gebhart/patrepeval huggingface dataset:
Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity. (1999)

Inhibitors of tumor angiogenesis and metastasis are rapidly emerging as important new drug candidates for cancer therapy. To facilitate the identification of such drugs, we recently developed novel and rapid in vitro assays for human angiogenesis and for the extracellular matrix-degrading enzyme heparanase, which has been implicated in tumor metastasis. In this study, sulfated oligosaccharides, which are structural mimics of heparan sulfate, were investigated as drug candidates because these compounds may interfere with heparan sulfate recognition by many angiogenic growth factors and may inhibit cleavage of heparan sulfate by heparanase. In the preliminary screening studies, it was found that inhibitory activity in both assay systems was critically dependent on chain length and degree of sulfation, highly sulfated linear oligosaccharides of five or more monosaccharides in length being the most active. However, two sulfated oligosaccharides stood out as potential antitumor drugs, phosphomannopentaose sulfate (PI-88) and maltohexaose sulfate, both of these compounds having the important property of simultaneously being potent inhibitors of in vitro angiogenesis and heparanase activity. Due to the ease of manufacture of the starting material, phosphomannopentaose, PI-88 was studied in more detail. PI-88 was shown to inhibit the primary tumor growth of the highly invasive rat mammary adenocarcinoma 13762 MAT by approximately 50%, inhibit metastasis to the draining popliteal lymph node by approximately 40%, and reduce the vascularity of tumors by approximately 30%, all of these effects being highly significant. Acute hematogenous metastasis assays also demonstrated that PI-88 was a potent (>90%) inhibitor of blood-borne metastasis. Thus, by the use of novel in vitro screening procedures, we have identified a promising antitumor agent.
Bridging infectious disease vaccines with cancer immunotherapy: a role for targeted RNA based immunotherapeutics (2015)

Tumor-specific immunotherapy holds the promise of eradicating malignant tumors with exquisite precision without additional toxicity to standard treatments. Cancer immunotherapy has conventionally relied on cell-mediated immunity while successful infectious disease vaccines have been shown to induce humoral immunity. Efficacious cancer immunotherapeutics likely require both cellular and humoral responses, and RNA based cancer vaccines are especially suited to stimulate both arms of the immune system. RNA is inherently immunogenic, inducing innate immune responses to initiate cellular and humoral adaptive immunity, but has limited utility based on its poor in vivo stability. Early work utilized 'naked' RNA vaccines, whereas more recent efforts have attempted to encapsulate RNA thereby protecting it from degradation. However, feasibility has been limited by a lack of defined and safe targeting mechanisms for the in vivo delivery of stabilized RNA. As new cancer antigens come to the forefront with novel RNA encapsulation and targeting techniques, RNA vaccines may prove to be a vital, safe and robust method to initiate patient-specific anti-tumor efficacy.
STAT3 and HIF1α Signaling Drives Oncogenic Cellular Phenotypes in Malignant Peripheral Nerve Sheath Tumors (2015)

This research reveals that aberrant STAT3 and HIF1a activity drives tumor progression in MPNSTs, indicating that inhibition of the STAT3/HIF1α/VEGF-A signaling axis is a viable treatment strategy.
Multifunctional reconfigurable MEMS integrated antennas for adaptive MIMO systems (2004)

Multi-input multi-output systems with associated technologies such as smart antennas and adaptive coding and modulation techniques enhance channel capacity, diversity, and robustness of wireless communications as has been proven by many recent research results both in theory and experiments. This article focuses on the antenna aspect of MIMO systems. In particular, we emphasize the important role of the reconfigurable antenna and its links with space-time coding techniques that can be employed for further exploitation of the theoretical performance of MIMO wireless systems. The advantages of the reconfigurable antenna compared to the traditional smart antenna are discussed. Establishment of reconfigurable antennas requires novel radio frequency microelectromechanical systems technology, which has recently been developed in the authors' group. We briefly introduce this technology with emphasis on its distinct advantages over existing silicon-based MEMS technologies for reconfigurable antennas. A reconfigurable antenna design that can change its operating frequency and radiation/polarization characteristics is described. Finally, we present the experimental and theoretical results from impedance and radiation performance characterization for different antenna configurations.
Photoreactivity of polymers with dimerizable side-groups: Kinetic analysis for probing morphology and molecular organization (1999)

The solid state photoreactivity of polymers with pendant chromophores of the cinnamic type has been examined by monitoring the reaction by UV spectroscopy. Two series of photosensitive polymers with polysiloxane or polyvinylamine main chains were selected to exemplify specific behaviors contrasting on various aspects with that of poly(vinyl cinnamate) as the reference photocross-linkable polymer. Valuable kinetic information was obtained from simple photoirradiation experiments for probing the physical structure of the condensed polymeric material and for studying the influence of chromophore content. Photoisomerization of the chromophore competes efficiently with dimerization for both the liquid polysiloxanes with cinnamic esters connected by long spacers and for the glassy cinnamoylated polyvinylamines, the density of sites paired for dimerization being expectedly low in these amorphous matrices. The variations of the quantum yield for dimerization in the neat polymers as a function of their composition are discussed and correlated to the changes of practical sensitivity for photocuring. For polysiloxanes with pendant cyanostyrylacrylic groups, the leveled reactivity observed with quantum yields at zero conversion independent on the macroscopic chromophore content in the samples is explained by phase separation leading to dispersed domains rich in photoreactive side-groups. The layered order evidenced by wide angle X-ray scattering is consistent with the clean and reversible photoreaction. In spite of the discussed structural differences, the variation of the normalized quantum yield for dimerization ΦDim/Φ0 as a function of conversion π is described by the same scaling law ΦDim/Φ0 = (1–π)3 as was established for the amorphous and homogeneous samples of cinnamoylated polysiloxanes or polyvinylamines.
Compaction of Clay Sediments in the Range of Molecular Particle Distances (1962)

Abstract The physical process of compaction of clay sediments and the inverse process of swelling can be discussed in terms of particle interaction forces. The swelling pressure in a given situation equals the nct repulsive force per unit area between the particles. The net repulsive force is the resultant of various repulsive and attractive forces. Two stages of swelling or compaction can be distinguished, one in which the particles are relatively far apart, and a second in which they arc separated by only a few monomolecular layers of water. In the first stage the swelling pressure is primarily due to double-layer repulsion (“osmotic swelling”). The pressures range from a fraction of one atmosphere to several times ten atmospheres. These pressures are of particular interest for foundation engineering problems. In the second stage the swelling pressures are dominated by the work of adsorption of the water layers on the clay surfaces. Tile pressures may reach several thousand atmospheres. Quantitative data on the swelling pressures in this range are derived from water vapor sorption isotherms combined with X-ray data on the c -spacing of expanding clays during dehydration. It is concluded that overburden pressures in nature will seldom be high enough to remove all adsorbed water from between parallel grain surfaces.
Pharmacological Strategies for Overcoming Multidrug Resistance (2006)

Multidrug resistance (MDR) is a major obstacle to the effective treatment of cancer. One of the underlying mechanisms of MDR is cellular overproduction of P-glycoprotein (P-gp) which acts as an efflux pump for various anticancer drugs. P-gp is encoded by the MDR1 gene and its overexpression in cancer cells has become a therapeutic target for circumventing multidrug resistance. A potential strategy is to co-administer efflux pump inhibitors, although such reversal agents might actually increase the side effects of chemotherapy by blocking physiological anticancer drug efflux from normal cells. Although many efforts to overcome MDR have been made using first and second generation reversal agents comprising drugs already in current clinical use for other indications (e.g. verapamil, cyclosporine A, quinidine) or analogues of the first-generation drugs (e.g. dexverapamil, valspodar, cinchonine), few significant advances have been made. Clinical trials with third generation modulators (e.g. biricodar, zosuquidar, and laniquidar) specifically developed for MDR reversal are ongoing. The results however are not encouraging and it may be that the perfect reverser does not exist. Other approaches to multidrug resistance reversal have also been considered: encapsulation of anthracyclines in liposomes or other carriers which deliver these drugs selectively to tumor tissues, the use of P-gp targeted antibodies such as UIC2 or the use of antisense strategies targeting the MDR1 messenger RNA. More recently, the development of transcriptional regulators appears promising. Also anticancer drugs that belong structurally to classes of drugs extruded from cells by P-gp but that are not substrates of this drug transporter may act as potent inhibitors of MDR tumors (e.g. epothilones, second generation taxanes). Taking advantage of MDR has also been studied. Bone marrow suppression, one of the major side effects of cancer chemotherapy, can compromise the potential of curative and palliative chemotherapy. It is conceivable that drug resistance gene transfer into bone marrow stem cells may be able to reduce or abolish chemotherapy-induced myelosuppression and facilitate the use of high dose chemotherapy. Clinical trials of retroviral vectors containing drug resistance genes have established that the approach is safe and are now being designed to address the therapeutically relevant issues.
Costimulatory B7 Molecules in the Pathogenesis of Infectious and Autoimmune Diseases (1996)

Most immune responses depend on the activation of T cells. This class of lymphocytes consists of functionally and phenotypically distinct populations, the best characterized of which are helper T cells and cytotoxic T cells. Distinctive molecules on the cell surface provide markers of these populations: CD4 for helper T cells and CD8 for cytotoxic T cells. CD4 and CD8 T cells recognize antigens through a T-cell antigen receptor composed of an α chain and a β chain. Other T cells bearing γ- and δ-chain receptors have been identified, but their function is less clear.CD4 helper T cells can be . . .
Effects of a 5-Lipoxygenase–Activating Protein Inhibitor on Biomarkers Associated With Risk of Myocardial Infarction (2005)

In patients with specific at-risk variants of 2 genes in the leukotriene pathway, DG-031 led to significant and dose-dependent suppression of biomarkers that are associated with increased risk of MI events.
Blind Source Separation: Theory and Applications (2014)

A systematic exploration of both classic and contemporary algorithms in blind source separation with practical case studies The book presents an overview of Blind Source Separation, a relatively new signal processing method. Due to the multidisciplinary nature of the subject, the book has been written so as to appeal to an audience from very different backgrounds. Basic mathematical skills (e.g. on matrix algebra and foundations of probability theory) are essential in order to understand the algorithms, although the book is written in an introductory, accessible style. This book offers
An in vitro biofilm model of subgingival plaque (2007)

The biofilm model described here closely reproduces the composition of the cultivable subgingival plaque both in the species present and in their relative proportions. Differences existed between biofilms grown from diseased and non-diseased sites with the former being characterized by the presence of periodontal pathogens at microbially significant levels.
Sulfasalazine Suppresses Drug Resistance and Invasiveness of Lung Adenocarcinoma Cells Expressing AXL (2007)

Metastasis and drug resistance are the major causes of mortality in patients with non-small cell lung cancer (NSCLC). Several receptor tyrosine kinases (RTKs), including AXL, are involved in the progression of NSCLC. The AXL/MER/SKY subfamily is involved in cell adhesion, motility, angiogenesis, and signal transduction and may play a significant role in the invasiveness of cancer cells. Notably, no specific inhibitors of AXL have been described. A series of CL1 sublines with progressive invasiveness established from a patient with NSCLC has been identified that positively correlates with AXL expression and resistance to chemotherapeutic drugs. The ectopic overexpression of AXL results in elevated cell invasiveness and drug resistance. Nuclear factor-kappaB (NF-kappaB) signaling activity is associated with AXL expression and may play an important role in the enhancement of invasiveness and doxorubicin resistance, as shown by using the NF-kappaB inhibitor, sulfasalazine, and IkappaB dominant-negative transfectants. In the current study, sulfasalazine exerted a synergistic anticancer effect with doxorubicin and suppressed cancer cell invasiveness in parallel in CL1 sublines and various AXL-expressing cancer cell lines. Phosphorylation of AXL and other RTKs (ErbB2 and epidermal growth factor receptor) was abolished by sulfasalazine within 15 min, suggesting that the inhibition of NF-kappaB and the kinase activity of RTKs are involved in the pharmacologic effects of sulfasalazine. Our study suggests that AXL is involved in NSCLC metastasis and drug resistance and may therefore provide a molecular basis for RTK-targeted therapy using sulfasalazine to enhance the efficacy of chemotherapy in NSCLC.
Reduction of 15‐hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma (2009)

Prostaglandin (PG) E(2) promotes gastrointestinal carcinogenesis and tumor progression. We determined the correlations between pattern of expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a catabolic enzyme for biological inactivation of PGE(2), in gastric adenocarcinoma and various clinicopathological factors and patient outcome in an attempt to elucidate its biological significance. In 35 of 71 cases of gastric adenocarcinoma, expression of 15-PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15-PGDH expression to be an independent predictor of poor survival. The proportion of Ki67-positive cells in 15-PGDH-negative adenocarcinoma was higher than that in 15-PGDH-positive adenocarcinoma. No differences were found in clinicopathological parameters between patients with cyclooxygenase-2 (COX-2)-positive tumors and those with COX-2 negative tumors. In an in vitro study, use of specific siRNA to silence 15-PGDH or a specific inhibitor of 15-PGDH enhanced cell proliferation in the gastric cancer cell line AGS, which expresses 15-PGDH. These findings suggest that reduction of 15-PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma.
Synergism between tobramycin and ceftazidime against a resistant Pseudomonas aeruginosa strain, tested in an in vitro pharmacokinetic model (1997)

Synergism between two antibiotics is usually tested by a checkerboard titration technique, or by time-kill methods. Both methods have the disadvantage that synergism is determined at constant concentrations of the antibiotics, which do not reflect reality in vivo. In the present study we determined whether synergism between tobramycin and ceftazidime can be found at declining concentrations below the MIC, and whether change in dosing sequence of the antibiotics would result in differences in killing. Three monotherapy and six combination therapy schedules were tested in an in vitro pharmacokinetic model, using a Pseudomonas aeruginosa resistant to both antibiotics. During all q8h dosing schedules the peak concentration (Cmax) was adjusted to the MIC for the strain of both antibiotics. During all monotherapy regimens bacterial growth was present, while all six combination therapy schedules showed significant killing. At t = 24 h there were no differences between all combination therapy schedules, but at t = 8 h the two combination therapy schedules with administration of tobramycin once daily showed a significantly faster killing. By using the area under the killing curve (AUKC) as a parameter for synergistic killing, simultaneous combination therapy starting with tobramycin once daily was significantly better than all other regimens. We conclude that there is synergism between tobramycin and ceftazidime at declining antibiotic concentrations below the MIC, resulting in a pronounced killing of a resistant Pseudomonas strain. Infections due to resistant Pseudomonas strains could possibly be treated by a synergistic combination of these drugs.
Inhibition of Human Breast Carcinoma Growth by a Soluble Recombinant Human CD40 Ligand (1999)

CD40 is present on B cells, monocytes, dendritic cells, and endothelial cells, as well as a variety of neoplastic cell types, including carcinomas. CD40 stimulation by an antibody has previously been demonstrated to induce activation-induced cell death in aggressive histology human B-cell lymphoma cell lines. Therefore, we wanted to assess the effects of a recombinant soluble human CD40 ligand (srhCD40L) on human breast carcinoma cell lines. Human breast carcinoma cell lines were examined for CD40 expression by flow cytometry. CD40 expression could be detected on several human breast cancer cell lines and this could be augmented with interferon-gamma. The cell lines were then incubated with a srhCD40L to assess effects on in vitro growth. srhCD40L significantly inhibited the proliferation of the CD40(+) human breast cancer cell lines. This inhibition could also be augmented with interferon-gamma. Viability was also affected and this was shown to be due to increased apoptosis of the cell lines in response to the ligand. Treatment of tumor-bearing mice was then performed to assess the in vivo efficacy of the ligand. Treatment of tumor-bearing SCID mice with the ligand resulted in significant increases in survival. Thus, CD40 stimulation by its ligand directly inhibits human breast carcinoma cells in vitro and in vivo. These results suggest that srhCD40L may be of clinical use to inhibit human breast carcinoma growth.
BAR expressolog identification: expression profile similarity ranking of homologous genes in plant species (2012)

Large numbers of sequences are now readily available for many plant species, allowing easy identification of homologous genes. However, orthologous gene identification across multiple species is made difficult by evolutionary events such as whole-genome or segmental duplications. Several developmental atlases of gene expression have been produced in the past couple of years, and it may be possible to use these transcript abundance data to refine ortholog predictions. In this study, clusters of homologous genes between seven plant species - Arabidopsis, soybean, Medicago truncatula, poplar, barley, maize and rice - were identified. Following this, a pipeline to rank homologs within gene clusters by both sequence and expression profile similarity was devised by determining equivalent tissues between species, with the best expression profile match being termed the 'expressolog'. Five electronic fluorescent pictograph (eFP) browsers were produced as part of this effort, to aid in visualization of gene expression data and to complement existing eFP browsers at the Bio-Array Resource (BAR). Within the eFP browser framework, these expression profile similarity rankings were incorporated into an Expressolog Tree Viewer to allow cross-species homolog browsing by both sequence and expression pattern similarity. Global analyses showed that orthologs with the highest sequence similarity do not necessarily exhibit the highest expression pattern similarity. Other orthologs may show different expression patterns, indicating that such genes may require re-annotation or more specific annotation. Ultimately, it is envisaged that this pipeline will aid in improvement of the functional annotation of genes and translational plant research.
A clonotype nomenclature for T cell receptors (2009)

T cell receptor (TCR) nucleotide sequences are often generated during analyses of T cell responses to pathogens or autoantigens. The most important region of the TCR is the third complementarity-determining region (CDR3) whose nucleotide sequence is unique to each T cell clone. The CDR3 interacts with the peptide and thus is important for recognizing pathogen or autoantigen epitopes. While conventions exist for identifying the various TCR chains, there is a lack of a concise nomenclature that would identify both the amino acid translation and nucleotide sequence of the CDR3. This deficiency makes the comparison of published TCR genetic and proteomic information difficult. To enhance information sharing among different databases and to facilitate computational assessment of clonotypic T cell repertoires, we propose a clonotype nomenclature. The rules for generating a clonotype identifier are simple and easy to follow, and have a built-in error-checking system. The identifier includes the V and J region, the CDR3 length as well as its human or mouse origin. The framework of this naming system could also be expanded to the B cell receptor.
Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study (2008)

The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy.