gebhart/patrepeval huggingface dataset:
Induction of UO-44 Gene Expression by Tamoxifen in the Rat Uterus and Ovary (2001)

A complementary DNA, uterine-ovarian-specific gene 44 (UO-44), has been isolated from tamoxifen-induced rat uterine complementary DNA library using differential display techniques. UO-44 transcripts are found to be abundant in the uterus and ovary. UO-44 gene expression in the uterus is strictly regulated by estrogens, tamoxifen, and GH, whereas the pure antiestrogen ICI 182780 is inhibitory. Treatment of ovariectomized rats and hypophysectomized rats with tamoxifen and GH, respectively, resulted in up-regulation of UO-44 expression in a dose-dependent manner. In situ hybridization revealed that UO-44 gene expression was restricted to the luminal and glandular epithelial cells of the uterus and to granulosa cells of medium-size ovarian follicles. Transfection studies showed that UO-44 was a membrane-associated protein. Because estrogens, tamoxifen, and GH are stimulators of uterine luminal epithelial cell growth in vivo, UO-44 protein may serve as a mediator of the effect of these compounds in inducing epithelial proliferation and differentiation in these tissues.
HCC-2, a human chemokine: Gene structure, expression pattern, and biological activity (1998)

Cloning and sequencing of the upstream region of the gene of the CC chemokine HCC-1 led to the discovery of an adjacent gene coding for a CC chemokine that was named "HCC-2." The two genes are separated by 12-kbp and reside in a head-to-tail orientation on chromosome 17. At variance with the genes for HCC-1 and other human CC chemokines, which have a three-exon-two-intron structure, the HCC-2 gene consists of four exons and three introns. Expression of HCC-2 and HCC-1 as studied by Northern analysis revealed, in addition to the regular, monocistronic mRNAs, a common, bicistronic transcript. In contrast to HCC-1, which is expressed constitutively in numerous human tissues, HCC-2 is expressed only in the gut and the liver. HCC-2 shares significant sequence homology with CKbeta8 and the murine chemokines C10, CCF18/MRP-2, and macrophage inflammatory protein 1gamma, which all contain six instead of four conserved cysteines. The two additional cysteines of HCC-2 form a third disulfide bond, which anchors the COOH-terminal domain to the core of the molecule. Highly purified recombinant HCC-2 was tested on neutrophils, eosinophils, monocytes, and lymphocytes and was found to exhibit marked functional similarities to macrophage inflammatory protein 1alpha. It is a potent chemoattractant and inducer of enzyme release in monocytes and a moderately active attractant for eosinophils. Desensitization studies indicate that HCC-2 acts mainly via CC chemokine receptor CCR1.
Plasmid-Determined Resistance to Antimicrobial Agents (1978)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Therapeutic Vaccines for Chronic Infections (2004)

Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases- human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.
Leptin Locally Synthesized in Carotid Atherosclerotic Plaques Could Be Associated With Lesion Instability and Cerebral Emboli (2012)

URL: www.Clinicaltrials.gov. Unique identifier: NCT00449306.
Synthesis and Applications of Supramolecular-Templated Mesoporous Materials (1999)

The unique structure of MCM-41 silicates (shown in the picture) has provided for extremely attractive properties—uniform pore sizes greater than 20 Å, surface areas exceeding 1000 m2 g−1, and long-range ordering of the pores. Recent research in supramolecular-templated mesoporous materials has led to a wide range of compositions, to uses in a variety of catalytic reactions, and to a better control of bulk morphologies.
Non-Contact Reflectance Photoplethysmography: Progress, Limitations, and Myths (2018)

Photoplethysmography (PPG) is a non-invasive method of measuring changes of blood volume in human tissue. The literature on non-contact reflectance PPG related to cardiovascular activity is extensively reviewed. We identify key factors limiting the performance of the PPG methods and reproducibility of the research as: a lack of publicly available datasets and incomplete description of data used in published experiments (missing details on video compression, lighting setup and subject's skin type), use of unreliable pulse oximeter devices for ground-truth reference and missing standard experimental protocols. Two experiments with 5 participants are presented showing that the quality of the reconstructed signal (1) is adversely affected by a reduction of spatial resolution that also amplifies the effects of H.264 video compression and (2) is improved by precise pixel-to-pixel stabilization.
Treatment of Thalassemia With Hydroxyurea: An Indispensable Alternative Therapy (2007)

First Department of Pediatrics, University of Athens School of Medicine, ‘Agia Sofia’ Children's Hospital, Thivon and Levadias, Goudi, Greece Reprints: Antonis Kattamis, MD, First Department of Pediatrics, University of Athens School of Medicine, ‘Agia Sofia’ Children's Hospital, Thivon and Levadias, Goudi 115 27, Greece (e-mail: [email protected]).
Hemoglobin and the Paracrine and Endocrine Functions of Nitric Oxide (2003)

Nitric oxide, a key factor in the maintenance of vascular tone, causes vascular smooth muscles to relax. Hemoglobin rapidly destroys nitric oxide, thereby limiting the activity of the gas to the local environment. Recent work suggests that nitric oxide reacts with hemoglobin at high oxygen tensions to form relatively long-lived products. At low oxygen tensions, these products release vasodilatory nitric oxide. This work is controversial, but it provides evidence of the potential of inhaled nitric oxide as a therapeutic agent.
Superactive estrogen receptors. Potent activators of gene expression. (1990)

We have constructed novel chimeric receptors consisting of the activation region of the herpes simplex virus transcription factor VP16 inserted into the amino-terminal region of the human estrogen receptor containing or lacking the hormone-binding region. By gene transfer into mammalian cells, these chimeric receptors behave in a hormone-dependent or hormone-independent manner, respectively, and are more efficient activators of gene expression than wild-type estrogen receptor. These studies indicate that a potent activation region from a viral transcription factor can be placed under hormonal control when introduced into a steroid receptor molecule and can enhance the receptor's potency (approximately 10-fold) in activating specific gene expression. It is likely that such chimeric molecules could be designed to increase selected target gene responses to any intracellular receptor in the course of cellular transfection, transformation, or transgenic animal experiments.
Synthesis of 2-Fluoro-6-O-propargyl-11,12-carbamate Ketolides. A Novel Class of Antibiotics (2000)

A novel class of 2-fluoro-6-O-propargyl-11,12-carbamate ketolide derivatives of erythromycin has been synthesized for antibacterial SAR studies. Replacement of the C2-hydrogen by a fluorine atom allows the synthesis of 6-O-propargylic ketones and electron-deficient 6-O-propargylic aromatic derivatives by preventing intramolecular C2-enolate Michael cyclization.
Performance of relational database management systems in intelligent networks and mobility environments (2002)

The handling of large amounts of data is crucial for operation and management of telecommunication systems like intelligent networks and mobility environments. Requirements like reliability, security and performance have been addressed by the database community for many years which is reflected in mature relational database management systems. We look at relational database systems to find out if and how they can be used to satisfy the database requirements of telecommunication applications. In the INDIA project we adopted relational database systems to handle the distribution and performance requirements of telecommunication applications, especially of intelligent networks. Our method is called atomic delayed replication (ADR). ADR allows a dynamic reconfiguration of data distribution for load balancing and makes migration of data to different nodes easy. We integrated ADR into the Philips IN prototype. We give a brief characterization of our ADR approach and carry out a performance evaluation. Further performance evaluation was done using an analytical model. Some major results are sketched. We applied our ADR approach to another application area in telecommunications, namely, a city-wide PCS (personal communication services) environment.
Optimizing Vaccine Allocation to Combat the COVID-19 Pandemic (2020)

Abstract The outbreak of COVID-19 has spurred extensive research worldwide to develop a vaccine. However, when a vaccine becomes available, limited production and distribution capabilities will likely lead to another challenge: who to prioritize for vaccination to mitigate the near-end impact of the pandemic? To tackle that question, this paper first expands a state-of-the-art epidemiological model, called DELPHI, to capture the effects of vaccinations and the variability in mortality rates across subpopulations. It then integrates this predictive model into a prescriptive model to optimize vaccine allocation, formulated as a bilinear, non-convex optimization model. To solve it, this paper proposes a coordinate descent algorithm that iterates between optimizing vaccine allocations and simulating the dynamics of the pandemic. We implement the model and algorithm using real-world data in the United States. All else equal, the optimized vaccine allocation prioritizes states with a large number of projected cases and sub-populations facing higher risks (e.g., older ones). Ultimately, the optimized vaccine allocation can reduce the death toll of the pandemic by an estimated 10–25%, or 10,000–20,000 deaths over a three-month period in the United States alone. Highlights – This paper formulates an optimization model for vaccine allocation in response to the COVID-19 pandemic. This model, referred to as DELPHI–V–OPT, integrates a predictive epidemiological model into a prescriptive model to support the allocation of vaccines across geographic regions (e.g., US states) and across risk classes (e.g., age groups). – This paper develops a scalable coordinate descent algorithm to solve the DELPHI–V–OPT model. The proposed algorithm converges effectively and in short computational times. Therefore, the proposed approach can be implemented efficiently, and allows extensive sensitivity analyses for scenario planning and policy analysis. – Computational results demonstrate that optimized vaccine allocation strategies can curb the death toll of the COVID-19 pandemic by an estimated at 10–25%, or 10,000–20,000 deaths over a three-month period in the United States alone. These results highlight the critical role of vaccine allocation to combat the COVID-19 pandemic, in addition to vaccine design and vaccine production.
Active specific T-cell-based immunotherapy for cancer: nucleic acids, peptides, whole native proteins, recombinant viruses, with dendritic cell adjuvants or whole tumor cell-based vaccines. Principles and future prospects. (1998)

Whereas tumor cells are poor immunogens, recombinant tumor cells or dendritic cells as well as engineered viruses have been demonstrated to elicit specific antitumor immune responses leading to tumor growth suppression and long-lasting immunity in mouse tumor models. Single cytotoxic T lymphocyte-defined epitope-based strategies have proved useful for immunization in tumor-bearing mice. This strategy is under investigation in human melanoma, along with adjuvants such as cytokines or dendritic cells. Flt3L is an in vivo dendritic-cell growth factor that offers new prospects in the field of active specific immunotherapy. These immunotherapeutic approaches are being tested in clinical trials, and may open up novel avenues for disease-free patients with poor prognostic factors.
RNA-Guided Human Genome Engineering via Cas9 (2013)

Bacteria and archaea have evolved adaptive immune defenses, termed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems, that use short RNA to direct degradation of foreign nucleic acids. Here, we engineer the type II bacterial CRISPR system to function with custom guide RNA (gRNA) in human cells. For the endogenous AAVS1 locus, we obtained targeting rates of 10 to 25% in 293T cells, 13 to 8% in K562 cells, and 2 to 4% in induced pluripotent stem cells. We show that this process relies on CRISPR components; is sequence-specific; and, upon simultaneous introduction of multiple gRNAs, can effect multiplex editing of target loci. We also compute a genome-wide resource of ~190 K unique gRNAs targeting ~40.5% of human exons. Our results establish an RNA-guided editing tool for facile, robust, and multiplexable human genome engineering.
Glucose transport in brain and retina: implications in the management and complications of diabetes (1999)

Neural tissue is entirely dependent on glucose for normal metabolic activity. Since glucose stores in the brain and retina are negligible compared to glucose demand, metabolism in these tissues is dependent upon adequate glucose delivery from the systemic circulation. In the brain, the critical interface for glucose transport is at the brain capillary endothelial cells which comprise the blood-brain barrier (BBB). In the retina, transport occurs across the retinal capillary endothelial cells of the inner blood-retinal barrier (BRB) and the retinal pigment epithelium of the outer BRB. Because glucose transport across these barriers is mediated exclusively by the sodium-independent glucose transporter GLUT1, changes in endothelial glucose transport and GLUT1 abundance in the barriers of the brain and retina may have profound consequences on glucose delivery to these tissues and major implications in the development of two major diabetic complications, namely insulin-induced hypoglycemia and diabetic retinopathy. This review discusses the regulation of brain and retinal glucose transport and glucose transporter expression and considers the role of changes in glucose transporter expression in the development of two of the most devastating complications of long-standing diabetes mellitus and its management.
Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity (1994)

Comparison of the anthrax toxin lethal factor (LF) amino acid sequence with sequences in the Swiss protein database revealed short regions of similarity with the consensus zinc-binding site, HEXXH, that is characteristic of metalloproteases. Several protease inhibitors, including bestatin and captopril, prevented intoxication of macrophages by lethal toxin. LF was fully inactivated by site-directed mutagenesis that substituted Ala for either of the residues (H-686 and H-690) implicated in zinc binding. Similarly, LF was inactivated by substitution of Cys for E-687, which is thought to be an essential part of the catalytic site. In contrast, replacement of E-720 and E-721 with Ala had no effect on LF activity. LF bound 65Zn both in solution and on protein blots. The 65Zn binding was reduced for several of the LF mutants. These data suggest that anthrax toxin LF is a zinc metallopeptidase, the catalytic function of which is responsible for the lethal activity observed in cultured cells and in animals.
Immunocytochemical demonstration of human proinsulin chimeric polypeptide within cytoplasmic inclusion bodies of Escherichia coli. (1983)

Immunocytochemical techniques were used to identify human proinsulin chimeric protein in cytoplasmic inclusion bodies of genetically modified Escherichia coli. Antibodies to proinsulin chimeric protein (human proinsulin coupled at its amino-terminus to a portion of the E. coli tryptophan E gene product) were localized in E. coli using post-embedding staining with protein A-peroxidase labelling for transmission electron microscopy. The observable distribution of the labelled antibody was limited to that portion of the E. coli cytoplasm occupied by inclusion bodies. The localization of human peptides as insoluble masses within the bacterial cytoplasm has important implications in relation to the synthesis, recovery and purification of pharmacologically useful substances produced through the application of recombinant DNA technology.
Evaluation of KCB-328, a new IKr blocking antiarrhythmic agent in pacing induced canine atrial fibrillation (2004)

The spectrum of effect of the three drugs differed significantly: propafenone showed the greatest success in AF termination, and both propafenone and KCB-328 appeared less proarrhythmic than dofetilide in this model.
Neurosurgical Applications of Transcranial Doppler Ultrasound (1995)

Neurosurgery Department, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235–8855
Gas-bubble enhanced heating in rabbit thigh in vivo (2003)

In this study, we propose a focused ultrasound surgery protocol that induces and then uses gas bubbles at the focus to enhance the ultrasound absorption and ultimately create larger lesions in vivo. MRI and ultrasound visualization and monitoring methods for this heating method are also investigated. Larger lesions created with a carefully monitored single ultrasound exposure could greatly improve the speed of tumor coagulation with focused ultrasound. All experiments were performed under MRI (clinical, 1.5T) guidance with one of two eight-sector spherically curved piezoelectric transducers (1.1 and 1.7 MHz). An ultrasound detector ring was fixed with the therapy transducer to monitor gas bubble activity during treatment. FUS exposures were delivered to the thighs of seven New Zealand white rabbits. The experimental, gas bubble-enhanced heating exposures consisted of a high amplitude 300 acoustic watt, half second pulse followed by a 7 W, 14 W, or 21 W continuous wave exposure for 19.5 seconds. The respective control sonications were 20-second exposures of 14 W, 21 W, and 28 W. During the exposures, MR thermometry was obtained, and MR T2-enhanced imaging was used to evaluate the resulting lesions. Specific metrics were used to evaluate the differences between the gas-bubble enhanced exposures and their respective control sonications: temperatures with respect to time and space, lesion size and shape, and their agreement with thermal dose predictions. The bubble-enhanced exposures showed a faster temperature rise and higher overall temperatures than the sonications without bubble formation. The MRI derived spatial temperature and thermal dose maps closely correlated with the resulting lesion as examined by T2-wieghted imaging. The lesions created with the gas-bubble enhanced heating exposures were 3 times larger by volume, were consistently more spherical in shape, and closer to the transducer than the control exposures. The study demonstrates that gas bubbles can reliably be used to create significantly larger lesions in vivo.
NRF2 Induction Supporting Breast Cancer Cell Survival Is Enabled by Oxidative Stress–Induced DPP3–KEAP1 Interaction (2017)

NRF2 is a transcription factor serving as a master regulator of the expression of many genes involved in cellular responses to oxidative and other stresses. In the absence of stress, NRF2 is constantly synthesized but maintained at low levels as it is targeted by KEAP1 for ubiquitination and proteasome-mediated degradation. NRF2 binds KEAP1 mainly through a conserved "ETGE" motif that has also been found in several other proteins, such as DPP3, which has been shown to bind KEAP1 and enhance NRF2 function upon overexpression. Here we demonstrate the interaction between endogenous DPP3 and endogenous KEAP1. We further show that the DPP3-KEAP1 interaction is strongly induced by hydrogen peroxide and that DPP3 is required for timely NRF2 induction and nuclear accumulation in the estrogen receptor (ER)-positive MCF7 breast cancer cells. Moreover, we present evidence that the binding of DPP3 to KEAP1 stabilizes the latter. Finally, we show that DPP3 is overexpressed in breast cancer and that elevated levels of <i>DPP3</i> mRNA correlate with increased NRF2 downstream gene expression and poor prognosis, particularly for ER-positive breast cancer. Our studies reveal novel insights into the regulation of NRF2 and identify DPP3 and an NRF2 transcriptional signature as potential biomarkers for breast cancer prognosis and treatment. <i>Cancer Res; 77(11); 2881-92. ©2017 AACR</i>.
Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells (1987)

Sulfated glycoprotein 2 (SGP-2) is the major protein secreted by rat Sertoli cells. Pulse-chase labeling shows that SGP-2 is synthesized as a cotranslationally glycosylated 64-kDa precursor that is modified to a negatively charged 73-kDa form before intracellular cleavage to the mature 47- and 34-kDa subunits. A plasmid cDNA library was constructed from immunopurified mRNA, and a recombinant clone containing the entire protein coding sequence of SGP-2 was isolated. The 1857-nucleotide cDNA consists of a 297-nucleotide 5' noncoding segment, a 1341-nucleotide coding segment, and a 219-nucleotide 3' noncoding sequence. The 5' noncoding region contains five ATG codons followed by four short open reading frames. The derived SGP-2 sequence has a molecular weight of 51,379 and contains six potential N-glycosylation sites. Proteolytic processing sites for the preproprotein were determined by amino-terminal sequencing of the isolated SGP-2 subunits. Northern blots show a wide tissue distribution for the 2.0-kb SGP-2 message, and computer sequence analysis indicates a significant relationship between SGP-2 and human apolipoprotein A-I.