gebhart/patrepeval huggingface dataset:
Roles of fetal G gamma-globin promoter elements and the adult beta-globin 3' enhancer in the stage-specific expression of globin genes. (1990)

The human fetal G gamma-globin and adult beta-globin genes are expressed in a tissue- and developmental stage-specific pattern in transgenic mice: the G gamma gene in embryonic cells and the beta gene in fetal and adult erythroid cells. Several of the cis-acting DNA sequences thought to be responsible for these patterns of expression are located 5' to the G gamma-globin gene and 3' to the beta-globin gene. To further define the locations and functional roles of these elements, we examined the effects of 5' truncations on the expression of the G gamma-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene. We found that sequences between -201 and -136 are essential for expression of the G gamma-globin gene, whereas those upstream of -201 have little effect on the level or tissue or stage specificity of G gamma-globin expression. The G gamma-globin upstream sequences from -201 to -136 were, furthermore, capable of activating a linked beta-globin gene in embryonic blood cells; however, a G gamma-globin fragment from -383 to -206 was similarly active in this assay, and the complete fragment from -383 to -136 was considerably more active than either of the smaller fragments, suggesting the presence of multiple cis-acting elements for embryonic blood cells. Our data also suggested the possibility of a negative regulatory element between -201 and -136. These results are discussed in relation to several DNA elements in the G gamma-globin upstream region, which have been shown to bind nuclear factors in erythroid cells. Finally, we observed that removal of the beta-globin 3'-flanking sequences, including the 3' enhancer, from the G gamma-globin upstream-beta-globin hybrid gene resulted in a 25-fold reduction in expression in embryonic blood cells. This suggests that the beta-globin 3' enhancer is potentially active at the embryonic stage and thus cannot be solely responsible for the fetal or adult specificity of the beta-globin gene.
A role for the human single-Stranded DNA binding protein HSSB/RPA in an early stage of nucleotide excision repair (1992)

The human single-stranded DNA binding protein (HSSB/RPA) is involved in several processes that maintain the integrity of the genome including DNA replication, homologous recombination, and nucleotide excision repair of damaged DNA. We report studies that analyze the role of HSSB in DNA repair. Specific protein-protein interactions appear to be involved in the repair function of HSSB, since it cannot be replaced by heterologous single-stranded DNA binding proteins. Anti-HSSB antibodies that inhibit the ability of HSSB to stimulate DNA polymerase alpha also inhibit repair synthesis mediated by human cell-free extracts. However, antibodies that neutralize DNA polymerase alpha do not inhibit repair synthesis. Repair is sensitive to aphidicolin, suggesting that DNA polymerase epsilon or delta participates in nucleotide excision repair by cell extracts. HSSB has a role other than generally stimulating synthesis by DNA polymerases, as it does not enhance the residual damage-dependent background synthesis displayed by repair-deficient extracts from xeroderma pigmentosum cells. Significantly, when damaged DNA is incised by the Escherichia coli UvrABC repair enzyme, human cell extracts can carry out repair synthesis even when HSSB has been neutralized with antibodies. This suggests that HSSB functions in an early stage of repair, rather than exclusively in repair synthesis. A model for the role of HSSB in repair is presented.
The Protective Effects of Allopurinol and Superoxide Dismutase‐Polyethylene Glycol on Ischemic and Reperfusion‐Induced Cochlear Damage (1991)

The purpose of this study was to assess the protective effects of allopurinol, a blocker of free oxygen radical (FOR) formation, and superoxide dismutase-polyethylene glycol (SOD-PEG), a scavenger of FORs, on ischemic and reperfusion-induced cochlear damage. Fifteen Wistar Kyoto rats (WKY) were randomly assigned to three groups: (1) a control group (5 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion as documented by laser Doppler flowmetry; (2) a drug-treated group (5 animals) that received allopurinol before ischemia/reperfusion; and (3) a drug-treated group (5 animals) that received SOD-PEG before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) of the cochlea was abolished, and the cochlear microphonic (CM) was reduced after ischemia. In contrast, both allopurinol and SOD-PEG-treated animals showed post-reperfusion sensitivity in CAP and CM measures. We interpret these results to indicate that damage to the cochlear from ischemia and subsequent reperfusion can be attenuated by pretreatment with allopurinol or SOD-PEG. This provides indirect evidence that FORs may be partially responsible for cochlear damage resulting from ischemic conditions.
A 4.25-Gb/s CMOS fiber channel transceiver with asynchronous tree-type demultiplexer and frequency conversion architecture (1998)

A single-chip 1.25-Gb/s 32:1, 1:32 transceiver, as specified in the emerging American National Standards Institute fiber channel standard, has been developed using 0.25-/spl mu/m CMOS technology. Newly developed features contributing to the achievement of 4.25-Gb/s operations include: 1) an asynchronous tree-type 1:8 demultiplexer, 2) an 8-10 bit parallel-to-parallel frequency conversion circuit, and 3) comma detection and word alignment logic. The transceiver consumes 600 mW in 4.25-Gb/s operations with a 2.5 V supply. This design helps achieve higher speed operations and only half the power dissipation of the fastest previously reported CMOS fiber channel design that includes an 8B10B encoder and a 10B8B decoder.
Phylogeny of the Genus Flavivirus (1998)

We undertook a comprehensive phylogenetic study to establish the genetic relationship among the viruses of the genus Flavivirus and to compare the classification based on molecular phylogeny with the existing serologic method. By using a combination of quantitative definitions (bootstrap support level and the pairwise nucleotide sequence identity), the viruses could be classified into clusters, clades, and species. Our phylogenetic study revealed for the first time that from the putative ancestor two branches, non-vector and vector-borne virus clusters, evolved and from the latter cluster emerged tick-borne and mosquito-borne virus clusters. Provided that the theory of arthropod association being an acquired trait was correct, pairwise nucleotide sequence identity among these three clusters provided supporting data for a possibility that the non-vector cluster evolved first, followed by the separation of tick-borne and mosquito-borne virus clusters in that order. Clades established in our study correlated significantly with existing antigenic complexes. We also resolved many of the past taxonomic problems by establishing phylogenetic relationships of the antigenically unclassified viruses with the well-established viruses and by identifying synonymous viruses.
Characterization of a native hammerhead ribozyme derived from schistosomes (2005)

A recent re-examination of the role of the helices surrounding the conserved core of the hammerhead ribozyme has identified putative loop-loop interactions between stems I and II in native hammerhead sequences. These extended hammerhead sequences are more active at low concentrations of divalent cations than are minimal hammerheads. The loop-loop interactions are proposed to stabilize a more active conformation of the conserved core. Here, a kinetic and thermodynamic characterization of an extended hammerhead sequence derived from Schistosoma mansoni is performed. Biphasic kinetics are observed, suggesting the presence of at least two conformers, one cleaving with a fast rate and the other with a slow rate. Replacing loop II with a poly(U) sequence designed to eliminate the interaction between the two loops results in greatly diminished activity, suggesting that the loop-loop interactions do aid in forming a more active conformation. Previous studies with minimal hammerheads have shown deleterious effects of Rp-phosphorothioate substitutions at the cleavage site and 5' to A9, both of which could be rescued with Cd2+. Here, phosphorothioate modifications at the cleavage site and 5' to A9 were made in the schistosome-derived sequence. In Mg2+, both phosphorothioate substitutions decreased the overall fraction cleaved without significantly affecting the observed rate of cleavage. The addition of Cd2+ rescued cleavage in both cases, suggesting that these are still putative metal binding sites in this native sequence.
Clinical andABCB11profiles in Korean infants with progressive familial intrahepatic cholestasis (2016)

Alterations in the transmembrane of the bile salt export pump in the Korean infants were different from those previously reported in Chinese, Japanease, Taiwanese, and European patients.
Functional Role of c-Src in IL-1-Induced NF- B Activation: c-Src Is a Component of the IKK Complex (2005)

Interleukin-1 (IL-1) mediates numerous host responses through the rapid activation of nuclear factor-kappa B (NF-kappa B), but the signal pathways leading to NF-kappa B activation are regulated at multiple stages. Here, we propose a novel regulatory system for IL-1-induced NF-kappa B activation by a tyrosine kinase, c-Src. The kinase activity of c-Src increases in an IL-1-dependent manner and the ectopic expression of c-Src augments IL-1-induced NF-kappa B activation, suggesting the involvement of c-Src in IL-1 signaling. However, a Src family inhibitor, PP2 failed to inhibit IL-1-induced NF-kappa B activation, and the expression of a c-Src mutant lacking kinase activity (c-Src KD) augmented IL-1-induced NF-kappa B activation as well as wild type c-Src, indicating that the tyrosine kinase activity is not required for IL-1-induced NF-kappa B activation. Furthermore, a physiological interaction between c-Src and I kappa B kinase gamma (IKK gamma) was observed, implying the involvement of c-Src in the IKK-complex. While c-Src augmented IL-1-induced IKK activation independent of its kinase activity, the region comprising amino acids 361-440 in the c-Src kinase domain are required for NF-kappa B activation. The same region of c-Src is also required for IL-1-induced IKK activation and the association with IKK gamma. Taken together, our results suggest that c-Src plays a critical role in IL-1-induced NF-kappa B activation through the IKK complex.
Single-Phase Fluid Flow in a Stratified Porous Medium With Crossflow (1984)

Abstract A new model is presented for a stratified reservoir. The model is used to study the influence of crossflow on pressure transient well tests and other single-phase flow problems. The reasons for single-phase crossflow in multilayer reservoirs are discussed. Solutions for linear and radial incompressible flow in a stratified reservoir with crossflow are presented; effects of reservoir parameters and crossflow on pressure are studied, and a criterion for considering crossflow between layers is suggested.
Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis (2016)

The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney in a robust and sustainable manner. Using bioluminescence imaging in mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered to overexpress miRNA-let7c (miR-let7c-MSCs), selectively homed to damaged kidneys and upregulated miR-let7c gene expression, compared with nontargeting control (NTC)-MSCs. miR-let7c-MSC therapy attenuated kidney injury and significantly downregulated collagen IVα1, metalloproteinase-9, transforming growth factor (TGF)-β1, and TGF-β type 1 receptor (TGF-βR1) in UUO kidneys, compared with controls. In vitro analysis confirmed that the transfer of miR-let7c from miR-let7c-MSCs occurred via secreted exosomal uptake, visualized in NRK52E cells using cyc3-labeled pre-miRNA-transfected MSCs with/without the exosomal inhibitor, GW4869. The upregulated expression of fibrotic genes in NRK52E cells induced by TGF-β1 was repressed following the addition of isolated exosomes or indirect coculture of miR-let7c-MSCs, compared with NTC-MSCs. Furthermore, the cotransfection of NRK52E cells using the 3'UTR of TGF-βR1 confirmed that miR-let7c attenuates TGF-β1-driven TGF-βR1 gene expression. Taken together, the effective antifibrotic function of engineered MSCs is able to selectively transfer miR-let7c to damaged kidney cells and will pave the way for the use of MSCs for therapeutic delivery of miRNA targeted at kidney disease.
Synthetic Lethal Screens as a Means to Understand and Treat MYC-Driven Cancers (2014)

Although therapeutics against MYC could potentially be used against a wide range of human cancers, MYC-targeted therapies have proven difficult to develop. The convergence of breakthroughs in human genomics and in gene silencing using RNA interference (RNAi) have recently allowed functional interrogation of the genome and systematic identification of synthetic lethal interactions with hyperactive MYC. Here, we focus on the pathways that have emerged through RNAi screens and present evidence that a subset of genes showing synthetic lethality with MYC are significantly interconnected and linked to chromatin and transcriptional processes, as well as to DNA repair and cell cycle checkpoints. Other synthetic lethal interactions with MYC point to novel pathways and potentially broaden the repertoire of targeted therapies. The elucidation of MYC synthetic lethal interactions is still in its infancy, and how these interactions may be influenced by tissue-specific programs and by concurrent genetic change will require further investigation. Nevertheless, we predict that these studies may lead the way to novel therapeutic approaches and new insights into the role of MYC in cancer.
Physical and genetic characterization of the glnA--glnG region of the Escherichia coli chromosome. (1981)

We have cloned and characterized a fragment of the Escherichia coli chromosome spanning glnA, the structural gene for glutamine synthetase (L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2]. The fragment also carriers glnG, whose product is necessary for regulation of glnA expression, and a previously unidentified gene whose function we have not discovered. Transcription of glnA and the newly identified gene occurs divergently from a region between the two genes. Transcription of glnA proceeds toward glnG, which is transcribed in the same direction. A region of DNA between glnA and glnG contains genetic information whose loss may result in the inability to reduce expression of glnA and other operons in response to ammonia (the GlnC phenotype).
Clinical uses of the medicinal leech (2011)

The medicinal leech, Hirudo medicinalis, is an excellent example of the use of invertebrates in the treatment of human disease. Utilized for various medical indications since the ancient times, the medicinal leech is currently being used in a narrow range of well-defined and scientifically-grounded clinical applications. Hirudotherapy is most commonly used in the setting of venous congestion associated with soft tissue replantations and free flap-based reconstructive surgery. This is a comprehensive review of current clinical applications of hirudotherapy, featuring a comprehensive search of all major medical search engines (i.e. PubMed, Google Scholar, ScientificCommons) and other cross-referenced sources. The authors focus on indications, contraindications, practical application/handling of the leech, and therapy-related complications.
Angiotensin-converting enzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis. (1994)

In rats with ascending aortic stenosis, chronic ACE inhibition with fosinopril improved survival, decreased the extent of LV hypertrophy, and improved cardiac function despite persistent elevation of LV systolic pressure. The favorable effects of fosinopril may be related in part to inhibition of the effects of cardiac ACE on myocyte hypertrophy rather than to systemic hemodynamic mechanisms.
LINC power amplifier combiner method efficiency optimization (2000)

Linear amplification using nonlinear components (LINC) is a method of vector summing two constant amplitude phase-modulated signals to achieve power amplification. The theoretical efficiency of the LINC power amplifier has been reported as 100% since highly efficient nonlinear constant amplitude amplifiers can be used. However, the 100% efficiency performance is only possible at one or two loads along the power output curve. The bulk of the papers regarding LINC has focused on clever implementations of the signal vector decomposition as well as methods to achieve highly linear signal separation. There has been little regard in the literature to the signal combiner implementation necessary to achieve the high power-added efficiency (PAE) of the LINC radio frequency (RF) power amplifier. Efficiency is not an intrinsic property of the combiner implementations, however, the combiner method is the single biggest contributor to efficient performance of a LINC RF power amplifier. This paper develops an analysis method that determines the efficiency of the LINC power amplifier as a function of the amplitude modulation statistics. This can be employed to design the RF communication system amplitude modulation characteristics and to tradeoff and optimize the RF transmitter PAE.
A video browser that learns by example (1996)

: This thesis investigates the role of learning in a video browsing venue. Regions of significant change are preselected automatically from video sequences in a television situation comedy. These regions, which often depict portions of actors, are presented to the user for interactive labeling. The user specifies regions which are positive and negative examples of the actors and the computer trains by analyzing the regions with respect to a bank of signal models. Other regions in the video database, similar to the positive training examples, are found automatically. A feature of this work is the integration of high-level information, as encapsulated by the show&amp;apos;s script and closed captions, and low-level signal feature analysis, as derived from similarity measures. The pooling of these descriptors constrains the search. Results of a database query are presented to the user during an interactive session. Given sufficient training data and user feedback, the computer learns the pattern o...
Solution conformation of enopeptin A, a depsipeptide antibiotic, using 2D NMR and restrained molecular dynamics studies. (1994)

Studies on the solution conformation of the cyclic depsipeptide antibiotic enopeptin A have been carried out using 2D NMR and molecular modelling techniques. The proton resonances of the antibiotic in DMSO-d6 have been assigned by the use of TOCSY and ROESY experiments. The interproton distance information obtained from the ROESY experiments have been used as the basis for elucidating the probable structures in solution. The restrained molecular dynamics technique was applied to calculate the structures in solution, and six resultant structures with fewer distance constraint violations were obtained that satisfy the experimental restraints very well. The conformation of the cyclic moiety of the molecules is well defined whereas the aliphatic chain segment is disordered.
Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. (1997)

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.
Gene delivery in malignant B cells using the combination of lentiviruses conjugated to anti‐transferrin receptor antibodies and an immunoglobulin promoter (2014)

The present study demonstrates that gene expression can be restricted to malignant B cells and suggests that this dual targeted gene therapy strategy may help to circumvent the potential side effects of certain TfR1-targeted protein delivery approaches.
ZD6474 Suppresses Oncogenic RET Isoforms in a Drosophila Model for Type 2 Multiple Endocrine Neoplasia Syndromes and Papillary Thyroid Carcinoma (2005)

Patients with hereditary medullary thyroid carcinoma (MTC) associated with multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC (FMTC) have mutations in the RET proto-oncogene. Approximately 40 percent of patients with papillary thyroid carcinoma (PTC) typically have either intrachromosomal or extrachromosomal rearrangements that join the promoter and NH(2)-terminal domains of unrelated genes to the COOH-terminal fragment of RET. The RET point mutations associated with MEN2A, MEN2B, or FMTC, or the chromosomal breakpoints and translocations associated with PTC, typically activate the RET receptor tyrosine kinase (RTK). RET kinase inhibitors are likely to be beneficial for patients with hereditary MTC, where currently there is no effective chemotherapy or radiation therapy. Recently, the low molecular weight tyrosine kinase inhibitor ZD6474 was found to block the enzymatic activity of RET-derived oncoproteins in cultured cell lines. We have developed a Drosophila model for MEN2A and MEN2B diseases by targeting oncogenic forms of RET to the developing Drosophila eye. Here we show that, when fed orally, ZD6474 suppressed RET-mediated phenotypes within the context of this in vivo model. Importantly, ZD6474 showed high efficacy and very low toxicity. This compound failed to significantly suppress an activated form of another RTK, the Drosophila epidermal growth factor receptor, nor did it suppress the activity of downstream components of the RET/Ras pathway. Our results support the view that targeting chemical kinase inhibitors such as ZD6474 to tissues with oncogenic forms of RET is a useful treatment strategy for RET-dependent carcinomas.
Stable-locking bandwidth in sidemode injection locked semiconductor lasers (1991)

An analytical expression for the possible sidemode locking bandwidth, consistent with the formula for peak-mode injection locking, is derived. Small-signal analysis is then applied to investigate the stable part of the locking range. The results demonstrate that sidemode injection locking offers relaxed operational requirements for frequency matching, with enhanced bandwidth, while retaining the traditional benefits of injection locking.