gebhart/patrepeval huggingface dataset:
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells (2004)

Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Replicate DNA array experiments identified 52 genes differentially expressed in nu61 tumors compared with SCC-61 tumors. Of these, 19 genes were in the IFN-signaling pathway and moreover, 25 of the 52 genes were inducible by IFN in the nu61 cell line. Among the genes involved in IFN signaling, STAT1alpha and STAT1beta were the most highly overexpressed in nu61 compared to SCC-61. STAT1alpha and STAT1beta cDNAs were cloned and stably transfected into SCC-61 tumor cells. Clones of SCC-61 tumor cells transfected with vectors expressing STAT1alpha and STAT1beta demonstrated radioprotection after exposure to 3 Gy (P < 0.038). The results indicate that radioresistance acquired during radiotherapy treatment may account for some treatment failures and demonstrate an association of acquired tumor radioresistance with up-regulation of components of the IFN-related signaling pathway.
HPMA copolymer–anticancer drug–OV-TL16 antibody conjugates. II. Processing in epithelial ovarian carcinoma cells in vitro (1998)

The binding, internalization, subcellular trafficking and in vitro cytotoxicity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-anti-cancer drug-OV-TL16 antibody (Ab) conjugates in the ovarian carcinoma OVCAR-3 cell line have been investigated. Adriamycin (ADR) and meso chlorin e6 mono(N-2-aminoethylamide) (Mce6) photosensitizer were used as anti-cancer drugs. Targeted (Ab-containing) conjugates were compared with non-targeted HPMA copolymer-drug conjugates and with free drugs. Targeted conjugates were taken up rapidly by cells and detected within lysosomes by confocal fluorescence microscopy. The ADR attached to polymer chains via a degradable GFLG spacer was released from the conjugate, diffused via the lysosomal membrane into the cytoplasm and ultimately accumulated in the cell nuclei. In contrast, conjugates containing ADR bound via the GG spacer accumulated in the lysosomes, but no fluorescence could be detected in the cell nuclei. Binding the drugs to a non-targeted HPMA copolymer decreased their cytotoxicity in vitro. The IC50 dose increased from 2 microM for free ADR to 150 microM for P(GFLG)-ADR (P is the HPMA copolymer backbone) and from 0.34 microM for free Mce6 (with light) to 290 microM for P-(GG)-Mce6. However, attachment of OV-TL16 Abs rendered HPMA copolymer-drug conjugates biorecognizable by OVCAR-3 cells and markedly increased their cytotoxicity. The IC50 doses were 4.4 and 0.38 microM for the targeted conjugates P(GFLG)-ADR-Ab and P(GG)-Mce6-Ab (with light), respectively. Biorecognition was shown to be specific by inhibition experiments with free Ab. The findings indicate the potential of these conjugates as effective agents in the treatment of ovarian cancer.
Miniature Passive Pressure Transensor for Implanting in the Eye (1967)

A newly developed method for measurement of intraocular and other physiological pressures consists of a novel displacement transducer contained in a distensible pillbox small enough (3 to 60 μl) to be implanted in the eye of a small laboratory animal. Nothing pierces or even touches the globe. This passive resonant transensor absorbs energy from an oscillating detector coil outside of the animal at a frequency dependent upon the pressure in the eye. Passive operation provides extended life, but limits useful range to less than 10 transducer diameters, which has proved sufficient for intraocular pressure measurement.
An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice (2014)

Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer's disease (AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor, decreased Aβ in brain interstitial fluid in a dose-dependent manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram. Citalopram arrested the growth of preexisting plaques and reduced the appearance of new plaques by 78%. In healthy human volunteers, citalopram's effects on Aβ production and Aβ concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable isotope labeling kinetics, with CSF sampling during acute dosing of citalopram. Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo. This change was associated with a 38% decrease in total CSF Aβ concentrations in the drug-treated group. The ability to safely decrease Aβ concentrations is potentially important as a preventive strategy for AD. This study demonstrates key target engagement for future AD prevention trials.
β-Catenin as Oncogene--The Smoking Gun (1997)

Three reports [Korinek et al. ( p. 1784 ), Morin et al . ( p. 1787 ), and Rubinfeld et al . ( p. 1790 )] in this issue provide new evidence about the molecular pathway that goes awry in colon cancer and melanoma. The protein β-catenin, previously known to be associated with the colon-cancer-causing adenomatous polyposis coli protein, is shown to be an oncogene in its own right. In his Perspective, Peifer discusses the normal functions of these proteins in mammals and flies and how their dysfunction can lead to cancer.
Tamoxifen enhances apoptotic effect of cisplatin on primary endometrial cell cultures. (2003)

CDDP induced apoptosis in all cultures regardless of hormonal environment, while TAM significantly enhanced CDDP-induced apoptosis in steroidal deficient media in an additive manner. These are novel findings depicting CDDP's effect on normal endometrium, singularly and combined with TAM.
Effect of Concentration on HPAM Retention in Porous Media (2014)

Summary This paper investigates the effect of hydrolyzed polyacrylamide (HPAM) polymer concentration on retention in porous media by use of both static and dynamic measurements. Consistent results by use of these two methods show that different polymer-retention behaviors exist in dilute, semidilute, and concentrated regions. In both the dilute and concentrated regions, polymer retention has little dependence on concentration. In contrast, in the semidilute region, polymer retention is concentration dependent. If a porous medium is first contacted sufficiently with dilute polymer solution to satisfy the retention, no significant additional retention occurs during exposure to higher HPAM concentrations. On the basis of the experimental results, a concentration-related retention mechanism is proposed that considers the orientation of the adsorbed polymer molecules and the interaction between molecular coils in solution. By use of this model, we explain why polymer retention does not show much dependence on concentration in the dilute and concentrated regimes. Further, in the semidilute region, we explain how moderate coil interactions lead to mixed adsorbed-polymer orientation and magnitude on rock surfaces, and retention becomes concentration dependent. In field applications of polymer and chemical floods, reduced polymer retention may be achieved by first injecting a low-concentration polymer bank.
A population screening test for antibody to measles virus. (1981)

In areas where sporadic cases of measles continue to occur in spite of vaccination programs, the availability of a simple screening test for determination of seropositivity to measles virus is desirable. A sensitive radioimmunoassay (RIA) screening test (ST) for the detection of IgG antibody to measles virus, based on a solid phase RIA, is described. The assays were performed on polyvinyl microtiter plates for which the RIAST requires only 5 microliters of serum per subject. Antigen consisted of a sonicated extract of measles virus-infected Vero cells. Rabbit antihuman IgG specific for the Fc-segment of human IgG, labeled with 125I, was used to detect human IgG bound to viral antigen. The basic RIA method was characterized by carrying out full titrations of sera of 53 healthy adults, 10 children, and 13 patients with measles-associated illness. These sera were also tested by the hemagglutination inhibition (HI) technique; most of the measles sera were also tested by complement fixation (CF). RIAST results (expressed as binding ratios) obtained for 52 healthy adults are compared with their RIA serum titers. Of the 200 sera of patients of various ages tested by the RIAST, 63 borderline sera were also tested by HI. The RIAST, which does not require serum treatment other than inactivation, proved to be more sensitive as an indicator of seropositivity than HI. Implications of the results and practical applications of the screening test are discussed.
Adipo-Myokines: Two Sides of the Same Coin—Mediators of Inflammation and Mediators of Exercise (2013)

This review summarizes the current literature regarding the most discussed contraction-regulated moykines like IL-6, IL-15, irisin, BDNF, ANGPTL4, FGF21, myonectin and MCP-1. It is suggested that the term myokine is restricted to proteins secreted from skeletal muscle cells, excluding proteins that are secreted by other cell types in skeletal muscle tissue and excluding proteins which are only described on the mRNA level. Interestingly, many of the contraction-regulated myokines described in the literature are additionally known to be secreted by adipocytes. We termed these proteins adipo-myokines. Within this review, we try to elaborate on the question why pro-inflammatory adipokines on the one hand are upregulated in the obese state, and have beneficial effects after exercise on the other hand. Both, adipokines and myokines do have autocrine effects within their corresponding tissues. In addition, they are involved in an endocrine crosstalk with other tissues. Depending on the extent and the kinetics of adipo-myokines in serum, these molecules seem to have a beneficial or an adverse effect on the target tissue.
Solvent-Programmed Microchip Open-Channel Electrochromatography (1998)

Open-channel electrochromatography in combination with solvent programming is demonstrated using a microchip device. Channel walls were coated with octadecylsilanes at ambient temperatures, yielding stationary phases for chromatographic separations of neutral dyes. The electroosmotic flow after coating was sufficient to ensure transport of all species and on-chip mixing of isocratic and gradient elution conditions with acetonitrile-buffer mixtures. Chips having different channel depths between 10.2 and 2.9 μm were evaluated for performance, and van Deemter plots were established. Channel depths of about 5 μm were found to be a good compromise between efficiency and ease of operation. Isocratic and gradient elution conditions were easily established and manipulated by computer-controlled application of voltages to the terminals of the microchip. Linear gradients with different slopes, start times, duration times, and start percentages of organic modifier proved to be powerful tools to tune selectivity and analysis time for the separation of a test mixture. Even very steep gradients still produced excellent efficiencies. Together with fast reconditioning times, complete runs could be finished in under 60 s.
In Vitro Effects of Anti-HIV Immunotoxins Directed against Multiple Epitopes on HIV Type 1 Envelope Glycoprotein 160 (1996)

We have used a panel of anti-gp160 MAbs to construct anti-HIV immunotoxins by coupling antibodies to ricin A chain (RAC). The ability of the immunotoxins to kill HIV-1-infected cells and halt the spread of infection was tested in tissue culture on persistently and acutely infected cell lines and primary lymphocyte cultures stimulated with phytohemagglutinin (PHA blasts). Laboratory strains and clinical isolates of HIV both were tested. The constitution and antigen-binding capacity of the immunotoxins were confirmed by ELISA and indirect immunofluorescence. Immunotoxins that bind epitopes exposed on the cell surface effectively killed persistently infected cells, although killing was not directly proportional to binding of immunotoxin to cell. The activity of anti-gp41, but not anti-gp120, immunotoxins was markedly enhanced in the presence of soluble CD4 or peptides corresponding to the CDR3 region of CD4. CD4-mediated enhancement of anti-gp41 immunotoxin activity was observed for laboratory strains neutralized by sCD4 and for clinical isolates that were resistant to neutralization by sCD4. Immunotoxin action was potentiated by brefeldin A, bafilomycin A1, cortisone, and an amphipathic fusion peptide, but not by cytochalasin D, nocodazol, monodansyl cadaverine, or trans-retinoic acid. Anti-HIV immunotoxins are useful tool with which to study the functional expression of gp120/gp41 antigens on the surface of HIV-infected cells, as well as potential AIDS therapeutics. Because these studies relate to the accessibility of viral antigens to antibody-mediated attack, these studies also have relevance for vaccine development.
Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28 (2007)

The haplotypes significantly associated with reduced area under concentration curve ratios and neutropenia contained UGT1A1*6 or *28, and both of them should be genotyped before irinotecan is given to Japanese and probably other Asian patients.
Impact of pulmonary arterial hypertension (PAH) on the lives of patients and carers (2013)

Background: There are limited data on the broader impact of PAH, beyond the physical symptoms, on the lives of patients and carers. Aims &amp; objectives: To better understand how and to what extent PAH affects four main areas of patients’ and carers’ lives: physical, practical, emotional and social, including information needs. Methods: An international, self-reported survey was developed in collaboration with a multidisciplinary steering committee of PAH specialists and patient association representatives. The survey comprised a qualitative phase 1: patient (n = 25) and carer (n = 15) interviews to identify themes, and a quantitative phase 2: online/postal questionnaire completed by patients (n = 326) and carers (n = 129) in five EU countries. Recruitment was mainly via patient associations. Results: 56% of patients and 57% of carers felt that PAH had a very significant impact on their daily lives. Patients frequently described feelings of anger and frustration and emotions commonly associated with depression. Patients also felt isolated, primarily because PAH is not a ‘visible’ disease. PAH also has a marked impact on intimacy and relationships for patients and carers. Employment was affected for patients (85%) and carers (29%), resulting in a reduced household income for many families. Patients and carers described a lack of information from healthcare professionals on the wider aspects of PAH, stating that patient associations are the most important source for this information. Conclusions: PAH has a major global impact on patients and carers. Survey results highlight the need for multidisciplinary and multidimensional care, focusing on QoL and including collaboration with patient associations.
Transfer of an ovine metallothionein-ovine growth hormone fusion gene into swine. (1997)

An ovine metallothionein-1a (oMT1a)-ovine growth hormone (oGH) fusion gene was microinjected into 400 pig zygotes, the zygotes were transferred into recipient females, and 15 founder transgenic pigs were born. Of 12 transgenic pigs assayed, five expressed high levels of oGH (> 900 ng/mL plasma), one expressed low levels of oGH (10 to 30 ng/mL), and six did not express oGH. Dietary supplementation with 2,000 ppm of zinc for 6 d induced a 20-fold increase in plasma oGH in the transgenic pig with low expression but did not induce expression in the six transgenic pigs with no constitutive oGH expression. The average daily gain of five transgenic pigs with elevated oGH was similar to that of non-transgenic littermates during a 9-wk feeding trial (P = .52). The liver, kidney, adrenal, and thyroid weights were all significantly heavier for the oGH-expressing transgenic pigs than for non-transgenic littermates. Total carcass fat, longissimus muscle fat, subcutaneous backfat thickness, and loin eye area were lower and carcass protein and water content and beta R fiber area of longissimus muscle were higher in the transgenic pigs with elevated oGH than in their littermate controls (P < .05 for each). The data indicate that even though the oMT1a promoter was more inducible by zinc than was previously reported for the mouse MT promoter in swine, the former provided a higher level of oGH expression than the mouse MT promoter.
A monolithic power op amp (1988)

The standard junction-isolated power process has been modified by the addition of polycrystalline-film resistors to solve the topological problems encountered in making 90-W, 80-V, 10-A power transistors and connecting them together for a push-pull output. An all n-p-n output stage that holds crossover distortion to 0.01% while driving a 4- Omega load, even with the quiescent current below 20 mA, has been developed. It is stable with all reactive loads and does not have the spurious-oscillation problems observed with the familiar quasicomplementary amplifier. These innovations are described along with the design of a complete power op amp, the LM12. The prevention of failures from substrate currents which occur when the output is driven outside the supply by inductive loads is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
New Biomarker for Neovascular Age-Related Macular Degeneration: Eotaxin-2 (2012)

Recently, eotaxin-CCR3 was reported to play an important role in choroidal neovascularization (CNV) development and was documented to be superior than vascular endothelial growth factor-A treatment when tested in CNV animals. As eotaxin studies are lacking in the human age-related macular degeneration (AMD) patients, we sought to determine whether eotaxin-2 (CCL24) has any association with inflammatory processes that occur in CNV. CCL24 levels were determined by enzyme linked immunosorbant assay (ELISA) after normalization to total serum protein and levels of ELISA were correlated to various risk factors in about 133 AMD patients and 80 healthy controls. The CCL24 levels were significantly higher in wet AMD patients as compared with dry AMD and normal controls. There was a significant difference when compared among wet AMD patients (i.e., minimally classic, predominantly classic, and occult). We also report significant difference in the CCL24 levels of Avastin-treated and untreated AMD patients. This study shows that CCL24 levels were found to be significantly increased in AMD patients despite Avastin treatment as compared with normal controls and those without Avastin, indicating that CCL24 may have an association with CNV and may be an important target to validate future therapeutic approaches in AMD in tandem with Avastin treatment.
Multi-wavelength imaging with the adaptive optics scanning laser Ophthalmoscope (2006)

The adaptive optics scanning laser ophthalmoscope has been fitted with three light sources of different wavelengths to allow simultaneous or separate imaging with one, two or three wavelength combinations. The source wavelengths used are 532 nm, 658 nm and 840 nm. Typically the instrument is used in dual-frame mode, performing imaging at 840 nm and precisely coincident retinal stimulation in one of the visible wavelengths. Instrument set-up and single-detector image capture are described. Simultaneous multi-wavelength imaging in the living human retina is demonstrated. The chromatic aberrations of the human eye lead to lateral and axial shifts, as well as magnification differences in the image, from one wavelength to another. Measurement of these chromatic effects is described for instrument characterization purposes.
Prevalence of Hypogonadism among Men with Weight Loss Related to Human Immunodeficiency Virus Infection Who Were Receiving Highly Active Antiretroviral Therapy (2000)

Previous studies have indicated that there is a significant prevalence (50%) of hypogonadism among men with acquired immunodeficiency syndrome (AIDS)-associated wasting, and for these patients testosterone administration has been shown to increase lean body mass and improve quality of life. However, the prevalence of hypogonadism is not known among men with weight loss related to human immunodeficiency virus (HIV) infection who are receiving highly active antiretroviral therapy (HAART). From 1997 through 1999, we investigated total and free testosterone levels in 90 men who were <90% of ideal body weight or had weight loss of >10% from preillness weight; 71% of these subjects were receiving HAART. Twenty-one percent of the subjects receiving HAART had low free testosterone levels. No correlation was seen between weight, CD4 cell count, medication status, and other clinical factors. These data suggest that hypogonadism remains relatively common in men with AIDS wasting, despite treatment with HAART. HIV-infected men with wasting syndrome should be screened for hypogonadism and receive physiological androgen replacement therapy if they are hypogonadal.
Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders (2012)

Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs). Propionic acid (PPA) and its related short-chain fatty acids (SCFAs) are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio). SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible environmental agents that can trigger ASDs or ASD-related behaviors and deserve further exploration in basic science, agriculture, and clinical medicine.