gebhart/patrepeval huggingface dataset:
Targeting the Tumor Microenvironment in Cancer: Why Hyaluronidase Deserves a Second Look (2011)

Increased extracellular matrix (ECM) deposition is a characteristic observed in many solid tumors. Increased levels of one ECM component-namely, hyaluronan (HA)-leads to reduced elasticity of tumor tissue and increased interstitial fluid pressure. Multiple initial reports showed that the addition of hyaluronidase (HYAL) to chemotherapeutic regimens could greatly improve efficacy. Unfortunately, the bovine HYAL used in those studies was limited therapeutically by immunologic responses to treatment. Newly developed recombinant human HYAL has recently been introduced into clinical trials. In this article, we describe the role of HA in cancer, methods of targeting HA, and clinical studies performed to date, and we propose that targeting HA could now be an effective treatment option for patients with many different types of solid tumors.
Selective Synthesis and Characterization of CdSe Nanorods and Fractal Nanocrystals (2002)

CdSe nanorods and dendritic fractals were synthesized through a novel controllable solution-phase hydrothermal method. Soluble selenite was employed to provide a highly reactive Se source in the synthesis. Both morphologies and phases of the CdSe products could be successfully controlled by choosing appropriate complexing agents to adjust the dynamics of the reaction process. Reaction temperature and Cd/Se ratio in raw materials were also important parameters influencing the morphologies and phases of the products. The phase structures, morphologies, and optical properties of the CdSe products were investigated by XRD, TEM, HRTEM, and UV-vis and photoluminescence spectroscopies. The formation mechanisms of the nanorods and fractals were investigated and discussed on the basis of the experimental results.
The miR-30 MicroRNA Family Targets smoothened to Regulate Hedgehog Signalling in Zebrafish Early Muscle Development (2013)

The importance of microRNAs in development is now widely accepted. However, identifying the specific targets of individual microRNAs and understanding their biological significance remains a major challenge. We have used the zebrafish model system to evaluate the expression and function of microRNAs potentially involved in muscle development and study their interaction with predicted target genes. We altered expression of the miR-30 microRNA family and generated phenotypes that mimicked misregulation of the Hedgehog pathway. Inhibition of the miR-30 family increases activity of the pathway, resulting in elevated ptc1 expression and increased numbers of superficial slow-muscle fibres. We show that the transmembrane receptor smoothened is a target of this microRNA family. Our results indicate that fine coordination of smoothened activity by the miR-30 family allows the correct specification and differentiation of distinct muscle cell types during zebrafish embryonic development.
Analysis of Bcl-2 family protein expression after treatment of leukemia cell lines with homoharringtonine (2008)

2350 The natural product alkaloid Homoharringtonine (HHT) [omacetaxine mepesuccinate- USAN/INN designation] has produced encouraging results in clinical trials as a therapy for patients with CML resistant to tyrosine kinase inhibitor therapies. HHT has been shown to be an effective inhibitor of proteins synthesis (via inhibition of the elongation step of polypeptide synthesis) and to induce apoptosis and inhibit angiogenesis. In clinical studies of CML patients that are resistant to imatinib mesylate, HHT treatment has been shown to decrease BCR-ABL transcript levels which raises the possibility that HHT may be affecting alternate molecular pathways. Long term HHT treatment (>16 hr) of BCR-ABL and non-BCR-ABL positive leukemia cells activates apoptosis and modulates expression of bcl-2 family proteins and proapoptotic caspases. To further delineate the early (
Process integration and device performance of a submicrometer BiCMOS with 16-GHz f/sub t/ double poly-bipolar devices (1989)

Submicrometer-channel CMOS devices have been integrated with self-aligned double-polysilicon bipolar devices showing a cutoff frequency of 16 GHz. n-p-n bipolar transistors and p-channel MOSFETs were built in an n-type epitaxial layer on an n/sup +/ buried layer, and n-channel MOSFETs were built in a p-well on a p/sup +/ buried layer. Deep trenches with depths of 4 mu m and widths of 1 mu m isolated the n-p-n bipolar transistors and the n- and p-channel MOSFETs from each other. CMOS, BiCMOS, and bipolar ECL circuits were characterized and compared with each other in terms of circuit speed as a function of loading capacitance, power dissipation, and power supply voltage. The BiCMOS circuit showed a significant speed degradation and became slower than the CMOS circuit when the power supply voltage was reduced below 3.3 V. The bipolar ECL circuit maintained the highest speed, with a propagation delay time of 65 ps for C/sub L/=0 pF and 300 ps for C/sub L/=1.0 pF with a power dissipation of 8 mW per gate. The circuit speed improvements in the CMOS circuits as the effective channel lengths of the MOS devices were scaled from 0.8 to 0.4 mu m were maintained at almost the same ratio.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Assessing Probability of Ancestry Using Simple Sequence Repeat Profiles: Applications to Maize Inbred Lines and Soybean Varieties (2003)

Abstract Determining parentage is a fundamental problem in biology and in applications such as identifying pedigrees. Difficulties inferring parentage derive from extensive inbreeding within the population, whether natural or planned; using an insufficient number of hypervariable loci; and from allele mismatches caused by mutation or by laboratory errors that generate false exclusions. Many studies of parentage have been limited to comparisons of small numbers of specific parent-progeny triplets. There have been few large-scale surveys of candidates in which there is no prior knowledge of parentage. We present an algorithm that determines the probability of parentage in circumstances where there is no prior knowledge of pedigree and that is robust in the face of missing data and mistyped data. The focus is parentage of an inbred line having uncertain ancestry. The algorithm is a variation of a previously published hybrid-focused algorithm. We describe the algorithm and demonstrate its performance in determining parentage of 43 inbred varieties of soybean that have been profiled using 236 SSR loci and from seven inbred varieties of maize that were profiled using 70 SSR loci. We include simulations of additional levels of missing and mistyped data to show the algorithm's utility and flexibility.
Learned helplessness and social avoidance in the Wistar-Kyoto rat (2014)

The Wistar-Kyoto (WKY) rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs' phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs' behavior to that of Sprague-Dawley (SD), Wistar, and Spontaneously Hypertensive (SHR) rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST). WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness). WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs' behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e., neonatal handling) that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression.
Assays for Hydrophilic and Lipophilic Antioxidant Capacity (oxygen radical absorbance capacity (ORACFL)) of Plasma and Other Biological and Food Samples (2003)

Methods are described for the extraction and analysis of hydrophilic and lipophilic antioxidants, using modifications of the oxygen radical absorbing capacity (ORAC(FL)) procedure. These methods provide, for the first time, the ability to obtain a measure of "total antioxidant capacity" in the protein free plasma, using the same peroxyl radical generator for both lipophilic and hydrophilic antioxidants. Separation of the lipophilic and hydrophilic antioxidant fractions from plasma was accomplished by extracting with hexane after adding water and ethanol to the plasma (hexane/plasma/ethanol/water, 4:1:2:1, v/v). Lipophilic and hydrophilic antioxidants were efficiently partitioned between hexane and aqueous solvents. Conditions for controlling temperature effects and decreasing assay variability using fluorescein as the fluorescent probe were validated in different laboratories. Incubation (37 degrees C for at least 30 min) of the buffer to which AAPH was dissolved was critical in decreasing assay variability. Lipophilic antioxidants represented 33.1 +/- 1.5 and 38.2 +/- 1.9% of the total antioxidant capacity of the protein free plasma in two independent studies of 6 and 10 subjects, respectively. Methods are described for application of the assay techniques to other types of biological and food samples.
Compressed image file formats: JPEG, PNG, GIF, XBM, BMP (1999)

Preface. Acknowledgments. 1. Introduction. The Representation of Images. Vector and Bitmap Graphics. Color Models. True Color versus Palette. Compression. Byte and Bit Ordering. Color Quantization. A Common Image Format. Conclusion. 2. Windows BMP. Data Ordering. File Structure. Compression. Conclusion. 3. XBM. File Format. Reading and Writing XBM Files. Conclusion. 4. Introduction to JPEG. JPEG Compression Modes. What Part of JPEG Will Be Covered in This Book? What are JPEG Files? SPIFF File Format. Byte Ordering. Sampling Frequency. JPEG Operation. Interleaved and Noninterleaved Scans. Conclusion. 5. JPEG File Format. Markers. Compressed Data. Marker Types. JFIF Format. Conclusion. 6. JPEG Human Coding. Usage Frequencies. Huffman Coding Example. Huffman Coding Using Code Lengths. Huffman Coding in JPEG. Limiting Code Lengths. Decoding Huffman Codes. Conclusion. 7. The Discrete Cosine Transform. DCT in One Dimension. DCT in Two Dimensions. Basic Matrix Operations. Using the 2-D Forward DCT. Quantization. Zigzag Ordering. Conclusion. 8. Decoding Sequential-Mode JPEG Images. MCU Dimensions. Decoding Data Units. Decoding Example. Processing DCT Coefficients. Up-Sampling. Restart Marker Processing. Overview of JPEG Decoding. Conclusion. 9. Creating Sequential JPEG Files. Compression Parameters. Output File Structure. Doing the Encoding. Down-Sampling. Interleaving. Data Unit Encoding. Huffman Table Generation. Conclusion. 10. Optimizing the DCT. Factoring the DCT Matrix. Scaled Integer Arithmetic. Merging Quantization and the DCT. Conclusion. 11. Progressive JPEG. Component Division in Progressive JPEG. Processing Progressive JPEG Files. Processing Progressive Scans. MCUs in Progressive Scans. Huffman Tables in Progressive Scans. Data Unit Decoding. Preparing to Create Progressive JPEG Files. Encoding Progressive Scans. Huffman Coding. Data Unit Encoding. Conclusion. 12. GIF. Byte Ordering. File Structure. Interlacing. Compressed Data Format. Animated GIF. Legal Problems. Uncompressed GIF. Conclusion. 13. PNG. History. Byte Ordering. File Format. File Organization. Color Representation in PNG. Device-Independent Color. Gamma. Interlacing. Critical Chunks. Noncritical Chunks. Conclusion. 14. Decompressing PNG Image Data. Decompressing the Image Data. Huffman Coding in Deflate. Compressed Data Format. Compressed Data Blocks. Writing the Decompressed Data to the Image. Conclusion. 15. Creating PNG Files. Overview. Deflate Compression Process. Huffman Table Generation. Filtering. Conclusion. Glossary. Bibliography. Index. 0201604434T04062001
Fatty acid synthase: A metabolic oncogene in prostate cancer? (2003)

In 1920, Warburg suggested that tumors consistently rely on anaerobic pathways to convert glucose to ATP even in the presence of abundant oxygen [Warberg, 1956] despite the fact that it is less efficient for energy supply than aerobic glycolysis. The reasons for this remain obscure to date. More often than not, the microenvironment of solid tumors contains regions of poor oxygenation and high acidity. In this context hypoxia can act in an epigenetic fashion, inducing changes in gene expression and in metabolism for survival. It is reasonable to assume that only the tumor cells capable of developing an unusual tolerance to limiting oxygen availability and to the acidosis resulting from excessive lactate production, can survive. In addition to the striking changes that occur in glucose metabolism, studies in human cancer patients suggest that there is often also an increase in free fatty acid turnover, oxidation and clearance [Legaspi et al., 1987; Hyltander et al., 1991]. For instance, a lipid mobilizing factor produced by tumor cells appears to be responsible for the increase in whole body fatty acid oxidation [Russell and Tisdale, 2002]. Fatty acids synthesis in tumor tissues also occurs at very high rates, as first demonstrated more than half a century ago [Medes et al., 1953]. Importantly, (14)C glucose studies have shown that in tumor cells almost all fatty acids derive from de novo synthesis despite adequate nutritional supply [Sabine and Abraham, 1967; Ookhtens et al., 1984; Weiss et al., 1986]. In addition, tumors overexpressing fatty acid synthase (FAS), the enzyme responsible for de novo synthesis of fatty acids, display aggressive biologic behavior compared to those tumors with normal FAS levels, suggesting that FAS overexpression confers a selective growth advantage. Here, we will review the roles that FAS plays in important cellular processes such as apoptosis and proliferation. In addition, speculations on the putative role of FAS in the altered metabolic pathways of prostate cancer cells will be explored. Because of the frequent overexpression of this enzyme prostate cancer, FAS constitutes a therapeutic target in this disease.
Electric field dependence of optical absorption near the band gap of quantum-well structures (1985)

We report experiments and theory on the effects of electric fields on the optical absorption near the band edge in GaAs/AlGaAs quantum-well structures. We find distinct physical effects for fields parallel and perpendicular to the quantum-well layers. In both cases, we observe large changes in the absorption near the exciton peaks. In the parallel-field case, the excitons broaden with field, disappearing at fields \ensuremath{\sim}${10}^{4}$ V/cm; this behavior is in qualitative agreement with previous theory and in order-of-magnitude agreement with direct theoretical calculations of field ionization rates reported in this paper. This behavior is also qualitatively similar to that seen with three-dimensional semiconductors. For the perpendicular-field case, we see shifts of the exciton peaks to lower energies by up to 2.5 times the zero-field binding energy with the excitons remaining resolved at up to \ensuremath{\sim}${10}^{5}$ V/cm: This behavior is qualitatively different from that of bulk semiconductors and is explained through a mechanism previously briefly described by us [D. A. B. Miller et al., Phys. Rev. Lett. 53, 2173 (1984)] called the quantum-confined Stark effect. In this mechanism the quantum confinement of carriers inhibits the exciton field ionization. To support this mechanism we present detailed calculations of the shift of exciton peaks including (i) exact solutions for single particles in infinite wells, (ii) tunneling resonance calculations for finite wells, and (iii) variational calculations of exciton binding energy in a field. We also calculate the tunneling lifetimes of particles in the wells to check the inhibition of field ionization. The calculations are performed using both the 85:15 split of band-gap discontinuity between conduction and valence bands and the recently proposed 57:43 split. Although the detailed calculations differ in the two cases, the overall shift of the exciton peaks is not very sensitive to split ratio. We find excellent agreement with experiment with no fitted parameters.
985. Studies in the polyene series. Part LII. Oxidation of vitamin A1 and retinene1 by manganese dioxide (1957)

H. B. Henbest, E. R. H. Jones and T. C. Owen, J. Chem. Soc., 1957, 4909 DOI: 10.1039/JR9570004909
Histidine-Proline-rich Glycoprotein as a Plasma pH Sensor (1998)

The middle domain of plasma histidine-proline-rich glycoprotein (HPRG) contains unusual tandem pentapeptide repeats (consensus G(H/P)(H/P)PH) and binds heparin and transition metals. Unlike other proteins that interact with heparin via lysine or arginine residues, HPRG relies exclusively on histidine residues for this interaction. To assess the consequences of this unusual requirement, we have studied the interaction between human plasma HPRG and immobilized glycosaminoglycans (GAGs) using resonant mirror biosensor techniques. HPRG binding to immobilized heparin was strikingly pH-sensitive, producing a titration curve with a midpoint at pH 6.8. There was little binding of HPRG to heparin at physiological pH in the absence of metals, but the interaction was promoted by nanomolar concentrations of free zinc and copper, and its pH dependence was shifted toward alkaline pH by zinc. The affinity of HPRG for various GAGs measured in a competition assay decreased in the following order: heparin > dermatan sulfate > heparan sulfate > chondroitin sulfate A. Binding of HPRG to immobilized dermatan sulfate had a midpoint at pH 6.5, was less influenced by zinc, and exhibited cooperativity. Importantly, plasminogen interacted specifically with GAG-bound HPRG. We propose that HPRG is a physiological pH sensor, interacting with negatively charged GAGs on cell surfaces only when it acquires a net positive charge by protonation and/or metal binding. This provides a mechanism to regulate the function of HPRG (the local pH) and rationalizes the role of its unique, conserved histidine-proline-rich domain. Thus, under conditions of local acidosis (e.g. ischemia or hypoxia), HPRG can co-immobilize plasminogen at the cell surface as well as compete for heparin with other proteins such as antithrombin.
Uniform High Current Field Emission of Electrons from Si and CNF FEAs Individually Controlled by Si Pillar Ungated FETs (2007)

We report the demonstration of the first dense (10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> emitters / cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ), high current (10 mA) array of individually ballasted field emitters that use vertical ungated field effect transistors (FETs) as current limiters. Each silicon or carbon nanofiber (CNF) emitter is individually connected in series with a silicon pillar ungated FET or current limiter (Fig. 1). The ungated FET takes advantage of the saturation of carrier velocity in silicon to obtain current source-like behavior - required for uniform and high current operation with small power dissipation.
Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity (2000)

Chemical modification of proteins with polyethylene glycol (PEGylation) can increase plasma half-lives, stability, and therapeutic potency. To make a PEGylated recombinant immunotoxin with improved therapeutic properties, we prepared a mutant of anti-Tac(Fv)-PE38 (LMB-2), a recombinant immunotoxin composed of a single-chain Fv fragment of the anti-human Tac monoclonal antibody to the IL-2 receptor alpha subunit fused to a 38-kDa fragment of Pseudomonas exotoxin. For site-specific PEGylation of LMB-2, one cysteine residue was introduced into the peptide connector (ASGCGPE) between the Fv and the toxin. This mutant LMB-2 (cys1-LMB-2), which retained full cytotoxic activity, was then site-specifically conjugated with 5 or 20 kDa of polyethylene glycol-maleimide. When compared with unmodified LMB-2, both PEGylated immunotoxins showed similar cytotoxic activities in vitro but superior stability at 37 degrees C in mouse serum, a 5- to 8-fold increase in plasma half-lives in mice, and a 3- to 4-fold increase in antitumor activity. This was accompanied by a substantial decrease in animal toxicity and immunogenicity. Site-specific PEGylation of recombinant immunotoxins may increase their therapeutic potency in humans.
Hepatic gene therapy: adenovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes. (1993)

We have combined a receptor-mediated DNA delivery system with the endosomal lysis ability of adenovirus and shown that DNA can be delivered into primary hepatocytes, resulting in a high level of gene expression. When asialoorosomucoid conjugated with poly(L-lysine) was used to deliver the Escherichia coli beta-galactosidase gene into primary hepatocytes through binding with the hepatic asialoglycoprotein receptor, only a low level of beta-galactosidase was detectable, with less than 0.1% of the hepatocytes being transfected. This level of activity can be greatly enhanced by the cointernalization of the DNA.protein complex with a replication-defective adenovirus, resulting in 100% of the hepatocytes staining blue with 5-bromo-4-chloro-3-indolyl beta-D-galactoside. Quantitative analysis of beta-galactosidase expression also showed a 1000-fold enhancement of activity. To test the applicability of this DNA delivery system for the correction of phenylketonuria, a metabolic disorder that causes severe mental retardation in children, we have delivered the human phenylalanine hydroxylase (PAH) gene to hepatocytes derived from a PAH-deficient mouse strain and demonstrated complete reconstitution of enzymatic activity. This method shows great promise for efficient gene delivery to the liver for correction of hepatic disorders.
Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands (2002)

Telomeres of human chromosomes contain a G-rich 3'-overhang that adopts an intramolecular G-quadruplex structure in vitro which blocks the catalytic reaction of telomerase. Agents that stabilize G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation step catalyzed by telomerase and can therefore act as antitumor agents. We have identified by Fluorescence Resonance Energy Transfer a new series of quinoline-based G-quadruplex ligands that also exhibit potent and specific anti-telomerase activity with IC50 in the nanomolar concentration range. Long term treatment of tumor cells at subapoptotic dosage induces a delayed growth arrest that depends on the initial telomere length. This growth arrest is associated with telomere erosion and the appearance of the senescent cell phenotype (large size and expression of beta-galactosidase activity). Our data show that a G-quadruplex interacting agent is able to impair telomerase function in a tumor cell thus providing a basis for the development of new anticancer agents.