gebhart/patrepeval huggingface dataset:
Capsid-Incorporation of Antigens into Adenovirus Capsid Proteins for a Vaccine Approach (2010)

Some viral vectors are potent inducers of cellular and humoral responses; therefore, viral vectors can be used to vaccinate against cancer or infectious diseases. This report will focus on adenovirus (Ad)-based vectors. Traditional viral-vector vaccination embodies the concept that the vector uses the host-cell machinery to express antigens that are encoded as transgenes within the viral vector. Several preclinical successes have used this approach in animal model systems. However, in some instances, these conventional Ad-based vaccines have yielded suboptimal clinical results. These suboptimal results are ascribed, in part, to preexisting Ad serotype 5 (Ad5) immunity. To address this issue, the "antigen capsid-incorporation" strategy has been developed to circumvent the drawbacks associated with conventional transgene expression of antigens by Ad vectors. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. Incorporating immunogenic peptides into the Ad capsid offers potential advantages. Importantly, vaccination by means of the antigen capsid-incorporated approach results in a strong humoral response, similar to the response generated by native Ad capsid proteins. This strategy also allows for the boosting of antigenic specific responses. This strategy may be the way forward for improved vaccine schemes, especially for those infections requiring a strong humoral antigenic response.
The Metabolic Disposition of Etodolac in Rats, Dogs, and Man (1981)

The metabolic disposition of etodolac (etodolic acid) was studied after oral and intravenous administration of the 14C-labeled or unlabeled drug to rats and dogs, and after oral administration of the drug to man. In all species, peak serum drug levels were attained within 2 hr after dosing. In rats and dogs, virtually all of the oral dose was absorbed; etodolac represented 95% of the serum radioactivity in rats and 75% in dogs. Serum levels in all species were generally dose-related. The elimination portion of the serum drug concentration/time curves was characterized by several peaks, which in rats were shown to be due to enterohepatic circulation. Tissue distribution studies in rats showed that radioactivity localized primarily in blood vessels, connective tissue, and highly vascularized organs (liver, heart, lung, and kidney) and that the rate of elimination of radioactivity from tissues was similar to that found in the serum. The apparent elimination half-life of etodolac averaged 17 hr in rats, 10 hr in dogs, and 7 hr in man. Etodolac was extensively bound to serum proteins. Liver microsomal cytochrome P-450 levels were unaltered in rats given etodolac daily for 1 week. The primary route of excretion in rats and dogs was via the bile into the feces. Preliminary biotransformation studies in dogs showed the presence of the glucuronide conjugate of etodolac in bile, but not in the urine. Glucuronide conjugates were not seen in the rat. Four hydroxylated metabolites in rat bile were tentatively identified. It was concluded that, in rats and dogs, etodolac is well absorbed, is subject to extensive enterohepatic circulation, undergoes partial biotransformation, and is excreted primarily into the feces.U
Long hydrocarbon chain diols and diacids with central ether or ketone moieties that favorably alter lipid disorders. (2006)

Long hydrocarbon chain derivatives with bis-terminal hydroxyl or carboxyl groups and various central moieties (ketone, ether, ester, amide, carbamate, etc.) have been synthesized and evaluated for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes as well as for their effects on lipid, glycemic and body weight variables in female obese Zucker fatty rats following one and two weeks of oral administration. The most active compounds were found to be symmetrical with four to five methylene groups separating the ether or ketone central functionality from the gem dimethyl, cycloalkyl or methyl/aryl substituents. Cycloalkyl substitution alpha to the carboxyl group in keto-acids lowered the in vitro activity to micromolar values. Furthermore, in vivo biological activity was found to be greatest for cyclopropyl-substituted ketone derivatives, particularly the ketodiacid with five methylene groups on each side of the central ketone functionality, which was identified as an HDL elevator and was also found to reduce insulin and glucose.
Immunoediting of Cancers May Lead to Epithelial to Mesenchymal Transition (2006)

Tumors evade both natural and pharmacologically induced (e.g., vaccines) immunity by a variety of mechanisms, including induction of tolerance and immunoediting. Immunoediting results in reshaping the immunogenicity of the tumor, which can be accompanied by loss of Ag expression and MHC molecules. In this study, we evaluated immunoediting in the neu-transgenic mouse model of breast cancer. A tumor cell line that retained expression of rat neu was generated from a spontaneous tumor of the neu-transgenic mouse and, when injected into the non-transgenic parental FVB/N mouse, resulted in the development of a strong immune response, initial rejection, and ultimately the emergence of neu Ag-loss variants. Morphologic and microarray data revealed that the immunoedited tumor cells underwent epithelial to mesenchymal transition accompanied by an up-regulation of invasion factors and increased invasiveness characteristic of mesenchymal tumor cells. These results suggest that immunoediting of tumor results in cellular reprogramming may be accompanied by alterations in tumor characteristics including increased invasive potential. Understanding the mechanisms by which tumors are immunoedited will likely lead to a better understanding of how tumors evade immune detection.
Effect of Gilbert Damping Term on the Current Induced Magnetization Switching of Ring-Shaped Spin Valve Structures (2007)

In this paper, we present a micromagnetic study of the effect of the Gilbert damping term on the magnetization reversal properties of a ring-shaped PSV. The transition between the two stable vortex states of the storage layer is modeled by applying a write current pulse and considering the effects of the Ampere field and spin-transfer torque. The magnetization switching mechanism is investigated for different amplitude and duration of the current pulse. The optimal switching behavior under varying damping coefficient is discussed. We observe that apart from the current pulse amplitude and duration, the damping coefficient also has a significant effect on magnetization switching properties, especially for short current pulses
Characterization of soluble, salt-loaded, degradable PLGA films and their release of tetracycline (1998)

A local drug delivery system has been designed to release tetracycline over a period of 30 days from poly (lactide-co-glycolide) films. Incorporation of either soluble salt excipients or low molecular weight polymeric species has been found to modulate the release kinetics of the system. The following research describes the fabrication of the delivery system, monitors tetracycline release from the system, and fully characterizes the degradation of the polymer films via scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and X-ray diffraction techniques. Results show that the modulation via use of salts occurs without changing the inherent degradation rate of the system. We suggest that this phenomenon may be due to the increased amount of swelling and uptake of buffer by the films loaded with soluble salt. Uptake, therefore, may be creating microscopic pores that permit further diffusion of tetracycline from the polymer matrix as well as allow the free monomers to leave the system, thereby preventing autocatalysis within the system.
PREDICTION OF MUNICIPAL SOLID WASTE GENERATION BY USE OF ARTIFICIAL NEURAL NETWORK: A CASE STUDY OF MASHHAD (2008)

Accurate prediction of municipal solid waste's quality and quantity is crucial for designing and programming municipal solid waste management system. But predicting the amount of generated waste is difficult task because various parameters affect it and its fluctuation is high. In this research with application of feed forward artificial neural network, an appropriate model for predicting the weight of waste generation in Mashhad, was proposed. For this purpose, a time series of Mashhad's generated waste which have been arranged weekly, from 2004 to 2007, was used. Also, for recognizing the effect of each input data on the waste generation sensitive analysis was performed. Finally, different structures of artificial network were investigated and then the best model for predicting Mashhad's waste generation was chosen based on mean absolute error (MAE), mean absolute relative error (MARE), root mean square error (RMSE), correlation coefficient (R 2 ) and threshold statistics (TS) indexes. After performing of the mentioned model, correlation coefficient (R 2 ) and mean absolute relative error (MARE) in neural network for test have been achieved equal to 0.746 and 3.18% respectively. Results point that artificial neural network model has more advantages in comparison with traditional methods in predicting the municipal solid waste generation.
Continuous anti-interleukin 10 antibody administration depletes mice of Ly-1 B cells but not conventional B cells. (1992)

Ly-1 B cells have the distinctive property of continuous self-replenishment and, as we have shown previously, can be further distinguished from conventional B cells on the basis of greatly elevated constitutive and inducible production of the recently described cytokine interleukin 10 (IL-10). To test the possibility that IL-10 acts as either an autocrine or paracrine growth factor for Ly-1 B cells, we treated mice continuously from birth to 8 wk of age with a monoclonal rat IgM antibody that specifically neutralizes mouse IL-10. Mice treated in this way lacked peritoneal-resident Ly-1 B cells, contained greatly reduced serum immunoglobulin M levels, and were unable to generate significant in vivo antibody responses to intraperitoneal injections of alpha 1,3-dextran or phosphorylcholine, antigens for which specific B cells reside in the Ly-1 B cell subset. In contrast, conventional splenic B cells of anti-IL-10-treated mice were normal with respect to total numbers, phenotype, and in vitro responsiveness to B cell mitogens and the thymus-dependent antigen trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH). The mechanism of Ly-1 B cell depletion appeared to be related to elevation of endogenous interferon gamma (IFN-gamma) levels in anti-IL-10-treated mice, since coadministration of neutralizing anti-IFN-gamma antibodies substantially restored the number of peritoneal-resident Ly-1 B cells in these mice. These results implicate IL-10 as a regulator of Ly-1 B cell development, and identify a procedure to specifically deplete Ly-1 B cells, thereby allowing further evaluation of the role of these cells in the immune system.
The Architecture of the Atrioventricular Conduction Axis in Dog Compared to Man: (1995)

Although the disposition of the conduction system in dog and man is basically similar, there are important differences which relate to the gross anatomy. The anatomic substrate for functional duality of the inputs to the atrioventricular node remains unclear, since our study confirms that the concept of insulated atrionodal tract has no morphologic basis.
Diffusion-limited Reaction of Free Nitric Oxide with Erythrocytes (1998)

Concentration changes of nitric oxide (NO) were monitored using an NO-sensitive electrode in phosphate-buffered saline (PBS) with either free oxyhemoglobin (oxyHb) or red blood cells (RBCs). In aerated PBS, the half-life of 0.9 microM NO is greater than 4 min. NO is undetectable (<50 nM) when added to a solution of oxyHb because the reaction of NO with oxyHb is rapid. The disappearance rate of NO in PBS containing RBCs is rapid, compared with PBS, but it is much slower (by a factor of approximately 650) than with an equivalent solution of free oxyHb. The half-life of NO is inversely proportional to the concentration of RBCs, independent of oxyHb concentration inside RBCs, and the disappearance rate of NO is first order in NO concentration and first order in the concentration of RBCs. After all the oxyHb reacts with NO to form methemoglobin, the disappearance rate of NO slows greatly. These data indicate that the reaction of NO with oxyhemoglobin within RBCs is limited by the diffusion of NO into the cell, which has also been shown previously for the reaction of O2 with deoxyhemoglobin. Experimental data show that the half-life of NO in the presence of 2.1 x 10(6) RBCs/ml is 4. 2 s. From this value, we estimate that the half-life of NO in whole blood (5 x 10(9) RBCs/ml) will be 1.8 ms. A simple analytical expression for the half-life of NO in PBS with RBCs was derived in this study based on a spherical diffusion model. The calculated half-life of NO from the expression is in good agreement with the experimental values.
Metagenomic Detection of Viral Pathogens in Spanish Honeybees: Co-Infection by Aphid Lethal Paralysis, Israel Acute Paralysis and Lake Sinai Viruses (2013)

The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and "unknown", emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees.
Fetal liver myelopoiesis occurs through distinct, prospectively isolatable progenitor subsets (2001)

Hematopoietic fate maps in the developing mouse embryo remain imprecise. Definitive, adult-type hematopoiesis first appears in the fetal liver, then progresses to the spleen and bone marrow. Clonogenic common lymphoid progenitors and clonogenic common myeloid progenitors (CMPs) in adult mouse bone marrow that give rise to all lymphoid and myeloid lineages, respectively, have recently been identified. Here it is shown that myelopoiesis in the fetal liver similarly proceeds through a CMP equivalent. Fetal liver CMPs give rise to megakaryocyte-erythrocyte-restricted progenitors (MEPs) and granulocyte-monocyte-restricted progenitors (GMPs) that can also be prospectively isolated by cell surface phenotype. MEPs and GMPs generate mutually exclusive cell types in clonogenic colony assays and in transplantation experiments, suggesting that the lineage restriction observed within each progenitor subset is absolute under normal conditions. Purified progenitor populations were used to analyze expression profiles of various hematopoiesis-related genes. Expression patterns closely matched those of the adult counterpart populations. These results suggest that adult hematopoietic hierarchies are determined early in the development of the definitive immune system and suggest that the molecular mechanisms underlying cell fate decisions within the myeloerythroid lineages are conserved from embryo to adult. (Blood. 2001;98:627-635)
Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer (2006)

Research on molecular mechanisms underlying the carcinogenesis of non-small cell lung cancer (NSCLC) may provide gene targets in critical pathways valuable for improving the efficacy of therapy and survival of patients with NSCLC. However, the molecular markers highly sensitive for the prognosis and treatment evaluation of NSCLC are not yet available. To explore candidates, we conducted an oligonucleotide microarray study with three pairs of NSCLC and normal lung tissue, and determined 8 differentially expressed genes including the Human MutT homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lung-specific X protein (Lun X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also incorporated for further analysis. The expression profiles of the twelve genes in seventy pairs of NSCLC tumor and normal lung tissue were then detected quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR). The data of the membrane array and qRT-PCR were compared for consistency and the potential of these mRNA markers in clinical application. The results showed that membrane array and qRT-PCR obtained consistent data for the tested genes in both sensitivity and specificity (correlation coefficient 0.921, p<0.0001). For patients' clinicopathological characteristics, the overexpression of hMTH1, SPD, HABP 2, ITGA11, COL11A1, and CK-19 was significantly correlated with the pathological stage (p<0.05). In addition, the overexpression of hMTH1, SPD, ITGA11, and COL11A1 was correlated with lymph node metastasis and poor prognosis. This is the first report relating SPD to a prognosis marker for NSCLC. Moreover, the combined detection of these four mRNA markers by membrane array had a sensitivity of 89% and a specificity of 84% for NSCLC, significantly higher than these markers had achieved separately. In conclusion, we identified mRNA markers for NSCLC prognosis and therapy evaluation from differentially expressed genes determined by using micro-array. Further studies are needed to collect the data of the mRNA markers used in clinical practice.
The schiff base complex of yeast 5‐aminolaevulinic acid dehydratase with laevulinic acid (1999)

The X-ray structure of the complex formed between yeast 5-aminolaevulinic acid dehydratase (ALAD) and the inhibitor laevulinic acid has been determined at 2.15 A resolution. The inhibitor binds by forming a Schiff base link with one of the two invariant lysines at the catalytic center: Lys263. It is known that this lysine forms a Schiff base link with substrate bound at the enzyme's so-called P-site. The carboxyl group of laevulinic acid makes hydrogen bonds with the side-chain-OH groups of Tyr329 and Ser290, as well as with the main-chain >NH group of Ser290. The aliphatic moiety of the inhibitor makes hydrophobic interactions with surrounding aromatic residues in the protein including Phe219, which resides in the flap covering the active site. Our analysis strongly suggests that the same interactions will be made by P-side substrate and also indicates that the substrate that binds at the enzyme's A-site will interact with the enzyme's zinc ion bound by three cysteines (133, 135, and 143). Inhibitor binding caused a substantial ordering of the active site flap (residues 217-235), which was largely invisible in the native electron density map and indicates that this highly conserved yet flexible region has a specific role in substrate binding during catalysis.
Mercury Content in Pacific Troll-Caught Albacore Tuna (Thunnus alalunga) (2005)

Abstract Ninety-one albacore tuna (Thunnus alalunga) captured during the 2003 commercial fishing season were tested for total mercury content in muscle tissue. The fish were harvested between 32.72°N (off Southern California) and 48.30°N (off the northern tip of Washington) between July and November. Fish weighed from 3.14 to 11.62 kg and were 50.8-86.4 cm long. Total mercury content in the albacore muscle tissue ranged from 0.027 ppm (μg/g) to 0.26 ppm. The average total mercury content was 0.14 ± 0.05 ppm, which is below the U.S. Food and Drug Administration action level and Canadian standards (1.0 ppm methylmercury and 0.50 ppm total mercury, respectively). Total mercury concentrations showed positive correlations with length and weight of albacore (R2= 0.40 and 0.38, respectively), but there was no correlation with date of capture or lipid content. Results indicate that Pacific troll-caught albacore have low levels of total mercury in the edible flesh and are well within international safety standards for mercury levels in fish.
Opportunities and perspectives for developing orexin receptor antagonists (2014)

EDITORIAL article Front. Neurosci., 12 June 2014Sec. Neuropharmacology https://doi.org/10.3389/fnins.2014.00158
Hypervalent Iodine in the Synthesis of Bridgehead Heterocycles: A Facile Route to the Synthesis of 6‐Arylimidazo[2,1‐b]thiazoles Using [Hydroxy(tosyloxy)iodo]benzene (2006)

Abstract α‐Tosyloxyketones (2), readily accessible through hypervalent iodine oxidation of enolizable ketones (1) using [hydroxy(tosyloxy)iodo]benzene (HTIB) in acetonitrile, exclusively generates the 6‐arylimidazo[2,1‐b]thiazoles (4) on treatment with commercially available 2‐aminothiazole (3).