gebhart/patrepeval huggingface dataset:
Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade (2012)

Breast cancer is immunogenic, and infiltrating immune cells in primary breast tumors convey important clinical prognostic and predictive information. Furthermore, the immune system is critically involved in clinical responses to some standard cancer therapies. Early breast cancer vaccine trials have established the safety and bioactivity of breast cancer immunotherapy, with hints of clinical activity. Novel strategies for modulating regulators of immunity, including regulatory T cells, myeloid-derived suppressor cells and immune checkpoint pathways (monoclonal antibodies specific for the cytotoxic T-lymphocyte antigen-4 or programmed death), are now available. In particular, immune checkpoint blockade has enormous therapeutic potential. Integrative breast cancer immunotherapies that strategically combine established breast cancer therapies with breast cancer vaccines, immune checkpoint blockade or both should result in durable clinical responses and increased cures.
Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo‐controlled clinical trial (2012)

This new treatment provides an opportunity to investigate the role of neutrophils in severe asthma with potential clinical benefits. Larger studies of longer duration are needed to evaluate the impact on other outcomes of asthma including exacerbations.
A new Volterra predistorter based on the indirect learning architecture (1997)

Nonlinear compensation techniques are becoming increasingly important. We present a new Volterra-based predistorter, which utilizes the indirect learning architecture to circumvent a classical problem associated with predistorters, namely that the desired output is not known in advance. We utilize the indirect learning architecture and the recursive least square (RLS) algorithm. Specifically, we propose an indirect Volterra series model predistorter which is independent of a specific nonlinear model for the system to be compensated. Both 16-phase shift keying (PSK) and 16-quadrature amplitude modulation (QAM) are used to demonstrate the efficacy of the new approach.
Generation and Analysis of 25 Mb of Genomic DNA from the Pufferfish Fugu rubripes by Sequence Scanning (1999)

We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences have been minimally edited and searched against protein and DNA databases. These data are all displayed on a searchable, publicly available web site at. With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%-50% of each clone. This essentially random data set covers nearly 25 Mb (>6%) of the Fugu genome and forms the basis of a series of whole genome analyses which address questions regarding gene density and distribution in the Fugu genome and the similarity between Fugu and mammalian genes. The Fugu genome, with eight times less DNA but a similar gene repertoire, is ideally suited to this type of study because most cosmids contain more than one identifiable gene. General features of the genome are also discussed. We have made some estimation of the syntenic relationship between mammals and Fugu and looked at the efficacy of ORF prediction from short, unedited Fugu genomic sequences. Comparative DNA sequence analyses are an essential tool in the functional interpretation of complex vertebrate genomes. This project highlights the utility of using the Fugu genome in this kind of study.
Protein‐free transfection of CHO host cells with an IgG‐fusion protein: Selection and characterization of stable high producers and comparison to conventionally transfected clones (2006)

In order to improve the current techniques of cell cultivation in the absence of serum, we have developed a protein-free transfection protocol for CHO cells, based on the Nucleofector technology. After starting with a heterogeneous pool of primary transfectants which express the fusion protein EpoFc, we isolated single clones and compared them with parallel clones generated by lipofection in serum-dependent cultivation. Our intensive characterization program was based on determination of specific productivity (q(p)) and analysis of genetic parameters. In two nucleofection experiments, transfection with 5 microg of DNA resulted in best productivities of the primary cell pools. After subcloning, the q(p) could be raised up to 27 pg x cells(-1) x day(-1). While the serum-dependent transfectants exhibited specific productivities up to 57 pg x cells(-1) x day(-1) in serum-dependent cultivation, a significant decrease that resulted in the range of q(p) of the protein-free transfectants was observed after switching to protein-free conditions. Investigation of genetic parameters revealed higher mRNA levels and gene copy numbers (GCN) for the protein-free adapted serum-dependent transfectants. Therefore, we assume that problems during protein-free adaptation (PFA) lead to a less efficient translation machinery after serum deprivation. We describe the generation of stable-producing recombinant CHO clones by protein-free transfection of a protein-free adapted host cell line, which reduces the risk of adverse clonal changes after PFA. The main advantage of this approach is the earlier predictability of clone behavior, which makes the generation of production clones by protein-free transfection, a viable and highly efficient strategy for recombinant cell line development.
High affinity histamine-binding and antihistaminic activity of the salivary nitric oxide-carrying heme protein (nitrophorin) of Rhodnius prolixus. (1994)

The salivary glands of Rhodnius prolixus contain a nitrosyl-heme protein, named nitrophorin, that releases the vasodilatory and antiplatelet compound nitric oxide (NO). Because imidazole compounds such as histamine can interact with Fe(III) heme proteins, we investigated whether such substances could interact with Rhodnius nitrophorins. Both imidazole and histamine, but not histidine can produce full of the difference spectra of the Soret band in the 1-3 microM concentration range (at a heme protein concentration of 0.4 microM). The apparent K0.5 for the binding of histamine with the heme protein is below 1 microM. Furthermore, the complex histamine-heme protein does not dissociate after molecular sieving chromatography. To investigate whether histamine could displace NO from the native nitrosyl nitrophorins, histamine was added to the native heme proteins, leading to displacement of the bound NO as observed by changes in the absorption spectra as well as by the production of nitrite. Finally, the antihistamine effect of the heme protein was demonstrated by its inhibition of the histamine-provoked contractures of the guinea pig ileum. It is concluded that histamine, a common autacoid found at the site of injury and exposure to antigenic substances such as the site of feeding by hematophagous arthropods, can be scavenged by the nitrosyl nitrophorin of R. prolixus, which, in return, will release the vasodilatory and platelet inhibiting NO to counteract the host hemostatic response.
Insulin-induced egr-1 Expression in Chinese Hamster Ovary Cells Is Insulin Receptor and Insulin Receptor Substrate-1 Phosphorylation-independent (1995)

Insulin's effects primarily are initiated by insulin binding to its plasma membrane receptor and the sequential tyrosine phosphorylation of the insulin receptor and intracellular substrates, such as insulin receptor substrate-1 (IRS-1). However, studies suggest some insulin effects, including those at the nucleus, may not be regulated by this pathway. The present study compared the levels of insulin binding, insulin receptor and IRS-1 tyrosine phosphorylation, and phosphatidylinositol 3'-kinase activity to immediate early gene c-fos and egr-1 mRNA expression in Chinese hamster ovary (CHO) cells expressing only neomycin-resistant plasmid (CHONEO), overexpressing wild type human insulin receptor (CHOHIRc) or ATP binding site-mutated insulin receptors (CHOA1018K). Insulin binding in CHONEO cells was markedly lower than that in other cell types. 10 nM insulin significantly increased tyrosine phosphorylation of insulin receptor and IRS-1 in CHOHIRc cells. Phosphorylation of insulin receptor and IRS-1 in CHONEO and CHOA1018K cells was not detected in the presence or absence of insulin. Similarly, insulin increased phosphatidylinositol 3-kinase activity only in CHOHIRc cells. As determined by Northern blot, nuclear run-on analysis, and in situ hybridization, insulin induced c-fos mRNA expression, through transcription, in CHOHIRc cells but not in CHONEO and CHOA1018K cells, consistent with previous reports. In contrast, all three cell types showed a similar insulin dose-dependent increase of egr-1 mRNA expression through transcription. These data indicated that insulin-induced egr-1 mRNA expression did not correlate with the levels of insulin binding to insulin receptor or phosphorylation of insulin receptor and IRS-1. These results suggest that different mechanisms are involved in induction of c-fos and egr-1 mRNA expression by insulin, the former by the more classic insulin receptor tyrosine kinase pathway and the latter by a yet to be determined alternative signal transduction pathway.
Expression and role of the universal stress protein, UspA, of Escherichia coli during growth arrest (1994)

The synthesis of the small, cytoplasmic protein UspA universal stress protein A) of Escherichia coli is induced as soon as the cell growth rate falls below the maximal growth rate supported by the medium, regardless of the condition inhibiting growth. The increase in UspA synthesis appears to be the result of induction of the monocistronic uspA gene. Induction of this gene during a heat-shock treatment is demonstrated to be the result of transcriptional activation of a sigma 70-dependent promoter which has previously been shown to be activated also during carbon starvation-induced growth arrest. Mutant cells lacking UspA grow at rates indistinguishable from the isogenic parent at different temperatures and in the presence of different growth inhibitors but are impaired in their ability to survive prolonged periods of complete growth inhibition caused by a variety of diverse stresses, including CdCl2, H2O2, DNP, CCCP exposure, and osmotic shock. Moreover, the uspA mutation results in an increased sensitivity of cells to carbon-source starvation (i.e. glucose, glycerol or succinate depletion). Also, the mutation causes a marked alteration in the timing of starvation protein expression but protein expression during steady-state growth appears to be normal. The results presented have prompted us to postulate that UspA may have a general protective function related to the growth arrest state.
A Multi-channel infrastructure based on DCF access mechanism for Wireless LAN Mesh Networks compliant with IEEE 802.11 (2005)

The mesh topology based on the standard IEEE 802.11 for wireless LANs appears to be a very promising architecture for achieving a ubiquitous wireless Internet access in the future. However, the current IEEE 802.11 protocol is aimed at single access point (AP) environments and many problems related to the wireless meshed interconnection of APs and mobile terminals (MTs) remain to be solved. Some proposed solutions to build such mesh architectures are based on single-channel ad-hoc oriented schemes in which IEEE 802.11 protocol has been modified. The main problem with this type of schemes, however, lies in the very low performance of the single-channel architecture itself. The task group S of IEEE 802.11 is currently working out standards for IEEE 802.11-compliant mesh architectures in a number of usage scenarios including residential, office and campus/community/public access network but a lot of work remains to be done since the group was established just on last year. In this paper we propose a new multi-channel mesh architecture for hot zones which works using a distributed coordination function (DCF)-based technique for interconnecting APs. A major advantage of our proposed scheme is that, putting routing issues aside, it introduces no change into the MAC protocol of IEEE 802.11. Our simulations results obtained in OPNET show a good performance of our proposed scheme in terms of throughput and delay. We also show interesting results related with the size of packets and the mesh architecture itself that could lead to further research in the future
In vivo imaging of the rat anatomy with nuclear magnetic resonance. (1980)

Live rats were imaged by nuclear magnetic resonance (NMR). These images demonstrated fine detail and high object contrast. Motion artifacts are not apparent in 4-minute images, and major blood vessels are demonstrated as regions of low signal intensity because of blood flow. Selective contrast enhancement is possible by varying NMR imager accumulation parameters.
Advances in cancer immunology and cancer immunotherapy. (2016)

After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models.
A 10-amino acid sequence of fibroblast growth factor 2 is sufficient for its mitogenic activity on neural progenitor cells (1997)

During development of the central nervous system, neurons and glia are generated from immature neural progenitor cells (NPCs). Basic fibroblast growth factor (FGF-2) is a mitogen for these cells both in vitro and in vivo. However, it is not known whether other members of the FGF family have similar mitogenic effects on NPCs. We have found that FGF-4, in addition to FGF-2, is a mitogen for NPCs isolated from fetal and adult central nervous systems. Other family members have no proliferative effects on these cells. FGFs transduce signals to the cytoplasm through a family of transmembrane tyrosine kinase receptors (FGFR-1-4) or their isoforms. The high-affinity receptor binding sites are found in two regions of the FGF-2 molecule. We have examined the involvement of these sites in mitogenic signaling. Synthetic peptides corresponding to sequences in FGF-2 receptor binding sites were examined in [3H]thymidine incorporation assays for their agonist or antagonist activity. A 10-aa sequence present in the first receptor binding domain has been found to act as an antagonist, blocking the mitogenic effects of FGF-2. Chemical crosslinking studies using 125I-labeled FGF-2 showed specific reduction in binding of radiolabeled FGF-2 to its receptors present on the membranes of NPCs. The identification of this sequence will assist in the study of pathways involved in signal transduction for mitogenesis in these cells and elucidate the role of FGF-2 and FGF-4 during normal development and in the pathogenesis of disease.
Viscoelastic Surfactant Fracturing Fluids: Applications in Low Permeability Reservoirs (2000)

Abstract The introduction of viscoelastic surfactant (VES) base fracturing fluids has changed the way industry views fracturing fluids and proppant transport during a fracture treatment.1 Elimination of polymers allows one to achieve highly conductive proppant packs with no polymer damage. Retained permeability and leakoff control are two of the most important requirements for fracturing fluids. Traditional and new generations of cross-linked gels provide good leakoff control, but they often adversely affect the retained permeability of the proppant pack. In addition, minimizing frac-height growth and increasing effective fracture length are a few other advantages of using VES fluids.2 In the majority of cases in low permeability formations, a long and conductive fracture is the ultimate aim of hydraulic fracturing. Borate or metal crosslinked guar fluids, because of their inherent high viscosity, typically result in height growth rather than increased fracture length. With VES fluids proppant transport is based on the elasticity and structure rather than the viscosity of fluid. Therefore VES fluids efficiently transport proppants at lower viscosities. At the same time, VES fluids let one achieve a better fracture geometry, that with minimum fracture height and maximum fracture length. Pressure transient analysis and tracer studies have shown that this non-damaging low viscosity fluid can give longer effective frac-length even when using much less fluid and proppant volumes (Figure 1). Reduced friction pressure is another added advantage while using VES fluids. Hence VES fluid is the fluid of choice when fracturing is performed through coiled tubing.3,4 Simplicity and reliability of this two component system are the other features of this fluid that attract the industry globally.5 The use of VES technology is now extended to other oilfield applications, such as selective matrix diversion,6 filtercake removal,7 and coiled tubing clean out. VES technology is also defining new engineering practices in hydraulic fracturing that cannot be accomplished with conventional fluid systems, such as fracturing through coiled tubing.
The TNF-Family Ligand TL1A and Its Receptor DR3 Promote T Cell–Mediated Allergic Immunopathology by Enhancing Differentiation and Pathogenicity of IL-9–Producing T Cells (2015)

The TNF family cytokine TL1A (Tnfsf15) costimulates T cells and type 2 innate lymphocytes (ILC2) through its receptor DR3 (Tnfrsf25). DR3-deficient mice have reduced T cell accumulation at the site of inflammation and reduced ILC2-dependent immune responses in a number of models of autoimmune and allergic diseases. In allergic lung disease models, immunopathology and local Th2 and ILC2 accumulation is reduced in DR3-deficient mice despite normal systemic priming of Th2 responses and generation of T cells secreting IL-13 and IL-4, prompting the question of whether TL1A promotes the development of other T cell subsets that secrete cytokines to drive allergic disease. In this study, we find that TL1A potently promotes generation of murine T cells producing IL-9 (Th9) by signaling through DR3 in a cell-intrinsic manner. TL1A enhances Th9 differentiation through an IL-2 and STAT5-dependent mechanism, unlike the TNF-family member OX40, which promotes Th9 through IL-4 and STAT6. Th9 differentiated in the presence of TL1A are more pathogenic, and endogenous TL1A signaling through DR3 on T cells is required for maximal pathology and IL-9 production in allergic lung inflammation. Taken together, these data identify TL1A-DR3 interactions as a novel pathway that promotes Th9 differentiation and pathogenicity. TL1A may be a potential therapeutic target in diseases dependent on IL-9.
Susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to a new quinolone, trovafloxacin (CP-99,219) (1996)

The susceptibilities of mycoplasmas to a new quinolone, trovafloxacin (CP-99,219), were compared with those to sparfloxacin and ofloxacin. Mycoplasma pneumoniae was as susceptible to trovafloxacin (MIC = 0.25 microgram/ml) as to sparfloxacin and fourfold less susceptible to ofloxacin. Mycoplasma hominis was highly susceptible to trovafloxacin (MIC = 0.06 microgram/ml) and sparfloxacin (MIC = 0.03 microgram/ml) and less susceptible to ofloxacin (MIC = 0.5 microgram/ml). Ureaplasma urealyticum was most susceptible to trovafloxacin, with susceptibilities ranging from 0.06 to 0.5 microgram/ml compared with 0.25 to 1.0 microgram of sparfloxacin per ml and 1 to 4 micrograms of ofloxacin per ml.
Action of progesterone on contractile activity of isolated gastric strips in rats (2003)

The study suggested that progesterone can inhibit the contractile activity of isolated gastric strips in rats and the mechanism seems to be a direct one except that the action on gastric body is mediated through prostaglandin and adrenergic alpha receptor partly.
Local delivery of paclitaxel using the double‐balloon perfusion catheter before stenting in the porcine coronary artery (2001)

Paclitaxel is a new cancer chemotherapeutic agent that has been approved for clinical use in patients with a variety of different cancers. Paclitaxel inhibits cell proliferation by an action on microtubules. The aim of this study was to evaluate the safety and efficacy of locally delivered paclitaxel after coronary stent implantation. A novel double-balloon perfusion catheter was used to deliver the drug locally in the pig coronary artery. Twenty-seven domestic pigs underwent stent implantation of the left anterior descending artery. In the treatment group (n = 11), paclitaxel (10 ml; 10 micromol/l) was delivered using the double-balloon perfusion catheter prior to stent implantation. The control group received stent implantation only (n = 16). The animals were sacrificed 4 weeks later. Vessels were perfusion-fixed and morphometric analysis was performed using conventional techniques. In addition, the extent of injury was determined at each stent-strut area. Correlation of local injury and neointimal thickness was evaluated by linear regression. Neointimal thickness (paclitaxel 1.0 +/- 0.4 vs. control 0.7 +/- 0.3 mm), neointimal area (paclitaxel 4.1 +/- 2.2 vs. control 2.4 +/- 1.1 mm(2)), and the lumen area (paclitaxel 2.1 +/- 1.9 vs. control 2.5 +/- 0.9 mm(2)) did not show significant differences between both groups. Medial area (3.3 +/- 2.3 vs. 1.6 +/- 0.4 mm(2)) was larger in the vessels treated with paclitaxel (P < 0.05). Linear regression failed to show any difference in the response to injury between the two groups. Local delivery of paclitaxel with the double-balloon-perfusion catheter did not reduce neointima formation following stent implantation in native pig coronary arteries.