gebhart/patrepeval huggingface dataset:
Polyenylphosphatidylcholine improves the lipoprotein profile in diabetic patients. (1994)

Patients with diabetes mellitus commonly exhibit pathological lipoprotein profiles and concomitant cardiovascular or peripheral atherosclerotic complications. Thirty non-insulin-dependent diabetics with secondary hyperlipidemia received 2.7 g 3-sn-polyenylphosphatidylcholine (PPC) or placebo daily, orally over a 2-month period under randomized, double-blind trial conditions, to investigate the efficacy and tolerance of the treatment. This period was followed by a one-month observation phase without investigational medication. Serum LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides were determined on days 1, 14, 28, 56 and 84. After 56 days of treatment with PPC, the primary variable of effectiveness, LDL cholesterol, decreased significantly (p = 0.0174) by 17% from 191 +/- 31 to 159 +/- 36 mg/dl, whereas values did not change in the placebo group. Total cholesterol (TC) in serum decreased by 16% from 303 +/- 22 to 255 +/- 23 mg/dl with PPC. In the placebo group, only a slight decrease from 292 +/- 27 to 289 +/- 41 mg/dl occurred. Mean serum triglyceride (TG) levels fell by 9% from 194 +/- 32 to 177 +/- 27 mg/dl in the PPC group. In the control group, values increased from 193 +/- 34 to 202 +/- 41 mg/dl. The differences in LDL, TC and TG between the treatment groups were statistically significant; p = 0.0014, p = 0.0001 and p = 0.007, respectively. HDL cholesterol in serum increased 12% from 50 +/- 10 to 55 +/- 13 mg/dl after PPC application. The control group did not show any alteration of mean HDL cholesterol level at any time.(ABSTRACT TRUNCATED AT 250 WORDS)
Immune responses and protection against vaginal infection after nasal or vaginal immunization with attenuated herpes simplex virus type‐2 (1999)

We compared nasal and vaginal immunizations using attenuated herpes simplex virus type-2 (HSV-2) for protection against vaginal infection with wild-type HSV-2. Mice were immunized once intranasally, intravaginally after progestin (DP) treatment, or intravaginally with scarification after oestradiol treatment. Compared with vaginal immunizations, nasal immunization did not increase immunoglobulin A (IgA) plasma cell numbers in the vagina or elicit a higher antiviral IgA titre in vaginal secretions. Both types of vaginal immunizations increased the number of immunoglobulin G (IgG) plasma cells in the vagina and the secretion/serum titre ratio of IgG antiviral antibody, indicating local production of virus-specific IgG in these groups. Cell-mediated immunity in the vagina, as indicated by memory T-cell secretion of interferon-gamma (IFN-gamma) in situ 20 hr after HSV-2 challenge, was essentially equivalent in the vaginally immunized groups but significantly lower in the nasal group, while lymphocyte recruitment to the vagina was similar in all three groups. All three immunizations protected all mice from neurological disease after challenge, but vaginal DP immunization induced the greatest immunity against reinfection of the vaginal epithelium.
Alkaline cleavage of ginsenosides. (1987)

The genuine sapogenin 20 (S) -protopanaxatriol (1) and its corresponding prosapogenin 20 (S) -ginsenoside-Rh1 (3) were prepared by direct treatment of the peracetate of 20 (S) -ginsenoside-Rg2 in an alcoholic alkaline solution. Two kinds of alkaline conditions were compared.
Double‐blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients (2004)

Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P < 0.05, Fisher's exact test). The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD.
THE REACTION PRODUCTS OF INDOLS WITH DIAZOESTERS (1935)

In conformity with findings of previous work on indols and in contradistinction to more recent work on pyrrols, the action of diazoesters on indol leads to 3-substituted as well as a small amount of 1:3-disubstituted derivatives. The formation of 2-substituted derivatives could not be demonstrated. The reaction discussed is a convenient one for the synthesis of a wide diversity of indol compounds.
High frequency variability of transcephalic electrical impedance &#x2014; A new parameter for monitoring of neonatal cerebral circulation? (1992)

Transcephalic electrical impedance, ECG, respirogram and arterial blood pressure were continuously monitored for 30 minutes at 8-hour intervals during the first day of life in 50 neonates at the neonatal intensive care unit. In 10 infants who developed severe intracerebral haemorrhage high-frequency fluctuatios of impedance signal were significantly lower when compared to controls or infants with mild intraventricular haemorrhage. The fluctuations seemed to be also small in infants with cerebral echodensities and periventricular leucomalacia. This could imply disturbed control of cerebral circulation in these critically ill newborns. We conclude that the variability of the transcephalic electrical impedance is an interesting new parameter for monitoring cerebral circulation which may be helpful already during the first day of life.
Imaging of tumor in patients with indium-111-labeled biotin and streptavidin-conjugated antibodies: preliminary communication. (1990)

Tumor localization in patients has been achieved through the in vivo use of streptavidin and biotin. In these preliminary studies, the monoclonal antibody HMFG1 was conjugated with streptavidin and 1 mg was administered intravenously to each of 10 patients with documented squamous cell carcinoma of the lung. Two to 3 days later, 111In-labeled biotin was also administered intravenously. No evidence of toxicity was observed. Background radioactivity levels were reduced in liver (1% ID at 24 hr) and kidneys (2%) and in all other normal tissues and blood. Images of lung tumor were obtained in as little as 2 hr following administration of labeled biotin. In eight patients, tumor was detected with labeled biotin alone without the previous administration of streptavidin-conjugated antibody but in three of these patients, the images were improved with the prior administration of conjugated antibody. These results suggest that this approach may improve the tumor-to-normal tissue radioactivity ratios in radioimmunotargeting.
Targeting of Mitogen-Activated Protein Kinases and Phosphatidylinositol 3 Kinase Inhibits Hepatocyte Growth Factor/Scatter Factor–Induced Angiogenesis (2003)

These data indicate that MEK and PI3K inhibitors represent a promising approach to the clinical management of pathological conditions characterized by overt HGF/SF-induced angiogenesis.
Compensation Issues and the Meaning of Section 85 of the RMA (2002)

Section 85 of the Resource Management Act 1991 (RMA) prohibits compensation claims arising from the effect of planning restrictions, but provides that persons having an interest in land can apply to the Environment Court to change a plan provision where it would render the land incapable of reasonable use. Judicial pronouncements to date have asserted that relief is only available where the proposed plan change does not endanger planning controls. The article contends that this approach is unwarranted, when considered in light of the RMA's presumption that all reasonable forms of land use are permissible. Indeed the current judicial approach has the effect of enabling councils to promulgate restrictive zoning controls with impunity, as the landowner has no other remedy. In contrast, the author argues that on a correct interpretation, s 85 should be seen as a linchpin of the RMA defining and limiting the ability of local authorities to control and direct land use by means of prescriptive land controls such as zoning.
Time Series Analysis of Non-Gaussian Observations Based on State Space Models from Both Classical and Bayesian Perspectives (2000)

Summary The analysis of non-Gaussian time series by using state space models is considered from both classical and Bayesian perspectives. The treatment in both cases is based on simulation using importance sampling and antithetic variables; Markov chain Monte Carlo methods are not employed. Non-Gaussian disturbances for the state equation as well as for the observation equation are considered. Methods for estimating conditional and posterior means of functions of the state vector given the observations, and the mean-square errors of their estimates, are developed. These methods are extended to cover the estimation of conditional and posterior densities and distribution functions. The choice of importance sampling densities and antithetic variables is discussed. The techniques work well in practice and are computationally efficient. Their use is illustrated by applying them to a univariate discrete time series, a series with outliers and a volatility series.
DNA polymerases in biotechnology (2014)

EDITORIAL article Front. Microbiol., 01 December 2014Sec. Evolutionary and Genomic Microbiology Volume 5 - 2014 | https://doi.org/10.3389/fmicb.2014.00659
DNA crosslinking and biological activity of a hairpin polyamide-chlorambucil conjugate (2003)

A prototype of a novel class of DNA alkylating agents, which combines the DNA crosslinking moiety chlorambucil (Chl) with a sequence-selective hairpin pyrrole-imidazole polyamide ImPy-beta-ImPy-gamma-ImPy-beta-Dp (polyamide 1), was evaluated for its ability to damage DNA and induce biological responses. Polyamide 1-Chl conjugate (1-Chl) alkylates and interstrand crosslinks DNA in cell-free systems. The alkylation occurs predominantly at 5'-AGCTGCA-3' sequence, which represents the polyamide binding site. Conjugate-induced lesions were first detected on DNA treated for 1 h with 0.1 micro M 1-Chl, indicating that the conjugate is at least 100-fold more potent than Chl. Prolonged incubation allowed for DNA damage detection even at 0.01 micro M concentration. Treatment with 1-Chl decreased DNA template activity in simian virus 40 (SV40) in vitro replication assays. 1-Chl inhibited mammalian cell growth, genomic DNA replication and cell cycle progression, and arrested cells in the G2/M phase. Moreover, cellular effects were observed at 1-Chl concentrations similar to those needed for DNA damage in cell-free systems. Neither of the parent compounds, unconjugated Chl or polyamide 1, demonstrated any cellular activity in the same concentration range. The conjugate molecule 1-Chl possesses the sequence-selectivity of a polyamide and the enhanced DNA reactivity of Chl.
Production of herpesvirus of turkeys in microcarrier culturing system--a new method for production of vaccine against Marek's disease. (1985)

A microcarrier (MC) culturing system for production of a vaccine against Marek's disease virus is presented. Cytodex-3 beads (Pharmacia) and DE-53 microgranular (Whatman) are the recommended microcarriers. Primary cells from chick embryo as well as cells from a quail cell line (QT-6, established from a Japanese quail) were found to be good hosts for growth of herpesvirus of turkeys (HVT). HVT, the vaccine strain against Marek's disease, was successfully grown and harvested on the above mentioned MCs and cells. The findings of this study, open new possibilities in the production of HVT for various purposes such as basic research and vaccine preparation.
International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (2016)

As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.
Routing using a pyramid data structure (2003)

A general-purpose routing algorithm is proposed. Ideas behind both the maze-running algorithm and the hierarchical routing algorithm are combined into a hybrid routing algorithm. The new algorithm demonstrates a speed compatible to a hierarchical router and produces routings with quality equivalent to that by a maze router. Hybrid routing is based on the maze-running method with a third search dimension added. The extra search space is built by recursively constructing a hierarchy of coarser grid meshes. A user-given parameter can turn this algorithm into a pure maze router, a pure hierarchical router, or a wide spectrum of hybrid routers with different speed/quality characteristics between the extremes. With this approach, it is possible to handle easily a routing of large size, such as those encountered in the sea-of-gate layout.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Field use of D2 18O to measure energy expenditure of soldiers at different energy intakes (1989)

To test the application of doubly labeled water under adverse field conditions, energy expenditures of 16 special operations soldiers were measured during a 28-day field training exercise. Subjects were matched by fat-free mass and divided equally between an ad libitum ready-to-eat meal diet and a 2,000 kcal/day lightweight ration. Subjects recorded intakes daily, and body composition was measured before and after the exercise. At the beginning of the study, subjects moved to a new northerly location and, therefore, a new water supply. To compensate for this, a group of soldiers who did not receive heavy water was followed to measure isotopic base-line changes. Energy expenditure by doubly labeled water was in agreement with intake/balance (3,400 +/- 260 vs. 3,230 +/- 520 kcal/day). The overall coefficient of variation of energy expenditure by doubly labeled water was half that of intake/balance (7.6 vs. 16.1%). The coefficient of variation of repeat measures with doubly labeled water was 7.3%. Energy expenditure of the ready-to-eat meal group, 3,540 +/- 180 kcal/day, was not significantly different from the lightweight ration group, 3,330 +/- 301 kcal/day. Doubly labeled water was valid under field conditions.
Modulation of murine macrophage function by IL-13. (1993)

Activated macrophages are important effector cells for immune response to many parasites and immune responses are strongly modulated in part by the effect of Th cell-derived cytokines on macrophages. Th1-derived cytokines such as IFN-gamma are strong stimulators of macrophage activation, while cytokines produced by Th2 cells, including IL-4 and IL-10, have been shown under some conditions to inhibit macrophage activities associated with inflammatory responses. IL-13, a recently described cytokine produced by Th2 cells, is also capable of down-modulating macrophage activity in a manner similar to that previously described for IL-4. Treatment of activated macrophages with IL-13 reduces the production of inflammatory monokines in response to IFN-gamma or LPS, both potent stimulators of these factors. In addition, IL-13 decreases the production of nitric oxide by activated macrophages. Nitric oxide has been implicated in both macrophage cytotoxicity and macrophage-associated immunosuppression. The suppression of nitric oxide by IL-13 leads to a decrease in parasiticidal activity by activated macrophages. However, our data indicate that IL-13 has pleiotropic effects, while the inflammatory potential of activated macrophages is significantly reduced, the potential of other macrophage subsets is unimpaired. These data indicate that IL-13 could be a potent modulator of immune responses in vivo, with effects that may embrace both macrophage suppressive and macrophage potentiating functions.
Intratracheal and oral administration of SM‐276001: A selective TLR7 agonist, leads to antitumor efficacy in primary and metastatic models of cancer (2012)

Topical TLR7 agonists such as imiquimod are highly effective for the treatment of dermatological malignancies; however, their efficacy in the treatment of nondermatological tumors has been less successful. We report that oral administration of the novel TLR7-selective small molecule agonist; SM-276001, leads to the induction of an inflammatory cytokine and chemokine milieu and to the activation of a diverse population of immune effector cells including T and B lymphocytes, NK and NKT cells. Oral administration of SM-276001 leads to the induction of IFNα, TNFα and IL-12p40 and a reduction in tumor burden in the Balb/c syngeneic Renca and CT26 models. Using the OV2944-HM-1 model of ovarian cancer which spontaneously metastasizes to the lungs following subcutaneous implantation, we evaluated the efficacy of intratracheal and oral administration of SM-276001 in an adjuvant setting following surgical resection of the primary tumor. We show that both oral and intratracheal TLR7 therapy can reduce the frequency of pulmonary metastasis, and metastasis to the axillary lymph nodes. These results demonstrate that SM-276001 is a potent selective TLR7 agonist that can induce antitumor immune responses when dosed either intratracheally or orally.
Interleukin-12 Therapy of Cutaneous T-Cell Lymphoma Induces Lesion Regression and Cytotoxic T-Cell Responses (1999)

Progression of cutaneous T-cell lymphoma (CTCL) is associated with profound defects in cell-mediated immunity and depressed production of cytokines, which support cell-mediated immunity. Because we have observed marked defects in interleukin-12 (IL-12) production in CTCL and because IL-12 is critical for antitumor cytotoxic T-cell responses, we initiated a phase I dose escalation trial with recombinant human IL-12 (rhIL-12) where patients received either 50, 100, or 300 ng/kg rhIL-12 twice weekly subcutaneously or intralesionally for up to 24 weeks. Ten patients were entered: 5 with extensive plaque, 3 with Sezary syndrome, and 2 with extensive tumors with large cell transformation. One patient with Sezary syndrome dropped out after 1 week for personal reasons. Subcutaneous dosing resulted in complete responses (CR) in 2 of 5 plaque and partial responses (PR) in 2 of 5 plaque, and 1 of 2 Sezary syndrome (overall response rate CR+PR 5 of 9, 56%). A minor response also occurred in 1 of 5 plaque patients. Intralesional dosing resulted in individual tumor regression in 2 of 2 patients. Biopsy of regressing lesions showed a significant decrease in the density of the infiltrate in all cases and complete resolution of the infiltrate among those with clinical lesion resolution. An increase in numbers of CD8-positive and/or TIA-1-positive T cells were observed on immunohistochemical analysis of skin biopsy specimens obtained from regressing skin lesions. Adverse effects of rhIL-12 on this regimen were minor and limited and included low-grade fever and headache. One patient discontinued rhIL-12 at week 6 because of depression. These results suggest that rhIL-12 may augment antitumor cytotoxic T-cell responses and may represent a potent and well-tolerated therapeutic agent for CTCL.
Improved Stimulation of Human Dendritic Cells by Receptor Engagement with Surface-modified Microparticles (2003)

Dendritic cells (DC) need to be stimulated before they can function to initiate immune responses. This study investigates whether microparticles loaded with antibodies specific for selected receptors expressed by DC can induce stimulation of these cells. Plain microparticles were compared with microparticles which were surface-loaded with specific antibodies for human CD40, Fc(gamma), alpha(v)beta3 and alpha(v)beta5 integrin receptors. The antibodies were either physically adsorbed or covalently linked to the microparticle surface. Anti-CD40 antibody and human IgG immobilised on the surface of microparticles induced enhanced DC maturation and activation as expressed by CD83 and CD86 upregulation. IL-12 secretion was induced at a detectable but relatively low level. Both anti-integrin antibodies (anti-alpha(v)beta3 and anti-alpha(v)beta5) induced comparable and considerable maturation of DC, but only anti-alpha(v)beta3 antibody induced significant activation of DC, whereas anti-alpha(v)beta5 did not. The stimulatory effects were most pronounced by employing microparticles with covalently linked antibodies, but were also observed to a minor extent when the antibodies were physically adsorbed to polystyrene and biodegradable poly(lactide-co-glycolide) microparticles. Engineering of microparticles by surface conjugation of specific ligands to stimulate DC may increase the effectiveness of microparticulate vaccine delivery systems.
Telomerase reverse transcriptase genes identified in Tetrahymena thermophila and Oxytricha trifallax (1998)

Telomerase reverse transcriptase (TERT) has been identified as the catalytic subunit of the chromosome end-replicating enzyme in Euplotes, yeasts, and mammals. However, it was not reported among the protein components of purified Tetrahymena telomerase, the first telomerase identified and the most thoroughly studied. It therefore seemed possible that Tetrahymena used an alternative telomerase that lacked a TERT protein. We now report the cloning and sequencing of a Tetrahymena thermophila gene whose encoded protein has the properties expected for a TERT, including large size (133 kDa), basicity (calculated pI = 10.0), and reverse transcriptase sequence motifs with telomerase-specific features. The expression of mRNA from the Tetrahymena TERT gene increases dramatically at 2-5 h after conjugation, preceding de novo addition of telomeres to macronuclear DNA molecules. We also report the cloning and sequencing of the ortholog from Oxytricha trifallax. The Oxytricha macronuclear TERT gene has no introns, whereas that of Tetrahymena has 18 introns. Sequence comparisons reveal a new amino acid sequence motif (CP), conserved among the ciliated protozoan TERTs, and allow refinement of previously identified motifs. A phylogenetic tree of the known TERTs follows the phylogeny of the organisms in which they are found, consistent with an ancient origin rather than recent transposition. The conservation of TERTs among eukaryotes supports the model that telomerase has a conserved core (TERT plus the RNA subunit), with other subunits of the holoenzyme being more variable among species.
Gene assemblyviaone-pot chemical ligation of DNA promoted by DNA nanostructures (2018)

A gene was obtained from 14 oligonucleotides self-assembled and chemically ligated in a DNA nanostructure.
Biological Characterization of ARRY-142886 (AZD6244), a Potent, Highly Selective Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor (2007)

ARRY-142886 is a potent and selective MEK1/2 inhibitor that is highly active in both in vitro and in vivo tumor models. This compound is currently being investigated in clinical studies.