gebhart/patrepeval huggingface dataset:
Heat‐inducible expression of FLP gene in maize cells (1995)

The soybean heat-shock gene promoter (Gmhsp 17.5-E) has been used to direct expression of gusA and FLP genes in maize cells. At inducible temperatures, in transient expression assays, gusA gene expression controlled by the heat-shock promoter is about 10-fold higher than the expression directed by the CaMV 35S promoter. The Gmhsp 17.5-E promoter preserves its regulatory functions in heterologous maize cells after random integration into genomic DNA. Heat-shock inducible expression of the FLP gene was investigated by co-transformation of the FLP expression vector (pHsFLP) and a recombination test vector (pUFNeoFmG) into maize protoplasts. Co-transformed protoplasts were incubated at 42 degrees C for 2 h. This treatment induced recombination of 20-25% of the available FRT sites in transient assays. As a result of heat-shock treatment of stably co-transformed maize cells, activation of gusA gene expression and an associated decrease or elimination of NPT-II activity in transgenic maize lines was observed. Molecular evidence was obtained of the expected DNA excision process catalyzed by the FLP protein in maize transgenic cells. Thus, the experiments presented in this paper indicate that the FLP protein can recognize and subsequently recombine the FRT target sites that had integrated into plant genomic DNA, and that regulated expression of the FLP gene is possible in maize cells using the soybean heat-shock promoter.
Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG (2002)

Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions.
MicroRNA-203 inhibits cell proliferation by repressing ΔNp63 expression in human esophageal squamous cell carcinoma (2011)

Our data implied that miR-203 could inhibit cell proliferation in human ESCC through ΔNp63-mediated signal pathway. Therefore, we propose that miR-203 might be used as a therapeutic agent for human ESCC.
High levels of energy expenditure in obese women. (1986)

Total free living energy expenditure was compared in lean and obese women by the new doubly labelled water method and partitioned into basal metabolism and thermogenesis plus activity by whole body calorimetry. Average energy expenditure was significantly higher in the obese group (10.22 versus 7.99 MJ/day (2445 versus 1911 kcal/day); p less than 0.001) resulting from an increase in the energy cost of both basal metabolism and physical activity. Self recorded energy intakes were accurate in the lean subjects but underestimated expenditure by 3.5 MJ/day (837 kcal/day) in the obese group. Basal metabolic rate and energy expenditure on thermogenesis plus activity were identical in the two groups when corrected for differences in fat free mass and total body mass. In the obese women in this series there was no evidence that their obesity was caused by a metabolic or behavioural defect resulting in reduced energy expenditure.
Statistical Analysis of fMRI Time-Series: A Critical Review of the GLM Approach (2011)

Functional magnetic resonance imaging (fMRI) is one of the most widely used tools to study the neural underpinnings of human cognition. Standard analysis of fMRI data relies on a general linear model (GLM) approach to separate stimulus induced signals from noise. Crucially, this approach relies on a number of assumptions about the data which, for inferences to be valid, must be met. The current paper reviews the GLM approach to analysis of fMRI time-series, focusing in particular on the degree to which such data abides by the assumptions of the GLM framework, and on the methods that have been developed to correct for any violation of those assumptions. Rather than biasing estimates of effect size, the major consequence of non-conformity to the assumptions is to introduce bias into estimates of the variance, thus affecting test statistics, power, and false positive rates. Furthermore, this bias can have pervasive effects on both individual subject and group-level statistics, potentially yielding qualitatively different results across replications, especially after the thresholding procedures commonly used for inference-making.
Morphology, distribution, and variability of the epicardiac neural ganglionated subplexuses in the human heart (2000)

Concomitant with the development of surgical treatment of cardiac arrythmias and management of myocardial ischemia, there is renewed interest in morphology of the intrinsic cardiac nervous system. In this study, we analyze the topography and structure of the human epicardiac neural plexus (ENP) as a system of seven ganglionated subplexuses. The morphology of the ENP was revealed by a histochemical method for acetylcholinesterase in whole hearts of 21 humans and examined by stereoscopic, contact, and bright-field microscopy. According to criteria established to distinguish ganglionated subplexuses, they are epicardiac extensions of mediastinal nerves entering the heart through discrete sites of the heart hilum and proceeding separately into regions of innervation by seven pathways, on the courses of which epicardiac ganglia, as wide ganglionated fields, are plentifully located. It was established that topography of epicardiac subplexuses was consistent from heart to heart. In general, the human right atrium was innervated by two subplexuses, the left atrium by three, the right ventricle by one, and the left ventricle by three subplexuses. The highest density of epicardiac ganglia was identified near the heart hilum, especially on the dorsal and dorsolateral surfaces of the left atrium, where up to 50% of all cardiac ganglia were located. The number of epicardiac ganglia identified for the human hearts in this study ranged from 706 up to 1,560 and was not correlated with age in most heart regions. The human heart contained on average 836 +/- 76 epicardiac ganglia. The structural organization of ganglia and nerves within subplexuses was observed to vary considerably from heart to heart and in relation to age. The number of neurons identified for any epicardiac ganglion was significantly fewer in aged human compared with infants. By estimating the number of neurons within epicardiac ganglia and relating this to the number of ganglia in the human epicardium, it was calculated that approximately 43,000 intrinsic neurons might be present in the ENP in adult hearts and 94,000 neurons in young hearts (fetuses, neonates, and children). In conclusion, this study demonstrates the total ENP in humans using staining for acetylcholinesterase, and provides a morphological framework for an understanding of how intrinsic ganglia and nerves are structurally organized within the human heart.
A Survey of Pain, Pressure, and Discomfort Induced by Commonly Used Oral Local Anesthesia Injections (2005)

Intraoral local anesthesia is essential for delivering dental care. However, it is often perceived by some patients as the most painful and in some instances as the only painful part of the treatment, leading in extreme cases to avoidance of dental care. The present study measured the variables of pain, pressure, and discomfort caused by 4 commonly used local anesthesia injections: local infiltration, mental nerve block, inferior alveolar nerve block, and periodontal ligament injections. Patients were asked to grade pain, discomfort, and pressure on a visual analog scale as associated with needle insertion, operator finger position in the mouth, and pressure at injection. The inferior alveolar injection was graded to be the most painful followed by periodontal ligament and then mental nerve block injections. The periodontal ligament injections yielded the highest pressure scores. The inferior alveolar block injection yielded significantly more discomfort than local infiltration and mental nerve block injections when comparing finger and needle position. Local infiltration in the anterior maxillary region yielded the highest needle insertion and finger position discomfort scores. The present study suggests that the dental operator should be aware of local anesthesia injection pain, pressure, and discomfort together with efficacy of technique.
Deep Learning for Real-Time Atari Game Play Using Offline Monte-Carlo Tree Search Planning (2014)

The combination of modern Reinforcement Learning and Deep Learning ap-proaches holds the promise of making significant progress on challenging appli-cations requiring both rich perception and policy-selection. The Arcade Learning Environment (ALE) provides a set of Atari games that represent a useful bench-mark set of such applications. A recent breakthrough in combining model-free reinforcement learning with deep learning, called DQN, achieves the best real-time agents thus far. Planning-based approaches achieve far higher scores than the best model-free approaches, but they exploit information that is not available to human players, and they are orders of magnitude slower than needed for real-time play. Our main goal in this work is to build a better real-time Atari game playing agent than DQN. The central idea is to use the slow planning-based agents to pro-vide training data for a deep-learning architecture capable of real-time play. We proposed new agents based on this idea and show that they outperform DQN. 1
Single Quantum Dot-Based Nanosensor for Multiple DNA Detection (2010)

Owing to their unique optical properties, quantum dots (QDs) with different colors have been applied for simultaneous detection of multiple analytes. However, the use of single QD for multiplex detection of analytes with single-molecule detection has not been explored. Here we report a single QD-based nanosensor for multiplex detection of HIV-1 and HIV-2 at single-molecule level in a homogeneous format. In this single QD-based nanosensor, the QD functions not only as a fluorescence pair for coincidence detection and as a fluorescence-resonance-energy-transfer (FRET) donor for FRET detection but also as a local nanoconcentrator which significantly amplifies the coincidence-related fluorescence signals and the FRET signals. This single-QD-based nanosensor takes advantage of a simple 'mix and detection' assay with extremely low sample consumption, high sensitivity, and short analysis time and has the potential to be applied for rapid point-of-care testing, gene expression studies, high-throughput screening, and clinical diagnostics.
An AMIA Perspective on Proposed Regulation of Privacy of Health Information (2000)

As part of the Health Insurance Portability and Accountability Act of 1996 (HIPAA), Congress set a deadline for itself of Aug 21, 1999, to pass comprehensive confidentiality legislation. Because Congress failed to meet this deadline, according to the provisions of HIPAA, the Secretary of the Department of Health and Human Services (HHS) is required to issue final regulations by Feb 21, 2000. On Nov 3, 1999, the HHS published a Notice of Proposed Rule Making (NPRM) entitled “Standards for Privacy of Individually Identifiable Health Information” (45 CFR 160-164) pursuant to the requirements of Section 264 of HIPAA. Usually, the public has 60 days from the issuance of the NPRM to comment on the proposed rules. Because of the complex nature of this issue and the large number of anticipated comments from the public, the Secretary extended the deadline of the comment period an additional 45 days. Consequently, it is unlikely that final regulations will be issued by the original Feb 21 deadline. AMIA developed and submitted a formal response to the NPRM, which is published on the AMIA Web site (www.amia.org). This editorial comment summarizes some of the key points contained in the comments to the NPRM.

AMIA has been a strong advocate for enactment of comprehensive federal legislation to protect the confidentiality of personal health information. We believe that routine use of computer-based patient record (CPR) systems holds great promise for improving the quality of health care delivery in the United States while decreasing its costs, consistent with the Institute of Medicine's 1991 recommendation that the United States adopt the CPR as an essential technology for health care.1 However, the potential of this information management tool can be realized only if the public is confident that safeguards can be put in place to protect the confidentiality of individually …
Expression of influenza A virus internal antigens on the surface of infected P815 cells. (1981)

A panel of hybridoma antibodies was used to study the expression of the 2 major internal influenza A virus proteins, matrix protein (M), and nucleoprotein (NP) on the surface of influenza A-infected P815 cells. Using a sensitive radioimmunoassay (RIA) performed with live infected P815 cells only minute amounts of M were detectable, whereas M was not detected in 3 other cell-surface assays. In contrast, NP was detected in 10-fold greater amounts than M and 10- to 50-fold lower amounts than the viral glycoproteins by RIA. Furthermore, the presence of NP could be demonstrated by immunofluorescence, microcytotoxicity, and agglutination assays performed on live infected cells.
Identification of 118 Arabidopsis Transcription Factor and 30 Ubiquitin-Ligase Genes Responding to Chitin, a Plant-Defense Elicitor (2007)

Chitin, found in the cell walls of true fungi and the exoskeleton of insects and nematodes, is a well-established elicitor of plant defense responses. In this study, we analyzed the expression patterns of Arabidopsis thaliana transcription factor (TF) and ubiquitin-ligase genes in response to purified chitooctaose at different treatment times (15, 30, 60, 90, and 120 min after treatment), using both quantitative polymerase chain reaction and the Affymetrix Arabidopsis whole-genome array. A total of 118 TF genes and 30 ubiquitin-ligase genes were responsive to the chitin treatment. Among these genes, members from the following four TF families were overrepresented: APETALA2/ethylene-reponsive element binding proteins (27), C2H2 zinc finger proteins (14), MYB domain-containing proteins (11), and WRKY domain transcription factors (14). Transcript variants from a few of these genes were found to respond differentially to chitin, suggesting transcript-specific regulation of these TF genes.
Epicuticular Leaf Wax of Euphorbia helioscopia L. (Euphorbiaceae) (1993)

The epicuticular wax of Euphorbia helioscopia was fractionated into fatty acids, hydrocarbons, wax esters, aldehydes, methyl esters, triterpenol acetates, alcohols, sterols, and polar components. The composition of the fractions was determined by GC, GC-MS, HPLC. Main components within these lipid classes are hentriacontane, wax esters C 46 and C 48 , octacosanal, hexacosanol and octacosanol, hexadecanoic acid, and β-sitosterol. Lupeol and its acetate were also confirmed.
Nucleoside Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase (2004)

The development of novel compounds that can effectively inhibit both wild type and the most consensus resistant strains of human immunodeficiency virus type 1 (HIV-1) is the primary focus in HIV disease management. Combination therapy, comprising at least three classes of drugs, has become the standard of care for acquired immunodeficiency syndrome (AIDS) or HIV-infected individuals. The drug cocktail can comprise all three classes of HIV inhibitors, including nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). Due to their competitive mode of inhibition and requirement for metabolic activation, almost all NRTI drugs lack the virological potency of NNRTI or PI drugs. However, data from clinical trials indicate that sustained viral suppression could not be achieved with NRTI, NNRTI or PIs alone. Therefore, the NRTIs will remain essential components of highly active antiretroviral therapy (HAART) for the foreseeable future, because they enhance the virological potency of the regimen, they do not bind excessively to protein and most regimens are small pills/tablets given once a day. It has become apparent in recent years that the prolonged use of certain NRTIs exhibits adverse events as a class, limiting the length of time for which they can be safely used. Of major clinical concern is their association with the potentially fatal lactic acidaemia and hepatic steatosis. These class events, as well as individual drug effects, such as peripheral neuropathy, are linked to delayed mitochondrial destruction. In addition to toxicity, the development of resistance-conferring mutations against exposure to nucleoside analogs currently in use influences long-term therapeutic benefits. Of critical importance for the evaluation of new NRTIs are recent studies showing that the efficiency of discrimination or excision by pyrophosphorolysis in the presence of nucleotides of a given NRTI is a key determinant in the emergence of one or the other resistance pathway.
Tumor reversion holds promise (2010)

In the present issue of the journal, Makoto Noda and colleagues present a screening assay for anti-cancer drugs based on tumor reversion, identifying a series of hitherto unsuspected compounds that are of potential therapeutic interest. More specifically, the assay is based upon triggering the promoter of Reck, which functions as an inhibitor of metalloproteinases. Among the pharmaceutical agents that were able to activate the Reck promoter, 1/3 were known anti-cancer drugs which act through different cytopathic mechanisms. The second group comprises drugs that inhibit growth of bacteria, plasmodium falciparum, fungi and worms. The third category consists of “drugs related to the function of the central nervous system”.

Now, here comes the interesting and original idea of the paper. Activation of Reck induces “flat revertants” and Noda used this system already to clone the K-rev gene [1,2]. Flat revertants have a history of their own that started when investigators in the early 1960s used the NIH3T3 cells to assay the transforming potential of oncoviruses and oncogenes. A couple of years later in 1968, when Robert Pollack stepped into the field, he made a remarkable observation. Some of the cells infected with SV40 or polyoma viruses no longer showed the typical oncogenic phenotype, but instead, acquired a flat morphology [3]. These cells had also lost their oncogenic potential and were therefore named “flat revertants”. This reversion of the malignant phenotype was in line with the experiments initiated by Askanazy in teratocarcinoma cells at the beginning of the 20th century and later expanded to different species and cell types [4]. The most spectacular tumor reversion experiments have been carried out in plants by Braun [4]. Various approaches, using different biological systems [5,6,7] led to the identification of at least 300 genes that could be implicated in the tumor reversion process, including siah1, PS1, TSAP6, TCTP, Integrin receptors, and Nodal. Interestingly, Nodal is an embryonic morphogen recently found to be a key plasticity gene in aggressive tumor cells. Down-regulation of Nodal in this plastic phenotype results in reversion to a lineage specific cell type and tumor suppression [8].

Targeting tumor reversion genes in order to induce a suppression of the malignant phenotype has already led to the identification of a series of anti-histaminic, neuroleptic and anti-depressive drugs that inhibit intra-cellular levels of TCTP, a key gene in tumor reversion [9]. Other genes such as PS1, a predisposition gene to familial Alzheimer’s disease targeted by gamma-secretase inhibitors are tested in Kaposi sarcoma patients [4].

Tumor reversion as used here in Noda’s study [10] can be a fast-track for the identification of new anti-cancer drugs when we are still far away from understanding how reversion functions at the molecular level, and this is a major future challenge.
Inclusion of a furin-sensitive spacer enhances the cytotoxicity of ribotoxin restrictocin containing recombinant single-chain immunotoxins (2000)

Chimaeric toxins have considerable therapeutic potential to treat various malignancies. We have previously used the fungal ribonucleolytic toxin restrictocin to make chimaeric toxins in which the ligand was fused at either the N-terminus or the C-terminus of the toxin. Chimaeric toxins containing ligand at the C-terminus of restrictocin were shown to be more active than those having ligand at the N-terminus of the toxin. Here we describe the further engineering of restrictocin-based chimaeric toxins, anti-TFR(scFv)-restrictocin and restrictocin-anti-TFR(scFv), containing restrictocin and a single chain fragment variable (scFv) of a monoclonal antibody directed at the human transferrin receptor (TFR), to enhance their cell-killing activity. To promote the independent folding of the two proteins in the chimaeric toxin, a linear flexible peptide, Gly-Gly-Gly-Gly-Ser, was inserted between the toxin and the ligand to generate restrictocin-linker-anti-TFR(scFv) and anti-TFR(scFv)-linker-restrictocin. A 12-residue spacer, Thr-Arg-His-Arg-Gln-Pro-Arg-Gly-Trp-Glu-Gln-Leu, containing the recognition site for the protease furin, was incorporated between the toxin and the ligand to generate restrictocin-spacer-anti-TFR(scFv) and anti-TFR(scFv)-spacer-restrictocin. The incorporation of the proteolytically cleavable spacer enhanced the cell-killing activity of both constructs by 2-30-fold depending on the target cell line. However, the introduction of linker improved the cytotoxic activity only for anti-TFR(scFv)-linker-restrictocin. The proteolytically cleavable spacer-containing chimaeric toxins had similar cytotoxic activities irrespective of the location of the ligand on the toxin and they were found to release the restrictocin fragment efficiently on proteolysis in vitro.
Role Of cGMP And Ca2+ In Vertebrate Photoreceptor Excitation And Adaptation (1992)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Role of Mitochondria in Oxidative Stress and Aging (2002)

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and of aging. We have investigated the role of Complex I in superoxide radical production and found by combined use of specific inhibitors of Complex I that the one-electron donor in the Complex to oxygen is a redox center located prior to the sites where three different types of coenzyme Q (CoQ) competitors bind, to be identified with an Fe-S cluster, most probably N2, or possibly an ubisemiquinone intermediate insensitive to all the above inhibitors. Short-chain coenzyme Q analogues enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analogue idebenone is particularly effective, raising doubts about its safety as a drug. The mitochondrial theory of aging considers somatic mutations of mitochondrial DNA induced by ROS as the primary cause of energy decline; in rat liver mitochondria, Complex I appears to be most affected by aging and to become strongly rate limiting for electron transfer. Mitochondrial energetics is also deranged in human platelets upon aging, as demonstrated by the decreased Pasteur effect (enhancement of lactate production by respiratory inhibitors). Cells counteract oxidative stress by antioxidants: CoQ is the only lipophilic antioxidant to be biosynthesized. Exogenous CoQ, however, protects cells from oxidative stress by conversion into its reduced antioxidant form by cellular reductases. The plasma membrane oxidoreductase and DT-diaphorase are two such systems: likewise, they are overexpressed under oxidative stress conditions.