gebhart/patrepeval huggingface dataset:
Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma (2011)

Antiangiogenic therapy can produce transient tumor regression in glioblastoma (GBM), but no prolongation in patient survival has been achieved. We have constructed a nanosystem targeted to tumor vasculature that incorporates three elements: (i) a tumor-homing peptide that specifically delivers its payload to the mitochondria of tumor endothelial cells and tumor cells, (ii) conjugation of this homing peptide with a proapoptotic peptide that acts on mitochondria, and (iii) multivalent presentation on iron oxide nanoparticles, which enhances the proapoptotic activity. The iron oxide component of the nanoparticles enabled imaging of GBM tumors in mice. Systemic treatment of GBM-bearing mice with the nanoparticles eradicated most tumors in one GBM mouse model and significantly delayed tumor development in another. Coinjecting the nanoparticles with a tumor-penetrating peptide further enhanced the therapeutic effect. Both models used have proven completely resistant to other therapies, suggesting clinical potential of our nanosystem.
Medicaid and privately financed orthodontic patients have similar occlusal and psychosocial outcomes (2011)

Occlusal and psychosocial outcomes from orthodontics in MC and PP were comparable, despite worse MC malocclusions at baseline.
Opposite effects on tumor growth depending on dose of an immunomodulatory polysaccharide with or without cyclophosphamide. (1985)

Opposite effects on the growth of the F10 variant of B16 melanoma--inhibitory and stimulatory--were found with varying doses of the polysaccharide levan. Low (0.1 and 1 mg) daily doses inhibited, while high (5 and 10 mg) doses enhanced tumor growth. In combined cyclophosphamide-levan treatment, these opposite effects were more pronounced.
Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery. (1995)

Heat shock treatment induces expression of several heat shock proteins and subsequent post-ischemic myocardial protection. Correlations exist between the degree of stress used to induce the heat shock proteins, the amount of the inducible heat shock protein 70 (HSP70) and the level of myocardial protection. The inducible HSP70 has also been shown to be protective in transfected myogenic cells. Here we examined the role of human inducible HSP70 in transgenic mouse hearts. Overexpression of the human HSP70 does not appear to affect normal protein synthesis or the stress response in transgenic mice compared with nontransgenic mice. After 30 min of ischemia, upon reperfusion, transgenic hearts versus nontransgenic hearts showed significantly improved recovery of contractile force (0.35 +/- 0.08 versus 0.16 +/- 0.05 g, respectively, P < 0.05), rate of contraction, and rate of relaxation. Creatine kinase, an indicator of cellular injury, was released at a high level (67.7 +/- 23.0 U/ml) upon reperfusion from nontransgenic hearts, but not transgenic hearts (1.6 +/- 0.8 U/ml). We conclude that high level constitutive expression of the human inducible HSP70 plays a direct role in the protection of the myocardium from ischemia and reperfusion injury.
Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis. (1994)

Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)
The Genomic Rate of Molecular Adaptation of the Human Influenza A Virus (2011)

Quantifying adaptive evolution at the genomic scale is an essential yet challenging aspect of evolutionary biology. Here, we develop a method that extends and generalizes previous approaches to estimate the rate of genomic adaptation in rapidly evolving populations and apply it to a large data set of complete human influenza A virus genome sequences. In accord with previous studies, we observe particularly high rates of adaptive evolution in domain 1 of the viral hemagglutinin (HA1). However, our novel approach also reveals previously unseen adaptation in other viral genes. Notably, we find that the rate of adaptation (per codon per year) is higher in surface residues of the viral neuraminidase than in HA1, indicating strong antibody-mediated selection on the former. We also observed high rates of adaptive evolution in several nonstructural proteins, which may relate to viral evasion of T-cell and innate immune responses. Furthermore, our analysis provides strong quantitative support for the hypothesis that human H1N1 influenza experiences weaker antigenic selection than H3N2. As well as shedding new light on the dynamics and determinants of positive Darwinian selection in influenza viruses, the approach introduced here is applicable to other pathogens for which densely sampled genome sequences are available, and hence is ideally suited to the interpretation of next-generation genome sequencing data.
Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke (2005)

A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.
Genomic profile, smoking, and response to anti-PD-1 therapy in non-small cell lung carcinoma (2015)

The recent successes of immune checkpoint therapies have established a new era for the treatment of patients with cancer, yet the predictors of response remain largely undetermined. We recently demonstrated that the genomic landscape of lung cancers substantially influences the response to programmed cell death 1 receptor (PD-1) blockade, providing new insights into the molecular determinants of the response to immunotherapy.
Peptide Ribonucleic Acids (PRNA). 2. A Novel Strategy for Active Control of DNA Recognition through Borate Ester Formation (2000)

The effect of adding borax and boric acids on the nucleobase orientation and recognition behavior of novel mono- and oligomeric peptide ribonucleic acids (PRNAs) has been investigated. The base orientation of 5‘-amino-5‘-deoxyuridine and 5‘-amino-5‘-deoxycytidine was shown by CD and NOE difference spectral studies to switch from anti to syn in borate buffer or upon addition of borax. The origin of this phenomenon is elucidated to be the cooperative effect of the cyclic borate esterification of the sugar's cis-2‘,3‘-diol and the hydrogen-bonding interaction between the sugar's 5‘-amino proton and the base's 2-carbonyl oxygen. Because this new strategy for switching the base orientation through the addition of borate is potentially applicable to the recognition control of nucleic acids if the sugar's 5‘-proton and cis-2‘,3‘-diol remain unmodified, we synthesized a series of PRNAs, in which the 5‘-amino-5‘-deoxypyrimidine ribonucleoside moiety was appended to a mono- or oligo(γ-l-glutamic acid) backbone through the 5‘-amino group. The orientation switching through the addition of borate was also confirmed with the monomeric model, and the switching efficiency was enhanced for oligomeric γ-PRNA. Finally, it was unambiguously demonstrated that the γ-PRNA 8-mer with an isopoly(l-glutamic acid) backbone can form a tight complex with DNA, and further, the recognition of DNA with γ-PRNA 8-mer is controlled by the borate added as an external factor.
Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity. (1998)

Interactions between complementary receptors on leukocytes and endothelial cells play a central role in regulating extravasation from the blood and thereby affect both normal and pathologic inflammatory responses. CD44 on lymphocytes that has been "activated" to bind its principal ligand hyaluronate (HA) on endothelium can mediate the primary adhesion (rolling) of lymphocytes to vascular endothelial cells under conditions of physiologic shear stress, and this interaction is used for activated T cell extravasation into an inflamed site in vivo in mice (DeGrendele, H.C., P. Estess, L.J. Picker, and M.H. Siegelman. 1996. J. Exp. Med. 183:1119-1130. DeGrendele, H.D., P. Estess, and M.H. Siegelman. 1997. Science. 278:672-675. DeGrendele, H.C., P. Estess, and M.H. Siegelman. 1997. J. Immunol. 159: 2549-2553). Here, we have investigated the role of lymphocyte-borne-activated CD44 in the human and show that CD44-dependent primary adhesion is induced in human peripheral blood T cells through T cell receptor triggering. In addition, lymphocytes capable of CD44/HA-dependent rolling interactions can be found resident within inflamed tonsils. In analysis of peripheral bloods of patients from a pediatric rheumatology clinic, examining systemic lupus erythematosus, and a group of chronic arthropathies, expression of CD44-dependent primary adhesion strongly correlates with concurrent symptomatic disease, with 85% of samples from clinically active patients showing elevated levels of rolling activity (compared with only 4% of inactive patients). These rolling interactions are predominantly mediated by T cells. The results suggest that circulating T lymphocytes bearing activated CD44 are elevated under conditions of chronic inflammation and that these may represent a pathogenically important subpopulation of activated circulating cells that may provide a reliable marker for autoimmune or chronic inflammatory disease activity.
Oral administration of Enterococcus faecalis FK-23 suppresses Th17 cell development and attenuates allergic airway responses in mice (2012)

Evidence is increasing that oral administration of probiotics can attenuate asthmatic responses both in murine models and clinical trials. T-helper 17 (Th17) cells, a subset of CD4+ T cells have been implicated as having an important role in the development of several allergic disorders, but the relationship between oral administration of probiotics and Th17 development has not been well studied. BALB/c mice were given lysed Enterococcus faecalis FK-23 (LFK) orally for 28 days. After sensitization by subcutaneous injection of ovalbumin (OVA) on Days 14 and 21 and 1% OVA inhalation on Days 25, 26 and 27, they were challenged with a 5% OVA aerosol on Day 28. Twenty-four hours later, airway resistance and accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF) and lung tissues were determined. Ιnterleukin (IL)-17-expressing CD4+ lymphocytes isolated from lung, spleen and lamina propria of the intestine were detected by flow cytometry. The expression of IL-6 and TGF-β mRNA was assessed by real-time PCR. Increases in airway hyperresponsiveness, and numbers of total leukocytes and mast cells in BALF induced by OVA challenge were significantly suppressed by oral administration of LFK. The increased percentage of IL-17-expressing CD4+ cells from lung, spleen and intestine in OVA-challenged mice was reduced following LFK treatment. We conclude that the oral administration of LFK suppresses the asthmatic response and that this is associated with attenuation of Th17 cell development.
Selective deprotection by reductive cleavage with radical anions (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective deprotection by reductive cleavage with radical anionsRobert L. Letsinger and Jeffrey L. FinnanCite this: J. Am. Chem. Soc. 1975, 97, 24, 7197–7198Publication Date (Print):November 1, 1975Publication History Published online1 May 2002Published inissue 1 November 1975https://pubs.acs.org/doi/10.1021/ja00857a058https://doi.org/10.1021/ja00857a058research-articleACS PublicationsRequest reuse permissionsArticle Views206Altmetric-Citations24LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
TLR5 activation induces secretory interleukin-1 receptor antagonist (sIL-1Ra) and reduces inflammasome-associated tissue damage (2010)

Toll-like receptor-5 (TLR5)-mediated detection of flagellin induces nuclear factor (NF)-κB-mediated transcription of host defense gene expression, whereas recognition of intracellular flagellin by interleukin (IL)-1-converting enzyme protease-activation factor (IPAF) results in maturation/secretion of the inflammasome cytokine IL-1β. The potent effects of IL-1β are counter-regulated by secretory IL-1 receptor antagonist (sIL-1Ra). We studied the roles of flagellin receptors in regulating the expression of IL-1β and sIL-1Ra and their subsequent roles in inflammation. Flagellin induced sIL-1Ra in intestinal epithelia and macrophages in a dose- and time-dependent manner, whereas IL-1β was only induced in macrophages. In vivo, flagellin-induced sIL-1Ra, but not IL-1β, was absolutely dependent upon TLR5 expressed on non-hemopioetic cells. Thus, loss of TLR5 increased the IL-1β/sIL-1Ra ratio on flagellin treatment, which correlated with increased inflammatory pathology in response to this product. Furthermore, the flagellin/TLR5 interaction was important for the induction of sIL-1Ra and limiting inflammatory pathology on Salmonella infection. Finally, reduced sIL-1Ra levels in TLR5KO mice correlated with spontaneous colitis. Taken together, we demonstrate that intestinal epithelia, despite not expressing IL-1β, secrete sIL-1Ra in a TLR5-dependent manner suggesting that loss of TLR5 may promote inflammation by increasing IL-1β activity. Thus, optimizing the balance between inflammasome cytokines and their endogenous inhibitors might prove a useful strategy to treat inflammatory disorders.
Magnesium and the Growth of Escherichia coli (1968)

Abstract The growth of cells of Escherichia coli has been studied in media with varying amounts of magnesium. Experiments in which the content of magnesium in the medium and in the cell have been directly measured reveal that the growth rate of magnesium-limited wild type cells is half-maximal at extracellular concentrations of 1 to 3 x 10-6 m. Mutants have been isolated which require 100 times this concentration for half-maximal rate of growth. Supplementation of the medium with calcium or strontium enables the mutants to grow on the same low levels of magnesium as the wild type even though calcium or strontium cannot replace magnesium as an essential growth factor. Cells harvested in the exponential phase of growth from medium not limited in magnesium lose one-third to two-thirds of their total magnesium upon treatment with ethylenediaminetetraacetate. In contrast, magnesium-starved cells retain nearly all of their magnesium when treated with EDTA. In a sonic extract of magnesium-starved cells, 15% of the total magnesium is not sedimentable at 100,000 x g. When such an extract is passed over Sephadex G-25 or G-50, 75 to 80% of the magnesium is free to diffuse into the gel.
Introduction (1997)

The modern period, by which is normally meant the era after the French Revolution, has been one of extreme violence. Beginning with the Revolutionary and Napoleonic wars, a radically new form of war was practised by Western countries. Napoleon introduced new tactics and strategy into warfare, and had at his disposal a new means of motivating men to fight each other. After Napoleon these innovations were supplemented with the radically more destructive means of warfare created by the application of systematic scientific research to industrial production. Thus throughout the nineteenth century invention after invention, coupled with new rational forms of mass production and standardization, gave armies the tools for unprecedented levels of slaughter.
Field reversed configuration lifetime scaling based on measurements from the Large s Experiment (1993)

Flux, energy and particle lifetimes have been measured in the new Large s Experiment field reversed configuration (FRC) facility. By careful control of the formation process, it was possible to form symmetric, quiescent FRCs, with s values higher than 4, in the one year of operation of the device. A wide range of plasma conditions was achieved, with ion temperatures varying between 0.1 and 1.5 keV. The lifetimes continue to scale approximately with the rs2/ρi parameter found in earlier work, with a coefficient proportional to xs to a power between 0.5 and 1
Akt/PKB Signaling in Cancer: A Function in Cell Motility and Invasion (2006)

The PI 3-K signaling pathway has been the subject of intense investigation for over a decade because it regulates a multitude of cellular processes. Deregulation of this pathway often results in human diseases such as cancer. The serine/threonine kinase Akt, a major PI 3-K target in all cells, has received considerable attention because it provides tumor cells with enhanced survival capacity. Many tumors and tumor cells display elevated Akt protein expression and activity, and many of the proteins which regulate Akt itself are also often mutated in cancer. For this reason, Akt has become a viable drug target for cancer therapy. However, recent studies have shown that Akt can also function as a suppressor of tumor cell migration and invasion, phenotypes which are directly linked to metastatic tumor progression. Here we review these findings and consider the unexpected notion that Akt may function as a metastasis suppressor.
Method of oocyte activation affects cloning efficiency in pigs (2008)

The following experiments compared the efficiency of three fusion/activation protocols following somatic cell nuclear transfer (SCNT) with porcine somatic cells transfected with enhanced green fluorescent protein driven by the chicken beta-actin/rabbit beta-globin hybrid promoter (pCAGG-EGFP). The three protocols included electrical fusion/activation (NT1), electrical fusion/activation followed by treatment with a reversible proteasomal inhibitor MG132 (NT2) and electrical fusion in low Ca(2+) followed by chemical activation with thimerosal/dithiothreitol (NT3). Data were collected at Days 6, 12, 14, 30, and 114 of gestation. Fusion rates, blastocyst-stage mean cell numbers, recovery rates, and pregnancy rates were calculated and compared between protocols. Fusion rates were significantly higher for NT1 and NT2 compared to NT3 (P < 0.05). There was no significant difference in mean nuclear number. Pregnancy rate for NT2 was 100% (n = 19) at all stages collected and was significantly higher than NT1 (71.4%, n = 28; P < 0.05), but was not significantly higher than NT3 (82.6%, n = 23; P < 0.15). Recovery rates were calculated based on the number of embryos, conceptuses, fetuses, or piglets present at the time of collection, divided by the number of embryos transferred to the recipient gilts. Recovery rates between the three groups were not significantly different at any of the stages collected (P > 0.05). All fusion/activation treatments produced live, pCAGG-EGFP positive piglets from SCNT. Treatment with MG132 after fusion/activation of reconstructed porcine embryos was the most effective method when comparing the overall pregnancy rates. The beneficial effect of NT2 protocol may be due to the stimulation of proteasomes that infiltrate donor cell nucleus shortly after nuclear transfer.