gebhart/patrepeval huggingface dataset:
Self-setting bioceramic microscopic protrusions for transdermal drug delivery (2014)

Microneedle (MN) technology offers both an efficient and a minimally invasive transdermal drug delivery strategy. The current MNs, made of silicon and metal, have poor biocompatibility and low drug loading, while the polymer MNs have some constraints related to mechanical strength and storage conditions. In this study, self-setting bioceramics were explored as substitutes for the current MN materials for the first time. Self-setting bioceramic microneedles were fabricated using a master mold by a procedure under mild conditions, which could minimize the drug degradation during fabrication and also facilitates a higher drug loading capability than the other current ceramic microneedles. The drug release and mechanical strength were correlated with the microstructure and porosity of the needles. As observed by SEM and microCT, the ceramic paste could fully fill the geometry of the mould and was cured into an array of micro-sized needles. The drug release study showed that the release rate from this type of MN array could be controlled by the bulk surface area, porosity and resorption rate of the ceramic needles. Applying the MNs to porcine skin indicated that the needles were able to pierce the stratum corneum of the skin. We successfully prepared the bioceramic needles that have high mechanical strength and are resorbable, which can promote safe, efficient and successful transdermal drug delivery.
Green electricity production with living plants and bacteria in a fuel cell (2008)

The world needs sustainable, efficient, and renewable energy production. We present the plant microbial fuel cell (plant-MFC), a concept that exploits a bioenergy source in situ. In the plant-MFC, plants and bacteria were present to convert solar energy into green electricity. The principal idea is that plants produce rhizodeposits, mostly in the form of carbohydrates, and the bacteria convert these rhizodeposits into electrical energy via the fuel cell. Here, we demonstrated the proof of principle using Reed mannagrass. We achieved a maximal electrical power production of 67 mW m−2 anode surface. This system was characterized by: (1) nondestructive, in situ harvesting of bioenergy; (2) potential implementation in wetlands and poor soils without competition to food or conventional bioenergy production, which makes it an additional bioenergy supply; (3) an estimated potential electricity production of 21 GJ ha−1 year−1 (5800 kWh ha−1 year−1) in Europe; and (4) carbon neutral and combustion emission-free operation. Copyright © 2008 John Wiley & Sons, Ltd.
SGK1 Kinase Upregulates GLUT1 Activity and Plasma Membrane Expression (2006)

Phosphatidylinositol 3-kinase (PI3 kinase) inhibition disrupts the ability of insulin to stimulate GLUT1 and GLUT4 translocation into the cell membrane and thus glucose transport. The effect on GLUT4 but not on GLUT1 is mediated by activation of protein kinase B (PKB). The serum- and glucocorticoid-inducible kinase SGK1, a further kinase downstream of PI3 kinase, regulates several transporters by enhancing their plasma membrane abundance. GLUT1 contains a consensus site ((95)Ser) for phosphorylation by SGK1. Thus, the present study investigated whether GLUT1 is regulated by the kinase. Tracer-flux studies in Xenopus oocytes and HEK-293 cells demonstrated that GLUT1 transport is enhanced by constitutively active (S422D)SGK1. The effect requires the kinase catalytical activity since the inactive mutant (K127N)SGK1 failed to modulate GLUT1. GLUT1 stimulation by (S422D)SGK1 is not due to de novo protein synthesis but rather to an increase of the transporter's abundance in the plasma membrane. Kinetic analysis revealed that SGK1 enhances maximal transport rate without altering GLUT1 substrate affinity. These observations suggest that SGK1 regulates GLUT1 and may contribute to or account for the PI3 kinase-dependent but PKB-independent stimulation of GLUT1 by insulin.
Molecular approach to thermogenesis in brown adipose tissue: cDNA cloning of the mitochondrial uncoupling protein. (1985)

The uncoupling protein (UCP) of mammalian brown fat is a specialized and unique component responsible for energy dissipation as heat. Translation and immunoprecipitation from sucrose-fractionated mRNA indicated that the mRNA of UCP sedimented at 14-16 S. A recombinant cDNA library prepared from mRNA of thermoactive brown fat enriched for UCP mRNA has been constructed and cloned in Escherichia coli. Recombinant plasmids were screened by differential colony hybridization to a cDNA probe complementary to poly(A)+ RNA isolated from thermogenic or from weakly thermogenic brown fat. Several differentially hybridizing plasmids were shown to contain UCP cDNA sequences by their ability to select a mRNA coding for an in vitro translation product that was immunoprecipitable with antibodies against UCP. Blot hybridization of brown fat mRNA to a 32P-labeled UCP cDNA probe revealed two major species of mRNA (15S and 18S). As compared to non-thermogenic tissue, a strikingly increased hybridization to the probe was observed with brown fat mRNA from thermoactive tissue. Moreover, hybridization was observed with RNA of brown adipose tissue from rat, hamster, or mouse but not with RNA from rat or mouse liver.
Controlling Antibody Orientation on Charged Self-Assembled Monolayers (2003)

The orientation of antibodies on surfaces is critical to the performance of biosensors. Due to the charge distribution within an antibody molecule, it is hoped that the orientation of adsorbed antibodies can be controlled by adjusting microenvironments (e.g., surface and solution properties). In this work, we investigated the orientations of two types of monoclonal anti-human chorionic gonadotropin (anti-hCG) adsorbed on NH2 (positively charged) and COOH (negatively charged) terminated self-assembled monolayers (SAMs) by surface plasmon resonance (SPR) biosensors. Adsorbed antibody molecules on surfaces were also characterized by atomic force microscopy. Results show that the orientation of the IgG1 type antibody is better on the NH2 surface than on the COOH surface, as indicated by a higher hCG to adsorbed anti-hCG ratio on the NH2 surface from SPR experiments. However, for the IgG2a type antibody, the antigen-to-antibody ratio, and thus the orientation of the adsorbed IgG2a, is similar on the NH2- and COOH-terminated SAM surfaces. Surface charge affects the orientation of IgG2a less than IgG1 due to the smaller dipole moment of IgG2a compared to IgG1. This work provides not only a fundamental understanding of how microenvironments affect protein behavior on surfaces but also a useful guide to designing surfaces for applications, such as biosensors and biomaterials.
The Application of Chemically Modified Fused Silica Fibers in the Extraction of Organics from Water Matrix Samples and their Rapid Transfer to Capillary Columns (1989)

Abstract A technique for water sample analysis is presented which uses chemically modified fused silica optical fibers as micro solid phase extractors. The small size of the fibers (100 µm o. d. ) allows for direct introduction into the on column injector port of a high resolution gas chromatograph (GC), where the analytes are thermally desorbed. This eliminates the need for solvents and syringes which are used in liquid-liquid or solid phase extraction techniques. Thus, this method lowers cost and analysis time per sample, as well as eliminates possible sources of error. Results show that the efficiency and selectivity of this technique are dependent upon the thickness and polarity of the stationary phase. Initial results indicate that the limit of detection for 2-naphthol and FID detection is approximately 5 ng/g with a linear response range of 5 orders of magnitude.
Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse‐controlled release for obesity (2010)

Short-term phentermine DCR treatment resulted in significant reduction in weight and improvement of metabolic parameters, including waist circumference and some lipid profiles, without clinically severe adverse events. Further study is needed to show long-term efficacy and safety of phentermine DCR in Korean patients with obesity.
Immunochemotherapy With Rituximab and Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Significantly Improves Response and Time to Treatment Failure, But Not Long-Term Outcome in Patients With Previously Untreated Mantle Cell Lymphoma: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG) (2005)

The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.
Promoting Dendritic Cell Migration by Airway Epithelial Cells through Interleukin‐17A‐Induced CCL20 Expression (2010)

We previously demonstrated that IL‐17A is a potent inducer of both human β‐defensin (hBD) 2 and CCL20/macrophage inflammatory protein (MIP)‐3α expression in well‐differentiated primary human airway epithelial cell (AEC) cultures. In addition to having a common anti‐microbial activity, both hBD2 and CCL20 are principal chemotactic ligands specific to CCR6‐positive dendritic cells (DC) and T lymphocytes. To further explore the chemotactic significance of IL‐17A in the mouse model, we conducted studies using isolated primary mouse AECs and Cc10‐Il17 transgenic animals. Consistent with human AECs, well‐differentiated mouse AECs also expressed elevated mCcl20 when treated with mIL‐17A. This induction was time‐ and dose‐dependent on the IL‐17A treatment, and the induction was inhibited by isohelenin, a specific inhibitor of NF‐κB activation. Chemotactic assays showed that conditioned media from mIL‐17A‐treated mouse AEC cultures stimulated the migration of CCR6‐positive mouse bone marrow‐derived dendritic cells (BMDC) in vitro ; this chemotactic activity was blocked by anti‐CCL20 neutralizing antibody. We found a persistent elevation of mCcl20 message and the presence of CCR6‐positive DCs in bronchoalveolar lavage fluids, accompanied by increased mucin production in the lungs of Cc10‐Il17 transgenic mice, which overexpress IL‐17A specifically in the airway. Blocking the migration of CCR6 expressing cells in vivo lowered mucin production in the airway. These results suggest a functional role of IL‐17A/CCL20 in regulating CCR6‐positive DC migration and mucous cell metaplasia. This research was supported in part by grants from NIH (HL077902, HL077315, and ES00628)
Characterization of an aromatic amino acid-dependent Listeria monocytogenes mutant: attenuation, persistence, and ability to induce protective immunity in mice (1993)

A transposon insertion mutant of Listeria monocytogenes was shown to be deficient in prephenate dehydratase, an enzyme acting late in the pathway for biosynthesis of phenylalanine. This mutant had reduced virulence in mice. The mutant and parent strains persisted to the same extent in the tissues of infected mice and elicited similar degrees of splenomegaly. Mice vaccinated with the mutant were protected significantly from subsequent challenge with virulent L. monocytogenes.
A Monte Carlo estimation of tissue optical properties for use in laser dosimetry (1995)

In certain clinical situations, such as photodynamic therapy, light dosimetry should be considered. The propagation of light in tissues is influenced by fundamental or microscopic optical properties, namely absorption mu a and scattering mu s coefficients, refractive index n and anistropy factor g. These optical parameters can be determined experimentally by direct and/or indirect methods when tissue macroscopic properties, such as reflectance, transmittance or collimated transmittance from a tissue slab, are measured. The method described in this work provides graphical, and in simple cases analytical, 'inverse' solutions to determine tissue microscopic properties from measured macroscopic parameters. The graphs necessary for this inversion have been calculated and are provided. The method can be applied in either direct or indirect techniques and it does not depend on limitations introduced by assumptions and approximations when using theoretical models. It can also be applied for any tissue type, detector geometry and experimental apparatus. The accuracy of the method is very good over a wide range, unlimited in practice, of values of optical properties. Finally, the results of this work are in good agreement with theoretical and experimental results of other investigators.
Neuropeptide Y: a powerful modulator of epithelial ion transport (1986)

Neuropeptide Y (NPY) is a major gut peptide localized in the intestinal mucosa of several mammalian species. Ileal mucosa from rabbit and guinea-pig was mounted in Ussing chambers in order to study the effect of NPY on short circuit current. Neuropeptide Y inhibited the short circuit current when applied to the serosal side of the tissue. The maximum change in short circuit current was -50 +/- 6 microA cm-2 in the rabbit ileum and -49 +/- 14 microA cm-2 in the guinea-pig ileum. The EC50 was 3 X 10(-8) M in both species. Pretreatment of rabbit ileum with the alpha 2-adrenoceptor antagonist, yohimbine (1 X 10(-6) M) for 10 min did not reduce the response of the tissue to neuropeptide Y (1 X 10(-7) M). When applied serosally to rabbit ileal mucosa, the related peptide YY caused a maximum change in short circuit current of -60 +/- 13 microA cm-2; the EC50 was 2 X 10(-9) M. Isotopic flux studies in rabbit ileum showed that 1 X 10(-7) M neuropeptide Y enhanced mucosal-to-serosal Na+ and Cl- fluxes and reduced serosal-to-mucosal Cl- flux. Replacement of chloride with gluconate on both sides of the tissue significantly reduced the change in short circuit current produced by neuropeptide Y (1 X 10(-7) M), as did a similar replacement of bicarbonate. It is concluded that neuropeptide Y and peptide YY are the most potent neurotransmitters or hormones so far described in their ability to attenuate electrogenic transport in the small intestine.
Human autoantibodies to poly(adenosine diphosphate-ribose) polymerase recognize cross-reactive epitopes associated with the catalytic site of the enzyme. (1989)

The factors responsible for the production of autoantibodies against self-components are not well understood. We have identified monospecific human autoantibodies to poly(ADP-ribose) polymerase (ADPRP) in the sera of rheumatic patients. Since this nuclear enzyme has been extensively characterized, and its entire structure is known, we could investigate in detail the epitope specificity of the human autoantibodies, and their effects on the biological functions of the enzyme. All sera with autoantibodies to ADPRP recognized the NAD-binding domain of the enzyme, as demonstrated by either immunoblotting or immunoprecipitation of partially proteolyzed ADPRP. The autoantibodies also inhibited the catalytic activity of the purified enzyme, as measured by the transfer of ADP-ribose from [32P]NAD to either histones or to ADPRP itself. Because comparative structural analyses have shown that the active sites of enzymes are often conserved during evolution, we tested the ability of the autoantibodies to react with ADPRP from lower eukaryotes. The human autoantibodies reacted with ADPRP in cellular extracts from mammalian, avian, amphibian, arthropod, and protozoan cells, and also inhibited the catalytic activity of the various enzymes. Collectively, these experiments indicate that the human autoantibodies to ADPRP recognize a distinct group of evolutionarily conserved antigenic determinants that are closely related to the catalytic site of the enzyme. The results are consistent with the hypothesis that the epitope selectivity of human autoantibodies to ADPRP is influenced by cross-reactive antigens in the external environment.
Virulence, Speciation and Antibiotic Susceptibility of Ocular Coagualase Negative Staphylococci (CoNS) (2014)

S. epidermidis was found to be predominant in causing the ocular complications. Slime production, heamagglutination, protease and lipase activities could be the putative virulence factors of CoNS. Antibiotic susceptibility patterns of CoNS against antibacterial agents revealed maximum resistance to beta lactam groups, and the resistance was found to be higher to oxacillin, and lowest to vancomycin.
The human albumin gene. Characterization of the 5‘ and 3‘ flanking regions and the polymorphic gene transcripts. (1986)

We have characterized the 5' and 3' regions of the human albumin gene with respect to nucleotide sequences, mRNA transcription initiation and polyadenylation. There are at least two transcription initiation sites and two polyadenylation sites in the human albumin gene. The multiple transcription initiation sites are utilized almost equally. The two polyadenylation sites are used differentially, with the site proximal to the protein termination codon dominating. The "TATA" and the "CCAAT" boxes are present at about 30 and 90 nucleotides upstream of the putative cap sites. About 250 nucleotides immediately 5' to the transcription initiation sites are highly conserved among the human, rat, and chicken. Within the 1-kilobase pair 5' flanking region of the human albumin gene there are 8- and 35-base pair alternating purine/pyrimidine sequences, primarily consisting of dG and dT, and three nucleotide segments exhibiting homology to the proposed progesterone receptor-binding site. In these and other characteristics, the 5' flanking region of the human albumin gene is distinct from the corresponding region of the human alpha-fetoprotein gene. Each of the two polyadenylation sites of the human albumin gene is preceded by a AATAAA hexamer. In addition, the first polyadenylation site has several conserved sequences believed to play a role in the 3'-end formation. The second polyadenylation site lacks these signals which may explain why it is used less frequently. In spite of these differences the two polyadenylation sites show a high overall sequence similarity, suggesting that they arose by duplication. There is no major difference between the normal liver and hepatoma cells in the relative utilization of multiple sites for transcriptional initiation and polyadenylation of the human albumin gene, suggesting that the albumin mRNA polymorphism has no direct relevance to hepatocarcinogenesis.
Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany (2020)

2019-nCoV Transmission from Asymptomatic Patient In this report, investigators in Germany detected the spread of the novel coronavirus (2019-nCoV) from a person who had recently traveled from China...
Microvesicles from Mesenchymal Stromal Cells Are Involved in HPC-Microenvironment Crosstalk in Myelodysplastic Patients (2016)

Exosomes/microvesicles (MVs) provide a mechanism of intercellular communication. Our hypothesis was that mesenchymal stromal cells (MSC) from myelodysplastic syndrome (MDS) patients could modify CD34+ cells properties by MVs. They were isolated from MSC from MDS patients and healthy donors (HD). MVs from 30 low-risk MDS patients and 27 HD were purified by ExoQuick-TC™ or ultracentrifugation and identified by transmission electron microscopy, flow cytometry (FC) and western blot for CD63. Incorporation of MVs into CD34+ cells was analyzed by FC, and confocal and fluorescence microscopy. Changes in hematopoietic progenitor cell (HPC) properties were assessed from modifications in microRNAs and gene expression in CD34+ cells as well as viability and clonogenic assays of CD34+ cells after MVs incorporation. Some microRNAs were overexpressed in MVs from patients MSC and two of them, miR-10a and miR-15a, were confirmed by RT-PCR. These microRNAs were transferred to CD34+ cells, modifying the expression of MDM2 and P53 genes, which was evaluated by RT-PCR and western blot. Finally, examining CD34+ cells properties after incorporation, higher cell viability (p = 0.025) and clonogenic capacity (p = 0.037) were observed when MVs from MDS patients were incorporated. In summary, we show that BM-MSC release MVs with a different cargo in MDS patients compared with HD. These structures are incorporated into HPC and modify their properties.
Inhibition of human telomerase by 2′- O -methyl-RNA (1998)

Telomerase, a ribonucleoprotein up-regulated in many types of cancers, possesses an RNA template necessary to bind and extend telomere ends. The intrinsic accessibility of telomerase to incoming nucleic acids makes the RNA template an ideal target for inhibition by oligonucleotides. We report here that 2'-O-methyl-RNA (2'-O-meRNA), an oligonucleotide chemistry known to exert sequence-specific effects in cell culture and animals, inhibits telomerase with potencies superior to those possessed by analogous peptide nucleic acids (PNAs). Potent inhibition relative to PNAs is surprising, because the binding affinity of 2'-O-meRNAs for complementary RNA is low relative to analogous PNAs. A 2'-O-meRNA oligomer with terminal phosphorothioate substitutions inhibits telomerase sequence-selectively within human-tumor-derived DU145 cells when delivered with cationic lipids. In contrast to the ability of 2'-O-meRNA oligomers to inhibit telomerase, the binding of a 2'-O-meRNA to an inverted repeat within plasmid DNA was not detectable, whereas binding of PNA was efficient, suggesting that the relative accessibility of the telomerase RNA template is essential for inhibition by 2'-O-meRNA. Inhibition of telomerase by 2'-O-meRNA will facilitate probing the link between telomerase activity and sustained cell proliferation and may provide a basis for the development of chemopreventive and chemotherapeutic agents.
Transfection Efficiency of Cationic Lipids with Different Hydrophobic Domains in Gene Delivery (2010)

The structure of cationic lipids is a major factor for their transfection activity. A cationic lipid generally contains four functional domains: a hydrophilic headgroup, a linker, a backbone domain, and a hydrophobic domain. The structure of the hydrophobic domain determines the phase transition temperature and the fluidity of the bilayer and influences the stability of liposomes, the DNA protection from nucleases, the endosomal escape, the DNA release from complex, and the nuclear penetration. Also, toxicity of the lipids is influenced by the hydrophobic domain. The compounds used for gene delivery are classified according to the structure of the hydrophobic domain as follows: aliphatic chains, steroid domain, and fluorinated domain. In this review, we summarized recent research results concerning the structures of the hydrophobic domain, in order to find the effect of the hydrophobic domain on transfection efficiency. Understanding these would be very important for scientists to prepare novel cationic lipids and design novel formulations with high transfection efficiency.