gebhart/patrepeval huggingface dataset:
Design, Synthesis, and Characterization of a Cationic Peptide That Binds to Nucleic Acids and Permeabilizes Bilayers (1997)

We have designed a cationic amphipathic peptide, KALA (WEAKLAKALAKALAKHLAKALAKALKACEA), that binds to DNA, destabilizes membranes, and mediates DNA transfection. KALA undergoes a pH-dependent random coil to amphipathic alpha-helical conformational change as the pH is increased from 5.0 to 7.5. One face displays hydrophobic leucine residues, and the opposite face displays hydrophilic lysine residues. KALA-mediated release of entrapped aqueous contents from neutral and negatively charged liposomes increases with increasing helical content. KALA binds to oligonucleotides or plasmid DNA and retards their migration in gel electrophoresis. It displaces 50% of ethidium bromide from DNA at a charge ratio (+/-) of 0.9/1. In cultured cells, KALA assists oligonucleotide nuclear delivery when complexes are prepared at a 10/1 (+/-) charge ratio. KALA/DNA (10/1)(+/-) complexes mediate transfection of a variety of cell lines. The KALA sequence provides a starting point for a family of peptides that incorporate other functions to improve DNA delivery systems.
Correlations between predicted protein disorder and post-translational modifications in plants (2014)

tokmak@phoenix.kobe-u.ac.jp or tetsuya.sakurai@riken.jp Supplementary information: Supplementary data are available at Bioinformatics online.
First Record Of Axymyiidae (Diptera: Nematocera: Axymyioidea) From Wisconsin (2001)

The nematoceran fly family, Axymyiidae, is recorded from Wisconsin for the first time. A single adult female Axymyia furcata was collected in flight near a dead log along a forested path in south central Wisconsin on 24 April 2000.
Treatment of CD33-directed Chimeric Antigen Receptor-modified T Cells in One Patient With Relapsed and Refractory Acute Myeloid Leukemia (2014)

We conducted a clinical trial to assess the feasibility and efficacy of CD33-directed chimeric antigen receptor-modified T cells (CART-33) for the treatment of refractory acute myeloid leukemia (AML). A 41-year-old male patient with AML was enrolled and received a total of 1.12 × 10(9) autologous CART-33 cells, of which ~38% were transduced with CAR. The CART-33 infusion alone induced rigorous chills and fevers; drastic fluctuations of his preexisting pancytopenia; elevated serum cytokine levels, including interleukin (IL)-6, IL-8, tumor necrosis factor-α, and interferon-γ; slight transient hyperbilirubinemia within 2 weeks; a subsequent intermittent moderate fever; and reversed fluctuation of the pancytopenia. A marked decrease of blasts in the bone marrow was observed on examination 2 weeks after therapy, and there was a gradual increase until florid disease progression occurred at 9 weeks after the cell infusion. These observations warrant further research on CART-33 treatment in refractory AML and may spur efforts to extend the CART-33-induced tumor burden to the preparation of other intensive strategies, such as hematopoietic stem cell transplantation. This study is registered at www.ClinicalTrials.gov as NCT01864902.
Intraepithelial γδ T Cells May Bridge a Gap between Innate Immunity and Acquired Immunity to Herpes Simplex Virus Type 2 (2004)

Mice depleted of gammadelta T cells by in vivo administration of anti-TCRgammadelta monoclonal antibodies showed susceptibility against an intravaginal infection with herpes simplex virus type 2 (HSV-2). The systemic Th1 response was impaired in the gammadelta T-cell-depleted mice. Mice deficient in the Vdelta1 T subset were susceptible to an intravaginal infection with HSV-2. Intraepithelial gammadelta T cells bearing Vdelta1 may help protect against intravaginal infection with HSV-2 through promoting the systemic Th1 response.
Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2 (1997)

CC chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of CC chemokines. Mice generated by gene targeting to lack CCR2 exhibit normal leukocyte rolling but have a pronounced defect in MCP-1-induced leukocyte firm adhesion to microvascular endothelium and reduced leukocyte extravasation. Constitutive macrophage trafficking into the peritoneal cavity was not significantly different between CCR2-deficient and wild-type mice. However, after intraperitoneal thioglycollate injection, the number of peritoneal macrophages in CCR2-deficient mice did not rise above basal levels, whereas in wild-type mice the number of macrophages at 36 h was approximately 3.5 times the basal level. The CCR2-deficient mice showed enhanced early accumulation and delayed clearance of neutrophils and eosinophils. However, by 5 days neutrophils and eosinophils in both CCR2-deficient and wild-type mice had returned to near basal levels, indicating that resolution of this inflammatory response can occur in the absence of macrophage influx and CCR2-mediated activation of the resident peritoneal macrophages. After intravenous injection with yeast beta-glucan, wild-type mice formed numerous large, well-defined granulomas throughout the liver parenchyma, whereas CCR2-deficient mice had much fewer and smaller granulomas. These results demonstrate that CCR2 is a major regulator of induced macrophage trafficking in vivo.
Occult melanoma in lymph nodes detected by antiserum to S‐100 protein (1984)

Sections of 1,273 nodes from 58 patients with melanoma were stained in an immunoperoxidase assay using an antiserum to S-100 protein and aminoethyl carbazole as indicator. By the hematoxylin and eosin (H. and E.) technique, 128 nodes were seen to contain melanoma (10%); by the anti-S-100 protein technique, 363 (29%) were found to be tumor-positive. The additional tumor-positive nodes contained single tumor cells or small groups of tumor cells and were adjacent to nodes that were partly or wholly replaced by melanoma. Penetration of nodes by single tumor cells was seldom seen in node groups containing no tumor that was visible on H. and E. staining. The anti-S-100 protein approach more accurately identified those patients who would die of their recurrent disease less than 5 years after lymphadectomy.
Anti-tuberculosis Activity of Quassinoids. (1997)

In vitro evaluation of anti-tuberculosis activity was conducted for fifty-six quassinoids isolated in our laboratory from Simaroubaceous plants, Ailanthus altissima (= Aa, 10 compounds), Brucea antidysenterica (= Ba, 16 compounds), Picrasma ailanthoides (= Pa, 14 compounds), and Brucea javanica (= Bj, 16 compounds). Of the compounds tested, shinjulactone K (1), ailanthone (2), shinjudilactone (3), and dehydrobruceantin (4) were the most potent. Although the activities were very low (0-19%), the resulting data provided a picture of structure-activity relationships.
Post-translational processing of murine IL-1: evidence that ATP-induced release of IL-1 alpha and IL-1 beta occurs via a similar mechanism. (1998)

In response to LPS, peritoneal macrophages produce IL-1, but, for the most part, newly synthesized cytokine molecules remain cell associated. Externalization and proteolytic processing of pro-IL-1 beta can be initiated by extracellular ATP. In this study, kinetics and inhibitor sensitivity of the stimulus-coupled mechanism were investigated with [35S]methionine-labeled macrophages. Optimal ATP concentrations required to promote cytokine post-translational processing suggest the involvement of a P2Z type of receptor. Proteolysis of pro-IL-1 beta initiates within 7.5 min of ATP addition; 17-kDa mature IL-1 beta is observed first intracellularly and subsequently extracellularly. In contrast, ATP-treated cells do not contain 17-kDa IL-1 alpha. Macrophages exposed to ATP continuously or only for a 15-min pulse release IL-1 alpha, IL-1 beta, and lactate dehydrogenase (LDH). Proteolytic maturation of IL-1 beta exceeds that of IL-1 alpha in both formats, but pulsed cells process the externalized cytokines more efficiently. Ethacrynic acid and DIDS (4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid) block ATP-induced proteolysis of pro-IL-1 beta and prevent release of pro-IL-1 alpha/beta and LDH; they do not inhibit ATP-induced K+ (86Rb+) efflux. Ethacrynic acid inhibits release of both forms of IL-1 with a similar concentration dependence; within the arrested cells, procytokines accumulate in a Triton-insoluble fraction. An IL-1 beta-converting enzyme inhibitor blocks proteolysis of IL-1 beta, but it does not prevent release of pro-IL-1 alpha, pro-IL-1 beta, or LDH. These results indicate that ATP stimulates externalization of both IL-1 alpha and IL-1 beta. The ATP-induced cytokine release mechanism is accompanied by cell death and requires activity of an anion transport inhibitor-sensitive component, but this pathway operates independently of cytokine proteolytic processing.
Relation Between Hospital Primary Angioplasty Volume and Mortality for Patients With Acute MI Treated With Primary Angioplasty vs Thrombolytic Therapy (2000)

In this study, patients with AMI treated at hospitals with high or intermediate volumes of primary angioplasty had lower mortality with primary angioplasty than with thrombolysis, whereas patients with AMI treated at hospitals with low angioplasty volumes had similar mortality outcomes with primary angioplasty or thrombolysis.
Synergistic inhibition of human glioma cell line by temozolomide and PAMAM‐mediated miR‐21i (2012)

Abstract Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly and with a high frequency. Efforts to overcome chemoresistance are, therefore, critically needed. In present study, a poly(amidoamine; PAMAM) dendrimer was used as a vector to deliver microRNA‐21 inhibitor (miR‐21i) into U87 cells and the chemosensitivity of the combination effect of miR‐21i and TMZ for glioma therapy was investigated. Flow cytometry analysis showed the uptake efficiency of microRNA‐21 inhibitor after complexation with PAMAM. Real‐time PCR and in situ hybridization indicated that, compared with TMZ or miR‐21i treated cells, cells simultaneously treated with miR‐21i and TMZ showed a remarkable decrease in the microRNA‐21 (miR‐21) level. The transfection of miR‐21i enhanced the chemosensitivity by significantly decreasing the IC50 value of TMZ to glioma cells. Knockdown of miR‐21 promoted the cells' apoptosis, and at the same time, inhibited cell invasion. In conclusion, the combination treatment of glioma cells with TMZ and miR‐21i could yield a synergistic effect in inhibition of human glioma cell line. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Proton Transport from Dendritic Helical‐Pore‐Incorporated Polymersomes (2009)

Abstract The ability to add synthetic channels to polymersome (polymer vesicle) membranes could lead to novel membrane composites with unique selectivity and permeability. Proton transport through two different synthetic pores, self‐assembled from either a dendritic dipeptide, (6Nf‐3,4‐3,5)12G2‐CH 2 ‐Boc‐L‐Tyr‐L‐Ala‐OMe, or a dendritic ester, ( R )‐4Bp‐3,4‐dm8G1‐COOMe, incorporated into polymersome membranes are studied. Polymersomes provide an excellent platform for studying such transport processes due to their robustness and mechanical and chemical stability compared to liposomes. It is found that the incorporated dendritic dipeptide and dendritic ester assemble into stable helical pores in the poly(ethylene oxide)‐polybutadiene (PEO‐PBD) polymersomes but not in the poly(2‐methyloxazoline)‐poly(dimethylsiloxane)‐poly(2‐methyl oxazoline) (PMOX‐PDMS‐PMOX) polymersomes. The incorporation is confirmed by circular dichroism (CD), changes in purely synthetic mechanical strength (e.g., areal expansion modulus) as assessed by micropipette aspiration, and cryo‐TEM. In addition to the structural analyses, a transport measurement shows the incorporated dendritic helical pores allow facile transport of protons across the polymersome membranes after up to one month of storage. This integration of synthetic porous channels with polymersome substrates could provide a valuable tool for studying active transport processes in a composite membrane. These composites will ultimately expand the family of biologically inspired porous‐membrane mimics.
Methoxylation of Desazadesferrithiocin Analogues:  Enhanced Iron Clearing Efficiency (2003)

The impact of altering the octanol-water partition properties (log P) of analogues of desazadesferrithiocin, (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid, on the ligands' iron clearing properties is described. Increasing chelator lipophilicity can both substantially augment iron clearing efficiency in Cebus apella primates as well as alter the mode of iron excretion, favoring fecal over urinary output. The complications of iron overload are often associated with the metal's interaction with hydrogen peroxide, generating hydroxyl radicals (Fenton chemistry) and, ultimately, other related deleterious species. In fact, some iron chelators actually promote this chemistry. All of the compounds synthesized and tested in the current study are shown to be both inhibitors of the iron-mediated oxidation of ascorbate, thus removing the metal from the Fenton cycle, and effective radical scavengers.
Loss of heterozygosity on 10q23.3 and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions (2005)

LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.
Charge assisted laser desorption/ionization mass spectrometry of droplets (2008)

We propose and evaluate a new mechanism to account for analyte ion signal enhancement in ultraviolet-laser desorption mass spectrometry of droplets in the presence of corona ions. Our new insights are based on timing control of corona ion production, laser desorption, and peptide ion extraction achieved by a novel pulsed corona apparatus. We demonstrate that droplet charging rather than gas-phase ion-neutral reactions is the major contributor to analyte ion generation from an electrically isolated droplet. Implications of the new mechanism, termed charge assisted laser desorption/ionization (CALDI), are discussed and contrasted with those of the laser desorption atmospheric pressure chemical ionization method (LD-APCI). It is also demonstrated that analyte ion generation in CALDI occurs with external electric fields about one order of magnitude lower than those needed for atmospheric pressure matrix assisted laser desorption/ionization or electrospray ionization of droplets.
Amplification of closed circular DNA in vitro (1998)

The polymerase chain reaction is a powerful technique used to amplify nucleic acids in vitro. The reaction produces linear products, and as of yet, closed circular products have not been possible. Since the replicatively competent form of many DNA molecules is the closed circular form, it would be adventitious to amplify closed circular DNA as closed circular molecules. Until now, these molecules could only be amplified in vivo in appropriate host cells. Here, we describe an in vitro procedure, ligation-during-amplification (LDA), for selective amplification of closed circular DNA using sequence-specific primers. LDA is useful for site-directed mutagenesis, mutation detection, DNA modification, DNA library screening and circular DNA production.
Rapid incorporation kinetics and improved fidelity of a novel class of 3′-OH unblocked reversible terminators (2012)

Recent developments of unique nucleotide probes have expanded our understanding of DNA polymerase function, providing many benefits to techniques involving next-generation sequencing (NGS) technologies. The cyclic reversible termination (CRT) method depends on efficient base-selective incorporation of reversible terminators by DNA polymerases. Most terminators are designed with 3'-O-blocking groups but are incorporated with low efficiency and fidelity. We have developed a novel class of 3'-OH unblocked nucleotides, called Lightning Terminators™, which have a terminating 2-nitrobenzyl moiety attached to hydroxymethylated nucleobases. A key structural feature of this photocleavable group displays a 'molecular tuning' effect with respect to single-base termination and improved nucleotide fidelity. Using Therminator DNA polymerase, we demonstrate that these 3'-OH unblocked terminators exhibit superior enzymatic performance compared to two other reversible terminators, 3'-O-amino-TTP and 3'-O-azidomethyl-TTP. Lightning Terminators show maximum incorporation rates (k(pol)) that range from 35 to 45 nt/s, comparable to the fastest NGS chemistries, yet with catalytic efficiencies (k(pol)/K(D)) comparable to natural nucleotides. Pre-steady-state kinetic studies of thymidine analogs revealed that the major determinant for improved nucleotide selectivity is a significant reduction in k(pol) by >1000-fold over TTP misincorporation. These studies highlight the importance of structure-function relationships of modified nucleotides in dictating polymerase performance.
Selection on the Human Immunodeficiency Virus Type 1 Proteome following Primary Infection (2006)

Typically during human immunodeficiency virus type 1 (HIV-1) infection, a nearly homogeneous viral population first emerges and then diversifies over time due to selective forces that are poorly understood. To identify these forces, we conducted an intensive longitudinal study of viral genetic changes and T-cell immunity in one subject at < or =17 time points during his first 3 years of infection, and in his infecting partner near the time of transmission. Autologous peptides covering amino acid sites inferred to be under positive selection were powerful for identifying HIV-1-specific cytotoxic-T-lymphocyte (CTL) epitopes. Positive selection and mutations resulting in escape from CTLs occurred across the viral proteome. We detected 25 CTL epitopes, including 14 previously unreported. Seven new epitopes mapped to the viral Env protein, emphasizing Env as a major target of CTLs. One-third of the selected sites were associated with epitopic mutational escapes from CTLs. Most of these resulted from replacement with amino acids found at low database frequency. Another one-third represented acquisition of amino acids found at high database frequency, suggesting potential reversions of CTL epitopic sites recognized by the immune system of the transmitting partner and mutation toward improved viral fitness in the absence of immune targeting within the recipient. A majority of the remaining selected sites occurred in the envelope protein and may have been subjected to humoral immune selection. Hence, a majority of the amino acids undergoing selection in this subject appeared to result from fitness-balanced CTL selection, confirming CTLs as a dominant selective force in HIV-1 infection.
Effects of Branching Architecture and Linker on the Activity of Hyperbranched Polymer−Drug Conjugates (2009)

Drug release from hyperbranched polymer-drug conjugates and the subsequent activity are influenced by the branching architecture and the linker. To gain an understanding of these effects, we used hyperbranched polyol and G4-OH polyamidoamine (PAMAM) dendrimer with methyl prednisolone (MP) as the model drug. The drug was conjugated to dendrimer or polyol using a glutaric acid (GA) or a succinic acid (SA) spacer. Drug payload was the highest with polyol, while in the case of dendrimer, a higher payload was achieved with the GA than the SA spacer. Cell uptake of the polymer conjugates in A549 lung epithelial cells was higher than that of the free drug, and the conjugates largely localized in the cytosol. The anti-inflammatory activity of polymer conjugated MP, as measured by inhibition of prostaglandin synthesis, was the highest for MP-SA-dendrimer conjugate, followed by MP-GA-polyol conjugate, and then MP-GA-dendrimer conjugate. This study suggests that the branching architecture and spacer influence the drug payload and pharmacological activity of a drug-nanopolymer conjugate, which may significantly influence the in vivo efficacy of these nanodevices. This has key implications in the eventual in vivo efficacy of these nanodevices.
Gastrin and Colon Cancer: A Unifying Hypothesis (1996)

Recently, a variety of studies in vivo as well as in vitro have demonstrated that gastrointestinal hormones can influence the rate of proliferation of neoplastic cells. The widespread use of omeprazole, which increases serum gastrin, coupled with the findings that omeprazole causes gastric carcinoid tumors in rats and that a significant number of patients with adenocarcinoma of the colon have increased serum gastrin have focussed attention on the relationship between gastrin and colon cancer. In the present paper, we have reviewed the experimental findings in humans, experimental animals, and colon cancer cells in tissue culture that bear on the possible relationships between gastrin and colon cancer. Based on these findings, we have proposed two hypotheses that can account for the increased serum gastrin that occurs in some patients with colon cancer.
Encapsulation of orange oil in a spray dried double emulsion (2001)

Encapsulation is an important technique being used to protect sensitive food materials like flavours from deterioration. The capsule wall isolates them from the atmospheric oxygen, moisture, temperature and light. Encapsulation also masks some objectionable flavours, e.g. fish oil and some bitter antibiotics. In this study orange oil was encapsulated in the inner compartment of a double emulsion belonging to the type O1-W-O2 where O1 is orange oil, W is water and O2 is vegetable oil. In order to make orange oil double emulsion suitable for use in dry mixes, it was secondarily coated with wall materials of lactose and caseinate using spray drying technique. Entrapment of orange oil in such structure is also expected to slow down the release of volatiles and guarantee more protection for orange oil against atmospheric conditions. This method may have a potential application in different types of food or pharmaceutical products where maximum protection for flavours or slow release are required. This study includes detailed preparation of the spray dried double emulsion, evaluation of the encapsulation efficiency using light and scanning electron microscope and calculation of the yield percent of the encapsulated oil. In a separate paper we will examine the efficiency of spray dried double emulsion to control the release of orange oil by GC.
Fluid bolus therapy (2015)

Nowadays, several parameters are available to assess fluid responsiveness. Clinicians need to know all of them, with their limitations, without forgetting that the final aim of all therapies is to improve the microcirculation.