gebhart/patrepeval huggingface dataset:
The Neurophysiology of Acupuncture: A Viewpoint (1997)

Acupuncture is a specialised sensory stimulation that is analysed through sensory neural pathways. Therefore to understand its action we have to analyse the anatomy, physiology and pharmacology of the nervous system, aided with a knowledge of neuroendocrinology and the chemoarchitecture of the brain. Various neural theories have been developed to explain the mechanisms of acupuncture. It is now evident that acupuncture reacts at local, regional (spinal cord) and general (brain) levels. Therefore, inserting one or more needles at particular points (or areas) of the body activates neural pathways on three different levels, provoking local, regional, and general reactions. The local reaction is a multifactorial phenomenon. The electric injury potential due to the needle, the presence and synthesis of opioid peptides at the site of injury, and substance P, histamine like substances, bradikinin, serotonin and proteolitic enzyme release around the needle, all occur during needling. The regional reaction concerns the activation of a larger area (2–3 dermatomes) via reflex arches. We can analyse the viscero-cutaneous, cutaneo-visceral, cutaneo-muscular and viscero-muscular reflexes and also the vegetative, stretch and polysynaptic segmental reflexes. The general reaction mainly activates the brain central mechanism of internal homoeostasis. We can explain the action of acupuncture in acute and chronic pain syndromes, in addiction and in psychiatric disease through the role of central neurotransmitters and the modulatory systems that are activated by acupoints: opioid, non-opioid and central sympathetic inhibitory mechanisms.
Canonical WNT signaling pathway and human AREG (2006)

AREG (Amphiregulin), BTC (beta-cellulin), EGF, EPGN (Epigen), EREG (Epiregulin), HBEGF, NRG1, NRG2, NRG3, NRG4 and TGFA (TGFalpha) constitute EGF family ligands for ERBB family receptors. Cetuximab (Erbitux), Pertuzumab (Omnitarg) and Trastuzumab (Herceptin) are anti-cancer drugs targeted to EGF family ligands, while Gefitinib (Iressa), Erlotinib (Tarceva) and Lapatinib (GW572016) are anti-cancer drugs targeted to ERBB family receptors. AREG and TGFA are biomarkers for Gefitinib non-responders. The TCF/LEF binding sites within the promoter region of human EGF family members were searched for by using bioinformatics and human intelligence (Humint). Because three TCF/LEF-binding sites were identified within the 5'-promoter region of human AREG gene, comparative genomics analyses on AREG orthologs were further performed. The EPGN-EREG-AREG-BTC cluster at human chromosome 4q13.3 was linked to the PPBP-CXCL segmental duplicons. AREG was the paralog of HBEGF at human chromosome 5q31.2. Chimpanzee AREG gene, consisting of six exons, was located within NW_105918.1 genome sequence. Chimpanzee AREG was a type I transmembrane protein showing 98.0% and 71.4% total amino-acid identity with human AREG and mouse Areg, respectively. Three TCF/LEF-binding sites within human AREG promoter were conserved in chimpanzee AREG promoter, but not in rodent Areg promoters. Primate AREG promoters were significantly divergent from rodent Areg promoters. AREG mRNA was expressed in a variety of human tumors, such as colorectal cancer, liver cancer, gastric cancer, breast cancer, prostate cancer, esophageal cancer and myeloma. Because human AREG was characterized as potent target gene of WNT/beta-catenin signaling pathway, WNT signaling activation could lead to Gefitinib resistance through AREG upregulation. AREG is a target of systems medicine in the field of oncology.
Effect of Pore Structure on CO2 Adsorption Characteristics of Aminopolymer Impregnated MCM-36 (2015)

The CO2 adsorption characteristics of a pillared 2-dimensional porous silicate material impregnated with amine containing polymers have been investigated. It was determined that the introduction of amine polymer deteriorates the CO2 capture kinetics of the MCM-36 supported amine adsorbents compared to that of the bare material, due to the fact that with the addition of a higher loading of amine polymer the diffusion of CO2 through the 2-dimensional interlayer mesoporous channels of MCM-36 becomes greatly hindered. This pore blocking sets an upper limit to the CO2 capture performance of the polymer impregnated MCM-36 and greatly reduces the utility of using this sort of amine-solid adsorbent for carbon capture. Interestingly, these results suggest that for 2-D channel solid supports there is an optimal amine loading which is not likely to be equal to the maximum loading, and which can be determined and utilized to obtain the maximum improvement over the original materials. The study performed in this work for the MCM-36 material could therefore be applied to other porous supports to determine these optimum loadings and be used to more easily compare and contrast the alterations to capture characteristics which occur upon amine loading for a wide range of materials. It is believed this will make it more straightforward to determine which solid supports hold the promise for greatly improved capture characteristics upon amine loading and allow the field to more quickly determine avenues for fruitful development. These results also suggest the need for a new sort of support structure for amine loaded solids, one which can allow us to decouple amine loading from increasing diffusion resistance so that high amine efficiency can be maintained throughout the range of increased amine loadings.
CERK1, a LysM receptor kinase, is essential for chitin elicitor signaling in Arabidopsis (2007)

Chitin is a major component of fungal cell walls and serves as a microbe-associated molecular pattern (MAMP) for the detection of various potential pathogens in innate immune systems of both plants and animals. We recently showed that chitin elicitor-binding protein (CEBiP), plasma membrane glycoprotein with LysM motifs, functions as a cell surface receptor for chitin elicitor in rice. The predicted structure of CEBiP does not contain any intracellular domains, suggesting that an additional component(s) is required for signaling through the plasma membrane into the cytoplasm. Here, we identified a receptor-like kinase, designated CERK1, which is essential for chitin elicitor signaling in Arabidopsis. The KO mutants for CERK1 completely lost the ability to respond to the chitin elicitor, including MAPK activation, reactive oxygen species generation, and gene expression. Disease resistance of the KO mutant against an incompatible fungus, Alternaria brassicicola, was partly impaired. Complementation with the WT CERK1 gene showed cerk1 mutations were responsible for the mutant phenotypes. CERK1 is a plasma membrane protein containing three LysM motifs in the extracellular domain and an intracellular Ser/Thr kinase domain with autophosphorylation/myelin basic protein kinase activity, suggesting that CERK1 plays a critical role in fungal MAMP perception in plants.
New structures in complex formation between DNA and cationic liposomes visualized by freeze—fracture electron microscopy (1994)

Structures formed during interaction of cationic liposomes and plasmid DNA were studied by freeze-fracture electron microscopy and their morphology was found to be dependent on incubation time and DNA concentration. These structures were formed with liposomes composed of DC-Chol and DOPE after 30 min incubation at DNA:lipid concentrations encompassing maximal transfection activity. They resembled liposome complexes (meatballs) and additionally bilayer-covered DNA tubules (spaghetti), whereby the DNA-tubules were found to be connected to the liposome complexes as well as occurring free in the suspension. At later times and higher DNA-to-liposome ratios the complexes grow larger while their membranes become discontinuous, allowing the self-encapsulation of the DNA. The relative transfection potency of the various morphologically distinct structures is discussed.
Intratumoral Delivery and Suppression of Prostate Tumor Growth by Attenuated Salmonella enterica serovar typhimurium Carrying Plasmid-Based Small Interfering RNAs (2007)

The facultative anaerobic, invasive Salmonella enterica serovar typhimurium (S. typhimurium) has been shown to retard the growth of established tumors. We wondered if a more effective antitumor response could be achieved in vivo if these bacteria were used as tools for delivering specific molecular antitumor therapeutics. Constitutively activated transcription factor signal transducer and activator of transcription 3 (STAT3) promotes the survival of a number of human tumors. In this study, we investigated the relative efficacies of attenuated S. typhimurium alone or combined with Stat3-specific small interfering RNA (siRNA) in terms of tumor growth and metastasis. The bacteria preferentially homed into tumors over normal liver and spleen tissues in vivo. S. typhimurium expressing plasmid-based Stat3-specific siRNAs significantly inhibited tumor growth, reduced the number of metastastic organs, and extended the life time for C57BL6 mice bearing an implanted prostate tumor, versus bacterial treatment alone. These results suggest that attenuated S. typhimurium combined with an RNA interference approach might be more effective for the treatment of primary as well as metastatic cancer.
Isoform-specific retinoid-X receptor (RXR) antibodies detect differential expression of RXR proteins in the pituitary gland (1995)

There are three known isoforms of the retinoid-X receptor (RXR): RXR alpha, RXR beta, and RXR gamma. RXR alpha and RXR beta messenger RNAs are widely expressed, whereas RXR gamma messenger RNA is restricted to only a few tissues, including embryonic pituitary gland. Little is known about the level of expression and cell distribution of RXR proteins in the adult pituitary gland. To examine these issues further, we raised isoform-specific polyclonal antibodies against each of the known mouse RXR isoforms using synthetic peptides containing isoform-specific epitopes from the amino-terminal region. The specificity of each antibody was confirmed by immunoprecipitation, Western immunoblot analysis, and electrophoretic mobility shift assay with supershift studies of in vitro translated RXR isoforms. Immunocytochemical analysis showed that anti-RXR alpha and anti-RXR beta antisera stained the nuclei of most pituitary cells. In contrast, anti-RXR gamma antiserum stained the nuclei of only a few cells throughout the pituitary. In the hypothyroid state, however, a marked increase in both the number and density of RXR gamma-immunostained nuclei were observed compared to those in the euthyroid state. Double immunostaining studies of hypothyroid rat pituitary with antibodies against pituitary hormones indicated that RXR gamma protein was predominantly expressed in thyrotropes. Antibody supershift experiments using nuclear extracts of adult rat whole pituitary and rodent pituitary cell lines showed that anti-RXR gamma antibody could alter the mobility of protein-DNA complexes formed only from nuclear extracts of rat whole pituitary and thyrotropic TtT-97 cells. In contrast, anti-RXR alpha and anti-RXR beta antibodies could supershift protein-DNA complexes formed from nuclear extracts of all cell lines tested. RXR gamma protein expression in TtT-97 cells also was observed by Western immunoblot analyses. Therefore, there is thyrotrope-predominant expression of RXR gamma protein. We speculate that RXR gamma may play a role in the regulation of thyroid hormone target genes in thyrotropes and possibly cell type differentiation in the pituitary.
Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination (1997)

It is generally thought that an effective vaccine to prevent HIV-1 infection should elicit both strong neutralizing antibody and cytotoxic T lymphocyte responses. We recently demonstrated that potent, boostable, long-lived HIV-1 envelope (Env)-specific cytotoxic T lymphocyte responses can be elicited in rhesus monkeys using plasmid-encoded HIV-1 env DNA as the immunogen. In the present study, we show that the addition of HIV-1 Env protein to this regimen as a boosting immunogen generates a high titer neutralizing antibody response in this nonhuman primate species. Moreover, we demonstrate in a pilot study that immunization with HIV-1 env DNA (multiple doses) followed by a final immunization with HIV-1 env DNA plus HIV-1 Env protein (env gene from HXBc2 clone of HIV IIIB; Env protein from parental HIV IIIB) completely protects monkeys from infection after i.v. challenge with a chimeric virus expressing HIV-1 env (HXBc2) on a simian immmunodeficiency virusmac backbone (SHIV-HXBc2). The potent immunity and protection seen in these pilot experiments suggest that a DNA prime/DNA plus protein boost regimen warrants active investigation as a vaccine strategy to prevent HIV-1 infection.
Quantitative Assessment of the Cell Penetrating Properties of RI-Tat-9:  Evidence for a Cell Type-Specific Barrier at the Plasma Membrane of Epithelial Cells (2004)

Penetration of epithelial cells represents the rate-determining step for the absorption of many drugs and pharmaceutical macromolecules such as proteins and nucleic acid therapeutics. While the potential of using cell-penetrating peptides (CPPs) to facilitate absorption has been increasingly recognized, the mechanism of cell penetration and the uptake into certain cells have recently been called into question due to methodological artifacts. Therefore, the objective of this study was to quantitatively assess the ability of RI-Tat-9, a proteolytically stable CPP, to penetrate epithelial cell monolayers. The permeability of RI-Tat-9 with two epithelial cell lines, Madin-Darby canine kidney (MDCK) and Caco-2 cells, was comparable to the leakiness of the respective intact monolayers. Microscopic imaging showed that fluorescence-tagged RI-Tat-9 did not enter these cells, further supporting a paracellular transport mechanism. Although insufficient data were generated in these studies to generalize the observed phenomenon, the entry of RI-Tat-9 into nonepithelial T lymphocytic MT2 cells, possibly by endocytosis, suggested that a cell type-specific barrier might exist that controlled uptake of RI-Tat-9 by cells. Compared to that in MT2 and HeLa cells, the active uptake of the peptide into MDCK monolayers was much slower and showed no dependence of cell energy. Furthermore, the equilibrium binding of RI-Tat-9 to MDCK cells at 0 degrees C was indicative of an interaction with a nonspecific receptor. A correlation between binding density and concentration difference across a leaky separation barrier suggested that repulsion of free peptide molecules by bound peptide molecules at the MDCK monolayer surface may be significant at micromolar concentrations. The results of this study quantitatively show that Tat CPP uptake into two commonly used epithelial cell types is minimal and possibly cell type-specific. Implications for Tat CPP-assisted drug delivery are discussed.
Nucleotide Sequence Repetition: A Rapidly Reassociating Fraction of Mouse DNA (1966)

The separated complemnentary strands of a minor component in mouse DNA reassociate with each other much more rapidly than do the complementary strands of other DNA's including those of the principal part of mouse DNA. This difference in capacity of the strands to reassociate can be used to effect a preparative separation of the minor component from the principal fraction. The rate constant for reassociation of the minor component, compared with those of viral and bacterial DNA's, indicates that the minor component consists of a short nucleotide sequence present in about one million copies.
The potential role of podoplanin in tumour invasion (2006)

Podoplanin is a small mucin-like transmembrane protein, widely expressed in various specialised cell types throughout the body. Here, we revisit the mechanism of podoplanin-mediated tumour invasion. We compare molecular pathways leading to single and collective cell invasion and discuss novel distinct concepts of tumour cell invasion.
Effect of Lepidium meyenii (Maca) on spermatogenesis in male rats acutely exposed to high altitude (4340 m) (2004)

Lepidium meyenii (Maca) is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m in the central Andes. Maca is traditionally employed in the Andean region for its supposed fertility-enhancing properties. The aim of this study was to test the hypothesis that Maca can prevent high altitude-induced testicular disturbances. Adult male rats were exposed for 21 days to an altitude of 4340 m and treated with vehicle or aqueous extract of Maca (666.6 mg/day). The lengths of the stages of the seminiferous epithelium and epididymal sperm counts were obtained at 0, 7, 14 and 21 days of exposure. The stages of the seminiferous tubules were assessed by transillumination. A dose-response study was also performed at sea level to determine the effect of Maca given to male rats at doses of 0, 6.6, 66.6 and 666.6 mg/day for 7 days on body weight, seminiferous tubule stages and epididymal sperm count. The length of stage VIII and the epididymal sperm count were increased in a dose-dependent manner in Maca-treated rats but treatment reduced the length of stage I. At the highest dose, sperm count increased 1.58 times, the length of stage VIII increased 2.4 times and the length of stage I was reduced 0.48 times compared with the value at dose 0. Exposure to high altitude resulted in a reduction in epididymal sperm count after 7 days and lower values were maintained up to 21 days. Altitude reduced spermiation (stage VIII) to half and the onset of spermatogenesis (stages IX-XI) to a quarter on days 7 and 14 but treatment with Maca (666.6 mg/day) prevented these changes. Data on transillumination and epididymal sperm count in the Maca-treated group exposed to high altitude were similar to those obtained at sea level. Maca increased the sperm count on day 21 of exposure to high altitude to values similar (1095.25 +/- 20.41x10(6) sperm, means +/- S.E.M.) to those obtained in the Maca-treated group at sea level (1132.30 +/- 172.95x10(6) sperm). Furthermore, in the Maca-treated group exposed for 21 days to high altitude, epididymal sperm count was higher than in the non-treated group at sea level (690.49 +/- 43.67x10(6) sperm). In conclusion, treatment of rats with Maca at high altitude prevented high altitude-induced spermatogenic disruption.
Five years survival in metastatic non‐small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial (2003)

Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells. However, the clinical results available at present with melatonin and chemotherapy in the treatment of human neoplasms are generally limited to the evaluation of 1-year survival in patients with very advanced disease. Thus, the present study was performed to assess the 5-year survival results in metastatic non-small cell lung cancer patients obtained with a chemotherapeutic regimen consisting of cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/day orally in the evening). The study included 100 consecutive patients who were randomized to receive chemotherapy alone or chemotherapy and melatonin. Both the overall tumor regression rate and the 5-year survival results were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years, whereas a 5-year survival was achieved in three of 49 (6%) patients treated with chemotherapy and melatonin. Moreover, chemotherapy was better tolerated in patients treated with melatonin. This study confirms, in a considerable number of patients and for a long follow-up period, the possibility to improve the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant administration of melatonin. This suggests a new biochemotherapeutic strategy in the treatment of human neoplasms.
High-Resolution Mapping of Tumor Redox Status by Magnetic Resonance Imaging Using Nitroxides as Redox-Sensitive Contrast Agents (2006)

This study shows that MRI can be successfully used to co-register tissue redox status along with anatomic images, thus providing potentially valuable biochemical information from the region of interest.
The Expression of Osteoprotegerin and RANK Ligand and the Support of Osteoclast Formation by Stromal-Osteoblast Lineage Cells Is Developmentally Regulated**This work was supported by Grant AG-04875 from the National Institute on Aging. (2000)

The one or more molecular mechanisms that determine the obligatory sequence of resorption followed by formation during bone remodeling is unclear. RANK ligand (RANK-L) is an essential requirement for osteoclastogenesis, and its activity is neutralized by binding to the soluble decoy receptor, osteoprotegerin (OPG). Because both molecules are produced by osteoblast lineage cells, we studied their developmental regulation in a conditionally immortalized human marrow stromal (hMS[2-15]) cell line. These cells can simulate the complete developmental sequence from undifferentiated precursor(s) to cells with the complete osteoblast phenotype that are capable of forming mineralized nodules. During osteoblast differentiation, RANK-L messenger RNA levels decreased by 5-fold, whereas OPG messenger RNA levels increased by 7-fold, resulting in a 35-fold change in the RANK-L/OPG ratio. OPG protein also increased by 6-fold. Mouse bone marrow cells generated osteoclast-like cells in coculture with undifferentiated hMS(2-15) cells, but did not when cocultured with hMS(2-15) cells in varying stages of differentiation, unless an excess of RANK-L was added. Thus, undifferentiated marrow stromal cells with a high RANK-L/OPG ratio can initiate and support osteoclastogenesis, but after differentiation to the mature osteoblast phenotype, they cannot. We speculate that the developmental regulation of OPG and RANK-L production by stromal/osteoblast cells contributes to the coordinated sequence of osteoclast and osteoblast differentiation during the bone remodeling cycle.
Do Sensor Glucose Levels Accurately Predict Plasma Glucose Concentrations During Hypoglycemia and Hyperinsulinemia? (2002)

Although hyperinsulinemia may contribute to modest discrepancies between plasma and sensor glucose levels, the CGMS is able to accurately track acute changes in plasma glucose when calibrated across a range of plasma glucose and insulin levels.