xylos Corporation. Testing was performed in shear to simulate forces on a torn tendon repair and pull-off to simulate those on a tendon reattachment to bone. Compared to unaugmented suture, grafts increased suture fixation strength from 10% to 60% in shear and from 0% to 36% in pull-off with the bovine pericardium graft, providing significant improvement in both tests. In no cases (even unaugmented) did the suture pull directly through the tendon, but instead sliced along it, demonstrating that the interface between the suture and the tendon determines fixation strength. Grafts function by increasing the area, friction, and nature of this interface, not by acting as a barrier for suture pull-through.
Simulation of surface evolution during ion bombardment (1988)

Some theoretical aspects of surface topography evolution during ion beam erosion are discussed. In particular, the theory of characteristics is considered in some detail and its limitations pointed out. Further theoretical development based on the Huygens principle of wave propagation is discussed also with respect to numerical evaluation of surface evolution. A new numerical algorithm based on the contemporary theoretical concepts of surface and edge propagation is proposed and compared with existing numerical models and theoretical expectations.
SYFPEITHI (2007)

Reverse immunology has been used for about 12 years in order to identify T-cell epitopes from pathogens or tumor-associated antigens. In this chapter, we discuss the advantages and pitfalls of T-cell epitope prediction compared to classical experimental procedures such as epitope mapping and cloning experiments. We introduce our three established programs, SYFPEITHI, PAProc, and SNEP, which are freely accessible at no cost in the World Wide Web for the prediction of either HLA-peptide binding or proteasomal processing of antigens. We demonstrate the performance of our epitope prediction programs with several examples and in comparison to other epitope prediction programs available. We also reflect the actual possibilities and limitations of such computer-aided work.
Protein quantification from complex protein mixtures using a proteomics methodology with single-cell resolution (2001)

We have developed an extremely sensitive technique, termed immuno-detection amplified by T7 RNA polymerase (IDAT) that is capable of monitoring proteins, lipids, and metabolites and their modifications at the single-cell level. A double-stranded oligonucleotide containing the T7 promoter is conjugated to an antibody (Ab), and then T7 RNA polymerase is used to amplify RNA from the double-stranded oligonucleotides coupled to the Ab in the Ab-antigen complex. By using this technique, we are able to detect the p185(her2/neu) receptor from the crude lysate of T6-17 cells at 10(-13) dilution, which is 10(9)-fold more sensitive than the conventional ELISA method. Single-chain Fv fragments or complementarity determining region peptides of the Ab also can be substituted for the Ab in IDAT. In a modified protocol, the oligonucleotide has been coupled to an Ab against a common epitope to create a universal detector species. With the linear amplification ability of T7 RNA polymerase, IDAT represents a significant improvement over immuno-PCR in terms of sensitivity and has the potential to provide a robotic platform for proteomics.
Antimycobacterial activities of antisense oligodeoxynucleotide phosphorothioates in drug-resistant strains. (1996)

Strains of Mycobacterium smegmatis, a mycobacterium which shares genetic sequences, grows more rapidly, and is nonpathogenic in man as compared with Mycobacterium tuberculosis, were utilized for the initial development of new antimycobacterial therapy. Drug-resistant strains of M. smegmatis which are known to arise in a manner identical to the emergence of drug-resistant strains of M. tuberculosis were isolated and utilized as models for the antimycobacterial activities of modified and unmodified oligodeoxynucleotide phosphorothioates in broth cultures. Under normal conditions, oligodeoxynucleotide phosphorothioates do not enter mycobacteria, and several strategies were successfully utilized to afford entry of oligonucleotides into the mycobacterial cells. One involved the presence of very low levels of ethambutol, which enables the entry of oligonucleotides into mycobacteria because of its induced alterations in the cell wall, and another involved the utilization of oligonucleotides covalently attached to a D-cycloserine molecule, whereby entry into the mycobacterial cell is achieved by a receptor-mediated process. Another low molecular weight, covalently attached ligand that enabled the entry and subsequent antimycobacterial activities of oligodeoxynucleotide phosphorothioates in the absence of a cell wall modifying reagent was biotin. Significant sequence-specific growth inhibition of wild-type, as well as of drug-resistant, M. smegmatis was obtained by modified oligonucleotides complementary in sequence to a specific region of the mycobacterium aspartokinase (ask) gene when utilized in combinations with ethambutol (as compared to ethambutol alone) or as D-cycloserine or biotin covalent adducts without the presence of any other cytotoxic or cytostatic agent.
Immunogenicity and Antitumor Effects of Vaccination with Peptide Vaccine +/− Granulocyte-Monocyte Colony-Stimulating Factor and/or IFN-α2b in Advanced Metastatic Melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696 (2009)

Immune response to vaccination correlates with prolonged survival in patients with metastatic melanoma and is not enhanced by immunomodulatory cytokines as tested in this trial.