gebhart/patrepeval huggingface dataset:
Sustained cytokine delivery for anticancer vaccination: liposomes as alternative for gene-transfected tumor cells. (1998)

Vaccination with tumor cells genetically engineered to produce interleukin (IL)-2 is an attractive strategy to enhance antitumor immune responses. The improved antitumor immunity upon vaccination with IL-2 gene-modified tumor cells may be due to the prolonged presence of the cytokine at the vaccination site. Because liposomes have been used for sustained delivery of a variety of agents, we compared the protective effect of vaccines consisting of IL-2 gene-modified B16 melanoma cells to that of vaccines composed of IL-2 liposomes and irradiated melanoma cells. The results indicate that both approaches equally protect against a lethal challenge with B16 melanoma cells. More than 20% of the protected animals developed vitiligo at the vaccination and/or tumor challenge site.
Ethanol Induces Fatty Acid Synthesis Pathways by Activation of Sterol Regulatory Element-binding Protein (SREBP) (2002)

Alcoholic fatty liver is the earliest and most common response of the liver to alcohol and may be a precursor of more severe forms of liver injury. The mechanism by which ethanol causes fatty liver and liver injury is complex. We found that in both rat H4IIEC3 and McA-RH7777 hepatoma cell lines, ethanol induced transcription of a sterol regulatory element-binding protein (SREBP)-regulated promoter via increased levels of mature SREBP-1 protein. This effect of ethanol was blocked by addition of sterols. This effect is likely mediated by acetaldehyde, because the effect was only seen in cell lines expressing alcohol dehydrogenase, and inhibition of ethanol oxidation by 4-methylpyrazole blocked the effect in the hepatoma cells. Furthermore, the aldehyde dehydrogenase inhibitor cyanamide enhanced the effect of ethanol in the hepatoma cells. Consistent with these in vitro findings, feeding mice a low fat diet with ethanol for 4 weeks resulted in a significant increase in steady-state levels of the mature (active) form of SREBP-1. Activation of SREBP-1 by ethanol feeding was associated with increased expression of hepatic lipogenic genes as well as the accumulation of triglyceride in the livers. These finding suggest that metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 and that this effect of ethanol may contribute to the development of alcoholic fatty liver.
High-Speed Vibrational Imaging and Spectral Analysis of Lipid Bodies by Compound Raman Microscopy (2009)

Cells store excess energy in the form of cytoplasmic lipid droplets. At present, it is unclear how different types of fatty acids contribute to the formation of lipid droplets. We describe a compound Raman microscope capable of both high-speed chemical imaging and quantitative spectral analysis on the same platform. We used a picosecond laser source to perform coherent Raman scattering imaging of a biological sample and confocal Raman spectral analysis at points of interest. The potential of the compound Raman microscope was evaluated on lipid bodies of cultured cells and live animals. Our data indicate that the in vivo fat contains much more unsaturated fatty acids (FAs) than the fat formed via de novo synthesis in 3T3-L1 cells. Furthermore, in vivo analysis of subcutaneous adipocytes and glands revealed a dramatic difference not only in the unsaturation level but also in the thermodynamic state of FAs inside their lipid bodies. Additionally, the compound Raman microscope allows tracking of the cellular uptake of a specific fatty acid and its abundance in nascent cytoplasmic lipid droplets. The high-speed vibrational imaging and spectral analysis capability renders compound Raman microscopy an indispensible analytical tool for the study of lipid-droplet biology.
Endoscopic Management of Cerebrospinal Fluid Leaks (2002)

To examine the diagnosis and treatment of patients with cerebrospinal fluid (CSF) rhinorrhea, a cohort of 36 patients treated between 1993 and 2000 were examined to consider the role of imaging and other diagnostic tests such as the presence of beta-transferrin in nasal secretion. The etiology of the condition was considered and was found to be congenital in 7 patients and acquired in 29 patients of which in 15 patients it was traumatic, in 12 patients it occurred spontaneously, and in 2 patients it was associated with Wegener's granulomatosis. Where it was possible to obtain nasal secretion, beta-transferrin proved a highly sensitive and specific test and imaging included computed tomography (CT), CT cisternography, and magnetic resonance imaging (MRI) of which fine detail coronal CT and MRI proved the most helpful. In six patients neither imaging nor beta-transferrin could be used to confirm the diagnosis in which case intrathecal fluorescein was used. Repair was performed endoscopically in all cases with one exception where the defect was felt to be too large for this technique. Middle turbinate mucosa, cartilage, and fascia were the preferred repair materials in the anterior skull base whereas dermalfat was preferentially used in the sphenoid. The overall success rate for an endoscopic approach was 94% although in three cases a second endoscopic procedure was required to produce closure and external approaches were used in two additional patients. The use of a diagnostic algorithm is helpful in both confirming the presence of CSF rhinorrhea and the optimum approach. In the vast majority of cases an endoscopic repair will be successful and it avoids many of the complications associated with craniotomy, particularly in a young population. Therefore, it is our preferred option, although surgeons must be prepared for alternative procedures should these prove necessary.
Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma (2000)

In the majority of cases, FNA of palpable thyroid nodules allows for the identification of thyroid carcinoma and the planning of subsequent appropriate therapy. This can be achieved by using simple and inexpensive procedures, if cooperation among clinicians, pathologists, and nuclear physicians is maximized.
Eriocalyxin B Inhibits STAT3 Signaling by Covalently Targeting STAT3 and Blocking Phosphorylation and Activation of STAT3 (2015)

Activated STAT3 plays an important role in oncogenesis by stimulating cell proliferation and resisting apoptosis. STAT3 therefore is an attractive target for cancer therapy. We have screened a traditional Chinese herb medicine compound library and found Eriocalyxin B (EB), a diterpenoid from Isodon eriocalyx, as a specific inhibitor of STAT3. EB selectively inhibited constitutive as well as IL-6-induced phosphorylation of STAT3 and induced apoptosis of STAT3-dependent tumor cells. EB did not affect the upstream protein tyrosine kinases or the phosphatase (PTPase) of STAT3, but rather interacted directly with STAT3. The effects of EB could be abolished by DTT or GSH, suggesting a thiol-mediated covalent linkage between EB and STAT3. Site mutagenesis of cysteine in and near the SH2 domain of STAT3 identified Cys712 to be the critical amino acid for the EB-induced inactivation of STAT3. Furthermore, LC/MS/MS analyses demonstrated that an α, β-unsaturated carbonyl of EB covalently interacted with the Cys712 of STAT3. Computational modeling analyses also supported a direct interaction between EB and the Cys712 of STAT3. These data strongly suggest that EB directly targets STAT3 through a covalent linkage to inhibit the phosphorylation and activation of STAT3 and induces apoptosis of STAT3-dependent tumor cells.
Free radicals and aging of the skin (1992)

Cutaneous aging is the result of genetically determined or intrinsic aging superimposed by degenerative changes due to actinic irradiation, also called photoaging. The manifestations of cutaneous aging, as it relates to the perception of age, is caused by ultraviolet light, in particular in those parts of the body exposed daily to solar radiation. Free radical generation in the skin by UV light and from other sources, such as cellular infiltrations or the xanthine oxidase reaction, may be detected by direct and indirect methods. The decrease in antioxidant enzymes and small molecular weight antioxidants such as glutathione, vitamin E and ubiquinone upon exposure to UV light is an indication that the pro-antioxidant balance can be overwhelmed by acute or chronic photo-oxidative stress. Antioxidant supplementation is therefore a means for prevention or at least retardation of premature cutaneous aging.
ELECTROCHEMISTRY IN THIN LAYERS OF SOLUTION (1973)

NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document. New electrodes for electrochemistry in thin layers of solution have been constructed which are easier to use and give more reproducible data than previous designs. The theory of voltammetry, chronopotentiometry and chronocoulometry in thin layers is derived and verified for simple systems using these electrodes. The particular advantages of the thin layer approach for study of systems in which adsorption of the reactants can occur and for elucidation of the stoichiometry of complicated reactions have been exploited in the present work. The extent of adsorption of the I[subscript 2] - I[superscript -], CoY[superscript -] - CoY[superscript -2] and FeY[superscript -] - FeY[superscript -2] couples (H[subscript 4]Y = ethylenediaminetetraacetic acid) at platinum electrodes has been determined. About 2 x 10[superscript -9] mole/cm.[superscript 2] of iodide ion or 2 x 10[superscript -9] mole/cm.[superscript 2] of iodide were shown to be adsorbed in a non-electroactive state. An additional 1 x 10[superscript -9] mole/cm[superscript 2] of iodine but no iodide was adsorbed in an electroactive state. About 3.1 x 10[superscript -10] mole/cm[superscript 2] of CoY[superscript -] or 4.7 x 10[superscript -10] mole/cm[superscript 2] of CoY[superscript -2] are adsorbed at bright platinum electrodes. No adsorption of FeY[superscript -] or FeY[superscript -2] was detected. The stoichiometry of the electrochemical oxidation of PtCl[subscript 4][superscript -2], PtBr[subscript 4][superscript -2] and PtI[subscript 4][superscript -2], and of the electrochemical reduction of PtCl[subscript 6][superscript -2], PtBr[subscript 6][superscript -2] and PtI[subscript 6][superscript -2] and their hydrolysis products has been examined. The effect of acidity and halide concentration on these reactions was investigated. The reduction of PtCl[subscript 6][superscript -2] leads to PtCl[subscript 4][superscript -2] in solutions containing sufficient acid or chloride, but proceeds directly to platinum metal in neutral, chloride-free solutions. The reduction of PtBr[subscript 6][superscript -2] yields PtBr[subscript 4][superscript -2] in 1 F bromide solutions, but proceeds to the metal in either acid or neutral bromide-free solutions. The oxidation of PtCl[subscript 4][superscript -2] in 1 F chloride solutions appears to give a mixture of PtCl[subscript 6][superscript -2] and Pt(OH)[subscript 2]Cl[subscript 4][superscript -2] , whereas the oxidation of PtBr[subscript 4][superscript -2] in 1 F bromide solutions gives simply PtBr[subscript 6][superscript -2]. The products of hydrolysis of PtCl[subscript 6][superscript -2] and PtBr[subscript 6][superscript -2] are more readily reduced than are the parent complexes.
Proximal Tubule Function and Response to Acidosis (2013)

The human kidneys produce approximately 160-170 L of ultrafiltrate per day. The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by reabsorbing approximately 60%-70% of the water and NaCl, a greater proportion of the NaHCO3, and nearly all of the nutrients in the ultrafiltrate. The proximal tubule is also the site of active solute secretion, hormone production, and many of the metabolic functions of the kidney. This review discusses the transport of NaCl, NaHCO3, glucose, amino acids, and two clinically important anions, citrate and phosphate. NaCl and the accompanying water are reabsorbed in an isotonic fashion. The energy that drives this process is generated largely by the basolateral Na(+)/K(+)-ATPase, which creates an inward negative membrane potential and Na(+)-gradient. Various Na(+)-dependent countertransporters and cotransporters use the energy of this gradient to promote the uptake of HCO3 (-) and various solutes, respectively. A Na(+)-dependent cotransporter mediates the movement of HCO3 (-) across the basolateral membrane, whereas various Na(+)-independent passive transporters accomplish the export of various other solutes. To illustrate its homeostatic feat, the proximal tubule alters its metabolism and transport properties in response to metabolic acidosis. The uptake and catabolism of glutamine and citrate are increased during acidosis, whereas the recovery of phosphate from the ultrafiltrate is decreased. The increased catabolism of glutamine results in increased ammoniagenesis and gluconeogenesis. Excretion of the resulting ammonium ions facilitates the excretion of acid, whereas the combined pathways accomplish the net production of HCO3 (-) ions that are added to the plasma to partially restore acid-base balance.
Role of EGFR mutations in the pathogenesis of lung adenocarcinomas. (2006)

▴ Tang X, Shigematsu H, Bekele BN, et al. EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res2005;65:7568–72

[OpenUrl][1][Abstract/FREE Full Text][2]



The epidermal growth factor receptor (EGFR) is found in 40–80% of non-small cell lung cancers (NSCLC). Somatic mutations of the tyrosine kinase domain of EGFR have been reported in patients with NSCLC who had clinical responses to treatment with tyrosine kinase inhibitors targeted against EGFR . However, little is known about the …

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Variable channel reservation mechanism for wireless networks with mixed types of mobility platforms (2002)

The study of mobile networks with users following different mobility behaviour has been considered. Obtaining a low dropping probability, and consequently a good grade of service, seems only possible using channel reservation schemes. We have studied the performance of a variable reservation mechanism (proposed by Oliver and Paradells (see 4th Workshop on Mobile Multimedia Communications MoMuC'97, Seoul, South Korea, 1997)) considering that not all the mobile stations move in the same way. We have studied two scenarios mixing mobiles at different speeds that move around following predictable or non-predictable mobility patterns. In this environment we show that the mentioned mechanism improves the grade of service of the network.
Enhanced delivery of antisense oligonucleotides with fluorophore-conjugated PAMAM dendrimers (2000)

PAMAM dendrimers are cationic polymers that have been used for the delivery of genes and oligonucleotides to cells. However, little is known about the behavior of dendrimer–nucleic acid complexes once they reach the cell interior. To pursue this issue, we prepared dendrimers conjugated with the fluorescent dye Oregon green 488. These were used in conjunction with oligonucleotides labeled with a red (TAMRA) fluorophore in order to visualize the sub-cellular distribution of the dendrimer–oligonucleotide complex and of its components by two-color digital fluorescence microscopy. The 2′-O-methyl antisense oligonucleotide sequence used in these studies was designed to correct splicing at an aberrant intron inserted into a luciferase reporter gene; thus effective delivery of the antisense agent results in the expression of the reporter gene product. The dendrimer–oligonucleotide complex remained associated during the process of uptake into vesicular compartments and eventual entry into the nucleus. Since the pharmacological activity of the antisense compound was manifest under these conditions, it suggests that the dendrimer–oligonucleotide complex is functionally active. A surprising result of these studies was that the Oregon green 488-conjugated dendrimer was a much better delivery agent for antisense compounds than unmodified dendrimer. This suggests that coupling of relatively hydrophobic small molecules to PAMAM dendrimers may provide a useful means of enhancing their capabilities as delivery agents for nucleic acids.
Electrophoretic and Dielectrophoretic Field Gradient Technique for Separating Bioparticles (2007)

We describe a new device for separation of complex biological particles and structures exploiting many physical properties of the biolytes. The device adds a new longitudinal gradient feature to insulator dielectrophoresis, extending the technique to separation of complex mixtures in a single channel. The production of stronger local field gradients along a global gradient allows particles to enter, initially transported through the channel by electrophoresis and electroosmosis, and to be isolated according to their characteristic physical properties, including charge, polarizability, deformability, surface charge mobility, dielectric features, and local capacitance. In this work, the separation mechanism is described in terms of the relevant electromechanical principles, and proof-of-principle is demonstrated using various bacteria cells as model systems. The results demonstrate the selectivity of the technique and suggest that it may form the foundation for a versatile and useful tool for separating mixtures of complex biological particles and structures.
Kinetics and Activation Parameters for Oxidations of Styrene by Compounds I from the Cytochrome P450BM-3 (CYP102A1) Heme Domain and from CYP119 (2009)

Cytochrome P450 (CYP or P450) enzymes are ubiquitous in nature where they catalyze a vast array of oxidation reactions. The active oxidants in P450s have long been assumed to be iron(IV)-oxo porphyrin radical cations termed Compounds I, but P450 Compounds I have proven to be difficult to prepare. The recent development of an entry to these transients by photo-oxidation of the corresponding iron(IV)-oxo neutral porphyrin species (Compounds II) permits spectroscopic and kinetic studies. We report here application of the photo-oxidation method for production of Compound I from the heme domain of CYP102A1 (cytochrome P450(BM-3)), and product and kinetic studies of reactions of styrene with this Compound I transient and also Compound I from CYP119. The studies were performed at low temperatures in 1:1 (v:v) mixtures of glycerol and phosphate buffer. Single-turnover reactions at 0 degrees C gave styrene oxide in good yields. In kinetic studies conducted between -10 and -50 degrees C, both Compounds I displayed saturation kinetics permitting determinations of binding constants and first-order oxidation rate constants. Temperature-dependent functions for the binding constants and rate constants were determined for both Compounds I. In the temperature range studied, the Compound I transient from the CYP102A1 heme domain bound styrene more strongly than Compound I from CYP119, but the rate constants for oxidations of styrene by the latter were somewhat larger than those for the former. The temperature-dependent functions for the first-order oxidation reactions are as follows: log k = 13.2-15.2/2.303RT and log k = 13.3-14.6/2.303RT (kilocalories per mole) for Compounds I from the CYP102A1 heme domain and CYP119, respectively.
Wound and Serum Levels of Tobramycin With the Prophylactic Use of Tobramycin-Impregnated Polymethylmethacrylate Beads in Compound Fractures (1988)

Antibiotic-impregnated polymethylmethacrylate (PMMA) beads have been useful in treating orthopedic infections. Local delivery has been reported to establish wound antibiotic levels well above the therapeutic range while avoiding serum levels associated with increased incidence of side effects. After operative debridement, 70 patients with compound fractures were treated prophylactically with tobramycin-impregnated PMMA beads. Observations of antibiotic levels in 27 patients demonstrated antibiotic levels in the wound drainage and clot that were significantly in excess of the usual therapeutic range for tobramycin and simultaneous nontoxic serum levels. Significant levels of tobramycin can be achieved in the extracellular fluid at the fracture site when tobramycin-impregnated PMMA beads are placed in the wound after irrigation and debridement.
Retracted: Formin‐like2 regulates Rho/ROCK pathway to promote actin assembly and cell invasion of colorectal cancer (2015)

Formin-like2 (FMNL2) is a member of the diaphanous-related formins family, which act as effectors and upstream modulators of Rho GTPases signaling and control the actin-dependent processes, such as cell motility or invasion. FMNL2 has been identified as promoting the motility and metastasis in colorectal carcinoma (CRC). However, whether FMNL2 regulates Rho signaling to promote cancer cell invasion remains unclear. In this study, we demonstrated an essential role for FMNL2 in the activations of Rho/ROCK pathway, SRF transcription or actin assembly, and subsequent CRC cell invasion. FMNL2 could activate Rho/ROCK pathway, and required ROCK to promote CRC cell invasion. Moreover, FMNL2 promoted the formation of filopodia and stress fiber, and activated the SRF transcription in a Rho-dependent manner. We also demonstrated that FMNL2 was necessary for LPA-induced invasion, RhoA/ROCK activation, actin assembly and SRF activation. FMNL2 was an essential component of LPA signal transduction toward RhoA by directly interacting with LARG. LARG silence inhibited RhoA/ROCK pathway and CRC cell invasion. Collectively, these data indicate that FMNL2, acting as upstream of RhoA by interacting with LARG, can promote actin assembly and CRC cell invasion through a Rho/ROCK-dependent mechanism.
High-Performance Carbon Nanotube Field-Effect Transistor With Tunable Polarities (2005)

State-of-the-art carbon nanotube field-effect transistors (CNFETs) behave as Schottky-barrier-modulated transistors. It is known that vertical scaling of the gate oxide significantly improves the performance of these devices. However, decreasing the oxide thickness also results in pronounced ambipolar transistor characteristics and increased drain leakage currents. Using a novel device concept, we have fabricated high-performance enhancement-mode CNFETs exhibiting n- or p-type unipolar behavior, tunable by electrostatic and/or chemical doping, with excellent OFF-state performance and a steep subthreshold swing (S=63 mV/dec). The device design allows for aggressive oxide thickness and gate-length scaling while maintaining the desired device characteristics.