gebhart/patrepeval huggingface dataset:
Modulation of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) by interferon-γ in a human salivary gland cell line (1997)

Gelatinases have been shown to be regulated by many cytokines and growth factors, and have been implicated in the pathogenesis of certain autoimmune diseases via tissue destruction. High levels of several cytokines, including IFN-gamma and TNF-alpha, have been demonstrated in the salivary gland microenvironment of patients with Sjogren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of this disease is not well understood. We hypothesized that IFN-gamma with or without (+/-) TNF-alpha could be playing a role in the pathogenesis of SS via the regulation of matrix metalloproteinase (MMP) levels. This study examined the role of IFN-gamma and (+) TNF-alpha in the regulation of the matrix metalloproteinases, MMP-2 (72 kD gelatinase A) and MMP-9 (92 kD gelatinase B). A human salivary gland cell line (HSG) has been used as a possible in vitro model to study the role of IFN-gamma + TNF-alpha in the pathogenesis of SS. The HSG cell line, in the presence of IFN +/- TNF-alpha, displays increased MMP-2 and MMP-9 gelatinolytic activity, protein and RNA levels. The increase in MMP activity was partially blocked with an antibody against the IFN-gamma receptor, and this was associated with a complete inhibition of the previously described IFN-gamma +/- TNF-alpha antiproliferative effect. However, incubation of IFN-gamma treated HSG cells with the synthetic MMP inhibitor BB94 did not alleviate this antiproliferative effect. In addition, we demonstrate that there are very high levels of MMP-9 in the saliva of patients with SS when compared to healthy control subjects. These data suggest that cytokines could be regulating MMP production by salivary epithelial cells and thus indicate a potential role for these cells in the pathogenesis of SS.
Metabonomics: the use of electrospray mass spectrometry coupled to reversed‐phase liquid chromatography shows potential for the screening of rat urine in drug development (2002)

The application of liquid chromatography/mass spectrometry (LC/MS) followed by principal components analysis (PCA) has been successfully applied to the screening of rat urine following the administration of three candidate pharmaceuticals. With this methodology it was possible to differentiate the control samples from the dosed samples and to identify the components of the mass spectrum responsible for the separation. These data clearly show that LC/MS is a viable alternative, or complementary, technique to proton NMR for metabonomics applications in drug discovery and development.
Tumor irradiation enhances the tumor-specific distribution of poly(L-glutamic acid)-conjugated paclitaxel and its antitumor efficacy. (2000)

The poly(L-glutamic acid)-paclitaxel (PG-TXL) conjugate has been shown to exhibit significantly greater antitumor activity than conventionally formulated paclitaxel (TXL) against solid tumors (Li et al., Cancer Res., 58: 2404-2409, 1998). Here we report that local tumor irradiation enhanced the distribution of PG-TXL given 24 h later to ovarian OCa-1 carcinoma implanted i.m. in C3Hf/Kam mice. Radiation significantly increased tumor uptake of PG-TXL and tumor vascular permeability, caused elevation of the serum concentration of vascular endothelial growth factor, and arrested OCa-1 cells in the G1 phase of cell cycle. The enhancement factors, as measured by incremental tumor growth delay compared with PG-TXL alone, ranged from 1.36-4.44. Complete tumor regression was also observed at a higher radiation dose (>10 Gy) and a higher PG-TXL dose (>80 mg equivalentTXL/kg). Furthermore, combined radiation and PG-TXL produced a significantly greater tumor growth delay than treatment with radiation and TXL when both drugs were given at the same equivalent TXL dose of 60 mg/kg 24 h after tumor irradiation (enhancement factors, 4.44 versus 1.50). These data suggest that conjugation of TXL to poly(L-glutamic acid) is necessary for improved response and that the supra-additive effect of combined radiation and PG-TXL therapy is due in part to modulation of the enhanced permeability and retention effect of macromolecules by radiation. We propose a treatment strategy combining radiation and macromolecular chemotherapy that may have important clinical implications in terms of scheduling and optimization of the therapeutic ratio.
rac, a novel ras-related family of proteins that are botulinum toxin substrates (1989)

A new family of ras-related proteins, designated rac (ras-related C3 botulinum toxin substrate) has been identified. rac1 and rac2 cDNA clones were isolated from a differentiated HL-60 library and encode proteins that are 92% homologous and share 58% and 26-30% amino acid homology with human rhos and ras, respectively. Nucleotide sequence analysis predicts both rac1 and rac2 proteins to contain 192 amino acids with molecular masses of 21,450 and 21,429 daltons, respectively. rac1 and rac2 possess four of the five conserved functional domains in ras associated with binding and hydrolysis of guanine nucleotides. They also contain the COOH-terminal consensus sequence Cys-X-X-X-COOH which localizes ras to the inner plasma membrane and the residues Gly12 and Ala59, at which sites mutations elicit transforming potential to ras. The rac transcripts, particularly rac2, display relative myeloid tissue selectivity. Both rac1 transcripts (2.4 and 1.1 kilobases (kb] increase when HL-60 cells differentiate to neutrophil-like morphology. In contrast, differentiation of U937 cells to monocyte-like morphology causes no change in the 2.4-kb mRNA and a decrease in the 1.1-kb mRNA species. rac2 mRNA (1.45 kb) increases 7-9-fold and 3-fold upon differentiation of HL-60 and U937 cells, respectively. Neither rac mRNAs are present in a Jurkat T cell line, and unlike rac1, rac2 mRNA is absent in human brain and liver tissue. Transfection experiments permitted the demonstration that rac1 and rac2 are substrates for ADP-ribosylation by the C3 component of botulinum toxin. The data suggest that racs are plasma membrane-associated GTP-binding proteins which could regulate secretory processes, particularly in myeloid cells.
Metaphylactic Effect of Mitomycin C with and without Hyaluronidase after Transurethral Resection of Bladder Cancer: Randomized Trial (1989)

In a randomized trial 2 groups of 28 patients who had undergone transurethral resection of bladder tumors were treated with 20 mg. mitomycin C alone or with 200,000 units hyaluronidase to determine whether adjuvant hyaluronidase would improve tumor recurrence rates. Patient groups were comparable statistically. In the group receiving additive hyaluronidase the percentage of tumor recurrences was decreased significantly (p less than 0.05). Side effects were not increased. Thus, adjuvant hyaluronidase appears to have a role in the metaphylaxis of bladder tumors. The potential reduction of the hyaluronidase dose without loss of protective action and the role of additive hyaluronidase in the systemic treatment of metastatic urothelial tumors remain to be investigated.
SSAHA: A Fast Search Method for Large DNA Databases (2001)

We describe an algorithm, SSAHA (Sequence Search and Alignment by Hashing Algorithm), for performing fast searches on databases containing multiple gigabases of DNA. Sequences in the database are preprocessed by breaking them into consecutive k-tuples of k contiguous bases and then using a hash table to store the position of each occurrence of each k-tuple. Searching for a query sequence in the database is done by obtaining from the hash table the "hits" for each k-tuple in the query sequence and then performing a sort on the results. We discuss the effect of the tuple length k on the search speed, memory usage, and sensitivity of the algorithm and present the results of computational experiments which show that SSAHA can be three to four orders of magnitude faster than BLAST or FASTA, while requiring less memory than suffix tree methods. The SSAHA algorithm is used for high-throughput single nucleotide polymorphism (SNP) detection and very large scale sequence assembly. Also, it provides Web-based sequence search facilities for Ensembl projects.
High performance shape memory polymer networks based on rigid nanoparticle cores (2010)

Smart materials that can respond to external stimuli are of widespread interest in biomedical science. Thermal-responsive shape memory polymers, a class of intelligent materials that can be fixed at a temporary shape below their transition temperature (T(trans)) and thermally triggered to resume their original shapes on demand, hold great potential as minimally invasive self-fitting tissue scaffolds or implants. The intrinsic mechanism for shape memory behavior of polymers is the freezing and activation of the long-range motion of polymer chain segments below and above T(trans), respectively. Both T(trans) and the extent of polymer chain participation in effective elastic deformation and recovery are determined by the network composition and structure, which are also defining factors for their mechanical properties, degradability, and bioactivities. Such complexity has made it extremely challenging to achieve the ideal combination of a T(trans) slightly above physiological temperature, rapid and complete recovery, and suitable mechanical and biological properties for clinical applications. Here we report a shape memory polymer network constructed from a polyhedral oligomeric silsesquioxane nanoparticle core functionalized with eight polyester arms. The cross-linked networks comprising this macromer possessed a gigapascal-storage modulus at body temperature and a T(trans) between 42 and 48 degrees C. The materials could stably hold their temporary shapes for > 1 year at room temperature and achieve full shape recovery <or= 51 degrees C in a matter of seconds. Their versatile structures allowed for tunable biodegradability and biofunctionalizability. These materials have tremendous promise for tissue engineering applications.
Expression of Janus Kinase 3 in Human Endothelial and Other Non-lymphoid and Non-myeloid Cells (1996)

Members of the Janus kinase (Jak) family of protein tyrosine kinases have recently been implicated in the proximal signal transduction events of cytokine receptors. Jak3, a newly discovered member of this family, is believed to be normally limited in its expression to cells of the lymphoid and myeloid lineages. Herein we show that Jak3 is expressed in primary human vascular cells, as well as other non-lymphoid and non-myeloid cell types. Reverse transcriptase-polymerase chain reaction and Northern blot analysis revealed that Jak3 mRNA was expressed at low levels in human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells (HASMC), A549 (human lung carcinoma), and DLD-1 (human colon adenocarcinoma) cells. Higher basal levels of Jak3 mRNA were detected in HMEC-1 (human microvascular cell line) and HepG2 (human hepatocellular carcinoma) cells. Jak3 mRNA expression was induced in HUVEC, HMEC-1, and HASMC by treatment with interleukin-1beta, tumor necrosis factor-alpha, interferon-gamma, and lipopolysaccharide. Jak3 protein was detectable at low levels in untreated HMEC-1, and these levels increased significantly with cytokine treatment. Furthermore, Jak3 protein was phosphorylated upon treatment of these cells with interleukin-4. This work shows that Jak3 is expressed or inducible in human vascular endothelial, vascular smooth muscle, and other non-lymphoid and non-myeloid cells, suggesting a broader role for Jak3 in the cytokine signal transduction of these cells.
Interactions of human papillomavirus transforming proteins with the products of tumor suppressor genes (1993)

Human papillomaviruses (HPVs) contribute to the development of almost all cervical cancers, a common and often fatal human disease. The mechanisms by which the HPVs function in malignant progression appear to be related to the activity of the two viral oncoproteins, E6 and E7, which form complexes with several cell proteins normally involved in controlling cell growth. Of particular interest has been the association of E6 with p53 and E7 with Rb, both products of tumor suppressor genes. Expression of E6 and E7 is likely to overcome the regulation of cell proliferation normally mediated by proteins like p53 and Rb, allowing uncontrolled growth and providing the potential for malignant transformation. These activities of E6 and E7 support the importance of the tumor suppressor proteins in the maintenance of normal cell proliferation and provide novel approaches to understanding the mechanisms by which they function.
Epidermal Growth Factor Receptor Pathway Analysis Identifies Amphiregulin as a Key Factor for Cisplatin Resistance of Human Breast Cancer Cells (2007)

The use of platinum complexes for the therapy of breast cancer is an emerging new treatment modality. To gain insight into the mechanisms underlying cisplatin resistance in breast cancer, we used estrogen receptor-positive MCF-7 cells as a model system. We generated cisplatin-resistant MCF-7 cells and determined the functional status of epidermal growth factor receptor (EGFR), MAPK, and AKT signaling pathways by phosphoreceptor tyrosine kinase and phospho-MAPK arrays. The cisplatin-resistant MCF-7 cells are characterized by increased EGFR phosphorylation, high levels of AKT1 kinase activity, and ERK1 phosphorylation. In contrast, the JNK and p38 MAPK modules of the MAPK signaling pathway were inactive. These conditions were associated with inactivation of the p53 pathway and increased BCL-2 expression. We investigated the expression of genes encoding the ligands for the ERBB signaling cascade and found a selective up-regulation of amphiregulin expression, which occurred at later stages of cisplatin resistance development. Amphiregulin is a specific ligand of the EGFR (ERBB1) and a potent mitogen for epithelial cells. After exposure to cisplatin, the resistant MCF-7 cells secreted amphiregulin protein over extended periods of time, and knockdown of amphiregulin expression by specific short interfering RNA resulted in a nearly complete reversion of the resistant phenotype. To demonstrate the generality and importance of our findings, we examined amphiregulin expression and cisplatin resistance in a variety of human breast cancer cell lines and found a highly significant correlation. In contrast, amphiregulin levels did not significantly correlate with cisplatin resistance in a panel of lung cancer cell lines. We have thus identified a novel function of amphiregulin for cisplatin resistance in human breast cancer cells.
Selection for Resistance to mCry3A-Expressing Transgenic Corn in Western Corn Rootworm (2011)

To investigate the development of resistance to mCry3A, a laboratory colony of the western corn rootworm, Diabrotica virgifera virgifera LeConte, was established from field survivors of mCry3A-expressing (MIR604) corn, Zea mays L. Feral adults emerging from MIR604 (selected) and isoline (control) field plots were collected and returned to the laboratory. Progeny of each colony was reared one generation on isoline corn and then crossed reciprocally with a nondiapausing colony. The resulting nondiapausing progeny were then reared on greenhouse corn in accordance with the wild type parent's origin (on MIR604 or isoline corn). After four, seven, and 10 total generations of selection, the resistance ratio of the selected colony was 0.5, 4.3, and 15.4 in terms of lethal concentration (LC)50 values in toxicity assays, with the latter two LC50 values being significant. After seven generations of selection in total, selected and control colonies were screened on MIR604 and isoline corn under field conditions. There was a significant colony x corn pedigree interaction in terms of plant damage. There was no significant difference in damage between MIR604 and isoline corn, whereas this difference was significant for the control colony. After 14 generations of selection, a seedling bioassay was performed. Again, there was a significant colony x corn pedigree interaction, this time in terms of the number of larvae recovered. There was no significant difference in the number of larvae recovered from MIR604 and isoline corn for the selected colony, whereas this difference was significant for the control colony, although larval size was greater on isoline corn for both colonies. Resistance has developed in western corn rootworm laboratory colonies to all Bt proteins currently registered for corn rootworm management, which emphasizes the importance of adhering to resistance management plans for maintaining product efficacy.
Immunotyping of Chlamydia trachomatis with Monoclonal Antibodies (1985)

Rapid and precise immunotyping of Chlamydia trachomatis was achieved by testing whole organisms (elementary bodies) in the microimmunofluorescence test with monoclonal antibodies. Monoclonal antibodies were produced with standard techniques by using an immunization schedule that encouraged the development of immunotype-specific antibodies. Fifteen monotypic or multitypic (subspecies) monoclonal antibodies were chosen for use in a two-step typing system that required strains of C. trachomatis to be tested against six to eight monoclonal antibodies for classification. Immunotyping with monoclonal antibodies was studied by testing 313 strains, typed with the previous method that utilized immunized mouse antisera, that represented each of the 15 established serovars. The two-step monoclonal antibody method resulted in a classification similar to the current one. Only one strain typed differently with the two methods. With the monoclonal antibody method, available lymphogranuloma venereum (LGV) serovars L1 and L3 could not be differentiated from trachoma serovars E and G, respectively, unless the strains had been identified as LGV. Monoclonal antibody typing was simpler to perform and more precise; it allowed easy differentiation between closely related serovars. Three new types were discovered among the strains previously classified as serovars D, I, and L2. These are tentatively being considered subtypes and are labeled D', I', and L2'.
Paclitaxel-resistant Human Ovarian Cancer Cells Have Mutant β-Tubulins That Exhibit Impaired Paclitaxel-driven Polymerization (1997)

Acquired resistance to paclitaxel can be mediated by P-glycoprotein or by alterations involving tubulin. We report two paclitaxel-resistant sublines derived from 1A9 human ovarian carcinoma cells. Single-step paclitaxel selection with verapamil yielded two clones that are resistant to paclitaxel and collaterally sensitive to vinblastine. The resistant sublines are not paclitaxel-dependent, and resistance remained stable after 3 years of drug-free culture. All cell lines accumulate [3H]paclitaxel equally, and no MDR-1 mRNA was detected by polymerase chain reaction following reverse transcription. Total tubulin content is similar, but the polymerized fraction increased in parental but not in resistant cells following the paclitaxel addition. Purified tubulin from parental cells demonstrated paclitaxel-driven increased polymerization, in contrast to resistant cell tubulin, which did not polymerize under identical conditions. In contrast, epothilone B, an agent to which the resistant cells retained sensitivity, increased assembly. Comparable expression of beta-tubulin isotypes was found in parental and resistant cells, with predominant expression of the M40 and beta2 isotypes. Sequence analysis demonstrated acquired mutations in the M40 isotype at nucleotide 810 (T --> G; Phe270 --> Val) in 1A9PTX10 cells and nucleotide 1092 (G --> A; Ala364 --> Thr) in 1A9PTX22 cells. These results identify residues beta270 and beta364 as important modulators of paclitaxel's interaction with tubulin.
Interaction of picornavirus 2C polypeptide with the viral negative-strand RNA (2001)

The picornavirus membrane-associated polypeptide 2C is believed to be required for viral RNA synthesis. Hepatitis A virus (HAV)- and human rhinovirus (HRV)-encoded recombinant 2C proteins have been expressed, purified and examined for their ability to interact with the terminal sequences of viral positive- and negative-strand RNAs. The results demonstrate that both the HAV- and the HRV-encoded 2C polypeptide specifically interact with the 3'-terminal sequences of the negative-strand RNA, but not with the complementary sequences at the 5' terminus of the positive-strand RNA. This interaction was detected by both mobility gel shift and UV cross-linking assays. Furthermore, complex formation exhibited dose-dependency and competition assays confirmed specificity. These results are consistent with our previous observation using the poliovirus 2C protein. The implication of the picornavirus 2C protein binding to the 3'-terminal sequence of the negative-strand untranslated region in viral RNA synthesis is discussed.
Femtosecond Laser Flap Creation for Laser in situ Keratomileusis: Six-month Follow-up of Initial U.S. Clinical Series (2003)

Femtosecond laser corneal flap creation is a safe and effective alternative to traditional mechanical microkeratomes. Standard LASIK nomograms appeared to apply equally well to the all-laser LASIK procedures. The potential for improved flap safety, reproducibility, flexibility, as well as for additional corneal applications are now being explored.
High-Precision Pointing and Attitude Determination and Control on ExoplanetSat (2012)

ExoplanetSat is a 10 10 34-cm, 5-kg space telescope designed to detect exoplanets around the brightest Sun-like stars via the transit method. Achieving this objective while meeting strict mass, volume, and power constraints necessitates an innovative highprecision pointing and attitude determination and control subsystem (ADCS) design. This paper will present the overall ADCS hardware and software design of ExoplanetSat. The software description will focus on the payload operation during slews (ecient window generation for stars entering the eld of view) as well as the guidance, navigation, and control algorithms for high-precision pointing with two-stage actuation. Analyses and results on the achievable pointing precision using a high-delity simulation will be presented. To demonstrate this two-stage control idea in hardware, a testbed on a spherical air bearing was designed, fabricated, and tested at the Massachusetts Institute of Technology (MIT) Space Systems Laboratory (SSL) in collaboration with Draper Laboratory. This hardwarein-the-loop testbed successfully demonstrated precision pointing, raising this subsystem to a technology readiness level (TRL) of 5. Furthermore, results from this testbed were used to validate the simulation results, thereby increasing the condence in results produced by the simulation.