gebhart/patrepeval huggingface dataset:
A physiological role of the adenosine A 3 receptor: Sustained cardioprotection (1998)

Adenosine released during cardiac ischemia exerts a potent, protective effect in the heart. A newly recognized adenosine receptor, the A3 subtype, is expressed on the cardiac ventricular cell, and its activation protects the ventricular heart cell against injury during a subsequent exposure to ischemia. A cultured chicken ventricular myocyte model was used to investigate the cardioprotective role of a novel adenosine A3 receptor. The protection mediated by prior activation of A3 receptors exhibits a significantly longer duration than that produced by activation of the adenosine A1 receptor. Prior exposure of the myocytes to brief ischemia also protected them against injury sustained during a subsequent exposure to prolonged ischemia. The adenosine A3 receptor-selective antagonist 3-ethyl 5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) caused a biphasic inhibition of the protective effect of the brief ischemia. The concomitant presence of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) converted the MRS1191-induced dose inhibition curve to a monophasic one. The combined presence of both antagonists abolished the protective effect induced by the brief ischemia. Thus, activation of both A1 and A3 receptors is required to mediate the cardioprotective effect of the brief ischemia. Cardiac atrial cells lack native A3 receptors and exhibit a shorter duration of cardioprotection than do ventricular cells. Transfection of atrial cells with cDNA encoding the human adenosine A3 receptor causes a sustained A3 agonist-mediated cardioprotection. The study indicates that cardiac adenosine A3 receptor mediates a sustained cardioprotective function and represents a new cardiac therapeutic target.
Coherent Optical Receiver for Linear Optical Phase Demodulation (2007)

A novel optical coherent receiver architecture for linear optical phase modulation is presented. A proof-of-concept demonstration has been performed using discrete components and at low frequency. High dynamic range has been confirmed at 3.13 mA average photocurrent; 124.3 dBHz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2/3</sup> , corresponding to a 131.5 dBHz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2/3</sup> if a shot-noise limited noise floor were achieved (here limited by low-frequency 1/f-type noise). Further, efforts to increase the operating frequency to the GHz region and beyond has been outlined in the efforts to develop compact, low latency integrated chip technology and the development of novel sampling downconversion receiver architectures.
Fluorescence lifetime plate reader: Resolution and precision meet high-throughput (2014)

We describe a nanosecond time-resolved fluorescence spectrometer that acquires fluorescence decay waveforms from each well of a 384-well microplate in 3 min with signal-to-noise exceeding 400 using direct waveform recording. The instrument combines high-energy pulsed laser sources (5-10 kHz repetition rate) with a photomultiplier and high-speed digitizer (1 GHz) to record a fluorescence decay waveform after each pulse. Waveforms acquired from rhodamine or 5-((2-aminoethyl)amino) naphthalene-1-sulfonic acid dyes in a 384-well plate gave lifetime measurements 5- to 25-fold more precise than the simultaneous intensity measurements. Lifetimes as short as 0.04 ns were acquired by interleaving with an effective sample rate of 5 GHz. Lifetime measurements resolved mixtures of single-exponential dyes with better than 1% accuracy. The fluorescence lifetime plate reader enables multiple-well fluorescence lifetime measurements with an acquisition time of 0.5 s per well, suitable for high-throughput fluorescence lifetime screening applications.
Microfluidic Fabrication of Monodisperse Biocompatible and Biodegradable Polymersomes with Controlled Permeability (2008)

We describe a versatile technique for fabricating monodisperse polymersomes with biocompatible and biodegradable diblock copolymers for efficient encapsulation of actives. We use double emulsion as a template for the assembly of amphiphilic diblock copolymers into vesicle structures. These polymersomes can be used to encapsulate small hydrophilic solutes. When triggered by an osmotic shock, the polymersomes break and release the solutes, providing a simple and effective release mechanism. The technique can also be applied to diblock copolymers with different hydrophilic-to-hydrophobic block ratios, or mixtures of diblock copolymers and hydrophobic homopolymers. The ability to make polymer vesicles with copolymers of different block ratios and to incorporate different homopolymers into the polymersomes will allow the tuning of polymersome properties for specific technological applications.
Improving the Evidence Base for Treating Older Adults With Cancer: American Society of Clinical Oncology Statement (2015)

The American Society of Clinical Oncology (ASCO) convened a subcommittee to develop recommendations on improving the evidence base for treating older adults with cancer in response to a critical need identified by the Institute of Medicine. Older adults experience the majority of cancer diagnoses and deaths and make up the majority of cancer survivors. Older adults are also the fastest growing segment of the US population. However, the evidence base for treating this population is sparse, because older adults are underrepresented in clinical trials, and trials designed specifically for older adults are rare. The result is that clinicians have less evidence on how to treat older adults, who represent the majority of patients with cancer. Clinicians and patients are forced to extrapolate from trials conducted in younger, healthier populations when developing treatment plans. This has created a dearth of knowledge regarding the risk of toxicity in the average older patient and about key end points of importance to older adults. ASCO makes five recommendations to improve evidence generation in this population: (1) Use clinical trials to improve the evidence base for treating older adults with cancer, (2) leverage research designs and infrastructure for generating evidence on older adults with cancer, (3) increase US Food and Drug Administration authority to incentivize and require research involving older adults with cancer, (4) increase clinicians' recruitment of older adults with cancer to clinical trials, and (5) use journal policies to improve researchers' reporting on the age distribution and health risk profiles of research participants.
Cell culture processes for monoclonal antibody production (2010)

Animal cell culture technology has advanced significantly over the last few decades and is now generally considered a reliable, robust and relatively mature technology. A range of biotherapeutics are currently synthesized using cell culture methods in large scale manufacturing facilities that produce products for both commercial use and clinical studies. The robust implementation of this technology requires optimization of a number of variables, including 1) cell lines capable of synthesizing the required molecules at high productivities that ensure low operating cost; 2) culture media and bioreactor culture conditions that achieve both the requisite productivity and meet product quality specifications; 3) appropriate on-line and off-line sensors capable of providing information that enhances process knowledge; and 4) good understanding of culture performance at different scales to ensure smooth scale-up. Successful implementation also requires appropriate strategies for process development, scale-up and process characterization and validation that enable robust operation that is compliant with current regulations. This review provides an overview of the state-of-the art technology in key aspects of cell culture, e.g., engineering of highly productive cell lines and optimization of cell culture process conditions. We also summarize the current thinking on appropriate process development strategies and process advances that might affect process development.
Ozonolysis Problems That Promote Student Reasoning (2006)

The structural features inherent in acyclic monoterpenes that follow the isoprene rule often lead to unique sets of ozonolysis products from which their structures, excluding stereochemistry, can be determined from molecular formulas only. This article shows with three examples how students may elucidate the structures of these compounds by analysis of the oxidative and reductive workup products. The oxidative and reductive workup products of 66 compounds that follow the isoprene rule are provided in the Supplemental Material. Fifty of them give a unique set of products from which a single structure can be elucidated by the techniques exemplified in the article. The remaining 16 compounds give products that satisfy two structures. The problems vary in difficulty, affording instructors of beginning organic or qualitative organic analysis courses a set of degradation problems that complement spectral and synthetic problems in engaging students to apply their knowledge and enhance their reasoning skills while solving challenging problems.
Clinical prospects for new thyroid hormone analogues (2005)

Purpose of review Scientists have been studying liver-selective thyroid hormone analogues developed between the late 1980s through the late 1990s to validate their utility in treating hypercholesterolemia, diabetes, atherosclerosis, and obesity. Several thyromimetics with agonistic or antagonist properties have recently been developed and their clinical utility is being explored. This review presents the progress of several thyromimetics with potential clinical utility and provides an assessment of the potential of second-generation thyromimetics with varying pharmacologic profiles. Recent findings GC-1 exhibits cholesterol-lowering effects in hypothyroid mice, cholesterol-fed rats, and cynomolgus monkeys. DITPA (3,5-diiodothyropropionic acid) is currently being investigated for use in treating congestive heart failure. In rat and rabbit postinfarction models, DITPA administration in combination with captopril or as monotherapy caused an increase in cardiac output and a decrease in left ventricular end-diastolic pressure without chronotropic or significant metabolic effects. DITPA treatment induces arteriolar growth and improves maximal perfusion potential of hypertrophied myocardium surviving a myocardial infarction. Thyroid hormone receptor-β-selective agonists, GC-24, KB-141, and KAT-681, as well as the thyroid hormone receptor-α-selective and thyroid hormone receptor-β-selective antagonists dronedarone and NH-3 show promise in treating hypercholesterolemia, hyperlipidemia, hepatocarcinogenesis, heart failure, and hyperthyroidism. Summary Thyroid hormone receptors orchestrate a diverse array of physiologic activities in an isoform-specific manner. These activities include fetal and postnatal development, regulation of lipid inventory, and effects on cardiac performance. As a result, thyroid hormone analogues that selectively modulate thyroid hormone receptor isoforms serve as potential therapeutics in treating several metabolic and cardiac-related diseases.
Protective Effects of Estrogen and Selective Estrogen Receptor Modulators in the Brain1 (2002)

Within the last few years, there has been a growing interest in the neuroprotective effects of estrogen and the possible beneficial effects of estrogen in neurodegenerative diseases such as stroke, Alzheimer disease, and Parkinson disease. Here, we review the progress in this field, with a particular focus upon estrogen-induced protection from stroke-induced ischemic damage. The important issue of whether clinically relevant selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene and estrogen replacement therapy can exert neuroprotection is also addressed. Although the mechanism of estrogen and SERM neuroprotection is not clearly resolved, we summarize the leading possibilities, including 1) a genomic estrogen receptor-mediated pathway that involves gene transcription, 2) a nongenomic signaling pathway involving activation of cell signalers such as mitogen-activated protein kinases and/or phosphatidylinositol-3-kinase /protein kinase B, and 3) a nonreceptor antioxidant free-radical scavenging pathway that is primarily observed with pharmacological doses of estrogen. The role of other potential mediatory factors such as growth factors and the possibility of an astrocyte role in neuroprotection is also discussed.
Inhibition of Translation of Hepatitis C Virus RNA by 2′-Modified Antisense Oligonucleotides (1999)

Inhibition of hepatitis C virus (HCV) gene expression by antisense oligonucleotides was investigated using both a rabbit reticulocyte lysate in vitro translation assay and a transformed human hepatocyte cell expression assay. Screening of overlapping oligonucleotides complementary to the HCV 5' noncoding region and the core open reading frame (ORF) identified a region susceptible to translation inhibition between nucleotides 335 and 379. Comparison of 2'-deoxy-, 2'-O-methyl-, 2'-O-methoxyethyl-, 2'-O-propyl-, and 2'-fluoro-modified phosphodiester oligoribonucleotides demonstrated that increased translation inhibition correlated with both increased binding affinity and nuclease stability. In cell culture assays, 2'-O-methoxyethyl-modified oligonucleotides inhibited HCV core protein synthesis with comparable potency to phosphorothioate oligodeoxynucleotides. Inhibition of HCV core protein expression by 2'-modified oligonucleotides occurred by an RNase H-independent translational arrest mechanism.
Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy (2004)

In humans, the pathways of memory T-cell differentiation remain poorly defined. Recently, adoptive cell transfer (ACT) of tumor-reactive T lymphocytes to metastatic melanoma patients after nonmyeloablative chemotherapy has resulted in persistence of functional, tumor-reactive lymphocytes, regression of disease, and induction of melanocyte-directed autoimmunity in some responding patients. In the current study, longitudinal phenotypic analysis was performed on melanoma antigen-specific CD8+ T cells during their transition from in vitro cultured effector cells to long-term persistent memory cells following ACT to 6 responding patients. Tumor-reactive T cells used for therapy were generally late-stage effector cells with a CD27Lo CD28Lo CD45RA- CD62 ligand- (CD62L-) CC chemokine receptor 7- (CCR7-) interleukin-7 receptor alphaLo (IL-7RalphaLo) phenotype. After transfer, rapid up-regulation and continued expression of IL-7Ralpha in vivo suggested an important role for IL-7R in immediate and long-term T-cell survival. Although the tumor antigen-specific T-cell population contracted between 1 and 4 weeks after transfer, stable numbers of CD27+)CD28+ tumor-reactive T cells were maintained, demonstrating their contribution to the development of long-term, melanoma-reactive memory CD8+ T cells in vivo. At 2 months after transfer, melanoma-reactive T cells persisted at high levels and displayed an effector memory phenotype, including a CD27+ CD28+ CD62L- CCR7- profile, which may explain in part their ability to mediate tumor destruction.
Considerations of handheld respiratory rate estimation via a stabilized Video Magnification approach (2017)

Respiratory rate can be a vital indicator of illness; however, tracking this is a non-trivial process. Phase-based Eulerian Video Magnification (EVM) is an exciting spatiotemporal video processing approach able to reveal subtle breathing motions within video sequences; however, its results are variant to large motions and camera blur. In the case of camera motion, a compensation strategy of stabilizing (without smoothing) the video has the may reduce estimation error in handheld cases. This work explores the extent of removing motion artefacts and its impact on identifying subtle breathing motions. Tests across six indoor scenes show a reduction mean breathing estimate error for 4 of 6 cases and highlights the sensitivity of this approach to unwanted body movements. The results of this project suggest the plausibility that non-smoothing video amplification processes can be an effective method to track breathing motion and that implementing correction techniques which may allow a smartphone to provide a compact, non-invasive, online breathing monitor.
The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater (1990)

1. We describe the actions of GR43175, a 5-hydroxytryptamine1 (5-HT1)-like receptor agonist, on neurogenically-mediated plasma protein extravasation within an important pain-sensitive intracranial tissue, the dura mater. 2. GR43175 markedly attenuated extravasation of 125I-albumin from blood vessels within ipsilateral dura mater when administered to rats (100 micrograms kg-1) fifteen minutes before unilateral electrical trigeminal stimulation (1.2 mA, 5 Hz, 5 ms, 5 min); the ratio (stimulated/unstimulated sides) decreased from 1.81 to 1.23, P less than 0.005). 3. GR43175 (100 micrograms kg-1, i.v., rats; 30 micrograms kg-1, guinea-pigs) decreased the leakage of radiolabelled albumin from 163% to 119% (P less than 0.005, guinea-pig) or from 174 to 118% (P less than 0.05, rat) above vehicle-treated controls when injected ten minutes before systemic capsaicin treatment (0.5 or 1 mumol kg-1, i.v.). 4. GR43175 (30-300 micrograms kg-1) did not block plasma protein extravasation within extracranial tissues of rats and guinea-pigs innervated by the trigeminal nerve (conjunctiva, eyelid and lip). 5. The protein leakage which followed the i.v. administration of 5-HT (1 mumol kg-1) or neuropeptides which mediate neurogenic plasma extravasation, substance P (0.3 nmol kg-1 or 1 nmol kg-1) and neurokinin A (1 nmol kg-1), was not blocked by GR43175 (100, 300 micrograms kg-1) despite the presence of leakage in amounts equivalent to that following neurogenic stimulation. 6. GR43175 (100 micrograms kg-1) decreased bradykinin (10 mumol kg-1)-induced extravasation from 142 to 115% above vehicle-treated animals (P less than 0.05). 7. These results demonstrate an important action of GR43175 on neurogenic mechanisms in dural blood vessels. Since the ergot alkaloids possess a similar profile of drug activity, it is suggested that drugs useful in the treatment of acute vascular headaches may share a similar mechanism of action.
Clinical trials of antiangiogenic agents (1997)

Acquisition of new blood vessels is a required step in malignant transformation, tumor growth, and metastasis. Inhibition of angiogenesis is one of the most promising new strategies for the treatment of malignant neoplasms. In recent years, several antiangiogenic compounds, including TNP-470, matrix metalloproteinase inhibitors, carboxyamidotriazole, and tecogalan sodium, have entered clinical trials. In this we review, we look at the results of early clinical trials of these agents and discuss the new angiogenesis inhibitors in preclinical development.
A Human Cytomegalovirus-Encoded microRNA Regulates Expression of Multiple Viral Genes Involved in Replication (2007)

Although multiple studies have documented the expression of over 70 novel virus-encoded microRNAs (miRNAs), the targets and functions of most of these regulatory RNA species are unknown. In this study a comparative bioinformatics approach was employed to identify potential human cytomegalovirus (HCMV) mRNA targets of the virus-encoded miRNA miR-UL112-1. Bioinformatics analysis of the known HCMV mRNA 3' untranslated regions (UTRs) revealed 14 potential viral transcripts that were predicted to contain functional target sites for miR-UL112-1. The potential target sites were screened using luciferase reporters that contain the HCMV 3'UTRs in co-transfection assays with miR-UL112-1. Three of the 14 HCMV miRNA targets were validated, including the major immediate early gene encoding IE72 (UL123, IE1), UL112/113, and UL120/121. Further analysis of IE72 regulation by miR-UL112-1 with clones encoding the complete major immediate early region revealed that the IE72 3'UTR target site is necessary and sufficient to direct miR-UL112-1-specific inhibition of expression in transfected cells. In addition, miR-UL112-1 regulation is mediated through translational inhibition rather than RNA degradation. Premature expression of miR-UL112-1 during HCMV infection resulted in a significant decrease in genomic viral DNA levels, suggesting a functional role for miR-UL112-1 in regulating the expression of genes involved in viral replication. This study demonstrates the ability of a viral miRNA to regulate multiple viral genes.
Traumatic Brain Injury in the United States: A Public Health Perspective (1999)

Traumatic brain injury (TBI) is a leading cause of death and disability among persons in the United States. Each year, an estimated 1.5 million Americans sustain a TBI. As a result of these injuries, 50,000 people die, 230,000 people are hospitalized and survive, and an estimated 80,000-90,000 people experience the onset of long-term disability. Rates of TBI-related hospitalization have declined nearly 50% since 1980, a phenomenon that may be attributed, in part, to successes in injury prevention and also to changes in hospital admission practices that shift the care of persons with less severe TBI from inpatient to outpatient settings. The magnitude of TBI in the United States requires public health measures to prevent these injuries and to improve their consequences. State surveillance systems can provide reliable data on injury causes and risk factors, identify trends in TBI incidence, enable the development of cause-specific prevention strategies focused on populations at greatest risk, and monitor the effectiveness of such programs. State follow-up registries, built on surveillance systems, can provide more information regarding the frequency and nature of disabilities associated with TBI. This information can help states and communities to design, implement, and evaluate cost-effective programs for people living with TBI and for their families, addressing acute care, rehabilitation, and vocational, school, and community support.
A Newly Created Splice Donor Site in Exon 25 of the MyBP-C Gene Is Responsible for Inherited Hypertrophic Cardiomyopathy With Incomplete Disease Penetrance (2000)

Penetrance of this mutation was incomplete and age-dependent. The large number of asymptomatic carriers and the good prognosis support the interpretation of benign disease.
Structure of the Operator-binding Domain of Bacteriophage Repressor: Implications for DNA Recognition and Gene Regulation (1983)

To understand the structural basis for sequence-specific recognition of DNA and the molecular basis of gene regulation, we have undertaken a crystallographic study of the repressor from bacteriophage λ. The λ repressor binds to two operator regions (0L and 0R) in the bacteriophage DNA, thereby preventing transcription of other bacteriophage genes while stimulating transcription of its own gene (for recent review, see Ptashne et al. 1980; Johnson et al. 1981). Repressor dimers bind to three sites within each of the operator regions (0L and 0r). Each binding site contains 17 bp, and the sequence of each site has an approximate twofold rotational symmetry.
Retinaldehyde Alleviates Rosacea (1999)

This study indicates that retinaldehyde has beneficial effects on the vascular component of rosacea.