gebhart/patrepeval huggingface dataset:
A second transcriptionally active DNA-binding site for the Wilms tumor gene product, WT1. (1993)

The putative Wilms tumor suppressor gene, wt1, encodes a zinc-finger protein that binds to the DNA sequence 5'-GCGGGGGCG-3'. We previously reported that WT1 has separable domains that function either to activate or suppress transcription. We now have identified a second WT1 binding sequence (5'-TCCTCCTCCTCCTCTCC-3') 3' to the transcription initiation site of the platelet-derived growth factor A-chain gene by DNase I footprinting and gel mobility shift assays. WT1 requires both 5' and 3' binding sites for transcriptional suppression; however, WT1 functions as a transcriptional activator when it binds to either the 5' or 3' site alone. This second WT1 binding sequence functions equally well as the previously identified 5'-GCGGGGGCG-3' sequence when analyzed in transient transfection assays. A core DNA sequence recognized by WT1 was defined by using related synthetic oligonucleotides. We also identified sequences similar to the WT1 binding site within the promoter regions of five other growth-related genes and demonstrated that each of these sequences also binds WT1 in gel mobility shift assays. These results thus identify a second WT1 binding site and suggest that additional growth-related genes may be transcriptionally influenced by WT1.
Bone marrow cells for cardiac regeneration: the quest for the protagonist continues (2004)

See also article by Hattan et al. [11] (pages 334-344) in this issue .

The past few years have witnessed an explosion of research on methods to achieve myocardial repair via cellular transplantation or mobilization of endogenous cells [1]. Several different cell types, including skeletal myoblasts [2], c-kit+/Sca-1+/lin− bone marrow (BM) cells [3], BM mesenchymal stem cells (MSCs) [4], BM ‘side-population’ (SP) cells [5], endothelial progenitor cells (EPCs) [6], and cardiac stem cells (CSCs) [7], have been utilized in an effort to achieve cardiac reconstitution and restoration of function following myocardial infarction (MI). The evidence accumulated over the past few years indicates that left ventricular (LV) function and adverse LV remodeling can be ameliorated via cell-based therapies, and the preliminary results from several small-scale, mostly non-randomized, clinical trials have been encouraging [8–10]. However, the mechanism(s) underlying the observed functional improvement remains unclear and the debate regarding the advantages of one candidate cell versus another continues unabated.

So, what characteristics should a cell have in order to be selected for therapeutic use in humans? The answer is simple: it has to differentiate into cardiomyocytes that are connected both mechanically and electrically with native myocytes (contracting in synchrony with adjacent cells) and be able to form vascular structures in order to get blood supply in the scar. Thus far, very few cell types have been shown to do all of these things.

In this issue of the Journal, Hattan, Kawaguchi, and colleagues … 

*Corresponding author. Tel.: +1 502 852 7959; fax: +1 502 852 7147. Email address: buddha{at}louisville.edu
The Application of a Compact Multispectral Imaging System with Integrated Excitation Source to In vivo Monitoring of Fluorescence During Topical Photodynamic Therapy of Superficial Skin Cancers¶ (2001)

A novel, compact and low-cost multispectral fluorescence imaging system with an integrated excitation light source is described. Data are presented demonstrating the application of this method to in vivo monitoring of fluorescence before, during and after topical 5-aminolevulinic acid photodynamic therapy of superficial skin cancers. The excitation source comprised a fluorescent tube with the phosphor selected to emit broadband violet light centered at 394 nm. The camera system simultaneously captured spectrally specific images of the fluorescence of the photosensitizer, protoporphyrin IX, the illumination profile and the skin autofluorescence. Real-time processing enabled images to be manipulated to create a composite image of high contrast. The application and validation of this method will allow further detailed studies of the characteristics and time-course of protoporphyrin IX fluorescence, during topical photodynamic therapy in human skin in vivo.
Synthesis of stoichiometric hydroxyapatite by a Gel route from the aqueous solution of citric and phosphonoacetic acids (1995)

Stoichiometric hydroxyapatite has been successfully synthesized by a gel route from an aqueous solution containing calcium nitrate and phosphoacetic acid. A viscous aqueous solution [ gel ] was otained during concentration with heating.
Memory Retrieval Requires Ongoing Protein Synthesis and NMDA Receptor Activity-Mediated AMPA Receptor Trafficking (2015)

Whereas consolidation and reconsolidation are considered dynamic processes requiring protein synthesis, memory retrieval has long been considered a passive readout of previously established plasticity. However, previous findings suggest that memory retrieval may be more dynamic than previously thought. This study therefore aimed at investigating the molecular mechanisms underlying memory retrieval in the rat. Infusion of protein synthesis inhibitors (rapamycin or anisomycin) in the amygdala 10 min before memory retrieval transiently impaired auditory fear memory expression, suggesting ongoing protein synthesis is required to enable memory retrieval. We then investigated the role of protein synthesis in NMDA receptor activity-mediated AMPA receptor trafficking. Coinfusion of an NMDA receptor antagonist (ifenprodil) or infusion of an AMPA receptor endocytosis inhibitor (GluA23Y) before rapamycin prevented this memory impairment. Furthermore, rapamycin transiently decreased GluA1 levels at the postsynaptic density (PSD), but did not affect extrasynaptic sites. This effect at the PSD was prevented by an infusion of GluA23Y before rapamycin. Together, these data show that ongoing protein synthesis is required before memory retrieval is engaged, and suggest that this protein synthesis may be involved in the NMDAR activity-mediated trafficking of AMPA receptors that takes place during memory retrieval.
Automotive electronics (1994)

We live in a rapidly changing world where none of us is clairvoyant. Our desire, but inability, to forecast the future includes the next frontiers of high technology. This rapidly changing environment produces many new venues that drive future change. The rapid growth of automotive electronics has always had its new "frontiers." This article addresses the practical aspects and issues.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Unraveling oxyntomodulin, GLP1's enigmatic brother (2012)

Oxyntomodulin (OXM) is a peptide secreted from the L cells of the gut following nutrient ingestion. OXM is a dual agonist of the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) combining the effects of GLP1 and glucagon to act as a potentially more effective treatment for obesity than GLP1R agonists. Injections of OXM in humans cause a significant reduction in weight and appetite, as well as an increase in energy expenditure. Activation of GCGR is classically associated with an elevation in glucose levels, which would be deleterious in patients with T2DM, but the antidiabetic properties of GLP1R agonism would be expected to counteract this effect. Indeed, OXM administration improved glucose tolerance in diet-induced obese mice. Thus, dual agonists of the GCGR and GLP1R represent a new therapeutic approach for diabetes and obesity with the potential for enhanced weight loss and improvement in glycemic control beyond those of GLP1R agonists.
Possible Unifying Mechanism of Picornavirus Genome Replication (2014)

This chapter summarizes all the pertinent experimental evidence that is currently available and proposes a unified model for picornavirus RNA replication. These data are derived from three types of experiments. In the simplest type, purified enzymes are used to study biochemical reactions in vitro. The second in complexity are those studies that use crude replication complexes isolated either from infected cells or from coupled translation/replication reactions of viral RNA. Finally, the most difficult method involves studying reactions in the infected cell itself. The proteins of the P3 domain are those that are most directly involved in the process of RNA synthesis. During translation of poliovirus RNA the P3 precursor is generated from the polyprotein by a fast cleavage event at the amino terminus of the 3A-coding region. The RNA polymerases of poliovirus and human rhinoviruses (HRV)2 are dependent in vitro on an RNA template and on a primer, either RNA, DNA, or VPg. Properties and functions of proteins encoded by the P3 domain of the poliovirus polyprotein are discussed. Mutational analysis of the heteropolymeric sequences in the 3 ' nontranslated region (NTR) of entero- and rhinoviruses indicated that this region is important for RNA replication. Prior to the initiation of minus-strand RNA synthesis, the RNA polymerase has to recognize its own viral RNA in a pool of cellular mRNAs and then select it as the only template for transcription.
Hydrophobicity drives the systemic distribution of lipid-conjugated siRNAs via lipid transport pathways (2018)

Efficient delivery of therapeutic RNA beyond the liver is the fundamental obstacle preventing its clinical utility. Lipid conjugation increases plasma half-life and enhances tissue accumulation and cellular uptake of small interfering RNAs (siRNAs). However, the mechanism relating lipid hydrophobicity, structure, and siRNA pharmacokinetics is unclear. Here, using a diverse panel of biologically occurring lipids, we show that lipid conjugation directly modulates siRNA hydrophobicity. When administered in vivo, highly hydrophobic lipid-siRNAs preferentially and spontaneously associate with circulating low-density lipoprotein (LDL), while less lipophilic lipid-siRNAs bind to high-density lipoprotein (HDL). Lipid-siRNAs are targeted to lipoprotein receptor-enriched tissues, eliciting significant mRNA silencing in liver (65%), adrenal gland (37%), ovary (35%), and kidney (78%). Interestingly, siRNA internalization may not be completely driven by lipoprotein endocytosis, but the extent of siRNA phosphorothioate modifications may also be a factor. Although biomimetic lipoprotein nanoparticles have been explored for the enhancement of siRNA delivery, our findings suggest that hydrophobic modifications can be leveraged to incorporate therapeutic siRNA into endogenous lipid transport pathways without the requirement for synthetic formulation.
Reduction of out-of-band radiation in OFDM based overlay systems (2005)

In orthogonal frequency-division multiplexing (OFDM) based overlay systems the reduction of the out-of-band radiation is one of the most essential topics. In this paper, two approaches are considered: the conventional windowing of the OFDM signal in time domain and the recently presented concept of cancellation carriers (CCs) where CCs are inserted at the borders of the used OFDM spectrum to suppress the sidelobes of the transmit signal. From an exemplary overlay scenario in the very high frequency (VHF) band, requirements on sidelobe suppression are derived. Simulation results show that by combining windowing with the CC concept the out-of-band radiation can be reduced significantly, and thus, enabling a successful coexistence of two systems in the VHF band
Potent HIV protease inhibitors: the development of tetrahydrofuranylglycines as novel P2-ligands and pyrazine amides as P3-ligands (1993)

A series of protease inhibitors bearing constrained unnatural amino acids at the P2-position and novel heterocycles at the P3-position of compound 1 (Ro 31-8959) were synthesized, and their in vitro enzyme inhibitory and antiviral activities were evaluated. Replacement of P2-asparagine of compound 1 with (2S,3'R)-tetrahydrofuranylglycine resulted in improvement in enzyme inhibitory as well as antiviral potencies (compound 23). Interestingly, incorporation of (2S,3'S)-tetrahydrofuranylglycine at the P2-position proved to be less effective. The resulting compound 24 was 100-fold less potent than the 2S,3R-isomer (compound 23). This stereochemical preference indicated a hydrogen-bonding interaction between the tetrahydrofuranyl oxygen and the residues of the S2-region of the enzyme active site. Furthermore, replacement of P3-quinolinoyl ligand of 1 with various novel heterocycles resulted in potent inhibitors of HIV proteases. Of particular interest, compound 2 with (2S,3'R)-tetrahydrofuranylglycine at P2 and pyrazine derivative at P3 is one of the most potent inhibitors of HIV-1 (IC50 value 0.07 nM) and HIV-2 (IC50 value 0.18 nM) proteases. Another important result in this series is the identification of compound 27 in which the P2-P3-amide carbonyl has been removed. The resulting compound 27 has exhibited improvement in antiviral potency while retaining the enzyme inhibitory potency similar to compound 1.
Recursive Searching over Trees for Quick Solution of the Nearest Point Problems (1994)

This article evaluates an asymptotic performance of a binary tree that finds one among some sample points given beforehand that is the nearest in an 1-bit Hamming space to an arbitrary reference point.
Physicochemical Activation of Recombinant Latent Transforming Growth Factor-beta's 1, 2, and 3 (1990)

Native and recombinant forms of transforming growth factor-beta 1 (TGF-beta 1) are synthesized predominantly as biologically latent complexes. Physicochemical analysis demonstrates that the more recently described TGF-beta 2 and TGF-beta 3 are also latent, and reveals a common series of sharply defined parameters for activation. Human recombinant latent TGF-beta's 1 and 2 show identical profiles of activation by acid and base; the transition from latency occurs between pH 4.1 and 3.1, and between pH 11.0 and 11.9. The profile for chicken recombinant latent TGF-beta 3 is slightly shifted with activation between pH 3.1 and 2.5, and between pH 10.0 and 12.3. Thermal activation of native and recombinant latent TGF-beta 1 occurs over the temperature ranges of 75-100 degrees C and 65-100 degrees C, respectively, with complete activation after 5 min at 80 degrees C. Temperatures above 90 degrees C result in thermal denaturation of TGF-beta 1 itself. Recombinant latent TGF-beta's 2 and 3 are also activated over this temperature range; however, maximum activation occurs at 100 degrees C. These results suggest common elements in latent complex structure despite differences between the TGF-beta subtypes in pro-region primary sequence.
Physical properties of diphenyldiacetylenic liquid crystals (1989)

Optical and electro-optic properties of two highly conjugated diphenyldiacetylenic liquid crystals (LCs) [1.4-bis-(4-propylphenyl)-butadiyne, abbreviated as PTTP-mm] and their eutectic mixture were characterized in the nematic range. These LCs are found to exhibit extraordinarily high birefringence and very low viscoelastic coefficient. Their figure of merit is significantly higher than that of the widely used commercial LC mixture BDH-E7. Potential application of PTTP-mm in modulating infrared radiation is addressed.
Economic importance and biological control of Lygus and Adelphocoris in North America / (1987)

By
Hydrolysis of Cellulose by Amorphous Carbon Bearing SO3H, COOH, and OH Groups (2008)

The hydrolysis of cellulose into saccharides using a range of solid catalysts is investigated for potential application in the environmentally benign saccharification of cellulose. Crystalline pure cellulose is not hydrolyzed by conventional strong solid Brønsted acid catalysts such as niobic acid, H-mordenite, Nafion and Amberlyst-15, whereas amorphous carbon bearing SO 3H, COOH, and OH function as an efficient catalyst for the reaction. The apparent activation energy for the hydrolysis of cellulose into glucose using the carbon catalyst is estimated to be 110 kJ mol (-1), smaller than that for sulfuric acid under optimal conditions (170 kJ mol (-1)). The carbon catalyst can be readily separated from the saccharide solution after reaction for reuse in the reaction without loss of activity. The catalytic performance of the carbon catalyst is attributed to the ability of the material to adsorb beta-1,4 glucan, which does not adsorb to other solid acids.
Precision genetics for complex objectives in animal agriculture (2010)

Indirect modification of animal genomes by interspecific hybridization, cross-breeding, and selection has produced an enormous spectrum of phenotypic diversity over more than 10,000 yr of animal domestication. Using these established technologies, the farming community has successfully increased the yield and efficiency of production in most agricultural species while utilizing land resources that are often unsuitable for other agricultural purposes. Moving forward, animal well-being and agricultural sustainability are moral and economic priorities of consumers and producers alike. Therefore, these considerations will be included in any strategy designed to meet the challenges produced by global climate change and an expanding world population. Improvements in the efficiency and precision of genetic technologies will enable a timely response to meet the multifaceted food requirements of a rapidly increasing world population.
Development of highly stable galectins: Truncation of the linker peptide confers protease‐resistance on tandem‐repeat type galectins (2005)

Galectin-9 and galectin-8, members of beta-galactoside-binding animal lectin family, are promising agents for the treatment of immune-related and neoplastic diseases. The proteins consist of two carbohydrate recognition domains joined by a linker peptide, which is highly susceptible to proteolysis. To increase protease resistance, we prepared mutant proteins by serial truncation of the linker peptide. As a result, mutant forms lacking the entire linker peptide were found to be highly stable against proteolysis and retained their biological activities. These mutant proteins might be useful tools for analyzing the biological functions and evaluating the therapeutic potential of galectin-9 and galectin-8.
Inhibition of Human Immunodeficiency Virus Type 1 Replication by Nuclear Chimeric Anti-HIV Ribozymes in a Human T Lymphoblastoid Cell Line (1998)

Human immunodeficiency virus (HIV) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the HIV life cycle, many different strategies have been developed including transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ribozymes, and intracellular antibody fragments. In this paper, we have tested in a human T lymphoblastoid cell line the antiviral activity of ribozymes specifically designed to co-localize inside the nucleus with the Rev pre-mRNA before it is spliced and transported to the cytoplasm. This result was obtained by inserting the ribozyme in the spliceosomal U1 small nuclear RNA (snRNA) and in a derivative that has perfect complementarity with the 5' splice site of the Rev pre-mRNA. These ribozymes were tested in human T cell clones and were shown to be very efficient in inhibiting viral replication. Not only were the p24 levels in the culture medium drastically reduced but so were the intracellular HIV transcripts. Control disabled ribozymes enabled us to show the specificity of the ribozyme activity. Therefore, these constructs have potential utility for gene therapy of HIV-1 infection.
Structure, characterization, and expression of the rat oxytocin receptor gene. (1995)

The multiple hormonal and neurotransmitter functions of the nonapeptide oxytocin are mediated by specific oxytocin receptors (OTRs). In most target tissues, the number of OTRs is strongly regulated. Specifically, in the uterus, a dramatic OTR upregulation precedes the onset of parturition. To study the molecular mechanisms underlying OTR regulation, we have isolated and characterized recombinant bacteriophage lambda EMBL3 genomic clones containing the rat OTR gene, using sequence information derived from a human myometrial OTR cDNA. The rat OTR gene spans > 20 kb and contains three exons. A 97-bp intron is in the 5' untranslated region and a > 12-kb intron interrupts the coding region between transmembrane domains 6 and 7. The promoter region lacks an apparent TATA or CCAAT box but contains multiple putative interleukin-response elements [six NF-IL6 (C/EBP beta) and four APRF (STAT3) binding motifs], supporting the notion that interleukins may mediate labor induction via transcriptional activation of the OTR gene. The predicted amino acid sequence is 93% identical to the human OTR sequence but only 48% and 38% identical to the rat V1 and V2 vasopressin receptor sequences, respectively. At parturition, the OTR gene is highly expressed in the rat uterus and gives rise to at least three transcripts (2.9, 4.8, and 6.7 kb) which differ in the length of their 3' untranslated regions.
Application of IR and NIR fiber optic imaging in thermographic and spectroscopic diagnosis of atherosclerotic vulnerable plaques: preliminary experience (2000)

Despite major advances in cardiovascular science and technology during the past three decades, approximately half of all myocardial infarctions and sudden deaths occur unexpectedly. It is widely accepted that coronary atherosclerotic plaques and thrombotic complications resulting from their rupture or erosion are the underlying causes of this major health problem. The majority of these vulnerable plaques exhibit active inflammation, a large necrotic lipid core, a thin fibrous cap, and confer a stenosis of less than 70%. These lesions are not detectable by stress testing or coronary angiography. Our group is exploring the possibility of a functional classification based on physiological variables such as plaque temperature, pH, oxygen consumption, lactate production etc. We have shown that heat accurately locates the inflamed plaques. We also demonstrated human atherosclerotic plaques are heterogeneous with regard to pH and hot plaques and are more likely to be acidic. To develop a nonsurgical method for locating the inflamed plaques, we are developing both IR fiber optic imaging and NIR spectroscopic systems in our laboratory to detect hot and acidic plaque in atherosclerotic arterial walls. Our findings introduce the possibility of an isolated/combined IR and NIR fiber optic catheter that can bring new insight into functional assessment of atherosclerotic plaque and thereby detection of active and inflamed lesions responsible for heart attacks and strokes.